Contents | Zoom in | Zoom out*44/ For navigation instructions please click here Search Issue | Next Page +VOFt7PMVNFt*TTVF JDD +6/&*446& Do Not Copy, Penalties Apply 44 Years in Dermatologic Surgery: A Retrospective Treatment of Poikiloderma of Civatte With Ablative Fractionated Laser Resurfacing: Prospective Study and Review of the Literature Treatment of Pruritus in Mild-to-Moderate Atopic Dermatitis With a Topical Non-Steroidal Agent © 2009-Journal of Drugs in Dermatology. All Rights Reserved. This document contains proprietary information, images and marks of Journal of Drugs in Dermatology (JDD). Anti-TNF Agents for the Treatment of Psoriasis No reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD. If you feel you have obtained this copy illegally, please contact JDD immediately. Photodynamic Therapy With Low-Strength ALA, Repeated Applications and Short Contact Periods (40-60 Minutes) in Acne, Photoaging and Vitiligo Are Ointments Better Than Other Vehicles for Corticosteroid Treatment of Psoriasis? /FXT 7JFXT BOE3FWJFXT 1JQFMJOF1SFWJFXT $MJOJDBM5SJBM3FWJFX Contents | Zoom in | Zoom out For navigation instructions please click here Search Issue | Next Page Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F Proudly Supported by Introducing the first and only once-daily combination acne treatment with adapalene and benzoyl peroxide Do Not Copy, Penalties Apply NEW Epiduo™ Gel—enhanced efficacy and convenience for your mild to moderate acne patients1,2 * At week 12, statistically more Epiduo™ Gel patients were rated as (IGA) clear or almost clear in comparison to the monotherapy arms1,2 * Significant clearing of both inflammatory (67%) and noninflammatory © 2009-Journal of Drugs in Dermatology. All Rights Reserved. lesions (59%) at week 121 This document contains proprietary information, images and marks of Journal of Drugs in Dermatology (JDD). * Easy-to-use application No reproduction or use of any portion of the contentsonce-daily of these materials may be made without the express written consent of JDD. If you feel you have obtained this copy illegally, please contact JDD immediately. Prescribe NEW Epiduo™ Gel for your mild to moderate acne patients Important Safety Information Epiduo™ Gel is a retinoid and antimicrobial combination product indicated for the topical treatment of acne vulgaris in patients 12 years and older. The most common adverse events associated with use of Epiduo™ Gel are erythema, scaling, dryness, stinging and burning. In addition, in clinical trials, adverse events reported in greater than 1% of patients treated with the Gel included contact dermatitis and skin irritation. Excessive exposure to sunlight and sunlamps should be avoided during treatment, and use of sunscreen products and protective clothing is recommended. Concomitant use of irritating topical products (like products containing resorcinol, salicylic acid or sulfur) should be avoided. Epiduo™ Gel has not been tested in pregnant or nursing women, or with the elderly. Pregnancy Category C. Please see brief summary of Prescribing Information on next page. THE ADVANTAGE IS CLEAR Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F A BEMaGS Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page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© 2009-Journal of Drugs in Dermatology. All Rights Reserved. %" # This document contains proprietary information, images and marks of Journal of Drugs in Dermatology (JDD). ! $ % # & '( #$ # ) 3 !, No reproduction or use of any portion of the contents of these materials may !, be made without the express written consent of JDD. 3 %" # + + 5 + 5 +)) +) 4 % . please contact JDD immediately.) + If you feel you have obtained this copy illegally. %% %7) . % % % %7 - # - # 5" 5" B='BB B='BB & =9 $ .## #! ! !%& %% !. !. % . % 4 4 ) ) +" * ##( 10%* ##( '' % 2 %. 4 ) 4 ) % .< 4 4 * &! # &! &"! ! % .# .< .% F G F G H4 H4 :?I :?I . 8)< ').)? '( &/(/ !2 . <)8 &/3&/ ! 0')( . ) + & & 3) 3) + 4 &! % . (88A (88A $ .# #$ % $ . 9'.9=8 . Weiss J. Adapalene-BPO Study Group. Phase 3 data. 2.9'. Adapalene-benzoyl peroxide.57(5):791-799. Data on file. Epiduo is a trademark. Penalties Apply References: 1. 2007. L. L. randomized double-blind.P.P. L. Thiboutot DM. Galderma Laboratories. Freeway Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . J Am Acad Dermatol.P. controlled study. a fi xed-dose combination for the treatment of acne vulgaris: results of a multicenter. Bucko A. et al.9=8 Do Not Copy. and Galderma is a registered trademark of Galderma Laboratories. L.P. 14501 N. Galderma Laboratories. ©2009 Galderma Laboratories. negligence. or transmitted in electrical or other forms or by any means without prior written permission from the Journal of Drugs in Dermatology (JDD). publisher. Do Not Copy. If you feel you have obtained this copy illegally. 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Del Rosso DO Philip Orbuch MD Martinez MD Zoe Diana Draelos MD Anna C. Toombs MD Lidia Rudnicka MD Kenneth Beer MD Michael P . Nehal MD Europe Doris Day MD FAAD Jorge J. Gupta MD PhD London. Sadick MD New York. Amonette MD Joseph C.the contentsMD of these materials mayJ. Shupack MD New York. Payne MD David E. Conejo-Mir MD Rex A. MA Hillary Johnson-Jahangir MD Robert Johr MD Jonathan Zippin MD PhD Englewood. Italy New York. Germany Elizabeth Hale MD New York. All Rights Reserved. NY Leon Kircik MD Louisville. NY Patricia Farris MD Metairie. PA SENIOR ASSOCIATE EDITORS Jeffrey Orringer MD Ann Arbor. Arroyo MD © 2009-Journal of Drugs in Dermatology. Bikowski MD Pittsburgh. NY Boston.contact JDD immediately. Katz MD John Zic MD Poong Myung Kim MD Marian Cantisano-Zilkha MD Amor Khachemoune MD John A. Pollack MD FRCPC Fresnada MD William Abramovits MD Lawrence F . FL New York. IL EDITOR OF CASE REPORTS Maurizio Podda MD PhD Frankfurt. Spencer MD St. Petersburg. 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NY CO-EDITOR-IN-CHIEF James M.be madeMD without the express written consent of JDD. CO PAST EDITORS Ritu Saini MD New York. Scheinfeld MD New York. Ocampo Candiani MD Francisco M. NY Henry W. Louis. FL Do Not Copy. NY Sherry H. British Columbia Isaac Brownell MD PhD New York. FL SENIOR EDITORS Robert Baran MD Cannes. MI Boca Raton. NY Keyvan Nouri MD Noah S. Berson MD Alysa R. Ontario Bradenton. NY MEDICAL EDITORIAL STAFF Alan R. TN Luigi Rusciani Scorza MD Rome. France C. Duvic MD Sheldon V.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 509 JUNE 2009 INTERNATIONAL EDITORIAL BOARD VOLUME 8 t ISSUE 6 Gerhard Sattler MD Darmstadt. Eichenfield MD Fitzgeraldo A. FL Neil S. Cockerell MD Rhoda S. CA Keyvan Nouri MD Miami. Moy MD Los Angeles. Wheeland MD Rana Anadolu Brasie MD Jeffrey Phillip Callen MD Bruce E. CamachoJames Q. Hruza MD FAAD W. FL Dee Anna Glaser MD St. pleaseA. Goldberg MD Nicholas Soter MD Jay G. Penalties Apply © 2009-Journal of Drugs in Dermatology. _______________ Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . All Rights Reserved. This document contains proprietary information. images and marks of Journal of Drugs in Dermatology (JDD). If you feel you have obtained this copy illegally. No reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F Do Not Copy. please contact JDD immediately. in Madga Reyes MD. Matilde Lorente MD. Tierney MD and C. Buckley. Raymond Allington. marks of Journal of Drugs in Dermatology (JDD). Are Ointments Better Than Other Vehicles for Corticosteroid Treatment of Psoriasis? Anna H. © 2009-Journal of Drugs Dermatology. All Rights This document proprietary information. Fernando Milláncontains MD. Feldman MD. Repeated Applications and Short Contact Periods (40-60 Minutes) in Acne. William R. images andMelendez.A BEMaGS Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page JUNE 2009 VOLUME 8 F ISSUE 6 ORIGINAL ARTICLES 44 Years in Dermatologic Surgery: A Retrospective Perry Robins MD Treatment of Poikiloderma of Civatte With Ablative Fractional Laser Resurfacing: Prospective Study and Review of the Literature Emily P. R. Rossana Schianchi MD. George Vavruska. (SBDFXBZ1IBSNBDFVUJDBMT UIFNBLFSPG"MEBSB JTQSPVEUP TQPOTPSDPNQMJNFOUBSZTVCTDSJQUJPOTUPUIFJournal of Drugs in DermatologyGPSBMM64CBTFEEFSNBUPMPHZSFTJEFOUT Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . Perry Robins. Joaquín No reproduction or use of Miguel any portion of the contents Maria Navarro. Treatment of Pruritus in Mild-to-Moderate Atopic Dermatitis With a Topical Non-Steroidal Agent Do Not Copy. William Hanke MD MPH FIGURE 1. Adrián Lloret MD. Paolo De Micheli MSc. Zivkovich and Steven R. Del Rosso DO Photodynamic Therapy With Low-Strength ALA. Richard Moraites (page 519). Kircik MD and James Q. Navarro MD of these materials may be made without the express written consent of JDD. High-intensity light source emitting in the yellow and orange spectrum (page 562).Reserved. Left to right: Theodore Tromovitch. Photoaging and Vitiligo Gabriel Serrano MD. If you feel you have obtained this copy illegally. PhD FIGURE 1. Frederic Mohs. Luisa Lunardon MD Anti-TNF Agents for the Treatment of Psoriasis Leon H. please contact JDD immediately. Penalties Apply Stefano Veraldi MD PhD. Effective and Underutilized Dermatologic Therapy Genomics of Skin Aging: Practical Ap plications Sympos Douglas N. Park MD. J DD Penalties Apply NT TO Intramuscular Triamcinolone: A Safe. Natalie Semchyshyn MD ISSUE 6 New Supplement Coming Soon Painful Parotid Hypertrophy With Bulimia: A Report of Medical Management A SUPPLEME Kelly K. original magnification: X100) (page 573). Chappell MD. November 9. images and marks of Journal of Drugs in Dermatology (JDD). Robins MD American Soc ium Proceedings. please contact JDD immediately. Focal acantholytic dyskeratosis of the epidermis (Hemotoxylin-eosin stain. 2008 Look for this supplement with your July issue of JDD or eJDD. iety for Derm ato 2008 Annua l Meeting. Arlene Ruiz de Luzuriaga MD MPH F Do Not Copy. This document contains proprietary information. Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . No logic Surger y vember 9.A BEMaGS Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page JUNE 2009 VOLUME 8 CASE REPORTS Localized Dyskeratotic Plaque With Milia Associated With Sorafenib Jeaneen A. No reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD. Rebecca C. 200 8 *44/: 1545 9616 +VMZt VPMVNFt July © 2009-Journal of Drugs in Dermatology. Symposium Proceedings. Burkemper MD. This supplement to the Journal of Drugs in Dermatology is sponsored by P&G Beauty & Grooming FIGURE 2. American Society for Dermatologic Surgery 2008 Annual Meeting. Nicole M. Tung MD. All Rights Reserved. *TTVF supp lement) 2009 Supplement Genomics of Skin Aging: Practical Applications If you feel you have obtained this copy illegally. Los Angeles. Rossi AB.1% were limited to mild or moderate irritation of the skin. RETIN-A MICRO 0.P. © 2009 Ortho Dermatologics 09DD0052 Printed in USA Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . RETIN-A MICRO 0. J Microencapsul. 2. The Microsponge ® Delivery System (MDS): a topical delivery system with reduced irritancy incorporating multiple triggering mechanisms for the release of actives. PUMP Study Group. Calif: OrthoNeutrogena.04% and 0. 0.1% are indicated for topical application in the treatment of acne vulgaris.U. Eichenfield LF. 2 Start with satisfaction in mind LIFY DOSIN MP G1 SI †3 ENT OVERU EV SE PR 4 C L TRETI NO TRO IN ON Do Not Copy. Embil K. RETIN-A MICRO is a trademark of Ortho Dermatologics.P.04%/0. Phase 4 study to assess tretinoin pump for the treatment of facial acne. d on ata .1% discontinued due to irritation. 2008. Nighland M. please contact JDD immediately. 3.04% and 0. ___________ This document contains proprietary information.1% [prescribing information]. The most common adverse reactions to RETIN-A MICRO 0. If you feel you have obtained this copy illegally. Penalties Apply © 2009-Journal of Drugs in Dermatology. Ortho Dermatologics. sfa U. 4.3% of patients using RETIN-A MICRO 0. et al.* L con ow firms Irr ita tio n. Nacht S. 1996. *Reported at the end of the 12-week P. Study. 104 male and female acne sufferers between the ages of 13 and 36 completed the study. RETIN-A MICRO (tretinoin gel) microsphere. 1. Data on file.13(5):575-588. Please see brief summary of prescribing information on the next page. May 2006.3 References: 1. † Data based on a consumer preference study designed to evaluate preference of Pump versus tube delivery.M. All Rights Reserved. J Drugs Dermatol.7(12):1129-1136.04% and 6% of patients using RETIN-A MICRO 0. images and marks of Journal of Drugs in Dermatology (JDD).04% and 0.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F Hig P h S ublish ati ed P.1% showed a visible reduction in total mean lesion count in as little as 2 weeks with full benefit of therapy seen after 7 weeks. No reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD.M cti . 0. .Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F New Zealand white rabbits were treated with Retin-A Micro (tretinoin gel) microsphere.? /:>0> :1 .1%. 77D 1:= ./8494>?0=0/ ?:..D . .4.9/ 82 62 /. 0.0/10?.9/ 82 62 /.D B3470 B0.>0/ incidences of certain alterations. /.40>.=0/?:-049. typical of retinoid49/@.-0?3.71:=8.?4:9> B0=09:?:->0=A0/.? .0..=0.71:=8.? .9.=49274E.=8..D%4847.78. including domed head and hydrocephaly.:77.?4:9>49?34>>. 3:@=> .=>?:.=0A09?4920>?4:9:1?30/=@2&30=0. but a few alterations that may be associated Brief Summary B4?3?=0?49:490C.=:>.=0.C48@8
[email protected]=0 9:=8.? 82 62 9.:>@=0B0=0>009"?30=. adjusted for (MICROSPONGE® System) to enable inclusion of the active ingredient.D ?480>?308.74E0/ 1:=?:?. these effects were not seen.=0. 9.:>0/?:.=029. tretinoin. This formulation uses teratogenic effects at doses up to 17 t480> 82 62 /.9>D>?084. tretinoin in non Retin-A Micro (tretinoin gel) microsphere formulations was not teratogenic in IMPORTANT NOTE: This information is a BRIEF SUMMARY of the complete prescribing =. OR INTRAVAGINAL USE.1%.-@?10?. in an aqueous ?:?.7-:/D>@=1.6>?:.=0.4.04% is a formulation containing 0./:>0:1?=0?49:49 after topical administration of Retin-A Micro ?=0?49:49 207 84.1% and 0.>0/.0. by weight.?>.490/49>?:.7=0>:=. 0.D49 FOR TOPICAL USE ONLY.7-:/D>@=1. patented methyl methacrylate/glycol dimethacrylate crosspolymer porous microspheres any dose after topical administration of Retin-A Micro (tretinoin gel) microsphere.=0.0.77D1:=>4C3:@=>?: ® Retin-A Micro (tretinoin gel) microsphere.4..0.04%.. ORAL.D?308..C48@8
[email protected] gel. pregnant rabbits.?>?@/D:1?3034230>??:.=0A09?4920>?4:9/4/9:?>3:B or 0.9/=.9>D>?084.1% := 82 62 /. NOT FOR OPHTHALMIC.9?=..82 62 /.//4?4:9?:.7/:>0 82 62 /. tretinoin for topical treatment of acne vulgaris.--4?>0C.?4:9>B0=049.--4?>B30924A0949/:>0>:1..D?=0?49:49B3470=0>?=. 0. 9/.. =0>@7?4924910?.9/49.7 ?=0?49:49 3./:>0 information provided with the product and therefore should not be used as the basis after topical administration of Retin-A Micro (?=0?49:4920784.0=?.74E0/1:=?:?.=. 62.?0 08:77409? ..?4:9>.0 If a reaction suggesting sensitivity occurs. gel topically). mice.77D4>8:=0>4847.740/%@.9/ 9:=8. At these topical doses.0 .?>B309./@>0:1..:>@=0/@0?::./.1% and 0. respectively.>B49/:=.:?09?4.3.:>@=0?:>@97423?49./:>09:=8..=4. variations in teratogenic doses among various strains of rats have CONTRAINDICATIONS: This drug is contraindicated in individuals with a history of sensitivity -009=0.C48@83@8..=009.740/.=:...=029. 49 =.7>: -0 0C.749.=40?.=:?0..:=?0/B309 82 62 /.?4:9 :1 ?30 /=@2 B:@7/ -0 0C.9. before prescribing the product.0=9@80=.:9?.=0.=:>.D-04==4?.9>D>?084.DB.D ?480>?308. rabbits.=:?0.?/:>0>2=0. and mucous membranes.C48@83@8.?>%# .--4?> B309 eyes. hamsters. Oral tretinoin has -009>3:B9?:-010?:?:C4.?4:9:90.:=?>. It should be discontinued if hypersensitivity to any of its other species in its handling of tretinoin.=0. five of the reports describe the rare birth defect category holoprosencephaly (defects associated with incomplete midline development of the forebrain).@7.==.=:>.?>.:=. The with tretinoin..@..=0.?0/ clinical use of Retin-A.9/ >3:@7/-060.9.7 for prescribing the product.>8. Oral tretinoin has been shown to be teratogenic in rats.=0=0.740>3@80=@>>3:=? -09?:>.D?480>?308..7:90&34=?D 3@8. paranasal creases of the nose.47:1?:.>>:.0=409.7-:/D>@=1.4949/4A4/@. F&=0?49:493.=:/@.77D sunlight as a result of the use of tretinoin.9>D>?084.0. .9/A.:=?>49?0=8>:1=4>6?:?3010?@>4>9:?69:B9 F$0?49 4./:>09:=8. The safety and efficacy of the 2=0.380?.=D=4->3.=?4.9>?3.4.9 82 62 /. delayed ossification of several bones occurred The physician should be thoroughly familiar with the complete prescribing information in rabbits..?82 62 /.?=0.9/>3:@7/-0@>0/ .@?0=490/0.?0=-@?9:90B0=0:->0=A0/.. Patients who may be required to have considerable >@90C../8494>?0=0/ 82 62 /.9>D>?084.7@/492>@97. tion.77D49/:>0> indicated for topical application in the treatment of acne vulgaris.A:4/0/ F)0.?809? has been established from these cases...:=?0/ 9?30.?.?0>&=0?49:49B..4>0 B4?3 ?30 .C48@8
[email protected]/1:=?:?.04%. 0. with utmost caution in patients with this condition..4.:800C.9.?:@>>649.D-0.9 . is 8.7?3:@2349.77D. patients should be directed to temporarily reduce the amount Topical tretinoin in animal teratogenicity tests has generated equivocal results.=4.D?480>?308.?4A0.=:?=0?49:4920784.:?09?4.30=0 .:7/..A0-009 during the day may be helpful.@?4:9'>0:1>@9>.7-09014?5@>?4140>?30.> -009 >3:B9 ?: -0 10?:?:C4.=0>@7?49249>6070?.?4:9.9 . degree of irritation warrants.=0.E08..7>8.7 use of this product in the treatment of other disorders have not been established.D?480>?308. Retin-A Micro should be Retin-A Micro (tretinoin gel) microsphere.?30=0C?=080>>@.D1=:8?30 Non-Teratogenic Effects: &:. and subhuINDICATIONS AND USAGE: Retin-A Micro (tretinoin gel) microsphere.9.>.9 reactions to any of its components.?>B30924A09:=.7A.7=0>:=.?409?>@9/0=?=0.0>>4A0 >649 /=D90>> 8.. (assuming .-:74.77D.C48@8
[email protected]>D>?084.4?D>3:=?090/:=64960/?.D:=2=0. or discontinue 1:=?0=. discontinue use temporarily.. tables.==.>-009=0.740/?:.9D/=@2.=48.77D:=?:.9 82 62 /.D .74E0/1:=?:?.?0=?3. F'9./8494>?0=0/..0>>4A07D/=D=0/>B:7709:=-74>?0=0/ 1?30 reported.:8.?4:9>49:>>414.?0/ -D .49)4>?.?4:9> General: were observed at all doses.0/ 41 >: @>0 :1 . 0.=4.@>0>0A0=04==4?.>?0=.4. ?3.7=4>6?:?3010?@> be advised not to use the product until fully recovered because of heightened susceptibility to )4?3B4/0>.74E0/1:=?:?.=4. This summary has been prepared by deleting information body surface area. however.7A.>0/ Information for Patients: A Patient Information Leaflet has been prepared and is included with 49?=.D9:8:72@>8:960DB34.0..7>:8..=?:3@8.?4:9>.?349=.C48@83@8. >429414.0:1?30>0>.?0= use all together.0../:>0. body surface area). 82 62 /.?492?:.8.30=0 9:=8.D:97D41?30./:>09:=8.>0/>6070?.=0.9 PRECAUTIONS: >D>?084.7-:/D>@=1.A0 C.74E0/1:=?:?.B.>?:.779@8-0=:1-4=?3/010.=0. fetal malformations were reported for doses of 10 ingredients is noted.>>3:@7/-0849484E0//@=492?30@>0:1 There are no adequate and well-controlled studies in pregnant women.?0/0C.7-:/D>@=1..04%./@7?.>0> of temporally associated congenital malformations have been reported during two decades of . Dose-related increases in embryolethality and abortion also were F&30>649:1. and patients with sunburn should @>0//@=492. and references.1% and 0..4.?0/?08. However. Although no definite pattern of teratogenicity and no causal association . In rats.9/?3:>0B4?34930=09?>09>4?4A4?D?:?30>@9>3:@7/0C0=.?480>?308.3. Efficacy at reduced frequencies of application has not been established.7:?3492:A0=?=0..9:8./8494>?=.=0.?:2094.7>:-009=0.:=?0/?:. Similar results have also been reported in pigtail macaques.4.90:@>=0.4.:8809/0/B3090C.?:2094. There is evidence or frequency of application of the medication.:>@=0..47D/:>0:1 2:1 from the complete prescribing information such as certain text.7?=0?49:4949)4>?. the mouth.70?07D:>>4140/ 3. use of the medication should be discontinued. a consistent finding in rats when dams were treated topically or orally with retinoids.9/. a dose-dependent increase of supernumerary ribs was observed.99:?-0. D.82 62 /. 3..77D.007:17480>#.6.9 0.@?4:9>3:@7/-00C0=. medicated or abrasive soaps and cleansers.=:>... There are.=:>.=?4..@7.? . astringents..4. or spices should be used with caution because of possible interaction with tretinoin.30=0 ..=0. Drug Interactions: Concomitant topical medication.30=0 .4. products with high concentrations of alcohol.=. products that have a strong drying effect. Avoid contact Animal Toxicity Studies: In male mice treated topically with Retin-A Micro (tretinoin gel) B4?3?30.0.C48@8
[email protected]/ >D>?084.74E0/1:=?:?. however no adequate and well-controlled studies in pregnant women.:84?.740/?:.7 84.4>0/B4?3?30./:>0..:9..7-:/D>@=1.9?@>0:1?:. ?480>?308.20:1$0?49 4.=:?=0?49:4920784.9/9:=8. := 82 62 /.D ?=0?49:49 . := . 04%.. is begun.?4:9>.74. with no pathological changes were observed at the two highest doses.=.0=:C4/0>@71@==0>:=.3 82 62 /.1:= /..=0.=B0423?-@? with Retin-A Micro (tretinoin gel) microsphere. 9:=8.4/ human systemic dose after topical administration of Retin-A Micro (tretinoin gel) microsphere.1% and 0.74E0/1:=?:?. but without any underlying pathological changes. ?480> ?30 8. 0. It also is advisable to allow the effects of such preparations to subside before use of Retin-A Micro (tretinoin gel) microsphere. Impairment of Fertility: 9.04%.49492-09E:D7.7>?@/D49B34.7-:/D>@=1.:9?.:@9?0=.C48@8 :A0=?30.D>.0. B006/0=8.90..49:7:=>.@7. in female mice there was a reduction in ovarian weights. Carcinogenesis. Mutagenesis..?4:949?0>?4..=0.=0/@.1% and 0.D74.D. at 0. Similarly. .? .1?0=?3014=>?/:>0>0.09?=.=:>.7>>@220>?492?3.049/4.?4:9:1?=0?49:493:@=>..?0/ 49.1%).>8. .?4:9>:1?=0?49:49..9/:>0 9?34>>?@/D?30=0B.?0>?3./8494>?0=0/ .>049?30.:6490?4.>.74..=0. These concentrations are near the tretinoin concentration of these clinical formulations is probably related to ingestion.@?.0B0=0./:>0>.9/ 1:=8@7.?:C4..>?@/D4984.4.?0/B4?3?30.9?:=0>?=.?0?:C4 84..80/:>0>&308.?4:9?: mous cell carcinomas and papillomas in the treatment area were observed in some female @9=0>?=.04% and 0. ?480>?308.>>:.7.1?0=?:.?>D>?084.7>?3.4.=.490/.4?D:->0=A0/ mice. A dose-related incidence of liver tumors in male mice was observed at ?3:>0>.C48@8>D>?084.:>@=04>2=0.948./:>0=07.7.:9.?0=. Male and female dogs treated with Retin-A Micro (tretinoin gel) (0.0C.??30>D>?084.C48@8
[email protected]:@>><@.948.30=0 ./8494>?0=0/ 84.490/.. := 82 62 /.D?=0?49:49 . :=. ?0C.=00C.=:?=0?49:49 strain of mice.?@=.77D?:70=..C48@8
[email protected]>>3:B0/9:0A4/09.?0//:>0 &:1?=0?49:49..0:1 reduced testicular or ovarian weights or pathological changes.@?4:9>3:@7/-00C0=.. There was 9: 0A4/09.@==0/.. 1:@=?480>?308.0.=.9/ 1:
[email protected]8.740/?:.=0.D=0>./:>0.?0 1:= ?30>0 ?@8:=> 49 ?34> /=@2>.?4A07D1:= /.@>0 ?30D B0=0 B4?349 ?30 -.?480>?308.7 :.@==09. body surface area. ..62=:@9/ 9..77DB3099:=8.49:2094.9>D>?084.0.=0?B:.98476.0.7 9:=8. The biological significance of these findings is not clear because they :.0 :1 .9/ 82 62 /.9/ human systemic dose after topical administration of Retin-A Micro (tretinoin gel) microsphere.9/ Nursing Mothers: ?4>9:?69:B9B30?30=?34>/=@24>0C.=0?0/49
[email protected]84760.7-:/D>@=1.C48.4>0/B309$0?49 4.=0?0/493@8.=0>...@>08.:?09?4.C48@8 .4.?/:>0>?3.?4:9>.=0 .0 =.9D -0.74E0/1:=?:?...00/0/?30/0=8.74E0/1:=?:?.?4A07D&30>0/:>0>.7 B309 . 77D4>/01490/ Geriatric Use: Safety and effectiveness in a geriatric population have not been established.8:1$0?49 4..74E0/1:=?:?.20/. .7@/0>@114..:>0>:1.948... 62.> 2=.740/?:. ..4.:>@=0 Pediatric Use: Safety and effectiveness in children below the age of 12 have not been established.4.9>D>?084.47D?:../8494>?0=0/?:..30=0 .77D?:84.90C.7>?@/40>:1$0?49 4.C48@83@8. ?=0?49:49B.=:/4/9:?49.9/ over to determine whether they respond differently from younger subjects./:>0.>.=0.9>D>?084.:=.0=>:9 7494.@=.=:>...D :1 gel) microsphere. is administered to a nursing woman.70C. 82 62 /.?>. ?:>D>?084.7-:/D>@=1.409?9@8-0=>:1>@-50.0.=4>:9>:1?30.
[email protected]//.C48@83@8.:8.1% or 0.=:?=0?49:4920784.:>@=0?308.0 ?480>?308. 0.04%./:>0 9:=8. is intended for topical micronucleus assay.60:1(4?.A0>3:B9.0=?.82?=0?49:49 62-:/DB0423? Dermal carcinogenicity testing has not been performed with Retin-A Micro (tretinoin gel) ADVERSE REACTIONS: microsphere.D:.>>..42809?0/84.?0/B4?30C./5@>?0/?:.=:>.:?09?4.749?. :1?30>0>?@/40>?:3@8.:8.4.:>4?4A01:=49/@.-:74.=?414.9?:70=.9//.@="=.?4:94>..80>4/00110.9.?4:9:1>?=@.?0=>?@/D49.. If these effects occur.8:@9?>:1?30/=@2 .9>4>9:?. If you feel you have obtained this copy illegally.. reportedplease to have heightened to sunlight while under treatment with tretinoin. Some individuals have been ultraviolet irradiation sources.?>.4/:=-0??0==0>@7?>B477-0:-?.D?30 #.?:C4.=D7.740/0C.@==09?0C.0>>4A07D=0/0/08..?3.>>:.0>>4A0:=.>?3:>0.?0 This document contains proprietary information.?4:9...9/ &30.42809?.7>8.:>@=0?:>@97423?:=.D093.:7D80=B.9.?4:9/4/9:? However.?409?>>3:@7/849484E00C..4?D49?3080>.7.7 8..>.0>>4A07D9:8:=0=.:8.. :A0=.. both of which were negative. @>0:97D 180/4.=.D70. the medication should either be discontinued until the integrity ?@8:=42094.7:1.0>@220>??3.4?D.?:@>-74>?0=0/:= © 2009-Journal of Drugs in Dermatology.:.=..9/902.:81:=?8.9/'(7423?1=:8. All Rights Reserved.490/. Temporary hyperhypopigNo reproduction or use.=.?@=.1%.?:2090>4> 8. 0.?:C4. %?@/40>493.:800C.:?09?4.9/?0=.:909?:1?300C.04%. contactsusceptibility JDD immediately..?:=&34> :1?30>6494>=0>?:=0/:=?3080/4..->09.=20.=6.4.007492:=/4>.3:?: True contact to topical tretinointhe is rarely encountered.. &30>649:1. images and marks of Journal of Drugs in Dermatology (JDD).=60/=0/90>>.409?.4.9. 0.49>09>4?4A049/4A4/@. efficacy has not been established for lower dosing frequencies.:80?30093.49:2090>4>-D ?=0?49:497?3:@23?30>429414.0809?:1.1% and 0.>-009.0.7 mentation has been reported with repeated application of tretinoin.:914=80/49. 0110.?4A01:=2090?4.30=0>3.70.=>48@7./?:?30>.:>@=0?:?=0?49:498..04% or 0.0 of any portion of the contents of these materials mayallergy be made without express written consent oforJDD.70A07?30.:9.849 chromosomal aberrations in the in vitro chromosomal aberration assay in mammalian cells in Rx only.7-49:84.?0>.74920>?4:9:17.4=70>>.?4A.49:2094. The mutagenic potential of tretinoin was evaluated in the Ames assay and in the in vivo mouse OVERDOSAGE: Retin-A Micro (tretinoin gel) microsphere.?.0?30 crusted.71:=2090?4.>:7.?409?.:909?>:1?3084.?09?!:> . ?30..?4:9>3:@7/-0./:>0>:1'(.D-0.0:180?. 7-:/D>@=1. Do Not Copy. and the mouse micronucleus assay.9/8:?474?DB0=0>009.0=8.? 82 62 /.9/9:=8. Penalties Apply In dermal Segment I fertility studies of another tretinoin formulation in rats..9?/0.77D..:@9?.74E0/1:=?:?..77D>429414.D?480> ?308.4. HGPRT forward mutation assay./:>0.0 area)..70>?=0. and slight (not statistically significant) increases in the number and percent of nonviable 08-=D:>49108..C48@83@8.?0/B4?3 .>0>49>..=0.740/?:.9>D>?084. slight (not statisti. D.82 62 /. .740/?:. decreased survival of neonates and 2=:B?3=0?..0.9/9:=8.4.9/.C48@83@8.?480>?308./:>0 .?4:9B0=0:->0=A0/.74E0/1:=?:?.7-:/D>@=1.7 Segment I and Segment III studies in rats with tretinoin...9>D>?084.=/.=0.?/:>0>490C.77D.0>>:1.-:A0B0=0:->0=A0/ 9:=.. ?4:9 /.04%.9 ?:.0. In another study..7 -:/D >@= face area after topical administration of Retin-A Micro (tretinoin gel) microsphere.82 62 /.=:>.30=0 .? /:>0> :1 ?: 82 62 /.74E0/1:=?:?.9 >D>?084.D ?480>?303@8. 0.74E0/ 1:= ?:?. 0.=0. Pregnancy: Teratogenic Effects: Pregnancy Category C.1%) some alterations were seen in vertebrae and ribs of offspring.7/:>09:=8. have not been performed in any species. /:>0 :1 ?=0?49:49 9:=8..D> ?: ?480> ?30 8.7-:/D>@=1. Dermal fertility and perinatal development studies with Retin-A Micro (tretinoin gel) microsphere.1% or 0. pregnant Distributed by: OrthoNeutrogena ( % "!""$& " ! # $ '& ! :>92070> H" #.C48@8
[email protected] :9 20>?. In a study of pregnant rats treated with topical application of Retin-A Micro (tretinoin gel) 84. . RETIN-A MICRO®4>..0@?4.7?3 9.=6:1. ® MICROSPONGE 4>.=/49.=024>?0=0/?=.=024>?0=0/?=.!047#3.7 9.=6:1"=?3: .7 0.@-749" Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F ../08.=8./08. © 2009-Journal of Drugs in Dermatology. advanced photostable technology No or use of any portion of the contents of these materials may be made without the express written consent of JDD. Inc. 2009 Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . Penalties Apply There’s no such thing as over protective when it comes to baby’s skin. + reproduction scientifically shown maintain levels of broad If youto feel you have high obtained this copy illegally. All Rights Reserved.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F #1 Dermatologist Recommended Baby Sunblock Do Not Copy. natural colloidal oatmeal formula is as gentle to baby’s skin as water that’s the beauty of nature+science © Johnson & Johnson Consumer Companies. please contact JDD immediately. This document contains proprietary information. images and marks of Journal of Drugs in Dermatology (JDD). spectrum protection against UVA and UVB rays + fragrance free. 2008. Prescribing Information. waxy skin by maintaining a moist skin environment. Frequently reported adverse events in Atopiclair-treated and vehicle-treated groups were burning (6. vehicle-controlled study. Atopiclair nonsteroidal cream does contain shea butter (Butyrospermum parkii). vehicle-controlled clinical study to examine the efficacy and safety of MAS063DP (Atopiclair®) in the management of mild to moderate atopic dermatitis in adults. burning. including atopic dermatitis and allergic contact dermatitis.8%). Rx Onlyinformation. Boguniewicz M. 3. Graceway Pharmaceuticals. Atopiclair nonsteroidal cream is indicated to manage and relieve the itching. J Drugs Dermatol. Abramovits W. randomized.152(6):854-859. www.0001) G Controls recurring flares 1. All Rights Reserved. J Pediatr.1%) and stinging (8. Penalties Apply BREAKS THE ITCH SCRATCH CYCLE–FAST G Itch relief significantly better than vehicle as early as day 3 and at all time points 1 measured during 43-day study (P<. LLC. Data on file. Atopiclair® Nonsteroidal Cream. which is beneficial to the healing process.com Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F .2 G Supports healthy skin-barrier function 3. LLC. a derivative of shea nut oil (not peanut oil). TN ATP080807 www.5(3):236-244.com For external use only. Please see adjacent Prescribing Information. and pain experienced with various types of dermatoses. Boguniewicz M. 2. If you feel you have obtained this copy illegally.3% vs 2. Bristol. Under the supervision of a healthcare professional. please contact JDD immediately. A multicenter. Zeichner JA. Eichenfield LF. MAS063DP is effective monotherapy for mild to moderate atopic dermatitis in infants and children: a multicenter. et al. peanut or animal derivatives. images and marks of Journal of Drugs in Dermatology (JDD). wheat. Patients with a known allergy to nuts or nut oils should consult their physician before using this topical preparation. randomized. References: 1.atopiclairUS. ©2009 Graceway Pharmaceuticals. Atopiclair nonsteroidal cream does not contain milk. avoid contact with eyes.9% vs 7.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F IN THE MANAGEMENT OF ATOPIC DERMATITIS Do Not Copy. Atopiclair nonsteroidal cream helps to relieve dry. 2006.4 © 2009-Journal of Drugs in Dermatology.gracewaypharma. 4. This document contains proprietary 100g tube No reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD. which is beneficial to the healing process. b Manufactured under license from Sinclair Pharmaceuticals Ltd. Do not freeze. two-year history of severe pruritus involving her eyelids and How Supplied: 100g tube. she still has residual pigmentation. Atopiclair nonsteroidal cream is indicated to manage and relieve the itching. Capryloyl glycine.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page JUNE 2009 VOLUME 8 A BEMaGS F ISSUE 6 DEPARTMENTS News. burning. and massage gently into the skin. Ingredients: Atopiclair is an off-white. Patients with a known allergy to nuts or nut oils should consult their physician before using this topical preparation. Arachidyl alcohol. Glyceryl 2009-Journal of Drugs in Dermatology. If the skin is broken. Sodium hydroxide. Atopiclair nonsteroidal cream does not contain milk. cover Atopiclair nonsteroidal cream with a dressing of choice. Pentylene glycol. LLC™ Bristol. Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . and numerous topical medications had been ineffective. known history of hypersensitivity to any of the ingredients. Ethylhexylglycerin. a If you feel you have obtained copy please contact JDD immediately. Atopiclair nonsteroidal cream does contain shea butter (Butyrospermum parkii). peanut or animal derivatives. Godalming Surrey UK. but the tissue hypertrophy and lichenification have gone and the pruritus has not recurred. Ascorbyl No reproduction use of any of the contents of glycol. tetraisopalmitate. proprietary information. Telmesteine. Penalties Apply a ATOPICLAIR™ Rx Only NONSTEROIDAL CREAM FOR TOPICAL DERMATOLOGICAL AND EXTERNAL USE ONLY. Ethylhexyl palmitate. AVOID CONTACT WITH EYES. Disodium EDTA. DMDM hydantoin. This(anti-oxidant). All Rights Reserved. stearate. these materials may be made without the express written consent of JDD. Allantoin. Atopiclair nonsteroidal cream helps to relieve dry. GU7 2AB Distributed by Graceway Pharmaceuticals. Arachidyl glucoside. a derivative of shea nut oil (not peanut oil). Vitis vinifera. Propylportion gallate. including atopic dermatitis and allergic contact dermatitis. Indications for Use: Under the supervision of a healthcare professional. Sodiumorhyaluronate. Store at room temperature up to 25°C (77°F). TN 37620 A101 0207 PATENT PENDING Several courses or oral corticosteroids had given temporary relief only. and she had developed tissue Precautions: Do not use the product if the packaging is damaged or after expiration date. periorbital areas of her face. Other Patient Information: The formulation contains no dyes or fragrances and is well FIGURE 1. PEG-100 stearate. Bisabolol. hypertrophy and lichenification secondary to rubbing a). nonsteroidal cream comprised of Deionized water. Views and Reviews Pipeline Previews Clinical Trial Review READER SERVICES 9 FIGURE 3. (page 582). Localized neurodermatitis. © Behenyl alcohol. Tocopheryl acetate Glycyrrhetinic Carbomer. FTN: The patient had a tolerated and safe for patients of all ages. images olamine. document containsacid. Butyrospermum parkii. and pain experienced with various types of dermatoses. Directions for Use: Apply Atopiclair nonsteroidal cream to the affected skin areas 2 to 3 times a day (or as needed). waxy skin by maintaining a moist skin environment. Treatment with maintenance pilocarpine resulting in reduction of parotid gland size (page 578). Piroctone and marks of Journal of Drugs in Dermatology (JDD). wheat. JDD Buyers Resource Do Not Copy. and Butylene Cautions: The use of Atopiclair nonsteroidal cream is contraindicated in anythis patient withillegally. Eight weeks after one triamcinolone injection b). $/44HERAPYISPERFORMEDUSINGTHE3MART8IDE$/4#/2LASERSYSTEM. Penalties Apply $/44HERAPYTMISTHELATESTINNOVATIONFORSKINRESURFACING © 2009-Journal of Drugs in Dermatology.A BEMaGS Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page F I’ve got a secret… …it’s about the DOT! Do Not Copy. All Rights Reserved. ABLATIVESKINRESURFACINGWITHRAPIDHEALING If you feel you have obtained this copy illegally. please contact JDD immediately. images and marks of Journal of Drugs in Dermatology (JDD). $/44HERAPYISIDEALFORTREATMENTOFPIGMENT. FEATURINGTHEUNIQUE$/43CANNERWITHInfinite Delivery OptionsFOR No reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD. This document contains proprietary information. SKINLAXITYTEXTURE. WRINKLESANDACNESCARS )TSABOUTCHOICE)TSABOUTCONTROL)TSABOUTTHE$/4 3INGLE4REATMENT s -INIMAL$OWNTIME s /UTSTANDING2ESULTS Before After #OURTESYOF$EBORAH33ARNOFF. -$ Manufactured by Distributed by ECLIPSEMED. .TD s TOLLFREE s ________________ WWWECLIPSEMEDCOM s ________________ WWWDOTTHERAPYCOM Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . Do Not Copy. who spoke at a conference for plastic surgeons on a new surgical technique that showed promise for successfully treating skin cancers. come competent in performing the procedure. at the annual meeting of the Americonsidered chemosurgery to be “black magic” and and the can Academy of Ophthalmology and Otolaryngology (AAOO) in © 2009-Journal All Rights Reserved. many of my colleagues were upset because they In October 1970 in Las Vegas. Nevertheless. the American Academy of stopped. After five weeks. I made arrangements to observe Dr. Without the are the best equipped to treat them. William R. George Vavruska. it was called chemosurgery. Slowly the merits of the technique became apparent. Chemosurgery was so named because of the fixative used. as noted. Drs. To my dismay. preferably by a method that chemical. Buckley. chemosurgery was later years. There were only 20 of us at that meeting who were at that time performing this technique in North America. Chemosurgery was a word that very few dermatologists had heard. Mohs as a visiting physician in Madison. and the concept of a dermagery. In my first year (1966). if I had wanted to practice surgery I should have become a plastic which were treated using serial excisions of fresh tissue. and one practically unknown to all other physicians in the medical community. The zinc surgeon. My vision was that wounds healed spontaneously and uneventfully. dermatologists are not surgeons. Mohs lectured on chemosurgery. Development of Mohs Surgery It was then. Perry Robins. dermatologists could beFollowing the surgical removal of eyelid cancers in this fashion. an application of a paste made with zinc chloride on cutaneous skin cancers.300 patients per year by the late 1980s. which intrigued me. As a result. and. Not only has this prediction come true. (now known as Mohs micrographic surgery). Frederic Mohs. and chloride paste was not employed for fear of damaging the globe. presented a number cases of tumors on or around the eyelids If you feel you havewisdom obtainedwas this copy please contact JDDofimmediately. where he was performing chemosurgery daily. but many centers may even have multiple Mohs surgeons on staff. zinc paste to be painful.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F JUNE 2009 519 70-6. one cannot imagine how different the field of dermatology was in 1965. we treated 70 patients with the numbers increasing to 1. As a consequence of the growing success and popularity of the technique. with additional training. and recently shortened to Mohs surgery. Penalties Apply Dr. Mohs’ textbook. tologist performing surgery was. and then returned to New York to put what I had learned into practice. with the exception of a few surgeons who had heard Dr. Conventional that illegally. it was referred to as the fresh tissue technique. when I was to take my the next intentional step in a young medical career. In 1965 a group of doctors who were performing Mohs surgery gathered at the annual meeting of the American Academy of In December. Las Vegas—now two organizations. Dr. followed by excision and histologic examination of the layers. 1970 at the annual Mohs Conference.1 dermatologists. A few attempts were made of to Drugs have in meDermatology. it was clear that. at the start of my practice at New York University (NYU) Medical Center. R. Dermatology (AAD) in Chicago (Figure 1). In provided the highest cure rate. Ted Tromovitch and Sam Stegman presented “104 cases of surgery Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . Left to right: Theodore Tromovitch. I purchased a “how-to” kit. dermatologists logically gravitated to Mohs surgery. Wisconsin. a technique for the staged removal of skin cancers using the in situ fixation of cutaneous tissue. thus. my role as a student began to evolve into that of an educator. a jar of zinc chloride paste and Dr.% INTRODUCTION From today’s perspective. Alfred Kopf predicted 25 years ago there would be a Mohs surgeon in all of the leading medical centers in the country. removed from the faculty at NYU and expelled fromimages the and Ophthalmology (incorporated in 1979) and the American AcadeThis document contains proprietary information.&t*446& COPYRIGHT © 2009 ORIGINAL ARTICLES JOURNAL OF DRUGS IN DERMATOLOGY 44 Years in Dermatologic Surgery: A Retrospective 1FSSZ3PCJOT. named Frederic Mohs. American of or Dermatology (AAD). Frederic Mohs speak at a conference. what would be an unintentional step toward a life-long career in skin cancer education. unheard of. Raymond Allington. Richard Moraites. marks of Journal of Drugs in Dermatology (JDD). It all began when a colleague of mine mentioned a general surgeon. belief was thatmaterials my may of Otolaryngology—Head and Neck Surgery of 1981)—we NoAcademy reproduction use of any portion ofTheir the contents of these be made without the express written consent(as of JDD. In the early days. FIGURE 1. as physicians trained to recognize skin cancers. the name was changed to Mohs micrographic surnot yet a part of the medical lexicon. several stages could be done within a day. Recurrence of basal cell carcinoma (of the cheek) following multiple excisions and grafts. b) Extent of lesion following Mohs surgery. the cases that were referred to my practice for treatment were not random. Not infrequently. b) Extent of lesion following Mohs surgery. FIGURE 2. Most were very difficult and extensive. They reported four recurrences. All Rights Reserved. FIGURE 3. three months post-op. The cure rate with the fresh tissue technique was equal to that of the paste. except in cases of extensive. and many patients could be treated in one day. b. Fortunately. Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . please contact JDD immediately. fingers and other extremities they could possibly be saved. c. c) Post-Mohs with full-thickness graft. By 1974. a. we comThisthe document contains proprietary images and marks of Journal of Drugs in Dermatology (JDD).&t*446& without using zinc chloride chemical fixative” (a technique they called “chemosurgery fresh tissue technique”). use of anyinitially portion of the punch contentscards of these If you feel you have obtained this copy illegally. the organs were saved. poorly-defined squamous cell carcinomas. both primary and recurrent. I began a study on the efficacy of this new fresh tissue technique. both the shaft and glans penis. Norecords reproduction or patients.3 Between 1965 and 1980. or sclerosing basal cell carcinomas (BCCs) involving areas known to have high recurrence rates. repairs could be carried out done immediately. The borders were poorly demarcated and morphea-like.5 We continued to develop and publish studies illustrating the effectiveness of the Mohs technique.4 A compendium of some notable data is provided.2 In 1972. These patients were also scheduled for amputation. I found it unnecessary to use the zinc chloride paste. if necessary. Darrell information. most of the cancers were not extensive and the digits were saved. ears. however. The technique was far more advantageous: less pain and swelling. including the timing of patients’ self-identification and reporting of lesions. With assistance of Dr. Some tumors had been operated on as many as 10 times. less postoperative bleeding. c) Healing by second intention. through the Mohs technique. b. namely the nasolabial fold.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 520 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. Penalties Apply A number of patients were referred to me with cancers on their fingers. 13PCJOT later with software. Fortunately. Mohs surgery was superior in terms of saving vital organs which previously would have been deemed unsalvageable and widely excised to a point of lost function or fully amputated. and inner canthus. Basal cell carcinoma (of the ear) with a history of three recurrences. and what we found to be successful treatments for a variety of common and rare tumors (Figures 2–4). patients were referred with lesions on the penis. Do Not Copy. and found a series of statistically interesting trends among our patients. Tumors Treated With Mohs Basal cell carcinoma Sebaceous carcinoma Squamous cell carcinoma Angiosarcoma Dermatofibrosarcoma protuberans Cylindroma Merkel’s cell carcinoma Atypical fibroxanthoma Microcystic adnexal carcinoma Keratoacanthoma Malignant fibrous histiocytoma (MFH) Melanoma c. a) Upon presentation. to record and study the medical history and habits of patients. my colleagues and I made great efforts a. and were scheduled for amputation because physicians at that time were unaware that. Rigel. puterized of our with andmaterials may be made without the express written consent of JDD. Early in my practice. a) Upon presentation. © 2009-Journal of Drugs in Dermatology. With the development of the fresh © tissue technique in 1975. 5. waiting longer will shift the the opportunity to train a plastic surgeon from Israel. Upon completion of his fellowship. Minimize Revisions came to me from abroad for training in Mohs surgery and subsequently established units in their own respective countries. techniques that are established. what did you do wrong?” Most often. was our first fellow (for the year 1968/69). “Doctor. things can go wrong. the patient should avoid alcohol and aspirin.&t*446& 13PCJOT Pearls Of Wisdom 1. Never Promise “No Scar” The object of all surgery is to make the scar as least noticeable as possible. surgery. In many instances. t(PPEEPDUPS*MJLFUPJOTUJMMDPOmEFODFJOUIFQBUJFOUPG the ability of the physician. the longer you can wait. With interest grew exponentially. this lack of general awareness did not stop Drs. Three Keys to a Good Result It is important to remind the patient that there are three componentns to achieving a good result. Isaac patient’s focus. reconstructive surgery. predictable. with his expertise in repairs. rarely did I have more than two applicants for the fellowship. Dr. the first stage to be completed now. The First Mohs Fellowships Under the direction of Dr. If the patient is expecting a scar and you produce an inconspicuous one. t(PPEQBUJFOU*UJTJNQPSUBOUUPJOTUSVDUUIFQBUJFOUUPCF compliant: follow written instructions. Penalties Apply 4. FIGURE 4. Doctors If you feel you have obtained this also copy illegally. 21-year-old college student with a squamous cell carcinoma on the bridge of the nose. so the patient will not ask. Even under the best of circumstances. My philosophy is to attempt to do the simplest procedure first. Victor Witten and Harvey Blank from requesting funding from the Miami Dermatology Society to establish a chemosurgery unit at the University of Miami in 1969. I also had reoperate. The patient may ask. In the first 10 years. will sometimes take what could be a simple repair and convert it into a complex procedure. a leading dermatology healing in the third stage starts at six months and continues for a period of up to two years. wound care. and good luck. b) Extent of lesion following chemosurgery. you’re a hero. Interest in Mohs surgery grew very slowly. Do the Simplest Procedure b. with each of training No reproduction use of any portion of the contents these materials mayresults. The program included instruction in dermatopathology. a) Upon presentation. reproduceable. despite the building interest in Mohs. Henry “Bud” Menn. images and marks of Journal of Drugs in Dermatology (JDD). as a more extensive procedure could run into complications and produce a larger scar. Try to convince the patient to wait six months or longer before you agree to lished the first European unit in Munich. Alfred Kopf. we established the first ever “one-year” fellowship training program in Mohs surgery. a. 2. the second stage to be done to fine-tune the repair in three to six weeks. there are about 70 training This documentToday contains proprietary information. In the event that the second stage is necessary. be made without the express written consent of JDD. A Two-Stage Procedure Tell the patients in advance that wound repair requires two stages. Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . “Why not?” To this. anesthetics. he was not happy that he had to devote a full year to training since. you inform the patient that they were told this in the beginning. Dr. When it comes to revisions. However. we went on to teach rethat bothered the patient is fully resolved at six months. the patient will get programs that offer aorone-year fellowship. Publicizing Mohs Surgery In the early 1970s. good center receiving 20 to 30 applications annually. You will often discover that the imperfection Zilinsky. c.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 521 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. t(PPEMVDLo4VSHFSZJTBIFBMJOHBSU*UJTOPUBQFSGFDUTDJFODF 2009-Journal of Drugs in Dermatology. anatomy. Germany. a good doctor. Also. to tell them that this is textbook quality work. when the fibroblasts are realigned. Many physicians. A revision may not be necessary. Wound constructive surgery. Do Not Copy. who estabof correction in the maximum amount of time. to exercise their skills and ability. All Rights Reserved. use discretion. oncology. from Geissinger Medical Center. Assure your patient that you will make every effort to minimize the size and visibility of the scar . the better. and prosthetics. you can answer that they have such healthy skin that it was not necessary. c) Post reconstructive surgery after one year. I recommend wide undermining and a simple closure when possible. a second stage will not be necessary. it was impossible to get an article on Mohs surgery published. Your goal as a surgeon should be to do the minimum amount One of the earliest trainees was Dr. please contact JDD immediately. and tried-and-true. 3. When approached with an article on the subject. limit activities and sun exposure post-surgery. nobody wanted a Mohs surgeon nor would they have known what value the technique represented. a good patient. classic repairs. Gunther Burg. at that time. 6% were recurrent. A two-year study during this period. 17 patients (each of whom had one lesion each) were female (3 lesions being primary and 14 recurrent). Metastasis of BCC Of my first 3. If you feelayou have obtained this copy please contact JDD Recurrence in Young Women In a two-year study of 19 patients between the ages of 21 and 30 who were referred for Mohs surgery for basal cell carcinomas.9 cm. and two patients were men. Sheldon Pollack and I published two cases involving basal cell carcinomas invading cartilage. patients with large exophytic neoplasms however. Ear – the antibiotic can reduce the chance of pseudomonas. the antibiotic can possibly reduce swelling which causes the pain in the ear. Almost 10% (8. 8 Mohs surgery and Antibiotics There are two sites for which I strongly recommend the use of antibiotics prophylactically. Dr. Recurrence Related to Sex of Patient Recurrence was higher in men (3. be due to less frequent self-examination by men.743 men (53. that hospitalization was notimmediately. This document contains proprietary information. Dr. I believe we are seeing an increase in the number of younger patients for a variety of reasons. Penalties Apply Over 5 cm . Cases Referred for Mohs For the first 20 years of my practice.7 Do Not Copy. In men. Hand – all lesions are treated post-operatively with oral antibiotics because. Also. we noted that four patients developed metastases. Tumor glides along the perichrondium and extends laterally further than it appears clinically. one with a primary lesion and the other with a recurrent lesion. One sees tumor in the bone when radiation has been unsuccessful in eradicating a skin cancer. radiation was used as the last resort when other methods had proved unsuccessful. 5-Year Cure Rate Related to Size Under 1 cm . This difference could. etc. Men claimed they had them a shorter time. 50. If you ever had a patient with a pseudomonal infection.99. In the early days. Two hundred seventy-one males had primary lesions and 363 of the lesions were recurrent.&t*446& 13PCJOT Early Observations in Mohs Sex of Patients Men have more skin cancers than do women.they extended only short distance in depth andillegally.211 women (46.863 patients. Age of Patients My youngest skin cancer patient was 10 years old and my oldest was 101.2% I have seen photos where considerable deformities hadReserved.170 cases showed that 199 were primary in females and 337 were recurrent. utility workers. are aware of skin cancers and come to see physicians sooner. historically. fishermen. men were usually in the driver’s seat and women in the passenger seat of an automobile. female patients would seek medical attention sooner.82%) were greater than 5 cm. Size of Lesions Almost half of the lesions were between 2 and 2.2%) than women (1.2%). a newer further study revealed that both men and women both had lesions more frequently on the left side of the face than the right. at least historically men have been employed outdoors more than have women (as construction workers. Twent-five percent of patients said they had the lesion(s) for less than one year. but rarely do they invade bone.6% BCC in Bone I have found BCCs involving the periostium. Men had significantly larger lesions than did females. One of my early studies showed that men had more lesions on the left side of the face and women had more lesions on the right.4% of cases were primary lesions and 49. images and marks of Journal of Drugs in Dermatology (JDD). June Robinson. All Rights and ears. the lesions were larger and present for a longer period of time. Today it is rare to see lesions as large as 2-3 cm. postal carriers. It is possible that women had originally been treated less aggressively for fear of scars or disgurement. recording 1. This was attributed to the fact that. you would never want to see another since the infection becomes increasingly difficult to treat.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 522 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. women felt their lesions were present longer. Exophytic Lesions theofearly days.92. probably. Perhaps this is because. Patients are more aware of growths on their face and body. 15 years later. However. necessary. without the express written consent of that JDD. perhaps. in one study 3. People are spending more time in the sun. for aesthetic reasons.8%) versus 3. BCC in Cartilage It is extremely rare to see BCC involving cartilage. the swelling and pain in the hand is likely to be more severe than in another part of the body. In the March 1980 issue of the Journal of the American Academy of Dermatology.8%). Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . I soon learned No reproduction orIn use any portion of the contents of these materials may be were madehospitalized. Duration of Lesions The average duration is 2 to 5 years. been caused by removal of cartilage from noses © 2009-Journal of Drugs incosmetic Dermatology. In the past 20 years I have seen none. One of the signs of carcinoma in the bone is pitting of the outer table. Today I would estimate that less than 3% are recurrent lesions. should an infection occur.resulting in more exposure to the sun. 14%. Schering-Plough © 2009-Journal of Drugs in Dermatology. which he submitted to a plastic surgery journal. but the following case caused me to reconsider my thinking on the subject. I had been taught not to leave large wound areas uncovered. Allmany Rightsof Reserved. please contact JDD immediately. Journal of Dermatologic Surgery (Figure 5). I saw no other option but to create one.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 523 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. which I saw as a crucial contribution to medical literature. I had produced 24 video In 1975. images and marks of Journal of Drugs in Dermatology (JDD). many today would be surprised to know that the American Society for Dermatologic Surgery was originally not happy with the idea of my establishing the Journal of Dermatologic Surgery. There is no doubt that the establishment of the journal was the turning point in the acceptance of dermatologic surgery worldwide. occurred in the retroauricular area (50 cases. publication was monthly. which this wascopy an illegally. with concave surfaces yielding the best results. Looking back. It was summarily rejected on the grounds that it was inconceivable that dermatologists could practice surgery. An oft-neglected factor that may explain the high recurrence in auricular neoplasms has recently been reported by Dr. It was removed by Mohs surgery. John Zitelli published an excellent article highlighting this topic and indicated how to predict which type of wound would produce good results. and established it ascontains a 501 (c) (3) nonprofit organizaThis document proprietary information.&t*446& Recurrences by location following Mohs P. Keratoacanthoma In the late 1960s. George Popkin. Today. youIndex feel you have obtained Dermatologic Surgery extraordinary feat in those days. myorcolleagues and I of published four Nofirst reproduction use of any portion the contents of issues these materials may be made without the express written consent of JDD. I had forgotten how many achieved had good cosmetic results. The interest in dermatologic surgery exploded in the early 1980s. one of the foremost plastic surgeons of the time. Bailin et al. In one interesting case. the journal was acquired by Elsevier and then. I co-authored a paper with Dr. the tumor was quite large in depth and periphery. and prior to the presentation. I arranged sponsorships with leading pharmaceutical companies to provide a complimentary subscription for every dermatology resident in the U. The patient was referred for Mohs surgery. with the support of Dr. He then returned to my office concerned about a possible new lesion. With an educational grant. there was a patient with a KA of the right cheek who had been treated three times. the wound had completely granulated in. Robins In a 1981 article in Head & Neck Surgery. the journal is highly referenced and one of the leading journals in dermatology. all KAs were treated as SCCs. keratoacanthomas (KA) were considered benign conditions that were not always treated aggressively. Penalties Apply journal. reviewed over 100 of such cases (of the 6.9 The ear is composed of different embryonic fusion planes and it has been determined that malignant neoplasm often follow these planes. the journal grew to five issues and. a peer-reviewed showed these tapes at their booth at the AAD annual journal. by the American Society of Dermatologic Surgery (ASDS).S. The type of proposed repair frightened the young patient to such an extent that he was lost to follow-up for 18 months. tion. This acceptance and acknowledgement of its merits would have been delayed for many years without it. The year. From that point on. I reported that the highest recurrences. by the fourth year. Granulation Early on. I recently lectured on the subject of wounds left to granulate. Other dermatological journals had no interest. Upon examination of the scalp. Do Not Copy. I launched the tapes on all aspects of dermatologic surgery. rejected it based on the reasoning that a similar article was published a year previously and that there would not be any interest.and pre-auricular regions are probably related to the embryonic development of the auricle. as none existed. Journal of and the journal was listed in Ifthe Medicus. A young man with a defect about 6” in diameter on the scalp involving the periosteum (but not involving bone) was referred to me for Mohs surgery.000 cases I had had in my career). where he was warned that it could be dangerous to leave this wound to heal by granulation because of the risk of bone necrosis and imminent infection. A very short time later. clinically and histologically. a mass in the right neck was diagnosed as metastatic SCC. After losing money for 20 years. recently. since it is difficult to distinguish between the two. and was cosmetically acceptable. (the first time this had been done). FIGURE 5. With the support of the Schering-Plough Corporation. for many years we had the journal translated and distributed in Europe and South America. at that time. Thomas Reese. the patient was referred to the plastic surgery clinic at NYU Medical Center for repair. No channels existed for the advances we were discovering daily. Because of the size of the surgical effect. Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . The patterns of growth and spread of cutaneous carcinomas of the auricular and post. The second year. 7 recurrences). Gabrielle (”Coco”) Chanel returned from a vacation in the French Riviera with a tan. Pathak and the photobiology committee.000 middle schools. and has been held on a biennial basis ever since. Certain forms of tuberculosis were also treated with sunlight exposure. the SCF raises the awareness of skin dollars research or advanced cancer and promotes sun-safecontains behavior around information. instituted in 1987. MB.” a program designed to help consumers recognize and select safe and effective sun-protection products. I do not regret all the walls I had to tear down and that standard has led to corporate promotion of sun-safe to prove that Mohs surgery is the most effective technique for products. detecting. the SCF is the only foundation that is solely dedicated to the Since 1981. served as camps nationwide. cancers ofcontact the skin. It has been featured as a useful guide to sun protection products on such programs as “Good Morning America” and in the Washington Post.or sweat-resistance. awnings and umbrellas.training. Play it Safe in the Sun and the tabloid Sun the members of which whose members were authorities on the Day News. At the World Congress meetings. In 1979. The Skin Cancer Foundation Thirty years ago. the highest available SPF infeel sunyou screens 12. Spanish. my patients complained that no one had ever told them the sun was harmful to their health. an expert in SPF based at Harvard University. Sunlight was the accepted therapy for rickets. To this day. This has not been the case. Madhukar Pathak. Los Angeles Times and Reader’s Digest. As a matter of fact. SPF 15 became the minimum acceptable standard for CONCLUSION sun protection among the medical and scientific communities. illustrated book. another 501 (c) (3) nonprofit organization. International outreach and advocacy came to the forefront with the establishment of the International Advisory Council. associated with a carefree lifestyle and “upper crust” social status. All Rights Reserved. and laundry products that provide UV protection for fabrics. With the same year. designed to educate the public and the medical profession about preventing.The If you have was obtained this Skin copy illegally. and treating skin cancer. including pharmaceutical employees. Over the years we’ve supported number scientific studies relating to No reproduction or use of any portion of the contents of these materials may be made without a the expressof written consent of JDD. messages and educational activities to elementary schools and PhD. The SCF Fellowship proas a core organizational member of the National Council on © 2009-Journal of Drugs in Dermatology. most of the SCF’s funding has come from appreciative patients (including two patients who donated total of $1. There are 23 countries represented on the Council. Robins dation’s newly instituted “Seal of Recommendation. doctors from all over the world share the most recent information on skin cancer.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 524 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. when the sun’s ultraviolet radiation (UVR) was suggested as a medical treatment for many ailments. Cancer Foundation was the first organization to recommend and The Children’s Sun Protection Program was another effort we promote the use of a sun screen with an SPF number of 15.&t*446& meetings to groups of 50-100 dermatologists. and is now carried on more than 570 sun-protection products. I founded The Skin Cancer Foundation (SCF). SCF—International Outreach. The Seal of Recommendation is granted to such products as sunglasses and window glass film. a then-common childhood disease caused by Vitamin D deficiency. and claims of water. Members are involved in public education and work to make skin cancer education a priority around the world. including Australia. phototoxicity and contact irritancy. Many patients were older and had grown up with the belief that sun exposure was healthy. the foundation assembled a photobiology committee. soon tans were erroneously. ed to include an online program for 20. Portugal. These videos were also on loan by Schering-Plough.5 million). so the foundation presents its newest materials on skin cancer to journalists in addition to the local government and professionals. Brazil. Israel. Research & Campaigns The first World Congress on Cancers of the Skin (which the SCF co-sponsors with organizations from the host nation) took place in 1983. over 500 physicians attended a conference of the World Congress of Cancers of the Skin in Tel Aviv. Looking back. Do Not Copy. Penalties Apply In 1979. and we have translated the literature into French. in the 1920s. The Skin Cancer Foundation has also funded nearly fight against skin cancer. nurses and educators. sun-protective clothing. the Philippines and Sweden. In May of this year. Our children’s programs have been expandthe committee’s chair from its inception until his death in 2005. desiring that “healthy look. Local press coverage of this event is important in raising skin cancer awareness among the population. The committee verifies the claims of the products submitted by confirming test results on SPF levels. to all practicing dermatologists. That began early on to reach this vulnerable population. Thanks to the efforts of Dr. In addition. watching these tapes in their entirety was not uncommon. An SPF of at least 15 was required to obtain the foun- Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . has awarded hundreds of thousands of Skin Cancer Prevention. P. the fashionable view of sun tanning was originally popularized when. and 100 pilot research and clinical studies. Ireland. we were the first organization to provide sun safety effects of ultraviolet radiation on the skin. At the time. please JDD immediately. German and Italian.” These beliefs hailed back to the late nineteenth and early twentieth centuries. albeit popularly. using mineral oil and iodine to enhance a suntan. many of the members of the dermatology community were skeptical. the world. without charge. as they foresaw that the SCF would compete with the Dermatology Foundation for funds. As an independent organization. images and This document proprietary marksto of doctors Journal offor Drugs in Dermatology (JDD). gram. 6. images and marks of Journal of Drugs in Dermatology (JDD)... my staff. Robinson JK... Robins P... languages.... Henkind P. my technicians have shared in this feeling of achievement.... Chemosurgery: My 15 years of experience.. American College of Mohs Micrographic Surgery (now American College of Mohs Surgery).. Lew R.. J Dermatol Surg Oncol. J Dermatol Surg Oncol. the late Dr. Predicting recurrence of basal-cell car- Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F ... congresses.... J Dermatol Surg Oncol. Tucker HM. with their knowledge and training. founder and past president. please contact JDD immediately.. I am also happy to say that. Robins the treatment of skin cancers... Bailin PL.2(6):499-505... Menn H... I am also pleased that doctors I have trained have gone on to train others... 1974..... J Dermatol Surg Oncol. the American Academy of Dermatology.. in the dermatologic societies of over 14 countries.... My intention in presenting this paper is to encourage any of you to continue to pursue your objectives even in the face of lack of support or outright rejection.... films......... 1981. Robins P and Albom M... J Dermatol Surg Oncol.... videos.... Arch Dermatol.... Cutaneous carcinoma of the auricular and periauricular region.......com _______________ Do Not Copy.. 1984. Rigel DS. 4.. Chemosurgery for the treatment of periorbital malignancy...1(1):49-51.... past World Congresses on Cancers of the Skin. organizations that I have contributed to and been responsible for have helped not only patients. my colleagues and doctors in other specialties. 7... International Society of Dermatologic Surgery.. and to show that dermatologists. American Society of Dermatologic Surgery. Prior recipients have included Dr.. J Am Acad Dermatol...... Tromovitch TA and Stegman SJ... Suite 209 New York. Day CL Jr.110(2):231-232. All Rights Reserved..Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 525 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6.. chairman. Robins holds (or has held) the following positions: professor Emeritus of Dermatology. Mohs’ surgery – fresh tissue technique.. obtained thisthis copy illegally. 1975........ MD 345 East 37th Street.. 1971... Doctorrobins@yahoo..... which helped make these projects come to fruition: Dr. If you you haveHistorically. Recurrent basal cell carcinomas in young women. He counts as his of greatest accolade honorary No reproduction or use any portion of the contents of memthese materials may be made without the express written consent of JDD. 1980...106(11):692-696.. workshops. Robins P. Robins P....... (212) 263-7222 Fax: . 1975. A multivariate analysis of factors affecting wound-healing time.. my nurses.. Robins P... I have been very fortunate that in my years practicing Mohs surgery many patients with skin cancers have been cured.. but the lay public.. New York University’s School of Medicine. Pollack SV. Dr. All the training programs.... 2...... are best equipped to perform that function... cinomas treated by microscopically controlled excision: A recurrence index score... and honorary member.1(2):37-41. If your goals have merit.75(6):1228-1235..... 5.. journals..7(10):807-810. Robins has been conferred honorary memberships © 2009-Journal of has Drugs in Dermatology..1980.... Wood BG.7(10):779-89... (212) 686-5842 E-mail:. past president. Dr. Robins P and Albom MJ.10(3):219-221.... Trans Am Acad Ophthalmol Otolaryngol.. 1981..... he had the opportunity to lecture in over 34 countries four different This document contains proprietaryininformation..... honor has been given to few Americans... Arch Otolaryngol. bership in the Spanish Academy offeel Medicine..... NY 10016 Phone: ..... Levine HL.. Penalties Apply Editorial note: Dr... Robins P. REFERENCES 1.. 3. To date..... Microscopically controlled excision of skin tumors. ADDRESS FOR CORRESPONDENCE Perry Robins. Friedman RJ. The Skin Cancer Foundation. George Popkin and the late Dr.. Alfred Kopf.. co-founder and past president.. my secretaries... in time you will prevail.... Alexander Fleming (the inventor of penicillin). Daniel Baker.. ACKNOWLEDGEMENTS 8.. founder and president.... Philip Casson.. Deep appreciation is extended to the following physicians for their unending support and encouragement....&t*446& P.. 9. Invasion of cartilage by basal cell carcinoma. secondary infection. MI 48220 Marketed and Distributed by Triax Pharmaceuticals. (See PRECAUTIONS . Pediatric Use: Safety and effectiveness in pediatric patients have not been established. Pregnancy: Teratogenic Effects: Pregnancy Category C: Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. caution should be exercised when topical corticosteroids are administered to a nursing woman. Conditions which increase the risk of systemic toxicity include the application of more potent steroids. TA100. and bilateral papilledema. LLC Cranford. Information for the Patient: Patients using topical corticosteroids should receive the following information and instructions: 1. It is for external use No reproduction or use of any portion of the contents of these materials may be made without the express written consent only. striae and miliaria. and the addition of occlusive dressings.PEDIATRIC USE. 4.2 times the human topical dose). an increased number of cervical ribs and one fetus with clubbed legs was reported. prolonged use. Studies to determine mutagenicity in Salmonella ryphimurium strains TA98. Parents of pediatric patients should be advised not to use tight-fitting diapers or plastic pants on a child being treated in the diaper area. irritation. Carcinogenesis. hypertrichosis. and TA92 with prednisolone and hydrocortisone have revealed negative results. and dryness. and fetal resorptions were observed in rats treated with 10% hydrocortisone butyrate. or for longer than two weeks. For rabbits. a dose-dependent increase in fetal resorptions was reported in rabbits. 3. This medication is to be used as directed by the physician. Children may absorb proportionally larger amounts of topical corticosteroids and thus be more susceptible to systemic toxicity. folliculitis. Inc. maceration of the skin. LLC Cranford.1%) Cream is indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. topical corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. document contains proprietary information. topical corticosteroids should This instituted. In teratogenicity studies. These reactions are listed in an approximate decreasing order of occurrence: burning.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F Rapid relief and restoration. itching.. Some corticosteroids have been shown to be teratogenic after dermal application in laboratory animals. LLC. Manifestations of adrenal suppression in children include linear growth retardation.2 and 2 times the human topical dose. HPA axis suppression. topical administration of 1% or 10% hydrocortisone butyrate in an ointment to pregnant Wistar rats (gestational days 6-15) or New Zealand white rabbits (gestational days 6-18) resulted in no teratogenic findings. ACTH stimulation test. without a visible trace Do Not Copy. please contact JDD immediately. 3 times the human topical dose) on gestational days 9 through 15.) If irritation develops. Therefore. NJ 07016 Protected under U. use over large surface areas. the use of an appropriate antifungal orand antibacterial agent of should be instituted. Manifestations of intracranial hypertension include bulging fontanelles. Locoid Lipocream® (hydrocortisone butyrate 0. skin atrophy. Patients should be advised not to use this medication for any disorder other than for which it was prescribed. ADVERSE REACTIONS: The following local adverse reactions are reported infrequently with topical corticosteroids but may occur more frequently with the use of occlusive dressings. 5. HPA axis suppression. including itching. Ferndale. irritation. be occlusive. favorable response does not occur promptly. Mutagenesis. However. images marks Journal ofIf aDrugs in Dermatology (JDD). The doses given to rats are approximately 8 to 80 times the human topical dose based on a body surface area comparison (assuming 100% absorption).S. RightsPRECAUTIONS Reserved. Allpreparation. Contraindicated in those patients with a history of hypersensitivity to any of the components of the preparation. dryness.V. Chronic corticosteroid therapy may interfere with the growth and development of children. and absence of response to ACTH stimulation. hyperglycemia. NJ 07016 By Ferndale Laboratories. licensed to Triax Pharmaceuticals.. Nevertheless. Patients should report any signs of local adverse reactions. manifestations of Cushing’s syndrome. the corticosteroid should be discontinued until the infection has been adequately controlled. and Impairment of Fertility: Long-term animal studies have not been performed to evaluate the carcinogenic potential or the effect on fertility of topical corticosteroids. in large amounts. headaches. delayed weight gain. 2. the doses given were approximately 0. Laboratory If you feel you have obtained this copy illegally. Increased resorptions were also noted in Wistar rats given subcutaneous administrations of hydrocortisone butyrate (9 mg/kg/day. as these garments may constitute occlusive dressings. Avoid contact with the eyes. In CS mice given subcutaneous administrations of 1 mg/kg/day (0. (See PRECAUTIONS. Nursing Mothers: It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. Prolonged use may produce reversible HPA axis suppression. perioral dermatitis. be discontinued and appropriate therapy In the presence of dermatological infections. and intracranial hypertension have been reported in children receiving topical corticosteroids. Manufactured for Triax Pharmaceuticals. Tests: The following tests may be helpful in evaluating the HPA axis suppression: Urinary free cortisol test. For Dermatological Use Only BRIEF SUMMARY—Please see full Prescribing Information for complete product information CONTRAINDICATIONS: Topical corticosteroids are contraindicated in those©patients with a history of hypersensitivity of the components of the General: Systemic absorption of topical corticosteroids has produced reversible 2009-Journal of Drugs toinanyDermatology. Penalties Apply The mid-potency cream with the highest concentration of barrier-enhancing lipids Locoid Lipocream® (hydrocortisone butyrate 0.) Rx only Locoid Lipocream is a registered trademark of Astellas Pharma Europe B. and glucosuria in some patients. May cause local adverse reactions. hypopigmentation. Systemically administered corticosteroids are secreted into breast milk in quantities not likely to have a deleterious effect on the infant. OVERDOSAGE: Topically applied corticosteroids can be absorbed in sufficient amounts to produce systemic effects. The treated skin area should not be bandaged or otherwise covered or wrapped of as toJDD. There are no adequate and well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids. low plasma cortisol levels. Patent LC-1008-02 Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page 131 B100 Rev 09/07 A BEMaGS F . acneiform eruptions. Cushing’s syndrome. allergic contact dermatitis.1%) Cream should not be used extensively on pregnant patients. Pediatric patients may demonstrate greater susceptibility to topical corticosteroid-induced HPA axis suppression and Cushing’s syndrome than mature patients because of a larger skin surface area to body weight ratio. Thus.4.1-5 While the lesions are most typically asymptomatic. AFP was both safe and effective for the treatment of the vascular. skin texture.1%) and skin laxity. 51. may be of value in PC. 70. lateral cheeks. 1 The most ity of patients (80−90%) had skin phototypes I or II.8 years) years). we set out to assess the efficacy of PC with AFP.1 The most common variant of positive reactions to fragrance mix and/or Balsam of Peru. lence of the condition was estimated © to2009-Journal be 1.. For erythema/telangiecatasia.6%). Pulsed dye.1-5 The pathogenesis of PC remains unknown.6%. Treatment sessions were administered at 6−8 week intervals with blinded physician photographic analysis of improvement at 2 months post-treatment. the mean score improved 66. further supporting the theory that it represents a distinct Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . For cosmetic outcome.7% (95% CI: 62.1 The mean duration from sult from a delayed hypersensitivity reaction to perfume and/or onset to diagnosis was 6. tosensitivity in the condition’s pathogenesis demonstrated that reproduction or use than of anymales portion(61. with symptoms been theorized that the reticular pigmentation observed may reincluding itching.3%.7 of the contents of these materials may be made without the express written consent of JDD. 8 PC is characterized clinically by a reddish-brown reticulate pattern of pigmentation. skin texture.8 It has Nearly half of patients (46%) were symptomatic. burning and flushing.05). the distribution of lesions on sun-exposed skin suggests a central pathogenesis mechanism for damage induced by ultraviolet radiation. 25% of patients with PC had also involved in 38% of patients.8 In PC present was the erythemato-telangiectatic clinical type (58%). 52.6%. associated with concomitant sparing of the photoprotected submental area. there was contact a significantly greater frequency of positive reactions If you feel you have obtained this comcopy illegally.5% (95% CI: 49.e. burning and flushing.1-4 The condition occurs most frequently in fair-skinned middle aged men and women. with an average of 1. 69.8%. KTP and Argon) are limited by side effect profiles and/or efficacy. 1-5 The majorlower inNo females (47. associated with telangiectasias and atro- PC is characterized by distinct histologic and ultrastructural features. please JDD immediately.1 including fragrance mixes.1-4 phic changes of the skin. the photopatch testing group.3%) dyschromia. the mean score improved 65.1 a positive photopatch test for any of the allergens tested. 71.1) -BTFSBOE4LJO4VSHFSZ$FOUFSPG*OEJBOB $BSNFM */ ABSTRACT Background: Previous laser treatments for Poikiloderma of Civatte (PC) (i. dyschromia. Results: The number of treatments required for improvement of PC ranged from 1 to 3. 55.91. INTRODUCTION Background P Do Not Copy. the estimated prevaof Drugs in Dermatology.7% (95% CI: 48.1-5 This document contains proprietarywas information.6 Other factors which have been implicated in the pathogenesis of the disease include genetic predisposition. and oftentimes produces significant dyschromia and skin texture abnormalities. none of the patients with PC had followed by the mixed type (22%) and the pigmented type (20%). images and marks of Journal of Drugs the in Dermatology (JDD).Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F JUNE 2009 527 70-6.2 years. mon pattern of distribution is the ‘v’ and sides of the neck as well to fragrances in the PC group relative to the control group (chi2 as the upper chest.0% (95% CI: 60. skin laxity and cosmetic outcome.8 Specifically.4%).%. pigmentary and textural components of PC. however. Design: A prospective pilot study for PC in 10 subjects with a series of 1−3 treatment sessions.&t*446& COPYRIGHT © 2009 ORIGINAL ARTICLES JOURNAL OF DRUGS IN DERMATOLOGY Treatment of Poikiloderma of Civatte With Ablative Fractional Laser Resurfacing: Prospective Study and Review of the Literature &NJMZ15JFSOFZ. progressive (82%) and irreversible. and upper chest. 66. Conclusion: In this prospective study.7% (95% CI: 61. Intense Pulsed Light. including itching. Given the high degree of safety and efficacy of ablative fractional photothermolysis (AFP) for photoaging. Penalties Apply oikiloderma of Civatte (PC) is a common benign condition with symmetric involvement of the neck.4% among dermaThe mean age at diagnosis significantly A recent study evaluating role of contact sensitivity and photologic patients.7-8 In clinical and epidemiologic studies of PC. creping and laxity after AFP has not been reported with prior laser treatments for PC. All Rights Reserved.%BOE$8JMMJBN)BOLF. there are case reports of associated symptoms.7%. The degree of improvement observed in wrinkling. erythema/telangiecatasia.1The face (preauricular and parotid gland) were value = 3. hormonal changes related to menopause and phototoxic or photoallergic reactions to chemicals in fragrances or cosmetics. 55. p<0.8%) at 2 months post treatment. Evaluation was performed of five clinical indicators.1 The disease course was slowly cosmetic ingredients. patch testing with a standard series. the microthermal zones of injury in the dermis produced by the NAFP also likely result in random hits to dermal vasculature. such as photoaging17-18. It is likely that both of these hypotheses of chromophore targeting of dermal vasculature and microthermal zones of heating resulting in random hits to dermal vasculture play a significant role in reducing telangiectasias after treatment with FP. a mottled appearance. different tissue compartments (i.12-14 While NAFP demonstrated modest improvements in conditions. NAFP may lead to microvascular destruction with clinical benefits of improved erythema and skin texture. is the dermal blood vessels. dyschromia and overall skin texture of the neck.9 The most constant findings were swelling and disruption of the collagen fibers as well as focal degeneration of the collagen bundles. flattened (84%) epidermis with hyperkeratosis (92%) and occasional follicular plugging (34%).17 in which the authors demonstrated histopathologic evidence of damage to dermal vasculature in patients undergoing NAFP. A histologic study analyzing the characteristic feature of PC in 50 patients revealed consistency in features of an atrophic (62%). provide morphologic evidence for the primary role of ultraviolet radiation in the pathogenesis of PC. The most likely target for absorption with the 1550 nm NAFP device. Reliant Technologies. cryotherapy..9 can be selected as targets. Hantash et al29 described the first use One of the most successful treatment modalities to date for PC of a novel “ablative” CO2 fractional resurfacing device (AFP) has been intense pulsed light (IPL).15. telangiectasias and skin texture abnormalities which characterize PC and the skin signs of photoaging.15 In several studies.9 The overall consistent changes in the dermal connective tissue. dermal melanin and sebaceous glands) at various skin depths Given the greater efficacy in the literature in the cutaneous signs of photoaging after AFP.&t*446& &5JFSOFZ $)BOLF and unique entity.15 The treatment parameters. including epidermal and dermal pigmentation and blood ing occurred for at least three months post-treatment. however. argon laser and potassium titanyl phosphate (KTP) laser have yielded largely unsatisfactory effects.30 IPL is noncoherent light. Penalties Apply Most recently in 2007.23 and PC. mode.15. severe pigmentation and scarring.29 In the initial in vivo studies including pulse duration.16 The authors postulated that with NAFP. contents of these materials may be made without the express written consent of JDD. as PDL targets primarily the vascular component of PC.29 With vessels in the papillary and reticular dermis. 26-29 texure.16 Herein. Car- Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . images and marks of Journal of Drugs Dermatology (JDD).12-14 However. in a broad waveablation and coagulation which extends through the stratum length spectrum of 515 to 1. we present the first prospective study of AFP for PC. PATIENTS AND METHODS The study protocol conformed to the guidelines of the 1975 Declaration of Helsinki and was approved by the St.200 nm. telangiectasias and surface texture able density and depth but which results in a confluent array of abnormalities. given its versatility in targetwhich produces an array of microthermal zones of a customizing superficial pigmentation.16 Through targeting dermal blood vessels. patients with significant textural and pigmentary abnormalities were only minimally improved with non-ablative energies. 26-29 we postulated that greater improvement in PC would be achieved with AFP relative to that previously reported with NAFP.16 The authors reported that two weeks after a single treatment with non-ablative fractionated photothermolysis (NAFP). blood vessels.10-11 NAFP technology demonstrated significant improvement in the treatment of diverse facets of the cutaneous signs of photoaging.22. adverse effects of PDL treatment of PC include purpura. clearance rates of greater than 75% of©both telangiectasias the greater degree of injury with fractionated CO2 and a greater and prolonged effect on in collagen remodeling. in the treatment of PC. Do Not Copy. corneum. To date. Mountain View CA) as reported by Behroozan et al. please contact JDD immediately. All Rights Reserved.9 The blood vessels were also invariably dilated in the majority of specimens (96%). significant improvement was effected in degree of erythema.16 Support for this hypothesis comes from a recent study by Laubach et al. there has been no single effective treatment modality for PC. dyschromia and laxity) manent hypo.17-18 Recent studies utilizing Pulsed dye laser (PDL) at 585 nm wavelength with fluences of 6-7 J/cm2 with a 5-mm spot size have shown significant efficacy.16 patients required multiple treatments to achieve significant results and even with multiple treatments. in the cutaneous signs of photoaging (rhytids.e.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 528 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6.9 The most consistent and prominent feature across all specimens (100%) was the presence of diffuse solar elastosis in the papillary dermis. significant Thishave document proprietary information. attempts to treat this condition by using electrosurgery.22. no significant change is typically observed in the pigmented component of the condition.16 In addition.30 The latest advance in laser technology reported to have significant improvements in the clinical appearance of PC is nonablative fractional photothermolysis (NAFP.and hyperpigmentation well asobtained changesthis in skin If you feelas you have copy illegally. delay between pulses and fludemonstrating the histologic and clinical effects of this protoence can all be varied to heat-specific targets and varying skin type ablative fractionated CO2 device. Hantash et al. epidermis and dermis. relative to NAFP. including the dyschromia. Vincent Hospital Institutional Review Board and Ethics Committee. several recent studies have demonstrated greater clinical improvement side effects have beenorreported IPLoffor including perNo reproduction use of anywith portion thePC. In the past.12-14 In addition. Fraxel SR. including prominent solar elastosis and degeneration of collagen bundles. including mottling and scarring. hyperpigmentation beencontains observed. 2009-Journal of Drugsand in Dermatology. confirmed with immunohistochemistry that persistent collagen remodeldepth. Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 529 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. mean score decreased and final date of follow-up. with an average of 1. Do Not Copy. blinded physician evaluprovement of PC ranged from 1 to 3. a history of keloid scarring. Dermal Optical Thermolysis (DOT) Laser (Eclipse Med. 71. and descriptive statistics of all outcomes were considered. Patients with PC usually seek treatment for cosmetic reasons to mean percentage change and 95% confidence intervals (CI) improve the erythematous.8%) (Table 1). Indiana.3%) (Table 1). During treatment. skin decreased from 3. 69. All patients were required to be available for longitudinal study over the course of the threeto-nine month study treatment and post-treatment evaluation.6marks at 2 months postoftreatment (p<0. For © 2009-Journal Drugs in Dermatology. a history of isotretinoin use in the year prior to laser treatment. Figures 3a-3b. All Rights as the percentage improvement between the initialoftreatment skin texture. current pregnancy.5% mean improvement (95% CI: 49. to 1. (95% CI:be 48. as were treatment number (Table 1). 500 pitch. Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F .600 nm) at settings of 20 Watts.7 pre-treatment to 1. RESULTS The trial was a prospective pilot study for the treatment in 10 patients presenting to our office for desired treatment of PC between July 2008-November 2008. A quartile scale post-treatment (p<0.2 at 2 months post treatment (p<0. pigmented and finely wrinkled apwere calculated. the degree of improvement was calculated 66. The number of treatment sessions required for significant imAt two months after the final treatment. skin laxity and overall cosmetic DISCUSSION outcome) the absolute score change. an ablative fractionated CO2 laser (10. Written informed consent was obtained from all patients prior to enrollment. CT) at a setting of 5 at a distance of 3–4 inches from the skin surface. which resolved within 48-72 hours post-treatment.4 pre-treatment If you feel you have obtained this copy illegally. skin texture. A bupivicane/lidocaine/tetracane topical local anesthetic mix was applied 30 minutes before treatment.6%) (Table 1).05). &5JFSOFZ $)BOLF The paired t-test was utilized to test the change in each clinical indicator score (erythema.55. the mean score provement in five clinical indicators: erythema. scores were recorded the date of final follow-up. patients reported minimal pain.&t*446& mel.6 at 2 months post treatFor each patient.0% mean improvement (95% CI: was utilized where ‘1’ signified no signs of skin change associat60. the mean score No reproduction or use of any portion of the contents of these materials may made without (Table the express written of JDD. A total of 10 patients with PC were treated with an ablative fractional photothermolysis device. Penalties Apply Cosmetic outcome of improvement in the features of PC was assessed by a blinded physician on photography at the 2 month posttreatment visit. Post-treatment 66. skin texture. a one-week post-operative visit and a two-month post-treatment visit. mean score decreased from 3.4 pre-treatment to and the final visitThis at two months after the final treatment.4 sesation of photographs was utilized to assess the degree of imsions (Table 1).6%. For erythema/telangiecatasia.2 at 2 months texture. Treatment was administered to the neck and upper chest with the Dermal Optical Thermolysis (DOT) Laser (Eclipse Med. skin laxity and overall cosmetic outcome) from baseline to month 2 posttreatment. This period involved a pre-operative evaluation. Clinical images of patients demonstrating improvement in PC The percent change in score was calculated as the score differare shown in Figures 1a-1b.05) for a 65.70. Only one patient experienced prolonged erythema and pruritus which persisted at the one week post-treatment visit which resolved completely by one month post-treatment.7% mean improvement (95% CI: 61. which was alleviated with the use of the topical and cold air anesthesia.1%) 1). Statistical Analysis decreased from 3. ma. Minimal post-operative erythema and edema were noted by patients. For each category (erytheures 4a-4b and Figures 5a-5b. skin laxity and overall cosmetic outcome. edema and pruritus were assessed at one week.2 at 2 months post treatment (p<0. P-values less than 0. at baseline on the date of the first treatment.6%.4%) for each category were recorded. proportion.55. with PC. known allergy to topical lidocaine anesthetic or any cosmetic procedure in the area(s) of treatment in the 12 months prior to the study. A quartile scale was utilized where ‘1’ signified no signs of skin change associated with PC and ‘4’ signified significant change in skin associated with PC. Pre-treatment scores were recorded from 3. the mean score decreased ed with PC and ‘4’ signified significant change in skin associated from 3. Shelton. 51. please contact JDD immediately.7 pre-treatment 1. Patients were seen for evaluation at one week and at two months after the procedure. images and of Journal Drugs in Dermatology (JDD).05). dyschromia.6 pre-treatment to a mean of 1. Figures 2a-2b. Incidence of side effects of erythema. dyschromia. 500 milliseconds.7%. raw percentage change.05).05 were considered statistically significant. Forced cold air was administered during treatment for anesthesia utilizing the Zimmer Cooler device (LaserMed. Dallas TX).7% mean improvement (95% CI: 62. In addition.3%. 1. For skin consent laxity. For dyschromia. the pre-treatment and post-treatment scores ment (p<0. Figence divided by the baseline score. Dallas TX).7% mean improvement document contains proprietary information. For overall cosmetic outcome.The distribution. The treatment area was thoroughly cleansed before the procedure with a gentle skin cleanser. The number of treatment sessions was determined by the degree of clinical improvement with treatment. dyschromia. theReserved. 52. given at six-to-eight-week intervals.8%. Patients received a series of 1–3 treatment sessions.05). Patients were excluded from the study if they had active infections. &t*446& &5JFSOFZ $)BOLF TABLE 1. % improvement 75% 75% 75% 75% 75% No reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD.3% 4 4 4 4 1 1 2 months post-treatment % improvement # treatment sessions Patient #4 2 61 y/o Caucasian Female pre treatment # treatment sessions 2 Patient #5 68 y/o Caucasian Female pre treatment 4 © 2009-Journal1 of Drugs in Dermatology. 1 2 months post-treatment This document contains proprietary information. Patient #6 73 y/o Caucasian Female pre treatment 3 3 4 4 4 2 months post-treatment 2 2 3 3 2 % improvement 33% 33% 25% 25% 50% # treatment sessions 1 Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . All Rights 1Reserved. Penalties Apply 4 4 4 4 4 1 1 2 2 1 75% 75% 50% 50% 75% 3 4 3 3 3 2 months post-treatment 2 2 3 3 2 % improvement 33.3% 50% 0% 0% 33. please contact JDD immediately. Treatment of Poikiloderma of Civatte with Ablative Fractional Photothermolysis Age/Gender Patient #1 Erythema/ Telangiectasia Dyschromia Texture Skin Laxity Overall Cosmetic Outcome 54 y/o Caucasian Female pre treatment 4 4 4 3 4 2 months post-treatment 1 1 1 1 1 % improvement 75% 75% 75% 75% 75% # treatment sessions 3 Patient #2 71 y/o Caucasian Female pre treatment 4 4 4 4 4 2 months post-treatment 1 1 1 1 1 % improvement 75% 75% 75% 75% 75% # treatment sessions 1 Patient #3 57 y/o Caucasian Female pre treatment Do Not Copy.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 530 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. # treatment sessions 1 If you feel you have obtained this copy illegally. images and marks of Journal of Drugs in Dermatology (JDD). 7% 52.4 3.3% 66.8% 2 months post-treatment % improvement # treatment sessions Mean pre-treatment score 95% CI: 1 69.11-14 With the small diameter of ectatic blood vessels in PC (0. This document contains proprietary information. 71.05 p<.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 531 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6.0% 33. copy illegally.05 p<.7% 49. Penalties Apply 4 4 3 3 4 1 1 1 1 1 75% 75% 66.0% 66.55. No reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD.6%.55.&t*446& Patient #7 &5JFSOFZ $)BOLF 62 y/o Caucasian Female pre treatment 3 3 2 2 3 2 months post-treatment 1 1 1 1 1 % improvement 66.1–10 skin of the adjacent neck.4 3.1 mm) which are primarily in pigmentation of the submental region with the hyperpigmented the papillary dermis and short thermal relaxation times of 0.4% 62.6%. with minimal risks of scarring and dyspigof 450 μsec.7% 66.7% 66.7 Mean post-treatment score 1.2 p value: pre vs post-treatment score p<.7% # treatment sessions 1 Patient #9 53 y/o Caucasian Female pre treatment 4 4 4 4 4 2 months post-treatment 1 1 2 1 1 % improvement 75% 75% 50% 75% 75% # treatment sessions 1 Patient #10 50 y/o Caucasian Female pre treatment Do Not Copy. One of the Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . the optimal settings for PDL treatment of PC were with a cation of the condition.0% 66. rupture characterized by thermal absorption of oxyhemoglobin. All Rights 48. Most importantly.7 3.7% 75% Average # Sessions Erythema/ Telangiectasia Dyschromia Texture Skin Laxity Overall Cosmetic Outcome 1. For PDL treatment of PC. fluences of 5-7J/cm2 and short pulse durations be relatively risk free.3% 61.3%.05 p<.11-14 For optimal improvement of PC.8%.70.1% Reserved.2 1.6 3.05 Mean % Improvement 65.2 1. vessel treatment sessions to minimize discomfort and cost.0% 50. images and marks of Journal of Drugs in Dermatology (JDD).7% 50.7% 51. Given the cosmetically sensitive loμsec.4 3.6 1.7%. contact JDD immediately.7% 50.7% # treatment sessions 1 Patient #8 65 y/o Caucasian Female pre treatment 3 3 2 3 3 2 months post-treatment 1 1 1 2 1 % improvement 66.05 p<. Geronemus20 reported resolution of photothermolysis. the physician attempts to match the normal (PDL) with a 585 nm wavelength. visible laser irradiation is the wavelength of 95% of the redness associated with PC following four treatments choice as it targets both hemoglobin and melanin.7% 66. both pigmentary and vascular 10-16 With selective components of the condition must be affected. and that results are obtained in a limited number of lation of small and superficial vessels characterizing PC. pearance that occurs in visibleIfareas on you the have neck obtained and upper firstplease treatment modalities studied for PC was pulsed dye laser you feel thischest. it is critical that an effective treatment spot size of 5 mm.11-14 While the PDL can result in photothermal coagumentation.6 1.6% © 2009-Journal60.5% 66. leads to the clinically undesirable side effect of purpura. of Drugs in Dermatology. In addition. were seen in 111 out of 135 patients (82%) after an average of three treatments. In a case report.30 Treatment fluences ranged between 32-36 J/cm2. including a post-treatment mottled response and hypervasculature. Wheeland and Applebaum and IPL. significant comPDL treatment of PC with improvement vascularity andmaterials plications associated both of theseconsent technologies.21 ablative fractionated CO2 laser technology (DOT Laser. TX). swelling and crusting as well as more modest improvements in skin colorGoldman and Fitzpatrick11 reported variable success rates with ation and texture with IPL. settings of 5-6J/cm2 and overlapping pulses of 360 μsec. Weiss et al. They observed a significant improvement of more than 75% in the telangiectasias and hyperpigmentation in the majority of patients (82%).15.22 In total. Behroozan et al. with 16 of 125 patients demonstrating 75% improvement after just a single treatment. Similarly. which lasted from 24 to 48 hours.82 (scale 0-5) improvement after an average of 2.and light-based failed to respond. Dallas. pigmentation as well as to effect improvements in trophic scarring in one of four patients. contact JDD immediately. Penalties Apply FIGURE 2a-2b.78 treatments (range 1-5).&t*446& &5JFSOFZ $)BOLF Intense pulsed light (IPL) has also been widely reported for PC with the advantages of the broad spectrum of visible and infrared light affecting both hemoglobin and melanin. adverse efskin texture and tightening. Dallas. Eclipse Med. the primary side effect observed included erythema and swelling immediately after treatment. In the largest patient series to date.22 reported five-year experience with treatment of the vascular and pigmentary changes of poikiloderma of Civatte with IPL. usually resolving within three to four days. Similarly. Herein. utilizing where higher fluences (5-7J/cm2) were noted to correlate the increasing risk of depigmentation.30 Of the remaining patients.16 demonstrated significant improvement in PC after a single treatment with nonpatients treated with PDL for PC in a study in the Netherlands. effects included a post treatment burning sensation and purpura While significant improvement in PC can be achieved with PDL 12 reported persisted for 7-10 days. with 6-7 J/cm2 and a 450 μsec pulse. Eclipse Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F .30 In terms of side effect profile.5 to 3. epidermal atrophy and hypermelanosis Given the limitations of these previous laser. Pre (left) and Post (right) treatment of Poikiloderma of Civatte in a 54-year old Caucasian female at 2 months after 3 treatment sessions with Ablative Fractional Photothermolysis (DOT Laser. the two endogenous chromophores affected in the condition. treatment side © 2009-Journal of Drugs in Dermatology. Pre (left) and Post (right) treatment of Poikiloderma of Civatte in a 54-year old Caucasian female at 2 months after 3 treatment sessions with Ablative Fractional Photothermolysis (DOT Laser. images and marks Journalofofthe Drugs in Dermatology (JDD).22 Do Not Copy. in order to simultaneously treat the pigmented and vascular component of poikiloderma.30 Similarly. includirregular pigmentation after treatment withhave a 585 nm PDL ing please transient prolonged purpura and permanent depigmentaIf you feel you obtained this with copy illegally. Rusciani et al. significant adverse events were modalities for PC. However.30 Each patient received three treatments at 3-week intervals.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 532 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6.30 A marked 75-100% reduction in poikiloderma lesions was observed in 142 of 175 patients (81. where vascular ectasias responded to treatment.5 μsec with a pulse delay of 10 to 20 μsec. the introduction of FP with its ability to target noted. ablative fractionated photothermolysis (NAFP).22 A significant proportion of the overall treatment effect was seen after the initial treatment.30 PDL treatment of PC. of review literature demonstrates This document contains proprietary information.0%). TX).30 Only three patients experienced blister formation which gradually resolved in seven days without pigmentary disturbance or scarring.15.22. however. No reproduction or use of any portioninofboth the contents of these may be made withoutwith the express written of JDD.30 FIGURE 1a-1b.22 The overall results for patients were grade 3. the cutoff filter parameters utilized initially were a 515-nm filter and a pulse duration of 2 to 4 μsec. Eclipse Med. Energy was delivered in double or triple-pulse trains of 2. may represent an ideal treatment fects of severe depigmentation were noted in six out of eight approach. All Rights Reserved. a significant reduction of 75-100% in the hyperpigmentation and telangiectasias associated with PC. tion associated with PDL and transient erythema. 14% presented with a clearance of 50-74% and 5% presented with a slight improvement from 25-49%.30 Mild purpura was noted in 32 of 175 patients.22. reported the treatment of 175 patients with PC with IPL. The degree of improvement obhyperpigmentation. 3. Poikilodermie reticule pigmentaire du visage et du cou.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 533 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. Pre (left) and Post (right) treatment of Poikiloderma of 1. Graham R.4 treatment sessions was needed to achieve 67% improvement in cosmetic outcome with ablative fractional photothermolysis. mechanism of action of fractionated laser resurfacing in PC is 7. predicted a greater and prolonged effect on induction of new collagen and remodeling of dermal collagen resulting in greater improvements in skin laxity and texture. Pre (left) and Post (right) treatment of Poikiloderma of Civatte in a 53-year old Caucasian female at 2 months after 1 treatment session with Ablative Fractional Photothermolysis (DOT Laser. TX). Stavrianeas NG. 2. Specifically. Georgala S. Stavrianeas Georgala S. Katoulis AC. 1995.and light-based modalities for PC. All Rights Reserved. Hantash et al. The Dermatol Venerol Rev. Eclipse Med. TX). creping and laxity after AFP has not 6. TX).16 with added benefits of 241. 2000. crusting.29 demonstrated that with AFP. our prospective study of AFP reported the additional benefits of significant improvement in skin texture and laxity. the safety profile of AFP on the neck makes this new technology particularly promising. Am J Clin Dermatol.29 Given the histologically documented effects of FP on dermal vasculature and collagen remodeling. after AFP the majority (7 out of 10) of our patients had 50-75% 233:1210. Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . Dallas. Pre (left) and Post (right) treatment of Poikiloderma of Civatte in a 57-year old Caucasian female at 2 months after 2 treatment sessions with Ablative Fractional Photothermolysis (DOT Laser. DISCLOSURES The authors have no relevant disclosures or conflicts of interest. ablative fractional photothermolysis has been demonstrated to achieve greater improvements in dyschormia and rhytids associated with photoaging relative to the original generation of non-ablative fractional devices. Poikiloderma of Civatte. images and of Journal of DrugsNG. al. improvement in skin texture and skin tightening. Eclipse Med. ment session with Ablative Fractional Photothermolysis Laser. in Dermatology A clinical and without epidemiological study. et(JDD). Graham-Little EG.6:165-173. an average of only 1. additional validation is needed with this and other ablative fractionated devices to better elucidate the safety and efficacy of AFP for the treatment of PC. In addition.24:385-7038. Med. Poikilodermie-Civatte. marks Katoulis AC. Familial cases of poikilopurely speculative. Ann Civatte in a 53-year old Caucasian female at 2 months after 1 treat© 2009-Journal(DOT of Drugs in Dermatology. please 2005. Sboukis D.27. a controlled microthermal zone of injury could be induced with stimulation of the wound healing response by adjacent intact skin. Br J Dermatol. Stavrianeas NG. Do Not Copy. However. Poikiloderma of Civatte: This document contains proprietary information. Dallas. given the limited scope of our study. Civatte A.19(4):444-448. Genetic implications in its pathogenesis? Clin Exp at varying skin depths leading to improvement in skin erytheDermal 1999. ma and texture in addition to simulation of collagen remodeling and neo-collagenesis. REFERENCES FIGURE 5a-5b. 1989.&t*446& FIGURE 3a-3b. Pérez-Bernal A. Given the historical reports of purpura. improvement in skin laxity and 9 out of 10 patients had 50-75% 5.26. scarring and permanent hyperpigmentation on the neck after treatment with other laser. Management of facial improvement in skin texture. Dallas. J Eurconsent Acad Dermatol No reproduction or use of any portion of the contents of these materials may be made the express written of JDD. we have achieved improvements in illegally. If you feelsimilar you have obtained this copy contact JDD immediately. Hell been reported with prior laser based modalities for PC. Muñoz-Pérez MA. 4. With the greater degree of injury with AFP technology. 1923.23-29 the rapid improvement in PC after treatment with this technology further underscores the versatility and potential for novel applications of this unique technology. 1928. relative to the previous case report of NAFP. What is poikiloderma of Civatte? Practitioner. Dallas. &5JFSOFZ $)BOLF Most recently. served in skin wrinkling. TX). Dermatol Syphilol.29 Utilizing human forearm skin in vivo.1(5):261-268. Penalties Apply FIGURE 4a-4b. 40:231surface pigmentation and vasculature. Eclipse Med. Katoulis AC. but may include microvascular destruction derma of Civatte. Similar to reports of rapid response to treatment with Intense Pulsed Light. Venereol. Hantash et al.6:605-620. Camacho F. Clark RE. 13... Prospective split-face trial of a fixed spacing array computed scanned fractional CO2 laser versus hand scanned 1550nm fractional for rhytids..... Meijs MM. 2007... Kapadia B... Alster TS.. 2002. Use of a micro-fractional 2940 nm laser Civatte with the potassium titanyl phosphate (KTP) laser.... 1990. Skin responses to fractional photoEmail:. Wanner M. Motta A. Dermatol Surg... 15. Applebaum J..55(6):234-5 Raulin C. can Society for Laser Medicine and Surgery Conference.34(8):1048-1053.. 13400 N......... Kissimee. Br J Dermatol. IN 46032 molysis for treatment of poikiloderma of civatte. In: 2008. William Hanke. Cassuto D. Hindson C..proprietary Treatmentinformation.. 10... 14. Br J Dermain the treatment of wrinkles and dyspigmentation. 2006.33(1):23-28.. J Eur Acad Dermatol Venereol... Dermatol Surg. 18.. Treatment of poikiloderma of Civatte with Dermatol Surg. Meridian Street. please contact JDD immediately.140(6):1191-1192. St... Cutaneous Laser Surgery.. 27. 19.. Scrimali L.......... Tanzi EL. Fitzpatrick RE. Novel use of erbium:YAG (2... Dermatology......550-nm erbium-doped fiber laser... Suite 290 Behroozan DS. Geronemus R. Jimenez-Acosta F.... Arch Dermatol. et al.... Lasers Surg Med.... 21.. Beasley K.. Abstract presented at Ameri- Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F .net _______________ thermolysis. 29... FL. Swann M....... Evaluation of the role of can Society for Laser Medicine and Surgery Conference. 17. 12..39(2):96-107... cwmhanke@sbcglobal. Stavrianeas NG. Resolution after ADDRESS FOR CORRESPONDENCE treatment with the pulsed dye laser. Blok FA. Treatment of poikiloderma of 28. 1994. Greve B.34(8):1112-1114. Goldman MP. 1999:19-178.. Grema H. Er:YAG versus CO2 ablative Katoulis AC... Phone: . Flashlamp-pumped pulsed dye laser ther2007. 25. Barnette D. J Cutan Laser Ther.. loderma of Civatte. 23. Stavrianeas NG..34(3):314-319... In vivo histological evaluation Louis: Mosby. April 2008. Ross V... Chan HH.32(2):298-301... Fractional photothermolysis for the treatment of telangiectatic matting: A case report. Alster TS.. Glaich AS. 2008. Monk BE..26(9):823-827.38(2):142-149. the pulsed dye laser: A series of seven cases. Weiss MA. Civatte using intense pulsed light source: Seven years of experience...... Abstract presented at AmeriCivatte: A histopathological and ultrastructural study... Dermatol Surg... Fractional phototherCarmel. FL. 2008.. Poikiloderma of Civatte......... 2006.1999... 24...940-nm) laser for fractional ablative photothermolysis in the treatment of photodamaged facial skin: A pilot study..34(5):426-438. Weiss RA. C. Fractional photothermolysis: Treatment of facial and nonfacial cutaneous photodamage with a 1. Poikiloderma of Civatte.... Fino P.1(1):45-48.. Sirago P... Lasers Surg Med.Treatment of poikiloderma of Civatte with the pulsed dye laser: A series of patients with severe depigmen© 2009-Journal of Drugs in Dermatology. Panayiotides JG. Menichini G. Hantash BM. Fax: . et al.. 9. &5JFSOFZ $)BOLF Katoulis AC...147(3):493-497..9(2):101-103.. Goldberg LH. Foulds IS. Katsarou A.&t*446& 8.. Bedi VP.. 11.. 2000.. April Goldman MP.. Sink RK. 2007. Dermatol Surg.. Weiss R.... 1990. (317) 660-4901 Laubach H. Treatment of poikiloderma of 16.. of poikiloderma This document contains images and marks of Journal of Drugs in Dermatology (JDD). Odo LM........ Haywood RM. 26... Abstract presented tol. Wheeland RG.. Herron GS.. If you feel you have obtained this copy illegally.32(2):78-87.. Laser treatment of vascular lesions. N C Med J. Fitzpatrick RE. tation. 20...126:547548. Cotterill JA.. Poikiloderma of fractional resurfacing: A split face study. Fractional photothermolysis of residual hemangioma. et al.. Weiss M..214(2):177-182.. Penalties Apply 22. Batta K.20(10):1248-1251. MD... 2008. Rius F. April 2008.. J Dermatol Surg Oncol. Yagima Odo ME. Dai T. (317) 660-4900 2006. contact sensitization and photosensitivity in the pathogenesis of poikiKissimee. et al.. Goldberg LH... Dermatol Surg. reproduction use of pulsed any portion the contents of these materials may be made without the express written consent of JDD.. Lasers Surg Med. All Rights Reserved. et al. 2004.. 16.. Fractional photothermolysis: A new concept for cutaneous remodeling using microscopic patterns of thermal injury. Lomeo G..... Friedman PM..... apy for poikiloderma of Civatte.. J Cosmet Laser Ther. 1999...... Glaich AS. of No Civatte with an or intense lightofsource. Rusciani A.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 534 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6.... Lapidoth M. 2007. de Rie MA..16(1):1230. Blankenship TM.. Kissimee. Lasers Surg Med. editors... Manstein D. et al. Goldman MP. IPL techology: A review.. Do Not Copy.. at American Society for Laser Medicine and Surgery Conference. FL. of a novel ablative fractional resurfacing device.. MPH 2003.. 3% at work: POWERFUL EFFICACY FOR MORE CHALLENGING ACNE1 BASELINE 2* Do Not Copy. Please see brief summary of Prescribing Information on adjacent page. noninferiority. investigator-blinded. dryness. 0. www.8%). the majority of cases were mild to moderate in severity. and decreased thereafter. 12-week. images Results seen asproprietary early as week 12 and marks of Journal of Drugs in Dermatology (JDD). 2 © 2009-Journal of Drugs in Dermatology. multicenter.6%). If you feel you have Proven tolerability *A phase 3b. skin discomfort (5. and total lesions1.com Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . scaling. Of the patients who experienced cutaneous irritation (erythema. and/or stinging/burning) during the clinical trial.A BEMaGS Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page F Proudly Supported by Differin® Gel. controlled clinical study of patients 12 to 35 years of age with acne vulgaris (N=172). Adverse events that occurred in greater than 1% of the subjects included dry skin (14. All Rights Reserved. and desquamation (1. No reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD. occurred early in treatment.differin. Penalties Apply WEEK 12 Patient 116 Highly effective for noninflammatory. inflammatory. please contact JDD immediately. 2 obtained this copy illegally.0%). This document contains information. Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page . + # ! # $& #) "$ &"# '% "! * "& "$ "# & "$ "$ !&$( ! 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Galderma Laboratories.27 1>6*7 6254 .=8 * 7>.P.P. .=..P...2<.A..com of Galderma Laboratories...@1. L. . = 2< 78= 478@7 @1.7 # ! . 27 1>6*7 6254 . www.5 2< *-6272<=.A.*>=287 <18>5. ..>0< *..*><.Differin and Galderma are registered trademarks..>0 2< .. 6*7B -.. L. L.A.P.=1..differin. =12< -. ©2007 Galderma Laboratories..<270 @86*7 ©2009 Galderma Laboratories.. L.. . *0.7..//..58@ =1.=2?.=B *7. $*/. 8/ .2.<< 27 9.7=< +.-2*=. 9*=2. Freeway .<=*+52<1. L.7 . 78= +.. 1*?.- Galderma Laboratories.P. N. . . =8 -.< 8/ *0.2*=.5 -2.85-.7=< *0.<987.*+8?.*.-2//. TX 76177 627. Penalties Apply Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F .<=*+52<1.78= 27.<< 27 0.. *7....- DIF-888 in USA 11/07 Do Not Copy..< 8/ # ! .=< B... =1. 5272. Fort Worth. <>+3..7.. 1*?. Freeway Fort Worth. 78= +. 14501 14501 N. TX 76177 DIFF-039 Printed05/09 *7.=B *7.*5 <=>-2..=1.5>-. @1.//.7 .=< $*/.2.=2?.=..B .. <>+3. 9*=2.7=5B =1*7 B8>70. suggested. multicenter.JDIFMJ. On the basis of the results of this study.&t*446& COPYRIGHT © 2009 ORIGINAL ARTICLES JOURNAL OF DRUGS IN DERMATOLOGY Treatment of Pruritus in Mild-to-Moderate Atopic Dermatitis With a Topical Non-Steroidal Agent 4UFGBOP7FSBMEJ. _−bisabolol. double-blind.9 RESULTS Eighty-nine Caucasian patients with mild-to-moderate AD were enrolled: 38 males (42. Statistical analysis revealed that differences between T0 versus T1.2.1–6 However. shea butter and tocopheryl acetate. sponsor-free. The three main ingredients contained in this product are glycyrrhetinic acid. hyaluronic acid. six weeks later (T2).9 mm from baseline). Other ingredients include: allantoin. and Rajka and Langeland in 1980 and 1989. Pruritus severity was evaluated by means of a 0-100 mm Visual Analogue Scale (VAS). Three main ingredients are contained in this product: glycyrrhetinic acid.3%). study on the anti-pruritic effect of Atopiclair in adult patients with mild-to-moderate AD. please contact JDD immediately. The Median Visual Analogue Scale (VAS) values were: at the start of the study (T0). METHODS Diagnosis and severity of AD was based on criteria proposed by Hanifin and Rajka. Rightstimes Reserved. Atopiclair showed efficacy in relief of pruritus in adult patients with mild-to-moderate atopic dermatitis. double-blind. This article presents an open.4DC 3PTTBOB4DIJBODIJ.001).9 years).JMBO *UBMZ C &VSPQFBO*OTUJUVUFPG%FSNBUPMPHZ . Change in VAS at the beginning of the study. respectively. appliedAllthree daily for six weeks. 20 10 0 VAS Pre-study VAS 3 Weeks Later VAS 6 Weeks Later VARIABLE FIGURE 1. study on the anti-pruritic activity of this product in adult patients with mild-to-moderate atopic dermatitis.%B B *OTUJUVUFPG%FSNBUPMPHJDBM4DJFODFT 6OJWFSTJUZPG. hyaluronic acid. capryloyl glycine.BOHJBHBMMJBOE3FHJOB&MFOB . Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . The product contains no parabens. multicenter.BHHJPSF1PMJDMJOJDP . If you feel you have obtained this copy illegally. median VAS was 24.7. two randomized. Neither other topical 40 products phototherapy/sunlight exposure were allowed. Primary objective of the study was the evaluation of pruritus after three and six weeks of treatment. INTRODUCTION A ® Do Not Copy. vehicle-controlled clinical studies clearly indicated that the product has efficacy in the treatment of AD.4. Two previous randomized.1 mm (–14. three weeks later (T1). peanut oil. images and marks ofnor Journal of Drugs in Dermatology (JDD).6 mm (–23. vehicle-controlled clinical studies provided evidence that Atopiclair is effective in the treatment of atopic dermatitis. limited. shea butter and tocopheryl acetate. median VAS was 34. median VAS was 48. perfumes or proteins.5 This article presents the results of an open. so far. although mild in severity. T0 versus T2 and T1 versus T2 were highly significant (p<0. sponsor-free. 30 reproduction or use of any portion of the contents of these materials No may systemic medications were used and only aof cleanser was No be made without the express written consent JDD. Side effects (local burning) were relatively common.4 mm from baseline).5 mm. telmesteine and Vitis vinifera extracts.JMBO *3$$4'PVOEBUJPO 0TQFEBMF.S. _−bisabolol. This document contains proprietary information. capryloyl glycine. Patients were examined after three (T1) and six weeks of treatment (T2). with an age ranging from 18 to 42 years (average age: 19. by Graceway 50 Pharmaceuticals.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F JUNE 2009 537 70-6.8 Informed written consent was provided by each patient. telmesteine and Vitis vinifera extracts.7%) and 51 females (57. sold as Zarzenda® in Europe via Intendis) was © 2009-Journal of Drugs in Dermatology.%C -VJTB-VOBSEPO. for which it was also named “GRA/Tel/Vv. Literature data for the agent are. Penalties Apply MEAN SCORE topiclair is a topical non-steroidal anti-inflammatory agent for the treatment of allergic diseases of the skin.” Other ingredients are allantoin.%1I%B 1BPMP%F. three weeks later and six weeks later. Atopiclair® (marketed in the U.JMBO *UBMZ ABSTRACT Atopiclair® (Zarzenda®) is a topical non-steroidal anti-inflammatory agent for the treatment of allergic diseases of the skin. such as irritant/allergic contact dermatitis and atopic dermatitis (AD). 4 mm from baseline). Paired t-test of VAS 3 weeks (T1) and 6 weeks (T2) later. Sixty-three patients (70. T0 versus T2 and T1 versus T2 were highly significant (p<0. 48. In all ofimmediately.603 MEAN SCORE 50 VAS 3 Weeks Later (T1) 24.603 10 VAS 6 Weeks Later 0 20 VAS Pre-study VAS 3 Weeks Later VAS Pre-study (T0) VARIABLE PAIRED VARIABLES FIGURE 2.001) (Figures 1-5).143 30 34. please contact JDD uct. median VAS was 24. © 2009-Journal of Drugs in Dermatology.5 mm (baseline) to 34.540 34. MEAN SCORE 40 30 20 10 FIGURE 3.or Twenty-six stopped thematerials by 13 Sixexpress (6.5%) because of you lowhave efficacy of the the treatment. product was reported This document proprietary information. and six patients (6. Penalties Apply 24.7%) written of these 13 patients No reproduction use of any patients portion of(29.1 mm (three weeks later) to 24.540 48. Repeated ANOVA measures. Paired t-test of VAS pre-study (T0) and 3 weeks later (T1). multicenter and based on a large group of evaluable patients). median VAS decreased from 48.5 mm (range: 34-64 mm).8%) contains concluded the study and were Burning atJournal the sites of application of the(JDD). images and marks of of Drugs in Dermatology considered evaluable. DISCUSSION In the group of evaluable patients.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 538 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. three weeks later (T1).603 25 20 15 10 0 0 VAS Pre-study (T0) VAS 6 Weeks Later (T2) VAS 3 Weeks Later (T1) PAIRED VARIABLES PAIRED VARIABLES FIGURE 4. without the consent of JDD.001). Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F .9 mm from baseline).1 mm (range: 12-76 mm) (–14. All Rights Reserved. VAS 6 Weeks Later (T2) FIGURE 5. These results are notable in consideration of the fact that Atopiclair is not a topical corticosteroid.6 mm (range: 12-58 mm) (–23. which were negative. median VAS was 34.143 30 20 24.143 35 30 Do Not Copy.6%). Atopiclair was effective in the treatment of pruritus in adult patients with mild-to-moderate AD.2%) the contents of these maypatients be made(14.540 50 40 MEAN MEAN SCORE 40 34. eight patients (9%) because of low adhesion to the protocol patch tests with the agent.&t*446& 50 47FSBMEJ 1%F. six weeks later (T2). these patients it was possible to perform If you feel obtained thisprodcopy illegally. In fact. stopped study: 12 patients (13. Paired t-test of VAS pre-study (T0) and 6 weeks later (T2). median VAS at the start of the study (T0) was 48. Statistical analysis revealed that differences between T0 versus T1. Despite the methodological characteristics of this study (open. although sponsor-free.6 mm (six weeks later) (p<0.JDIFMJ 34DIJBODIJ --VOBSEPO 48.7%) because of side effects. . 2006.4.&t*446& This study confirms the results of other clinical studies recently reported in the literature.. Its position within a topical paradigm for the treatment of atopic dermatitis..5 In a study by Belloni et al. allantoin or hyaluronic acid. Abramovits W...6 Furthermore... after 50 days of treatment. A multicenter.. randomized.. Aitken RC.... Exogenous Dermatol..5... ® MAS063D (Atopiclairor )... vehicle-controlled studies indicated that this agent achieves significant activity against pruritus. Gover M.. Abramovits W... 1992.. 2007. 1994:23-35.4... the presence of these compounds in numerous topical agents that actually possess a low effectiveness against pruritus would support the hypothesis that the anti-pruritic effect of this agent is due to telmesteine..document Hafeez ZH.. In research by Abramovits et al....92(Suppl):44-47............ Rajka G. ADDRESS FOR CORRESPONDENCE Stefano Veraldi.144(Suppl):13-14.12:67-74... vehicle-controlled If you feel you have obtained this copy illegally. vehiclecontrolled study to evaluate the efficacy and safety of of MAS063D (Atopiclair®).. Lerner EA.. A double-blind.. study. Grassi L.. In: Bernhard JD... Efficacyinformation.6 47FSBMEJ 1%F. 3. The anti-pruritic effect of Atopiclair may be due to the presence of several compounds... 1969. PhD Institute of Dermatological Sciences University of Milan Via Pace 9 20122 Milan. it was demonstrated that this agent inhibits the release of leukocyte collagenases and elastases..it Do Not Copy. 1989.. New York: McGraw-Hill. Atopiclair nonsteroidal cream. 2005... a median reduction of VAS of 58 mm. vehicle- Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F ....... Langeland T.. of a topical agent. the active product induced.. Moretti M. Veraldi S.. © 2009-Journal of Drugs in Dermatology. Hanifin JM. Diagnostic features of atopic dermatitis..62(10):989-993.... such as Vitis vinifera extracts... Grading of the severity of atopic dermatitis.. 11... All Rights Reserved.. Boguniewicz M. 8. Mechanisms and management of pruritus. 2:115-119.... Maibachproprietary HI.. Bisetti A...1... Penalties Apply As previously mentioned..... 54(Suppl):AB84... Eur J Dermatol. Skinmed.....Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 539 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6.2..5 In particular..7 to 1. 4.. This contains images and marks of Journal of Drugs in Dermatology (JDD). glycyrrhetinic acid. in comparison to 21 mm of the vehicle. Abramovits W. although mild in severity: in fact. Expert Rev Dermatol. Chemical mediators of itching..+39/02/55035109 Fax: .....6%).4(6):369..4. Abramovits W. side effects were limited burning... ______________ stefano. double-blind.2. Acta Derm Venereol... 9..5(3):236-244.. 2006.. The latter was rather common (13 out of 89 = 14......2. Proc R Soc Med..... two randomized.... itch severity (VAS score) decreased from 2. Rajka G.. However.... induced irritant contact dermatitis. Riv Ital Biol Med... vehicle-controlled.. 6... J Drugs Dermatol.. Hebert A... Belloni G.10 which are well-known chemical mediators of pruritus11 and are over-expressed in AD... Acta Derm Venereol.. please contact JDD immediately..2:301-305... Atopiclair™. Boguniewicz M.+39/02/50320779 E-mail:.... Patch tests demonstrated that the not a sensitizer. 5.... which lead to the increased proliferation of keratinocytes as well as the synthesis and release of pro-inflammatory and “pruritogenic” cytokines.... only six stopped treatment.. A randomised. Perlmutter A..15(1):31-36.. 2. Pinelli S. double-blind. in the treatment of mild to moderate atopic dermatitis.3 (p=0... Un nuovo farmaco mucoattivo con attività anti-proteasica: La telmesteina..use in the treatment laurylofsulphateNo reproduction of any portion of of sodium the contents these materials may be made without the express written consent of JDD.. 10..... 2005. A multicenter randomized...001)...... 2003. Measurement of feeling using visual analogue scales. to local patients patients agent is Further studies are necessary to confirm our results and to understand the anti-pruritic effect of Atopiclair in AD.veraldi@unimi.... DISCLOSURES None of the authors have any conflicts of interest to disclose. MD.. REFERENCES 1. This is an N-carboxy4-thiazolidine carboxylic acid which inhibits metalloproteases MMP2 and MMP9. _-bisabolol.... ed.. Itch..... Italy Phone: . 7.JDIFMJ 34DIJBODIJ --VOBSEPO controlled clinical study to examine the safety and efficacy of MAS063DP in the management of mild to moderate atopic dermatitis in adults. J Am Acad Dermatol. Gupta A... 1980.... double-blind clinical study to examine the safety and efficacy of MAS063DP in the management of AD. Villarama CD. Zhai H... PA Deborah S. FL Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . Weinkle. MD. CONFERENCE CHAIRMAN: VISIT US ONLINE AT: www. MD Professor Emeritus of Dermatology New York University Medical Center New York. images and marks of Journal of Drugs in Dermatology (JDD).A BEMaGS Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page F Define the Future of Dermatology Limited-Time Offer2009 and 1st. MD Founder. Petersburg. NY Alan Shalita. FL Do Not Copy. MD James Spencer. Bikowski Skin Care Center Sewickley. Register by July cess Pass receive the All Ac r a special to ODAC 2010 fo $699 with code reduced rate of 99 value! JDDJN – a $1. please contact miss – packed with interactive workshops.org ADVISORY BOARD: Perry Robins. MS Susan H. Rights Reserved. MD. the Orlando Dermatology &AllClinical © 2009-Journal of Drugs inAesthetic Dermatology.OrlandoDerm. NY Joseph B. live demos and presentations from JDD immediately. Bikowski. FAAD. This is anof event you can’t towithout the express written consent of JDD.5 ODAC 2010 January 15-18. MD Professor and Chairman of Dermatology SUNY Downstate Medical Center Brooklyn. FL Bay Area Medical Center Assistant Clinical Professor University of South Florida Bradenton. Sarnoff. the nation’s top thought leaders. FACP Director of Dermatology Cosmetique Dermatology Laser & Plastic Surgery LLP Greenvale. NY Director. Conference provides expert guidance to help you succeed in today’s constantly Noand reproduction or use of any portion of the contents these materials mayafford be made changing competitive environment. This document contains proprietary information. 2010 The Peabody Orlando Orlando. If you feel you have obtained this copy illegally. Spencer Dermatology & Skin Surgery Center St. Penalties Apply Now in its 7th year. 117:244-279. Salfeld JG. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther. Malignancies In clinical trials of all TNF inhibitors. Semin Arthritis Rheum. Cai A. including histoplasmosis. Abbott Park. including feel you have obtained this copy illegally.301:418-426. have been associated with reactivation of hepatitis B virus (HBV) in chronic carriers of this virus. disease.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F IMPORTANT SAFETY INFORMATION RISK OF SERIOUS INFECTIONS Patients treated with ENBREL are at increased risk for developing serious infections that may lead to hospitalization or death. candidiasis. Binding and functional comparisons of two types of tumor necrosis factor antagonists. Differences between anti-tumor necrosis factor-α monoclonal antibodies and soluble TNF receptors in host defense impairment. Neurologic Events TNF inhibitors. Transverse myelitis. Pa. Exercise caution when considering ENBREL for patients with these disorders. Etanercept: an overview. The risks and benefits of treatment with ENBREL should be carefully considered prior to initiating therapy in patients 1) with chronic or recurrent infection. All RightsIn Reserved. Patients should be tested for latent tuberculosis before ENBREL use and periodically during therapy. J Pharmacol Exp Ther. Humira® (adalimumab) Prescribing Information. 8. Solowski N. have been associated with rare cases of new onset or exacerbation of CNS References: 1. Broder M. Hematologic Events Rare cases of pancytopenia.36:159-167. Inc. Thousand Oaks. Calif. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids or were predisposed to infection because of their underlying disease. 2) Invasive fungal infections. during No and after treatment with ENBREL. Furst DE. The risk of lymphoma may be up to several-fold higher in RA and psoriasis patients. such as advanced or poorly controlled diabetes. Thousand Oaks. 3) who have resided or traveled in areas of endemic Adverse Events tuberculosis or endemic mycoses or 4) with underlying The most commonly reported adverse events in RA conditions that may predispose them to infections clinical trials were injection site reaction. demyelinating disorders (some presenting with mental status changes and some associated with permanent disability). clinical trials of all other adult © 2009-Journal of Drugs in Dermatology. images and marks of Journal of Drugs in Dermatology (JDD). Sasso EH. Ill. Tak PP. Consider discontinuing ENBREL if significant hematologic abnormalities are confirmed. including reactivation of latent tuberculosis. multiple sclerosis. Do Not Copy.49:S105-S111. Immunex Corporation. including ENBREL. 2006. 2005. Enbrel® (etanercept) Medication Guide. Tumor necrosis factor antagonists: different kinetics and/or mechanisms of action may explain differences in the risk for developing granulomatous infection. A causal relationship to ENBREL therapy remains unclear. Calif. Advise patients to seek immediate medical attention if they develop signs or symptoms of blood dyscrasias or infection. Reported infections include: 1) Active tuberculosis. Cather JC. 9. 5. coccidioidomycosis. Scallon B. 2. blastomycosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated. Remicade® (infliximab) Prescribing Information. viral and other infections due to opportunistic pathogens. et al. adverse events were similar to those This document contains proprietary information. development of signs and symptoms of infection reported in RA clinical trials. infection. optic neuritis.32(suppl 74):40-47. and 3) Bacterial. 4. The role of TNF inhibitors in the development of malignancies is unknown. such as listeriosis. Treatment for latent infection should be initiated prior to ENBREL use. 6. Beenhouwer DO. 2002. and cases of new onset or exacerbation of seizure disorders have been observed in association with ENBREL therapy. reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD. Tracey D. J Am Acad Dermatol. including ENBREL. A causal relationship to ENBREL therapy remains unclear. and headache. who tested negative for latent tuberculosis prior to initiating therapy. Enbrel® (etanercept) Prescribing Information. Goffe B. 2) who have been exposed to tuberculosis. including aplastic anemia. rather than localized. Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness. 2008. 7. ENBREL should be discontinued if a patient develops a serious infection or sepsis. Exercise caution in patients who have a previous history of significant hematologic abnormalities. please JDD immediately. Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . active infections or allergy to ENBREL or its components. Patients should be closely monitored for the indications. 3. J Rheumatol. Prescribers should exercise caution in prescribing TNF blockers for patients identified as carriers of HBV. Immunex Corporation. Wallis R. Dinarello CA. some fatal. 2003. and pneumocystosis. Penalties Apply Hepatitis B Reactivation TNF inhibitors. Patients with tuberculosis have frequently presented with disseminated or extrapulmonary disease. which may also contribute to HBV reactivation. Please see contact accompanying Brief Summary of full the possible development Ifofyou tuberculosis in patients Prescribing Information on following pages. more cases of lymphoma were seen compared to control patients. ENBREL should not be initiated in the presence of sepsis. aspergillosis. Klareskog L. have been reported. The majority of these reports occurred in patients on concomitant immunosuppressive agents. Malvern. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Abbott Laboratories. Centocor. images and marks of Journal of Drugs in Dermatology (JDD). This document contains proprietary information. No reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD. If you feel you have obtained this copy illegally.4 When released. Penalties Apply ENBREL © 2009-Journal of Drugs in Dermatology. TNF continues its normal function in the immune system1. ENBREL inhibits TNF activity 3. When bound to TNF.8 Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . please contact JDD immediately.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F ENBREL Do Not Copy. All Rights Reserved. Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F ® Enbrel (etanercept) binds reversibly to TNF 1 ENBREL continuously binds and unbinds to TNF 1. and improving physical function in patients with psoriatic arthritis. ENBREL is indicated for the treatment of adult patients (18 years or older) with chronic moderate to severe plaque psoriasis who are candidates for systemic No reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD. This document contains proprietary information.4 When released.4-6 mimicking the activity of naturally occurring soluble TNF receptors.3.7 When ENBREL is in the body. Because ENBREL suppresses the immune system. there is a dynamic and relative exchange of bound and unbound TNF to ENBREL. Please see Important Safety Information and Brief Summary of Prescribing Information on adjacent pages. it may increase the risk of infections. inhibiting the progression of structural damage of active arthritis.2 TNF plays a prominent role in the inflammatory process of plaque psoriasis and is recognized as an important target in its treatment. ENBREL can be used in combination with methotrexate in patients who do not respond adequately to methotrexate alone. TNF is biologically active and is able to perform its normal functions.1-4. therapy or phototherapy. *Psoriatic diseases are comprised of plaque psoriasis and psoriatic arthritis. All Rights Reserved.9 Do Not Copy.3 Anti-TNF therapies currently approved for psoriatic diseases* can be divided into two fundamentally different protein structures that help define their binding attributes: soluble TNF receptor fusion protein and monoclonal antibody. © 2009-Journal of Drugs in Dermatology. Penalties Apply The clinical significance of binding attributes is unknown.4. ENBREL is indicated for reducing signs and symptoms. ENBREL reduces inflammation and the signs and symptoms of moderate to severe plaque psoriasis. please contact JDD immediately. images and marks of Journal of Drugs in Dermatology (JDD). If you feel you have obtained this copy illegally.1 When bound to TNF.1.8 ENBREL. the only soluble form of a fully human TNF receptor. Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . binds to TNF trimers in a 1 to 1 relationship. Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page . !"" # $ $! . . . . . . . . . . . !"#$% . . . . . & . . . . . . . . . ' . . . ( . !)* % . . ' . . % 5+J K.3#5K+ / . +5K=+ 5. ( . % " . 0 ! % $. ( . . . . . . . . . 1 L . . . . . / . ' / . # . L 5 . . . . . . . . . / . . . 0 . . . - . ( . . L . . . # ( . . . . . . / . . . . . . . . . ( . . 5 8* . . 9 . . &:).<.< !):. % = + 3 . ( . . . . #. ( . . . . . . . . . . . ( . . . > . . . . . ( . . ( . ( 5 &9- ( . . ( . . !:?% !@?% # . ( .3 . ! " " !$ &. (& $. - (&% 3 . ( . . ((+ 0 & # #. . . . . . 3 . . . 0 . # . . > . . . . #. . . . :* /. . . . . - . % 3 ((+ 0 & . ! $. . . . # . . . ( . . . . . ( . . . ! % 4. . . . . # . . . 3 ) )@<A% > . ( !. . . . . A BEMaGS F " )& 0 +& - - +3. ( . - # . . +3. ( . . ! % . *& (( " 5 . . . . . ' . . ! ! . % E/ 5 . =F % # . ' . # B . B . . / . . . ' . . . - . . 5 . . ' &/ .3 # . . . ( . . . . . . . . . . . . ( . ! $.3 % # - ( . - &/ . % . !3C. . ( # 3C. . ( . 3C. . + 6@ /. . . . (&. . . -#.&&( . . . . . #. . 5 9< . . - . . . # . . . . A . . . ! % -# + &1$. (&1 # + &% # . . . . . 4 (& " . . . -. . . . . . . . . . # . . . . ( / . . . . . . . . . . . . . . ! ! -(&. . &&(% 5 . 0 . G5. 0 / . . . . . . D . H 5 7 Do Not Copy. Penalties Apply $ ( . # + & 5 . . . - . #. ( . . . #. ( . . 4 . 8 96@< - @ &@9@ . ! . 8 &9 % 5 . - . . < 6:&8 ))&@) - # 8- . > . . - . ( ! % #. ( . ( ! $. & &(()*% + *0& ( ( ( ( . -# + &% )))& ( # ! % $. - ( (*&% &'((& (& -( ! $. ( (& . ( &% . + . . . . 5 . -( . #.- . .( . . . . . . . . . . 5 0 . -. )*@ > B . . / ! . $+ (& ' . 0 . . . . % . +. . . . . ( . . . . -. . C . ( . . . . . -# + &% # . ! $. . . . . # . . . # 5 . . &9 ( . . . . . . 0 . # ( > B . . . ( :? . 1 . # . . . . . . . 2 . 2 . . . . . !@?% ! % % # . . . . . . ( !.3 I ) )@<A% . . . . . . . 2 3. & 0 ( . &. . . . 5 > B = #. ( . . . . . ! . ! ! $. . . % . !CD% . . . - (&% . . -. . # 5 . CD . . . . . . #. . . . . . 3 . . . . . ( # . . © 2009-Journal of Drugs in Dermatology. -# + &% . ! % -# + & $. All Rights Reserved. . . . . . . . . 4 . . / . . 0 . . CD . / This document contains proprietary information. . images and marks of Journal of Drugs in Dermatology (JDD). . ( . . . ( CD . . CD . . #.- . ( . . . #. . ( /. . No reproduction or use of any portion of the. . contents of these materials may be made without the express written consent of JDD. - ( . . 0 # . . . . ( . #. . ( . . #. . ( . / CD . ' . . (+&&1# +&&1 *. ( . ( . . please contact JDD immediately. If you feel you have obtained this copy illegally. . CD - . . . - . . . #. ( CD . / . . . . . " CD ' . # . . - . #. ( . . . . . . . CD . . ( . . . 5 5 6 . ( CD . . . + +( - . 4 . # CD . . . . . 3 -7 !37% .@- )@@- ( # . ( . - . . . # . . . . . ' . . . . ! . ( . . . . . 3 . . # . . . . . . . . . . . /. &? 5 . . . - . . . )-*::-8))-*<:& . . . . (&&&.(*& (+ (&**. (*0(. &/. / . & (*+ " 1&. &+#( . . (. &/. 0. 0(& 3 1 # . +3. ( 5 ( . .+. ( ( 0* ( ( &/ .. 0 ( (&&1 . . ! % . . . 0.(. * (& ( / . . (/. &(/ . 0 (&&2 . . . . ( . / . . . . . ( (( & . . . / . E" . . . # . !& 7 F ( ' . . *< ' . 9*@ .6 # . ( ' . . . . . ( . / . . . . ( . Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . 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Penalties Apply 7:) $ " $ ' &." $$& "> $ $$& . ! ) " + * / % Do Not Copy." $ $ $ $ $$" $" . $$& <& = $ " $ " &." . . / . "#$ 0 ' . ! H )6&% ! H 78.% ! H &)9% ! H 8)6% . 5 . . 1 5 . )? 79 9 78 . ! %GG 7& 76 9& :8 1 - 0 . ! -<5%GG 7& 7* :? 6) 3 . 1 . ! % < - . . 7) ! ) " + * / B . 7. !<5%GG ): &. &. )6 4 1 * )& )8 ): 400 6 9 )) * B . )7 )9 &9 &8 % )? . @ . 1 . / 6 9 . : ( . 3 7 : : 6 . 7 6 )& )) B 1 . ! !% . 7 6 )? )? ". ( 1 -( 7 6 &7 )8 . . / 7 & 8 * . . . 1 ( 0 . ) 6 . ' " 4 ) 8 )? )) / . . All Rights Reserved. . © 2009-Journal of Drugs in Dermatology. 88:& . + & 7 7 6 . . . . . images and marks of Journal of Drugs in Dermatology (JDD). I F 7 * 6 &9 ! )???? - % This document contains proprietary information. ? ?. . ! !% . )?? - " . ) & )8 : . # 7- any . . . )materials ) may )& : withoutD. 1 No reproduction or use of portion of the contents of these be made the express written consent of JDD. + . . 1 / 4 )? . !J"#$ L% F illegally. If you feel you have obtained this copy G5 . F please & contact ? JDD immediately. :- . . . . )))& ! !) +( 1 . . . . "#$ ' "% + - . + -C D . . . K# . . . . . - . . . . )? . . : GG5 . ! % . . -. . -<5 <5 . . -. % . * " " " "& $ . " ' $ $ 5 . -. 77 . * . . . .. 56) 7898::. . . ! . H ))? H &)7% . ) 8)8 . . )&:) & ) . . . 5 3 5 . . . . . !)?:& - % # D ( 3. ' .)7&?-)9. . 6> . . && &7 . 2 . < + . ))7& 5 . ' . )& )7 - ( . . ' . . ) 6> . " ( . = / . . 7 . E )..* F &??* 5 3 . !* 6 ' % ) -B ( A . . . - !.? - % ) . -. . -. - & ' . . . # 0 . . ! !) ' "- ( ) 5 < + / 1 . . ' "% . ?2 6.867. ! ( ) $"% 67.92 :&?))?62 :69&*6&2 7:966 .69:?2 6:?6:. . . *. D ' . = A . 0 . -. 6 . -. . . . . ! !) ' "% $' / . . ( ' . K . . ( ' . . 1 3 . 1 . . . . 4 1 . . . . . . )-***-87:-&976 . )7&? = / . # D ( 3. ______ E &??9 . . . 5 . Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F .)?) . / /. ). methtrexate. The annual cost of treating psoriasis nocyte hyperproliferation. Patients with moderate-to-severe disease are likely to benefit from systemic therapy. phototherapy. chiefly with cutaneous symptoms and has the potential devastating. In light of the chronic nature of this disease. Immunologic mechanisms are now accepted as the pathophysiologic basis for the development of psoriatic disease. particularly their adverse event profiles. please contactyears.&t*446& COPYRIGHT © 2009 ORIGINAL ARTICLES JOURNAL OF DRUGS IN DERMATOLOGY Anti-TNF Agents for the Treatment of Psoriasis -FPO). it affects an estitiation that produces psoriatic plaques was the result of keratimated 125 million people. The collection of long-term data is. Do Not Copy. Currently three anti-TNF agents — etanercept. therefore. therefore. Crohn’s disease and inflam- P Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F .8 and 7.S. Combination therapy should also be considered when managing psoriasis for such reasons as augmenting an inadequate response to monotherapy or improving tolerability.—approximately 2. but also maintains desirPsoriasis is a common disease. Conclusion: The treatment of plaque psoriasis with TNF-α antagonists is still a relatively recent addition to the pharmacologic armamentarium available to clinicians. in interpretation of data.) in 2004. Safety data also continue to be collected over the long-term.1 (HbA1c). the optimal standard tory visits to dermatologists in the United States (U. however.3% of ambulaable levels across several years. the emphasis will be on the longest-term data available. However. who treat patients with psoriasis must be cognizant of the glycemic control characterized by spot-checking fasting plasma chronic. such as 3 or 6 months.FEJDBM%JSFDUPS %FSN3FTFBSDI 1--$ -PVJTWJMMF .FEJDBM$FOUFS *OEJBOBQPMJT *OEJBOB .2% of It had long been thought that the abnormal epidermal differenthe population—have psoriasis. Long-term clinical data continue to accumulate and demonstrate sustained benefits with anti-TNF agents. physicians across several Clinical studies in diabetes emphasize If you feel you however.JSDJL. cytopenia.5 million persons in the U. From the data reviewed here. The annual cost of treating psoriasis may exceed $3 billion annually. worldwide. In fact. Combination therapy with an anti-TNF agent and phototherapy has shown considerably higher rates of response compared with either intervention alone.2 for psoriasis treatment would span years not months. cyclosporine and acitretin—also encompass several biologic agents that target immune mediators associated with the condition. According to the National Institutes of Health (NIH). All Rights Reserved. congestive heart failure and malignancies. between 5. Blood sugar levels This document contains proprietary information. an appropriate treatment model for psoriato negatively impact patients’ overall health and qualsismarks would that of used in in diabetes mellitus.2% of the population—have psoriasis. Discussion: Patients with mild disease may obtain symptomatic relief with topical agents and targeted phototherapy. Successful treatment is one that lowers HbA1c for a short period. it affects an estimated 125 million people. Penalties Apply INTRODUCTION Psoriasis and its effect on patients should not be trivialized. Differences exist among study designs and. lupus-like syndromes. infliximab and adalimumab — are FDA-approved for treatment of psoriasis. the improvements observed in the psoriasis study populations participating in clinical trials are dramatic. between 5. key safety considerations are infection. small but growing as results from newer studies emerge. images and of be Journal Drugs Dermatology (JDD). the frequency with which may exceed $3 billion annually.FEJDJOF -BT7FHBT /FWBEB ABSTRACT Introduction: Psoriasis is one of several systemic diseases that presents chiefly with cutaneous symptoms and has the potential to negatively impact patients’ overall health and quality of life.S. have motivated research and development of biologic agents. According to the National Institutes of Health (NIH). ity of life. lifelong character of the disease and of the potential for multisystem pathology.S. lifelong character of the disease and of the potential glucose but also by assessing glycosylated hemoglobin A1c for multisystem pathology.—approximately 2. accounting for 4. JDD immediately. Objective: The objective of this paper is to critically examine the anti-TNF studies to assess the efficacy and safety of the agents in patients with psoriasis and determine applicability of the data in clinical practice.%BBOE+BNFT2%FM3PTTP%0C B *OEJBOB6OJWFSTJUZ. worldwide. it soriasis is one of several systemic diseases that presents is a chronic condition that may be emotionally and physically © 2009-Journal of Drugs in Dermatology.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F JUNE 2009 546 70-6.FOUVDLZ C %FQBSUNFOUPG%FSNBUPMPHZ 6OJWFSTJUZPG/FWBEB4DIPPMPG. have obtained this copy illegally. the clinician can attempt to arrive at a satisfactory assessment of the benefits and risks of treatment with these agents. Similarly.5 million persons in the U. Physicians who treat patients with psoriasis must be cognizant of the chronic.8 and 7. Treatment strategies—which include topical treatment. prompt resolution of skin involvement. Shortcomings of the traditional agents. demyelinating disease. immediate concern of most is likely thematerials are may not be followed for just 3-month period but of are monitored NoThe reproduction or use of any portion of patients the contents of these made without theaexpress written consent JDD.3 psoriasis comorbidly occurs with other immunologic diseases such as rheumatoid arthritis (RA). 25 mg BIW. all groups vs.2% in the 50 mg BIW group. and between the 25 mg BIW etanercept and placebo groups at Week 8. 583 received at least one dose of study drug and were included in the primary analyses.&t*446& -. Etanercept: Efficacy in the Treatment Psoriasis 0. the mean level of improvement was 40. and resolution of psoriasis linked with decreased infiltration of mediators of inflammation and expression of genes for TNF-α.4.7%. 25 mg weekly.g. Patients with missing data at a given visit were assumed not to have met the response criteria for that end point.001. study (2003). Mean percentage improvement If you feel you haveof obtained this copy illegally.5 It is now accepted. etanercept 50 mg BIW to 25 mg BIW) would continue to benefit patients.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 547 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. Ninety-four percent of patients completed 12 Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . 52. interferon gamma (IFN-γ). all patients who received at least one dose placebo group (P < 0. PASI 75 had been clinical practice.9% in the etanercept 25 mg weekly group. 34%.2% in the di et al.50 mg BIW group. and written 3% in the placebo group (P < No reproduction or use of any portion of the contents of these materials be made without the express consent of JDD. In light of the chronic nature of psoriasis. The three agents that block TNF-α and are indicated for the treatment of psoriasis—etanercept. Demographic characteristics. methotrexate.0001. and missing post-baseline efficacy data were imputed using LOCF. phototherapy. and ILs. study (2005) evaluated etanercept and included assessment of a step-down dose for the group originally treated with 50 mg BIW to determine if the step-down dose (i. and 50 mg BIW groups. The median BSA affected by psoriasis was 23% and the baseline PASI was 16. These are proteins with the capacity to inhibit the autoimmune response mediated by one of the immune mediators such as B cells.0001. placebo).4 Observations that suggest immunologic mechanisms are involved in psoriatic disease include responsiveness to immunosuppressive agents such as methotrexate. Canada. 57% in the 25 mg BIW group. Reserved. In the Leonarmg BIW group. immediately..e. placebo).4.. the response rates for all three treatment groups and. compared with 14. PASI 75 response rates were 25%.6 of double-blind study treatment were included in the analyses At Week 24.5 Treatment Strategies Treatment strategies for psoriasis include topical treatments. tients in the etanercept 50 mg BIW group who had not attained disease history and severity of disease at baseline were comPASI 75 by Week 12. weeks of treatment and 88% completed 24 weeks of treatment.6 Do Not Copy. A total of 611 patients were randomized for treatment at 50 sites in the U. placebo). design. of these. Mean affected body surface area the dose reduction from 50 mg BIW to 25 mg BIW.1 The proportions of patients achieving PASI 75 were 49%. and 64. please A summary of etanercept study characteristics (e. T cells. The mean percentage improvements from baseline in PASI were statistically significant for all three etanercept treatment groups as early as Week 2.S. in cases of missing data or termination. images and marks ofby Journal of patients Drugs in Dermatology (JDD). and Western Europe. efficacy variables) is presented in Table 1.1 Patients with mild disease may benefit from topical agents and targeted phototherapy. cyclosporine. By Week 12. of these. with equal proportions completing treatment in each group.JSDJL +%FM3PTTP matory bowel disease suggest a common immunologic and/or inflammatory etiology. Of the 672 response rates for the three treatment groups during the 24 patients who were randomized. Of the 583 patients who received The objective of this paper is to critically examine the anti-TNF the study drug. infliximab and adalimumab—are the focus of this review. Penalties Apply Shortcomings in treatment of psoriasis with traditional agents motivated the quest for better treatment options and focused clinical attention on biologic agents.6% in the 25 mg BIW group. 32% did so by week 24.. At Week 24. and mean Psoriasis Area and Severity Index (PASI) was 18. the Papp et al. respectively. analyses were were either sustained or improved.4 As noted in Table 1. and 538 complettients with psoriasis and determine applicability of the data in © 2009-Journal of Drugs the in Dermatology. At Week 12. that epidermal hyperplasia is a reaction to the activation of the immune system in focal skin regions. ed the All fullRights 24 weeks of the study. and 0. Figure 1 illustrates the PASI based on last observations carried forward (LOCF). A notable observation concerned the 88 paof double-blind study treatment. 559 (96%) completed the initial 12 weeks of the studies to assess the efficacy and safety of the agents in pastudy.6 (BSA) was 28. from the baseline PASI at Week 12 was 68% in the etanercept 50 dosing.0% in the placebo group. They may be directly extracted from animal tissue or synthesized through recombinant deoxyribonucleic acid (DNA) technology. or TNF-α. 652 received at least one dose weeks of the study. all groups vs. 34%may in the 25 mg BIW group. contains data proprietary information. acitretin and biologic agents. 15% and 4% in the etanercept 50 mg twice weekly (BIW). 25 mg BIW. The necessity of treating psoriasis for the long term—often for the lifetime of the patient—requires that the clinician be especially alert for adverse effects that may emerge with extended periods of treatment. despite parable between the groups. and biologics. all contact groupsJDD vs. 44% and 59% for the etanercept 25 mg weekly. 557 continued to the second 12 weeks. for example. cyclosporine. exacerbation of symptoms in reaction to certain cytokines such as interferons and interleukin (IL)-2. achieved 49% of in the etanercept emphasis will beThis on document the longest-term available. Pre-specified efficacy analyses were performed on all randomized patients who received at least one dose of study drug. Statistically significant differences between the 50 mg BIW etanercept and placebo groups were noted as early as Week 4. and placebo groups. respectively (P < 0. Of 2.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 548 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6.546 entered the study and received at least one dose of study drug. et al (2007) 12 weeks. etanercept 50 mg BIW. Most patients whose treatment was interrupted at Week 12 regained responder status once treatment was reinitiated. At Week 24. had active but clinically stable plaque psoriasis involving at least 10% BSA. randomized. BSA group responders** discontinued No reproduction or use of any portion of the contents of these materials mayatbeweek made16without written consent of JDD. despite the reduction in the etanercept dose from 50 mg BIW to 25 mg BIW. the proportion of responders was significantly higher in the continuous treatment group compared with the interrupted treatment group: 71% versus 59. placebo-controlled Weeks 0–12 randomized to: etanercept 50 mg BIW etanercept 25 mg BIW. placebo Week 12: etanercept 25 mg BIW for all patients Primary: PASI 75 response rates at Week 12 Secondary: Improvement from baseline in Physician’s Assessment of Scalp Psoriasis. placebo-controlled Weeks 0–12 randomized to: etanercept 25 mg qW.0 days. Exclusion criteria included previous antibiotics within 1 week of the start of the study. skin condition other than psorisis that would interfere with evaluation. Dropouts prior to Week 12 were imputed to be non-responders and LOCF imputation was used after Week 12. Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . time to regain responder status after retreatment was 35. active skin infections within 4 weeks.7 -. DLQI response Primary: Proportion of PGA 24 weeks. double-blind followed by 132-week openlabel extension Weeks 0–12 randomized to etanercept 50 mg BIW or placebo. 618 patients were randomized to receive placebo (n = 307) or etanercept (n = 311). qW.6 The objective of the Moore et al. PGA DLQI = Dermatology Life Quality Index *Inclusion and exclusion criteria for the studies were as follows: Patients were at least 18 years of age. et al (2007) Tyring. DLQI response tx until relapse or 20 the express thenillegally.6 days. Weeks 12–132 all received etanercept 50 mg BIW Primary: PASI 75 response rate at Week 12 Secondary: PASI.5% (P < 0. and active guttate. if circumstances dictate. 2. erythrodermic or pustular psoriasis at the time of the screening visit. involvement. The authors suggested that although continuous etanercept therapy provided optimal benefits. Weeks 0–12: etanercept 50 mg responders open-label BIW for all patients Weeks 12 to Secondary: Improvement 24:Dermatology. 1. Mean time to relapse after discontinuing therapy was 39. patients who respond to etanercept may. and received photothereapy or systemic psoriasis therapy at least once or had been a candidate for such therapy.3% versus 72%. the proportion of Physician Global Assessment (PGA) responders was similar in each group: 71.&t*446& The results of this trial were remarkably consistent with a study by Leonardi and colleagues detailed above.0001). intermittent This document contains proprietary information. etanercept 25 mg BIW. safely discontinue and then reinitiate treatment with a high probability of recapturing the initial response. ** Responders defined as those who had attained scores on the PSA of 2 or lass and demonstrated improvement fromthe baseline. All patients who received at least one dose of study drug were included in the modified intent-to-treat (MITT) analysis. DLQI.JSDJL +%FM3PTTP At 12 weeks. TABLE 1. ContinuousAll group received © 2009-Journal of Drugs in Rights Reserved. double-blind.272 in the continuous treatment group. images and marks of Journal of Drugs in Dermatology (JDD). Penalties Apply Duration and Design* Dosing Efficacy Variables 24 weeks. non-responders received etanercept 50 mg qW Moore. BSA involvement. scored a minimum of 10 on the PASI (indicating moderate to severe psoriasis). Weeks 12–24: Placebo switched to etanercept 25 mg BIW Primary: PASI 75 response rates at Week 12 Secondary: PASI 50 and 90 response rates 24 weeks. et al (2003) Papp. (2007). reinitiated etanercept 50 mg If you feel you have obtained this copy please contact JDD immediately. Etanercept Clinical Trial Summary Study Leonardi. Baseline characteristics were similar between the two groups. This trial also demonstrated that patient response rates were maintained. Assessment of Scap Psoriasis. double-blind.274 in the interrupted study group completed the study.555 patients initially randomized. (2007) study was to compare the efficacy and safety of continuous etanercept therapy with a single round of discontinuation and retreatment. et al (2005) Do Not Copy.084 of the 1.117 of the 1. Table 2 shows responder status after continuous and interrupted therapies. and 1.7 In the phase III study by Tyring et al. from baseline in Physician’s etanercept 50 mg qW. 6) 94 (26.7) 3.8 PASI 75 response rates peaked at Week 48. Other exclusion criteria included a range of infections.3) PGA = Physician’s Global Assessment. Among the patients who lost their PASI 75 responses. All Rights Reserved.7 at Week 96 and from a baseline score of 18. (2001) study was a randomized. clinically significant laboratory abnormalities. A relatively small proportion (17.16 (0.9 Infliximab: Efficacy in the Treatment of Psoriasis The Chaudhari et al. Responder Status After Continuous Or Interrupted Etanercept This document contains proprietary information. baseline BSA involvement was 27.0) 556 (60. At Week 10. Figure 2 shows the response rates from the start of the trial to Week 96 for PASI 50.17 (0. responders No reproduction or use of any portion of the contents of these materials may be made without thePGA express written consent of JDD. Patients in whom efficacy was not maintained were eligible to have their dose raised to the previous 50 mg BIW level.4%) who attained a PASI 75 at Week 48 retained this response at Week 96 but 25.21 (0.6% lost their PASI 75 at Week 96.10 Do Not Copy. 4. Despite some loss in response rates over time.98) 650 (51.8) 111 (30.15 (0. Gordon KB.0 for the placebo/etanercept cohort to 6. score please contact JDD immediately.2.3) 648 (50. 2007:56(4):600. Patients had a history of plaque psoriasis for a minimum of 6 months and a history of topical corticosteroid failure. malignancies. 591 patients continued treatment into the open-label phase of the study. 9 at Week 120 and 7 at Week 144. © 2009-Journal of Drugs in Dermatology. Most patients (74. and the study was unblinded.S. the progressive change in scores was from a baseline value of 20. 2 and 6. Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . respectively. 75 and 90 for the two groups of patients. The authors speculated. et al. Kang S. patients were classified as either responders or nonresponders. U. as those judged less compliant in terms of the percentage of self-administered doses had a higher likelihood of worsening PASI scores. The proportion of patients achieving PASI 75 was a secondary end point. with permission from Elsevier. or had been treated with a range of biologic agents at any time. whether psoriasis-specific factors might not decrease the TNF dependency of the disease in patients treated with TNF antagonists.8 Rapid improvements in percentage of patients attaining PASI 50. Among the patients who increased their dose to 50 mg BIW (n = 122).8 In a third phase of the study. patient characteristics were similar between the two treatment groups. A history of psoriatic arthritis was present in 34.&t*446& of these. Moore A.9) 126 (35. however.8) 109 (30. patients initially treated with placebo then switched to etanercept at Week 13 experienced improvement in PASI scores by Week 24. 75% to 99% clearing.80) 3.9) 539 (58. open-label trial of continuous versus interrupted etanercept thereapy in the treatment of psoriasis. A randomized.3) 365 (28. with 63% of patients originally given etanercept and continued on etanercept treatment (etanercept/etanercept) and 61. Penalties Apply Compliance was considered a potential reason for the loss of efficacy in some patients during the study.3%. excellent or clear ratings on the PGA.0) 3.1% of those switched from placebo to etanercept (placebo/etanercept) attaining that level of response. At baseline. SD = Standard deviation Reprinted from J Am Acad Dermatol.2) 769 (84.7) 880 (69. (%) at baseline (SD) Week 16 No. placebocontrolled.5) 758 (59.73 3.19 (0. (%) Week 24 No. The primary efficacy outcome measure was PGA at Week 10 of the study.0) 766 (84. No. mean PASI scores were 19 at baseline.97) 894 (70.2% and baseline PASI was 18. systemic therapy in the previous 28 days. Patients were randomized to receive placebo or infliximab 5 mg per kilogram (mg/kg) or 10 mg/kg at Weeks 0.81) 3.8 -. (%) Continuous All patients Week 12 responders Week 12 non-responders 1272 (100) 907 (71.0) 357 (28. A positive response was defined as good. patients (n = 201) had their etanercept dose reduced to 50 mg weekly and were followed for an additional 48 weeks.9 for the etanercept/ etanercept cohort to 7. Patients were excluded if they used topical therapy in the previous 14 days. Treatment arm If you feel you have obtainedMean this copy PGAillegally. and 100% clearing of psoriatic plaques.5) 632 (68.JSDJL +%FM3PTTP the long-term findings provide evidence supporting the effectiveness of etanercept for the long-term treatment of psoriasis.5) 137 (37.5) Interrupted All patients Week 12 responders Week 12 non-responders 1274 (100) 917 (72.3 at Week 96. 75 and 90 were evident as early as Week 12 in patients initially treated with etanercept. ultimately supplying long-term data for up to 144 weeks.A BEMaGS Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page F 549 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. equivalent with 50% to 74% clearing.13 (0.3) 804 (88. or drug or alcohol abuse. double-blind trial of 10 weeks’ duration followed by an open-label phase to 16 weeks in adult patients who had moderate-to-severe plaque psoriasis involving at least 5% BSA. images and marks of Journal of Drugs in Dermatology (JDD).6) 90 (24. Non-responders in TABLE 2. (%) Week 20 No.4%) of the 132 patients who had not achieved a PASI 75 at Week 48 did so by Week 96.2 at Week 96.72) 3.4) 903 (71. Copyright © 2007 AmericanMedical Association. twice weekly. etanercept 25 mg BIW. Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . Lahfa M. Papp KA.004 vs.42% images and marks of Journal of Drugs in Dermatology (JDD). 40 30 If you feel you have obtained this 26% copy illegally. 50 mg of etanercept twice weekly vs placebo at week 12 (2-sided van Elteren test stratified by previous therapy) based on an intent-to-treat analysis using last observation carried forward. Poulin Y. placebo. regardless of whether they received study drug.143(6):724. It is noted that baseline characteristics were not consistent within each treatment group: mean age was 51 years in the infliximab 5 mg/kg group. 75% (PASI75). 87 80 70 All Rights Reserved.3.001 vs.10 85 80 74* 70 86 83 Etanercept 25 mg BIW Etanercept 50 mg BIW Placebo Percent of Patients 60 50 40 85 82 83 82 80 79 50 40 30 Etanercept/Etanercept Group Placebo/Etanercept Group 20 0 14 0 100 PASI75 Percent of Patients 90 80 70 60 60 41* 50 60 58 63 61 60 58 55 55 54 54 52 51 48 40 30 20 10 0 0 5 100 Etanercept 25 mg BIW PASI90 90 50% †‡ 87 85 60 10 Percent of Patients 70 87 76 Do Not Copy. 35 years in the 10 mg/kg group.10 -. the authors mentioned that infliximab response rates were higher than FIGURE 2.A BEMaGS Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page F 550 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. and 45 years in the placebo group. and assumes that patients with missing data at a given visit did not meet the response criteria. please contact JDD immediately. et al. Percentage of patients achieving a PASI 75 response (improvement from baseline of at least 75% in the Psoriasis Area and Severity Index) over time: sensitivity analysis. Although not a direct head-to-head comparison with differences in patient populations and study design. evenly divided between the three treatment groups. All rights reserved.6). excellent. 2007. BIW. © 2009-Journal of Drugs in Dermatology. while non-responders in the infliximab 10 mg/kg group were dropped from the study (see next study for discussion of the open-label phase of this trial). 2005. Arch Dermatol. 100 The beneficial effects of infliximab are observed in this relatively small study. placebo.0019 to 0. †P<0. et al. *P<.JSDJL +%FM3PTTP tients was 20. *P<0. 30 28 26 27 25 30 20 21* 29 ‡ 28 20 25 * 10 22 21 17 10 0 1 0 0 0 2 4 8 12 16 20 24 Weeks BL 12 24 36 48 60 72 23 23 84 96 Week This includes all randomized patients. A global phase III randomized controlled trial of etanercept in psoriasis: safety. ‡P<0. BL indicated original study baseline. Source: Tyring S. Analysis was done on the basis of intention to treat (ITT). Penalties Apply FIGURE 1. Gordon KB. Long-term safety and efficacy of 50 mg of etanercept twice weekly in patients with psoriasis. Differences between infliximab and placebo groups were significant with P values ranging from 0.001. and less severe disease (mean PASI 22.&t*446& the placebo group were assigned to receive infliximab 5 mg/kg or 10 mg/kg at Weeks 10. 60 This document contains proprietary information. Baseline PASI scores for the placebo pa- PASI50 90 Percent of Patients A total of 33 patients were included. Reprinted with permission from Blackwell Publishing. Tyring S.152(6):1309. efficacy. or clear ratings on the PGA compared with 2 (18%) in the placebo group. Non-responders in the infliximab 5 mg/kg group were offered a single infusion of infliximab at the 10 mg/kg level. and effect of dose reduction.0013 vs.1) was present in the 5 mg/kg group than the 10 mg/kg group (mean PASI 26. all randomized patients were included. 12 and 16. Responders in the placebo group were followed and treated with infliximab in the event of relapse.03. Br J Dermatol. Nine patients (82%) in the infliximab 5 mg/kg group and 10 (91%) in the infliximab 10 mg/kg group achieved the primary end point of good. Results for PASI 75 were similar: 9 (82%) in the infliximab 5 mg/ kg and 8 (73%) in the 10 mg/kg group reached this level of improvement compared with 2 (18%) in the placebo group. and 90% (PASI90) over time. ‡ 50 30 No reproduction or use of any‡portion of the contents of these materials may be made without the express written consent of JDD. Improvements in the Psoriasis Area and Severity Index scores of at least 50% (PASI50). 1 responder in the placebo group remained untreated through the entire duration of the trial. a desirable characteristic is one Week 10. confirmed a high level of efat 16 weeks.12 Do Not Copy. For PASI 90. the PGA was not used in the open-label extension. for PASI 50. and then every 8 weeks through to week 46. As in the first phase of the study. imab-treated patients revealed 64% of samples were negative psoriasis disease process. At maintained their response at Week 50 compared with 81% of 16 weeks.12 A total of 30 patients completed the first phase of the trial and continued to the open-label phase. Three patients in each infliximab group received one retreatment infusion and 4 patients in the 5 mg/kg group received two retreatment infusions. ITT statistical analysis was used. secondary end points included attainment of PASI 75 at Week 24 and the proportion of patients achievement of a PGA score of cleared (0) or minimal (1) at Week 10.11 infliximab. doufrom placebo to infliximab at Week 24 maintained higher proble-blind. This document contains proprietary information. images and of Journal of Drugs Dermatology (JDD). Patients in the placebo group were crossed over to infliximab therapy at Weeks 24. PASI scores improved with retreatment but not as much as was seen with the initial treatment. Baseline PASI was 22. and 6 began to lose response after Week 14.0001. A total of nine patients who initially responded to infliximab experienced a relapse of symptoms and were subsequently retreated. It is noteworthy that the patients who were switched The Reich et al. All Rights Reserved. whereas patients who received the 10 mg/kg infusion did not lose response until after Week 18.JSDJL +%FM3PTTP those for etanercept in studies to that point. Although response rates held steady through Week 24. With a illegally. Nail psoriasis was assessed using the Nail Psoriasis Severity Index (NAPSI). PASI 75 was employed to assess symptom improvement from baseline. it dropped to 67% at 26 weeks.12 There was a dose response regarding the duration of clinical benefit. Penalties Apply At Week 10. PASI 75 responder rates among the original infliximab treatment group declined from 80% to 61%. and 30. these proportions were 57% and 1%. placebo).11 Of the 378 enrolled patients. Some of the decline in response seen at Week of this response may relate at least partially to the intergroup 50 may have been due to declining plasma concentrations of baseline differences noted in the previous section. however. 29 received either 5 mg/kg or 10 mg/kg of infliximab. multicenter. respectively. 80% of infliximab-treated patients had attained PASI 75 compared with 3% in the placebo group. Of these.12 tients receiving infliximab 10 mg/kg.&t*446& -.8 in the placebo group and 22. Of note. Data obtained after two missed infusions or after study infusion discontinuation were excluded.11 formarks antibodies. 77 were randomized to placebo and 301 to infliximab 5 mg/kg. through 50JDD wasimmediately. In pasive results. 26. 27% were in positive. In general.11 The principal efficacy outcome measure was the proportion of patients achieving improvement from baseline to PASI 75 at Week 10. and that in vitro infliximab can lyse TNF-α–expressing cells. study (2005) was a phase III. Of the patients who received the 5 mg/kg dose.12 The Gottlieb et al. patients who received the 5 mg/kg infusions of infliximab at Weeks 0. Part plaque psoriasis. 2. 91% and 8%. 82% of patients receiving infliximab 5 mg/kg attained antibody-negative patients and 96% of patients with inconcluPASI 75. The authors surmise that these differences may be related to the pharmacokinetics Samples for analysis of antibodies to infliximab from 264 inflixof infliximab or. all comparisons vs. The open-label extension described in this provides valuCorrelation between antibodies maintenance of response No reproduction or use of any portion of study the contents of these materials may be made without the expressand written consent of JDD. 77% of patients who switched from placebo to infliximab at Week 24 maintained a PASI 75 response at Week 50. 73% maintained PASI 50 and 67% maintained PASI 75. Patients in the infliximab group received infusions of 5 mg/kg at Weeks 0. Patients who discontinued because of lack of efficacy or loss of response or who started disallowed non-topical medications were deemed non-responders in the per-protocol analysis. They suggest that these differences may be due to differences in study populations and/or differences in the route of administration. indicating a more ficacy and a rapid response with infliximab for treatment of prolonged duration of improvement for the higher dose.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 551 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. and 6 and then every 8 weeks through to Week 46. like the previous one.10 placebo for the treatment of patients with skin and nail lesions. to dose-dependent effects on the © 2009-Journal of Drugs in Dermatology.9 in the infliximab group. 40% maintained PASI 50 and 33% PASI 75. approximately 30% in both groups had psoriatic arthritis. alternatively. 39% of those with positive antibodies to infliximab that permits the treatments to be widely spaced across time. 73% had attained PASI 75 This study. Of those 29 patients. 17 (57%) maintained PASI 50 at Week 26 and 15 (50%) maintained PASI 75. and 10% were inconclusive. Among the 30 patients. this proportion dropped to 33% at 26 weeks. respectively (P < 0. 25 completed the trial and 4 discontinued. The two treatment groups were well balanced as to baseline disease characteristics and demographics. but they also indicate that the infliximab/TNF-α complex may be more stable than the etanercept/TNF-α complex. placebo-controlled trial comparing infliximab with portions of PASI 75 response than those who had been started Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . study (2003) describes the open-label extension of the previous study through Week 26. by Week 50. Of those who received the 10 mg/kg dose. evident: among PASI 75 responders at feel you have obtained this copy pleaseWeek contact drug that is given by infusion. 2. able data about the duration Ifofyou response to infliximab. 001 compared with placebo 80 kg at Weeks 16. † p=0. multicenter trial that compared two doses of infliximab and two schedules of administration: 3 mg/kg and 5 mg/kg given either on a continuous.12 Menter et al.13 As in the Reich study. 25. with permission from Elsevier. Other end points included PGA and change from baseline in the Dermatology Life Quality Index (DLQI). The comparison of the 5 mg/kg infusion with the 3 mg/kg infusion confirms that efficacy is—to some degree—dose-related. study (2006). 22. 2. double-blind. and 46. or central nervous system demyelinating disease were excluded.4% for * 60 * 40 Placebo 3 mg/kg infliximab 5 mg/kg infliximab 20 * † 0 0 2 6 10 Weeks Reprinted from J Am Acad Dermatol. and 1. 38. Although the development of antibodies to infliximab does not reliably predict those patients who will respond to treatment. et al.1% in the 3 mg/kg group. please contact JDD immediately. All patients received induction infusions at Weeks 0. (2007) performed a randomized. Weinstein GD. No reproduction or22. 2007. and 6. A total of 252 patients permanently discontinued the study agent through Week 50. Patients assigned to as needed maintenance received their original infliximab infusions only during visits in which the observed improvement in PASI from baseline was less than 75. compared with 0. Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . response rates were greatest among patients who received infliximab 5 mg/kg on an every-8-week basis and lowest among those in the infliximab 3 mg/kg as needed group.13 Do Not Copy.3% in the 3 mg/kg group.S.8% for infliximab 3 mg/kg every 8 weeks. placebo-controlled. All100 Rights Reserved. Patients assigned to every-8-week maintenance continued to receive original infliximab infusions at Weeks 14. an effect of antibodies was seen in terms of declining maintenance of response.&t*446& on infliximab.1% for infliximab 5 mg/kg as needed.001) (Figure 3).. multicenter study in which patients were randomized to receive subcutaneous (SC) injections of placebo or one of two adalimumab regimens: (1) 80 mg adalimumab at Week 0 fol- Percent of Patients Achieving PASI 75 Improvement from BaselineThrough Week 10 Of 835 patients enrolled. of Drugs in Dermatology (JDD). the results of comparing the steady.* * If you feel you have obtained this copy illegally. PASI 90 status was attained by 45. Patients who were antibody-positive were also at greater risk for developing infusion reactions than those who were antibody-negative. 314 to infliximab 5 mg/ kg. Adult patients with plaque psoriasis were enrolled by investigators in the U.13 The proportion of patients in each of the four treatment groups randomized at Week 14 that attained PASI 75 through Week 50 were 43. A randomized comparison of continuous vs. Following the FIGURE 3. Patients with lymphoproliferative disease.5% for infliximab 5 mg/kg every 8 weeks. 70.JSDJL +%FM3PTTP infliximab 3 mg/kg as needed. PGA and DLQI values were consistent with PASI 75 scores.5% in the infliximab 5 mg/kg group. provides strong confirmation of the early efficacy of infliximab for the treatment of plaque psoriasis. Overall. 54. to infliximab 5 mg/kg as needed. ITT analysis was used. 149 patients were assigned achieving PASI 75 through Week 10. the proportion of subjects attaining PASI 75 status was 75. 30.13 Adalimumab: Efficacy in the Treatment of Psoriasis In the Gordon et al. patients were 18 years of age or older with plaque psoriasis of at least one year’s duration and involving at least 5% BSA. placebo-controlled. Penalties Apply The primary efficacy end point was the proportion of patients attaining a PASI 75 at Week 10. history of cancer. or active tuberculosis. Patients were eligible for phototherapy or systemic therapy. At Week 10. 18.56(1):31e1-e15.9% of those in the placebo group (P < 0.001). Proportion of patients in the infliximab and placebo groups second randomization at Week 14. double-blind. 148 to infliximab 3 mg/kg as needed. and every 8 weeks thereafter.13 -. The study consisted of two phases: the first was a 12-week. lymphoproliferative disease.13 This study. and 149 © 2009-Journal of Drugswho in Dermatology. additional parameters included PASI 50 and PASI 90. and no history of serious infection. A placebo infusion was administered if PASI improvement was at least 75%. intermittent infliximab maintenance regimens over 1 year in the treatment of moderate-to-severe-plaque psoriasis.A BEMaGS Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page F 552 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. perhaps due to receiving loading-dose infusions later in the course of the study. 313 were randomly assigned to receive infliximab infusions of 3 mg/kg. to infliximab 3 mg/kg every 8 weeks. had a baseline PASI of at least 12 with at least 10% BSA involvement. 38. Canada and Europe. useand of any portion of the contents of 13 these materials may be made without the express written consent of JDD. like the others previously noted. The clinical efficacy of infliximab was apparent with a significantly greater number of patients achieving PASI 75 as early as Week 2. every 8-week maintenance schedule or on an as-needed basis. 150 to infliximab 5 mg/kg every 8 weeks. that is.001 compared with placebo crossed over to infliximab treatment all assigned to 5 images mg/ and marks of Journal This document containswere proprietary information. Feldman SR. every-8-week infusion schedule with the as-needed infusion schedule suggest that the former is more effective in achieving a beneficial response. and 208 to placebo.2% of those in the 5 mg/kg group and 37. The 183 placebo patients *p<0. Menter A.5% in the placebo group (P < 0. patients with infliximab antibodies were less likely to maintain a response at Week 50 than those whose status was either negative or inconclusive. e. the majority of patients in both groups maintained PASI 50 or better compared with baseline. Almost one-quarter (26 of 106) of the patients line and the proportion of patients who lose adequate response who completed the extension phase failed to attain PASI 50 bebetween Weeks 33 and 52.14 A total of 148 patients were randomized and 147 received at least one dose of study drug. had a clinical diagnosis of psoriasis for at least 6 months. Penalties Apply The authors suggested that there was a lower risk of relapse for patients continuing on adalimumab 40 mg EOW than for those receiving placebo.16 tween Weeks 24 and 60. of these. the 95% confidence interval for this calculation was too wide for statistical significance (0. therefore.34). 490 PASI 75 gate the time to relapse after either withdrawal of adalimumab responders were then re-randomized to adalimumab or placebo or dose reduction from 40 mg weekly to 40 mg EOW among pain period C. During the placebo-controlled period. The primary efficacy end points of the BIW injections demonstrated a higher likelihood of improvestudy were PASI 75 responder rate at Week 16 relative to basement on PASI.JSDJL +%FM3PTTP 50 following 12 weeks of adalimumab treatment. immediately. In the second part of the study. 140 completed the first 12-week phase. trial (2008) was a 52-week. The primary efficacy analysis was the time to relapse after randomization at Week 12 to Week 24 for patients who had been classified as responders at Week 12. Patients who completed this 12week trial were eligible to continue an extension study. Patient characteristics were similar between the adalitients with moderate-to-severe psoriasis who achieved a PASI mumab and placebo cohorts: mean BSA affected was 26%. placebo-controlled. then 40 mg EOW beginning at Week 13. Patients were eligible for the study if they were 18 years of age or older. Weeks 12 to 24. Patients receiving adalimumab 40 mg EOW who did not attain PASI 50 were eligible for dosage escalation to 40 mg weekly. baseline PASI score of 12 or greater. representing 100% improvement. followed by adalimumab 40 mg weekly. Exclusion This study demonstrated rapid efficacy with adalimumab and and criteria the same as for the previously discussed studies. all responders who had attained PASI patients with psoriasis. Patients who received adalimumab during the first 12 weeks continued their assigned dosages. The primary efficacy end points were the proportions of patients attaining PASI 75 at Week 12 for the initial blinded trial and at Week 24 for the extension. images markswere of Journal of Drugs in Dermatology (JDD).5%) of the patients in both the adalimumab 40 mg EOW group and the placebo group discontinued treatment after Week 24 due to poor response. The proportion of PASI 75 responders at Week 24 among the patients who were switched from placebo to adalimumab 40 mg EOW was similar to that achieved by patients initially on adalimumab 40 mg EOW at Week 12. No response reproduction any portion of the contents of these The please study contact designJDD called for three treatment periods (A. or (2) 80 mg adalimumab at Weeks 0 and 1 followed by 40 mg weekly beginning at Week 2. Efficacy evaluations were performed on a MITT (Modified Intent-To-Treat) principle and all patients with missing data were counted as non-responders. and stable plaque psoriasis for at least 2 months prior to screening.15 A minority of patients—11% of those receiving adalimumab 40 mg EOW and 26% of those receiving adalimumab 40 mg weekly—attained PASI 100. The authors speculated that possible reasons for this lack of response might include incomplete TNF A total of 1212 patients were randomized. responders at Week 12 were randomized to receive either adalimumab 40 mg EOW or placebo. and 106 completed the full 60 weeks of treatment.9% achieved this level of improvement by Week 12. randomized. 132 completed 24 weeks.001). 814 to adalimumab and inhibition or lack of responsiveness to TNF inhibition in some 398 to placebo. Twenty patients had their dosage increased from 40 mg EOW to 40 mg weekly. At Week 12.15 A total of 148 patients were entered in the open-label phase of the study in which all patients received an initial 80 mg SC injection of adalimumab at Weeks 0 and 1.. the proportion of patients receiving adalimumab 40 mg EOW who attained PASI 75 was 53%. as shown in Figure 4. response was rapid: 28% of patients attained PASI 50 by Week 2 and 91. Response wasmaterials may be made without the express written consent of JDD.16 This document contains proprietary information.14 The Menter et al. of those receiving adalimumab 40 mg weekly. doubleblind. At the conclusion of period B. which resulted in 40% of these patients attaining PASI 50 and 20% achieving a PASI 75. patients received weekly rather If who you feel you have obtained thisthan copy illegally. PASI 75 response rates at Week 60 were 64% for those in the adalimumab 40 mg weekly group and 58% in the adalimumab 40 mg EOW group. C). based on the estimate of the hazard ratio of risk for relapse. the median time to relapse during this period (i.14 -.&t*446& lowed by 40 mg every other week (EOW) starting with Week 1.15 Do Not Copy.14 75—580 adalimumab patients and 26 placebo patients—entered The objective of a later Gordon et al. In addition.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 553 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. A PGA was also performed at the time of patient evaluation. nearly all (98. base- Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . the primary end point) could not be calculated. However.7 for patients on adalimumab. making it impossible to calculate time to relapse during the follow-up period. sustained uportouse 60 of weeks of treatment. this proportion was 80% compared with 4% of those in the placebo group (P < 0. Conversely. B. which was 0. At Week 16. Placebo patients were switched to 80 mg adalimumab at Week 12. 26 patients failed to attain PASI 50 between Weeks 24 and 60. All and Rights or more a Reserved.37 to 1. and strongly dose-related. As in the previous study. study (2007) was to investiopen-label period B. phase III study in patients with moderate-to-severe chronic plaque psoriasis. Patient inclusion and exclusion criteria in this study were identical to those in the previous study. Moderate-tosevere plaque psoriasis was defined as BSA involvement of 10% © 2009-Journal of Drugs in Dermatology. 2008.17 TNF-α inhibitors have been used successfully for more than 10 years for the treatment of several conditions including psoriasis.58(1):108. ankylosing spondylitis and Crohn’s disease. One-half of the adalimumab patients who had attained PASI 75 response at 52 weeks. placebo-controlled. with permission from Elsevier. (n=398) (n=26)please contact JDD immediately. controlled phase III trial. In addition. †After 80 mg at week 16 and 40 mg at week 17.16 This study showed similar short-term efficacy for adalimumab in treating moderate-to-severe plaque psoriasis. eow. psoriatic arthritis.16 During period C. open label extension. The mean improvement in PASI scores from baseline at Week 16 in patients who attained PASI 75 was 92%. 63% and 34%.A BEMaGS Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page F 554 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. respectively. > PASI75 response PASI75 response This document contains proprietary information. All>Rights Reserved. and approximately 40% had severe psoriasis. PASI 75. PASI. RA. and marks of Journal Drugs in continue to periodimages B continue toofperiod C Dermatology (JDD). As exposure time in terms of number of patient-years grows. 71% of adalimumab-treated patients attained PASI 75 compared with 7% of placebo patients (P < 0. so does the accumulation of safety data. thereby illustrating good sustained response. and 100 response rates were 85%. et al. † without the 40 express mg adalimumab eow 40 mg adalimumab eow Placebo eow If you feel you have obtained this copy illegally.16 Gordon et al. The results of an additional 6-month treatment period (i.. OLE. 18 months total of continuous adalimumab treatment) were 87%. Reprinted from J Am Acad Dermatol. more than one-half had moderate psoriasis. Gordon K. Study design describing 3 treatment periods. Adalimumab therapy for moderate-to-severe psoriasis: a randomized. (n=22) Patients with <PASI75 response enter OLE OLE: 40 mg adalimumab eow 2:1 Randomization Week 0 Baseline Patients with PASI responses >50 and <75 enter OLE 16 33 52 *After 80 mg at week 0 and 40 mg at week 1. Period B SUSTAINED RESPONSE 17-week open label Period A INITIAL RESPONSE 16-week DBPC < 28 days 40 mg adalimumab eow* (n=814) Period C LOSS OF ADEQUATE RESPONSE 19-week DBPC 1:1 Randomization Screening 40 mg adalimumab eow (n=580) N=1. calculated as 89% at Week 33. defined as less than PASI 50. At the end of the previous 52-week study.e. Psoriasis Area and Severity Index. Patients both in the treatment and placebo groups with PASI 75 scores then entered open-label period B. Tyring K. During period B. DBPC.&t*446& line PASI was approximately 19.16 After 16 weeks of treatment. Penalties Apply FIGURE 4.212 40 mg adalimumab eow (n=250) Placebo eow (n=240) © 2009-Journal of Drugs in Dermatology. the rate at which patients randomized to placebo lost response. Twenty-eight percent of placebo patients lost adequate response by Week 52 compared with 5% of those continuing to receive adalimumab. every other week. 59% and 35%. double-blind. a total of 233 patients.001). was higher than that for patients receiving adalimumab. Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . it also demonstrated a good sustained level of response to 33 weeks. the improvement from baseline in these patients remained almost constant. as did the previous study. (2008) presents the latest data from the openlabel extension period of the study discussed directly above. Menter A. juvenile rheumatoid arthritis (JRA). Do Not Copy. 90.JSDJL +%FM3PTTP previous study failed to show: withdrawal of adalimumab was more likely to be associated with failure of adequate response than was continuation of treatment. respectively. it demonstrated what the -. No reproduction or use of any portion of the contents of these materials may be made written consent of JDD. were included in the ITT population of this extension. Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 555 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. such as Hodgkin’s lymphoma is not present.1 Therefore. A study of more than 2. and melanoma. individuals who are chronic carriers of the virus are at risk of reactivation with TNF-blocker use. Table 3 provides a summary for two of the key safety issues.11 per 100 patient-years for control subjects. etanercept 50 mg BIW. such as infection and malignancy. San Antonio. Gordon KB. ankylosing spondylitis. et al. 2008.35 *Includes patients in Amgen or Wyeth clinical trials of etanercept for approval indication (RA.32(74):8-12. All Rights Reserved. and 48%. For example. The most common AEs were headaches and injection site ecchymoses. Forty-nine trials analyzed. tuberculosis and lymphoma. named for John Cunningham the patient from whose brain the first isolates were obtained. J Rheumatol.4 SIR = 4. which is caused by the polyomavirus JC. Poster P2610. PsA. however. respectively. Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F .0% of all patients).23 Do Not Copy. Gottlieb AB.19-21 Recently. Penalties Apply Etanercept Safety Data An analysis of the incidence of AEs in three randomized. prescribing information for the three anti-TNF agents. please contact JDD immediately. If you feel you have obtained this copy illegally. 2. PML may become associated with etanercept and infliximab. TABLE 3. colon.JSDJL +%FM3PTTP Key Safety Considerations The key safety considerations with TNF-α antagonists include infection. Malignancies that occurred most frequently were breast. tuberculosis 2 (non-US patients) SIR = 1. particularly lymphoma. The incidence of AEs was almost exactly equal in the four treatment groups. 46%. This document contains proprietary information. in 2005 two patients with multiple sclerosis and one with Crohn’s disease treated with natalizumab developed PML. cytopenia. 50 mg weekly and 25 mg weekly groups as 51%. although there are indications that patients with psoriasis are at elevated risk for developing lymphoma. not psoriasis patients. Keystone EC. patients with RA. due to the immunosuppresive nature of the agents.386 patient years of etanercept exposure included in analyses.and gender-matched controls.52 per 100 patient-years for infliximab-treated patients and 0. Hepatitis B virus carriers may still be candidates for anti-TNF therapy. and melanoma.263 patients experienced an AE during the first 12 weeks of the studies.19 Similarly. AIDS is the underlying illness for 85% of PML cases. JRA. TX. It must be stressed that cases are extremely rare. it remains uncertain whether the use of TNF-α inhibitors also increases risk of lymphoma. placebo-controlled etanercept studies reported 471 of 1.18 Regarding malignancies other than lymphoma and nonmelanoma skin cancer. Clinical trial safety data of events of interest in patients receiving etanercept (Enbrel) across approved indications.2% of all patients) and placebo (1. lung. 18. Similar data for the psoriasis population are not currently available.22. with the distribution of AEs in placebo. sinusitis and influenza. clinicians are cautioned that. The most common infections were upper respiratory infections.4 per 100 patient-years for controls. congestive heart failure and malignancies. Still.20 Malignancy rates among etanercept-treated patients with psoriasis are discussed in the next section. demyelinating disease. PML. most reported cases occurred in patients also taking other immunosuppressive agents.458 patient-years exposure) ‡ Includes data from 9. No reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD. rates were similar to those expected in the general population. The most common malignancies observed were breast.083 5 7 pre-screen (non-US) 14 post-screen (3 in US) Lymphoma SIR = 2. whether receiving treatment or not. lupus-like syndromes. colorectal.460 patients in RA trials SIR=Standardized incidence ration Source: 1. † Includes data from 1298 patients in RA trials (2.93 SIR = 6. images and marks of Journal of Drugs in Dermatology (JDD). Gianni EH. The control subject rate was lower than expected. Tuberculosis and Lymphoma Data in Patients Treated With TNF-α Antagonists Serious AE Etanercept1* Infliximab2† Adalimumab2‡ M. while the rate for the infliximab-treated patients was similar to that expected in the general population. is the only known human viral demyelinating disorder. rates in infliximab clinical trials for all indications were 0. 56%.24 A warning for hepatitis B virus reactivation is included in the © 2009-Journal of Although Drugs in Dermatology. but caution should be used when prescribing the agents. February 1-5. are suspected as consequences of the immunosuppressive nature of TNF-α antagonists. RA may confound the accuracy of some results.&t*446& -. Poster presented at: American Aademy of Dermatology 66th Annual Meeting. rates in adalimumab clinical trials were 0. Safety of biologic therapies-an update. Serious complications. prostate. pooled safety data for these serious adverse events (AEs) are from RA patient populations. Much of the accumulated. Serious AEs (SAEs) occurred with comparable frequency in patients taking etanercept (1.700 patients followed for nearly 4 years showed an almost 3-fold elevated risk for developing lymphoma compared to age. 2005. Atrisk patients require close monitoring for signs and symptoms of active hepatitis infection with laboratory work and clinical evaluations performed regularly. a few reports of progressive multifocal leukoencephalopathy (PML) developing among patients treated with biologics have emerged. psoriasis as of May 2006. have a higher incidence of lymphoma than that of the general population. particularly when an underlying immunosuppressive disease.6 per 100 patient-years for adalimumab-treated patients and 0. patients was headache. there were four SAEs: two occurring in patients taking tibodies to infliximab but no relevant clinical symptoms related adalimumab 40 mg EOW and two in patients taking adalimum© 2009-Journal of Drugs inexDermatology. These patients were less likely to maintain response to treatment than those with negative or inconclusive tests for antibodies. Specific to malignancies.9%) treated 16-week. Penalties Apply Safety data is available for 1. 27 cases were recorded among etanercept-treated patients. with the 3 mg/kg as-needed dose experiencing the most reactions overall. The percentages and in 7 patients taking placebo. some of whom remained on etanercept treatment for up to 3 years. During the double-blind phase. computed to be an identiof patients reporting any AE were approximately comparable: cal rate of 0. and 6. and then every 8 weeks with placebo. Although headaches were most common in the etanercept 25 mg BIW group (68.9. with adalimumab 40 mg weekly during the open-label period.212 patients were originally enplacebo-treated patient reported arthritic knee pain. an AE occurred in 105 patients (70. fatigue. The longterm analyses divided patients into three etanercept treatment groups. did not show dose-related toxicity.3% in the placebo group to 78% in the adalimumab 40 mg weekly group. please contact JDD immediately. 15 had AEsNothat were described severe.25 Infliximab Safety Data -. open-label extension. 10-week study that enrolled 33 patients and included a trolled extension. itchy feet that resolved with discontinuation of infliximab and a illegally. placebo-consmall. SAEs were reported in 33 patients taking adalimumab pared with 3% of the placebo-treated patients.&t*446& Safety data for 5. and were stable across time.28). Two patients developed antinuclear anOverall. The four most common noninfectious AEs in the longterm groups were headache. In the short-term studies (n = 1. All Rights Reserved. The only inIn a 50-week study of 378 patients comparing infliximab 5 mg/ fectious AEs occurring in more than 2% of patients were upkg at Weeks 1. to this development was observed. nasopharyngeal infection. Of the other AEs. no lupus-like syndrome and no cebo. including placebo-treated patients. included was a group of patients who received continuous 50 mg BIW therapy. 2.10. Two infectious AEs were reported in patients tension. Rates.9%). no lymphoma.59.2. and in 46 adalimumabmore frequency in infliximab-treated than in placebo-treated EOW-treated patients (67. Antibody-positive patients were also at higher risk of experiencing infusion reactions than antibody-negative patients. images marksthe of Journal of Drugs in Dermatology (JDD).16 During a 6-month extension of this study in which 233 patients participated.14 Do Not Copy. In the with adalimumab was followed by a 12-week. 429 completed the 52 weeks of the study. sinusitis.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 556 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. double-blind phase of a long-term adalimumab trial. Again. adalimumab patients two squamous cell carcinomas and one basal cell carcinoma. There was one case of 82% of those on infliximab compared with 71% of those on platuberculosis.090 patient-years of exposure) were generated.246 patients in the infliximab studIn a 24-week study in which 12 weeks of open-label treatment ies discussed in the previous article of this supplement.245). and infections among the four treatment groups during the 50-week study.2% in the placebo/adalimumab group. and back pain. the end of the double-blind period. The most common AEs were nasopharyngitis and upper respiratory tract infections.12 experienced six SAEs and two serious infections. The expected number of events was 21. generating a standardized incidence ratio (SIR) of 1. Three infliximab patients experienced skin malignancies: demyelinating disorder. AE rates ranged from 67. Infusion reactions were most common in the as-needed groups for each dose. arthralgia. SAEs.06 events per patient-year.and long-term etanercept studies (4. Upper respiratory tract infection was the most common infectious AE. 3 patients infusion reactions to infliximab and 2 and taking 40 mg EOW dose and one was reported in a patient Thishad document contains proprietary information. If you feel you have obtained this copy In a 52-week study in which 1. patient developed taking 40 mgwithout weekly reproduction or use ofas any portionOne of the contents of these materials maythe be made thedose. there were no reported SAEs. and rhinitis were notably higher in infliximab-treated patients than in the placebo group at Week 14. the four most common noninfectious AEs were headache. injection site hemorrhage. Antibodies to infliximab developed in 237 of the 589 patients rerandomized to infliximab at Week 14.13 Adalimumab Safety Data Safety data is available for patients in the adalimumab studies described in the previous article of this supplement.6%) during the double-blind period. During the 12-week. Analyses determined that AE rates were comparable between all treatment groups. which were reported as events per 100 patient-years. Results for noninfectious and infectious AEs and SAEs were similar between the treatment groups. express written consent of JDD. During the open-label ab 40 mg weekly. per respiratory tract infection. and arthralgia. Two cases of tuberculosis and 12 malignancies were reported in the infliximab cohort. SAEs occurred in 14% of the adalimumab/adalimumab group compared with 2. injection site hemorrhage.JSDJL +%FM3PTTP regimens study (n = 589 patients treated long term) revealed comparable AEs. the rate in the 25 mg weekly group was 14.423 patients with moderate-to-severe psoriasis included in six short. for injection-site reaction ranged from 42 to 45 among the four treatment groups.17 The continuous versus intermittent infliximab maintenance Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . only headache. The extension phase (Weeks 12 to 50) revealed comparable AE rates of 78% between the placebo/adalimumab group and the adalimumab/adalimumab group. upper respiratory tract infection was the most common infectious AE. and 6% of the infliximab-treated patients experienced a SAE comsinusitis.11 rolled. the only AE that occurred with in 36 placebo-treated patients (52. 13 This figure was considerably higher than the proportion of patients on etanercept that According to information from the clinicaltrials. after the study Thisof document contains images and marks of Journal of Drugs in Dermatology (JDD).28 Do Not Copy. expecting a reduction in the incidence of dose-related AEs. effective.gov Web site attained that level of response. J Drugs Dermatol. Ten of the 14 subjects (71. mean affected BSA was 28% and the baseline PASI was 22.&t*446& 80 PASI75 PASI90 PASI100 60 40 20 0 4 Wk 8 Wk 12 Wk Source: Kircik L. 100 Mean Percentage of Patients (±95% CI) JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. in a trial Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . in different trials. Bagel J.A BEMaGS Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page F 557 Combined Therapy for the Treatment of Plaque Psoriasis Combined therapy offers the potential to improve upon the response provided by therapy with a single intervention and to employ drugs at less than their maximum dose.JSDJL +%FM3PTTP FIGURE 5.6. Reserved.26 Considerable proportions of the patients had prior systemic treatments. sponses likelyJDD to be highly encouraging to the patient as well If you feel you have obtained this copy illegally.5. With safe and effective options to manage their symptoms. The database for line. (2008) evaluated narrowband (310–312 nm wavelength) ultraviolet light B (NB-UVB) thrice weekly (TIW) in combination with etanercept 50 mg BIW in 86 patients with stable plaque psoriasis. It is well-known that early response to treated the effects of psoralen and ultraviolet light A (PUVA) comment reinforces compliance. marked. providing patients with with the improvements in the efficacy outcome measures.4%) restoration of quality of life is a signal of achievement in treatachieved PASI 75 by Week 8. Adalimumab will be continued. At 12 weeks. safety. the proportion of patients attaining ment of any disease. 2008. Patients who achieved PASI 75 of response may be problematic. the most common AEs were UVB-induced skin over. steroids and oral retinoids. improvement in PASI response was still increasing at the conclusion of the study. with some agents. Moreregard to safety. A total of 84% of the patients were assessed as having moderate.6% from baseable. Most patients (70. that proporfrom the US NIH.9% of patients attained PASI 75. ate combination adalimumab and UVB therapy in patients with psoriasis is currently recruiting patients (as of March 2008). early positive reperiod and was considered possibly No reproduction or useas of any portiontreatment-related. The study will include patients on adalimumab therapy for at least 6 weeks who have not experienced a 75% or greater reduction in PASI.0% attained PASI 100.12. 58. an interventional study designed to evalution ranged between about 50% and 60%.26 -. 62% of patients achieved PASI 75 after 12 weeks of UVB therapy. which proprietary occurred information. of the contents of these materials may be made the express consent of JDD.8% of patients and injection-site repromising options that may enhance efficacy while minimizing actions experienced by 16. in one study. and patient-reported outcomes.7% at Week 8.9. pleaseare contact immediately. equivalent to clear or almost clear of psoriasis. Most patients (69.26 CONCLUSION The chronicity of psoriasis means treatments must be availMean BSA affected by psoriasis improved by 83.8%) reached PASI 75 at Week 8. In the study under discussion. A 12-week study in 14 patients with severe psoriasis evaluatas to the clinician.27 between about 70% and 80%. the proportion of patients remaining patients who did not achieve PASI 50 or 75 were not who attained PASI 75 with infliximab at 10 to 16 weeks ranged able to do so by Week 12. Penalties Apply Of the 86 patients enrolled. et al.3%.There were two SAEs: one case © 2009-Journal of Drugs in Dermatology. and when the deleterious effects bined with etanercept. the growing use of combination therapy provides several injuries experienced by 62. we note that in or 50 maintained their improvement through Week 12 but the the clinical trials discussed above.9%) previously received treatment with topical steroids and many were treated with vitamin D analogues and tar compounds. including methotrexate. Almost three-quarters (74. Estimated completion date is February of 2010. Previous studies with NBUVB demonstrated significant clearing of skin lesions and. while UVB phototherapy is added to the regimen. As shown in Figure 5. adverse of angina pectoris that was not considered to be treatment-related and one case cellulitis.4%) of patients had a PGA score long-term analyses of biologic agents is still somewhat limited of 0 or 1. 26 Short-term PASIwithout 75 responses arewritten important. Curglobal assessment and the DLQI scores improved consistently rent long-term results are promising. and safe over the long term.7(3):249. Korman N. However.8 However. For example. 83 completed the 12-week study. 84. A recently published study by Kircik et al. Utilization of narrow-band ultraviolet light B therapy and etanercept for the treatment of psoriasis (UNITE): Efficacy. wk=week). Psoriasis Area and Severity Index (PASI) response over time (CI=confidence interval. Patients received PUVA treatment TIW of psoriasis symptoms on quality of life are considered. Patient but continues to grow as data are accumulated over time. maintenance PASI 50 was 85. Allevent Rightspotential.1% attained PASI 90 and 26. early and etanercept 25 mg BIW SC. or severe disease at baseline. All Rights Reserved. Leonardi CL. the proportion of PASI 75 responders increased from approximately 50% at Week 24 to 63% at Week 48. As previously discussed. Menter A. He is a consultant to QLT Inc..org/about/stats/index. Jr. It should be noted that there is only one combined therapy study employing NB-UVB in which more than a quarter of patients attained PASI 100. Medicis Pharmaceutical Corporation. SkinMedica. Moore A. data for etanercept and infliximab suggest PASI 75 response in approximately 60% of patients at the 1-year mark. and OrthoNeutrogena. Feldman SR. Etanercept as monotherapy in patients with psoriasis. MO: Elsevier Mosby. Year Book of Dermatology and Dermatologic If you feel you have obtained this copy illegally. 2007:49. The upper line represents the “as treated” population with the N values varying from 89 at Week 10 to 49 at Week 120.8 Comparison of efficacy data for the TNF-α inhibitors is made difficult by numerous factors. No reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD. Tyring S. A randomized. Inc.26 Effective Treatment Options The chart shows the proportion of patients in an open-label extension of adalimumab that attained PASI 75 at Week 120. et al. 2002.. efficacy. 2007. consultant or speaker from Amgen.JSDJL +%FM3PTTP The Value of Combination Therapy Clinicians may wish to consider combined therapy for a variety of reasons. in a trial of etanercept. while the lower line represents the ITT population of 92. Gottlieb A. From the data reviewed here. Krueger JG. N Engl J Med. The collection of long-term trial data is. Dr. et al. small but growing as results from newer studies emerge. In addition. (n=92) 0 0 10 20 30 40 50 60 70 80 90 10 110 120 Poster presented at American Academy of Dermatology Annual Meeting. contact JDD (n=75) 80 70 (n=53) (n=49) 73 76 78 41 43 41 (n=52) 82 75 3. The three anti–TNF-α agents all carry prominent warnings in the prescribing information with different verbiage but similar implications. and Warner Chilcott. In contrast. Accessed May 19.29 -. the proportion of PASI 75 responders dropped from 80% at Week 10 to 61% at Week 4612. and effect of dose reduction. Kircik has disclosed that he has received funding as an investigator. Unilever. Thus. 2008. As demonstrated. About psoriasis: Statistics. Ranbaxy Pharmaceuticals Inc. the combination of a biologic agent with phototherapy. (n=89) 60 56 50 61 54 53 40 30 4. images and marks of Journal Drugs inof Dermatology 100 Percent of Patients with PASI75 biologics.19-21 Dr.. Powers JL. management of psoriasis and psoriatic arthritis: Section 1. the clinician can attempt to arrive at a satisfactory assessment of the benefits and risks of treatment with these agents. Inc. of psoriasis andof guidelines care for the (JDD). 2008.46(1):1-23. whereas. et al. Washington DC.. principal among which is the absence of head-to-head studies.58(5):826-850. 10 6.psoriasis. Ltd. Matheson RT. Poster P 2777. National Psoriasis Foundation Web site. either NBUVB or PUVA. may offer a considerably higher rate of response as compared to either intervention alone. please Thiers BH.29 The treatment of plaque psoriasis with TNF-α antagonists is still a relatively recent addition to the pharmacologic armamentarium available to clinicians. Overview FIGURE 6. Lahfa M. 2005. Br J Dermatol. As the denominator declined. 2003. Del Rosso has disclosed that he has received grant/research support from Coria Laboratories. therefore. Figure 6 illustrates this difference. including inadequate response to monotherapy or problems involving tolerability. All warn against infection. Lang PG immediately. as accurately as able to gauge from the available data. the proportion of PASI 75 responders of the entire ITT population in this study declined to 41%. REFERENCES 1. open-label trial of Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . Obagi Medical Products. J Am Acad Dermatol. DISCLOSURES Do Not Copy. As treated (n varies) ITT (n=92) 20 5.152(6):1304-1312. Surgery 2007. a focus on safety issues becomes paramount. St Louis. Available at: http://www. A global phase 3 randomized controlled trial of etanercept in psoriasis: Safety. treatment of psoriasis with This document contains proprietary information. ending at 78% at Week 120. Adalimumab and long-term data. J Am Acad Dermatol. singling out tuberculosis as a risk and stating that patients should be screened and tested for latent tuberculosis before starting therapy. a factor that may often be overlooked is that efficacy analyses may not be carried out using the same statistical standards. Kang S. 7.php. Penalties Apply In light of the similar long-term efficacies demonstrated by the three TNF-α inhibitors and in consideration of the likely need to continue therapy for many years.. et al. the efficacies of the three TNF-α inhibitors are roughly comparable. Inc. February 2-6. and Stiefel Laboratories. Papp KA.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 558 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6.&t*446& of infliximab. 90 (n=60) 2. The immunologic basis for the treatment of psoriasis with new biologic agents. He is a scientific advisor to Allergan Inc.349(21):2014-2022. while the response rate for adalimumab may be somewhat lower. Glaxo Dermatology. What should be evident is that the present opportunity to confer positive systemic results and relief from symptoms is a major step forward in the treatment of psoriasis. Gordon KB. He is also a member of the speakers’ bureau for each of the aforementioned companies. Guidelines of care for the © 2009-Journal of Drugs in Dermatology. the proportion of patients attaining PASI 75 in the “as treated” analysis remained consistently high. . Poulin Y. 2008.. 20. Gottlieb AB.. 14. 2008...... Efficacy and safety of infliximab monotherapy for plaque-type psoria28. Poster P2731. 15...... sented at: Summer 2005 American Academy of Dermatology MeetChaudhari U..net ________________ Acad Dermatol.... New Tyring S..materials may be made without the express written consent of JDD. Mod Rheumatol. wedoderma@bellsouth. 2007. PA:proprietary Centocor. 9.. et al... Enbrel [package insert]... 2005. J Rheumatol © 2009-Journal of Drugs in Dermatology......... 24..7(3):245-253. Dooley LT..... J Am Acad Dermatol.. 22.... Humira [package insert]... J Drugs Dermatol.. 2007.. No reproduction or use of any portionAbbott of the Laboratories. et al.....17:72-74... et al... Psoriasis Forum..... PUVA therapy combined with lowAcademy of Dermatology 65th Annual Meeting. Wakasugi H. Yamamoto M.. randomized clinical trial. July 20-24..Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 559 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6.. Kircik.. NY. images and marks of Journal of Drugs in Dermatology (JDD)..54(3 suppl 2):S92S100. Malvern.58(1):106-115. Li S. 2008. Available at: http://www. ____ type psoriasis. Lancet. please contact JDD immediately. 11...56(1):31. Do Not Copy.. Blum RR.. Keystone EC... Infshow/NCT00638469? cond=psoriasis&intr=%22adalimumab%22&ra _______________________________________ liximab monotherapy provides rapid and sustained benefit for plaquenk=14. intermittent infliximab maintenance regimens over 1 year in the treatment of moderate-to-severe plaque psoriasis. Accessed June 12... 2003.....IL: 2009. 2007. 16.. DC. A randomized comparison of continuous vs. et al.. 2009. 2008. Gordon K. Clinical response to adalimumab treatment in patients with moderate-to-severe psoriasis: DouLeon H. Neurol Clin...&t*446& 8.clinicaltrial... Phone . Poster P1817.. J Am Acad Dermatol.. Indiana University Medical Center Gordon KB. Efficacy and safety profiles of Efficacy.55(4):598-606. light B therapy and etanercept for the treatment of psoriasis (UNITE): Tyring S. 13. mg of etanercept twice weekly in patients with psoriasis. Gordon KB.. Inc... safety. Papp K. Leonardi CL. J Am Acad Dermatol.. Leukoencephalopathy during administration of etanercept for refractory rheumatoid arthritis.. Langley R..... Dooley LT... 2006.. Penalties Apply 19. This document contains information. Woodson J.. Mulcahy LD.JSDJL +%FM3PTTP continuous versus interrupted etanercept therapy in the treatment of an integrated. Efficacy and safety of adalimum1169 Eastern Pkwy 2310 ab treatment in patients with moderate-to-severe psoriasis: A doubleLouisville.... Nestle FO.... Bagel J. Poster presented at: Summer 2007 psoriasis.74:8-12. Weber T. All Rights Reserved. Gordon KB.......gov/ct2/ Gottlieb AB... (502) 451-9000 Menter A... 2005... KY 40217 blind. IL.. Kircik L.. -.. 2001. et al. Baker DG.. Kricorian G... Tyring SK.366(9494):1367-1374.56(4):598-603.. Papp K.. Lancet.. Gu Y.... 2006... ing. Infliximab induction and maintenance mumab in a 12-week open-label extension study in patients with therapy for moderate-to-severe psoriasis: A phase 3. based on an integrated multistudy database.. randomized controlled trial and open-label extension study.. 17.. Gordon K. 2007. 2007. US National Institutes of Health.. Weinstein GD.. Arch Derma26. Gottlieb AB. et al. Romano P.... Chicago. et al. et al.58(2):AB129. Long-term safety and efficacy of 50 York. Remicade [package insert].. Feldman SR... Kircik L. Psoriasis patients treated continuously with adalimumab: Efficacy and safety results from months 12 to 18 [abstract].. MD ble-blind.... Leonardi CL. J Am E-mail.. moderate-to-severe plaque psoriasis. Takahashi H. UVB-311 after initial slow response to sis: a randomised trial. and patient-reported outcomes.. multicentre. Goffe BS.. Poster preWashington.. 29.56(2):AB193 Menter A.. February 2-6 2007.. ble-blind trial. Safety of biologic therapies–an update. Gordon K. Poulin Y... Chaudhari U.. Papp KA. Safety of long-term etanercept treatment in patients with moderate-to-severe plaque psoriasis: Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . North Chicago.. ADDRESS FOR CORRESPONDENCE Gordon KB..48(6):829-835. J Am Acad Dermatol.. Leonardi C. Thousand Oaks... If you feel youCA: have obtained copy illegally. 2007. 2005. 12. J Department of Dermatology Am Acad Dermatol. Etanercept monotherapy in patients with psoriasis: A summary of safety.. 23. 10. multistudy analysis.. Leonardi C....e1-e15. controlled phase 3 trial. Adalimumab therapy for moderFax . adalimumab in psoriasis. etanercept 50 mg twice weekly for up to 144 weeks in patients with 2008. J Am Acad Dermatol.. 18. dose etanercept in the management of severe psoriasis. Okun M. Gordon K.. 2009. Amgen andthis Wyeth. doumoderate-to-severe chronic plaque psoriasis.... contents of these 21.. Mulcahy LD. et al. August 2-5. Efficacy and safety of adaliReich K... Poster presented at: American 27. 2007..143(6):719-726.. J Am Acad Dermatol. American Academy of Dermatology Meeting... (502) 456-2728 ate-to-severe psoriasis: A randomized. Suppl. Utilization of narrow-band ultraviolet tol....13(1):4-11. Korman N.......357(9271):1842-1847..26:833-854.. et al. Gottlieb AB. Tyring S.. Langley RG. Frevert L.... Progressive multifocal leukoencphalopathy.. Baker DG. 25. One Solution Ointment 0. 2001. 3.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F There’s a lot of Flexibility in Topicort ® (Desoximetasone) Multiple Potencies1. secondary infection. Before prescribing. itching. Fisher’s Contact Dermatitis.A. Topicort ® is a registered trademark of Taro Pharmaceuticals North America. Hardman JG. patients should be evaluated for HPA axis suppression. TopicortThis Topicort Topicort Topicort LP Cream 0. Gel 0.05% LP Cream 0. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. Lippencott Williams & Wilkins. ® striae and miliaria. acneiform eruptions. dryness.S. perioral dermatitis. hypertrichosis. skin atrophy.29:55-69. 1989.05%may be made without the express written consent of JDD. Penalties Apply Topicort ® belongs to the class of “hypoallergenic corticosteroid”3 due to its reduced frequency of cross reactivity to other corticosteroids and has the further benefit of being propylene glycol and preservative free. Annu Rev Pharmacol Toxicol. images and ®marks of Journal of Drugs in Dermatology (JDD). Topicort ® treats a broad range of corticosteriod responsive dermatoses. McGraw-Hill. pp. Fifth Edition. Percutaneous Absorption of Drugs.25% any portion ofGel the contents of these materials If you feel you have obtained this copy illegally. The most common adverse reactions include burning. All Rights Reserved. 1799.. Stoughton RB. 2001.25% Multiple Choices. and Cream and Ointment 0.05%. No reproduction or use of0. Topicort ® Class II Class II (Desoximetasone) © 2009-Journal of Drugs Class in Dermatology. Class II IV ® document ® proprietary ® contains information. Gilman AG. please see complete prescribing information.25% Cream 0. folliculitis. maceration of the skin. Fowler JF. When used in large areas or under occlusive dressing. 2. Inc. 1. For More Information About Topicort and/or For Free Samples.05%. irritation. 203-7. Inc. February 2007 AD100-0002-R2 Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . 10th ed. Jr. hypopigmentation. Limbird LE. pg. please contact JDD immediately. allergic contact dermatitis. Call: 1-866-399-3124 ® ©2007 Taro Pharmaceuticals U. All rights reserved. Rietschel RL.2 Choice of 3 Vehicles t Propylene Glycol-Free t Preservative-Free t Class “C” Corticosteroid3 Do Not Copy. A BEMaGS Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page F Do Not Copy. No reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD. If you feel you have obtained this copy illegally. Penalties Apply © 2009-Journal of Drugs in Dermatology. please contact JDD immediately. images and marks of Journal of Drugs in Dermatology (JDD). ® ________ Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page AD 100-0002-R1 A BEMaGS F . All Rights Reserved. This document contains proprietary information. 5 mL of a hydroalcoholic gel vehicle. hyperpigmentations/dyschromia extragenital lichen sclerosus. 2 men) with lightalso been used to treat actinic cheilitis.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F JUNE 2009 562 70-6. All the patients received one treatment every 3–4 weeks up to a maximum of three treatments.%B .%B "ESJÈO-MPSFU. Objectives Vitiligo group. pustules and cysts).%B . France) for 12 minutes in yellow red (P2). cutaneous leishmaniasis. Repeated Applications and Short Contact Periods (40-60 Minutes) in Acne. months after the last session. and hands va.24 sebaceous hyperplasia25 and to (solar lentigines. Side effects were minimal and self-limited. Eterna Giovinezza). vitiligo on face.g.6 PDT has been also used to treat some instances of superficial basal cell carcinomas and Bowen disease.5. Each patient received three have been employing low-strength ALA (1-2%) to treat various treatment sessions. 26 years) had a minimum of 25 in- Products Levuderm-ALA (Mediderma.18 molluscum contagiosum.BSJB/BWBSSPD . patients.BEHB3FZFT. Levuderm-ALA Gel is a system consisting of a glass flask (containing a gel).6 or photoaging.8 Acne group. each spaced 3–4 weeks apart. the FDA approved the use of 20% aminolevulínic acid (ALA) for the treatment of multiple solar keratoses of the face and scalp.20 perioral dermatitis. This document contains proprietary information.JMMÈO. Penalties Apply Recent studies highlight the effectiveness of ALA-PDT in cases of photoaging7–11 and moderate-to-severe acne. spaced 3–4 weeks apart.17 hidradenitis suppuratito-moderate photoaging signs on the face. skin thinning. and vitiligo.%B B $MÓOJDB%FSNBUPMØHJDB4FSSBOP 7BMFODJB 4QBJO )PTQJUBM(FOFSBMEF7BMFODJB %FQBSUNFOUPG%FSNBUPMPHZ D 3FTFBSDIBOE%FWFMPQNFOU%FQBSUNFOU 4F4%FSNB-BCPSBUPSJPT 7BMFODJB 4QBJO C ABSTRACT Topical aminolevulinic acid (ALA) photodynamic therapy (PDT) is currently being used for the treatment of actinic keratosis of the face and scalp.2. freckles). skin conditions such as acne. 3 men) with moderateto-severe facial inflammatory acne were included. Eight patients (6 women. please contact JDD (1-2% Levuderm ALA) in various skin conditions such as acne. short incubation periods (30 to 60 minutes) Photographs were taken after each treatment session and 4 and three-to-four treatments sessions.3 The use of PDT for cutaneous and non-cutaneous malignancies was widely investigated by Dougherty and collaborators. METHODS The overall patient group consisted of 26 patients diagnosed with inflammatory acne. erythrosis and telangiectasias. age.4 In 1999. neck. All irradiation Rights Reserved. photoaging and vitiligo. 10 to 15 minutes). In two cases an intense pulse light (IPL) system was used (Epsilon 25). images and marks of Journal of Drugs in Dermatology (JDD). covered by a white cap (containing the ALA powder) and an orange applicator. Spain) 1% and 2% was used. Two patients © 2009-Journal of Drugs in Dermatology.12 vitiligo. SeSDerma. The patients aged 42 to 73 (mean age 55) had melasma.BUJMEF-PSFOUF. An evaluation was carried out 16 weeks after the last treatment session. cluded. the degree and extension of repigmentation was estimated by photographic comparison.%C +PBRVÓO. Spain) twice a day during the whole study. Do Not Copy. agedwritten 12–36consent years (mean No reproduction or use of any portion of the contents of these materials may be madeSix without the express of JDD. This study reports the results obtained after three to four treatments with ALA-PDT in patients with acne (n=12). 23) To evaluate the effectiveness and safety of low-strength exhibiting patches of immediately. full face) and at very low strengths (1-2%). hands or trunk were inIf you feel you have obtainedALA-PDT this copy illegally.1. The flask includes 7.19 rosacea. Valencia.3. Biophoton.22 localized scleroderma.. Twelve patients (9 women.&t*446& COPYRIGHT © 2009 ORIGINAL ARTICLES JOURNAL OF DRUGS IN DERMATOLOGY Photodynamic Therapy With Low-Strength ALA. ALA activation was usually performed with yellow (550 nm) or red light (630 nm. Patients aged 16 to 32 years (mean age.FMFOEF[D . Valencia.26 For the last two years the authors out evidence of solar keratoses. Photoaging and Vitiligo (BCSJFM4FSSBOP. ALA was applied on large areas (e. The selected patients had less than 20% of body inphotoaging. The white cap contains variable Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . through repeated applications (every volvement and had not received treatment for the last 12 weeks. withenhance wound healing.JHVFM/BWBSSP.5 flammatory lesions (papules. INTRODUCTION P hotodynamic therapy (PDT) has been used since 1900.%B 'FSOBOEP.23 fine wrinkles. Patients were advised to wash their face with a soapless cream (Hidraven. received with IPL (Quanta.21 were included.12–15 PDT has Photoaging group. photoaging (n=8) and vitiligo (n=6). Then. cal peels. Criteria: Patients with a history of photosensitivity (porphyria. photodermatoses. SeSDerma). France) which increases transdermal absorption from hydrophilic gel formulations. tients the treatment induced mild phototoxic reactions (erytheThe patients were controlled with serial pictures and clinical ma and scaling). After drying thecontents skin. which cleared completely after 1 week (Figure exams. with a single pulse of 17 ms. burning or any discomfort durand 16 weeks after the last treatment. PUVA. During the procedure most of the patients used protective goggles. acne scars had also improved. ALA penetration in the skin is enhanced by the presence in the gel vehicle of 5% diethylene glycol monoethyl ether (Transcutol®. Levudermreproduction use of any portion of the of these materials may be made without the express written consent of JDD. allowing the powdered ALA to be released into the glass container. 1% Levudthe third session (Figure 2A). photosensitizing drugs). All Rights acid peel were applied (SaliPeel. (4FSSBOP . Gattefosse. tacrolimus and pimecrolimus) for at least 1 month before the Mediderma). Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . In two of the paDuring the first patient visit. chemi© 2009-Journal of Drugs inVaDermatology. IPL. the same applied to laser. 2% Levuderm was used in patients with vitiligo. Saint Alban. SeSDerma) 2–3 times a day during the week after each treatment session. Participants were asked not to use any topical or systemic Protocol treatments (isotretinoin. The manufacturer recommends product use immediately after preparation and application within 2 hours. baseline photographs were taken. 1–2 layers of a salicylic beginning of the PDT. Patients did Digital photographs were taken after each treatment session not report tingling sensations. Two passes were applied (10 J/Cm2 each). Before treatment. Four months after the last treaterm was used. Treatment sessions were carried out at intervals of 3–4 weeks between sessions. The evidence of improvement was checked at each visit. you feel have obtained thisAfter copy illegally. t &UFSOBM(JPWJOF[[B 2VBOUBTZTUFN . to remove excess oil. images and marks of Journal of Drugs Dermatology (JDD). Spot size was 5 cm. leaving isolated areas of hyperpigmentation. Do Not Copy. UVB narrow-band or any other treatment that lencia. except those subjects with eyelid vitiligo (Figure 1). the skin was degreased (degreasing solution. the total number of sessions was four. steroids. This source was employed in two cases of skin photoaging. In both.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 563 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. 75% after the second session and 92% after skin was irradiated. phenylalanine. pulse width of 25 ms. RESULTS ALA was prepared and appliedIf every 10you minutes 4–6 times. The various topical gels were prepared just before their use by breaking the membrane inside the white cap. both components were mixed by shaking. fluences of 12 J/cm2. and spot size of 20x50 mm. Irradiation was carried out in the yellow-red spectrum (550-630 nm) for 4-12 minutes (P2) at 100 mW/cm2 (Figure 1). Thisthe document contains information. There were also no relapses at the end of the follow-up period (16 weeks). the application of a moisturizing cream was recommended (Hidraloe Face Cream. after formation of a proprietary white mask the skin was could affect the results of in the study. France) was the source predominantly used. fluence 20 J/ cm2 and pulse duration 17 ms. two passes at fluences of 6 J/cm2 were applied. please contact JDD immediately. Likewise. MediDerma Laboratories. In ment session the patients showed no signs of acne lesions and one patient. blocking UVB and UVA.3FZFT FUBM FIGURE 1. washedNo with abundantorwater.Reserved. Triwings (Biophoton. for 30 days after each treatment session. Light source: Several light sources were used. Highintensity light source emitting in the yellow and orange spectrum. The authors are currently carrying out chromatographic studies to determine for how long ALA remains stable once in contact with the gel. antibiotics. Finally the entire treatment session. The treatment with ALA-PDT showed a 50% reduction in the the last application.JMBO *UBMZ IBOEQJFDF of 570 nm (570-1200 nm). once in contact. a microdermabrasion pre-treatment was done.-PSFOUF . Penalties Apply Post-treatment: All treated patients were advised to avoid sun exposure for a minimum of 12 hours post-treatment and to use a sunscreen (Suny-SeS Sunscreen SPF 35. This source was employed in two cases of photorejuvenation and in two cases of acne. clotting defects and pregnant or nursing women were excluded from the study. Spain). Intense pulsed light: t &QTJMPO &WMBTFS $BTOJHP *UBMZ IBOE QJFDF PG nm. the product was left for 10 additional minutes number of lesions (counts) of inflammatory acne after the first before the skin was washed with soap and water. In cases of acne and photoaging. ing or after irradiation (Figures 3 and 4).&t*446& amounts of ALA HCl as a dry solid. 2B). 60 6.3%). when the skin is sion almost double repigmentation was observed. At the end exposed to light. In the last 5 years. 75% after the second session.83 20 1. cation and light source. case of persisThiseffects document contains proprietary images and marks of Journal of DrugsALA in Dermatology fied. a partial repigmentation of the lesions (25 and ic process dependent of the simultaneous presence of light and 40%) was observed in 4 of 6 patients (66. Do Not Copy. which completely cleared after 1 week. please contact JDDofimmediately. chest and ing Wood’s light. The fluorescence can be evaluated in the skin us(33. repeated (every 10 minutes) application on large patients received 4 PDT sessions with 2% ALA applied on the areas with ALA were carried out. hyperpigmented lesions attenuated in 90% of the cases. these In this study. one of them with segmental vitiligo (Figures 6 and 7) in chest and back. Four months after the last treatment session the patients showed no signs of acne lesions and acne scars had also improved. and its indications are limited to solar keratoses and certain cutaneous neoplasias. Rights Reserved. produces severe pain during irradiation.g.04 25 26.06 15 13. but satisfactory. Penalties Apply In the cases of photoaging. The follow up period was 6 months. to wit: tPGUIFDBTFTBGUFSUIFmSTUUSFBUNFOU tPGUIFDBTFTBGUFSUIFTFDPOEUSFBUNFOU BOE tPGUIFDBTFTBGUFSUIFUIJSEUSFBUNFOU FIGURE 2b. improved and diversiThe following side were observed: one information.6%). DISCUSSION Traditional photodynamic therapy (PDT) has some limitations: requires long contact periods (3-12 h). contact period. Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . Best responses were observed for the face. induces phototoxic reactions which last several days. mode of applitransitory hyperpigmentationIfthat disappeared spontaneously. In addition.strength of ALA. the whole face).25 Initial First Treatment Second Treatment Third Treatment FIGURE 2a. The degree of repigmentation bation periods (30 to 60 minutes). PDT has become more practical and its side effects have decreased significantly. while PpIX is very tion of more than 55% was observed in another two patients fluorescent. manner in most of cases (85%) after the third treatment. 10% almost completely satisfied and 2% moderately satisfied. focallyAll but on extended light sources to activate have also(JDD). and 92% after the third session. The study included 6 patients with vitiligo.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 564 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. Perifollicular repigmentation began after the first session. The long contact periods have been reduced from several hours (3-12 h) to 30-60 minutes and it is now used not only © 2009-Journal of Drugs in Dermatology. ALA does not show fluorescence. was assessed by photographic comparison. ALA-PDT showed 50% reduction in the number of lesions (counts) of inflammatory acne after the first treatment session. this property has been used to determine the neck. (not focalized) with brief inculesions at intervals of 30 days.50 5 0 0.may Theberelevant factors appropriate PDT include: tent localized rednessorthat lasted 72 hours one ofcase No reproduction use of any portion of theand contents theseofmaterials made without thefor express written consent of JDD. preparation the skin. you feel you have obtained this copy illegally. No side effects were appreciated.. produces a photodynamic reaction.75 2. a cytotoxof the therapy.&t*446& (4FSSBOP . Phototoxic reaction 24 hour after activation of 1% Levuderm-ALA. The cutaneous hyperemias and small telangiectasias diminished in a partial.42 10 0.-PSFOUF . A repigmentaoxygen. Patient satisfaction was assessed through a questionnaire participants were asked to complete: 88% of the patients were completely satisfied.areas (e. after the second sesALA is a precursor of protoporphyrin IX and.3FZFT FUBM Number of Lesions Mean and Standard Deviation 30 2. Skin surface (smoothing) and elasticity improved in all cases (Figures 4 and 5). reaction at the level of the sebaceous glands. knowledge.marks and everything depend on the clinician’s readiness and This document contains proprietary information. the fluorescence in the skin can be detected solar keratoses and superficial basal cell carcinomas and other between the fourth and the sixth application. a penetration enhancer. any source providing light of wavelengths in the absorption spectrum of the PpIX can be used. All light Rightssources Reserved. FIGURE 4. 540. blue light.&t*446& FIGURE 3. inside them transporting the ingredient and easing the generation of intracutaneous deposits. as it has been described in psoriasis where hyperkeratotic sites show a very low fluorescence in comparison with other sites where the horny layer was thin and the fluorescence higher. Transcutol does not seem to interact with the horny layer and it does not modify the lipid structure and cutaneous proteins. In the presence of Transcutol the intercellular spaces expand. 580 and 630 nm (Q bands) and 410 nm (Soret band) are used. but the authors believe that If you feel you have obtained thistreatcopy illegally. The activation of ALA is usually done using red light. At this wavelength (410 nm). In particular. of these have their advantages and disadvantages. The fluorescence neoplasias of the skin. images and of Journal ofwill Drugs in Dermatology (JDD). 10 and 20%. vascular lasers and intense pulse light. please contact JDD immediately.PpIX produced by Propionibacterium acnes.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 565 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. However. including SK. All © 2009-Journal of Drugs in Dermatology. virtually no side effects (phototoxic reactions) Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . Transcutol forms intracutaneous deposits of the applied drugs. As the skin is very accessible to light. Blue light has a very limited penetration (less than 0. hours). penetration is 0. Transcutol is a powerful solubilizing agent with capacity to solubilize hydrophilic and hydrophobic compounds. is its dermal penetration depth (2 mm). At present. 5.28. and repeated applications (evthat the use of high ALA concentrations (20%) is indicated in ery 10 minutes). When ALA concentration is also an important factor. wavelengths of 505.29 The peels should be carried out immediately before PDT application to remove the horny layer and to allow an even and deeper penetration of ALA.5 to 1 mm.29 Products used in this study contain Transcutol. The advantage of the longer wavelengths. These peels accentuate ALA penetration and contribute to improve the results in both acne and photoaging. further studies are needed to begins to decrease approximately 15 minutes after the applicadetermine the ideal strengths and contact periods for the differtion of the gel. For porphyrins. The use of low concentrations of ALA has many advantages. Penalties Apply The light source is another factor to keep in mind in PDT. moment of the accumulation of PpIX after ALA application and its clearing of the skin after interrupting the application.28 A thick horny layer can be a restrictive factor for the clinical response. In the first place. we tested a high intensity light source (100 mW/ Cm2) with excellent results and very short exposure times. reducing its systemic absorption. indicating that the application should be carried ent conditions to treat. Inflammatory acne before treatment with 1% ALA-PDT (Levuderm-ALA). It seems evident using low concentrations (1-2%).-PSFOUF . Very deep penetration is not necessary if lesions are intraepidermal. Do Not Copy. Improvement of acne lesions 2 months after the third longer wavelengths are preferable to target the photodynamic ment session with ALA-PDT. at best. incubation time of 1 hour has lapsed (Figure 9). Certainly may activate endogenous No reproduction or use of any portion of the contents of these materials may be made withoutthis the express written consent of JDD.3FZFT FUBM The preparation of the skin by means of a salicylic acid chemical peel or with microdermabrasion allows shortening the incubation period of ALA (minutes vs.5 mm) and may not reach the dermis and a lesion located at this level. especially those in the yellow (550) and red (630 nm) range or orange range. (4FSSBOP . allowing the diffusion of Transcutol and the ingredient. commercially out up to 10 minutes before exposure to light as long as the available ALA products in Spain range from 1. 13 and other authors16 with ALAPDT applied on the whole face for short contact periods (30–60 FIGURE 6. spaced by 1 month. acnes. wereimages ob. one which reproduction use of any portion of the contents of these may is beamade without the consent of JDD. decreases erythrosis and fades hyperpigmentations and dyschromia in patients with photoaging. In their study. respectively). Photoaging signs on the chest (solar lentigines. they would stimulate fibroblasts and collagen metabolism. as reported are observed compared to the use of high concentrations and elsewhere14 and appear to be related to destruction of P.and marks of Journal of Drugs in Dermatology (JDD). low amounts of ROS are formed. making PDT an excellent therapeutic option for the treatment of acne. lated to the treatment which. Lubart et al. even the skin color.7. resulting in an improvement of photoaging signs. glands or both. Lower strengths of ALA and short incubation that the ALA-PDT helps modulate the immune response in the periods will popularize the use of PDT and will allow a greater skin of the patients with vitiligo.&t*446& (4FSSBOP . The partial results obyou feel you have obtained please contact immediately. with virtually no side effects. in the past. whichThis cleared rapidly and proprietary spontaneously.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 566 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. It is important to consider the psychological aspects of the treatment together with the cosmetic results observed in all patients.has been short periods of contact haveIf reduced completely the this paincopy re. A synergistic antitumoral effect has been described can also potentially prevent the development of solar kerain vitro in HUT-78 cellular lines of Sezary syndrome combining toses and related skin cancers. a combination treatment could be used: application of low-strength ALA on the whole face and focalized applications of higher strengths of ALA on specific lesions.illegally. two treatment sessions were done. document contains information. the texture (roughness) and elasticity of the skin. The improvements seem to be long-lasting. Do Not Copy.8 Ruiz-Rodríguez et al.24 Recently we treated a 29-year-old woman with a long lasting genital litions. improves fine wrinkles. at low concentrations. as described in other autoimnumber of treatments and the use of PDT in cosmetic applicamune diseases such as extragenital lichen sclerosus. Cosmetic results were favorable and the procedure was well tolerated. described as an JDD autoimmune disease. © only two mild of phototoxic effectsAll onRights the sebaceous reactions. chen sclerosus with ALA-PDT and achieved great success. In this instance. dyschromia). In patients showing signs of photoaging.15 Taub. 20% ALA was applied for 4 h and the skin was irradiated with intense pulsed light (590-1200 nm) at fluences of 40 J/cm2. which destroy collagen fibers. Fading of the solar lentigines and dyschromia after 3 treatments sessions with 1% Levuderm-ALA activated by intense pulse minutes and 15–30 minutes. But when at inner depths of the tissue. served No (Figure 8). 2009-Journal Drugs in Dermatology. In this study. larger contact periods. be also postulated as a result of PDT damage. FIGURE 5.32 has proposed that PDT would produce high amounts of ROS (reactive oxygen species). Reserved. Studies by the authors show that ALA-PDT. In addition.3FZFT FUBM fuse solar keratoses on the face and scalp exhibiting signs of photodamage would benefit with PDT. In or addition. as well as solar keratoses. there light (570-1200 nm). encouraging the formation of new ones. they will shorten the number of treatment sessions and with PUVA. Penalties Apply In acne cases. the small telangiectasias. it may be possible that light in the blue range could be the most The authors predict that these procedures will be more effecappropriate. was a restrictive factor tained with just 4 treatments are very encouraging. is no doubt that low strengths of ALA are effective and safe. The results showed the removal of 34 from 38 solar keratoses in 17 patients in 3 months. It is possible in the use of PDT. enlarging the use of procedures employing LED lamps.9 reported the use of ALA-PDT to treat solar keratoses of the face and scalp as a part of a unique photorejuvenation procedure.-PSFOUF . In these cases. PDT could also be used in combination treatment tive. An inlasers and intense pulse light sources emitting radiation in the hibition of the formation of antibodies against melanocytes may absorption spectrum of PpIX. these low concentrations andmaterials Vitiligo disorder that isexpress difficultwritten to treat. the authors’ results confirm the positive results obtained by Goldman. patients with dif- Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . FIGURE 8. Bergeron A. Mukhtar H. Joaquín Melendez and Dr. Large surface photodynamic therapy with aminolevulinic acid treatment of actinic keratoses and beyond.3(1 Suppl):S32-S39. All Rights Reserved. Photodynamic photorejuvenation.3(1 Suppl):S8-S25.&t*446& (4FSSBOP . Merk H.55(1):115-121. II. J Drugs Dermatol.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 567 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. 5. Gold MH. Photodynamic therapy in dermatology: History and horizons. et al.3FZFT FUBM Do Not Copy. Dermatol Surg. 3. PDT may induce hyperpigmentation in normal volunteers accompanied by an absolute increase of the number of melanocytes with histological signs of activation. Liu Y. 2002. Spain. DISCLOSURES Dr. Dougherty TJ. The evolving role of aminolevulinic acid hydrochloride with photodynamic therapy in photoaging. Bitter P. No reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD. Photoradiation therapy. Photodynamic therapy in oncology: Mechanisms and clinical use. Cure of animal tumours with hematoporphyrin and light.3(1 Suppl):S26-S31. Kilmer S. please contact JDD immediately. Grindey GB. Taub AF. Pass Hl. J Natl Cancer Inst.-PSFOUF . 2204. Segmental vitiligo in a 12-year-old patient. 2000. Photorejuvenation with in- Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . 1993. This melanocyte activation may play a role in the treatment of hypopigmentation diseases. Valencia. © 2009-Journal of Drugs in Dermatology. J Natl Cancer Inst. Sadick NS.30 Finally. Penalties Apply FIGURE 7. Avram DK and Goldman MP. Sanz-Sanchez T.42(3):389-413. Kaufman JE. it has been observed in mice that the population of Langerhans cells falls 1-5 days after the procedure. 8. 4. spaced every 10 minutes (Wood’s light). PDT and PUVA.contains Maria Navarro belong to theimages re. 2004. Cancer Res. Fluorescence of the skin after 4 applications of 1% Levuderm-ALA. Cordoba S. This document proprietary information. 7.29 PDT may also induce an immunosuppressive effect in a way similar to that of UV phototherapy.and marks of Journal of Drugs in Dermatology (JDD). Photodynamic therapy in dermatology. Bissonette R. Weiss R. Fiel R. J Drugs Dermatol. 6. Cutis. 2002. Kalka K. Segmental vitiligo showing perifollicular partial repigmentation after 4 treatments sessions with 2% ALA-PDT (Levuderm-ALA). search and development department of SeSDerma Laboratories. REFERENCES 1. 1978. Gabriel Serrano is medical director of SeSDerma Laboratories. Dr. Photoradiation therapy for the treatment of malignant tumours. Effectiveness and safety of ALA-IPL in treating actinic keratoses and photodamage. 10. If you feel you have obtained this copy illegally. J Am Acad Dermatol. et al. Goldfarb A. 2. J Drugs Dermatol. 1975. Ruiz-Rodriguez R.38(8):26822635.28(8):742-744. 9.31 FIGURE 9. 2004. 69(6 Suppl):8-13.85(6):443-456. Dougherty TJ. 2002. visible light-induced skin rejuvenation.. Richey DF. tol. Chang Y. 2004. (4FSSBOP .. Horska Z. Bridges TM. MD Goldman MP. Sala R.2(4):293-396. 27. J Drugs Dermatol. 46004 Valencia. 25.3:S32-S39.ofTreatment of sebaceous NoMH.. 28. 5(2 Suppl):6-8. 2004.. 31. 19.. 2007. Katz BE. Bradshaw V.. Maiwald DC. Photodynamic therapy for perioral dermatitis. Gabriel Serrano. 2006. 200. Lasers Surg Med.. traviolet A in vitro in HUT-78 enhances by 5-aminolevulinic acid. et al. Ewalds E. The effect of psoralen plus ul- Do Not Copy. Treatment of inflammatory facial acne E-mail:. 12. Yanagishita T.. Laser-mediated photodynamicoftherapy lichen sclerosus. Capezzera R. Heterogeneity of fluorescence in psoriasis after application of 5-aminolaevulinic acid: An immunohistochemical study. 2004. reproduction of any portion the contents of these materials may be made without the express written consent of JDD. Bridges TN. Hayami J.. Dermatol Surg.-PSFOUF . Light therapy for hidradenitis suppurativa. 2001. et al. Br J Dermatol.34(5):320-327.. J Biomater Appl. Watanabe D. J Drugs Dermatol. 26. 18.. J Am Acad Dermatol.23(2-3):95-97. Photodynamic therapy: Other uses.. 15. Monfrecola G... Rathinam K. 2007. et al. Treatment of cutaneous leishmaniasis by photodynamic therapy.3(6):S10-S14. J Drugs Dermatol. Gold BradshaworV. Boring MN. please contact JDD immediately. vulgaris. © 2009-Journal Drugs of in Dermatology. Patel V. Gold MH.39(3):203-209. The influence of photodynamic therapy on the wound healing process in rats.22(1):1-3. If you therapy feel youwith have obtained this copy and a blue light source or intense pulse light source. Okamoto H. et al. 25(1):101-109.. Photodynamic therapy for the treatment of erythema.. Hopson B. 29. J Drugs Dermatol. J Drugs Dermatol.32(8):991-996. Efficacy of microdermabrasion preceding ALA application in reducing the incubation time of ALA in laser PDT.115(2):183-192. 16... gland hyperplasia by photodynamic 5-aminolevulinic acid illegally. Taub AF... J Drugs Dermatol.. This document contains proprietary information. J Drugs Dermatol. Immunosuppressive efof photodynamic therapy using methylaminolevulinate as sensitizer fects of photodynamic therapy by topical aminolevulinic acid. Hongcharu W. Procaccini EM...3(6):S15-S19.. Clinical and echographic analysis 30. Bradshaw VL. 21.3FZFT FUBM tense pulse light: Results of a multicenter study. et al.3(1):41-49... Photo2004. Spain Rojanamatin J. J Drugs Dermatol. Truong S. 2007.3(6):S6-S9. et al..&t*446& 11. A reasonable mechanism for Taub AF. Alexiades-Armenakas M.3(6):S25-S27 . papules. Topical ALA-photodynamADDRESS FOR CORRESPONDENCE ic therapy for the treatment of acne vulgaris. ______________
[email protected](2-3):147-155. J Photopulse light and heat source and ALA-PDT in the treatment of acne chem Photobiol B.6(2):140-142. 2004. pustules.... Enk CD.. et al.. Sugihara A.. Zane C. Choawawanich P. Penalties Apply Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . Friedmann H. Jayasree RS. D’Onofrio D..48(6):893-896. Lavie R. 2006. Katz B. J Invest Dermatol.. Gold MH.. Taylor CR.. Lubart R. 20. 2004.. J Drugs Dermatol..3(2):187-190. J Drugs Dermatol.com vulgaris with intense pulsed light and short contact of topical 5-aminolevulinic acid: A pilot study. Horio T.. Laser-mediated photodynamic therapy of actinic cheilitis. 2007. and severe flushing consistent with rosacea..Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 568 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. Alexiades-Armenakas M. Gupta AK. J Drugs Dermatol.. Rauch L. Hyperpigmentation Gold MH. 2006.. 23. 17.. et al.. 14.15(3):176-186. et al.3(5):548-551... J Drugs Dermatol. 2004. 13. Akita Y.use Boring MM. Biron JA. Boring MM. 22. Phtodynamic Therapy for the treatment of acne: A pilot study. images and marks of Journal of Drugs in Dermatology (JDD). 204. Dermatol Clin.. 2003.155(3):539-545. 32. 2006. et al. Laser Med Sci.. Smits T.The successful use of ALA-PDT in the treatment of recalcitrant molluscum contagiosum.. All Rights Reserved. The use of a novel intense induced by topical 5-aminolaevulinic acid plus visible light. Kleinpenning MM.5(2 Suppl):12-16. Boyce SM.. Boring MM. 24. 2003. A single-center study of aminolevulinic acid Clínica Dermatológica Serrano and 417 nm photodynamic therapy in the treatment of moderate to Grabador Esteve 3 severe acne vulgaris. 2007. dermatol Photoimmunol Photomed.. Bridges TN. J Dermain the treatment of photodamaged facial skin. 2007. Gardlo K. and a mnemonics database. Board simulated exam © 2009-Journal of Drugs in Dermatology. please contact JDD immediately. Are You Prepared? Now Perf orming Faster than Ev er! Do Not Copy.com/professional Provided through an educational grant from Stiefel Laboratories Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F .. All Rights Reserved. If you feel you have obtained this copy illegally.A BEMaGS Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page F The Dermatology Board Exam is in August. And for a LIMITED TIME. bulleted information. No reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD. which includes high-yield. images and marks of Journal of Drugs in Dermatology (JDD). Penalties ApplyIn-Review We’re Here to Help: Dermatology Online Practice Exam & Study System Thousands of questions Interactive study tools Timed.. Be prepared on exam day: Stiefel. a diagnostic exam. Cram for the exam with the Online Boot Camp. Online Boot Camp This document contains proprietary information. Nevertheless.8 One of the most bothersome sons could be confounded by multiple factors. images marks of Journal Drugs in Dermatology (JDD).S. even tachyphylaxis. The authorsofconcluded that clobetasol propionate is a very This document contains proprietary information.S. clinical trial refor many patients with psoriasis. and the resulting poor adherbe strengthened by a trial that compared the same corticosterence. Other clobetasol propionate preparations were also very effective: clear or almost-clear status was achieved by up to 80% with a lotion formulation at 4 weeks.1 Potent topical corticosteroids are the primary treatment for psoriasis in the U. However.PSHBOUPXO 8FTU7JSHJOJB $FOUFSGPS%FSNBUPMPHZ3FTFBSDI %FQBSUNFOUTPG%FSNBUPMPHZ 1BUIPMPHZBOE1VCMJD)FBMUI4DJFODFT 8BLF'PSFTU6OJWFSTJUZ4DIPPMPG. foam preparation at 2 weeks and 82% with a spray formulation at 4 The disappointing results are surprising considering the high ef. raising concerns about both short-term and long-term adherence to treatment. since psoriasis is a dry. ficacy potent corticosteroid exhibit clinical trials.3-5 One reason ointments are preferred for psoriasis is that they are thought to be more powerful than alternative preparations.).%1I%C B 8FTU7JSHJOJB6OJWFSTJUZ4DIPPMPG. Thus. Moreover. that of ointments in clinical trial settings. these products may not be best suitas other vehicles in clinical trials. scaly process an ointment vehicle is used to help moisturize and repair barrier function.7materials effective treatment for psoriasis and that other preparations may No reproduction or use ointments of any portion of the in contents of these may be made without the express written consent of JDD. the traditional approach of using topical corticosteroid ointment preparations for psoriasis is often frustrating because of treatment difficulty and poor results.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F JUNE 2009 570 70-6. then. for the treatment of psoriasis.&t*446& COPYRIGHT © 2009 ORIGINAL ARTICLES JOURNAL OF DRUGS IN DERMATOLOGY Are Ointments Better Than Other Vehicles for Corticosteroid Treatment of Psoriasis? "OOB). Much of the poor outcomes in psoriasis. Poor compliance may explain why topical corticosteroid haveplease efficacy similar toimmediately. All Rights Reserved. Ointments: Not Necessarily More Effective Warino et al7 reviewed the efficacy of clobetasol propionate formulations for psoriasis as determined by published clinical trials.9 Poor tolerof the relative efficacy of ointments versus other vehicles might ability of sloppy ointment vehicles. The analysis was limited by changes in what psoriasis outcome measures were used over time.FEJDJOF 8JOTUPO4BMFN /PSUI$BSPMJOB C ABSTRACT Topical corticosteroids are the most common treatment agent for psoriasis in the United States (U. INTRODUCTION M Do Not Copy. A previous systematic review of the efficacy of clinical trials of potent topical corticosteroids did not support greater efficacy or greater delivery of potent topical corticosteroids with ointment vehicles compared to other topical preparations. Topical psoriasis treatment is likely to be more successful when physicians and patients discuss what type of vehicle the patient will use and plan treatment accordingly. preference studies demonstrate that psoriasis patients often find application of ointment to be messy. while ointment vehicles may be as effective messiness of ointments. Research subjects’ adherence to treatment is better than clinic patients’ To the extent that non-compliance is caused by the perceived adherence. Non-ointment topical corticosteroid products exhibit excellent efficacy in clinical practice. contact JDD ments are less effective in clinical practice than in clinical trials.and weeks. Instead. Understanding aspects of psoriasis is the messiness of treatment.2 Conventional dermatologic wisdom holds that ointment preparations are best for treating psoriatic plaque. This article presents a challenge to the conventional wisdom that ointments are the best vehicles for psoriasis. Using clobetasol propionate ointment for 2 weeks resulted in 70% of subjects achieving at least 75% improvement in lesions.JWLPWJDIBBOE4UFWFO3'FMENBO. Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . and the comparitions are not taken as prescribed. Conventional dermatologic wisdom holds that ointment preparations provide the highest potency (due to their occlusive nature and moisturizing ability) and are best suited for psoriasis. likely relate less to actual medication failure and more to failure to apply the medication. 68% with a © 2009-Journal of Drugs in Dermatology. may make ointments an unattractive choice of treatment oid medication in different vehicles. Penalties Apply ost people with psoriasis have limited disease that should be amenable to topical treatment. also. ointments have the potential ed. If you feel you have obtained this ointcopy illegally.FEJDJOF . treatment for to be less effective among actual clinic patients if patients find psoriasis should focus on finding treatment options with which the ointment vehicle less tolerable. sults are not necessarily indicative of clinical practice. Recent compliance studies demonstrate that poor compliance to topical treatment is common among psoriasis patients and contributes to poor psoriasis treatment outcomes. Some 30 to 40 percent of medications taken for chronic condiThese clobetasol data are from different trials. This article presents evidence challenging the conventional belief that ointment vehicles are necessarily best for psoriasis.6 the patient is most likely to comply. 8 Many of the remaining 60% are also non-adherent.11 Patients found a foam vehicle’s characteristics of no residue. ingredients. seemingly more effective than clobetasol ointments and creams. Messy vehicles may adversely affect patients’ quality of life. greasy corticosteroid ointment. was heralded as a miracle.9 Patient preference studies using validated measures confirm that some patients report that they do not like applying Clobetasol Spray: An Effective Treatment ointments. poor adherence was a significant predictor of change in total disease severity. ". The diary stated.10. ability to continue daily tasks directly following application. Potent treatment. positively correlated with poor outcomes. measures that effectively ments in psoriasis occurring within hours of initiating Skin Cap reduce the inflammation in psoriasis clear the plaques. reproduction or use ofdescribed any portionpatients’ of the contents of these materials be made without the express written consent JDD.12. “No longer do patients need in stecorneum. poor outcomes are frequently due to poor adherence and not to poor absorption or non-response. they are not moisturizers. Skin Cap was found to contain topical corticosteroids.17 Skin Cap illustrated the importance tion and to skin with poor barrier function. particularly in real-life clinical practice. Methotrexate.4. Another reason for good compliance with Skin Cap was that patients were not afraid of the potential for corticosteroids side effects.19 when corticosteroid ointments may have been more potent and Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . methotrexate formarks clearing psoriasis plaques.&t*446& Many Patients Dislike Ointments Quantitative measures of patient preferences for different vehicles have been developed and used to assess patients’ preference for different topical vehicles.12 Poor adherence is worse in clinical practice and a major factor limiting the effectiveness of topical corticosteroid ointments. This document contains proprietary images and of Journal of Drugs in Dermatology (JDD).23 Do Not Copy. applied directly to the site of inflammaclobetasol propionate.23 probably at least in part because of past frustrathe-counter (OTC) medication for the treatment of psoriasis. ability to feel free of medication after application and the ability to apply to any body area.21 Some 40% of patients with psoriasis report non-adherence to their medication. occlusive preparation is not necessarily more potent than a non-moisturizing clobetasol propionate formulation. but immediately. cyclosporine and or PUVA ” The authors previously unTNFmay (tunor necrosis factor) inhibitors are highlyof effective psoNovisits.15 The product was presumed to be steroid-free.18 The high efficacy of Skin Cap was not due to a difference tologists to recommend corticosteroid ointments for psoriasis is in the bioavailability of clobetasol propionate with Skin Cap an anachronism. dating to an early time in vehicle development compared to approved clobetasol propionate preparations. Patients were more compliant with a spray of Skin Cap than they were with the more intrusive. Another study found histological improveizing may be of some benefit by itself. demonstrated that a greasy. The tendency for dermasis.10 Less messy preparations are preferred by some patients over ointment preparations. stain-free. Penalties Apply Patients often report that they find ointments messy and difficult to use. ingested or injected.13 Moreover.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 571 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. Not only are psoriatic lesions frustrating but treatment with the continued application of messy topical preparations for years is also frustrating. please contact JDD a one-second spray. Moisturizing the plaque is not a necessary condition roids inuncted. While moisturIf you feel you have obtained this copy illegally. however. The potency of topical corticosteroids is determined not only by how potent the active drug is at activating corticosteroid receptors and how well the vehicle delivers the drug into the skin. but also by whether the topical corticosteroid is actually applied. tion with greasy topical preparations. Poor Compliance to Topical Treatment The association between patient adherence practices and changes in psoriasis severity have been assessed using quantitative electronic monitors. Skin Cap. and no moreinformation.JWLPWJDI 4'FMENBO The effectiveness of Skin Cap was likely a matter of compliance.20 Many poor outcomes in psoriasis probably relate less to actual medication failure and more to failure to apply the medication. The well observed phenomenon of tachyphylaxis may represent the steady decrease in adherence to topical treatment rather than any loss of corticosteroid receptor function.12-14 These monitors were used to assess adherence to twice daily application of salicylic acid in a controlled trial of salicylic acid plus topical tacrolimus ointment versus salicylic acid plus placebo. conticosteroid vehicles that are less messy than ointments and that taining zinc pyrithione and sodium lauryl sulfate as its active are effective for delivering the active drug through the stratum © 2009-Journal of Drugs Dermatology. and fragrance-free as excellent or good by at least 95% of patients. responsive psoriatic plaques vanishing after only days of using riasis treatments. including ease of use. This OTC remreducing the inflammation and clearing psoriasis lesions. quick-drying. a spray clobetasol propionate that was more potent in clinical practice than any clobetasol propionate ointment. Ultimately.10 Many psoriasis patients don’t even bother to fill their In their treatment diary. DISCUSSION Across all medical disciplines. as they thought they were just using zinc pyrithione. It wasn’t the zinc. are highly effective at of patient compliance and treatment outcome. There are now topical corSkin Cap. All Rights Reserved. Those subjects receiving clobetasol foam rated the foam characteristics 61% superior to ointment. and 98% that they would be likely to comply with twice-daily dosing for 28 days with the foam as compared to 56% compliance with ointments. Shelley and Shelley describe an overprescriptions. edy.11 This vehicle was ranked as superior to other formulations based on impact of quality of life. a clinical Topical psoriasis treatment is likely to be more successful when trial found that topical zinc pyrithione added nothing to the effiphysicians and patients discuss what type of vehicle the patient cacy of topical clobetasol propionate in the treatment of psoriawill use and plan treatment accordingly. Poor adherence was common in the study.22. . The odds of the three nons when an aptly prescribed medi2006..54(2):212-220..
[email protected]% zinc pyriREFERENCES thione spray does not enhance the efficacy of clobetasol propionate 1... of life: of a 1998 National patient-memnever Primary nonadherence an outpatient clinic. et al. Spellman MC. Arch Dermatol. NC 27157-1071 9... Kirkland R.... Deja vu all over again: A poster version of this work was presented at the 2007 Annual Skin cap still contains a high-potency glucocorticosteroid. Feldman.. 7........... Feldman SR. McGraw-Hill Companies.......contains et al. Carroll CL. 2003. Rapp SR.. Rapp SR. Wake Forest University School of Medicine riasis and their compliance with medication.. Balkrishnan R. Int J Dermatol. Stealey KH.. Feldman SR. Kerdel FA. Feldman SR....70(3 Pt 1):327-332. PhD 8. Balkrishnan R. Johnson RA.. Arch Dermatol. Cento16.edu ______________ solution and foam vehicles: A quantitative assessment of vehicle preference. a less messy vehicle may be preferable for other patients..JWLPWJDI 4'FMENBO when patients’ adherence to treatment wasn’t recognized as a major factor driving the outcome of psoriasis treatment.49(1):79-82... 2004.. J Am Acad Dermatol....51(2):212-216.. please contact JDD immediately. clobetasol propionate foam 0. Rowlands CG and Danby FW. 2000. et al. Carroll CL.. substantial burden even when not extensive. consulting and speaking support from Galderma. Br 3. Management of Psoriasis. Camacho FT.. 20. PCM. Mosby New York. Feldman has received re15. Tachyphylaxis to topical corticosteroids: The more you © 2009-Journal Allthem. Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology. peutic tachyphylaxis to topically applied steroids in patients with pso2003:2324-2328... from Galderma Laboratories.&t*446& ".59(1):27-33..9(2):136-139. search... Medical Center Boulevard 1999. 2003:125-149... Clobetasol propionate for ADDRESS FOR CORRESPONDENCE psoriasis: are ointments really more potent? J Drugs Dermatol. Swanson DL. 6th edition. Exum ML. Wolff K. Urquhart J. Br J Dermatol.P...151(4):895-897. DISCLOSURES 14. Ms.. The best vehicle to use for psoriasis treatment may not be an ointment. use theReserved.. 11..... Eisen AZ... Patients with psoDepartment of Dermatology.. J Am Acad Dermatol. Penalties Apply Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F ... Patients with psoriasis prefer E-mail:.... J Health Psychol.. Winston-Salem.. images and of A..59:181-182... Feldman SR.. J Am No Results reproduction or use of any Psoriasis portion ofFoundation the contents of these materials may beredeemed: made without the express writteninconsent of JDD. While some psoriasis patients do prefer ointments and can be effectively treated with ointment preparations. Spellman MC. Feldman SR. clobetasol propionate in different vehicles. Bioavailability of 2004. Histopathology of psoriasis treated with cor. J Cutan Med Surg.marks Storm Andersen SE.. 6. 18.... If you feel you have obtained this copy illegally. 19. Abbott. riasis. Stern RS..22(3):272-276. Amgen. 1997. 2004.45(4):370-374.. Keil KA. Camacho FT.. 2006.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 572 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. Feldman SR. ConCutis. et al... Suurmond D. The efficacy and tolerability of Do Not Copy. Failure to demonstrate theraeral Medicine... Topical Glucocorticoids. Dr.. Reboussin DM... J Am Acad Dermatol. Balkrishnan R. Cutis..16(4):212-216. Housman TS. Feldman SR. Steven R... NY.41(4):581-583. Critical factors detion. One in 3 prescriptions are This document information... the best vehicle is likely to be the one the particular patient will best use... psychological Phone: ... Roling D. Feldman SR. Warner Chilcott. New York. Meeting of the American Academy of Dermatology.... Lehman PA. 2002.. termining the potency of topical corticosteroids.. non-absorption.. 1997:2:525-537.. 2003. Lebwohl M... Balkrishnan R. 2006. 5th edi21.. and is associated with 2003. Skin Pharmacol Appl Skin 2. netics/Stiefel. New York. Benfeldt E.. carries a 0. widespread treatment dissatisfaction. Pearce DJ... 4.... Fax: .... Jorizzo J.. 2005.. 13.7(3):185-192...41(4):546-549. et al..137(3):280-284....05% foam in the treatment of psoriasis. ACKNOWLEDGEMENTS 17.. non-response. Fortune DG.. Margolis D....... Am J Dermatopathol. Benson LM. In: Freedberg IM.. et al.05% in the treatment of mild to moderate plaque-type psoriasis of nonscalp regions... Richards HL.. The physical. Psoriasis... O’Sullivan TM.. Fitzpatrick’s Dermatology in Gen22.... et al.. Franz TJ. et al.. Koo J..141(6):801-803. Less messy corticosteroid preparations are now available that effectively deliver the active corticosteroid through the epidermal barrier.24(3):229-230. cine isn’t working: Non-compliance.... (eds). Mellen BG. Guzzo C. less they work? Clin Dermatol. NY... Valencia IC. Pittelkow MR.. Mellen BG.336-716-7740 and social impact of psoriasis. et al. and Coria.. Ford RO.. Van de Kerkhof. Acad Dermatol.. 2005:68-71.. 336-716-7732 10. L.. bership survey... Balkrishnan R. Theproprietary impact of psoriasis on quality 24.49(4):651-654. Wolff K. Gottlieb AB. J Investig Dermatol Symp Proc. zinc pyrithione..... Journal of Drugs in Dermatology (JDD). 2006. 5.. J Dermatolog Treat.... 1999. Astellas.. J Clin Pharmacol.. Psoriasis treatment Physiol..... 2003. Nijsten T. Shelley WB and Shelley ED. In: Bolognia JL.. J Am Acad Dermatol.. et al... Adherence to topical therapy decreases during the course of an 8-week psoriasis clinical trial: Commonly used methods of measuring adherence to topical therapy overestimate actual use.. Krueger G. 2008. The use of 0.5(6):527-532. Warino L.... Miller JJ.... NY. McGraw-Hill Companies. Dermatology.... Camacho FT. MD. 12.. 2001...17(3):133-135.. Better medication The Center for Dermatology Research is supported by a grant adherence results in greater improvement in severity of psoriasis. Austen KF.. in the United States at the end of the 20th century..of Drugs in Dermatology. 2002. Rapini RP 23. Psoriasis is common.. Electronic monitoring of medication adherence in skin disease: Results of a pilot study. J Am Acad Dermatol. Zivkovich has no conflicts to declare. Serup J. Carroll CL. Housman TS. A dermatologic diary: Portrait of a practice. Rights (eds). Pearce DJ. ofverrucous plaque located on hisdocument left upper lip. When the patient presented. there was a 4 cm by 3 cm hyperkeratotic.% /BUBMJF4FNDIZTIZO. Upon discontinuation of sorafenib. Since medications like sorafenib have a prolonged treatment course. reproduction use of portion of the present contents on of these areas of his body or any previous a similar The illegally. The lesion was neither images pru. He continued chemotherapy for another month before sorafenib was discontinued secondary to the unresolved skin eruption. this copy patient had been receiving sorafenib 400g. FIGURE 1. Within the plaque. $"4&3&1035 A 55-year-old Asian male with a past medical history of multifocal hepatocellular carcinoma.% /JDPMF. All Rights Reserved. The intra-oral cavity was moist and pink with no abnormal findings.JTTPVSJ "#453"$5 Sorafenib. Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . please contact JDD immediately. are likely to affect medication compliance and patient self-esteem.% %FQBSUNFOUPG%FSNBUPMPHZ 4BJOU-PVJT6OJWFSTJUZ4DIPPMPG. Penalties Apply As sorafenib continues to gain popularity in the treatment of end-stage renal and hepatocellular carcinomas. Focal acantholytic dyskeratosis of the epidermis (Hemotoxylin-eosin stain. a multitargeted kinase inhibitor used for the treatment of unresectable hepatocellular carcinoma and advanced renal cell carcinomas. If you history feel you of have obtainedrash. ritic norNo painful. he had been off sorafenib for three weeks. and nondescript. The most common and well-studied cutaneous side effect of sorafenib is the hand-foot skin reaction.and marks of Journal of Drugs in Dermatology (JDD). 4 cm x 3 cm hyperkeratotic. Do Not Copy.” The rash had been previously diagnosed as folliculitis and herpes zoster for which he received acyclovir without improvement. However sorafenib induces many other cutaneous side effects that tend to get reported under the broad. umbrella of “rash. original magnification: X100). erythematous and somewhat sclerotic plaque with multiple yellowish papules resembling milia. FIGURE 2. It therefore remains important for physicians to recognize and treat these cutaneous manifestations promptly. especially those which are cutaneous and visible. the incidence of both typical and atypical cutaneous side effects will increase. erythematous and somewhat sclerotic plaque located on his left upper cutaneous and mucosal lip (Figure 1). twice daily. there were multiple yellowish papules which resembled milia. for eight months when this skin eruption occurred. At the time he was also taking lamivudine.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F JUNE 2009 573 70-6. Since its introduction to the market. there have been various dermatologic side effects reported in the literature. the most well known being hand-foot skin reaction. received FDA approval in 2005. */530%6$5*0/ T he association between kinase inhibitors and the risk of developing cutaneous side effects is a well reported phenomenon in the literature.&t*446& COPYRIGHT © 2009 CASE REPORTS JOURNAL OF DRUGS IN DERMATOLOGY Localized Dyskeratotic Plaque With Milia Associated With Sorafenib +FBOFFO"$IBQQFMM.#VSLFNQFS. This article presents a case of an atypical localized cutaneous eruption with an unusual course and protracted resolution time associated with sorafenib therapy. This contains proprietary information. This article presents a patient with an atypical cutaneous side effect associated with sorafenib therapy. On physical examination. Thereorwere noany other lesions othermaterials may be made without the express written consent of JDD. hepatitis B and diabetes mellitus © an 2009-Journal Drugs in Dermatology. the hematologist noted some improvement of the lesion.FEJDJOF 4BJOU-PVJT . metformin and glipizide. presented with a two-month history of enlarging. their side effects. 3 cc of intralesional triamcinolone was given using two separate injections. During the next four weeks. %*4$644*0/ FIGURE 4. FMSlike tyrosine kinase-3 (Flt-3) and c-KIT. Sorafenib is a multikinase inhibitor which is FDA approved for the treatment of unresectable hepatocelluar carcinoma and advanced renal cell carcinoma. please contact JDD immediately. All Rights Reserved.05% gel every night and triamcinolone 0. There was also a lymphocytic infiltrate consisting of histiocytes and multinucleated giant cells surrounding the follicles (Figure 4). At this time the patient resumed sorafenib at a lower dose of 200 mg daily.and extracellular levels. After four weeks.2 Blocking VEGFR. Intralesional triamcinolone 5 mg/cc injections were added to the treatment regimen with the hope of achieving more rapid resolution. The bacterial. original magnification: X40). Three months following the discontinuation of both sorafenib and intralesional triamcinolone. Flt-3 and PDGFR-B effectively inhibits tumor angiogenesis while block- Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . respectively. which dramatically improved the appearance of the lesion (Figure 5). The bacterial. the patient’s cutaneous lesion almost © 2009-Journal of Drugs in Dermatology. it also inhibits RAF serine/threonine kinases C and B. white.1 In addition to inhibiting the receptor tyrosine kinases VEGFR 2 and 3 (Vascular Endothelial Growth Factor Receptor). sorafenib was discontinued by his hematologist/oncologist secondary to poor tumor response of the hepatocellular carcinoma.1% ointment every morning to the lesion. Penalties Apply FIGURE 3. sorafenib was increased to 200 mg twice daily. One week prior to the time of final injection. fungal and acid-fast bacilli cultures of the thick. which play important roles in the RAS/RAF/MEK/ERK pathway. The patient applied tazarotene 0.1. a total of 0. Granulomatous inflammation surrounding a ruptured follicle (Hemotoxylin-eosin stain. PDGFR-B (Platelet Derived Growth Factor Receptor Beta). c-KIT. Biopsy sent for direct immunofluorescence was negative. the lesion improved but did not resolve on this regimen. fungal and acid-fast bacilli smears and cultures performed on biopsied tissue from the left upper lip were negative. he later received one more 0. original magnification: X100). resolved completely except for a minor amount of residual erythema desquamation (Figure 6). Hyperkeratotic and dilated follicular infundibula and milia (Hemotoxylin-eosin stain. The patient was given the diagnosis of localized cutaneous drug eruption most likely related to sorafenib therapy. Do Not Copy. topical therapies were This document contains proprietary information.2 cc injection of triamcinolone 5 mg/cc with additional improvement.(JDD). It works by inhibiting tumor cell replication and angiogenesis at multiple intra.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 574 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6.&t*446& +$IBQQFMM /#VSLFNQFS /4FNDIZTIZO Punch biopsies were performed on the left upper cutaneous lip which showed focal acantholytic dyskeratosis (Figure 2) with hyperkeratotic and dilated follicular infundibula (Figure 3). If you feel you have obtained this copy illegally. milia-like contents expressed from the small papules was also negative. images and marks of and Journal of Drugs in Dermatology discontinued at this time. Subsequently. Gomori methenamine silver (GMS) and acid-fast bacilli (AFB) stains were negative for fungi and mycobacterium. No reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD. Topical therapy was continued. this does not appear to be the case in this patient. suggested treatment or expected resolution time. is hand-foot skin studies which report spontaneous resolution of cutaneous lereaction.PDGFR-B sorafenib experienced dermatologic effects whichthis includthere is a theoretical that minute vasculature in those areas If you feelside you have obtained copy illegally. keratoacanthomas. images and Journal of Drugs in Dermatology (JDD). effects to be as high 91% in the group treated with sorafenib.4 However. keratinocyte differentiation and/or proliferation because muleczema/xerosis.3. doublebe related to tirosyl-kinase inhibition.4 Side effects may also be dose dependent as they tend to resolve The most common dermatologic side effect of sorafenib therapy. The combination of topical and intralesional treatments helped the lesion improve in seven months despite the patient resuming sorafenib during that time.1. hyperkerathis case supports the evidence that sorafenib may indeed alter tosis of the skin or nipples. the cutaneous side effects of the drug were not thoroughly characterized and were usually given generalized descriptions such as “rash. Due to blockade VEGFRofand No reproduction or use of any portion of the contents of these may be made the express writtenofconsent JDD. erythema multiforme.” However. One report hypothesizes that they may discontinuation of the medication. epidermoid cysts. its location.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 575 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6.5 FIGURE 5. Since its advent. Previous reports of cystic lesions. vastiple side effects associated with sorafenib (such as keratoacan- Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . please contact JDDrisk immediately. patients with advanced renal cell carcinoma have experienced longer periods of progression-free survival. mouth. One randomized.1 components needed for repair resulting in a skin lesion. However. of various cutaneous side effects to occur in areas subjected a total of 85 patients found the incidence of dermatologic 4 to marks repeatofmicro-trauma and pressure such as the scalp.4 In our case. with dose reduction or discontinuation. it is not clear if discontinuation of sorafenib alone would have led to complete resolution of the eruption or how long this would have taken. as more patients gain access to sorafenib and the incidence of cutaneous side effects is now known to be very common.1 Cystic lesions are one of the rarer side effects of sorafenib. ing RAF kinases inhibits tumor cell growth. multiple studies have found that cutaneous side effects are a positive predictor of better treatment outcomes.3 Another theory links pathogenesis to lesion location by highlighting the tendency blinded. bullae. scalp dysesthesia. stomatitis.4 2 chemotherapy. This has recently been regarded as a separate entity sions without dose reduction and recurrence of lesions despite than the hand-foot syndrome which occurs with other types of resumption of therapy at a lower dose. anywhere between 19–40% of patients onmaterials nails. Improvement of the skin lesion with topical and intralesional therapies. acne. have occurred after six to 11 weeks of sorafenib dosed at 400 mg twice daily. melanocytic lesions and squamous cell carcinoma of the skin. ed rash and/or desquamation and 21–30% developed hand-foot would become vulnerable to micro-trauma due to inhibition of skin reaction. there are and the most well-described in the literature. This is especially true since eruption severity and the extent to which these symptoms impact daily The mechanism of the cutaneous side effects to sorafenib activities are guidelines in governing both the dosage and/or remains unknown. Thisas document contains proprietary information. culitis. hands andwithout feet. Penalties Apply When sorafenib was initially studied in large-scale phase 3 clinical trials. there was more improvement with topical therapy than with discontinuation of sorafenib alone. Although VEGFR is not found at the surface of keratinocytes.2. However. In two larger studies. including milia. the patient’s cutaneous side effect was late in onset (32 weeks) and only achieved minimal improvement upon discontinuation of sorafenib alone. folliculitis. the need for studies directed specifically at carefully reporting the various cutaneous presentations is important. exfoliative dermatitis. hair depigmentation.3. Although the plaque responded best to intralesional triamcinolone. These complications typically occur during the first 15 weeks of treatment and partial-to-complete resolution is usually achieved with either discontinuation or reduced-dose therapy. In addition. placebo-controlled phase 3 clinical trial which enrolled © 2009-Journal of Drugsside in Dermatology. alopecia. Do Not Copy.&t*446& +$IBQQFMM /#VSLFNQFS /4FNDIZTIZO FIGURE 6. Other less commonly reported cutaneous side effects are erythema. Hence. Patient after all treatments were stopped. All Rights Reserved. subungual splinter hemorrhages. these reports did not provide detailed descriptions of the lesion. ...17(6):549-550......... 4.... Sibaud V.. Annually updated Study No reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD....12(10):1178-1182.. A distinct cutaneous reaction to sorafenib and a multikinase inhibitor..... (314) 256-3431 E-mail: .... Nexavar (sorafenib) tablets..... +$IBQQFMM /#VSLFNQFS /4FNDIZTIZO 5. 2007. Chanco Turner ML..... Richetta AG. (314) 256-3430 Fax: .... Maroon MS. Carboni V...47(7):767-769.... Accessed August 1...... Eur J Dermatol. Beldner M... 2008...Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 576 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6.. 2008... skin and nail disease...........com/professional For more information......... MO 63104 Phone: .. 2007. Kong HH. Exclusive Exam Cram Pack This document contains proprietary information. images and marks of Journal of Drugs in Dermatology (JDD)... Maiani E. et al........... All Rights Reserved. et al. Escudier B.... 3. Sorafenib: Atypical cutaneous side effects...... Arch Dermatol.... Louis............. Sorafenib-induced eruptive melanocytic lesions. Wechsler J. a novel multikinase inhibitor. MD Department of Dermatology Saint Louis University School of Medicine 1402 South Grand Blvd.pdf. Available at: http://berlex.... gaining a better understanding of how sorafenib causes these cutaneous side effects will provide further insights into the pathogenesis of hair. 2008.. Guide CD-ROMs If you feel you have obtained this copy illegally. bayerhealthcare. 3&'&3&/$&4 1. J Drugs Dermatol.......... et al... Krasny M... Join the Penalties Apply Complim e Membersntary h for 2009 ip Graduate s! ALUMNI CLUB Members receive: © 2009-Journal of Drugs in Dermatology.6 More studies on the mechanism.....edu ___________ Do Not Copy... St.. Lountzis NI.. Int J Dermatol.7(6):588-589........ Inc... Burges GE....... and milia) can all be related to keratinocyte and keratin dysfunction... Bayer HealthCare Pharmaceuticals Inc.144(7):886-892. please contact JDD immediately. Prospective study of the cutaneous adverse effects of sorafenib.. Joncas V..... Autier J.&t*446& thomas.... Continued access to the Online Practice Exam & Study System Join TODAY at Stiefel... e-mail us at info-ETAS@pceny... 2.com ____________________ Provided through an educational grant from Stiefel Laboratories Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F ..144(6):820822... 2008.. ADDRESS FOR CORRESPONDENCE Natalie Semchyshyn.. Localized palmar-plantar epidermal hyperplasia: a previously undefined dermatologic toxicity to sorafenib.... Jacobson M.. et al. et al. Oncologist. 6......... In addition.. 2008.... Arch Dermatol..4.... and Onyx Pharmaceuticals.... hyperkeratosis..com/html/products/pi/Nexavar_PI.. treatment and expected resolution time of the cutaneous side effects associated with sorafenib therapy need to be conducted in order to help better direct treatment. Sammour R.. Sorafenib-induced palmoplantar hyperkeratosis...........nsemchys@slu.. 7. In addition. maintenance on pilocarpine therapy over the past 9 months has resolved her parotid pain without side effects.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F JUNE 2009 577 70-6. This tive values for comprehensive metabolic panel. Upon further are xerosis and acne. There was Ifno evidence ofthis lymphyouradiologic feel you have obtained copy illegally. irregular sal right hand. Compared to unaffected controls.&t*446& COPYRIGHT © 2009 CASE REPORTS JOURNAL OF DRUGS IN DERMATOLOGY Painful Parotid Hypertrophy With Bulimia: A Report of Medical Management . tooth decay with erosions. consistent with Russell’s sign. fine rhytides. the patient admitted to having a 10-year history of (abrasions on the dorsal hand caused by the upper teeth from active bulimia and secondary osteoporosis. Her current medicapigmentation. exOn the basis of her clinical history. Her eating disorder stimulation of the gag reflex) occurs in 30% of cases. Do Not Copy.1)C B /PSUIFBTUFSO0IJP6OJWFSTJUJFT$PMMFHFPG. complete blood group of patients may seek treatment for minimal dermatologcount with differential. self-induced vomiting) in order to avoid weight gain. All Rights Reserved.0 mg a day and was titrated to 5.2 Gupta and Gupta3 found a significant association between eating disorders and cheeks to temporomandibular joint syndrome. Symptomatic treatment with oral parotid hypertrophy pilocarpine hydrochloride tablets was initiated at a dosage of in a patient who presented with 5. In addition. acne. a rare but troubling manifestation is disfiguring parotid enlargement (sialoadenomegaly)..g. Massive due to bulimia was made. modest reduction in the parotid gland size was achieved (Figure 3). her bilateral cheeks overlying the is often associated with concomitant affective disorders—most parotid glands were markedly enlarged.Russell’s sign. Proposed theories include abnormal parotid adenopathy.%B 3FCFDDB$5VOH. laboratory and imaging studies. which was being dermatologic complaints.5 the etiology of the process glands (Figure 2). Penalties Apply Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . roughness and dark circles under tions included calcium and vitamin D supplementation. caries and mild parotid hypertrophy).3 unrealistic expectations puted tomography (CT) scan of the head and neck demonstrated bilateral massively parotid glands with Thisenlarged documenthomogeneous contains proprietary information. periodontal disease and level of 413 U/L (normal 0-137) accompanied by normal or negaconjunctival suffusion or hemorrhage may also be seen4. bulimia was first described in 1969. While benign parotid hypertrophy and no masses as well asordiffusely enlarged sublingual No reproduction use of any portion ofbilaterally the contents of these materials maythe be association made withoutbetween the express written consent of JDD. $"4&3&1035 %*4$644*0/ A 36-year-old Caucasian female presented with cosmetic Bulimia nervosa (BN) is an eating disorder characterized by recomplaints of sun damage and wrinkles. firm and tender to palcommonly depression and body-image distortion issues inpation. alopecia and hypertrichosis) and oral pathologies (e. hypertrichosis. sympathetic innervation. is still unknown.FMMZ.1.%. malnutrition.of what treatment can accomplish.enamel erosion. Laboratory tests revealed increased serum amylase dentin hypersensitivity.. estradiol the eyes. The patient stated that her dentist attributed her swollen cluding low self-esteem and self-criticism. Inspection of the oral cavity revealed 81% of individuals with eating disorders reported dissatisfacexcellent dentition (Figure 1). The patient declined fine needle aspiration. While commonly associated conditions due to binging and self-induced vomiting include cutaneous entities (e. anti-nuclear antibodies. Carotewas currently being managed by her primary care physician and noderma. images and marks of Journal of Drugs in Dermatology (JDD).1BSL. though the patient continues binge-purge behaviors despite multi-disciplinary intervention. a diagnosis of sialoadenomegaly FIGURE 1.3 The most common cutaneous manifestations of BN and an etonogestrel/ethinyl estradiol vaginal ring. cholinergic stimuli.g.g. therapist.FEJDJOF 3PPUTUPXO 0IJP C %FQBSUNFOUPG%FSNBUPMPHZ $MFWFMBOE$MJOJD #FBDIXPPE 0IJP "#453"$5 In eating disorders. physical examination. This article presents a case of painful sialoadenomegaly associated with hyperamylasemia in a bulimic patient successfully managed with pilocarpine.. anti-SSA and ic disease due to altered self-perception and may also possess SSB and angiotensin-converting enzyme (ACE) studies. alopecia. Com© 2009-Journal of Drugs in Dermatology. body image disturbance often extends beyond the realm of weight and shape into the dermatologic spectrum.0 mg three times daily. such as bulimia nervosa. Physical examcurrent binge eating that is followed by a compensatory behavination demonstrated scattered facial lentigines and fine ior (e. xerostomia. managed with a bite guard. Alswollen cheeks. She also had faint scars on her dortion with their skin appearance with respect to dryness. It forehead rhytides. please contact JDD immediately. while the pathognomonic Russell’s sign questioning.%C "SMFOF3VJ[EF-V[VSJBHB. con- Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . is extremely binge-purge activity.1. When present in bulimics. hyperlipidemia.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 578 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. Most frequent alterations include hypokalemic. both of which can exacerbate the body image and psychiatric issues in bulimic patients. The lack of complete regression of parotid hypertrophy in this patient may be explained by the fact that the she has been unable to refrain from binge-purge behaviors despite intervention. Sialograms are usually normal. flow rate compared to normal control patients.1BSL 35VOH "3VJ[EF-V[VSJBHB sarcoidosis. hypothyroidism. parotid hypertrophy may manifest as unilateral or bilateral painless enlargement of the glands. tumors. also found that the degree of patrophy—the enlargement of Ifparotid due illegally. hyperreduction of parotid gland size. autoimmune diseases including Sjögren’s syndrome and The most effective overall treatment of bulimia-associated parotid hypertrophy is a multi-disciplinary approach toward management of the underlying eating disorder.12 In their study.5% of these patients. gout. Amylase values may also be elevated. All Rights Reserved. Morbidity stems from cosmetic deformity and the risk of permanent enlargement. rare. Abstinence from binge-purge behaviors can lead to normalization of parotid gland size. In one series. Metabolic and endocrine disorders (diabetes mellitus. They found swelling in bulimia nervosa and has been documented in 10– that a serum amylase value of 75 U/L or greater when accom25% of individuals. lymphocytic infiltrate or fatty change. nutritional disorders and menopause) have also been associated with parotid enlargement.11 Gwirtsman at al. © 2009-Journal of Drugs in Dermatology. While the inboth parotid swelling and amylase values decreased during the cidence of parotid hypertrophy and adjunctive salivary gland abstinence phase for hospitalized bulimic patients. and infection.6 Ultrasonography can be used to rule out parotid hypertrophy. observed a relationship between parotid hypertrophy and hyperamylasemia. In the interim. Do Not Copy. however. the change in appearance is not often immediate. Parotid swelling usually occurs 2 to 6 days after a binge-purge episode. Fine-needle aspiration shows normal tissue with no inflammation.8 Benign parotid hypertrophy is observed in a variety of other conditions: inflammatory disorders such as bacterial or viral infection. images and marks ofasJournal Drugs in10Dermatology (JDD). you feelcellular you havecomponents obtained this copy contactPhilipp JDD immediately. may present as bilateral parotid enlargement. as seen in this young woman. It may regress or persist. 7 Salivary secretion studies have shown that people with bulimia have a reduced resting erosions.&t*446& . amylasemia was seen in 61% of binge-purge type patients with The degree of hyperamylasemia bulimia. This document contains proprietary information. Computed tomography (CT) scan of the head and neck showing bilateral significantly enlarged parotid and salivary glands. Malignant diseases. pituitary-adrenal axis disorders. granule depletion. Penalties Apply Electrolyte abnormalities often accompany parotid hypertrophy in people with bulimia. cessiveNo starch ingestion. andplease vomiting.9 chronic bulimia can lead to irreversible parotid enlargement. metabolic disorders and work hyperwasmay shown to bewithout proportional to the frequency binge eating reproduction or use of any portion of the contents of these materials be made the express written consent of JDD.6. FIGURE 2. persistent disfiguring parotid enlargement panied by parotid enlargement can help identify and monitor (sialoadenomegaly). occurring in less than 0. rotid enlargement correlated with the severity of dental enamel to chronic autonomic stimulation. stones. showing normal ducts and tributaries. liver disease. 10 et al. hypochloremic metabolic alkalosis due to vomitFIGURE 3. depending on the status of binge-purge activity and the pattern of gland enlargement.6 The course is often variable. Treatment with maintenance pilocarpine resulting in ing. and drug reactions to radioactive iodine I131 or anesthesia. Computed tomography (CT) scan of the head and neck usually shows only parotid enlargement with no masses. in ourofpatient. allergic reactions. including lymphomas and parotid neoplasia. While intermittent hypertrophy most often occurs in those who vomit at least once daily. .. Parotidectomy for bulimia: A dissenting view.. Zonnchen B. Hamm GI... A new treatment. All Rights logically devastating related conditions... Allevato M...... 6.. With this isofmind.. Riad M.... 44122 © 2009-Journal Drugs the in Dermatology. Berke GS. J Clin Psychiatry... During treatment. E-mail:.. Wilson JA.. Pyle RL.becki_tung@yahoo. Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F .. To confirm the diagnosis of bulimia-associated parotid hypertrophy. Philipp E........ 1991. 2007. it is presumed that the increased flow of saliva may serve to “decompress” the glands... Sialadenosis in bulimia..... Am J Psychiatry..... diarrhea..com ______________ encountered on physical examination. Herzog DB.5 mg daily for total treatment duration of two weeks. Hyperamylasemia and salivary gland enlargements in patients with eating disorders. dermatologist should be certain to inquire further regarding a and marks of Journal of Drugs in Dermatology (JDD). Pilocarpine has been reported to be a successful medical intervention in two refractory cases.. 9. 1993. Kessler RC.. which include flushing. 4.39(5):348-353... MD Department of Dermatology While bulimia is an eating disorder that may have numerous 26900 Cedar Rd...9 Pilocarpine is a parasympathetic muscarinic receptor agonist that increases secretions from glands. Concomitant medical therapy with oral pilocarpine can be employed to alleviate discomfort and modestly reduce gland size.7 In patients who are unable to cease purging activities. OHReserved.. Barton JR. In their first patient... Total dosage of pilocarpine is limited by adverse effects. Mitchell JE.. Hatsukami D. Dissatisfaction with skin appearance among patients with eating disorder and non-clinical controls... flushing and increased salivation. Gwirtsman HE.95(5):597-598.. associated dermatologic findings.....Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 579 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. 2.145(1):110-113.7....142(4):482-485. the patient experienced increased sweating....... as in our case..1(7591):426. Acta Otolaryngol. Int J Eating Disord..... Primary management of this entity aims to treat the underlying eating disorder..... suggested work-up includes serum electrolyte and amylase levels as well as imaging studies (ultrasound or CT scan).... identifying and addressing an occult eating disorder early on may prevent progression to refractory sialodenomegaly......... Rauch SD. Mehler et al.. hypotension and bronchospasm. Gupta AK.. 10. Biol Psychiatry. Phone: .. dosing began at 5 mg daily and was tapered to 2... Glorio R. While immediate post-operative results yielded early patient satisfaction and cosmetic improvement..... Two extreme cases of massive parotid enlargement were surgically treated with bilateral superficial parotidectomy.. Hudson JI.. Arch Otolaryngol Head Neck Surg. If you feel you havegroup obtained this copy illegally.. Hiripi E.. . In this of patients.... Characteristics of 275 patients with bulimia. Oral and dental complications in bulimic patients. Vomiting and parotid enlargement.111(2):392-395... Parotid hypertrophy with bulimia: A report of surgical management. The second patient was given a dose of 1... et al.. 2000.. 2001. The prevalence and correlates of eating disorders in the National Comorbidity Survey Replication. 3. symptomatic improvement.. et al.6 Non-invasive intervention may be advantageous because potential complications of surgery (facial nerve injury and permanent facial disfigurement) can be avoided. 1987...... Herold M. Wallace JA.119(7):787-788. which was associated with only minimal flushing. George DT. Laryngoscope. Tung... Pirk KM... 1991... Gupta MA.. Am J Otolaryngol.. 1985.. 1969.50(6):196-204....52(3):139-140.. Pope HG... longer term follow-up for these same parameters were not available. De Pablo A. Do Not Copy.. images Fax: .....7 Improvement was noted within two days...&t*446& servative treatment of parotid hypertrophy includes application of heat. J Clin Psychiatry.. 7. 11.. Eckert ED. Prevalence of cutaneous manifestations in 200 patients with eating disorders........ 1985......5 mg daily for one week. bradycardia... Parotid salivary secretory pattern in bulimia nervosa...... 1991. 1989. please contact JDD immediately.... Biebl W. Lavender S... Penalties Apply ADDRESS FOR CORRESPONDENCE Rebecca C... 8. While the exact mechanism of improvement is unknown. Int J Dermatol. Kinzl J. Kaye WH. 12... 216-444-5489 This document contains proprietary information.......... Lancet. profuse sweating and salivation...1BSL 35VOH "3VJ[EF-V[VSJBHB 3&'&3&/$&4 1...61(3):348-358...8(6):376-380. described treatment of two hospitalized patients with refractory bulimia-associated parotid hypertrophy who abstained from purging and were treated with ophthalmic pilocarpine given orally. 216-839-3879 patient’s habits or and if mild parotid swelling Noeating reproduction usebehaviors of any portion of the contents of theseismaterials may be made without the express written consent of JDD. massive parotid hypertroCleveland Clinic Beachwood phy is among the most cosmetically disfiguring and psychoBeachwood. %*4$-0463& None of the authors have any conflicts of interest to disclose... et al. salivary substitutes and sialogogues (including tart candies). Mehler PS.. Brit J Derm. Hyperamylasemia and its relationship to binge-purge episodes: Development of a clinically relevant laboratory test.... pilocarpine at higher doses (5 mg three times daily) offers safe... 5.. Calcaterra TC.10:423-431........ Primary indications are for treatment of glaucoma and xerostomia..... contact JDD immediately. */530%6$5*0/ I ntramuscular triamcinolone acetonide has been available since 1962 but. This author has not used this therapy for children under the age of 16 primarily because of concerns about its effect on bone growth. as well as a lack of understanding of its specific therapeutic benefits. The report describes the positive results attained in the treatment of many chronic. as well as the clinical indications and side effects seen by the author in his practice over time. Clinical Indications . are unique ofinformation.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F JUNE 2009 580 70-6. to marks use this technique. Indication for Intramuscular Triamcinolone Intramuscular triamcinolone is indicated in adults with chronic symptomatic recalcitrant steroid-responsive dermatologic conditions that cannot be adequately treated with topical medication or other simple measures alone. Frequency and Dosing There are no well-controlled studies in the literature to indicate a preferred frequency and dosing schedule and. Penalties Apply 1. and is then slowly released. more effective and did not lead to increased short-term side effects. the author an intuitive basis. There are few other patients for whom this treatment modality would be contraindicated. dermatocal medication aggressively has minimized this problem. intramuscular Thisthere document containsfeatures proprietary images and of Journal of Drugs Dermatology (JDD). injected 60made mg at least the six express weeks apart. dermatologic conditions requiring a systemic approach. Depending on the specific condition being ery day in his office practice. Dermatologists who oppose its use usually cite several concerns. It is necessary to avoid any leakage of the medication into the subcutaneous tissue in order to prevent localized atrophy or a sterile abscess from occurring. and in for many years thereafter. may have different preferences. therefore. it may lead to irregular absorption and unpredictable results. the use of oral corticosteroids allows the treating physician to adjust the dosage or discontinue it altogether depending on the clinical circumstances. challenging. there were times that 80 mg was somewhat tively in treating many chronic dermatologic conditions. If you feel you have obtained this copy illegally. The article presents the specific treated. its side effect profile will be similar to the well-documented side effects seen with long term oral corticosteroids. this proved to be triamcinolone that allow it of to any be portion used quite effecNo reproduction or use of the safely contentsand of these materials may be without writtenWhile consent of JDD. primarily because of safety concerns. In contrast to a depot injection. At the same time.ofatDrugs least inonDermatology. When the author first learned While these concerns may appear to ©be2009-Journal legitimate. safeplease and effective. This case report discusses the efficacy and safety of intramuscular triamcinolone acetonide. and its clinical effects will last for six to eight weeks or Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . Because of its strong safety profile and unique therapeutic efficacy. dermatologists who use intramuscular triamcinolone regularly All Rights Reserved.5-inch IM needle and to inject into the upper outer quadrant of the gluteal Intramuscular triamcinolone is an extremely effective antipruritic. there could be an early recurrence of symptoms one to technique which has allowed it to be used effectively in the two weeks prior to the next scheduled injection but using topitreatment of a wide variety of chronic. The slow. in order to be effective.&t*446& COPYRIGHT © 2009 CASE REPORTS JOURNAL OF DRUGS IN DERMATOLOGY Intramuscular Triamcinolone: A Safe. Since it is given as a depot injection deep into the muscle. steroid responsive. stretching the duration of the injections This author has treated thousands of patients over the past 30 to at least seven to eight weeks apart improved the potential years with this medication and currently continues to use it evmargin of safety. intramuscular triamcinolone should be considered as a primary therapy for many chronic. its use in dermatologic therapy has always been controversial.% /PSUI'MPSJEB%FSNBUPMPHZ"TTPDJBUFT +BDLTPOWJMMF '- "#453"$5 Although intramuscular triamcinolone acetonide has been available as a dermatologic therapy for many years. it is used sparingly or not at all by many dermatologists because of concern about its safety. Do Not Copy. therefore. along with description of the specific technique employed by the author.&5)0%4 Prutitus It is very important to use a 3 cc syringe and a 1. prolonged release of the medication makes its use primarily for the treatment of chronic conditions and. Effective and Underutilized Dermatologic Therapy %PVHMBT/3PCJOT. 2. logic conditions while at the same time being (intramuscular) safer than long-term oral corticosteroids. recalcitrant dermatologic conditions that cannot be adequately controlled by topical therapy alone. and this author uses it routinely to treat elderly patients as well as those with diabetes and hypertension. namely: muscle. Of course. intral- Nails Lichen plano-pilaris Oral and genital Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F .Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 581 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. Pruritic Conditions Not Relieved by Intramuscular Triamcinolone “Burning” conditions (scalp and genitalia) Neurologic conditions (stocking and glove. but not complete. since they also have antipruritic and other anti-inflammatory effects but. intramuscular triamcinolone can be very beneficial in achieving adequate control. scalp. Palms and soles (hyperkeratotic and acropustulosis) This document contains proprietary information. Psoriasis Prurigo simplex/generalized neurodermatitis Obsessive compulsive disorders Scabies Do Not Copy. partial. Localized alopecia areata can almost always be treated successfully with intralesional triamcinolone. and there can be transition TABLE 4. In widespread cases. All Rights Reserved. in many cases. images and marks of Journal of Drugs in Dermatology (JDD). because the condition is often chronic. Just as with other similar eruptions.Table 2 lists pruritic conditions that do not respond to intramuscular triamcinolone. response or lack of response to intramuscular triamcinolone may. “Booster” to topical therapy alone and. may contribute to the relative ineffectiveness of topical medications in severe cases. help to reach a specific diagnosis. unless the overall pruritus is controlled with the intramuscular triamcinolone. Chronic. even with those agents mild flares can occur. as well as other factors. beneficial in those circumstances. please contact JDD immediately. lower legs) Prurigo nodularis Pityriasis rosea Polycythemia vera TABLE 2. notalgia paresthetica) Hand and Foot Conditions Table 3 lists the four major types of chronic eruptions seen on the hands and feet. resolution of erosive oral lichen planus. Pruritic Conditions Idiopathic pruritus Idiopathic pruritus in the elderly usually responds quite well as do a wide variety of localized (Figure 1) and generalized conditions in which the itch/scratch mechanism is difficult to control with topical medication alone (Figure 2). and the “booster” effect from intramuscular triamcinolone used temporarily can be Psoriasis: Treatment-Resistant. This author has been able to obtain TABLE 5. This feature allows it to be extremely important in treating a large number of dermatologic conditions with intractable pruritus (Table 1). Localized Forms © 2009-Journal of Drugs in Dermatology. On the other hand. Penalties Apply Hodgkin’s disease.&t*446& even longer. Hyperkeratotic With the introduction of numerous biologic agents over the Occupational past few years we now have many therapeutic options to treat Acropustulosis more severe generalized psoriatic disease. Dermatitis herpetiformis TABLE 3. it is used to help control certain treatment-resistant localized forms of the disease (Table 4). The thickness of the palms and soles. Nails Table 5 lists those forms of lichen planus which not respond If you feel you havemay obtained this copy illegally. this author also prescribes topical corticosteroids. Generalized eczematous conditions Localized neurodermatitis (genital areas. periods when disease control is not ideal. Lichen Planus: Forms That May Not Respond To Topical but even partial resolution can allow other topical and intraleTherapy Alone sional therapy to be used more successfully. including alopecia totalis. the profound anti-inflammatory and antipruritic effects of intramuscular triamcinolone will have a six-to-eight week duration and allow topical measures to be more effective. Hand and Foot Conditions While this author does not use intramuscular triamcinolone Vesicobullous to treat generalized psoriasis. as well as other underlying malignancies. these conditions may remain resistant to treatment. Pruritus secondary to early CTCL may partially respond. However. In fact. Scalp Lichen Planus No reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD. symptomatic and widespread Alopecia Hypertrophic Table 6 lists the three forms of alopecia that may respond to intramuscular triamcinolone. %3PCJOT TABLE 1. Several courses or oral corticosteroids a small amount of hair regrowth is often seen after initiation had given temporary relief only. Do Not Copy. All are relatively unof the intralesional technique and are successful in a significant common except for chronic urticaria which responds quite well. The progress of the condition can be halted promptly by use of bi-monthly triamcinolone injections which may have to be continued for FIGURE 1. Alopecia universalis responds less and then add intramuscular triamcinolone if adequate control frequently to intramuscular triamcinolone than do other forms is not achieved. and several biopsies were read as “spongiotic dermatitis. The condition usually progresses over several years and often leads to extensive scarring and permanent hair loss. but there is a usually prescribe one or two non-sedating antihistamines. Treatment can usually be tapered off after sixin most cases. he had received a 6 to 7 week remission of his pruritus and most of his cutaneous changes had disappeared. Just as with widespread alopecia had been ineffective. of course. first. After one triamcinolone injection. The scarred follicles history of severe pruritus involving her eyelids and periorbital areas of will no longer grow hair but. substantial recurrence rate. All Rights Reserved. The etiology is not clear and. and numerous topical medications of the bi-monthly injections.” An extensive work-up had failed to reveal an underlying etiology. Localized neurodermatitis. to intramuscular triamcinolone. patients are always encouraged to use condition occurring primarily in African-American women (Figappropriate topical therapy along with other local measures. she still has residual pigmentation. please contact JDD immediately. A second injection gave him permanent relief of pruritus and resolution of all his cutaneous findings. but it is still worth trying since some cases do respond and there are few other effective alternatives. Miscellaneous pain of No thereproduction extensive injections required tothe treat the condition.&t*446& %3PCJOT a b FIGURE 2. FTN: The patient had a two-year six-to-twelve months before tapering off. FTN: The patient is a 67-yearold male with a 5-month history of a generalized extremely pruritic. esional therapy is usually impractical ofinformation. sis would not achieve any better results and would have more © 2009-Journal of Drugs in Dermatology.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 582 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. Generalized neurodermatitis. and she had developed tissue hypertrophy and lichenificamay fall out before the follicles are completely destroyed. Intramuscular triamcinolone will be a crucial factor in achieving control in the vast majority of patients with the conditions listCentral centrifugal cicatricial alopecia is a chronic progressive ed above and. hair her face. the use of intralesional triamcinolone on a monthly balichenification have gone and the pruritus has not recurred. treated with intramuscular triamcinolone. and tion secondary to rubbing a). Penalties Apply grooming practices. This author will to-twelve months. and several courses of oral corticosteroids had given only temporary relief of his pruritus. that theory is no longer considered valid. of the disease. associated morbidity. the associated This document containsbecause proprietary images and marks of Journal of Drugs in Dermatology (JDD). Eight weeks after one triamcinolone injection b). since it is a dynamic process. number of cases. ure 3). although it was at one time Even one or two injections may induce a long-term remission thought to be caused by the use of hot combs and other hair Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . and results are long lasting. Table 7 lists a number of conditions which may be successfully Intramuscular triamcinolone injections avoid the impracticality If you feel you have obtained this copy illegally. but the tissue hypertrophy and areata. excoriated eruption. or use of any portion of contents of these materials may be madeConditions without the express written consent of JDD. to achieve adequate control of the numerous chronic dermatologic conditions for which intramuscular triamcinolone is effective. Petechiae and purpura occur more frequently in older individuals with significant actinic damage. these are extremely If you feelside you effects have obtained this copy illegally. it does help to rebut the common misconception that has lead to much of the controversy about this therapy. lone as described in this report. The goal is always to use the least amount of medication required to achieve the desired outcome. hyperactivity and psychiatric symptoms because of triamcinolone acetonide’s low renal clearance rate. please contact JDD immediately. All Rights Bone-related side effects are among ©the major concerns Hirsutism (veryReserved. of course. if true. Serum glucose may increase 5-10 dL/mg three to five days following each injection and then returns to pretreatment levels. Localized lipoatrophy at the injection site can also occur if all the medication is not completely delivered into the muscle. in others. the plasma level decreased steadily and Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . therefore. They found Corticosteroids that the peak plasma level of triamcinolone acetonide occurred Increased appetite in the first one-to-two days and then fell rapidly over the next Weight gain and fluid retention five-to-six days to about one-third of its peak level and stayed steady for the next six to seven days. Penalties Apply PLEVA Pityriasis lichenoides chronica Cutaneous lymphoid hyperplasia Generalized granuloma annulare In contrast. bimonthly injections may have to be continued for a year or more while always attempting to gradually increase the duration between injections. There are several studies in the literature which help explain why. TABLE 9. Sclerodema TABLE 8. author’sNoexperience the useportion of intramuscular reproductionwith or use of any of the contentstriamcinoof these materials may be made without the express written consent of JDD. These side effects will. Conditions That May Be Successfully Treated With Intramuscular Triamcinolone Chronic urticaria Small plaque parapsoriasis Do Not Copy. Many of the patients may eventually return once or twice a year or even less often on an as-needed basis. Menstrual irregularities also occur. rare if they even occur at all. it is not symptomatic and will usually resolve gradually over a few months. That is. Intramuscular Triamcinolone Side Effects Petechiae and purpura Menstrual irregularlitis Mild hyperglycemia (3-5 days) Localized lipoatrophy 2009-Journal of Drugswith in Dermatology. it would require prolonged use of oral corticosteroids which would lead to significant morbidity. This author does not. rare) the long term use systemic corticosteroids. and sterile abscess formation should also be quite rare if careful injection technique is followed. Table 8 lists side effects seen with intramuscular triamcinolone. marksAbscess of Journal(very of Drugs rare)in Dermatology (JDD).Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 583 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. Kusama et al. Facial hirsutism in women occurs rarely. Except for appearance. It was felt that this peBloating and other GI symptoms riod represented an equilibrium between the slow continued Moon face and centripetal fat distribution release from the intramuscular depot and the slow excretion Insomnia. Table 9 shows side effects commonly seen with a short course of oral corticosteroids that are not seen with intramuscular triamcinolone if used seven to eight weeks apart. the clinical effects roughly parallel the persistence of the medication in the circulation which. Based on images the andSterile Thisof document contains proprietary information. In the author’s opinion. and premenopausal women should be warned about this in advance and may need to use hormonal therapy to prevent this problem. Women who are attempting to become pregnant should not be treated with this therapy except in unusual circumstances. Muscle weakness During the next week. Alopecia: Three Forms That May Respond to Intramuscular Triamcinolone t"MPQFDJBBSFBUBUPUBMJTVOJWFSTBMJT t$FOUSBMDFOUSJGVHBMDJDBUSJDJBMBMPQFDJB t-JDIFOQMBOPQJMBSJT TABLE 7. treated five Side Effects Commonly Seen With a Short Course of Oral patients with radioactively tagged triamcinolone acetonide and Corticosteroids That Are Not Seen With Intramuscular measured the plasma levels and urinary excretion.1 While this report does not explain why the anti-inflammatory effects of triamcinolone acetonide last long after its disappearance from the plasma.&t*446& %3PCJOT in some of the more severe and persistent cases while. hesitate to treat patients with diabetes. worsen over time the longer the oral corticosteroids are used. would lead to long-term side Side Effects TABLE 6. was gone by the end of the third week. If continued clinical adrenal suppression is a concern and. ance from the circulation. Cutis.4 and details of that case ical and legal realities.000 patients treated with long term oral corticosteroids. Kusama M. involves the femoral head but may involve other bones urinary excretion after intramuscular injection of triamcinolone acas well. at least based on the adrenal stimulation test that was used. after starting oral corticosteroids. There is only one report in the literature linking intramuscular 3. Metabolism. In a study of 244. there are several safeguards which can be used when following patients undergoing long-term therapy.6 However. did not develop prolonged adrenal suppression. the excessive shedding had stopped. teroids have been linked to a substantial number of others. nor was there any follow up given.8 mg of prednisone The author does not have any conflicts of interest to disclose. J Bone Miner Res.80:343-348. a day over an eight week period) do have a slightly higher risk of fracture compared to controls. Studies of plasma levels and cases. Reserved. The injections were continued for a year without any progression of her alopecia. A 38-year-old African-American woman who first noticed excess hair shedding six months previously and the clinical findings and biopsy results were consistent with the diagnosis of central centrifugal cicatricial alopecia. images and marks ofthe Journal of Drugs in Dermatology (JDD). there is a question of whether repeated injections every seven-to-eight weeks may induce prolonged adrenal suppression. is not well underthat theNoepisodic exposure from corticosteroids. Kumaoka. Sakauchi N. intramuscular triamcinolone has this study showed was that there is a rapid onset of fracture risk © 2009-Journal Drugs inof Dermatology. Zhang B.15(6):993-1000. Leufkens H. at least six weeks apart. Oral corticosteroids may inhibit osteoblast formation and promote apoptosis of osteocytes. but there was no discussion about whether any of those six patients had any clinical evidence of adrenal suppression. but oral corticosof oral corticosteroids and risk of fractures. key towithout its usethe is express its ability to suppress the underlying reproduction or use of any portion of the contents of these maythe be made written consent of JDD. then further testing can be done. Abenhaim L.5 mg/day of prednisone or less (80 mg of %*4$-0463&4 triamcinolone acetonide is equivalent to 1. The package insert for triamcinolone acetonide states that adrenal suppression lasts for 30–40 days following an intramuscular injection5 and this has been confirmed by other studies. Another potential side effect of long term (and rarely even short term) oral corticosteroids is avascular necrosis which. who found that. may this be less inflammatory response long after the medication’s disappearyou feel you have obtained copy illegally. since many of the dermatologic conditions treated by this modality may require prolonged therapy.5 years) intramuscular triamcinolone six weeks apart. but the risk of fracture is cor$0/$-64*0/ respondingly higher with a higher dosage. as well as a rapidofdecline 2 This fact suggests Although specific underlying mechanism that risk after stopping oral corticosteroids. in an intramuscular injectionIf eight weeks apart. and obtaining a morning cortisol level several days before the patient is scheduled to return for the next injection—if the level is low. the small vessels which supply the ends of the affected bones. nausea and anorexia. 1971.&t*446& %3PCJOT in this report. The fact that triamcinolone acetonide is gone from the circulation by the end of the third week with a subsequent fourto-five week break before another injection would likely mitigate against many of the side effects seen with long term oral corticosteroids. The only study in the literature to look at this issue was by Droszcz et al. Van Staa et al. make the association somewhat dubious. including review of systems looking for clinical signs of adrenal suppression such as fatigue. 2007. FIGURE 3. Use More than a third of the cases are idiopathic. thereby minimizing side effects that are normally seen with long-term oral corticosteroids. Short term corticosteroids and avascular necrosis: Medtriamcinolone with avascular necrosis.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 584 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6. This document contains proprietary information. Six of the 48 patients did develop adrenal suppression six weeks after their last injection. in a series of asthma patients treated with long-term (average 3. please contact JDD immediately. when givenmaterials stood. depression. If used as described Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . 42 of 48 patients had normal adrenocorticosteroid function six weeks after their last injection.7 The study was reassuring since it showed that most patients treated on a long-term basis. in most 3&'&3&/$&4 1. 2. showed that those treated with 2. FTN: Within a week after receiving her first triamcinolone injection. in my experience it would be quite rare. Do Not Copy.3 2000.20(6):590-596. harmful than continuous low-dose oral corticosteroid therapy. Cooper C. the relatively small amount of steroid used should make the risk for this side effect extremely small. An example of one of the side effects would be bone loss leading to an increased potential for fracture. Richard R. The underlying cause is ischemia due to occlusion of etonide. Penalties Apply effects. One finding that In the author’s experience. provenAlltoRights be a reliably effective and safe therapeutic modality. VanStaa T. . Assessment of adrenocortical function in asthmatic patients on long-term triamcinolone acetonide treatment..... Because being document proprietarytoday. please contact JDD immediately.... Lech B.. 904-396-0428 E-mail: ........ 904-354-4488 Fax: ..... information............ Not to be prejudiced.. MD North Florida Dermatology Associates 836 Prudential Drive #1507 Jacksonville.... imagine what it’s doing to your skin...31(7):337-343....... New Jersey: Bristol-Myers Squibb.. 1979. No reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD.322(7302):1589-1592. Droszcz W..... Robins..partnersandjeary................ %3PCJOT Nasser SM...... 6... Penalties Apply raisin is a grape that didn’t have the sense to get out of the sun..... et al.42(1):41-43.... healthy – truly healthy – feel is what’s sexy. Nothing looks better on you than the glowing....... 2006..... Ann All.. 7.................. Br Med J....com Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F ........com Do Not Copy... FL 32207 Phone: ...... Kenalog-40 (package insert).Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 585 JOURNAL OF DRUGS IN DERMATOLOGY +6/&t70-6.. Ewan P.. Princeton... Thorax.. ADDRESS FOR CORRESPONDENCE Douglas N.... but we humbly submit that human beings should have more sense than dumb grapes...... radiant © 2009-Journal of Drugs in Dermatology.... shine youThis were born contains with. All Rights Reserved..........&t*446& 4.... Sweet L.... If you you have obtained this copy illegally. Go with your own glow www.. www...... Mellinger R......org © 2008 The Skin Cancer Foundation Campaign created by partners + jeary.. ____________ DNRMD1@aol.............. Mikhail G.. And if the giant orb in the sky can do that to a little piece of fruit. Malunowicz E..skincancer.. 5.. Depot corticosteroid treatment for hay fever causing aseptic necrosis of both hips... 1973.. images and marks of Journal of Drugs in Dermatology (JDD)................... 2001. Parenteral long-acting corticosteroids: Effect on hypothalamic-pituitary adrenal function.... images and marks Journal of Drugs in Dermatology (JDD). they are exquisitely regulated by a number of different modalities.5 In this regard. pendent. NOS2. bacterial polysacchrides and endotoxins. NOS1. NO has many defined funccomplexes. requiring tetrahydrobiopterin (THB). can be used impacts such as NO’s ability to act as an anti-depressant15 and anti-pyretic. From Bench to Bedside: The Therapeutic Potential of Nitric Oxide in Dermatology tory cytokines. Sevto the location and amount of production. and also far-reaching ability to function as a free radical. Additionally. This specifically plays a role in vascular biology. Views and Reviews provides focused updates. in an atherosclerotic lesion may be potentiated by upregulated from neuronal cells). It levels and subsequent activation of protein kinase G (pkG). Biological Synthesis of of NO Themay earliest described of NO was itsconsent regulation of the vasNo reproduction or use any portion of the contents of these materials be made without role the express written of JDD. in-depth topic reviews and editorials concerning the latest developments in dermatologic therapies. for example.11 For example. NO’s ry and neurotransmitter actions of NO.2 development.16 As a free radical. S-nitrosylated proteins. isoforms of the enzyme nitric oxide synthase (NOS). Encompassing nearly notably via the soluble guanylyl cyclase (sGC) pathway. lived (being rapidly scavenged by hemoglobin) and concentrasuch as S-nitrosothiols. © 2009-Journal of Drugs in Dermatology.19.4 In signaling cascade leads to innumerable downstream events.14 In this every physiological system and relevant in many pathological paradigm. NO functions as a double-edged sword. NO has a notable influence in the human body. leading to the discovery of an everNitric oxide initiates multiple cellular signaling cascades. NOS2.23 further cellular damage NOS. involving key cells such as keratinocytes and fibroblasts.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F JUNE 2009 586 VOLUME 8 t*446& COPYRIGHT © 2009 DEPARTMENTS JOURNAL OF DRUGS IN DERMATOLOGY NEWS. The enzyme damage and adding to cellular stress. cal conditions.10 A fourth isoform. as its action is short eral mechanisms may account for long distance NO transport. Many tions in the skin. and nitrite. having been peroxide. NOS3. medical and scientific interest in nitric oxide (NO) Physiology of NO has grown exponentially. the total measured NO may also be attributable to a non-NOS source of NO. or is not only capable of generating peroxynitrite. from endothelial cells and neuronal NOS.8 It has become increasingly apparent that a solid clinically relevant physiologic states rely on NO as a critical sigunderstanding of nitric oxide’s functions will be advantageous naling component. FAD.24 This once again demis induced by a wide array of stimulants such as proinflamma- Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . facilitating both local biologic effects such as the vasodilatowith effects that are both cytoregulatory and cytotoxic. such as the availability of substrates and co-factors. Penalties Apply NO andofVascular Biology This document contains proprietary information. This effect only occurs at higher concentrations since characterized as both pro.7 liberated from these carriers are short lived in the body. but trosylating agents capable of both signaling and cellular damcan also be cytotoxic to host cells. for understanding and treating dermatologic diseases. InNADPH. such as with peroxynitrite (ONOO-) in the presence of suin the conflicting reports on NO’s role in cancer. NOS1 and NOS3 are constitutively deed. Meanwhile. such as hypertension.9 All NOS accounts for normal vascular homeostasis and perturbations of proteins generate NO through the conversion of L-arginine to this balance are relevant in a wide array of pathophysiologiL-citrulline. presence of scavengers. Both of these enzymes are calcium-deNOS2. calmodulin-regulated enzymes. and multi-site phosphorylation.17.21 acute respiratory distress syndrome22 and atherosclerosis. All Rights Reserved. endothelial dysfunction is a primary initiator of atheroexpressed and are known by the cell types in which they were sclerosis and while impaired NOS1 may be implicated in the enzymatically identified and subsequently cloned (endothelial development of this disease process. NOS1 constitutively If you feel you have copy illegally.14 Since first identified in 1986 as the endothelium derived relaxing factor. Nitric oxide is generated endogenously by obtained several this distinct culature via endothelial cells.18 although the actual NO species once 6. VIEWS & REVIEWS News. FMN. it may oxidize inducible NOS. has been proposed but its existence and function is the subject of some debate. In this model. further building upon the generates NO in a non-calcium dependent fashion. Do Not Copy. heme and oxygen.13 and may have either cytosolic or particulate localization.12 All isoforms are modulated by different signals. and neuropeptides. such as sex hormones. it may be that the effect of NO must be understood with regard NO is rapidly scavenged in most physiological conditions. mitochondrial NOS. most widening range of physiologic functions. A better example is found age. please contact JDD immediately. Not surprisingly. NO is able to generate potent niadvantageously to combat foreign invading pathogens. nitrosyl-metal tion dependent.and anti-oncogenic. expressed in endothelial cells and macrophages. many ways. is expressed in a wide array of cell types and THB and in turn uncouple NOS1.1 skeletal muscle physiology. neuroscience3 and immunology. NO binds to sGC leading to an increase in cyclic GMP processes.20 sickle cell disease. however. possibly dependent on cell maturaimmune response are especially relevant in the skin and partion. Do Not Copy.42 One of the major assailants to the skin is ultraviolet irradiation. the most studied and best-understood effect is the NOS2-mediated NO production in macrophages. and glial cells. NO is able to regulate skin flora through this non-NOS the major constituent of the epidermis.27–29 Furthermore. Fibroblasts.45 This study suggests that intake of external sources of NO precursors.32 Interestingly. Nitrite is a known constituent of © peroxide 2009-Journal of Drugs into Dermatology.8 but this expression is inconsistent across different cells. leafy greens. and fibrin. such as dark. Penalties Apply NO and Skin Biology Physiological Localization and Function Practically every cutaneous relevant cell type expresses some isoform of NOS and is therefore able to generate and release NO for a broad spectrum of physiologic processes. regand non-NOS-mediated NO production pathways. and UV-induced melanogenesis40 and development of erythema.46 Additionally. In the setting of acute UVA exposure. antimicrobial NO. may influence the innate and acute cutaneous response to UVR. and through membrane lipid peroxidation. and in the case of sweat. In addition.36 Additionally.4 Of these. the physical protection afforded by an intact epidermis is especially important and NO participates in establishing this essential defense mechanism. arthritis. neutrophils. ulate the structural framework of the skin by synthesizing extracellular matrix. NO has immunoregulatory functions via lymphocyte activation and proliferation and numerous lishing and maintaining circulation. a non-enzymatic pathway of NO production was elucidated. are the primary anti-mycobacterial defense. in response NOS235 and produce NO and hydrogen both blood and sweat. several infectious pathogens require arginine for cell survival and proliferation. exposure because of the synergistic roles of the NOS-mediated such as in wound healing. superficial vascular dermis and sweat.39 Due to its widespread distribution. NO is types. the increased susceptibility of illicit drug users towards pulmonary infections33 may be in part explained by the inability of alveolar macrophages to produce NO following the smoking of marijuana or the use of cocaine. In addition. depletes this store. not oxidative stress.37. express both NOS1 and dependent synthetic pathway. of protective protective mechanisms of the skin.31 In many instances. eosinophils. stantly exposed to foreign matter andyou organisms. Similarly. these products are quickly mobilized within 30 minutes to generate NO. eccrine glands express NOS3. as an enzyme inhibitor by disrupting Fe-S clusters.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F JUNE 2009 587 VOLUME 8 t*446& COPYRIGHT © 2009 DEPARTMENTS JOURNAL OF DRUGS IN DERMATOLOGY onstrates the dual nature of NO and stresses the importance of proper regulation of its function. tuberculosis.contact preventing pathogen access to the body. NO is critically important when mounting an immune response against organisms such as M.43 More recently. against microorganisms. NOS expression in dermal endothelial cells allows for tight control of blood flow. which only declines after three days and coincides with the time course of sun-induced erythema. Fibroblasts demonstrate both The effects of nitric oxide with respect to inflammation and NOS2 and NOS3 expression. melanocytes allel its functions systemically. SLE and able to participate in basic physiological roles such as estabpsoriasis. All Rights Reserved.26 This source of NO can exert its effects directly as a toxic species towards foreign pathogens. This proposed role of NO is supported by reports that endothelial cells are protected from UVA-induced apoptosis by NO44 and that UV-induced lesions in cutaneous lupus erythematosus demonstrate reduced expression of NOS2. this mechanism of protection is likely heightened during UVA finely regulated responses are also exhibited by NOS species. NOS activity. epithelial cells. so to speak. Keratinocytes. while orchestrating the Regulation of Inflammation and Immune Function complex steps of wound healing.43 In this regard. The skin is constantly exposed to this stressor capable of inducing oxidative cellular damage.34 With NO playing such an important role in the normal physiological response towards foreign invasion. NO may quench free radical damage that can result from UV radiation exposure if generated photoproducts are allowed to propagate unhindered. NO is a nonspecific product of have shown NOS3 and NOS2 expression. the acidity of the inflammatory stimuli. it is no surprise that it has such an important role in the primary barrier for the body against the outside world—the skin. Therefore. collagen. keratinocytes produce sustained concentrations of NO upon exposure to both UVA and UVB irradiation. where reactive nitrogen species. where NO is derived from biologically relevant NOrelated products in the human epidermis. As the skin is the primary barrier between the body and the external environment. As one of the skin’s primary defense mechanisms. resulting in an indirect inhibition of pathogen growth. that has been implicated in sepsis. as the epidermis con-materials No reproduction or use of any portion of the contents ofisthese be functions made without the express written consent of JDD. This maycontains act as one of the information.to NO. fibroblasts. If you feel have obtained this copy illegally. via the creation of NO from arginine.44 The acidifiedmay nitrite as a moat. forming a protective barrier Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F .25 released by macrophages. such as through the generation of peroxynitrite resulting in bacterial DNA damage and inhibition of repair/synthesis. please JDD immediately. It also promotes angiogenesis through upregulation of vascular endothelial growth factor (VEGF) via hypoxia inducible factor 1. found in the dermis.38 and Langerhans inflammation via activation of NOS2 in a wide variety of cell cells exhibit NOS2.41 NO and Immunology Barrier Function Nitric oxide is one of the most potent and essential effector molecules involved in host defense. cardinal broad skin surface allowsoffor theinreduction of nitrite This document proprietary images and marks of Journal Drugs Dermatology (JDD). such as interferon gamma30 and neutrophil superoxide release. NO is able to upregulate several antimicrobial pathways. resulting in keratinocyte cytoprotection from UVR-induced apoptosis. 48 With that in mind. keratinocytes and fibroblasts. please contact immediately.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F JUNE 2009 588 VOLUME 8 t*446& COPYRIGHT © 2009 DEPARTMENTS JOURNAL OF DRUGS IN DERMATOLOGY cytokine pathways. this data serves to highlight the line of defense in preventing and fighting host infection. berculosis. including immune cells (most importantly macrophages). M. p56. pendent on NO.53 likely seen in disease states activation furthers and aids this process. Neovascularization of the wound area.38. VEGF expression. The subsequent aggregation and clotting cascade results in a fibrin clot to seal the wound area while platelets initiate a series of events through cytokines and growth factors. dendritic branching of melanocytes. is also reliant healing is greatly dependent on precise concentrations of NO on appropriate NO production.50–52 However. both studies have found variable effects of NO on cultured keratinonon-enzymatic and NOS produced NO are critical as the first cytes and fibroblasts. and keratinocyte migration. NO production peaks due to widespread activation of NOS2 in many cell types.65. resulting in melanin production. All Rights well as biofilm-fortified species. remodeling and differentiation occurs over the next against both gram-positive and gram-negative bacteria was several months to re-establish normal tissue structure and demonstrated. likely in part due to wound macrophage generation of TGF β. protozoa. conflicting such as HSV-induced erythema multiforme. NO is not only an important effector molecule involved in facilitating an immune response to invading organisms. During this time. Using small paired wound tensile strength. TGFα. whereas high levels of NO inhibit mal models with reduced or absent NOS2 activity demonstrate fibroblasts and keratinocytes and are cytostatic. decreased collagen content. lower concensignificantly increased susceptibility to bacterial infection as trations are stimulatory. now at eradicate intracellular pathogens such as Mycobacterium tua lower concentration and dependent upon NOS1 production. Wound MMP activity. to recruit other mediators of wound healing. such as platelet derived growth factor (PDGF) and TGFβ. To control these signaling events. the organisms themselves can induce NOS2 overexpression. Furthermore. the collagen deposited in the de© 2009-Journal of Drugs in Dermatology. Admittedly. Melanocytes express NOS and phases: the inflammatory phase. WoundNoHealing replacement of the old the matrix are written severalconsent matrixofmetalloproteireproduction or use of any portion of the contents of these materials may be made without express JDD. Early evidence that NO functions as an antimicrobial agent is derived from in During the proliferative phase of wound healing. and requires the collective action of a great number of factors derived tissue inhibitor of metalloproteinase. general microbiocidal. Innate Antimicrobial Activity collagen. NO. Susceptibilty of epidermotropic viruses. leprae. specifiwith specific reference to NO. There are many reports on the wound healing process NO is known to be closely related to skin pigmentation. During this period. forms crosslinks and the short. unorganized fibers mature intoofstronger. and by interacting with other inflammatory mediators. By helping vasodilate the blood supply near the wound area. theJDD activity of which are regulated by fibroblast feel you have obtained this copy illegally. NO ensures that wound healing mediators and nutrients are able to gain access to the site. and NF-κB. such as the NO-induced nitrosylation of NF-κB. Leishmania species. NO recruits monocytes and neutrophils and promotes the expression of IL. generated to prevent delayed and improper healing of an acute Regulation of Pigmentation wound. This balance of acting in concert with respect to time and location. which prevents further activation of NOS2.66 molecule NO donors.54 These results now include multi-drug resistant organisms such as methicillin-resistant S. as the provisional tion. there is widespread agree26 ment that perturbation of NO production uniformly results in compared to normal wild type mice capable of producing NO. bacteria. broad-spectrum antibacterial properties Finally. The inflammatory phase of wound healing begins immediately aggregation of melanosomes by melatonin. images and marks of Journal Drugs in Dermatology (JDD). Penalties Apply Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F .61–63 This peak NO synthesis begins to decline after 3—6 days as the proliferative phase follows. and the eumelanin/ after wounding.40 Cyclic GMP upregulation resulting from NO generation stimulates tyrosinase acitivity. which downregulates NO synthesis. such as IFN-γ. Aiding in the This document contains proprietary information. helminths and fungi to NO has been demonstrated.57–60 NO’s role in wound healing can be best understood by its influence on the three distinct cally following UVR exposure. collagen synthesis. NO serves as a first line of defense against microbial invasion both as a direct. the proliferative phase and UVB-induced and paracrine-regulated melanogenesis is dethe differentiation/remodeling phase. and imof NO as a reactive free radical to battle infection. organized structures. becomes important and NO-mediated VEGF in epidermal and dermal damage. when platelets come into contact with exposed Do Not Copy. many regulatory systems exist whereby feedback and modifications affect NOS expression and NO production. Extensive research has highlighted the antimicrobial potential delayed wound healing.8 and TGF β.47 and TGFαinduced inhibition of NOS2. Regardless.56 veloping matrixReserved. and the ultimate wound strength. but it can also function as a cytotoxic agent against these pathogens. The process of recovery fromIf you a cutaneous wound is complex nases (MMP). NO positively influences wound fibroblasts. including TNFα. however. Additionally. Anidichotomy of NO function.64 Overall. producing severe inflammation that can result matrix is eroded. by modulating regulatory functions through the aforementioned pathways. the most vitro wound healing experiments showing that inflammatory important task is to generate and occupy the wounded area stimuli induce keratinocytes to produce NO through NOS2 to with a scaffolding matrix for regenerating tissue. aureus (MRSA)55 as function. Trypanosoma cruzi promotes keratinocyte and fibroblast proliferation and funcand Plasmodium falciparum and also to block viral replication. 74 Steven-Johnsons/toxic epidermolytic necrolysis. a multitude of projects designed to generate high intra-tumoral levels of NO have been pursued. it is reported that there is higher NOS2 expression in primary and metastatic melanomas as compared to levels observed in melanocytic nevi. it has been demonstrated that NO is involved in lymphatic vessel permeability and flow. depending on the concentration of NO produced. Over the past two decades. such as.83 Even more recently.85 Furthermore. This duality is currently the subject of great debate and therefore merits further examination. animals treated with a topical. and NO-induced DNA damage80.72. it is not surprising that a myriad of effects have been chronic inflammation is known to play an active role in the poobserved following the modification of NO levels in different tential progression to malignant transformation.and anti-carcinogenic.88 Additionally. It is clear that NO is involved in a multitude of signaling pathways that vary based on cell type and the level of NO produced. Dong et al.75 keloid formation. mild inidentified. the role of NO in both carcinogenesis and chemoprevention has received a great deal of attention. the ples of this potential role include the association of chronic cueffects of NO could be characterized as pro-malignant. Rightspromoting Reserved. In a comparative study between several nonmetastatic and highly metastatic melanoma clones. and endothelial cell proliferation through upregu- Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F .10 Two examtumor cell lines. epidermal protection. images and marks of Journal Drugs in Dermatology (JDD). No reproduction or use of any portion of the contents these materials may be made without thebarrier expressmaintenance written consentand of JDD. increased tion and manipulation as a therapeutic strategy.69 NO and Skin Pathophysiology Because of the defined roles of NO in cutaneous biology discussed above it is clear how perturbation of NO production and signaling might lead to the manifestation of pathologic states. It has been shown that NOS2ofexpressurveillance. NO acts as a potent anti© 2009-Journal Drugs in Dermatology. it is of clear that NO has a defined document information.73 atopic dermatitis. role in immune neous T-cell lymphoma. including the use of NO donor drugs and the transfection of a functional NOS2 gene. perfusion and vascular pertion with other medications for the treatment of systemic sclemeability.81 are ultimately the culprits. NO may function in an anti-carcinogenic role via the induced apoptosis of mutated cells or through modulation of growth responses and gene expression patterns. intensity).86 In fact. The dysregulation of NOS2 expression in inflammatory skin disease is well established. supporting the hypothesis that NO is involved in blood and lymphatic vascular formation in tumor tissues. as with so many other disease states. the increased density of lymphatic vessels in both melanoma at peritumoral and intratumoral locations is associated with increased NOS2 staining in tumor cells. FDA approved medical therapy such as Sildenafil for erectile dysfunction and Tumor expressed NOS2 is a proposed mediator of tumor angaseous NO for pulmonary hypertension are just a few examgiogenesis and metastasis formation because of NO’s ability ples.79 It could be Therapeutic Translation: Past. Since then. as lichen sclerosis et atrophicus and squamous cell of carcinoma. of a tumor. it was demonstrated that the nonmetastatic clones expressed much higher levels of endogenous NO.76 morphea/scleroderma77 and pitryriasis lichenoides78 all have known associations with NO dysregulation. In addition. clinicians are now using Sildenafil in combinato directly induce vessel dilation. Even though the full extent whereby NO If you feel you have obtained this copy illegally. well recognized and has therefore stimulated attempts to modulate NO production for therapeutic translation. Do Not Copy. contact JDD immediately. investigations thus far support a role for NO modulatensity). NO is able to further exert its anti-carcinogenic effects through the regulation of MMP levels. NOS2 expression is present throughout the epidermis70 and high levels of NOS2 are also found in patients with Sjogren’s syndrome with photosensitivity. sion may directly reflect the degree of proliferation/malignancy andplease in wound healing. at highly elevated concentrations. NO and Skin Cancer lation of VEGF and basic fibroblastic growth factor.82. which activates caspases and induces the release of massive quantities of cellular calcium both of which result in apoptosis. There is extensive evidence that tumor expressed NOS and subsequent NO production can be both pro.87 demonstrated the potential anti-carcinogenic features seen with increased expression of NOS2. A progression in NOS2 immunoreactivity was obcontributes to these key cutaneous processes has yet to be fully served ranging from Bowen’s disease (75% positive. However. wheretaneous wounds or destructive inflammatory processes. Penalties Apply Our understanding of NO’s role in the progression of skin cancer is continually evolving.68 However. More recently. and the linkage This between largecontains plaqueproprietary parapsoriasis and cutaFurthermore. In one study.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F JUNE 2009 589 VOLUME 8 t*446& COPYRIGHT © 2009 DEPARTMENTS JOURNAL OF DRUGS IN DERMATOLOGY pheomelanin ratio are influenced by NO.71 Psoriasis.67. its precise role in tumor pathophysiology has been a matter of great debate. to metastatic carcinoma (80% positive). dysregulation of this system may be involved in hypo. nonselective NOS inhibitor demonstrated decreased skin pigmentation following UVB exposure. cancerAll agent. apoptosis and inhibiting metastasis. to squamous cell carcinoma (75% positive. Present and Future that the local increase in concentration of nitrosamines. which The extensive role of NO in a wide spectrum of disease states is are well-known carcinogens.89 and by increasing the release of cytochrome c. endocrine.84 and that NOS2 activity often correlates with lymphangiogenesis and lymph node metastasis in head and neck squamous cell carcinoma. In cutaneous lupus erythematosus.or hypermelanosis found in hereditary. and post-inflammatory conditions. It appears that at modest concentrations. As a pro-carcinogenic factor. elevated NOS expression during Therefore. yet demonstrated accelerated wound closure and clearance of bacwe have barely breached the surface with respect to NO’s exact terial burden. NCX 1047.103 seek to use a transdermal application approach to deliver NO to an an underlying target area. in clinical trials. “Molecule of the Year” ber of the previously described limitations. Our understanding of the physiologic properties these nanoparticles on MRSA infected murine wound models of NO has grown exponentially over the past two decades. Developing approaches to topical delivery of nitric oxide has been a challenge. This review sought to demonstrate that NO is an extraordinarihydrogel/sugar-glass matrix nanotechnology platform was dely powerful and important signaling molecule integral to the veloped that relies on a sugar-based thermal reduction mechaproper regulation of normal physiology commonly implicated nism for the generation of NO (converting nitrite to NO) rather in many pathophysiologic events. anti-fungal tion techniques. However. One in particular. Penalties Apply Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . and these polymers do cutaneous leishmaniasis reported by the Cardiovascular Founnot lend themselves to rapid deployment and administration dation of Colombia104 was terminated because the treatment was deemed not effective enough. and/materials may be made without the express written consent of JDD. Many of the NO recompounds can be difficult to generate and maintain. nontoxic. or use of any portion of thetemperature. This document contains proprietary information. as the applicadermal applicationand is in the preclinical phase. in Dermatology (JDD).92 as well as an array of NO releasing oruct. there are many clinical studies investigating the delivthrough which NO exerts its extensive physiologic impact on Do Not Copy. as many of these has limited sustained release capabilities. Their proddelivery of gaseous NO. and the need for specific flow modula2 trials which are evaluating anti-bacterial (MRSA). It remains to be seen tions to varying degrees. there are no poly vinyl alcohol (PVA) with an NO donor. polytreat burns. an insoluble. A second company. rather then inhibition of NO production because it represents a burgeoning area of research with wide sweeping applications in the treatment of cutaneous disease. applied skin. While some. such as cardiovascular and pulmonary disease.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F JUNE 2009 590 VOLUME 8 t*446& COPYRIGHT © 2009 DEPARTMENTS JOURNAL OF DRUGS IN DERMATOLOGY rosis and Raynaud’s disease and find they alleviate symptoms and help to heal ulcers associated with these conditions. lists Dr. Confounding factors such as which is essential for the management of wounds. but a considerable number of projects have dermatologic applications. images and marks towards of Journalthe of Drugs The rateNoofreproduction release of NO depends upon pH. Topical application of in Physiology. The NO releasing materials also suffer limita(tinea pedis) and wound care applications. The use of nitrite with ascorbic acid whether these attempts to commercialize NO therapy towards requires a barrier to prevent skin and wound irritation and it dermatological applications will be fruitful. has N-acetyl-D. The use of gaseous NO is ing a different approach. is formulated for There are many benefits to all these systems. NIOXX. is designed to release NO at a local wound site to eniumdiolate (NONOate) polymer. we have only begun to elucidate the mechanisms Currently. One company. several of which are molsidomine (N-ethoxycarbomyl-3. but there is great 2009-Journal of Drugs Dermatology. It is therefore no surprise than NO-donor molecules. an NO donor. SNAP (S-Nitrosoreports of human clinical trials. Of these NO ancillary effects from other components in the formulation and donor species. NCX 1047 is tions of NO are widespread. with the NIH reporting 386 clinical trials involving NO as of April 2009. psoriasis and seborrheic dermatitis. a topical gel consisting of nitrite and ascorbic acid in a petganic molecules including: polyethyleneimine cellulose diazrolatum base. such as a trial of topical glyceryl trinitrate for extensor tendinosis.101 Exposure of these nanoparticles to moisture initiates the sustained release of the by Science in 1992 and was the focus of the 1998 Nobel Prize trapped NO over extended time periods. hydrogel dressing made by crosslinking ments with animal models have been completed. and the NO donor developed multiple NO releasing products.102 role in inflammation. thereby circumventing a good numthat NO received the prestigious award. tion is poorly controlled.93–99 the currently available NO delivery systems have as atopic dermatitis. despite the reported suca NO-donating ointment targeted towards skin disorders such cesses.IfEven more a composite you feel yourecently. All if Rights Reserved. many of these trials are directed at the treatment of skin disease. Even more so. While successful experimer-based NO donor. Nitric Bio is seeking to apply direct not practical given the cost. contents of these Conclusion or the structure of the amine.morpholinyl-sidnonimine).58 a chemical system utilizing sodium nitrite and ascorbate. Several corporations are dedicated to the development of NO although the rate of NO release and the delivered concentradelivery vehicles for the skin. Many are related to potential systemic effects and outcomes regarding nitric oxide. This review will focus on NO delivery as a therapeutic avenue. of more biocompatible coatings and©they have the abilityinto promise a nitric oxide releasing platform can be effectively generate NO spontaneously under physiological conditions. raising concerns as to toxicity. please contact JDD immediately. immune response and cell growth/death. One clinileasing polymers utilize complex reactions with organic molcal study of a controlled NO releasing patch for the treatment ecules. Taksignificant limitations and drawbacks.91 ery of NO for the treatment of numerous diseases.L-penicillamine). N-diazeniumdiolates100 have emerged as attractive candidates because their chemistry allows for the design cost of application will need to be addressed. More recent modalities that have been Ferid Murad (co-winner of the 1998 Nobel Prize for his work on evaluated and developed include continuous horizontal-flow the role of NO in physiology) as a research director.90. NICOX. difficulty in administering the gas gaseous NO to acute and chronic wounds. diabetic ulcers or eczema. NO-releasing drugs such as sodium nitroprusside and nitroglycerin have been used for over a century to enhance coronary vasodilation. They report phase for prolonged periods. have obtained this copy illegally. PhDb region of the rat brain. Proc Natl Acad Sci U S A.357(Pt 3):593ing of schistosomula of Schistosoma mansoni. Nitric oxide release accounts 1995. cada S. Physiol Rev.81(1):209-237. Gardner CR. Baylis SA. Ferrige AG. please Olds GR. Penalties Apply Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . it is important to continue to investigate the role of NO in cutaneous disease. Xiang J. Laurent F. Lohmann SM. In: Nitric a Department of Physiology and Biophysics. Raat NJ. Radi R. et al. Annu Rev Immunol. but also to establish a framework through which novel and creative therapeutics can be developed for acute and chronic skin disease.327(6122):524-526. 2003. et al. Nat Immunol. Hacker A. oxide isoforms. 18. 16. lar hypertrophy are associated with impaired endothelium-mediat2. BSa Jonathan Hale Zippin.332(1):27-37. Hospital-Weill Cornell Medical Center c Division of Dermatology. Fang FC. Induction of calcium-dependent nitric oxide synthases by 30. Internatl J Neuropsychopharmacol.10(2):99-107. Nitrite as a vascular endoAlbert Einstein College of Medicine b Department of Dermatology. Nature. Nitric oxide synthases: Roles. Hypertension and left ventricuNature. Reiter CD. 12. Steiner AA. Huang Z. polyamine pathways.98(13):730113. The nitric oxide and cGMP signal transduction system: regulation and mechanism of action. Arterioscler Thromb in normal human keratinocytes. Nitric oxide and the immune response. 25. materials may be made without the express written consent of JDD. Ellner Kearse LA. Alterations of the vascuapeutic for cancer. lar and the myocardial guanylate cyclase/cGMP-system induced by 6. Hypertension in mice References lacking the gene for endothelial nitric oxide synthase. 9. Circulation. for the biological activity of endothelium-derived relaxing factor. Wang R. Nitric oxide—A novel ther23.377(6546):239-242. McCann SM.91(11):5212-5216. potential determinants of host defense against the lumen-dwelling 2004.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F JUNE 2009 591 VOLUME 8 t*446& COPYRIGHT © 2009 DEPARTMENTS JOURNAL OF DRUGS IN DERMATOLOGY the skin and its likely association with numerous pathologic processes such as psoriasis and skin cancer. Role of arginase in killIf you feelRG. factor suppresses nitric oxide and hydrogen peroxide production 24. 14. 2005. Bredt DS. pathogen Giardia lamblia. Human dermal fibroblasts cepts and controversies. Mitochondrion.106(3):428Vasc Biol. and con28. et al. 2000. 2004. Diefenbach A. Nature. Weiner CP. Mitochondrial NO and reac29. Cell. you Nitric have obtained this copy illegally.14(2):162-168. Kaster MP. not only to further our understaning of cutaneous biology. Zou MH. Charles IG. Eckmann L. The acute respiratory distress syndrome. et al.2(1):907-916. 431.15:323-350. Constitutive nitric oxide synthase is present oxidase-derived superoxide and peroxynitrite. 10. muscle. Biochem J. Lacza Z. images and of Journal Drugs Dermatology (JDD). Localization of nitric ox21. Baudouin JE. Snyder SH. Kottenberg K. New York-Presbyterian crine nitric oxide reservoir that contributes to hypoxic signaling. immediately. cell disease vascular homeostasis and therapy. et al. Involvement of nitric oxide-cGMP pathway in the antidepressant-like effects of adenosine in the forced swimming test. 2008. Rosa AO. Uncoupling of endotheby keratinocytes. 615. 8. Laskin JD.106(3):419-427 function. Santos AR. MDc 17. Palmer RM. 1992. Gladwin MT. Pankotaia E. Schmidt HH.151(6):1557-1562. Knowles oxide synthases: 27.73(1):27-35. Röllinghoff M. lial nitric oxidase synthase by hypochlorous acid: Role of NAD(P)H 7. function and inhibition.347(6295):768-770. Gaston B and Stamler JS. cytoprotection. All Rights Reserved. Mashimo H. McCarthy HO.19(2):192-198. type 2 NO-synthase for IL-12 responsiveness in innate immunity. Gladwin MT. 1995. Curr Opin Hematol. 1997. 2001. Reece R. Vita JA. 2001. Mitochondrial nitric oxide synthase. Heck DE. Piacenza L. Csordasa A.marks MacMicking J. 1993.2(10):820-832. Bogdan C. Langford TD. Invest Dermatol. 1996. contact JDDJJ. Laskin DL. Adam Friedman.267(30):21277-21280.1178(2):153175. 2006.87(1):86-93.8(4):601-606. 1994. Kollef MH. Schuster DP. Am J Physiol Heart Circ Physiol. Branco LG. 1990. 20. Albert Einstein College of Medicine 2006. New Engl J Med. 1998. Pharm Acta Helv. 15.291(5):H2026-H2035. Cooper CE. 1994. Shiva S. Lizasoain I. 2001. 4.26(12):2688-2695. and vasodilation. Huang PL. Proc Natl Acad Sci U S A. Epidermal growth long-term hypertension in rats. Xu J. 5. Nat Rev Microbiol. Do Not Copy.3(4):187-204. Rodrigues AL.inNathan C. Antipyretic role of the NO-cGMP pathway in the anteroventral preoptic George Han. J Immunol. Shen YJ. Biochemistry of nitric oxide. J Exp Med. 19. Nitric oxide production trols. Kojda G. apoptosis in Trypanosoma cruzi: Contribution of the nitric oxide and 2006. Brookes PS. Antimicrobial reactive oxygen and nitrogen species: con© 2009-Journal of Drugs proin Dermatology. duce nitric oxide expresscontains both constitutive and inducible nitric 26. 1996. Coulter JA. Nathan C and Xie QW. Requirement for sex hormones. Nosynthase reproduction or useJ of any portion of the contents of these. Ghahary A. Treasure CB. et al. Pimental D. Therefore. Nitric oxide and macrophage Thisand document proprietary information. 2001. An emerging role for nitric oxide in sickle ide synthase indicating a neural role for nitric oxide. et al. Alderton WK. 3. 1. Hwang PM. Noack E. tolls. Structure.282(2):R584-R593. by human intestinal epithelial cells and competition for arginine as 11. Mon7306. Xie Z. Tachon P. 1980. et al. Stamler JS and Meissner G. Fang FC) 1999:37-55. Walter U. Peluffo G. Schindler H. Biochim Biophys Acta. 22. Oxide and Infection (ed. L-arginine-dependent suppression of tive nitrogen species production: Does mtNOS exist? Nitric Oxide.164(3):1478-1487. 1987. ofXie QW. 2002. Klein JL. Knowles RG. et al. Nitric Oxide. 1993. Physiology of nitric oxide in skeletal ed relaxation in human coronary resistance vessels. Moncada S. Am J Physiol Regul Integr Comp Physiol. Antunes-Rodrigues J. MD. J Invest Dermatol.78(6):915-918. J Biol Chem. Suschek CV. Chan J. 40. Enzyme-indepen64. Ghahary A. Abramson SB. 2001. 36.188(21):7344-7353. Stenger S. 1997.4(1):5-15. vascular endothelial or growth in angiogenesis. Hrabie JA. 2006.50(1):49-59. 34. 1540.284(5416):951-955. Evans MC.129(4):834-842. An update. by activated murine macrophages. Lehmann P. 41. 2003. J Invest Dermatol. Kolb-Bachofen V. Ghaffari A. Hassett DJ. 2004. Aberdam E.175(4):11112001. et al. 153. Nitric oxide and wound healing. may Singer AJ. Biol Res Nurs. et al. Richardson MS. 1997. Enhancement of fibropression of inducible nitric oxide synthase after UV irradiation in cublast collagen synthesis by nitric oxide. J Invest Dermatol. Friedternatl. derived keratinocytes but not fibroblasts. No reproduction use offactor any portion of the contents these materials be made without express written Pol.9:283-289. Efron DT. 1999.108(2):460-463. Ultraviolet-B-induced erythema is mediated by nitric 59. document contains proprietary information. 63.293(5):245-248. 60. Choi R. World Roméro-Graillet C. et al.17(15):2342-2344. 52. J Invest Derma2006.6:177-183.61(3):882-888.24(2):80-87. Arch Dermatol Res. Thüring H.107(6):815-821.274(3):689-696. Rec Res Devel Microbiol. please contact JDD immediately. 33. The presence of nichemotactic cytokines: Expressional modulation by nitric oxide in trite during UVA irradiation protects from apoptosis. 47. Rocha IM. Sakai M. et al. 2009. Aravamuthan M. © 2009-Journal of Drugs in Dermatology. Barbul A. 2002. 1996. 2008. Chem. and marks of Journal of Drugs in Dermatology (JDD). Donhauser N.21:399-426. EndotoxinAndonegui G. fibrotic and delayed healing. 57. Gross SS. 38. Frank S.12:17–21. Keratinocyte-derived Suschek CV. 1998. J Infect Dis. Antimicrobial tric oxide synthase and produce nitric oxide in cultured normal huproperties of nitric oxide using diazeniumdiolates as the nitric oxide man melanocytes. Trevani AS. Impairment of antimicrobial 1998. 1991. 1997. Witte MB. 46. Aberrant timing in epidermal ex62. Kämpfer H. 44. man skin: Current status and future prospects. 1995. Nitric Oxpathway to stimulate melanogenesis in human melanocytes. Hosoi J. 2000.111(2):286-291. oxide and prostaglandin E2 in combination. 2000. 2002. Raulli R. 1998. Beland JL. Crit Rev Immunol. 35. Nitric oxide in hu1995. Schroeder P. Role of nitric oxide in wound healKimura H. Xing Y. 1999. Nitric oxide proJ Surg. Aust O. Liew FY. Amin AR. 2004. Penalties Apply Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . 704. Front Biosci. Clark RA. Schaffer MR. Wetzler C. Selig J. Magliozzo RS. J Invest Dermatol.162(5):2922-2930. Pfeilschifter J. Immunohistochemical leishmaniasis by inhibition of nitric oxide synthase. Mills C. All Rights 2001. Aberdam E. plex virus type 1 (HSV-1)-induced pneumonia in mice by inhibition Lavnikova N. Nonspecific defense mechanism: The role of smokers of marijuana and cocaine. activity and nitric oxide production in alveolar macrophages from 51. J Exp Med. Bruch-Gerharz D. A BEMaGS F JUNE 2009 592 VOLUME 8 t*446& COPYRIGHT © 2009 DEPARTMENTS JOURNAL OF DRUGS IN DERMATOLOGY Science. et al. Suppression of herpes simkeratinocytes.110(1):1-7. et al. Adler H. Res Commun. duced by ultraviolet-irradiated keratinocytes stimulates melano58. J Exp Med. skin repair: Novel functions of an established mediator. et al. J Bacteriol. McMullin B. Reactivation of latent Shimizu Y. Tantry U. 2003. McLoughlin L. Adulterated effects of nitric oxide-generO’Donnell AE. Shay AH. FASEB J. and Stechmiller JK. Kuo PC. 1122.4(6):572taneous lupus erythematosus. Guillo LA. Esumi Reciprocal regulation between nitric oxideimages and ing.99(4):635-642. J Dermatol. Weerakoon R. Miller CC. Punzalan C. et al. Fehsel K. Bloom BR.111(1):149582. Macrophage arginine metabolism to ornithine/urea or terium tuberculosis by reactive nitrogen intermediates produced nitric oxide/citrulline: A life or death issue. Clancy RM. 1992. Cihlar RL. Suschek C. ThisH. 56. Thornton FJ. J Biol ide.187(4):700nitric oxide. J Invest Dermatol.185(9):1533ide production in fibroblasts. Kröncke KD. J Invest Dermatol. vitro and during cutaneous wound repair in vivo.117(4):880-885. J Invest Dermatol.14(1):21-29. Effect of nitric oxide mediated S-nitrosylation of p50 alters NF-kappa B-dependent donors on oxygen-dependent cytotoxic responses by neutrophils. The role of nitric oxide in in1998. 65. Kampfer H. Lipopolysaccharide and cytokines induce ni54. delaTorre A. 43. Ultraviolet B ra55.41(7):1141-1151. Krischel V. Biagoli N. J Immunol. Clement M. Biochem Biophys 2003. Arthritis Rheum. tol. sion of endothelial-type and inducible-type nitric oxide synthase in 53. Wetzler C. Gamberale R. 37.the Cutaneous woundconsent healing. Ruzicka T. If you feel you have obtained this copy illegally. Nitric oxide drives genesis.271(45):28052-28056. Whittaker K. Unique patterns of regulation of nitric oxof inducible nitric oxide synthase. Nitric oxide regulates wound Do Not Copy.341(10):738-746. 1999.183(4):1501-1512. 50. Pulmonary ating donors. et al. Pfeilschifter J. Roméro-Graillet C. Potential application diation acts through the nitric oxide and cGMP signal transduction of gaseous nitric oxide as a topical antimicrobial agent. J Exp Med. Hwang SH. 1996. J Leukoc Biol. 1999. Bruch-Gerharz D. Ueda H. et al.162(7):4101-4108. donor. Mowbray M. J Immunol. Chest. J Clin Invest. Frank S. Cox FEG. Barraud N. Parslew R. Immunol Today. Barbul A.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page 31. Engl J Med. Schroeder RA. 42. et al. 2002. Del-Pan NC. et al. Nitric Oxide. 32. Laskin DL. et al. Childress BBReserved. McElhaney-Feser G. mann PS. Clough GF. ible nitric oxide synthase and produce nitric oxide. Langerhans cells express inducide in biofilm dispersal of Pseudomonas aeruginosa. Kidney InRhodes LE.28(3):301-306. 49. Witte MB. Diegelmann RF.ofNJDD. Biphasic effect of dent NO stores in human skin: Quantification and influence of UV exogenous nitric oxide on proliferation and differentiation in skin radiation. Rizk M. ActaofBiochim 61. localization of nitric oxide synthase in normal human skin: Expres1996. Umemura Y. Kuhn A. 39. Xu S. flammation and immunity. gene transcription in ANA-1 murine macrophages.58(4):451-458.128(2):258-260. Involvement of nitric oxQureshi AA. Belgi G. 45. Killing of virulent Mycobac48. complications associated with illicit drug use. McLintock S. Wound healing: An overview of acute. Nitric oxide and human skin blood flow responses to expression of inducible nitric oxide synthase activity and producacetylcholine and ultraviolet light. Pulfer SK. Effects of nitric oxide up-regulated in melanoma cell lines: A potential mechanism for releasing poly(vinyl alcohol) hydrogel dressings on dermal wound Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . Biomaterials 2005. Ambach A. 2008. Massi D. Rothrock AR. intracellular translocation of pigment organelles in Xenopus laevis 2005.105(2):165-188. Current topics of physiol67. da Silvaor AM. Wang LF. with photosensitivity. Nitric oxide produc91. 2009 Mar 17. 1994. 71. Di Giunta G. Wilks M.marks Marxer SM. cium channel blockers. Hsiao M. 1998. Inhibition of nitric 83. Barbul A. 2001. Leibovich SJ. Watanabe M. Dooley A. 95. Ruzicka T. Oxide. et al. Toyoda M. Involvement of nitric pression in benign and malignant cutaneous melanocytic lesions. Shabani M. 1998. Proc Natl Acad Sci. Kolb-Bachofen V. Inverse correlation between 70. Perelman RO. Pharmacol Ther. Epidermal keratino2004. et al. et al. 1996. Schäffer MR. Lancet. Qureshi A. metastases formation.208(3):439-445. Nitric oxide modulates ogy and pharmacology in the lymphatic system. Cancer Metastasis Rev. Kolb JP. 66. 2006. Kaminaga H. 85. Seo W. Melanoma Res. Chem Mater. 2000. White WL. Bulgrin JP. cer) with topical nitrogen oxides. Robbins ME. Butler RD.147(6):1102-1108. images and of Journal of Drugs Dermatology (JDD). et al. Nablo BJ. 1993. 86. please contact JDD immediately. No reproduction useSotto of any portion of the contents these materials may be madeof without express written consent of JDD. sion and activity in the tight skin model mouse of fibrosis.89(7):3030-3034. tion of metastasis in K-1735 murine melanoma cells.14(4):327-334. lial cell/tumor cell interface. J Invest Derm. 2000. Loitto VM. Chronic infections and inflammatory pro97. Fehsel K. J Dtsch Dermatol Ges. 1996.16(12):574-580. Phillips R. Mizuno R. Nitric oxide produced by iNOS is livery of nitric oxide therapy to the skin of human subjects using a associated with collagen synthesis in keloid scar formation. Kagoura M. Dugas B.6(2):121-126.47(3):272-280. Inducible nitric oxide synthase ex69. Holmes A. Tantry U. Masters KS. Res. et al. Phillips PG. sclerosis with the endothelin-1 receptor antagonist bosentan and 75. Lassalle MW. Horikoshi T. Immunol tion therapy of severe digital ulcers in diffuse progressive systemic Today. Brunson D. Rheu1476. Hardwick JB. Klose JR. Role of nitric oxide in angiogenesis and mioxide synthesis in wounds: Pharmacology and effect on accumucrocirculation in tumors. Nitric oxide synthase in toxic epithe phosphodiesterase V inhibitor sildenafil. Belem P. Wound Repair Regen. Ohhashi T. Morohashi M. Cell Res. 74. trix metalloproteinase-9 expression and distribution at the endothe1998. in pityriasis lichenoides lesions. Schoenfisch MH. 92. Hsu YC. Enhancement of cesses as cancer risk factors: possible role of nitric oxide in carwound repair with a topically applied nitric oxide-releasing polymer. et al. Santucci M. Karlsson AM. and immunohistochemical analysis of inducible nitric oxide syn88. Igarashi S. 1996. Copeland P.inNablo BJ.194(2):194-200. Staroselsky X. J. Mossalayi MD. 2002. Smith DJ. Oshima H. Tsukazaki N. Adjei O. Nakahara M. Clin Sci. 2009. cyte expression of inducible nitric oxide synthase in skin lesions of 90. 82. J Cutaneous Pathol.344(8915):139. Do Not Copy. Nitric oxide synthase expreszwitterions derived from polyamines. et al. Fidler IJ.100(4):395-400. tochemical study of inducible nitric oxide synthase in skin cancers. J Pathol. Shimizu K. 2001. Dong AH. J Surg Res. FASEB J.4(3):353-362. 1994. Am J Physiol Lung Cell Mol Physiol. If you feel you have obtained this copy illegally. Arch Dermatol Res. 1992.290(1-2):3-8. Cancer Res. Ormerod AD. 81. J Cutaneous Path. Warren JB. Nilsson HM. Low-dose combination by human monocytes: Evidence for a role of CD23. Franchi A. Antimicrob Agents Chemother. Mutat Res. 96.48(8):2866-2870.8(2):247-251.7(5):497-500. Crespi CL. et al. 2001. Bonnekoh B. et al. 87. 1999. Pigment Cell cell carcinoma. et al. Birnby LM.17(1):77lation of collagen in wounds in mice. 84. et al. Treatment of Raynaud’s: Beyond calpsoriasis vulgaris. Fukumura D. 2004. Tucker AT. et al. Org Chem. Cell Motil Cytoskel. All Rights Reserved. Pigment J Pathol. 79.16(1):81-84. Keefer LK.17(1):55-75. Photoprovocation test 1994.30(2)5:253-264.13(5):358-363. dermal necrolysis and Stevens-Johnson Syndrome. Jain RK. Effects of melanogenesisthase activity correlates with lymphangiogenesis and vascular eninducing nitric oxide and histamine on the production of eumelanin dothelial growth factor-C expression in head and neck squamous and pheomelanin in cultured human melanocytes. Reddy B.286(5):L1055-L1065. DNA damage and mutation trial of treatment of Mycobacterium ulcerans disease (Buruli ulin human cells exposed to nitric oxide in vitro. Bartsch H. 330. Sardi I. 267. Weller R. Nitric oxide synthase activity is 98. 94. J Drugs Dermatol. Strandhoy J. Cancer Metastasis Rev. Inducible nitric oxide of synthase Preparation nitric the oxide (NO)-releasing sol-gels. Damais C.114(1):196-199. oxide in UVB-induced pigmentation in guinea pig skin. ImmunohisInhibition of implant-associated infections via nitric oxide release.15:4193-4199. Hrabie JA. Bergstrom KG. Nguyen T.58:1472© 2009-Journal of Drugs in Dermatology. 1994. cinogenesis. 1995. A novel method for the de76. Xie K. This document contains proprietary information. Eur J Surg. Br J Dermatol. et al. Epub ahead of print. Wink DA. Klitzman B. Matsui C. Low SY. Nitric oxide modulates caveolin-1 and maide and nitric oxide synthases in psoriasis. Nitric semi-permeable membrane. 2008. Joshi M.28(9):476-481.36(3):3252003. Pilot randomized double-blind 80. et al.54: 789-793. Prichard HL. Sasaki M. Detection of nitric ox89. MN. Ikomi F. Lerner L. Franchi A. Inducible nitric oxide syn68. melanophores. Therapy of cancer metastasis by activation of thase expression in patients with Sjogren’s syndrome associated the inducible nitric oxide synthase. Thornton FJ.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F JUNE 2009 593 VOLUME 8 t*446& COPYRIGHT © 2009 DEPARTMENTS JOURNAL OF DRUGS IN DERMATOLOGY healing.47(3):209-218.63(1):237-240. 2003. Qi X. Gollnick H. Kawai Y. 78. Schoenfisch MH. 93.26:6984-6990.165(3):26289. 2006. 73. Lucas S. Michel G. Massi D. Penalties Apply matolgy. New nitric oxide releasing 77. 2000. 72. Martinez L. A BEMaGS F JUNE 2009 594 VOLUME 8 t*446& COPYRIGHT © 2009 DEPARTMENTS JOURNAL OF DRUGS IN DERMATOLOGY healing in diabetic mice. Meyerhoff ME. Parzuchowski PG. 2000.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page 99. Clinical Trials. Han G. 102. 101. Natural Prod ts in have If you feelucyou obtained Skin Car e Natural Products in Skin Care this copy illegally. &/550 © 2009-Journal of Drugs in Dermatology. Br J Pharmacol. Wound collagen deposition in rats: effects of an NO-NSAID and a selective COX-2 inhibitor. Am J Sports Med. This document contains proprietary information. 2002. Appleyard RC. et al. This supplement to the Journal of Drugs in Dermatology is supported by a medical education grant from Johnson & Johnson Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F .124(41):12182-12191. Frost MC. Nelson J. Murrell GA. Placebo-Controlled Clinical Trial. Antimicrobial and healing efficacy of sustained release nitric oxide nanoparticles against Staphylococcus aureus skin infections. 2009 [Epub ahead of print]. Wound Repair Regen.10(5):286294. 104. *44/ +VOFt 7PMVNFt *TTVF SUPPL EMENT) Look for this supplement with your June issue of JDD.gov/ct2/show/study/NCT00317629. Sustained release nitric oxide releasing nanoparticles: Characterization of a novel platform based on nitrite containing hydrogel/glass composites. 2002.19(1):12-20. 2008. please contact JDD immediately. Nitric Oxide. Paoloni JA. Asfaha S. Navati MS. images and marks of Journal of Drugs in Dermatology (JDD). McKnight W. June 2009 Supplement: No reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD.129(4):681-686.gov. Wallace JL. 2003. J Amer Chem Soc. J Invest Derm. All Rights Reserved. Penalties Apply New CME Opportunity "4611-&. Han G. 100. or download it from our CME library at JDDonline. Chacko M. Topical Nitric Oxide Application in the Treatment of Chronic Extensor Tendinosis at the Elbow A Randomized.31(6):915-920. 2009 Do Not Copy. et al. Double-Blinded.com. Available at __________ http://clinicaltrials. Friedman A. Accessed April 13. 103. US National Institutes of Health. Muscara MN. Synthesis and characterization of polymethacrylate-based nitric oxide donors. If you feel you have obtained copy illegally. The was reproduction or use of any portion of the contents of these materials may be made without the3. The mean time to healing was 5 to 7 weeks in the AM group and 6 to 8 weeks in the standard treatment group. The results of this randomized controlled trial were published in the International Wound Journal. one for an adverse event (crying upon application) and one for lack of compliance. Inc. chin and upper lip. We trust you will find this information beneficial to your practice and research. repeated 72contact hours and week later. plus reports from physicians who wish to share their clinical experience with these new products. These departments may include additional information from the manufacturers.2% of the patients in the standard treatment group. The only noted side effect was mild erythema post-treatment. with a mean of 51%. After four months post-treatment. 84% of patients had a significant percentage of hair reduction. Two patients discontinued the study. perineal. In addition. The Reserved. Wright Medical Technology. 40mW).8 months of age with untreated. Argentum Medical. Criteria excluded hemangiomas that were periorbital. The full report can be found at Photomedicine and Laser Surlight device. The full report can be found in Pediatric Dermatology. FDA Boxed Warning for Botulinum Toxin Products The FDA recently announced that the manufacturers of botulinum toxin products will need to add a boxed warning regarding risks of Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F .8 express consent ofprocedure JDD. 27(2): 357-363.01% (m/V) of methylene blue solution applied to the vesicular stage of their her© 2009-Journal of Drugs in Dermatology. Imiquimod for Infantile Hemangioma A recent phase 2. In this study. The aim of the study was to evaluate the efficacy and safety of this home-use treatment for the Results showed a decrease in the frequency of vesicle recurrence and general public. or >100 cm2 in size. The study enrolled a total of 16 healthy infants up to 8. axilla. foams. proliferative superficial or mixed infantile hemangiomas. neck. the study evaluated mean time to healing with complete re-epithelialization between the 2 groups. Twenty-four after treatment. Acellular Matrix Skin Graft for Diabetic Foot Ulcers A new study published recently shows that treating diabetic foot ulcers with an acellular matrix (AM) skin graft led to faster healing than standard treatment. we will inform our readers about the latest drugs receiving Food and Drug Administration (FDA) approval. low this fluence. The aim was evaluate the healing of ulcers at 12 weeks in patients each type of therapy. home-use intense pulsed light device. and Laser Therapy evaluated hair removal with a novel. Results revealed complete healing in 69. lesions were then irradiated by a laser (660 nm. please JDD1immediately. open-label study examined the efficacy and safety of imiquimod in the treatment of superficial and mixed infantile hemangiomas. All Rights pes disease. Patients in the standard therapy group received moist-wound therapy with alginates. images and marks of Journal of Drugs inhours Dermatology (JDD). the patients had A recentNo report published in April 2009 in the Journal of Cosmetic repeated phototherapy with J/cm2written and 15mW. LLC). In total. 11 of 14 patients had improvement in erythema. No significant side effects were I–III were treated with three weekly therapies with an intense pulsed noted. hydrocolloids or hydrogels with daily dressing changes. 120 J/cm2. Do Not Copy. nonulcerated. The study enrolled four patients who had 0. bikini area.6% of the patients in the AM group and in 46. A total of 31 cutaneous areas were treated. They surmise that this may indicate that effects were limited to the superficial component. The authors conclude that topical imiquimod was well tolerated and that improvement was noted in lesion color but not in lesion size. including the gery.) that was sutured in place and covered with a silver-based nonadherent dressing (Silverlon. 26(2):203-212. The study enrolled 46 patients who were randomly assigned to AM therapy and 39 patients who were randomly assigned to standard therapy. March/April 2009.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F JUNE 2009 595 VOLUME 8 t*446& COPYRIGHT © 2009 DEPARTMENTS JOURNAL OF DRUGS IN DERMATOLOGY PIPELINE PREVIEWS Pipeline Previews brings to you information on the newest drugs and medical products as they become available to the dermatological community. Penalties Apply Patients treated with AM received one application of a human acellular dermal regenerative tissue graft (4x4 cm Graftjacket Regenerative Tissue Matrix-Ulcer Repair. Topical imiquimod was applied three to seven times per week for 16 weeks to the hemangiomas. This document contains proprietary information. April 2009. In addition. Home-Use Intense Pulsed Light Device Results indicated that the mean reduction in terminal hair counts was 47% after 4 week of follow-up and 41% after 6 months of follow-up. 29 patients with Fitzpatrick skin types an increase in the healing process. abdomen. Photodynamic Therapy for Herpes Simplex Labialis A recent report in Photomedicine and Laser Surgery examines photodynamic therapy (PDT) as an adjuvant therapy for the treatment of herpes labialis. the manufacturers will need to have a risk evaluation and mitigation strategy to ensure that benefits outweigh the risks. images and marks of Journal of Drugs in Dermatology (JDD). All Rights Reserved. This document contains proprietary information. The affected products are Botox and Botox Cosmetic (botulinum toxin type A. No reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD. be aware of the potential adverse events due to distant spread of toxin effects and understand that adverse effects can occur from several hours after injection up to several weeks after injection. In adults. including respiratory difficulty and death after use of these products for approved and unapproved uses. please contact JDD immediately. blepharospasm. Do Not Copy. no definitive serious adverse-event reports of this effect were associated with the use of Botox at the labeled dose of 20 units for glabellar lines or 100 units for severe primary axillary hyperhidrosis. dysphonia. Solstice Neurosciences) that are approved by the FDA for use in the glabella. In addition. If you feel you have obtained this copy illegally. Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . Penalties Apply © 2009-Journal of Drugs in Dermatology. loss of bladder control. Allergan) and Myobloc (botulinum toxin type B. treatment of strabismus. specifically those that can occur when the effects of the toxin spread outside of the intended treatment area. most reports of distant spread of toxin effects were noted when the products were used to treat spasticity or cervical dystonia. trouble breathing or swallowing.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F JUNE 2009 596 VOLUME 8 t*446& COPYRIGHT © 2009 DEPARTMENTS JOURNAL OF DRUGS IN DERMATOLOGY adverse events. The FDA recommends that healthcare professionals who use botulinum toxin products understand that the dosage strength differs among the products. This new warning stems from reports of systemic adverse reactions. Finally. dysarthria. The most serious cases occurred predominantly in children treated for cerebral palsy-associated limb spasticity. blurred or double vision or drooping eyelids. Notably. they should advise patients to seek medical treatment if they develop unexpected loss of strength or muscle weakness. cervical dystonia and primary axillary hyperhidrosis. Sponsored by PhotoCure. Penalties Apply Condition Intervention Phase Acne Vulgaris Drug: Benzoyl Peroxide/ Clindamycin Drug: Benzoyl Peroxide/ Adapaleme Phase 4 Condition Intervention Phase Acne Vulgaris Drug: Dapsone Drug: Tazarotene Phase 4 Study ID Numbers: MA-ACZ0802 ClinicalTrials.1% Monotherapy for Facial Acne Vulgaris Sponsored by Allergan. made without the express written consentwill of JDD. All whether Rights Reserved. and successfully complete the study. and 25–100 facial non-inflammatory lesions. lesion counts (papules and pigmentation score assessed after treatment. the reduction in noninflammatory lesion counts from baseline. Condition Intervention Phase Rosacea Condition Intervention Phase Acne Vulgaris Drug: Methyl aminolevulinate (MAL) PDT Phase 2 Study ID Numbers: PC TA203/08 ClinicalTrials. Medicis Pharmaceutical Corporation.1% Versus Tazarotene Cream 0. It is our goal to inform the reader of the status of select drug trials relevant to the practice of dermatology before this information is available through standard channels. the ability and willingness to follow all study procedures. ACNE A Comparative Study of the Tolerability of Two Combination Therapies for the Treatment of Acne Sponsored by Stiefel Laboratories. of Primary pustular Primary outcome measures include the No reproduction useMAL of any portion the contents these materials may berosacea. and. attend all scheduled visits. visit www.gov Identifier: NCT00834210 Study ID Numbers: C0000-401 ClinicalTrials. three or more nodules and/or cysts (diameter of 1cm or greater). Do Not Copy. Those included in the study will have facial acne vulgaris characterized by the following: 30–100 facial inflammatory lesions.1% compared with tazarotene cream 0.2% And Tretinoin with dark skin and vulgaris will be included.1% monotherapy in treating moderate to severe facial acne vulgaris. images and marks Gel of Journal of Drugs and in Dermatology (JDD). In this multicenter study.2% and Tretinoin 0. Those included in the study will meet the following criteria: male or female subjects at least 21 years of age. Dapsone Gel 5% and Tazarotene Cream 0.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F JUNE 2009 597 VOLUME 8 t*446& COPYRIGHT © 2009 DEPARTMENTS JOURNAL OF DRUGS IN DERMATOLOGY CLINICAL TRIAL REVIEW Clinical Trial Review is a JDD department designed to provide physicians with information on drugs undergoing clinical testing. lesion counts from baseline. capable of understanding and willing to provide signed and dated written voluntary informed consent (and any local or national authorization requirements) before any protocol specific procedures are performed. Female subjects of childbearing potential must have a negative pregnancy test at baseline and practice reliable method of contraception throughout the study. pleasechange contact JDD immediately. the reduction in inflammatory thema (flushing) at week 12.025% are effective safe in the treatment of papuloThisacne document contains proprietary information.gov.2% and Tretinoin 0. Secondcome measures will include: erythema score and other local ary outcome measures will include reduction in transient eryand non-local adverse events. non-rapidly regressing facial acne vulgaris. The patients 0. patients termine Clindamycin Phosphate 1.clinicaltrials.gov Identifier: NCT00887484 ROSACEA Photodynamic Therapy (PDT) With Methyl Aminolevulinate (MAL) Cream in Patients With Skin Type V or IV With Acne Vulgaris Safety and Efficay Study of Clindamycin Phosphate 1. The purpose of this study is to de© 2009-Journal of Drugs in Dermatology. inflammatory (papules and pustules) and non-inflammatory (open and closed comedones) facial lesions.gov Identifier: NCT00673933 Drug: Clindamycin Phosphate 1. The purpose of this study is to compare the tolerability of topical combination therapies in the treatment of facial acne. in good general health with documented diagnosis of acne vulgaris. stable disease. To participate in or learn more about these and additional trials.025% Gel to Treat Rosacea Sponsored by Massachusetts General Hospital. Secondary outpustules) from baseline to week 12 (end of treatment). will receive treatment or with PDT andofplacebo PDT. outcome measures will include: hypopigmentation andthis hyperabsolute in inflammatory If you feel you have obtained copy illegally.gov Identifier: NCT00823901 Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F .025% Gel Drug: Placebo Phase 2 Phase 3 Study ID Numbers: 2008-P-001828 ClinicalTrials. This is a 12-week evaluation of the safety and efficacy of dapsone gel 5% when used with tazarotene cream 0. or female. double-blind.gov Identifier: NCT00757042 Management of Pruritus With Xyzal in Atopic Dermatitis Sponsored by Derm Research. PLLC. male or female subjects of any race. tolerability and pharmacokinetics of AMG 157. It will be a welcome addition to our treatment armamentarium if a drug such as Xyzal can control pruritus associated with atopic der© 2009-Journal of Drugs in Dermatology. study. Claritin.gov Identifier: NCT00884325 Study ID Numbers: 32032 ClinicalTrials. In this study. Atopic dermatitis and gastrointestinal (GI) symptoms will be scored and followed throughout the study. ception throughout the study. placebo-controlled. Subject must have active AD affecting ≥10% body surface area. of Drugs in Dermatology of childbearing have a negative pregnancy children. inclusive. The change in inflammatory lesion count will be assessed at each post-baseline visit by an analysis of variance model (ANOVA) with factors treatment and center. healthy subjects must have a body mass index (BMI) between 18 to 32 kg/m2. female subjects must be of non-reproductive potential. Project number: 256-0024 ClinicalTrials. Study ID Numbers: 20070620 ClinicalTrials. test please result contact at Baseline and practice a reliable method of contratis (AD) associated with food allergens.The study will enrollimages 20 and This document contains proprietary information. previously documented If you feel you have obtained this copy illegally. before enrollment. A total of 20 participants will be recruited for the entire study. subject must have normal or clinically acceptable physical examination. and for Part B. Female subjects Each arm will consist of 10 participants. Rights Reserved. Atopic Dermatitis is a disease found in children. by skin or RAST test. Condition Intervention Phase Condition Intervention Phase Atopic Dermatitis Drug: Montelukast Drug: Placebo Phase 4 Atopic Dermatitis Drug: Levocetirizine dihydrochloride (Xyzal) Phase 4 Study ID Numbers: XYZ0801 ClinicalTrials. This study is a phase 1 single dose escalation study of AMG 157 in healthy subjects and subjects with moderate to severe atopic dermatitis.gov Identifier: NCT00557284 Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . male subjects with partners of childbearing potential should inform their partner of their participation in this clinical study and use highly effective methods of birth control during the study. 50% and 75% clearing compared to baseline. subjects with moderate papulopustular rosacea will be treated either with azelaic acid 15% gel topically plus an anti-inflammatory dose of doxycyline (40mg)daily or with metronidazole 1% gel topically once daily plus an anti-inflammatory dose of doxycycline (40mg) over at total of twelve weeks to determine the rapidity of improvement. Condition Intervention Phase Atopic Dermatitis Healthy Volunteers Drug: AMG 157 Phase 1 Do Not Copy. inclusive. Condition Intervention Phase Rosacea Drug: Azelaic acid gel plus 40 mg doxycycline Drug: Metronidazole plus doxycycline Phase 4 Study ID Numbers: 1402604. parallel group trial conducted in participants diagnosed with atopic dermatitis and food allergies. clinical laboratory tests and electrocardiogram (ECG) results. but not including treatment-by-center interaction. Penalties Apply ATOPIC DERMATITIS Efficacy Study of Montelukast in Atopic Dermatitis Induced by Food Allergens Sponsored by 1st Allergy & Clinical Research Center. subjects must be aged between 18 and 45 years. at least 18 marks yearsofofJournal age may be included in this (JDD). and BMI between 18 and 35 kg/m2. Inclusion criteria is as follows: subject must sign an Institutional Review Board (IRB) approved informed consent form before any study specific procedures. and the length of time to reach 25%. The purpose of the study is to evaluate the safety. JDD immediately. The study duration for participants will be approximately nine weeks.AllOutpatient. Most of the patients are not controlled with traditional antihistamines such as Clarinex. and Allegra.gov Identifier: NCT00855595 Safety Study of AMG 157 in Healthy Subjects and Subjects With Atopic Dermatitis Sponsored by Amgen. This study will be a randomized. matitis. 1—8 of age atopic dermatiNomale reproduction or use of years any portion of with the contents of these materials may be madepotential without themust express written consenturine of JDD. It is historically well known that the management of pruritus in atopic dermatitis is very difficult. the focus of the study is the mechanisms associated in children with AD induced by food allergies.A BEMaGS Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page F JUNE 2009 598 VOLUME 8 t*446& COPYRIGHT © 2009 DEPARTMENTS JOURNAL OF DRUGS IN DERMATOLOGY Efficacy of Topical Azelaic Acid 15% Gel Plus AntiInflammatory Dose Doxycycline or Metronidazole Gel 1% Plus Anti-Inflammatory Dose Doxycycline in Moderate Papulopustular Rosacea Sponsored by Intendis GmbH. inclusive. week 2. Condition Intervention Phase Bullous Pemphigold Drug: Rituximab Phase 1 Study ID Numbers: 6641-05-2R0 ClinicalTrials.gov Identifier: NCT00283712 Rituximab in the Treatment of Patients With Bullous Pemphigoid Do Not Copy. The trial is being conducted by Dr. 18 and 26. This trial will test this hypothesis by examining whether IVIg treatment given with cyclophosphamide results in a more rapid decline in circulating pemphigus antibodies than when given alone. The extent and activity of the disease. The trial is being conducted in patients with pemphigus that are not responding to. Sponsored by Duke University. A total of 12 patients will be treated in each arm of the trial. BP occurs more frequently in the elderly. BP is the most common of the autoimmune blistering diseases with an incidence of approximately 10 per 1. tense blisters located over the trunk and extremities. Bullous pemphigoid (BP) is an autoimmune blistering disease characterized clinically by the presence of severely itchy. an immunosuppressive drug often used to treat other autoimmune diseases including pemphigus. and this cycle will be repeated every other week for a total of 4 cycles. There will be a total of 9 study visits until Week 26: screening. This antibody This document contains proprietary information. zoneplease type contact XVII collagen (BPAg2) and against a 230 kd protein If you feel you have obtained this copy illegally. study entry. In addition. of patients shows the presence of a circulating anti-basement Study ID Numbers: 3343 membrane zone autoantibody. patients will also be asked to complete a tuberculosis (TB) questionnaire. medical and medication history. 2) the dose of corticosteroids required to treat the disease can be reduced. Penalties Apply The goal of the study is to determine whether there is a difference between the two treatments in the rate at which: 1) the activity and extent of the disease improves. images and marks of Journal of Drugs in Dermatology (JDD). skin assessments and blood collection. This study will determine the safety of treatment of bullous pemphigoid in patients resistant to therapy with systemic corticosteroids. The purpose of this study is to compare two standard treatments for pemphigus to determine which more effectively improves the clinical manifestations of the disease and decreases serum level of the autoantibodies that cause the disease. including rheumatoid arthritis and Crohn’s disease.gov Identifier: NCT00483119 be directed against a 180 protein of theconsent basement membrane No reproduction or use of any portion of the contents of these materials may be made without thekdexpress written of JDD. with rituximab plus systemic corticosteroids. half of the patients will be selected by chance to also be treated with cyclophosphamide. 18 and 26. Condition Intervention Phase Pemphigus Drug: Infliximab Drug: Prednisone Drug: Placebo Phase 2 Study ID Numbers: DAIT APV01 ClinicalTrials. a review of the disease activity log and adverse events experienced since the last visit. All patients will be treated with IVIg administered using a standard protocol. as well as the blood levels of pemphigus antibodies. vital signs measurement. and 3) the blood level of pemphigus antibodies decrease. Infliximab is a man-made antibody used to treat certain types of immune system disorders. will be measured at baseline prior to entry into the trial and periodically during the trial.000. Vulgaris Sponsored by the National Institute of Allergy and Infectious Diseases (NIAID).gov Identifier: NCT00286325 Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . additional skin biopsies of affected skin will be done at study entry and week 18. The cyclophosphamide is a pill that is taken 3 times a day. Direct immunofluorescence of Condition Intervention Phase the skin of patients with BP reveals a linear band of C3 and Pemphigus Drug: IVIG. JeanClaude Bystryn at the New York University Medical Center. and every 4 weeks thereafter. cyclophosphamide Phase 2 IgG at the basement membrane zone. All Rights Reserved. or have developed complications from. if patients have PV-associated lesions. Routine histopathology reveals a sub-epidermal blister most often with large numbers of eosinophils. Pemphigus vulgaris (PV) is a rare skin disorder that causes blistering of the skin and mucous membranes. standard treatment. This study will determine if infliximab given in combination with prednisone is a safe and effective treatment for adults with PV. Skin biopsies of unaffected skin will be done at study entry and weeks 10.000 population. Use of Infliximab for the Treatment of Pemphigus (BPAg1) found in the epidermal hemi-desmosome. JDD immediately. Each study visit will include a physical exam.has been found to ClinicalTrials. Patients will be asked to complete quality of life questionnaires at study entry and weeks 10. Examination of the sera Vulgaris © 2009-Journal of Drugs in Dermatology. The IVIg will be given daily for 4 days. In addition.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F JUNE 2009 599 VOLUME 8 t*446& COPYRIGHT © 2009 DEPARTMENTS JOURNAL OF DRUGS IN DERMATOLOGY IMMUNOBULLOUS DISORDERS Randomized Trial of IVIg With or Without Cyclophosphamide in Pemphigus Sponsored by the Food and Drug Administration (FDA). mmol/lAll ofRights ionic Reserved. with onset not exceeding 24 hours until the time of study drug administration Adolescents participating in PK part of the study may be enrolled without an active herpes labialis recurrence or with onset of signs/symptoms of a recurrent herpes labialis episode longer than 24 hours before study drug administration. Santa Fe. the eye. Patients treated with Xolair will be compared to patients receiving standard treatment with prednisone. as well as prodromal symptoms or active lesions suggestive of a recurrent episode of herpes labialis (i. relieving the symptoms of herpes as healing occurs. Zinc salts irreversibly inhibit herpes virus replication in vitro and are effective in treating herpes infections in vivo and have been shown in a clinical trial to be a effective topical treatment for HSL. Zinc gluconate is monographed No reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD. hydroxyethylcellulose. Zinc swabs contain 33 © 2009-Journal of Drugs in Dermatology. and. Conventional treatments include systemic steroids. having had cold sores in the past). Zinc for the Treatment of Herpes Simplex Labialis (HSL) Sponsors and collaborators: Integrative Medicine Institute. with general good health with a documented history typical for recurrent herpes labialis. NM. Penalties Apply Sponsored by University of Alabama at Birmingham. Pemphipoid one of OTC indications for Zinc and its salts is for the treatment Study ID Numbers: U3441S of cold sores. We propose that it will also be effective in the treatment of cicatricial pemphigoid. This study will assess the safety. Zinc in an emulsification of Benzalkonium chloCondition Intervention Phase ride. and has recently been shown to be effective for autoimmune blistering pemphigus. in the Cicatricial Homeopathic Pharmacopoeia of the United States (HPUS) and If you feel you have obtained this copy illegally.e. tolerability of a single 1500 mg dose of famciclovir in 50 adolescents with recurrent herpes labialis. however. are not successful with all patients. This is a pilot. Ritumimab has been very effective in the treatment of other autoimmune disorders.gov Identifier: NCT00584935 DERMATOMYOSITIS Safety and Pharmacokinetics of Famciclovir Single 1500 mg Dose in Adolescents With Recurrent Herpes Labialis Sponsored by Novartis Pharmaceuticals. mucous membranes. dapsone. Women’s Health Services. and soOcular Drug: Rituximab Phase 1 dium hydroxide (ph 7.gov Identifier: NCT00878072 Do Not Copy. sodium This document contains proprietary information. pathogenic IgE class autoantibodies have been identified in these patients. Condition Intervention Phase Bullous Pemphigoid Drug: Omalizumab Phase 4 Study ID Numbers: 100569 ClinicalTrials. ClinicalTrials. The current treatment for BP is non-specific immunosuppression. please contact JDD immediately. causing great morbidity in these patients. bullous pemphigoid (BP). The primary objective is to test the safety and efficacy of Xolair in the treatment of the autoimmune blistering disease. glycerin. The enrollment period for the study is 24 weeks: 16 weeks active treatment and 8 additional weeks of observation. Genetech. Inc. Eight of the 50 adolescents will also participate in the pharmacokinetics (PK) as- Condition Intervention Phase Herpes Simplex Labialis Drug: Zicam (Ionic zinc) Phase 3 Study ID Numbers: IMIZnc2008 ClinicalTrials.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F JUNE 2009 600 VOLUME 8 t*446& COPYRIGHT © 2009 DEPARTMENTS JOURNAL OF DRUGS IN DERMATOLOGY Efficacy and Safety of Omalizumab in Bullous Pemphigoid Sponsored by University of Iowa. Recently. Cicatricial pemphigoid is an autoimmune blistering disease which affects the skin. and Matrixx Initiatives. open label case-control study. All adolescents participating in the pharmacokinetics assessments must fast for at least 8 hours prior to Visit 1 and be willing to fast for an additional 2 hours after study drug administration. chloride. images and marks of Journal of Drugs in Dermatology (JDD). Southwest College of Naturopathic Medicine. Condition Intervention Phase Herpes Labialis Drug: Famciclovir Phase 2 Study ID Numbers: CFAM810B2305 ClinicalTrials. and immunosuppressive agents. Beth Israel Continuum Center for Health and Healing. These treatments.gov Identifier: NCT00809809 Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . New York. Evaluate the effectiveness of a topical preparation of zinc to treat cold sores. Inclusion criteria is as follows: Outpatient males or females 12 to 18 years of age. Progressive ocular disease can lead to irreversible damage and blindness. Zinc salt solutions applied to herpetic lesions decrease viral load and markedly improve healing rates. in a small subset of patients. Development of a more targeted approach to treatment may reduce morbidity.2). Biogen Idec.gov Identifier: NCT00472030 Clinical Trial Evaluating Rituximab in Ocular Cicatricial Pemphigoid sessment of famciclovir single 1500 mg dose. NY. cyclosporine.g. of the treatment. Based on the antimicrobial profile. The study will enroll approximately 76 patients at approximately 45 study centers in the United States and Germany. doubleblind. 2) prior steroid treatment with steroid discontinuation due to unacceptable morbidity. or 3) previous or current use (without symptom control or with unacceptable morbidity: e. PZ-601 also has activity against Gramnegative organisms including cephalosporin and quinolone resistant Enterobacteriaceae as well as Bacteriodes fragilis and peptostreptococci. evaluate images the and Inclusion follows: participants will have a CIU diagThis document marks ofcriteria Journalisofas Drugs in Dermatology (JDD). dose-ranging. parallel-group study. placebo-controlled.g.gov Identifier: NCT00671580 URTICARIA Study to Evaluate The Safety and Efficacy of Abatacept in Subjects With Chronic Urticaria Who Have Had an Inadequate Response to AntiHistamine Therapy A Study of Xolair (Omalizumab) in Patients With Chronic Idiopathic Urticaria (CIU) Who Remain Symptomatic With Antihistamine Treatment (H1) The Efficacy and Safety of Desloratadine With Levocetirizine in Treatment of Chronic Idiopathic Urticaria Sponsored by Lotus Pharmaceutical. and Pharmacokinetics of PZ-601 in the Treatment of Complicated Skin and Skin Structure Infection Sponsored by Protez Pharmaceuticals. The objective of this study is to compare the efficacy of desloratadine 5mg (Denosin®) and levocetirizine 5mg (Xyzal®) once daily in the treatment of patients with CIU over 6 weeks. azathioprine. and safety of desloratadine 5mg (Denosin®) and levocetirizine 5mg (Xyzal®) once daily in the treatment of subjects with CIU Condition Intervention Phase over 6 weeks. Bristol-Myers Squibb. The primary endpoint of thiscontains study proprietary will be toinformation. change No in reproduction average AM/PM pruritus from base-materials nosis ofbe more 3 months (by history). etc).gov Identifier: NCT00886795 Do Not Copy. methotrexate. please contact JDD immediately. hypertension from cyclosporine. active-controlled. double-blind.S.gov Identifier: NCT00346606 Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . Food and Drug Administration (FDA) to treat adults with skin and skin structure infections.A BEMaGS Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page F JUNE 2009 601 VOLUME 8 t*446& COPYRIGHT © 2009 DEPARTMENTS JOURNAL OF DRUGS IN DERMATOLOGY Safety. Condition Intervention Phase Urticaria Drug: Abatacept (Orencia®) Phase 1 Study ID Numbers: Tahoe-001 ClinicalTrials. randomized. Potential Efficacy. Secondary Objectives: To assess the efficacy cannot be physical urticaria).. parallel-group study of the efficacy and safety of a single subcutaneously administered omalizumab dose as add-on therapy for the treatment of adolescent and adult patients 12-75 years old who have been diagnosed with CIU and remain symptomatic despite treatment with therapeutic doses of an H1 antihistamine. PZ-601 is a potentially promising agent for the treatment of complicated skin and skin structure infections. Sponsored by Genetech. Condition Intervention Phase Skin Infections Drug: PZ-601 Drug: PZ-601 Drug: Standard of Care Phase 2 Sponsored by Johns Hopkins University. All Rights Reserved. Condition Intervention Phase Chronic Idiopathic Urticaria Urticaria Drug: Denosin® and Xyzal® Phase 4 Chronic Idiopathic Urticaria Drug: Omalizumab Drug: Placebo Phase 2 Study ID Numbers: Q4577g ClinicalTrials. as well as no underor usereflective of any portion of thescore contents of these may madethan without the express written consent of JDD.gov Identifier: NCT00866788 Study ID Numbers: 187CL1 ClinicalTrials. Penalties Apply Study ID Numbers: PZ-601-02 ClinicalTrials. This study is being done to find out if a drug called Abatacept (Orencia ®) is safe and effective in treating people with chronic urticaria (persistent hives). mycophenylate. multicenter. hydroxychloroquine. dapsone. The purpose of this study is to evaluate the potential effect and safety of two different doses of PZ-601 and to compare this with another antibiotic that is approved by the U. PZ-601 is a novel investigational carbapenem antibiotic with an antimicrobial spectrum of activity that includes pathogens responsible for community-acquired bacterial infections as well as multidrug-resistant Gram-positive pathogens and vancomycin-resistant enterococci. hemolysis from dapsone) of immunomodulatory treatment for urticaria (e. This is a randomized.. © 2009-Journal of Drugs in Dermatology. sulfasalazine. line recorded in the subjects’ Ifdiaries during theobtained first twothis weeks lying etiology clearly defined for urticaria (main manifestation you feel you have copy illegally. IVIg. Inc. The study is a Phase II. Participants will have one of the following three conditions: 1) previous or ongoing requirement for corticosteroids for symptom control OR. Statistics. 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The publication agreement also transfers ownership of the copyright for http://www. Dermatology Prior to all authors required to of sign a publication agreement in General ed. author names. Style Please consult the latest editions of the American Medical Association (AMA) Manual of Style. 1993. and all other matters of style. Available at: published. The affiliation should comprised of the department. stating that the manuscript content (including allyou figures. Koss MC. preferably no longer than 150 words. 2006. All hard copies must be accompanied by an identical digital copy on CD labeled with the lead author’s last name and formatted in Microsoft Word (DOC) or rich text format (RTF). The Pharmacologic Basis of Therapeutics. Table 2). East Hanover. including references and tables). please contact JDD immediately. Book Goodman A. dermatoheliosis.JDDonline. If you wish to have photographs returned.(JDD).php) All submissions must be clearly marked as articles (recommended: 2000-4000 words. Photographs. Reserved.Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F 602 INSTRUCTIONS TO AUTHORS (may be downloaded at www. institution (usually university or company). and charts) are each to be numbered in 1 consecutive series of Arabic numerals (eg. Pathak M. publication-ready). Figure 2. Note: Use of the aforementioned style guides does not signify an endorsement of said products. and skin This Agreement document contains proprietary information. Goodman L. each reference should be cited in the text with a superscripted Arabic numeral corresponding to the numeral listed sequentially in the reference list at the end of the article (eg.5 x 11 inch white paper with adequate margins. See below for requirements. Tables: Created in Microsoft Word. Accessed July 17. not in all capitals. Nopublication. 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Information on the products selected will be sent to you via e-mail and/or mail................. If you feel you have obtained this copy illegally............................... CONTRAINDICATIONS Naftin® Cream.........760................................ erythema (2%).... mutagenesis........................... Manufactured for: Merz Pharmaceuticals Greensboro.. Information for patients: The patient should be told to: 1........... tinea cruris and tinea corporis caused by the organisms Trichophyton rubrum....... 1% is for topical use only and not for ophthalmic use.... treatment should be discontinued and appropriate therapy instituted............. Contact Details: Nursing mothers: It in is Dermatology not known whether This document contains proprietary information..... Zip... © 2009-Journal of Drugs in Dermatology............... If irritation or sensitivity develops with the use of Naftin® Cream.......0522 Online: JDDonline............Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F &/5&3508*/ A set of surgical instruments by Anmuth Medical International $23 value5 ! Want more information on a product you’ve seen or read about in the JDD? It’s easy: check the box(es) and provide your contact details..... 1% isJDD administered to a nursing woman............... dryness (3%)........ 2...........php Mail: 1321 N...... no adequate and well controlled Triax Pharmaceuticals Locoid Lipocream® studies in pregnant women. Pregnancy: Teratogenic Effects: Pregnancy Category B: Reproduction studies have been performed in rats and rabbits (via oral administration) at doses 150 times or more the topical human dose and have revealed no evidence Taro Pharmaceuticals Topicort® of impaired fertility or harm to the fetus due to naftifine.........com/buyersresource. 1% is contraindicated in individuals who have shown hypersensitivity to any of its components............. Diagnosis of the disease should be confirmed either by direct microscopic examination of a mounting of infected tissue in a solution of potassium hydroxide or by culture on an appropriate medium.......... Keep Naftin® Cream......................... WARNINGS Naftin® Cream........ nose................... and Epidermophyton floccosum...... There are.... 11/08 Fax: 949.. Telephone ....... Avoid the use of occlusive dressings or wrappings unless otherwise directed by the physician........................ Burbank................................................. E-mail .. Cream.... 1% is indicated for the topical treatment of tinea pedis. PRECAUTIONS General: Naftin® Cream................................................................. impairment of fertility: Long-term animal studies to evaluate the carcinogenic potential of Naftin® Cream. in be human caution should written be exercised Naftin® Address............. this drug is excreted in human milk.. images and marks of Journal of Drugs (JDD)...... In vitro and animal studies have not demonstrated any mutagenic effect or effect on fertility... #VZFST3FTPVSDF COMPANY NAME Ƒ Ƒ Ƒ Ƒ Ƒ Ƒ Ƒ Ƒ Ƒ Ƒ Ƒ Ƒ Ƒ Ƒ Ƒ PRODUCT NAME ® Amgen Enbrel Eclipse Medical Smark Xide Dot ETAS Dermatology-In-Review Galderma Epiduo™ Galderma Epiduo™ Galderma Differin® Graceway INDICATIONS AND USAGE Naftin® Cream. the incidence of adverse reactions was as follows: burning/stinging (6%)................................... 1% have not been performed................... Trichophyton mentagrophytes...... please contact immediately...... Penalties Apply Atopiclair Johnson and Johnson Aveeno® Merz Naftin® NexTech BRIEF SUMMARY Rx ONLY NexTech Practice 2009 ODAC ODAC 2010 Conference OrthoNeutrogena Retin-A Micro® Carcinogenesis. 1% is for external use only.. 1% away from the eyes................. local irritation (2%)......... Country ........ 2009--the winner will be notified by e-mail............ ADVERSE REACTIONS During clinical trials with Naftin® Cream. without the express consentwhen of JDD. CA 91506 Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F ...... Ƒ YES! I would like to be entered in the raffle to win a set of surgical instruments by Anmuth Medical International........................... Other________________________________________ this drug should be used during pregnancy only if clearly needed. The drawing will be held on July 6th.. 1%. Because many drugs are excreted Name/Title...... NC 27410 © 2008 Merz Pharmaceuticals Rev........ All Rights Reserved...... Fax............................. Do Not Copy.... however...... Because animal reproduction studies are not always predictive of human response.... State .................... mouth and other mucous membranes.... Submit: Pediatric use: Safety and effectiveness in pediatric patients have not been established.... No reproduction or use of any portion of the contents of these materials may mademilk................. itching (2%)............ ' 4HEBRANDED PRESCRIPTIONTOPICAL ANTIFUNGALCREAM 4ARGETEDPOWER AGAINST4INEA0EDIS.42/$5#).A BEMaGS F &I ES GA R S T LA BL L C A N E R EA DO IN 3 0g M N A ND I N L Y A 9 0g P SIZ U M P Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page &UNGICIDAL0OWERINA AI UN #ONVENIENT0UMP !V TIF AN ). During clinical trials with Naftin® Cream. During clinical trials with Naftin® Gel. dryness. itching. images and marks of Journal of Drugs in Dermatology (JDD). the following adverse reactions were reported: burning/stinging. 1% are contraindicated in individuals who have shown hypersensitivity to any of their components and are for topical use only. This document contains proprietary information. erythema. See brief summary of prescribing information on the previous page. No reproduction or use of any portion of the contents of these materials may be made without the express written consent of JDD.com Naftin (naftifine HCl 1%) Cream and Gel. Penalties Apply © 2009-Journal of Drugs in Dermatology. please contact JDD immediately. local irritation. IMS NPA Data.naftin. 1%. If you feel you have obtained this copy illegally. All rights reserved. ® References: 1. #RURISAND#ORPORIS NOWOFFERSCONTROLLED APPLICATIONINAPUMP Do Not Copy. All Rights Reserved. 1%. rash. the following adverse reactions were reported: burning/stinging. erythema. Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page A BEMaGS F . © 2009 Merz Pharmaceuticals. &UNGICIDAL0OWER9OU#AN4RUST www. skin tenderness. itching. December 2008.