Comparison of Topical 5% Nicotinamid Gel Versus 2% Clindamycin Gel in the Treatment of the Mild-moderate Acne Vulgaris. a Double-blinded Randomized Clinical Trial

March 25, 2018 | Author: PennyStevana | Category: Acne Vulgaris, Drugs, Medical Specialties, Medicine, Clinical Medicine


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Journal of Research in Medical Sciences : The Official Journal of Isfahan University of MedicalSciences Medknow Publications Comparison of topical 5% nicotinamid gel versus 2% clindamycin gel in the treatment of the mild-moderate acne vulgaris: A double-blinded randomized clinical trial Zabiolah Shahmoradi, Farib Iraji, [...], and Azamosadat Ghorbaini Source of Support: Nil Conflict of Interest: None declared. Article information J Res Med Sci. 2013 Feb; 18(2): 115–117. PMCID: PMC3724370 Zabiolah Shahmoradi, Farib Iraji, Amir Hossein Siadat, and Azamosadat Ghorbaini Skin Disease and Leishmaniasis Research Center, Department of Dermatology, Isfahan University of Medical Sciences, Isfahan, Iran Address for correspondence: Dr. Farib Iraji, Skin Disease and Leishmaniasis Research Center, Department of Dermatology, Isfahan University of Medical Sciences, Isfahan, Iran. E-mail: ri.ca.ium.dem@ijarI Received 2012 Jul 29; Revised 2013 Jan 1; Accepted 2013 Jan 28. Copyright : © Journal of Research in Medical Sciences This is an open-access article distributed under the terms of the Creative Commons AttributionNoncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Journal of Research in Medical Sciences : The Official Journal of Isfahan University of Medical Sciences Medknow Publications Comparison of topical 5% nicotinamid gel versus 2% clindamycin gel in the treatment of the mild-moderate acne vulgaris: A double-blinded randomized clinical trial Zabiolah Shahmoradi, Farib Iraji, [...], and Azamosadat Ghorbaini and the effect of cytokines. Sixty female patients with mild or moderate acne vulgaris were recurited to be treated either with 5% nicotinamide or 2% clindamycin gel for 8 weeks.0001). the role of androgens. Materials and Methods: This was a randomized. Acne severity index (ASI) was used to evaluate response to treatment and SPSS software was used to analyze the data.2 ± 12. In the current study. However.[1] For a long-time. acne vulgaris remains prevalent in adults. as well as side effects such as diarrhea. nicotinamide. and . helping identification of potential new targets for acne therapy. clindamycin.27 in nicotinamide gel and clindamycin gel. Conclusion: Five percent nicotinamide gel is as effective as 2% clindamycin gel for treatment of mild to moderate acne vulgaris. No side effect was observed during the treatment.Additional article information Abstract Background: Acne vulgaris is considered one of the most common disorders for which patients seek dermatologic care. respectively (P > 0. and toll-like receptors. treatment INTRODUCTION Acne vulgaris is considered one of the most common disorders for which patients seek dermatologic care. Results: The mean of ASI at the baseline was 16. yeast infections. and associated inflammation.[1] Major factors contributing to the acne vulgaris include sebum secretion. topical and systemic antibiotic along with retinoid have been the mainstays of treatment for acne vulgaris. we evaluated efficacy of the 5% nicotinamide gel versus 2% clindamycin gel in the treatment of the mild-moderate acne vulgaris.05). bacterial growth. New molecular and clinical studies have advanced knowledge in areas such as sebocyte biology. The mean of ASI was significantly decreased compared with baseline ASI during the time in both groups (P < 0.5 and 18. there was not a significant difference regarding reduction of ASI between the nicotinamide and clindamycin gel (P = 0. dietary factors. accounting for at least 5-6 million visits to physicians a year. nicotinamide. Affecting the majority of the adolescent population. overuse of oral or topical antibiotics may contribute to the development of bacterial resistance. controlled clinical trial that was performed in 2009-2010.583).85 ± 8. with up to 40-50% of men and women in their 20 s and 10-20% in their 40 s reporting acne. Keywords: Acne. abnormal desquamation of follicles. However. = 385171). At the baseline. Isfahan University of Medical Sciences. Both physicians and patients were blinded to the type of treatment and the patients had been allocated randomized and instructed to apply the drug twice daily for a period of 8 weeks. . For determination of acne severity. and the number of the papules. acne severity index (ASI) was calculated for each patient as following: ASI: (2* pustules) + papules + (1/4* comedones). MATERIALS AND METHODS This was a randomized. demographic characteristic of the patients was obtained and recorded in especial questionnaires.[3] Moderate acne was defined as the presence of non-inflammatory lesions (including closed or open comedones) and the number of the papules and pustules to be <20 without any nodules or cysts. Iran (Registration No. pregnant and nursing patients or those who use oral contraceptive pill (OCP) were considered as the exclusion criteria for this study.[3] Reduction of ASI less than 30% was considered as weak response. t-test and ANOVA and Fisher exact test. In the current study. Furthermore. Informed consent was obtained from all the patients.[3.[2] Other medications that have been used for treatment of acne vulgaris include agents such as azelaic acid. 60 female patients with mild or moderate acne vulgaris were recurited to be treated either with 5% nicotineamide or 2% clindamycin gel. hepatic or endocrine disorders were excluded from the study. Patients were visited every 2 weeks in this period of time and the ASI score of the patients along with patient satisfaction and presence of side effects were recorded.6] The previous studies had used 4% nicotinamide gel for treatment of the acne vulgaris. we evaluated efficacy of the 5% nicotinamide gel versus 2% clindamycin gel in the treatment of the mild-moderate acne vulgaris as randomized clinical trial. such as nicotinamide. At the end of study. tea tree oil. Isfahan. Therefore. salicylic acid. cyproterone actate. Five percent nicotinamide gel and 2% clindamycin gel were provided by Isfahan Pharmacy School in the same containers. In this study. and etc. and pustules to be <10 without any nodules or cysts.photosensitivity. but with different labels of A and B. Patients who had received any topical or oral medication for acne vulgaris in the last 1 month was excluded from the study. 30% to 60% reduction was considered as moderate response and more than 60% reduction was considered as excellent response.5. the codes were revealed and the collected data was analyzed using SPSS (version 18) for Windows and statistical tests including. have been suggested for treatment of the acne vulgaris. Patients with history of allergy to the clindamycin or nicotinamide or history of renal.4. alternative treatments. controlled clinical trial that was performed in 2009-2010 in St-Alzahra hospital. Mild acne was defined as the presence of non-inflammatory lesions (including closed or open comedones). RESULTS Overall.27 in nicotinamide gel and clindamycin gel.5 and 18.83 ± 3. Fisher exact test showed that there was no significant difference regarding reduction of ASI between the nicotinamide and clindamycin gel (P = 0.53 years. have a stimulating effect on ceramide synthesis. The mean of ASI was continuously decreased during the visits in both groups and this reduction (final visit vs. respectively. In addition. speed up the differentiation of keratinocytes. is effective in ageing skin.0001) [Table 1].05).583) [Table 2]. It has been shown that topical application of niacinamide has a stabilizing effect on epidermal barrier function.17 ± 3.2 ± 12.05). smoothes out wrinkles and inhibits photocarcinogenesis and therefore.34 years and 21. and raise intracellular NADP levels. and this difference was not statistically significant (P > 0. The mean of ASI at the baseline was 16. and this difference was also not statistically significant (P > 0. respectively. Table 1 Comparison of acne severity index in the two groups during the treatment with nicotinamide and clindamycin gel However. No one was excluded from the study and all of the patients completed the study. baseline) was statistically significant as compared with baseline ASI in the both groups (P < 0. topical application of niacinamide improves the surface structure. and nitrogen mustard-induced irritation have also been suggested.85 ± 8.[7] . 60 patients (30 patients in the nicotinamide gel and 30 patients in the clindamycin gel) were evaluated in this study. seen as a reduction in transepidermal water loss and an improvement in the moisture content of the horny layer. rosacea. Table 2 Comparison of mean reduction of acne severity index by percent in the 2 groups during the treatment with nicotinamide and clindamycin gel DISCUSSION Nicotinic acid (niacin) and niacinamide (nicotinamide) are similarly effective as a vitamin because they can be converted into each other within the organism. Niacinamide can lead to increase in protein synthesis. Its antiinflammatory effects in acne. The mean of age in nicotinamide gel and clindamycin gel were 20. [10] In contrast. Our results clearly showed that 5% nicotinamide gel is at least as effective as 2% clindamycin gel for treatment of mild to moderate acne vulgaris. The authors concluded that 4% nicotinamide gel is of comparable efficacy to 1% clindamycin gel in the treatment of acne vulgaris. we evaluated possibly more potent 5% nicotinamide gel instead of usual 4% concentration and in contrast to the previous studied we compared this compound with 2% clindamycin gel instead of 1% clindamycin gel. Seventy-six patients were randomly assigned to apply either 4% nicotinamide gel or 1% clindamycin gel twice daily for 8 weeks.[13. To better evaluate the efficacy of 5% nicotinamide gel in the treatment of the acne vulgaris. 82% of the patients treated with nicotinamide gel and 68% treated with clindamycin gel were improved. which was considered to have resistance to local antibiotics due to no response to treatment was treated with the combination. the first study that used nicotinamide gel for treatment of acne vulgaris as a doubleblind clinical trial was performed by Shalita et al. Moreover. After 8 weeks. In their study. Considering these results along with the anti-inflammatory effects of the nicotine amid that may help to reduce post acne erythema and its anti-pigmentary effect that may help to reduce the severity of postinflammatory hyperpigmention after acne may suggest 5% nicotinamide gel as an appropriate treatment for acne vulgaris. the safety and efficacy of topically applied 4% nicotinamide gel was compared against 1% clindamycin gel for the treatment of moderate inflammatory acne vulgaris. we used a blinded protocol to have a more reliable result.19) beneficial results in the Physician's Global Evaluation of Inflammatory Acne.15] In the current study. Group A was treated with combination of 4% nicotinamide and 1% clindamycin combination. Group B was treated with plain 1% clindamycin and Group C. A total of 75 patients with inflammatory acne vulgaris were divided into three groups. when it was used for its effect as counteracting iodide aggravation in acne vulgaris. who showed that Topical 2% niacinamide may be effective in lowering the sebum excretion rate in Japanese individuals and casual sebum levels in Caucasian individuals. Both treatments produced statistically similar reductions in acne lesions. and acne severity.[11] The effect of nicotinamide on facial sebum was demonstrated by Draelos et al.14.[9] However. it was concluded that in addition of nicotinamide was not as much value as in treating inflammatory acne and results were some as for plain clindamycin and also the combination did not offer much relief in treatment of resistant acne.[12] It seems that nicotinamide along with the new suggested topical and systemic therapy can be effective for treatment of the acne vulgaris.The use of nicotinic acid for treatment of the acne vulgaris goes back to 1955. In addition. another research carried out by Sardesai and Kambli showed no benefit in combination of nicotinamide with clindamycin in the treatment of the acne. more randomized clinical trial (RCT) with higher number of the patients and longer follow-up is recommended. we observed no side effect during the treatment and the patients tolerated the treatment very well. At the end of 8 weeks. . both treatments produced comparable (P = 0.[8] Treatment of acne vulgaris with nicotinic acid induced vasodilatation was described by Marchand in the same year. Accepted 2013 Jan 28. 2013 Feb. provided the original work is properly cited.0001). Article information J Res Med Sci. and reproduction in any medium. controlled clinical trial that was performed in 2009-2010. Acne severity index (ASI) was used to evaluate response to treatment and SPSS software was used to analyze the data. which permits unrestricted use. PMCID: PMC3724370 Zabiolah Shahmoradi. and Azamosadat Ghorbaini Skin Disease and Leishmaniasis Research Center.583). Iran Address for correspondence: Dr. there was not a significant difference regarding reduction of ASI between the nicotinamide and clindamycin gel (P = 0. Department of Dermatology. Isfahan University of Medical Sciences.Footnotes Source of Support: Nil Conflict of Interest: None declared.ium. E-mail: ri. . Iran. Results: The mean of ASI at the baseline was 16. Farib Iraji. Isfahan.2 ± 12. Revised 2013 Jan 1.5 and 18. we evaluated efficacy of the 5% nicotinamide gel versus 2% clindamycin gel in the treatment of the mild-moderate acne vulgaris. Farib Iraji.27 in nicotinamide gel and clindamycin gel. Department of Dermatology. Amir Hossein Siadat. Skin Disease and Leishmaniasis Research Center. In the current study. Copyright : © Journal of Research in Medical Sciences This is an open-access article distributed under the terms of the Creative Commons AttributionNoncommercial-Share Alike 3. respectively (P > 0.05). Materials and Methods: This was a randomized.0 Unported. Isfahan. Articles from Journal of Research in Medical Sciences : The Official Journal of Isfahan University of Medical Sciences are provided here courtesy of Medknow Publications Abstract Background: Acne vulgaris is considered one of the most common disorders for which patients seek dermatologic care. Isfahan University of Medical Sciences. The mean of ASI was significantly decreased compared with baseline ASI during the time in both groups (P < 0. distribution.ca.dem@ijarI Received 2012 Jul 29. However.85 ± 8. 18(2): 115–117. Sixty female patients with mild or moderate acne vulgaris were recurited to be treated either with 5% nicotinamide or 2% clindamycin gel for 8 weeks. helping identification of potential new targets for acne therapy. However.[1] Major factors contributing to the acne vulgaris include sebum secretion. have been suggested for treatment of the acne vulgaris. Affecting the majority of the adolescent population. we evaluated efficacy of the 5% nicotinamide gel versus 2% clindamycin gel in the treatment of the mild-moderate acne vulgaris as randomized clinical trial.6] The previous studies had used 4% nicotinamide gel for treatment of the acne vulgaris.[3. treatment INTRODUCTION Acne vulgaris is considered one of the most common disorders for which patients seek dermatologic care.[1] For a long-time. and photosensitivity. Mild acne was defined as the presence of non-inflammatory lesions (including closed or open comedones). nicotinamide. and associated inflammation. salicylic acid. such as nicotinamide. acne vulgaris remains prevalent in adults. 60 female patients with mild or moderate acne vulgaris were recurited to be treated either with 5% nicotineamide or 2% clindamycin gel. nicotinamide. and toll-like receptors. = 385171). MATERIALS AND METHODS This was a randomized. and the number of the papules. with up to 40-50% of men and women in their 20 s and 10-20% in their 40 s reporting acne. Therefore. and etc. dietary factors. In the current study. Patients with history of allergy to the clindamycin or nicotinamide . and pustules to be <10 without any nodules or cysts. Iran (Registration No. No side effect was observed during the treatment. alternative treatments. cyproterone actate. bacterial growth.[3] Moderate acne was defined as the presence of non-inflammatory lesions (including closed or open comedones) and the number of the papules and pustules to be <20 without any nodules or cysts. Isfahan University of Medical Sciences. Keywords: Acne. accounting for at least 5-6 million visits to physicians a year. clindamycin.5. Isfahan. tea tree oil. and the effect of cytokines.Conclusion: Five percent nicotinamide gel is as effective as 2% clindamycin gel for treatment of mild to moderate acne vulgaris. New molecular and clinical studies have advanced knowledge in areas such as sebocyte biology. abnormal desquamation of follicles. Patients who had received any topical or oral medication for acne vulgaris in the last 1 month was excluded from the study. the role of androgens.[2] Other medications that have been used for treatment of acne vulgaris include agents such as azelaic acid. yeast infections. In this study.4. as well as side effects such as diarrhea. controlled clinical trial that was performed in 2009-2010 in St-Alzahra hospital. overuse of oral or topical antibiotics may contribute to the development of bacterial resistance. topical and systemic antibiotic along with retinoid have been the mainstays of treatment for acne vulgaris. demographic characteristic of the patients was obtained and recorded in especial questionnaires. and this difference was not statistically significant (P > 0. Informed consent was obtained from all the patients. respectively. Furthermore. 60 patients (30 patients in the nicotinamide gel and 30 patients in the clindamycin gel) were evaluated in this study. baseline) was statistically significant as compared with baseline ASI in the both groups (P < 0.or history of renal. No one was excluded from the study and all of the patients completed the study. but with different labels of A and B.83 ± 3. The mean of ASI at the baseline was 16. At the baseline. Table 1 Comparison of acne severity index in the two groups during the treatment with nicotinamide and clindamycin gel . t-test and ANOVA and Fisher exact test. and this difference was also not statistically significant (P > 0. hepatic or endocrine disorders were excluded from the study. Five percent nicotinamide gel and 2% clindamycin gel were provided by Isfahan Pharmacy School in the same containers. RESULTS Overall. At the end of study.2 ± 12. pregnant and nursing patients or those who use oral contraceptive pill (OCP) were considered as the exclusion criteria for this study.0001) [Table 1].05).17 ± 3.[3] Reduction of ASI less than 30% was considered as weak response.85 ± 8. Both physicians and patients were blinded to the type of treatment and the patients had been allocated randomized and instructed to apply the drug twice daily for a period of 8 weeks. the codes were revealed and the collected data was analyzed using SPSS (version 18) for Windows and statistical tests including.27 in nicotinamide gel and clindamycin gel.34 years and 21.05). The mean of age in nicotinamide gel and clindamycin gel were 20. acne severity index (ASI) was calculated for each patient as following: ASI: (2* pustules) + papules + (1/4* comedones). respectively.5 and 18. 30% to 60% reduction was considered as moderate response and more than 60% reduction was considered as excellent response. Patients were visited every 2 weeks in this period of time and the ASI score of the patients along with patient satisfaction and presence of side effects were recorded. The mean of ASI was continuously decreased during the visits in both groups and this reduction (final visit vs.53 years. For determination of acne severity. exact test showed that there was no significant difference regarding reduction of ASI between the nicotinamide and clindamycin gel (P = 0. After 8 weeks. A total of 75 patients with inflammatory acne vulgaris were divided into three groups. Both treatments produced statistically similar reductions in acne lesions.19) beneficial results in the Physician's Global Evaluation of Inflammatory Acne. and raise intracellular NADP levels. another research carried out by Sardesai and Kambli showed no benefit in combination of nicotinamide with clindamycin in the treatment of the acne.583) [Table 2]. and nitrogen mustard-induced irritation have also been suggested. the first study that used nicotinamide gel for treatment of acne vulgaris as a doubleblind clinical trial was performed by Shalita et al. 82% of the patients treated with nicotinamide gel and 68% treated with clindamycin gel were improved. rosacea. when it was used for its effect as counteracting iodide aggravation in acne vulgaris. is effective in ageing skin.[7] The use of nicotinic acid for treatment of the acne vulgaris goes back to 1955. It has been shown that topical application of niacinamide has a stabilizing effect on epidermal barrier function. speed up the differentiation of keratinocytes.[9] However. both treatments produced comparable (P = 0. Seventy-six patients were randomly assigned to apply either 4% nicotinamide gel or 1% clindamycin gel twice daily for 8 weeks. Its antiinflammatory effects in acne. Group A was treated with . topical application of niacinamide improves the surface structure. have a stimulating effect on ceramide synthesis. Niacinamide can lead to increase in protein synthesis. In their study.[8] Treatment of acne vulgaris with nicotinic acid induced vasodilatation was described by Marchand in the same year. Table 2 Comparison of mean reduction of acne severity index by percent in the 2 groups during the treatment with nicotinamide and clindamycin gel DISCUSSION Nicotinic acid (niacin) and niacinamide (nicotinamide) are similarly effective as a vitamin because they can be converted into each other within the organism. smoothes out wrinkles and inhibits photocarcinogenesis and therefore. seen as a reduction in transepidermal water loss and an improvement in the moisture content of the horny layer. The authors concluded that 4% nicotinamide gel is of comparable efficacy to 1% clindamycin gel in the treatment of acne vulgaris. and acne severity. In addition. the safety and efficacy of topically applied 4% nicotinamide gel was compared against 1% clindamycin gel for the treatment of moderate inflammatory acne vulgaris.[10] In contrast. [11] The effect of nicotinamide on facial sebum was demonstrated by Draelos et al. Iran Address for correspondence: Dr. it was concluded that in addition of nicotinamide was not as much value as in treating inflammatory acne and results were some as for plain clindamycin and also the combination did not offer much relief in treatment of resistant acne. 18(2): 115–117. 2013 Feb. PMCID: PMC3724370 Zabiolah Shahmoradi.combination of 4% nicotinamide and 1% clindamycin combination. Copyright : © Journal of Research in Medical Sciences .14. Farib Iraji. we observed no side effect during the treatment and the patients tolerated the treatment very well. Article information J Res Med Sci. Considering these results along with the anti-inflammatory effects of the nicotine amid that may help to reduce post acne erythema and its anti-pigmentary effect that may help to reduce the severity of postinflammatory hyperpigmention after acne may suggest 5% nicotinamide gel as an appropriate treatment for acne vulgaris. Isfahan. To better evaluate the efficacy of 5% nicotinamide gel in the treatment of the acne vulgaris. who showed that Topical 2% niacinamide may be effective in lowering the sebum excretion rate in Japanese individuals and casual sebum levels in Caucasian individuals. we used a blinded protocol to have a more reliable result. Our results clearly showed that 5% nicotinamide gel is at least as effective as 2% clindamycin gel for treatment of mild to moderate acne vulgaris.[13.[12] It seems that nicotinamide along with the new suggested topical and systemic therapy can be effective for treatment of the acne vulgaris. Moreover.ium. we evaluated possibly more potent 5% nicotinamide gel instead of usual 4% concentration and in contrast to the previous studied we compared this compound with 2% clindamycin gel instead of 1% clindamycin gel. which was considered to have resistance to local antibiotics due to no response to treatment was treated with the combination. Isfahan University of Medical Sciences. Group B was treated with plain 1% clindamycin and Group C. In addition. Amir Hossein Siadat. At the end of 8 weeks. Skin Disease and Leishmaniasis Research Center. Isfahan. and Azamosadat Ghorbaini Skin Disease and Leishmaniasis Research Center. more randomized clinical trial (RCT) with higher number of the patients and longer follow-up is recommended.ca. Footnotes Source of Support: Nil Conflict of Interest: None declared. Department of Dermatology.15] In the current study. Isfahan University of Medical Sciences.dem@ijarI Received 2012 Jul 29. Accepted 2013 Jan 28. Revised 2013 Jan 1. Farib Iraji. Iran. E-mail: ri. Department of Dermatology. [PubMed] 13.71:528–9. NilFroushzadeh MA. 1955. Diagnosis and treatment of acne. Naji SM. 1955. Current state of acne treatment: Highlighting lasers. Iraji F. J Cosmet Laser Ther.This is an open-access article distributed under the terms of the Creative Commons AttributionNoncommercial-Share Alike 3. Articles from Journal of Research in Medical Sciences : The Official Journal of Isfahan University of Medical Sciences are provided here courtesy of Medknow Publications REFERENCES 1. Siadat AH. [PubMed] 6. Nicotinic acid/niacinamide and the skin. Indian J Dermatol Venereol Leprol. Pharmacologic doses of nicotinamide in the treatment of inflammatory skin conditions: A review.73:94–6. and chemical peels. Marchand WE.3:88–93. [PubMed] 3. Parish LC. Draelos ZD. Smith JG. Shalita AR. Guerriero C. J Cosmet Dermatol. Iraji F. [PubMed] 15. Titus S.73:22–5.34:434–7. Indian J Dermatol Venereol Leprol. Dermatol Online J.75:279–82. Kambli VM. Moradi S. G Ital Dermatol Venereol. Armstrong AW. 2011. Comparison of efficacy of topical clindamycin and nicotinamide combination with plain clindamycin for the treatment of acne vulgaris and acne resistant to topical antibiotics. Indian J Dermatol Venereol Leprol.77:11–6. AMA Arch Derm. doubleblind.8:96–101. Indian J Dermatol Venereol Leprol. which permits unrestricted use. Gehring W.117:60–2. Baradaran EH. Niren NM. [PubMed] 12. [PubMed] 8. Momeni A. The effect of 2% niacinamide on facial sebum production. 2013 [PubMed] 14.17:2. 2006. 2004. [PubMed] 2. provided the original work is properly cited. Giovene GL. Efficacy of topical azelaic acid gel in the treatment of mild-moderate acne vulgaris. 2009. prospective trial. J Dermatolog Treat. Soltani A. Clindamycin lotion alone versus combination lotion of clindamycin phosphate plus tretinoin versus combination lotion of clindamycin phosphate plus salicylic acid in the topical treatment of mild to moderate acne vulgaris: A randomized control trial. Matsubara A. [PubMed] 7.147:491–7. 2007. [PubMed] 11.2% Myrtacine® and 4% vitamin PP for prevention and treatment of retinoid dermatitis in patients with mild to moderate acne.86:734–40. Efficacy and tolerability of topical 0. Int J Dermatol. Effect of Aloe vera topical gel combined with tretinoin in treatment of mild and moderate acne vulgaris: A randomized. photodynamic therapy. [PubMed] . Chalker DK. 2012. [PubMed] 10. Nicotinic acid as an agent for counteracting iodide aggravation in acne vulgaris. 2006. Smiles K. Kim RH. double-blind placebo-controlled study. Barefoot SW. [PubMed] 5. The efficacy of 5% topical tea tree oil gel in mild to moderate acne vulgaris: A randomized. Morteza-Semnani K. Topical nicotinamide compared with clindamycin gel in the treatment of inflammatory acne vulgaris. Siadat AH. Saeedi M. 2003.0 Unported. The efficacy of topical cyproterone acetate alcohol lotion versus placebo in the treatment of the mild to moderate acne vulgaris: A double blind study. 2007. Sadeghinia A. [PubMed] 4. Siadat AH. Jooya A. Cutis. Shahmoradi Z. Jooya A. distribution. Siadat AH. Sardesai VR. Enshaieh S. 2012. [PubMed] 9.12:26. Bettoli V. Mil Med. 1995. Am Fam Physician.69:138–9. and reproduction in any medium. 2006. Hajheydari Z. Veraldi S. Sofman MS. Iraji F. The treatment of acne vulgaris with nicotinic acid induced vasodilatation. Hodge J. Dermatol Online J.
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