PSORIATIC ARTHRITISSubclinical Entheseal Involvement in Patients with Psoriasis: An Ultrasound Study Marwin Gutierrez, MD,* Emilio Filippucci, MD,* Rossella De Angelis, MD,* Fausto Salaffi, MD,* Giorgio Filosa, MD,† Santiago Ruta, MD,‡ Chiara Bertolazzi, MD,* and Walter Grassi, MD* Objectives: The main aim of the present study was to determine the prevalence of subclinical entheseal involvement at lower limbs by ultrasound (US) in patients with psoriasis. The secondary aim was to determine the interobserver reliability of the Glasgow Ultrasound Enthesitis Scoring System (GUESS) and power Doppler (PD) technique in the assessment of enthesopathy. Methods: The study was conducted on 45 patients with psoriasis and 45 healthy sex- and agematched controls. All patients with no clinical evidence of arthritis or enthesitis underwent an US examination. All US findings were identified according to GUESS. The interobserver reliability was calculated in 15 patients with psoriasis. Results: A total of 450 entheses in 45 patients with psoriasis were evaluated by US. In 148 of 450 (32.9%) entheses, grayscale US found signs indicative of enthesopathy. In 4/450 (0.9%) entheses PD signal was detected. In the healthy population, US found signs of enthesopathy in 38 of 450 (8.4%) entheses and no PD signal was detected. The GUESS score was significantly higher in patients with psoriasis than in healthy controls (P ⬍ 0.0001). Both concordance correlation coefficient and unweighted values for US findings showed an excellent agreement (0.906 and 0.890, respectively). Conclusions: Our results indicate that both grayscale US and PD findings indicative of enthesopathy were more frequent in patients with psoriasis. The US ability to detect signs of subclinical enthesopathy should be the object of longitudinal investigations to define its value in predicting the clinical onset of psoriatic arthritis. © 2011 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 40:407-412 Keywords: ultrasound, psoriatic arthritis, psoriasis, enthesopathy, power Doppler P soriasis is 1 of the most common chronic inflammatory skin diseases, affecting approximately 1 to 3% of the world’s population. The prevalence of psoriatic arthritis (PsA) among patients with psoriasis was earlier reported as approximately 5 to 39% (1,2), the exact percentage being unknown. Little is known about the prevalence of entheseal involvement in patients with psoriasis (3). Some investigations indicate enthesis as the initial site of inflammation in spondyloarthropathies (SpA) *Clinica Reumatologica, Università Politecnica delle Marche, Jesi, Ancona, Italy. †Unità di Dermatologia, “A. Murri” Hospital, Jesi, Ancona, Italy. ‡Servicio de Reumatología, Hospital “Gral. San Martín” de La Plata, Buenos Aires, Argentina. The authors have no conflicts of interest to disclose. Address reprint requests to Marwin Gutierrez, MD, Clinica Reumatologica, Università Politecnica delle Marche, Ospedale “A. Murri”, Via dei Colli, 52, 60035, Jesi, Ancona, Italy. E-mail:
[email protected]. 0049-0172/11/$-see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.semarthrit.2010.05.009 (4), especially those of the lower limbs (5-7). The presence of enthesopathy in patients with psoriasis may be underestimated due to its often oligosymptomatic clinical involvement. Conventional radiography can demonstrate established bony erosions and spurs, but it gives little information about soft tissues, especially in the early phase of the disease (8,9). Magnetic resonance imaging has the ability to visualize both soft-tissue and bone marrow edema using multiplanar views, but it is mainly limited by high cost (10,11). There are a number of investigations describing the use of ultrasonography (US) in identifying the features of lower limb enthesitis in SpA (6,12-16). Moreover, US was found able to reveal a high prevalence of abnormal findings in asymptomatic entheses (14). The identification of enthesitis by US may precede by years its clinical onset or, in general, the diagnosis of PsA. 407 All US examinations were performed by an experienced sonographer (M.) who recorded tenderness elicited by pressure. Genoa. Study Design The study was conducted according to the Declaration of Helsinki and local regulations. mobilization.A.5 for healthy controls. Multiplanar US examinations of the quadriceps and patellar entheses were performed with the patient in the supine position with lower limbs extended.05 were considered statistically significant.1 for Windows XP (Microsoft Corp. SD were as follows: 24. The interobserver agreement was calculated using a kappa () test (un- . 3. Bone erosion was defined as a cortical interruption with a step-down contour defect and enthesophyte was defined as a step-up bony prominence at the end of normal bone profile. the settings of which were standardized with a pulse repetition frequency of 750 KHz and a Doppler frequency between 9. WA). or knee or ankle surgery and corticosteroid injection of the examined structures. Patients and healthy subjects underwent US assessments at random and were asked not to talk about their clinical condition with the US examiner.to 18-MHz broadband linear transducer. history of recent severe trauma at entheses scanned. using a MyLab 70 XVG (Esaote Biomedica. and 24. Before the study. These include the following: entheseal thickness of tendon. Entheseal thickness was measured at the point of maximal thickness 2 mm proximal to the bony insertion (normal value of thickness for each enthesis are represented in the table 1).) who scored the Psoriasis Area and Severity Index (PASI). age ⬍18 years. The secondary aims were to determine the interobserver reliability of the Glasgow Ultrasound Enthesitis Scoring System (GUESS) (6) and power Doppler (PD) technique in the assessment of entheseal involvement and to evaluate the correlation between GUESS and other clinical parameters. and Achilles tendon and plantar aponeurosis insertion into the calcaneal bone. and by an expert rheumatologist (R.and age-matched controls. The study was conducted on 45 patients with psoriasis and 45 healthy sex.) under the same scanning conditions of the experienced sonographer.1 and 11. to confirm the absence of entheseal involvement. US examinations were performed independently by a second investigator with less than 1 year of experience in musculoskeletal US (S. and enthesophytes. MATERIALS AND METHODS Patients A total of 47 patients were referred from the dermatologist with a definite diagnosis of psoriasis to be included in the study. 1. Italy) equipped with a 6.G.. P values less than 0.7. 23. Particular attention was paid on not compressing the tissues under examination to avoid the “blanching” of PD signal due to the transducer pressure (19). Ethical approval for the study was obtained from the local Ethics Committee and informed consent was obtained from both patients and healthy controls. Standard descriptive results were expressed as median and 95% confidence intervals for the median.408 The main aim of the present study was to determine the prevalence of subclinical entheseal involvement at lower limbs by US in patients with psoriasis.1 MHz. A 2 test was used to compare the distribution of PD US technique among different groups. Redmond. Patients with a diagnosis of psoriasis and without any clinical evidence of arthritis or enthesitis underwent an US examination of lower limbs. Two patients were excluded since tenderness was found by the rheumatologist at the Achilles enthesis.9. version 9.R. 22. Bursitis was defined as a well-circumscribed.6 to 24. Blood flow was examined in each enthesis using PD. Exclusion criteria were as follows: clinical evidence of arthritis. The following 5 entheses were scanned bilaterally: quadriceps insertion into the upper pole of the patella. Statistical Analysis Statistical analysis was performed using MedCalc. Both patients and healthy controls underwent a clinical examination by both an expert dermatologist (G.D.4. peripheral neuropathy of lower limbs. in 15 patients with psoriasis. Subclinical entheseal involvement in patients with psoriasis US Assessment US examinations were performed at the Rheumatology Department of the Università Politecnica delle Marche.2.66 for psoriatic patients. localized anechoic or hypoechoic area at the site of an anatomical bursa and which was compressible by the transducer (18). bony erosions.F. bursitis. All US findings indicative of enthesopathy according to GUESS (6) were investigated and documented in both transverse and longitudinal views (from proximal to distal and from medial to lateral aspects of the entheses). and contraction against resistance of the corresponding entheses. BMI ⬎30.4 to 24.) blinded to clinical data in a darkened room. CI 95% for the median. The Achilles tendon and the proximal plantar aponeurosis were examined with the patient lying prone with the feet hanging over the edge of the examination table at 90° of flexion (17). recruited from January 2008 to February 2009. the investigators reached a consensus on the US scanning technique to adopt and on US findings to interpret. or any systemic treatment for psoriasis in the previous 3 months before the beginning of the study. patellar tendon insertion into the lower pole of the patella and into the tibial anterior tuberosity. Each enthesis was scanned in grayscale to detect morphostructural changes and subsequently with PD technique to detect abnormal blood flow. The body mass index (BMI) median.5. The presence of the PD was considered positive if found within the tendon 2 mm proximal to the bony insertion and not at the body of the tendon or at the bursal level. To assess interobserver reliability. Figures 1 and 2 show the normal US findings at the investigated entheseal sites and the US features most representative of enthesopathy. PD signal was detected. and PASI) was compared using Spearman’s rank correlation coefficient ().4 mm aNormal bTotal values of the entheseal thickness. the entheseal sites with the highest number of US signs of enthesopathy were the quadriceps enthesis (13/450) (2. .9%) entheseal sites. respectively. (D) Plantar aponeurosis enthesis (pa). and 0. (E) Achilles enthesis (ac). whereas a value of more than 0. 0. Genoa. t ⫽ tibia.20 was considered poor. 0. US found at least 1 sign indicative of enthesopathy in 38 of 450 (8. (B) Proximal patellar enthesis (pp).9%) entheses (2 in the Achilles enthesis. Gutierrez et al.60 moderate. respectively.80 good.40 fair.61 to 0. In 148 of 450 (32. (C) Distal patellar enthesis (dp). 409 Table 1 Distribution of the Morphostructural Changes in the Study Population Bursitis Entheseal Thickness (patients/healthy (patients/healthy controls) controls) Quadriceps enthesis (n) Proximal patellar enthesis (n) Distal patellar enthesis (n) Achilles enthesis (n) Plantar aponeurosis enthesis (n) Totalb Enthesophyte (patients/healthy controls) Bone Erosion (patients/healthy controls) 9/7 21/5 31/3 9/3 3/0 0/0 0/0 0/0 4/1 0/0 20/6 10/5 8/0 27/8 1/0 0/0 0/0 2/0 3/0 0/0 73/18 4/1 66/19 5/0 a ⱕ6. 0. In 4/450 (0.81 to 1.8 for the CCC was considered significant. US images were obtained with a 6. In this group.29 mm ⱕ4.41 to 0.21 to 0. grayscale US found at least 1 sign indicative of enthesopathy. RESULTS A total of 450 entheseal sites in 45 patients with psoriasis were examined by US. The entheseal site with the highest number of signs of enthesopathy was the Achilles enthesis (43/450) (9. Italy).9%). and 1 in the distal patellar enthesis).4%). followed by distal patellar enthesis (41/450) (9. Correlation between GUESS score and covariates (psoriasis duration.1%). In the healthy population. (A) Quadriceps enthesis (q). value of abnormalities of patients with psoriasis and healthy subjects is 148 and 38. A value of 0 to 0.M. weighted for dichotomous scoring) and concordance correlation coefficient (CCC) and illustrated by Bland and Altman plots.9%).0001).00 excellent. p ⫽ patella. quadriceps enthesis (29/450) (6.to 18-MHz linear transducer using a MyLab 70 XVG US system (Esaote Biomedica. and plantar aponeurosis enthesis (4/450) (0.1 mm ⱕ4 mm ⱕ4 mm ⱕ5.4%) entheseal sites (P ⬍ 0. ca ⫽ calcaneous bone. 1 in the quadriceps enthesis.5%). BMI. st ⫽ sub cutaneous soft tissue.8%) and the Achilles en- Figure 1 Representative US images of the normal entheseal insertions on longitudinal scan. proximal patellar enthesis (31/450) (6. Note the typical fibrillar echotexture of tendon and its sharp margins (arrowheads). P ⫽ 0. Figure 3 Distribution of the entheseal thickness measurements by the 2 investigators (M. we decided to investigate the ability of US to identify entheseal involvement in patients with psoriasis without any clinical sign of musculoskeletal system involvement.094.9. the distal patellar enthesis (3/ 450) (0. 0. 0. thesis (12/450) (2.21. The GUESS score was significantly higher in patients with psoriasis than in healthy controls (P ⬍ 0.906 and 0.7%). The vertical white line indicates the exact point where the measurement was obtained.845. respectively).) on the Bland and Altman plot. st ⫽ subcutaneous soft tissue. and bone erosions) were 0. and S.795. US may be considered as an alternative imaging technique in the diagnosis of enthesopathy (21-23).22). enthesophytes.209.556). ca ⫽ calcaneous bone. US images were obtained using a MyLab 70 XVG US system with a 6. The values between the 2 investigators for the single abnormalities (thickness.12-15). followed by the proximal patellar enthesis (10/450) (2. Thus. ac ⫽ Achilles enthesis. the CCC of the thickness was 0. the BMI ( ⫺0.0001).6%). Table 1 provides the distribution of the morphostructural changes obtained in both the patients with psoriasis and the healthy controls at different entheseal levels.2%). The presence of PD signal was found more frequently in the entheses of patients with psoriasis compared with healthy controls (P ⬍ 0.165).1 MHz. A similar study has been recently conducted by Gisondi and coworkers (26). and 0. (C) Thickening of the plantar aponeurosis enthesis (6.990. There is evidence supporting the issue that PD strongly improves US accuracy in the assessment of enthesitis DISCUSSION Enthesitis has been indicated as a distinctive pathologic condition affecting patients with PsA (20).G. No PD signal was detected in healthy controls. Both CCC and unweighted values for the examined parameters showed excellent agreement (0. (A) Presence of abnormal PD signal to the bony insertion of distal patellar enthesis. t ⫽ tibia.to 18-MHz linear transducer and Doppler frequency of 9.890. bursitis. (B) Enthesophyte at Achilles enthesis level (curved arrow). pa ⫽ plantar aponeurosis enthesis. and the PASI ( ⫺0. . and the plantar aponeurosis enthesis (0/ 450) (0%). Figure 3 shows the distribution of the entheseal thickness measurements by the 2 investigators.1 mm).532). Its sensitivity in the detection of enthesitis has been demonstrated in patients with SpA (6.088. Because radiographs are not sensitive enough for the detection of early signs of entheseal involvement (8. The present investigation was performed in a higher number of patients using a latest generation US system equipped with a probe frequency reaching 18 MHz and very high-frequency PD. Moreover.R.410 Subclinical entheseal involvement in patients with psoriasis Figure 2 Representative US findings indicative of enthesopathy on longitudinal scan. High-resolution US has been shown to be of value in revealing subclinical joint and tendon inflammation in patients with chronic arthritis (24. using only grayscale US with a lower frequency probe (⬍15 MHz).990. P ⫽ 0. One hundred fifty entheses of 15 patients with psoriasis were examined by 2 investigators.0001). No statistically significant correlation was found between the GUESS score and the psoriasis duration ( ⫺0. (D) Deep retrocalcaneal bursitis (asterisk) at the Achilles enthesis level.25). respectively.820. according to Bland and Altman plot. P ⫽ 0. dp ⫽ distal patellar enthesis. Sonographic analysis of enthesopathy in the lower extremities of patients with spondylarthropathy. Dougados M. Filippis LG. and found in 4 of our patients (0. El-Dalati G. Pease C. A sonographic enthesitic index of lower limbs is a valuable tool in the assessment of ankylosing spondylitis. Barozzi L. A possible explanation may be related to both mechanical and local anatomic factors. Naredo E. 25. Lehtinen A. 26.41:694-700. The absence of PD in healthy controls suggests a very high specificity of this imaging technique. Gutierrez et al. Gibbon W. Emery P. Calin A. J Rheumatol 1999. Sánchez-Pernaute O. 7. Balint PV. Bartolone S. The US ability to detect signs of subclinical enthesopathy should be the object of longitudinal investigations to define its value in revealing subclinical PsA. Hayashi K. 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