Prevalence of Psoriatic Arthritis in Primary Care Patients With Psoriasis

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1 ARTHRITIS & RHEUMATOLOGY Vol. 68, No. 4, April 2016, pp DOI /art VC 2016, American College of Rheumatology Prevalence of Psoriatic Arthritis in Primary Care Patients With Psoriasis Maren C. Karreman, 1 Angelique E. A. M. Weel, 2 Myrthe van der Ven, 1 Marijn Vis, 1 Ilja Tchetverikov, 3 Tamar E. C. Nijsten, 1 Marlies Wakkee, 1 Johanna M. W. Hazes, 1 and Jolanda J. Luime 1 Objective. To estimate the prevalence of psoriatic arthritis (PsA) in primary care patients diagnosed as having psoriasis and to estimate the prevalence of musculoskeletal symptoms in psoriasis patients in primary care. Methods. We conducted a cross-sectional study in adult primary care patients with psoriasis. Responding patients reporting pain in joints, entheses, or the lower back were interviewed by telephone to determine eligibility and, if eligible, were invited for clinical evaluation. During clinical evaluation, skin, nails, joints, and entheses were assessed. Additionally, ultrasound of the enthesis was performed by an independent trained examiner if a patient had at least 1 tender enthesis (determined by the Leeds Enthesitis Index and the Maastricht Ankylosing Spondylitis Enthesitis Score). Patients who fulfilled the Classification of Psoriatic Arthritis (CASPAR) Study Group criteria were classified as having PsA. Results. We invited 2,564 psoriasis patients from databases of 97 participating general practitioners. Of 1,673 responders (65.2%), 841 (50.3%) were willing to participate. A total of 823 patients (32.1%) reported having musculoskeletal symptoms; 659 of these patients were determined to be eligible, 524 of whom were clinically evaluated. We identified 64 cases of established PsA and another 17 cases of newly diagnosed PsA, leading to a prevalence of 3.2% (95% confidence interval Supported by an investigator-initiated grant from Pfizer. 1 MarenC.Karreman,MD,MyrthevanderVen,MSc,Marijn Vis, MD, PhD, Tamar E. C. Nijsten, MD, PhD, Marlies Wakkee, MD, PhD, Johanna M. W. Hazes, MD, PhD, Jolanda J. Luime, PhD: Erasmus University Medical Centre, Rotterdam, The Netherlands; 2 Angelique E. A. M. Weel, MD, PhD: Erasmus University Medical Centre and Maasstad Hospital, Rotterdam, The Netherlands; 3 Ilja Tchetverikov, MD, PhD: Albert Schweitzer Hospital, Dordrecht, The Netherlands. Address correspondence to Maren C. Karreman, MD, Erasmus University Hospital, Department of Rheumatology, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands. m.karreman@erasmusmc.nl. Submitted for publication March 11, 2015; accepted in revised form November 24, [95% CI] ) among psoriasis patients in primary care. This prevalence would increase to 4.6% (95% CI ) if PsA cases based on enthesitis were also taken into account. Conclusion. Among psoriasis patients in primary care, the prevalence of PsA is conservatively estimated to be 3.2%, increasing to 4.6% if enthesitis is taken into account. The prevalence of musculoskeletal symptoms among psoriasis patients is comparable with the prevalence of musculoskeletal symptoms in the general population. Psoriatic arthritis (PsA) is the second most frequent inflammatory arthritis for which a rheumatologist is consulted (1). PsA is well treatable, and an increasing number of studies show that early diagnosis improves the outcome substantially (2 6). In most cases PsA is preceded by psoriasis, which affects 2 3% of the Western population (7 9). Estimates of the prevalence of PsA among psoriasis patients are numerous and range widely (6 42%) (10,11), and most data stem from secondary dermatologic care. However, most psoriasis patients at risk of PsA will visit their general practitioner first if having musculoskeletal symptoms, which enables early referral if PsA is recognized in a timely manner. Therefore, prevalence data from primary care are important. To our knowledge, only 2 studies have reported the prevalence of PsA in primary care. Both studies were performed in the UK and showed prevalences of 9.0% and 13.8% (12,13). The primary objective of this study was to give an estimate of the prevalence of PsA, including enthesitis, in psoriasis patients in primary care. The second objective was to estimate the prevalence of musculoskeletal symptoms in psoriasis patients. PATIENTS AND METHODS Patients. Between June 2013 and March 2014, 270 general practitioners from the Greater Rotterdam area in The 924

2 PREVALENCE OF PsA IN PSORIASIS IN PRIMARY CARE 925 Netherlands were invited to participate, initially by personal letter and then by telephone call if they did not respond to the letter. The 97 general practitioners who chose to participate (36% of those invited) selected their psoriasis patients age $18 years from their databases using International Classification of Primary Care (ICPC) code S91 (14). In The Netherlands, the ICPC is the standard for coding and classification of signs and symptoms in general practice. The identified psoriasis patients received invitations from their general practitioners asking them to participate. Patients were asked to return the reply slip, which contained 2 questions. The first question was whether they had regular joint symptoms, back symptoms, or tendon symptoms. The second question was whether they wanted to participate. In the accompanying letter, patients were asked to return the reply slip regardless of whether they wanted to participate. The exact wording of the reply slip is available upon request from the corresponding author. The patients who agreed to participate were telephoned by a trained interviewer to verify if they had regular joint and tendon symptoms or chronic low back pain (with chronic defined as.12 weeks and onset before age 45 years). The interviewer also verified that they had been diagnosed as having psoriasis and confirmed that they had sufficient knowledge of the Dutch language to complete the questionnaires. Ethics approval was obtained from the Dutch Medical Ethical Committee (approval no. M ), and written informed consent was obtained from all participating patients. Data collection. Data were collected by self-report questionnaires and clinical evaluation. Questionnaires. Patients were asked to complete 3 questionnaires related to their symptoms. The presence of inflammatory back pain was determined by the Assessment of SpondyloArthritis international Society (ASAS) questionnaire on Inflammatory Back Pain (15), which consists of 5 yes/no questions. To determine the presence of other musculoskeletal symptoms, the Psoriasis Epidemiology Screening Tool (PEST) questionnaire (16) and the Early ARthritis for Psoriatic patients (EARP) questionnaire (17) were used. These are both validated questionnaires developed as screening tools for PsA, consisting of yes/no questions on the presence of particular features such as joint swelling and swelling of the Achilles tendon. The PEST questionnaire also includes a manikin for patients to use in indicating stiff, swollen, or painful joints. Clinical evaluation. A trained research assistant completed a detailed history containing information about psoriasis and musculoskeletal symptoms (available upon request from the corresponding author), the presence of other features including dactylitis, uveitis, and inflammatory bowel disease, and family history. Physical examination focused on the skin, nails, joints, and entheses. Psoriasis severity was scored by the Psoriasis Area and Severity Index (PASI) (18). This provides a quantitative assessment of psoriasis based on the amount of body surface area involved and the degree of severity of erythema, induration, and scaling weighted by body area. The score ranges from 0 to 72, and ascore.10 is considered to represent moderate-to-severe psoriasis. The nails were visually inspected, and if an abnormality was observed, a photograph was obtained and was evaluated by a trained dermatologist who was unaware of the clinical presentation. The joints were evaluated for tenderness and swelling by manual palpation using the 66/68-joint count (19). The entheses were manually evaluated for tenderness using the Leeds Enthesitis Index (LEI) (20) and the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) (21). The LEI evaluates 6 entheseal sites (lateral epicondyle of the humerus, medial condyle of the femur, and Achilles tendon insertion, all bilaterally), and the MASES evaluates 13 entheseal sites (first and seventh costochondral joints, anterior and posterior superior iliac spine, iliac crest, and proximal insertion of Achilles tendon [all bilaterally] and the fifth lumbar spinous processus); the score on each instrument is the sum of all tender sites. Ultrasound evaluation of the enthesis. If clinical evaluation showed at least 1 tender enthesis, patients were referred for an ultrasound examination to be performed by an independent trained examiner (MvdV) using an Esaote Technos MyLab 60 (probe LA 435). The 6 entheses included in the Madrid Sonography Enthesitis Index (MASEI) (22) were examined bilaterally. These were the olecranon tuberosity, superior and inferior poles of the patella, tibial tuberosity, and superior pole (Achilles tendon) and inferior pole (plantar fascia) of the calcaneus. In addition to the MASEI, we included the lateral epicondyle tendon insertions (elbow). Enthesitis on ultrasound was defined as the presence of power Doppler signal (,2mmofthe bony cortex) or in the case of the plantar fascia an increased thickness of the enthesis (.4.4 mm) as power Doppler signal cannot be obtained at the plantar fascia (22,23). Referral to rheumatologist. Patients were advised to consult a rheumatologist if there were indications of underlying rheumatic disease. Referral criteria were set up, and these included an evident history of dactylitis or arthritis as well as current peripheral or axial manifestations. Peripheral manifestations were defined as arthritis in $1 joint upon physical examination or enthesitis at ultrasound examination. Possible axial manifestation was defined as low back pain for.12 consecutive weeks with onset before age 45 years and $2 of the following: 4 of 5 yes answers on the ASAS questionnaire on Inflammatory Back Pain, a family history of spondyloarthritis, a good response to nonsteroidal antiinflammatory drugs, or chronic low back pain for.5 years (24). Case definition. The diagnosis of PsA was based on the Classification of Psoriatic Arthritis (CASPAR) Study Group criteria (25), which specify that patients must have inflammatory articular disease in the joints, spine, or entheses. In addition, at least 3 of the following 5 items are required: the presence of psoriasis (current [2 points] or history), the presence of psoriatic nail dystrophy, the absence of rheumatoid factor, dactylitis (diagnosed by a rheumatologist), and radiographic evidence of juxtaarticular new bone formation. The presence of peripheral arthritis and axial disease was confirmed by a rheumatologist. There is no commonly accepted clinical definition of enthesitis, which is why we decided to use a combination of clinical characteristics and positive power Doppler signal at the enthesis (,2 mm of the bony cortex) (23). Clinical characteristics included self-reported pain at the enthesis (on either the PEST questionnaire or the EARP questionnaire or in the history) or the presence of a tender enthesis at clinical examination (LEI/ MASES). We did not accept the sole presence of power Doppler signal, as study data suggest that power Doppler signal could be present in nonclinical cases (26 28). Statistical analysis. Descriptive statistics were used for the prevalence of PsA and musculoskeletal symptoms, symptom duration, medication use, and other clinical features using Stata statistical software: release 13 (StataCorp). Because of missing information in different phases of patient recruitment on both the prevalence of PsA and the prevalence of mus-

3 926 KARREMAN ET AL same as the second with regard to the observed frequency of musculoskeletal symptoms, but the frequency of PsA was as observed among clinically evaluated patients only. Details on parameter estimates used in the sensitivity analysis are available upon request from the corresponding author. Figure 1. Recruitment of the psoriasis patients in primary care. ICPC 5 International Classification of Primary Care; MSS 5 musculoskeletal symptoms. RESULTS Source population. A total of 97 general practitioners participated, representing a source population of 158,046 patients age $18 years. Of these 158,046 patients, 2,647 were selected using ICPC code S91 for psoriasis (1.7%) (Figure 1). In the process of inviting patients for clinical evaluation, 83 patients (3.1%) reported not having psoriasis and were excluded, so eventually we had a population of 2,564 psoriasis patients (mean 6 SD age years, 51.6% men). Figure 2 shows the distribution of psoriasis patients by age category and sex. Invited patients. Of the 2,564 invited psoriasis patients, 1,673 (65.2%) returned the reply slip. Of these 1,673 responders, 841 (50.3%) were willing to participate and their eligibility was verified. Regular joint, tendon, and/or lower back symptoms were then mentioned by 659 patients (78.4%), who were subsequently invited for clinical evaluation. Of these 659 patients, 524 actually underwent clinical evaluation (Figure 1). Prevalence of musculoskeletal symptoms. Data on the prevalence of musculoskeletal symptoms were derived from 2 sources. First, we had a group of 832 patients who did not want to participate. Of these patients, 128 left blank the question about the presence of musculoskeletal symptoms. Among the other 704 patients, 164 (23.3%) reported having musculoskeletal symptoms. The second source was the group of 841 patients who were interested in participating; during telephone interviews, 659 of these 841 patients reported having regular musculoskeletal symptoms. Of these 659 patients, 581 (88.2%) reported regular episodes of joint symptoms, 332 (50.4%) culoskeletal symptoms, we performed a sensitivity analysis. We evaluated 3 scenarios in which we assumed what would have been the frequency of PsA and musculoskeletal symptoms if we had evaluated the patients who did not reply. In the first scenario, we applied our observed frequency of musculoskeletal symptoms among the responders to the nonresponders. Subsequently, we applied the observed frequency of PsA among the responders with musculoskeletal symptoms to the nonresponders. In the second scenario, we used for the nonresponders the frequency of musculoskeletal symptoms that we observed from the patients who returned their reply slips but who did not want to participate. For the frequency of PsA, we made the same assumption as in the first scenario. The third scenario is the Figure 2. Distribution of psoriasis in different age groups in a primary care population (n 5 2,564).

4 PREVALENCE OF PsA IN PSORIASIS IN PRIMARY CARE 927 Figure 3. Flow diagram of sources used for calculating the prevalence of musculoskeletal symptoms (MSS) and psoriatic arthritis (PsA) in a population of patients with psoriasis in primary care. * 5 did not want to participate but had a confirmed diagnosis of PsA. reported recurrent tendon symptoms, and 487 (73.9%) reported low back pain. Overall, 823 of 2,564 patients reported having regular musculoskeletal symptoms, which leads to a prevalence of 32.1%, assuming that no additional musculoskeletal symptoms would be found in patients who did not reply or who did not provide information on the reply slip about the presence of musculoskeletal symptoms (Figure 3). Clinically evaluated patients. The mean 6 SD age of the 524 evaluated patients was years, and 50.0% were men. The mean 6 SD duration of psoriasis was years, with 74% of psoriasis diagnoses confirmed by a dermatologist. The remaining 26% of psoriasis diagnoses were confirmed by the general practitioner. During clinical evaluation, 81 patients (15.5%) had nail abnormalities consistent with psoriatic nail dystrophy. The median PASI score in the study population was 2.2 (interquartile range 1 4). Table 1 provides the clinical details of those without PsA, those with established PsA, those with PsA newly diagnosed by a rheumatologist, and those with enthesitis. Prevalence of PsA. Established PsA. The frequency of established PsA was 2.5% (95% confidence interval [95% CI] ) (n 5 64). As with information about musculoskeletal symptoms, information about an established diagnosis of PsA was also derived from 2 sources. First, we had 13 patients who did not want to participate in the study but who already had a confirmed diagnosis of PsA. Second, we had another 51 patients with a confirmed diagnosis of PsA who did participate in the study (Figure 3). Newly diagnosed PsA. In addition to the established cases, PsA was also newly diagnosed by a rheumatologist in 17 cases. Within the PsA cases, 11 patients

5 928 KARREMAN ET AL Table 1. Characteristics of the 524 participating psoriasis patients* Patients with axial manifestations and peripheral arthritis (n 5 17) Patients with enthesitis (n 5 36) Patients with established PsA (n 5 51) Patients with psoriasis (n 5 420) Age, mean 6 SD years Men, no. (%) 8 (47.1) 17 (47.2) 21 (41.2) 216 (51.4) Body mass index, mean 6 SD kg/m Psoriasis symptom duration, median (IQR) years 15 (4 30) 20 (11 37) 20 (12 33) 15 (8 30) Psoriasis diagnosed by dermatologist, no. (%) 13 (76.5) 31 (86.1) 42 (82.4) 302 (71.9) Nail psoriasis, no. (%) 5 (29.4) 2 (5.6) 10 (19.6) 64 (15.2) PASI score, median (IQR) (range 0 72) 3 (1.3 4) 3.1 ( ) 1 (0 3) 2.2 (1 4) Musculoskeletal symptom duration, median (IQR) years Joints 12.5 (2 23) 10 (5 25) 12 (8 20) 8 (4 14) Lower back 18 (9 25) 33 (14 41) 8.5 (5 18) 12 (5 25) LEI score, median (IQR) (range 0 6) 0 (0 1) 1 (1 2) 0 (0 1) 0 (0 0) MASES, median (IQR) (range 0 13) 0 (0 3) 2 (0 3) 0 (0 2) 0 (0 0) * IQR 5 interquartile range; PASI 5 Psoriasis Area and Severity Index; LEI 5 Leeds Enthesitis Index; MASES 5 Maastricht Ankylosing Spondylitis Enthesitis Score. Patients diagnosed by the rheumatologist as having psoriatic arthritis (PsA). Patients who would be diagnosed as having PsA based on the Classification of Psoriatic Arthritis Study Group criteria. Patients already diagnosed at the beginning of the study as having PsA. Patients with musculoskeletal symptoms but without PsA. (64.7%) presented solely with peripheral arthritis. Five cases (29.4%) of axial PsA were diagnosed, and 1 patient (5.9%) presented with a combination of axial PsA and peripheral arthritis. Moreover, we also identified 36 cases of enthesitis, in which the inflammatory component was confirmed by ultrasound. Most of the patients with enthesitis decided not to undergo further evaluation by a rheumatologist, but most of them would have been classified as having PsA according to the CASPAR criteria. Overall prevalence and sensitivity analysis. We identified a total of 81 cases of PsA, of which 17 (21%) were newly diagnosed. This leads to a PsA prevalence of 3.2% (95% CI ) among all 2,564 primary care patients with psoriasis (Figure 3). This represents the situation in which no additional cases would be identified in nonresponders and in patients who declined participation. It is questionable whether this assumption holds true, and therefore we did a sensitivity analysis evaluating 3 scenarios. In the first scenario, we assumed an equal prevalence of musculoskeletal symptoms for responders and nonresponders. Among the 1,673 responders, 823 had musculoskeletal symptoms, leading to a prevalence of 49.2%. The prevalence of PsA among patients with musculoskeletal symptoms was 9.8% (81 PsA cases in 823 patients with musculoskeletal symptoms). We assumed that the prevalences we observed in the responders would also apply to the 891 nonresponders. This assumption would then increase the prevalence of PsA toward 4.8% (95% CI ). In the second scenario, we used the observed frequency of musculoskeletal symptoms among the nonparticipants who returned their reply slips. Among the 832 patients who indicated that they did not want to participate, 704 provided information about musculoskeletal symptoms, which were present in 164 of these 704 patients (23.3%) (Figure 3). In this scenario, when we assumed equal prevalence of PsA as in the first scenario (9.8%), the prevalence of PsA would increase toward 3.9% (95% CI ). In the third and final scenario, we used the same frequency of musculoskeletal symptoms as in the second scenario (23.3%), but we varied the prevalence of PsA. We used the frequency of PsA that we observed in all patients who were clinically evaluated, which leads to a PsA prevalence of 13.0%. Applying this prevalence of PsA to the nonresponders, the prevalence of PsA would increase toward 4.2% (95% CI ). Enthesitis. A total of 111 patients were referred for ultrasound evaluation of the enthesis. A combination of clinical and ultrasound enthesitis was present in 36 patients. As the CASPAR criteria suggest that the sole presence of enthesitis is sufficient to indicate inflammatory articular disease, adding the patients with enthesitis would increase the prevalence to 4.6% (95% CI ). The 3 scenarios in the sensitivity analysis would then lead to a prevalence of 7.0% (95% CI %) if assuming equal prevalences of musculoskeletal symptoms and PsA, 5.7% (95% CI ) if taking into account the frequency of musculoskeletal symp-

6 PREVALENCE OF PsA IN PSORIASIS IN PRIMARY CARE 929 toms in nonparticipants, and 6.2% (95% CI ) if varying the frequency of PsA. DISCUSSION In this large primary care based study we found a PsA prevalence of 3.2% (95% CI ) among 2,564 psoriasis patients; 21% of these cases of PsA were newly diagnosed. The prevalence of musculoskeletal symptoms was 32.1% (95% CI ). In these estimates, we assumed that no additional cases would be found among nonresponders. This was probably a harsh assumption, and we therefore did a sensitivity analysis in which the prevalence increased toward 7.0% (95% CI ) if cases were found in nonresponders as well. Literature about the prevalence of PsA in primary care is scarce (12,13). A higher prevalence of 8.6% (95% CI ) was observed by Ogdie et al (13). One of the explanations for this difference could be that they based the diagnosis of PsA on medical codes in a populationbased medical records database rather than on clinical examination. An even higher prevalence was reported by Ibrahim et al (13.8% [95% CI ]) (12), but that study had substantial nonresponse. The prevalence would decrease toward 1.9% if all initial patients were taken into account and no additional cases were found in nonresponders. More data are available from secondary care, where PsA prevalences range from 6% to 42% among psoriasis patients (10,29). This wide range is probably caused by the use of many different criteria sets, self-reported patient diagnosis, and diagnosis by the dermatologist. Defining PsA has proven to be challenging due to its clinical heterogeneity. In 2006, new classification criteria were established, the CASPAR criteria (25). Besides peripheral synovitis and axial disease, entheseal involvement was characterized as inflammatory articular disease. Enthesitis is established by manual palpation in which pain, redness, and swelling are considered. No detailed definition of these features is available, and, according to the CASPAR criteria, their identification is left to the discretion of the treating physician. If the enthesis lies deep within the surrounding tissue, it is difficult to locate the enthesis and observe redness and swelling. Pain itself is no sign of underlying inflammation, as it could be related to overuse, metabolic disease, or aging (27). To overcome these difficulties, we chose to combine signs of inflammation on ultrasound with clinical symptoms, as we think that this is an acceptable definition of enthesitis. Patients who fulfill this definition are classified as having PsA according to the CASPAR criteria. The prevalence of musculoskeletal symptoms among all initially invited psoriasis patients was 32.1%, increasing to 49.2% among patients returning their reply slips. These numbers fall well into the estimated prevalences of musculoskeletal symptoms in the general population of 39.7% (30) and 53.9% (31) in The Netherlands. It seems that musculoskeletal symptoms are not more frequent among psoriasis patients than among the general population. Our study has certain strengths and limitations. One of the strengths of this study is the large population of psoriasis patients. We invited 2,564 psoriasis patients in primary care databases and achieved a response rate of 65.2%. This is a high response rate for a primary care study, as one has to depend on general practitioners to recruit patients. Patients are invited to the study via the general practitioner, so investigators themselves cannot recruit patients. Second, our study provides prevalence estimates for primary care, and, as mentioned before, only 2 studies thusfarhavereportedonprevalenceinaprimarycaresetting (12,13). Among the limitations are misclassification of psoriasis, ethnicity, self selection of patients, selection by musculoskeletal symptoms, and missed cases. Psoriasis was identified by applying the ICPC code in the general practitioner databases. Some misclassification (3.1%) occurred, possibly related to the general practitioner initially considering the skin problem to be psoriasis, a determination which was changed later on without updating the ICPC code. Ethnic and geographic variation play a role in the prevalence of psoriasis (32) and also in PsA prevalence. For example, 1% of Asian psoriasis patients are affected by PsA versus 10 42% in Europe and North America (33). In our study population, ;98% were of Caucasian origin. This should be taken into account when interpreting the results. Self selection related to symptoms might have been an issue, as we observe that the mean 6 SD age of evaluated patients was years, and people of older age tend to have more joint symptoms. The ideal population would be younger, as we know that the peak incidence of PsA is between ages 30 and 50 years. It could therefore be possible that we missed some cases among the younger patients who did not participate. In addition, we only invited patients with regular episodes of musculoskeletal symptoms. This might have left us with missed cases, as patients could have had symptom-free synovitis or enthesitis. However, we think that the chance of missing a substantial number of cases in this way is negligible. Missed cases of established PsA might be an issue, although we explicitly asked patients to contact us independent of symptom state.

7 930 KARREMAN ET AL In conclusion, we conservatively estimated the prevalence of PsA among psoriasis patients in primary care to be 3.2%, increasing to 4.6% if enthesitis is taken into account. The prevalence of musculoskeletal symptoms among psoriasis patients is comparable with the prevalence of musculoskeletal symptoms in the general population. ACKNOWLEDGMENTS We gratefully thank all participating general practitioners and participating patients. In addition, we would like to thank Marie-Louise Lenssinck and Esther Hofland for their contribution to data collection and the staff of The Dutch Institute of Rheumatology BV, Rotterdam, The Netherlands, for their support. AUTHOR CONTRIBUTIONS All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. Karreman had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study conception and design. Weel, Vis, Tchetverikov, Nijsten, Hazes, Luime. Acquisition of data. Karreman, van der Ven, Wakkee. Analysis and interpretation of data. Karreman, Luime. ROLE OF THE STUDY SPONSOR Research support for the study was funded by Pfizer and provided by The Dutch Institute of Rheumatology BV, a contract research organization. Pfizer had no role in the study design or in the collection, analysis, or interpretation of the data, the writing of the manuscript, or the decision to submit the manuscript for publication. Publication of this article was not contingent upon approval by Pfizer. REFERENCES 1. Savolainen E, Kaipiainen-Seppanen O, Kroger L, Luosujarvi R. Total incidence and distribution of inflammatory joint diseases in a defined population: results from the Kuopio 2000 arthritis survey. 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8 PREVALENCE OF PsA IN PSORIASIS IN PRIMARY CARE 931 rent acute anterior uveitis without spondylarthritis. Arthritis Rheum 2009;60: Prey S, Paul C, Bronsard V, Puzenat E, Gourraud PA, Aractingi S, et al. Assessment of risk of psoriatic arthritis in patients with plaque psoriasis: a systematic review of the literature. J Eur Acad Dermatol Venereol 2010;24 Suppl 2: Van der Linden MW, Westert GP, de Bakker DH, Schellevis FG. Second national study into diseases and actions in general practice. Symptoms and disorders in the population and in general practice. Utrecht/Bilthoven: Netherlands Institute for Health Services Research/RIVM2004. In Dutch. URL: nl/sites/default/files/bestanden/ns2_rapport1.pdf. 31. Picavet HS, Schouten JS. Musculoskeletal pain in the Netherlands: prevalences, consequences and risk groups, the DMC(3)- study. Pain 2003;102: Chandran V, Raychaudhuri SP. Geoepidemiology and environmental factors of psoriasis and psoriatic arthritis. J Autoimmun 2010;34:J Alamanos Y, Voulgari PV, Drosos AA. Incidence and prevalence of psoriatic arthritis: a systematic review. J Rheumatol 2008;35: DOI: /art Clinical Images: Synovial leishmaniasis The patient, a 49-year old man, presented in 2010 with bloody rhinorrhea and an ulcerated and crusted lesion in his left nostril. He had longstanding ankylosing spondylitis (AS), which had been treated with adalimumab since Biopsy of the lesion revealed a dense mononuclear cell infiltrate with intracellular parasites consistent with mucosal leishmaniasis. The facts that he lived in an endemic area and was an immunocompromised host were further suggestive of this diagnosis. Adalimumab was discontinued, and he was treated succesfully with a 5-day course of intravenous (IV) liposomal amphotericin B (total dose 975 mg) (1). After 3 months and a full ear, nose, and throat examination, adalimumab was reintroduced due to a florid reactivation of AS, leading to good clinical control of the disease within 1 month. Two years later, he returned with persistent right knee monoarthritis of 3 weeks duration. Ibuprofen was added to the anti2tumor necrosis factor treatment for 2 weeks, but the knee arthritis did not improve. Knee aspiration yielded 68 ml of turbid, yellowish synovial fluid (SF) with a leuckocyte count of 3,500/ml. There was no evidence of leishmanial amastigotes on Giemsa-stained smears, and polymerase chain reaction (PCR) analysis for Leishmania in SF and in whole blood peripheral blood mononuclear cells yielded negative results. Laboratory tests showed an increase in acute-phase reactant levels, a low hemoglobin level (10.4 gm/dl), and polyclonal hypergammaglobulinemia. Needle synovial biopsy was performed, showing an intense diffuse inflammatory mononuclear cell infiltrate with the presence of numerous intracytoplasmic Leishmania amastigotes (a) (hematoxylin and eosin [H&E] stained; original magnification 3 400). The diagnosis was then confirmed by a positive PCR result in DNA extracted from paraffin-embedded synovium. Adalimumab was stopped, and the patient was re-treated with IV liposomal amphotericin B (3 mg/kg/day for 5 days), with mild improvement of the knee arthritis. Two months later, another synovial biopsy was performed, showing complete disappearance of the intracellular parasites (b) (H&E stained; original magnification 3 10 [inset Giemsa stained; original magnification 3 400]) together with a negative result of synovial tissue PCR testing for Leishmania. These findings demonstrate that, as described in dogs (2), leishmaniasis could localize in the synovium in humans, and a negative PCR finding in SF does not rule out the presence of the parasitic infection. Since leishmaniasis is known to recur in immunocompromised subjects (3,4), we suggest a pathologic synovial examination in patients with previous Leishmania infection and otherwise unexplained arthritis. 1. Garcia-Gonzalez E, Guidelli GM, Bardelli M, Maggio R. Mucocutaneous leishmaniasis in a patient treated with anti-tnf-a therapy. Rheumatology (Oxford) 2012;51: Sbrana S, Marchetti V, Mancianti F, Guidi G, Bennett D. Retrospective study of 14 cases of canine arthritis secondary to Leishmania infection. J Small Anim Pract 2014;55: Perello-Roso A, Lopez-Aldeguer J, Garcia-Gasco P, Blanes M. Polyarthritis caused by Leishmania in a patient with AIDS. Clin Infect Dis 1996;22: Mellor-Pita S, Yebra-Bango M, Tutor de Ureta P, Sanz J, Lopez A. Polyarthritis caused by Leishmania in a patient with human immunodeficiency virus. Clin Exp Rheumatol 2004;22:131. Giacomo Maria Guidelli, MD Renato De Stefano, MD Mauro Galeazzi, MD Enrico Selvi, MD Siena University Hospital Siena, Italy