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Objective A decline in the frequency of AA amyloidosis secondary to RA and infectious diseases has been reported. We aimed to determine the change in the frequency of AA amyloidosis in our Behçet’s syndrome (BS) patients and to summarize the clinical characteristics of and outcomes for our patients, and also those identified by a systematic review. Methods We identified patients with amyloidosis in our BS cohort (as well as their clinical and laboratory features, treatment, and outcome) through a chart review. The primary end points were end-stage renal disease and death. The prevalence of AA amyloidosis was estimated separately for patients registered during 1976–2000 and those registered during 2001–2017, in order to determine whether there was any change in the frequency. We searched PubMed and EMBASE for reports on BS patients with AA amyloidosis. Risk of bias was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. Results The prevalence of AA amyloidosis was 0.62% (24/3820) in the earlier cohort and declined to 0.054% (3/5590) in the recent cohort. The systematic review revealed 82 cases in 42 publications. The main features of patients were male predominance and a high frequency of vascular involvement. One-third of patients died within 6 months after diagnosis of amyloidosis. Conclusion The frequency of AA amyloidosis has decreased in patients with BS, which is similar to the decrease observed for AA amyloidosis due to other inflammatory and infectious causes. However, AA amyloidosis is a rare, but potentially fatal complication of BS.

Objectives CYC remains an important treatment option for Behçet’s syndrome (BS) patients with life-threatening manifestations. However, adverse events may occur with CYC and this has led to increased use of biologic agents in other vasculitides. We investigated short and long term adverse events associated with CYC use in BS patients. Methods We conducted a retrospective chart review of all BS patients treated with CYC between 1972 and 2006. Patients were called in and a standard form was used for collecting demographic characteristics, indication for CYC, its cumulative dose and short term adverse events, defined as those causing discontinuation of CYC, hospitalization and/or death, long term adverse events, including infertility and malignancy, and outcome. Results Of 5790 BS patients, 198 (3.4%) had used at least one dose of CYC. Main indications were vascular or neurological involvement. After a median follow-up of 17 years, 52 (26%) patients had died, 113 (57%) could be contacted, and 33 (17%) were lost to follow-up. Vascular involvement was the leading cause of death (n = 27). Seventeen (9%) patients experienced short term adverse events with haemorrhagic cystitis being the most common. After a median follow-up of 25 years (interquartile range: 15–26 years), 17 malignancies occurred in 15 (8%) patients. Infertility was experienced by 26 (30%) patients. Conclusion Long term adverse events such as malignancy and infertility were major problems in our BS patients treated with CYC. These results underline the need for safer treatment modalities that are at least as effective as CYC.

Objectives Lower extremity deep vein thrombosis (LEDVT) is a serious complication of Behçet’s syndrome. Management constitutes mainly of administration of immunosuppressives, but the predictors of relapse and the optimal choice of immunosuppressives remain unclear. In this prospective study, we aimed to detect the risk and predictors of relapse and treatment response to different modalities. Methods All Behçet’s syndrome patients who presented with a first episode of acute LEDVT between 2010 and 2014 were prospectively followed with a standard protocol. Acute LEDVT was confirmed by Doppler ultrasonography. Serial planned Doppler ultrasonography assessments were performed during follow-up and additionally repeated in case of clinical suspicion. Recanalization rate was assessed at each visit. Our first-line treatment strategy consisted of AZA and CSs. IFN-alpha was used in patients who were refractory to or could not tolerate AZA or had concomitant eye involvement requiring further treatment. Results Thirty-three patients with LEDVT (26 M/7 F) were prospectively followed for 40.7 ± 13.4 months. Among the 33 patients, 23 relapses were observed in 15 patients. Relapse rates were 29%, 37% and 45% at 6, 12 and 24 months, respectively. Among the possible predictors of relapse, poor recanalization was the only significant factor [hazard ratio 4.34 (95% CI 1.96, 10.0)]. Overall 29 patients were treated with AZA and 17 with IFN-alpha. The relapse rate was lower and recanalization rate was higher with IFN-alpha compared with AZA (12% vs 45% and 86% vs 45%). Conclusion The relapse rate for LEDVT in Behçet’s syndrome is high despite AZA treatment. IFN-alpha seems to be a promising agent for preventing LEDVT relapses and achieving good recanalization.

Objectives Infliximab (IFX) is increasingly being used for the treatment of severe manifestations of Behçet’s syndrome (BS). However, emergence of new manifestations has also been occasionally reported during IFX treatment. We aimed to assess the frequency of new manifestations in our BS patients treated with IFX. Methods A chart review was conducted to identify all BS patients treated with IFX in our clinic between 2004 and 2020. Demographic data, indications for IFX initiation, concomitant treatments and outcomes were recorded. A new manifestation was defined as the emergence of a new organ involvement or mucocutaneous manifestation developing for the first time during IFX treatment or within 12 weeks after the last infusion of IFX. Results Among our 282 patients who used IFX, 19 (7%) patients had developed a total of 23 new manifestations during a mean follow-up of 20.0 (15.3) months. Patients with vascular involvement were more likely to develop a new manifestation (12/19, 63%). Initial manifestations that required IFX were in remission at the time of new manifestation in 14/19 patients. IFX treatment was intensified (n = 6) and/or glucocorticoids, immunosuppressives or colchicine was added to IFX (n = 21). IFX was switched to another agent for the remaining manifestations (n = 8). These treatment modifications led to remission in 17/19 patients. Conclusion New manifestations developed during IFX treatment in 7% of our patients with BS. They could be managed by intensifying IFX treatment or adding other agents in the majority of these manifestations.

BackgroundImmunogenicity of tumor necrosis factor alpha inhibitors (TNFis) has been recognized as an important problem that may cause loss of efficacy and adverse events such as infusion reactions. TNFis are being increasingly used among patients with Behçet syndrome (BS) and scarce data exist on this topic.ObjectiveWe aimed to investigate the prevalence of anti-infliximab (IFX) antibodies in patients with Behçet syndrome together with suitable controls.MethodsWe collected serum samples from 66 consecutive Behçet syndrome patients (51 M, 15 F, mean age 37 ± 9 years) who were treated with IFX. Additionally, similarly treated 27 rheumatoid arthritis, 53 ankylosing spondylitis, 25 Crohn’s disease patients, and 31 healthy subjects were included as controls. Samples were collected just before an infusion, stored at −80°C until analysis, and serum IFX trough levels and anti-IFX antibodies were measured by ELISA. We used a cut-off value of 1 μg/ml for serum IFX trough level, extrapolating from rheumatoid arthritis studies.ResultsAnti-IFX antibodies were detected in four (6%) Behçet syndrome, five (18.5%) rheumatoid arthritis, three (12%) Crohn’s disease, and one (2%) ankylosing spondylitis patient. The median serum IFX trough level was significantly lower in patients with anti-IFX antibodies compared to those without antibodies [2.32 (IQR: 0.6–3.6) vs. 3.35 (IQR: 1.63–5.6); p = 0.019]. The serum IFX trough level was lower than the cut-off value in 6/13 (46%) patients with anti-IFX antibodies and in 25/158 (16%) patients without anti-IFX antibodies (p = 0.015). Among the four Behçet syndrome patients with anti-IFX antibodies, two experienced relapses and two had infusion reactions.ConclusionsImmunogenicity does not seem to be a frequent problem in Behçet syndrome patients treated with IFX, but may be associated with relapses and infusion reactions, when present.

An unmet need exists for reliable, validated, and widely-accepted outcome measures for randomized clinical trials in Behçet's syndrome. The Outcome Measures in Rheumatology (OMERACT) Behçet's Syndrome Working Group, a large, multidisciplinary group of experts in Behçet's syndrome and patients with Behçet's syndrome, had an objective of developing a core set of data-driven outcome measures for use in all clinical trials of Behçet's syndrome.The core domain set was developed through a comprehensive, iterative, multistage project that included a systematic review, a focus group meeting and qualitative patient interviews, a survey among experts in Behçet's syndrome, a Delphi exercise involving both patients and physician experts in Behçet's syndrome, and use of the data, insight, and feedback generated by these processes to develop a final core domain set.All steps were completed and domains were delineated across the organ systems involved in this disease. Since trials in Behçet's syndrome often focus on specific manifestations and not on the disease in its entirety, the final proposed core set includes 5 domains mandatory for study in all trials in Behçet's syndrome (disease activity, new organ involvement, quality of life, adverse events, and death) with additional subdomains mandatory for study of specific organ-systems. The final core set was endorsed at the 2018 OMERACT meeting.The core set of domains in Behçet's syndrome provides the foundation through which the international research community, including clinical investigators, patients, the biopharmaceutical industry, and government regulatory bodies can harmonize the study of this complex disease, compare findings across studies, and advance development of effective therapies.

Objective: To assess the efficacy and safety of treatment modalities for major organ involvement of Behçet's syndrome (BS), in order to inform the update of the EULAR recommendations for the management of BS.Methods: A systematic literature review of all randomized controlled trials, controlled clinical trials, or open label trials assessing eye, vascular, nervous system or gastrointestinal system involvement of BS was performed. If controlled trials were not available for answering a specific research question, uncontrolled studies or case series were also included.Results: We reviewed the titles and abstracts of 3927 references and 161 studies met our inclusion criteria. There were only nine randomized controlled trials. Observational studies with IFN-α and monoclonal anti-TNF antibodies showed beneficial results for refractory uveitis. Meta-analysis of case-control studies showed that immunosuppressives decreased the recurrence rate of deep vein thrombosis significantly whereas anticoagulants did not. CYC and high dose glucocorticoids decreased mortality in pulmonary arterial aneurysms and postoperative complications in peripheral artery aneurysms. Beneficial results for gastrointestinal involvement were obtained with 5-ASA derivatives and AZA as first line treatment and with thalidomide and/or monoclonal anti-TNF antibodies in refractory cases. Observational studies for nervous system involvement showed improved outcome with immunosuppressives and glucocorticoids. Meta-analysis of case-control studies showed an increased risk of developing nervous system involvement with ciclosporin-A.Conclusion: The majority of studies related to major organ involvement that informed the updated EULAR recommendations for the management of BS were observational studies.

Objective.The Outcome Measures in Rheumatology (OMERACT) Vasculitis Working Group has been working toward developing a data-driven core set of outcome measures for use in clinical trials of Behçet’s syndrome [Behçet disease (BD)]. This paper summarizes the group’s work through OMERACT 2016, discussions during the meeting, and the future research agenda.Methods.Qualitative patient interviews were conducted among 20 patients with BD who have different types of organ involvement. A 3-round Delphi among BD experts and patients was initiated to identify domains, subdomains, and outcomes to be assessed in clinical trials of BD. The results of these studies were discussed during OMERACT 2016 and next steps were planned.Results.Patients’ perspectives and priorities were identified through qualitative interviews that identified candidate domains and subdomains for inclusion in the Delphi and characterized some shortcomings of the currently used patient-reported outcomes in BD. The first round of the Delphi was completed and several domains or subdomains were endorsed by the experts and/or the patients. Because many more items were endorsed than would be feasible to assess during a clinical trial, rating and ranking of items by physicians and patients was planned as a next critical step. The challenges of assessing specific organ system involvement was also discussed.Conclusion.The OMERACT Behçet Syndrome Working Group research program will identify core domains for assessment in BD with the goal of developing a core set of outcome measures for use in all trials of BD with the option to incorporate additional outcomes for specific organ involvement.

Case reports and series suggest that Takayasu's arteritis (TAK) can co-exist with other inflammatory disorders. We conducted a formal study to look specifically at the frequency of such inflammatory disorders in a large cohort of TAK followed by a single tertiary centre.There were 238 patients registered with a diagnosis of TAK. Of these, 19 died, 18 were lost to follow-up and 3 did not wish to respond to our questionnaire. The remaining 198 (175 F/23 M) patients were called back at the outpatient clinic. A standardised form sought whether the patient was also diagnosed with inflammatory bowel disease (IBD), ankylosing spondylitis (AS), Behçet's syndrome (BS), autoimmune or any other inflammatory disorder. The presence of skin-mucosa lesions, inflammatory eye disease and inflammatory back pain were also specifically sought for.We identified 37 (19%) patients with inflammatory bowel disease (n=12, 6%), ankylosing spondylitis (n=15, 8%) or Behçet's syndrome (n=10, 5%). Thirteen (6.5%) patients had systemic or localised autoimmune disease and 9 (4.5%) miscellaneous inflammatory diseases. Among the 139 patients without any concomitant disease, inflammatory back pain (n=49, 35%) was the most common feature, followed by recurrent oral ulcer (n=20, 14%) erythema nodosum (n=17, 12%), arthritis (n=12, 9%) papulopustular lesions (n=8, 6%) and uveitis/scleritis (n=6, 4%). Only 64 patients (32%) did not have any concomitant disease/condition or specific clinical feature.TAK does co-occur with IBD, AS and less frequently with BS in about 1/5 of the patients, at least in a hospital setting. There is no clear temporal pattern. The high prevalence of inflammatory back pain in the dorsal spine in TAK needs further scrutiny.

Superior vena cava syndrome (SVCS) is a medical emergency which can also be seen in Behçet's syndrome (BS). Having noted that BS patients with SVCS frequently complained of sleep disturbances, snoring and sleep apnea, suggesting obstructive sleep apnea (OSA), we formally surveyed the risk for OSA among BS patients.We studied 28 patients, all male, with SVCS (Group 1), 129 with vascular involvement without a SVCS (Group 2) and 151 with no vascular involvement (Group 3). In addition, 100 apparently healthy individuals (Group 4) were studied. The Berlin questionnaire (BQ), a validated screening tool with a high sensitivity and modest specificity that identifies individuals with high-risk for OSA, was administered to all study participants.The study groups were similar with regard to age (Group 1, mean age: 44.3±9.7; Group 2, mean age: 41.5±8.7, Group 3, mean age: 40.4±9.4 and Group 4, mean age: 42.1±9.4) mean body mass index and the frequency of hypertension and other comorbidities. The frequency of those patients at high-risk for OSA according to the BQ was 57%, 17%, 17% and 11% in Groups 1, 2, 3 and 4, respectively (p0.05). Age-adjusted ORs of OSA compared to healthy controls (Group 4) was 11.00 (95%CI: 4.01-30.07) for Group 1, 1.78 (95%CI: 0.81-3.94) for Group 2, 1.92 (95%CI: 0.90-4.14) for Group 3.BS patients with SVCS are at high risk for OSA. This is probably due to the external pressure of the significant presence of venous collaterals that surround the upper airways. Our results should be further confirmed by polysomnography, and future research should be carried out to clarify the causes of this association.

Background: Mycophenolate mofetil (MMF) has been increasingly used in various rheumatic diseases. It may also be a safe and effective treatment option for Behcet’s syndrome (BS) where oral immunosuppressives other than azathioprine and cyclosporine are not available. Objectives: We aimed to report our experience with MMF in BS patients with major organ involvement. Methods: We retrospectively reviewed the charts of all BS patients who started using MMF between 2016 and 2018. Demographic characteristics, MMF indication, history of previous immunosuppressive agents, concomitant therapies with MMF, adverse events and outcome were recorded from the chart review. Results: We evaluated 39 BS patients (M/W: 30/9, mean age: 39 ± 8 years) treated with MMF during a mean follow-up of 18 ± 13 months. Of 39 patients, 31 received MMF for maintenance of remission therapy, while 8 had active disease at the initiation of MMF. The main indications were vascular involvement in 26, eye involvement in 11, and neurologic involvement in 2 patients. Among the 26 patients with vascular involvement, 13 had deep vein thrombosis, 6 had pulmonary artery involvement, and 3 had arterial involvement. Twenty-nine patients started MMF after azathioprine due to adverse events such as leucopenia, gastrointestinal intolerance and elevation of liver enzymes. MMF was chosen in 2 patients because of concomitant use of warfarin, that may be problematic with azathioprine. The remaining 8 patients were treated with MMF due to active disease despite azathioprine. In 20/39 (50%) patients MMF was used concomitantly with biologics (infliximab in 15 and adalimumab in 5). One patient additionally used cyclosporine-A and 7 patients used low-dose prednisolone. At the end of follow-up, 33 of the patients were still using MMF. The reasons for MMF discontinuation were recurrent superficial thrombophlebitis in 3 patients with previous lower extremity deep vein thrombosis, fear from adverse events, desire of pregnancy and itching in 1 patient each. There were no serious adverse events or adverse events leading to discontinuation except for itching. None of the patients experienced exacerbation of mucocutaneous lesions during MMF treatment. Conclusion: MMF seems to be a safe and effective alternative especially when used for maintenance of remission or in addition to biologic agents in active patients with major organ involvement. Disclosure of Interests: Sinem Nihal Esatoglu: None declared, Emir Cemre: None declared, Vedat Hamuryudan Consultant for: Abbvie, Amgen, BMS, Jansen, MSD, Pfizer, UCB, Speakers bureau: Abbvie, Amgen, BMS, Jansen, MSD, Pfizer, UCB, Yilmaz Ozyazgan Speakers bureau: ABBVIE, Didar Ucar: None declared, Zekayi Kutlubay: None declared, Serdal Ugurlu: None declared, Emire Seyahi: None declared, Melike Melikoglu: None declared, Izzet Fresko: None declared, Sebahattin Yurdakul: None declared, Hasan Yazici: None declared, Gulen Hatemi Consultant for: Abbvie, Amgen, BMS, Janssen, MSD, Pfizer, UCB, Speakers bureau: Abbvie, Amgen, BMS, Jansen, MSD, Pfizer, UCB

Background The usual onset of Behcet syndrome (BS) is in the 3. decade. Older age-onset defined as fulfilling the ISG criteria after 40 years of age is rare. One study from our center had reported the severity of eye disease was not different between early onset (≤ 24 years) and late onset (≥ 25 years) group. (1). While there is ambiguity in the definition of older onset, a few case series (2,3) coming mostly from ophthalmology or dermatology settings describe a similar or less severe clinical picture among late onset patients (pts) compared to early onset. Objectives To evaluate clinical characteristics of older onset pts and to compare them with classic onset pts. Methods The charts of 3335 BS pts who were registered between 2000 and 2010 were reviewed retrospectively. Pts who fulfilled ISG criteria for BS after 40 years of age were defined as older onset, while those who fulfilled the criteria before 30 as classic onset. For each older onset chart, 2 consecutively registered early onset charts were selected. Only clinical manifestations at presentation were recorded. A clinical activity index (1) was modified and calculated. Results There were only 134(70 M/64 F) pts with older onset BS, which gave a prevalence of 4% in the whole cohort. Age of onset was 40-44 years of age in 54 pts, 45-49 years in 47 and 50+ in the remaining 32. As controls 268(163 M/105 F) classic onset pts were selected. Demographic and clinical characteristics among older and classic onset pts are described for males and females separately, in Table. The frequency of skin manifestations, arthritis and eye disease as well as the mean clinical activity scores were significantly higher among male classic onset pts compared to older onset male pts. Interestingly, the frequency of those with positive pathergy test, vascular involvement and severe eye involvement did not seem to be different among older and classic onset male pts. On the other hand, clinical characteristics and total activity scores were similar between older and classic onset groups among females (Table). The main limitation is that the information was based solely on patient’s charts and outcome information was not available. Conclusion Compared to classic onset pts, males tend to be less frequent in older cohort. At presentation, older onset male pts had significantly less frequent skin, joint, eye disease, and significantly lower total activity scores compared with classic onset pts. There was no difference between the classic and older onset group, among females. References [1] Yazici H, et al. Ann Rheum Dis.1984. [2] Tsai J, et al. J Eur Acad Dermatol Venereol.2008. [3] Citirik M, et al. Ophthalmologica. 2011. Disclosure of Interests Gul Guzelant Ozkose: None declared, Yilmaz Ozyazgan Speakers bureau: ABBVIE, Cem Mat: None declared, Vedat Hamuryudan Consultant for: Abbvie, Amgen, BMS, Jansen, MSD, Pfizer, UCB, Speakers bureau: Abbvie, Amgen, BMS, Jansen, MSD, Pfizer, UCB, Hasan Yazici: None declared, Emire Seyahi: None declared

Background: Behcet’s syndrome (BS) has a heterogeneous expression involving many organ systems and is diagnosed by recognizing the coexisting manifestations. Several patients initially have few of these manifestations and do not fulfill the International Study Group (ISG) criteria. When these are major organ manifestations, failure to recognize BS and treat promptly may lead to permanent damage in these organs. Objectives: The aim of this study is to highlight the magnitude of this problem by surveying the frequency, presentation patterns and outcome of patients who did not fulfill ISG criteria when they presented to our clinic, but were followed and treated for manifestations strongly suggesting BS. Methods: We conducted a retrospective chart review of all BS patients who were registered between 2003 and 2008. Among these 2385 patients, 199 (8%) BS patients who did not fulfill ISG criteria at their initial visit were included in this study. Patients were called and a standard form was used for collecting demographic characteristics, BS manifestations at initial visit and during follow-up and treatment. Results: Among the 199 patients (M/W: 90/109, mean age: 34 ± 11 years) who did not fulfill ISG criteria when they presented to our clinic, 70 (35%) had major organ involvement. The types of major organ involvement that led to a diagnosis of BS at initial visit despite not fulfilling ISG criteria were eye involvement in 37, vascular involvement in 29 (venous thrombosis in 22, arterial aneurysms in 7), nervous system involvement in 3 and gastrointestinal (GI) involvement in 1 patient. Thirty-five patients (18%) had a family history of BS. Of 199 patients, 167 had at least one more visit with a median follow-up of 11 years (IQR: 7-12). We were able to contact 116 of these patients and saw that 53 had fulfilled ISG criteria in the meantime. Among the 51 patients that we were not able to contact, 17 had fulfilled criteria while they were being followed in our clinic. Thus, a total of 70 (42%) patients fulfilled ISG criteria after a median follow-up of 1.5 years (IQR: 1-4.25). All but 2 patients who developed eye involvement during the follow-up had fulfilled ISG criteria with a new mucocutaneous manifestation. After a median follow-up of 4 years (IQR: 1-7), 23 (14%) patients had developed at least one non-criteria BS manifestation, including vascular involvement in 10, arthritis in 13, neurologic involvement in 2 patients and GI involvement in 1 patient. Among the 81 patients who developed at least one new manifestation, 16 (20%) were under immunosuppressive or interferon-alpha treatment at the time they developed their new manifestation. The remaining 65 patients had only received colchicine. Among the 29 patients who had vascular involvement at initial visit, 7 (24%) had a vascular relapse at different vascular site. Three patients had another rheumatologic diagnosis (ankylosing spondylitis, seropositive rheumatoid arthritis and sarcoidosis) at the end of the follow-up. Conclusion: In our 10-year follow-up cohort study, 42% of the 167 incomplete BS patients had fulfilled ISG criteria within a median duration of 1.5 years. Sixty-two (37%) of these had major organ involvement that could have caused severe morbidity and mortality if the diagnosis of BS was missed and patients were untreated. Disclosure of Interests: : Sinem Nihal Esatoglu: None declared, Seyda Bilgin: None declared, Cem Sulu: None declared, Vedat Hamuryudan Consultant for: Abbvie, Amgen, BMS, Jansen, MSD, Pfizer, UCB, Speakers bureau: Abbvie, Amgen, BMS, Jansen, MSD, Pfizer, UCB, Zekayi Kutlubay: None declared, Serdal Ugurlu: None declared, Emire Seyahi: None declared, Melike Melikoglu: None declared, Izzet Fresko: None declared, Sebahattin Yurdakul: None declared, Hasan Yazici: None declared, Gulen Hatemi Consultant for: Abbvie, Amgen, BMS, Janssen, MSD, Pfizer, UCB, Speakers bureau: Abbvie, Amgen, BMS, Jansen, MSD, Pfizer, UCB

Background: There is an unmet need for reliable, validated, and widely-accepted outcome measures for clinical trials in Behcet’s syndrome (BS). Objectives: The Outcome Measures in Rheumatology Clinical Trials (OMERACT) Behcet’s Syndrome Working Group has worked to advance the creation of a data-driven Core Domain Set for use in all clinical trials. Methods: The Core Domain Set was developed through a comprehensive, iterative, multi-stage, multi-year project that followed the methodologically rigorous processes and standards set forth by OMERACT: i) a systematic review; ii) a survey among experts in BS; iii) an outcome measures interest group meeting during the International Conference on Behcet’s Disease; iv) qualitative patient interviews; v) a three-round modified Delphi exercise involving both patients with BS and a multidisciplinary set of physicians expert in BS, focused on obtaining consensus on the domains of illness necessary in the study of BS; and vi) utilization of the data, insight, and feedback generated by the outlined processes to develop a final Core Domain Set. The final Core Set was presented and put up for a vote of endorsement at the 2018 OMERACT meeting. Results: All steps in the processes outlined were completed. The systematic review clearly demonstrated the substantial variability in the domains studied in clinical trials of BS and a lack availability of validated outcome measures in BS. The survey of physicians, the in-person meeting of experts, and the qualitative research with patients all helped generate an extensive list of candidate domains and sub-domains to consider for use in clinical trials. It also become clear that there was a need and strong interest in delineating domains across the several major organ systems involved in this disease and in recognizing that clinical trials in BS often focus on specific manifestations and not the disease in its entirety. The Delphi involved 74 physicians expert in BS from 21 countries and from a wide range of specialties, and 64 patients from 10 countries. The Delphi utilized both ratings and rankings to prioritize the 56 domains and sub-domains originally under consideration. The final proposed Core Set included 5 sub-domains mandatory for study in all trials in BS, with additional sub-domains mandatory for study of specific organ-systems when that system is the focus of a trial: mucocutaneous (2 additional sub-domains), ocular (4), central nervous system (3), musculoskeletal (2), vascular (4), and gastrointestinal (2). The final Core Set was strongly endorsed at the 2018 OMERACT meeting. Conclusion: Multiple disease-related domains in BS have been identified by physicians and patients as important to address in clinical trials, leading to the development and endorsement of a final Core Set of Domains for use in clinical trials in BS. The Core Set provides the foundation through which the international research community, including clinical investigators, patients, the biopharmaceutical industry, and government regulatory bodies can harmonize the study of this complex disease, compare findings across studies, and advance development of effective agents. Disclosure of Interests: : Gulen Hatemi Consultant for: Abbvie, Amgen, BMS, Janssen, MSD, Pfizer, UCB, Speakers bureau: Abbvie, Amgen, BMS, Jansen, MSD, Pfizer, UCB, Alexa Meara: None declared, Yesim Ozguler: None declared, Haner Direskeneli: None declared, Alfred Mahr: None declared, Beverley Shea: None declared, Esen Cam: None declared, Ahmet Gul: None declared, Yusuf Yazici Shareholder of: Samumed, LLC, Consultant for: Celgene Corporation, BMS, Genentech, Sanofi, Employee of: Samumed, LLC, Peter Tugwell: None declared, Hasan Yazici: None declared, Peter Merkel: None declared

Background While thrombosis in Behcet’s Syndrome (BS) is considered to be mainly caused by inflammation in the vessel wall, several prothrombotic factors have been studied with inconsistent results. Objectives We aimed to perform a systematic review of clinical studies investigating the thrombophilic factors in BS. Methods The online database of PubMed was searched with the keyword “Behcet*” in four languages (English, German, French and Turkish) from inception up to May 2018. Titles and/or abstracts of all studies were screened independently by two reviewers (GG and BY) for studies reporting on thrombosis, fibrinolysis, endothelial factors and comparing BS patients with and without thrombosis. Conflicts were solved by a third reviewer (GH). The pooled odds ratios (OR) with 95%CI were calculated for binary outcomes and standardized mean differences (MD) were calculated for continuous outcomes by using RevMan 5.3. Results Of 9937 articles, 9373 were excluded due to repetition and inappropriate study design after reviewing titles and abstracts. Full text review of the remaining 564 articles yielded 86 papers meeting our predetermined inclusion criteria. Several factors such as protein C, protein S, active protein C resistance, anti-thrombin III, plasminogen, plasminogen activator inhibitor, fibrinogen, factor 7, factor 12, thrombin activatable fibrinolysis inhibitor, anticardiolipin antibodies, antis2 Glycoprotein1 antibodies and methylenetetrahydrofolate reductase gene C677T mutation were not different in BS patients with thrombosis compared to those without thrombosis. On the other hand, vascular endothelial growth factor levels, P-selectin glycoprotein ligand-1, platelet-activating factor seemed to be more frequent in BS patients with thrombosis in the few studies reporting on these, including a small number of patients. Among the 11 parameters with controversial results across studies, meta-analysis showed significantly higher homocysteine levels, higher factor 8 levels, more frequent Factor V Leiden mutations and higher von Willebrand factor levels in BS patients with thrombosis, whereas the pooled difference was not significant for mean platelet volume, tissue plasminogen activator, prothrombin gene mutations, lupus anticoagulant, P-selectin level, erythrocyte aggregation and thrombomodulin level (Table). Conclusion Among the several prothrombotic factors that were studied in BS patients, factor V Leiden mutation, high homocysteine levels, factor 8 levels and von Willebrand factor levels may be associated with thrombosis in BS. Studies investigating these factors together in a large number of patients together with appropriate controls are needed to confirm these results. MD: mean difference, OR: odds ratio, tPA: tissue plasminogen activator Disclosure of Interests: Gul Guzelant Ozkose: None declared, Berna Yurttas: None declared, Sinem Nihal Esatoglu: None declared, Vedat Hamuryudan Consultant for: Abbvie, Amgen, BMS, Jansen, MSD, Pfizer, UCB, Speakers bureau: Abbvie, Amgen, BMS, Jansen, MSD, Pfizer, UCB, Hasan Yazici: None declared, Gulen Hatemi Consultant for: Abbvie, Amgen, BMS, Janssen, MSD, Pfizer, UCB, Speakers bureau: Abbvie, Amgen, BMS, Jansen, MSD, Pfizer, UCB

We take the following three main messages from Porter and colleagues’ thoughtful viewpoint article.1 1. Although disease classification criteria are developed for research purposes, they are commonly used for diagnosis in the clinic. This common practice is wrong since the prior probabilities for the targeted disease are always higher in the research and lower in clinical practice settings. Therefore, the use of the same criteria for diagnosis in general practice would cause an unacceptably high number of false positives in that setting. 2. The use of classification criteria for research purposes, the usual setting being enroling patients into clinical trials, is also problematic. Such criteria can not only cause exclusion of patients who would benefit from the drug used in the study, but also the inappropriate inclusion of patients with no disease into the formal study. The authors give suitable examples for both scenarios. 3. The authors conclude that since the current disease criteria represent much hard work by experts in the field we …

The p-value is commonly misused. We hypothesised that a close cooperation with a statistician would go along with a more proper use of p-values. We considered a close cooperation present, when a statistician was a coauthor, or a formal statistical help was acknowledged in a study report.Randomised controlled trials published in 2015-16 in 4 widely read rheumatology journals were searched for a close cooperation with a statistician, the inclusion of effect sizes, confidence intervals, exact rather than relative p-values and the omission of p-values in tables depicting trial entry data.There were only 28/133 (21%) articles in which a formal statistical help was acknowledged (Group I). The rest (Group II) gave no acknowledgement of a close cooperation. Reporting of effect sizes (96% vs. 71%) and exact p-values (88% vs. 69%) were more in Group I (p=0.01, and p=0.08, respectively).While a formal acknowledgement of a close cooperation was notably infrequent at 21%, this went along with improvement in some aspects of p-value reporting. If substantiated by further studies, we propose that a formally acknowledged statistical help should improve p-value reporting. Like all professionals, statisticians would like their name/office to be formally associated with their good work.

The faecal calprotectin (FC) test is widely used as a non-invasive method for identifying intestinal inflammation. A recent study suggested FC may help to diagnose gastrointestinal involvement of Behçet's syndrome (GIBS). We aimed to determine whether FC helps to distinguish active from inactive intestinal involvement in GIBS.We tried to contact 70 GIBS patients registered in our tertiary multidisciplinary clinic. We prospectively collected faecal specimens and serum from 39 GIBS patients who gave informed consent assessing calprotectin and CRP levels followed by a colonoscopy. We included 47 Crohn's disease (CD) patients as controls. Active disease was defined as having ulcer/s on colonoscopy. We filled the Disease Activity Index for Intestinal Behçet's Disease (DAIBD) and Crohn's Disease Activity Index (CDAI). The cut-off for positive FC was defined as ≥150 μg/g.Ulcers were detected in 12/39 GIBS patients. Sensitivity and specificity of the FC test for active disease was 91.7 (95%CI:61.5-99.8) and 74.1% (95%CI:53.7-88.9). Median FC and CRP levels and DAIBD scores were higher among patients with ulcers, whereas serum calprotectin and CDAI scores were not. A negative FC test was the only significant predictor of remission (OR:37.04, 95%CI:2.4-561.6; p=0.009) on multivariate analysis. Among CD patients, 16/25 active patients and 3/22 patients in endoscopic remission had a positive FC test (OR:11, 95%CI:11-49).FC, but not serum calprotectin seems to be a useful non-invasive tool for assessing disease activity in GIBS. Whether the presence of oral ulcers can cause false positive results remains to be studied.

1980-2000 arası Türk romanında baba figürünün aileekonomisindeki rolünün analizi yapıldı. Hayatımızın süzgeci dönem romanımızdababanın aile ekonomisindeki yerinin fotoğrafı çekildi. Romanımızda Türkiye’nin sosyal gerçeğinde olduğu gibi egemen olanbabalık modeli, evin geçimini sağlayan aile babasıdır. Erkeğin babalık rolünüyerine getirebilmesindeki en etkili faktör ekonomidir. Kültürel ve sosyalhayatımızın temel mührü İslamî açıdan aile reisi olan koca (en-Nisâ 4/34),karısının ve çocuklarının nafakasını karşılamakla sorumludur. Türkiye’de en yaygın babalık biçimi erkeğin geçimsorumluluğunu büyük ölçüde tek başına üstlendiği, kadınların sadece ev işiyaptıkları, kız çocukların okutulmakla birlikte erkek çocuklarla eşitgörülmediği modernleşmiş aile babalığı şeklindedir. Babanın romanımızdakiekonomik portresi, baba etrafındaki ekonomik yönden çeşitli fikirler ve tenkitlerleaile ve toplum hayatımızın yönelişlerine teşhis ve planlamada katkısağlayabilir., Father figure in scope of family economy in Turkish novelswritten during 1980-2000 has been analyzed. We have taken the photo of thefather's place in family economy in our periodic novels, which act as a filterof our lives. The most efficient factor that makes sure the male fulfills hisfatherhood role is, economical. The father is responsible from the subsistenceof his wife and children, as he is the head of the family according to Islam(Sura An-Nisa 4/34), which is the main seal of our cultural and social life.Economical portrait of the father in our novels, through criticism and variouseconomical ideas around the father may make contributions in scope of thetendencies of our family and social life.

Henoch-Schonlein purpura is a relatively common vasculitis mainly affecting children. It is characterized by purpuric skin rash, abdominal cramping, and haematuria. Skin biopsies taken from Henoch-Schonlein purpura lesions disclose perivascular IgA deposits. FMF is an autoinflammatory disease characterized by recurrent attacks of fever lasting 2-3 days which resolve spontaneously. Typical manifestations of the disease are peritonitis, pleuritis, pericarditis, arthritis and erysipelas-like erythema usually affecting the lower limbs. Over the years many reviews emphasized the clinical impression that Henoch-Schonlein purpura is more common among FMF patients than in healthy control population. In this review we summarize these reports and show that sometimes Henoch-Schonlein purpura associated with FMF differs from typical isolated Henoch-Schonlein purpura, and this is also the case with polyarteritis nodosa and SpA associated with FMF. It is suggested that these clinical manifestations (polyarteritis nodosa, Henoch-Schonlein purpura and SpA) should be considered to be associated with FMF as part of what we call FMF rather than as co-existing additional separate clinical entities.

Several new treatment modalities with different mechanisms of action have been studied in patients with Behçet's syndrome (BS). The aim of the current effort was to update the recommendations in the light of these new data under the auspices of the European League Against Rheumatism (EULAR) Standing Committee for Clinical Affairs. A task force was formed that included BS experts from different specialties including internal medicine, rheumatology, ophthalmology, dermatology, neurology, gastroenterology, oral health medicine and vascular surgery, along with a methodologist, a health professional, two patients and two fellows in charge of the systematic literature search. Research questions were determined using a Delphi approach. EULAR standardised operating procedures was used as the framework. Results of the systematic literature review were presented to the task force during a meeting. The former recommendations were modified or new recommendations were formed after thorough discussions followed by voting. The recommendations on the medical management of mucocutaneous, joint, eye, vascular, neurological and gastrointestinal involvement of BS were modified; five overarching principles and a new recommendation about the surgical management of vascular involvement were added. These updated, evidence-based recommendations are intended to help physicians caring for patients with BS. They also attempt to highlight the shortcomings of the available clinical research with the aim of proposing an agenda for further research priorities.

Menstruation triggers several conditions such as migraine, recurrent aphthous stomatitis and acne vulgaris in healthy individuals. There is evidence that Behçet's syndrome (BS) and familial Mediterranean fever (FMF) may exacerbate during menstruation. The aim is to assess whether BS and FMF patients experience menstrual flares.Females of reproductive age with BS and FMF seen consecutively at the outpatient clinic of Cerrahpasa Medical Faculty at Istanbul, as well as apparently healthy hospital workers were studied using a standardised questionnaire. BS patients were asked whether they experienced increased skin-mucosa lesions during the menstrual period. A similar questionnaire assessing this time the frequency of abdominal pain, chest pain and fever attacks was given to the patients with FMF. The healthy controls received both questionnaires.A total of 200 BS patients, 240 FMF patients and 250 healthy controls were studied. The most commonly reported symptom among both BS patients (51%) and healthy controls (62%) was the acneiform lesion. At least 79% patients with FMF reported attacks with menstruation, notably abdominal pain which, majority thought, could be differentiated from dysmenorrhea. Additionally, 76% of healthy controls reported having abdominal pain consistent most probably with dysmenorrhea.This survey showed that, in 68% of the patients with BS at least one skin mucosa lesion was exacerbated with menstruation, this was most commonly acneiform lesion. Menstruation had a slightly stronger effect on FMF, triggering at least one symptom in 79%. The main limitation of the study was the self-reported assessment methodology.

The prognosis of uveitis in Behçet's syndrome (BS) has improved over decades. Whether this is related to the use of more aggressive management strategies is not known.This is a retrospective study of BS patients who received infliximab (IFX) for refractory eye disease between 2003-2015. The patients were divided into two groups according to the date of onset of in IFX treatment as before and after 2013. We compared the two groups in terms of disease characteristics at the onset of IFX treatment and response to treatment.There were 43 patients in the old and 14 patients in the new group. The duration of uveitis and previous immunosuppressive treatment before the initiation of IFX were significantly shorter in the new group compared to the old group (p=0.043 and p=0.028, respectively). The baseline visual acuity (VA) at the initiation of IFX was better in the new group, but this was only significant for the left eye. Treatment with IFX was effective in both groups in preserving VA and this was more pronounced in the new group. Attack frequency under IFX was significantly lower in the new group (p0.001).IFX seems to be initiated earlier and also in less severe cases during the course of BS uveitis than before. Despite the few numbers of patients and relatively short duration of follow-up, our results give a hint that this change has improved the outcome.

Behcet's syndrome (BS) is a multisystem vasculitis with an unknown etiology and an unique geographic distribution. The pathogenesis of BS is complex and currently not fully understood. Since the 1970's there have been different attempts to classify BS within the specific group of diseases such as spondyloarthritis, autoimmune and more recently autoinflammatory disease. However current evidence suggests that BS does not easily fit into any one of these diseases and we propose the possibility that the construct we take as BS might represent more than one disease. The management of BS usually depends on clinical presentation and organ involvement. Traditional immunosuppressives and concomitant use of corticosteroids have been the main therapeutic choice for many years. There is growing experience with biologic therapeutics especially with tumor necrosis factor-alpha (TNF-alpha) antagonists in the management of refractory eye, gastrointestinal and neurologic involvement in BS. In this review we have proposed a different perspective about the disease mechanisms of BS and have summarized the current management strategies in BS in the light of available evidence.

Objective. Some features of Behcet's syndrome (BS) tend to go together. We aimed to explore the association and timing of various vascular events in both the venous and the arterial vascular tree. Methods. We conducted a chart survey on the type and time of vascular involvement of BS. The cross- relationships of involvement were assessed by phi correlation coefficients. Multiple correspondence ana- lysis was used to identify patterns of vascular involvement. The risk of vascular recurrence was also estimated. Results. We identified 882 patients with vascular involvement among 5970 BS patients (14.7%). Deep vein thrombosis (DVT), almost always in the legs, was the most frequent single vascular event (592/882; 67.1%). The cumulative risk of a recurrent vascular event was 38.4% at 5 years. Patients with extrapul- monary artery involvement (EPAI) were significantly older than those with venous and pulmonary artery involvement (PAI). There were significant correlations between dural sinus thrombosis (DST) and PAI, BuddChiari syndrome (BCS) and inferior vena cava syndrome (IVCS) and between IVCS and superior vena cava syndrome (SVCS). Multiple correspondence analysis further indicated clustering of PAI, DST, BCS, IVCS and SVCS. However, EPAI and DVT clustered separately from forms of vascular disease, the separate clustering of the DVT being attributed to its propensity to occur solo. Conclusion. The most common type of vascular involvement in BS is solo DVT, almost always occurring in the legs. Various forms of venous disease in BS segregate together and PAI is included in this group. EPAI segregates separately.

Familial Mediterranean fever (FMF) is characterised by recurrent attacks of fever and serositis. It may affect the peritoneum, pleura, synovia and the skin. Usually the liver is intact in FMF. Recently, this concept was challenged by some groups which claimed that hepatitis is a feature of FMF and that non-alcoholic liver disease (NAFLD) and cryptogenic cirrhosis are more common among FMF patients. Scope of this paper is to critically review the relevant literature and to answer the question whether or not the liver is involved in FMF.We used Medline, Embase, Scopus and Web of Science database for searching articles dealing with FMF and the liver since 1960. We also reviewed some manuscripts which were not identified by the above searching engines.Some cases reported that hepatitis is a feature of FMF based upon transaminase elevations without liver biopsy. Due to this questionable diagnosis and the paucity of similar reports, it seems that hepatitis is not a feature of FMF. Cryptogenic cirrhosis is considered as the end stage of NAFLD. Since NAFLD is prevalent in 25% of the general population it is more plausible to relate the occurrence of cryptogenic cirrhosis in FMF patients to NAFLD rather than to FMF. M694V mutation carriage was relatively more frequent among FMF patients with cryptogenic cirrhosis or "hepatitis".The literature review indicates that FMF and liver disease are not generally associated. However, carriage of M694V mutations may play a role in the pathogenesis of liver disease.

To estimate the prevalence of Behçet's disease (BD) in Jordan, with the additional aim of comparing this prevalence among hospital workers in other geographical areas.In the first stage of our survey, 2,569 employees from 6 hospitals in north Jordan were interviewed using a screening questionnaire to identify individuals with recurrent oral ulcers (ROU), a previous diagnosis of BD (PDBD) and/or any major symptom related to BD. In the second stage, all individuals with ROU or PDBD identified at stage 1, were examined by 2 rheumatologists for the presence/confirmation of BD according to the International Study Group (ISG) criteria. Pathergy test was performed according to recommendations.ROU were present in 210 (8.2%) individuals. BD was confirmed in 10 employees with PDBD. Seven more BD patients were found. Mean age of 17 BD patients was 38.6±10.7 (range 26-65 y). M: F was 2.4:1. Pathergy test was positive in 8/17. A family history of ROU or BD was noted in 9 (52%) and 3 (25.0%), respectively, compared to 227 (8.9%) and 62 (2.6%) in the whole group, excluding the BD patients (p0.001 and 0.008, respectively). The prevalence rate of BD in the north of Jordan was estimated as 66:10.000 (95% CI 34.8 to 97.5:10000).The results of this first ever survey indicated that the prevalence of BD in the north of Jordan is among the highest in the world. This prevalence can now be compared to hospital workers in other geographical areas.

Although skin-mucosa lesions are common in almost all patients with Behcet syndrome (BS), clinical properties may differ from one patient to another. Within BS, there are subsets with different organ involvement and hence probably different pathological pathways. These subsets can be described as a) solo skin-mucosa disease with no major organ involvement, b) eye disease, c) seronegative spondyloarthropathy-like disease (arthritis, enthesopathy, and folliculitis), d) Crohn-like disease, and finally the topic of this chapter: e) vascular disease. In the vascular disease subset, not surprisingly, several types of vascular involvement may be observed in the same individual. These subsets may make up the total clinical picture all at the same time or step by step with each relapse. Significant correlations exist between cerebral vascular thrombosis and pulmonary artery involvement, intracardiac thrombi and pulmonary artery involvement, Budd-Chiari syndrome, and inferior vena cava syndrome. Lower extremity vein thrombosis is often present in these associations and even precedes them. The recognition of these clusters is not only important in diagnosis and management but also in basic science, including genetic studies.

Gastrointestinal involvement is rare in Behçet's syndrome (BS) patients from the Mediterranean basin. We report the demographic and disease characteristics, treatment modalities, and outcome of patients with gastrointestinal involvement in BS (GIBS). We retrospectively reviewed the charts of all BS patients in our BS clinic with a diagnosis of GIBS. Patients were invited to the clinic to assess their outcome. Among 8763 BS patients, we identified 60 with GIBS (M/F: 32/28, mean age at diagnosis: 34 ± 10, mean follow-up: 7.5 ± 4 years), after excluding 22 patients with mimicking symptoms. Six (10%) had juvenile-onset BS. The most common intestinal localization was ileocecal region (36/59, 61%) mainly as big oval ulcer/s. Initial treatment was azathioprine for moderate to severe (n = 37) and 5-ASA for mild cases (n = 16). Anti-TNFs and/or thalidomide provided remission in 12 of 18 (67%) refractory patients. Emergency surgery was required in 22 patients. Nine patients did not receive postoperative immunomodulators and 8 relapsed. Overall, 48 of 60 (80%) patients were in remission (29/48 without treatment) at the time of survey. Three recently treated and 2 refractory patients were still active, 3 had died due to non-GI-related reasons, and 4 were lost to follow-up. Careful evaluation for excluding mimickers is important during the diagnosis of GIBS. Azathioprine seems to be a good choice as first-line treatment with high remission rates and few adverse events. Thalidomide and/or TNF-alpha antagonists may be preferred in resistant cases. Surgery may be required for perforations or massive bleeding, and postoperative immunosuppressive treatment is necessary for preventing postoperative recurrences.

Haemoptysis occurring in a Behçet's syndrome (BS) patient with pulmonary artery involvement (PAI) during follow-up is usually regarded as PAI relapse. However, bronchial artery enlargement (BAE) may be the source of haemoptysis in some patients.A chart review at the end of December 2014 revealed 118 patients with PAI in our centre since 1979. Nine (all men) had recurrent haemoptysis during follow-up which could not be explained with relapse of PAI.Haemoptysis recurred a median of 1.5 years (IQR: 9 months-5 years) during follow-up. Thorax CT scans did not show relapse of PAI or emergence of BAE. The patients were treated empirically but continued to complain of occasional haemoptysis thereafter. BAE was detected in 8 patients after a median follow-up of 9 years (IQR: 5-12 years). Six patients underwent bronchial artery embolisation that was repeated in 3. One patient with severe pulmonary hypertension died 3 weeks later. The remaining 5 are under follow-up for between 5 months-9 years. Pulmonary infarction and mild hemiparesis occurred in 2 patients after embolisation. One patient died with haemoptysis before undergoing embolisation. Another one with small BAE is under follow-up for 8 years without embolisation. The source of bleeding could not be determined in 1 patient who is now haemoptysis free for 5 years.BAE may be the source of recurring and fatal haemoptysis in BS patients with PAI during follow-up. Embolisation appears to be a life-saving procedure.

Pulmonary artery aneurysms (PAAs) are well known causes of mortality and morbidity in Behçet disease (BD). However, pulmonary artery involvement in BD is not limited to PAA; the other main type of pulmonary artery involvement is pulmonary artery thrombus (PAT), with or without associated PAA. In addition, other types of lung disease like nodules and cavities in the lung parenchyma are frequently associated with pulmonary artery involvement, and can be misinterpreted as being due to infection. We surveyed the clinical, radiologic, and laboratory characteristics and outcome of 47 BD patients with pulmonary artery involvement and the associated findings, all seen and followed at a single dedicated tertiary care center.We identified 47 (41 male, 6 female) patients in whom pulmonary artery involvement was diagnosed, who were registered in the multidisciplinary clinic at Cerrahpasa Medical Faculty between January 2000 and December 2007. Mean age at diagnosis was 29 ± 8 years, and mean disease duration to the onset of pulmonary artery involvement was 3.6 ± 4.8 years. Hemoptysis was the most common presenting symptom (79%) followed by cough, fever, dyspnea, and pleuritic chest pain. Thirty-four of 47 patients (72%) presented with PAA, including 8 with associated PAT. The remaining 13 patients (28%) had isolated PAT. Patients with isolated PAT in general have clinical features similar to patients with PAA. However, hemoptysis was less frequent and voluminous in patients with isolated PAT. Most (91%) of the patients had active disease outside the lungs when they presented with pulmonary artery involvement.Forty (85%) patients had nodules and 6 (13%) had cavities when first seen. Peripheral venous thrombosis was present in 36 of 47 (77%) patients, and intracardiac thrombi in 12 of the 36 (33%) patients. Nodules, cavities, and intracardiac thrombi were mainly present in the acute stages of pulmonary artery involvement.Pulmonary artery involvement is usually multiple, and involves mostly descending branches of the pulmonary artery. Pulmonary artery involvement may disappear, but arterial stenosis or occlusions usually develop at the same location. After a mean follow-up of 7 years, 12 of 47 (26%) patients were dead; patients with larger aneurysms were more likely to die. Sixteen of 47 (34%) patients were symptom free, and the remaining 40% had mild dyspnea (13/47) and/or small bouts of hemoptysis (8/47).Pulmonary artery pressure may be elevated, and may indicate a poor prognosis. Mediastinal lymphadenopathy and mild pleural and pericardial effusions may also be observed. Corticosteroids and immunosuppressive agents are the mainstays of treatment; however, refractory cases may require embolization, lobectomy, cavitectomy, and decortication.

The study by Mahr and colleagues, which is reported in this issue of Arthritis & Rheumatism (1), gives us important new insight into the prevalence of Behcet’s disease (Behcet’s syndrome [BS], as we prefer to call this condition) that will be useful in resource allocation and aid in the understanding of disease mechanisms, the traditional aims of epidemiology. In addition, their data allow us to consider how we can improve our diagnostic abilities using epidemiology as a guide. Mahr et al (1) report a BS prevalence rate of 7.1 per 100,000 adults in a suburb of Paris, France. As expected, non-European subgroups, including subjects of Asian and North African descent, had substantially higher prevalence rates compared with the native European population. The same group of investigators previously examined the frequencies of other vasculitides in the same geographic area, using almost identical sources of case ascertainment (2). In both instances, the authors used a capture–recapture analysis to check the validity of their sources of case ascertainment and to estimate the missing-case rate. The capture–recapture method, which has thus far been used infrequently in rheumatology, is an epidemiologic tool that allows the use of multiple samples from a single population, providing a shortcut to traditional whole population studies (3). The following 3 important conditions must be met for the capture– recapture method to have a workable validity: the population studied must be closed, like a fish pond; the likelihood of representation of the trait being examined should be equal in each sample; and capture by 1 source should not increase or decrease the likelihood of capture by another source. It is often argued that, unlike in veterinary work where the method has found wide use, the capture– recapture method generally underestimates the true disease rate when used in human medicine (4), where the fulfillment of the above 3 conditions is understandably difficult. Nevertheless, the method does give us an approximation of the underestimation. The underestimation was 20% in the study by Mahr et al published in this issue of Arthritis & Rheumatism (1) and 25% in their previous study (2), and the nonresponder rates were also quite similar (43% in the present study and 47% in the previous study). Despite the possible shortcomings of the methodology used, the fact that nearly identical methodology was used in an identical population in both studies gives us the unique opportunity to compare the frequency of BS with the frequencies of the other vasculitides in the heart of Europe. In the area near Paris, BS is several times more common than each of the 4 other vasculitides, while it is almost as common as all of them combined (Table 1). The formal designation of a disease as “orphan” in Europe requires a frequency of 1 per 2,000 inhabitants (5), and it is clear that the frequencies of BS and the other vasculitides are well within the boundaries of this definition. However, a disease can also be an “orphan” in the eyes of the physician, and we have reason to suggest that BS is considerably more orphan in this sense when compared with the other vasculitides. This contention is supported by a comparison of the space allocated to BS in standard textbooks of rheumatology with that allocated to the other vasculitides. One such well-known source (6) has 5 pages allocated to BS compared with 12 for Wegener’s granulomatosis and 7 for Churg-Strauss syndrome. In light of the new information reported by Mahr and colleagues, we hope that BS will become less “orphan” and receive more attention in textbooks, medical education and training, public policy and government, and foundationand pharmaceutical industry–supported research. Both genetic and environmental variables have been described in the etiology of BS. It has been almost Hasan Yazici, MD, Emire Seyahi, MD, Sebahattin Yurdakul, MD: University of Istanbul, Istanbul, Turkey. Address correspondence and reprint requests to Hasan Yazici, MD, Professor of Medicine, Chief, Division of Rheumatology and Department of Medicine, Cerrahpasa Medical Faculty, University of Istanbul, Safa sok. 17/7, Kadikoy, Istanbul 81310, Turkey. E-mail: hyazici@attglobal.net. Submitted for publication July 18, 2008; accepted in revised form September 17, 2008.

Adhesion molecules have a role in many vasculitic disorders. Our aim was to evaluate the status of adhesion molecules in nodular lesions of Behçet syndrome (BS) and compare them with results for the 2 most common types of panniculitis, erythema nodosum (EN) and nodular vasculitis (NV). We included the data for 28 patients with nodular lesions of BS, 24 with EN, and 22 with NV. A panel of monoclonal antibodies against E-selectin, P-selectin, vascular cell adhesion molecule-1, platelet endothelial cell adhesion molecule-1, and intercellular adhesion molecule (ICAM)-1 were applied. The distribution and intensity of adhesion molecules were assessed. There were no statistically significant differences between the BS and control groups in regard to these adhesion molecules except for ICAM-1. The percentage of strongly ICAM-1-stained endothelial cells in subcutaneous fat tissue in relation to the total number of endothelial cells was the lowest in BS (P= .0208). Because many lesions of BS were related to an enhanced inflammatory response, the lower percentage of ICAM-1 expression seems counterintuitive.