Tocilizumab as a first line biologic agent in rheumatoid arthritis patients with inadequate response to disease-modifying anti-rheumatic drugs: real life experience from the TReasure Registry.

OBJECTIVES: To evaluate the retention rate, treatment response and safety of tocilizumab (TCZ) as first-line biologic treatment in rheumatoid arthritis (RA) patients with inadequate response to disease-modifying anti-rheumatic drugs (DMARD-IR). METHODS: The TReasure Registry is a multicentre, web-based registry of RA and spondyloarthritis patients across Turkey. DMARD-IR RA patients who received TCZ as first-line biologic treatment were included in this registry for efficacy and safety. Demographic and clinical data, treatments, and adverse events were collected. Drug retention rate was estimated using Kaplan-Meier analysis. RESULTS: Among 642 RA patients who ever used TCZ, 258 DMARD-IR RA patients (male/female: 18.2%/81.8%, mean age, 54.41 years) received TCZ as first-line biologic. The median disease duration was 97 (range, 60-179) months and the median TCZ treatment duration was 15 (range, 6-28) months. At the 6th and 12th months of TCZ treatment, the decrease in disease activity scores from baseline was significant. The Kaplan-Meier analysis revealed the retention rate of TCZ at the 12th, 24th, 36th, and 60th months as 81.1%, 73.8%, 66.2%, and 63.6%, respectively. Fifty-seven (22%) patients discontinued TCZ; the main reason being primary or secondary inefficacy (n=29). CONCLUSIONS: Over 80% drug retention rate at 12th month of TCZ treatment in this real-world study was concordant with previously conducted TCZ clinical studies. Significant reductions not only in the disease activity score-28 but also in the simplified disease activity index (SDAI) and clinical disease activity index (CDAI) scores, along with health assessment questionnaire (HAQ) scores, supported the impact of TCZ in RA management with a good safety profile.

Neurologic manifestations of Behçet disease: rheumatology experience.

OBJECTIVE: Neurologic involvement in Behçet disease (BD) is a rare manifestation. Herein, we aimed to evaluate the clinical features and treatment choices of neuro-Behçet (NB) patients. METHODS: There were records of 800 BD patients between 1998 and 2021. Fifty-five of the BD patients had NB and the files of these patients were retrospectively evaluated. Patients were grouped into three subgroups: 22 (40%) had non-parenchymal, 25 (45%) had parenchymal, and 8 (15%) had both parenchymal and non-parenchymal (mixed) involvement. RESULTS: Of the 55 patients, 32 were male. Twenty-six of the NB patients were diagnosed with BD simultaneously. The most common complaint was headache (n = 24, 44%). The most affected site was periventricular white matter (n = 21, 38%). All patients had received corticosteroids. Azathioprine (AZA; n = 39, 71%) was the most common immunosuppressive agent after corticosteroids, followed by cyclophosphamide (n = 16, 29%). CONCLUSION: Neurologic involvement is a rare complication of BD but is related to increased mortality and morbidity. Neurologic manifestations may be the initial symptom of BD, thus leading to diagnosis. Both neurology and rheumatology specialists should be aware of this rare condition.

Predictors of persistent inflammation in familial Mediterranean fever and association with damage.

OBJECTIVE: Persistent inflammation is an insidious and less studied feature of FMF. We investigated clinical determinants of persistent inflammation and its associations with individual damage items. METHODS: This is a cross-sectional analysis of 917 FMF patients, who fulfilled the Tel Hashomer criteria and had at least 6 months' follow-up. Patients were stratified based on whether they had persistent inflammation. We used logistic regression analysis to investigate independent predictors of persistent inflammation and the associated individual damage items. RESULTS: One hundred and forty-two (15%) patients had persistent inflammation. Active FMF (54%) was the most prominent reason for the persistent inflammation. Spondylarthritis (16%), other inflammatory arthritis (8%) and IBD (2%) were other frequent reasons. Male gender, history of exertional leg pain, inflammatory comorbidities, M694V homozygosity, colchicine resistance, lower education levels and musculoskeletal attack dominance were found to be the independent predictors of persistent inflammation. Earlier disease onset led to a tendency towards persistent inflammation. Patients with persistent inflammation were more likely to suffer damage. There is an increased risk of developing proteinuria, amyloidosis and renal insufficiency. CONCLUSION: We identified, for the first time, the predictors of persistent inflammation in adult FMF patients and related individual damage items of the Autoinflammatory Disease Damage Index. Persistent inflammation is insidious and one of the chief causes of damage; therefore, especially patients with these predictors should be followed up more closely. If detected, underlying inflammatory comorbidities should be assessed meticulously as early detection and proper treatment strategies may favourably impact the natural history of the disease.

Appendectomy history is associated with severe disease and colchicine resistance in adult familial Mediterranean fever patients

Background/aim: Peritonitis attacks of Familial Mediterranean Fever (FMF) usually requires emergency medical admissions and it's hard to distinguish a typical abdominal attack from surgical causes of acute abdomen. Therefore, history of abdominal surgery, particularly appendectomy, is very common in patients with FMF. However, history of appendectomy might also give some clues about the course of FMF in the adulthood. This study was to determine whether the history of appendectomy help to anticipate disease course of FMF in the adulthood. Materials and methods: All patients recruited from FMF in Central Anatolia (FiCA) cohort, comprising 971 adult subjects. All patients fulfilled the Tel Hashomer criteria. Demographic data, FMF disease characteristics, co-morbid conditions, past medical history, surgical history and disease complications were meticulously questioned and laboratory features and genotype data (if available) were recruited from patient files. Results: Appendectomy history was evident in 240 (24.7%) subjects. Disease onset was earlier and peritonitis is strikingly more prevalent (97.1% vs. 89.6%, p < 0.001) in appendectomized patients. These patients had reported almost two fold more frequent attacks in the last year compared to appendix intact patients (median 3.5 vs. 2 attacks, p = 0.001) without a difference in frequency of musculoskeletal and skin attacks. Severe disease was more common (10% vs. 5.9%, p = 0.038) due to involvement of more attack sites throughout the life and more frequent attacks. Appendectomy patients had used higher daily doses of colchicine to control disease (1.43 ± 0.6 mg vs. 1.27 ± 0.52 mg, p = 0.002) but colchicine resistance was also more common in these patients, 15% vs. 6.7% respectively, p < 0.001. Conclusion: Appendectomy history is common in FMF patients and associated with frequent serositis attacks in adulthood. These patients require higher colchicine doses with a lower rate of response and more need for Interleukin-1 antagonist therapies.

Phenotypic characterization of Familial Mediterranean Fever patients harboring variants of uncertain significance

Background/aim: Familial Mediterranean Fever (FMF) is the prototype of hereditary autoinflammatory disorders and caused by mutations on the MEFV gene located on the short arm of chromosome 16. Although some MEFV variants are clearly associated with disease phenotype, there are numerous variants with unknown clinical association which are termed as variants of uncertain significance (VUS). Here, we present clinical correlations of VUS in a large cohort of adult FMF patients from three tertiary centers located in Central Anatolia. Materials and methods: All patients were recruited from FMF in Central Anatolia (FiCA) cohort. Demographic (sex, age at disease onset) and clinical features (disease characteristics, attack frequency, mean colchicine dose, colchicine nonresponsiveness, amyloidosis, and persistent inflammation) of patients with VUS were compared with those harboring pathogenic variants. Disease severity and damage were also evaluated using international severity score for FMF (ISSF) and autoinflammatory disease damage index (ADDI), respectively. Results: Among 971 participants included, MEFV gene analysis results were available for 814 patients. Twenty-six (3.2%) patients had single heterozygous VUS and 54 (6.6%) had pathogenic/VUS complex heterozygous variants. Patients with single heterozygous VUS had similar demographic/clinical features, ISSF and ADDI scores compared to those with single heterozygous pathogenic variant (p > 0.05 for all). No difference was observed in the demographic and clinical features of patients with single heterozygous pathogenic mutation and pathogenic/VUS complex heterozygous variant (p > 0.05 for all). ISSF and ADDI scores were lower in pathogenic/VUS complex heterozygous patients than those harboring single pathogenic mutation (p = 0.006 and 0.004, respectively). Conclusion: Our findings suggest that patients with single heterozygous VUS has mild FMF phenotype similar to those with single pathogenic mutation. Pathogenic/VUS complex heterozygosity does not lead to a more severe clinical phenotype than having a single pathogenic variant.

Intestinal microbiota composition of patients with Behçet's disease: differences between eye, mucocutaneous and vascular involvement. The Rheuma-BIOTA study.

OBJECTIVES: Changes in microbiota composition affect the aetiology and patho-genesis of chronic diseases, including Behçet's disease (BD). However, no studies have analysed the potential gut microbiota changes among different clinical forms of BD. This study evaluated the intestinal microbiota composition of patients with BD and healthy controls and also compared differences between patients with BD with respect to eye, mucocutaneous, and vascular involvement. METHODS: In this prospective cohort study, 27 patients diagnosed with BD according to the International Study Group criteria and 10 age- and sex-matched healthy controls were included. Detailed intestinal microbiota analysis was performed. RESULTS: There were no differences between the BD group and the control group in terms of alpha and beta microbial diversity and abundance indices (p>0.05). Actinomyces, Libanicoccus, Collinsella, Eggerthella, Enetrohabdus, Catenibacterium, and Enterobacter were significantly higher in the BD group than in the control group. In addition, Bacteroides, Cricetibacter, Alistipes, Lachnospira, Dielma, Akkermansia, Sutterella, Anaerofilum, Ruminococcease-UCG007, Acetanaerobacterium, and Copropaacter were lower in the BD group than in the control group. When we compared three different system involvement (eye, mucocutaneous, and vascular), the linear discriminant analysis effective size revealed a difference for the following genera: Lachnospiraceae NK4A136 in the uveitis group; Dialister, Intestinomonas, and Marvinbryantia in the mucocutaneous group; and Gemella in the vascular group. CONCLUSIONS: The composition of intestinal microbiota was significantly different in patients with BD compared with healthy adults. Ours is the first study to show differences in microbiota composition in isolated mucocutaneous, eye, and vascular involvement. These findings should be evaluated in a larger series.

Factors associated with damage in patients with familial Mediterranean fever.

OBJECTIVES: Defining predictors of damage would improve patient care. We applied damage indexes to patients with familial Mediterranean fever (FMF) and identified the predictors of damage. METHODS: This is a cross-sectional analysis of 926 FMF patients, who fulfilled the Tel-Hashomer criteria and had at least six months of follow-up. Patients were stratified according to their damage status (damage vs. no damage) defined with autoinflammatory disease damage index (ADDI) and modified ADDI (excluding musculoskeletal pain). We used logistic regression analysis to investigate independent predictors of damage for both indexes. RESULTS: Mean disease duration was 21.6±11.9 years. 527 patients (57%) had damage according to ADDI. Median ADDI score was 1 (0-11). Most common FMF-related damages were observed in musculoskeletal, reproductive and kidney domains. Female gender, inflammatory comorbidity, colchicine resistance, colchicine nonadherence, musculoskeletal attack dominance, diagnostic delay, follow-up time, and smoking history remained independent predictors of damage according to ADDI score. The rate of patients with damage defined by modified ADDI was only to 23%. M694V/M694V homozygosity, female gender, musculoskeletal attack dominance, colchicine resistance, persistent inflammation, follow up time and family history of amyloidosis were found to be predictors of damage according to modified ADDI score. CONCLUSIONS: Our study is the first to apply comprehensive damage indexes to FMF patients and identified predictors of damage. Factors linked to a severe FMF phenotype, including M694V homozygosity and persistent inflammation, were associated with only modified ADDI. Our findings justify the concerns about musculoskeletal pain and might point to the need for re-evaluation of ADDI for FMF patients.

Familial Mediterranean fever is associated with a wide spectrum of inflammatory disorders: results from a large cohort study.

Familial Mediterranean fever (FMF) is characterized by recurrent short-lived/self-limiting inflammatory attacks. Besides these, a substantial number of patients with FMF present with a variety of other inflammatory diseases; however, this issue has not been systematically studied previously. Hence, we aimed to investigate the frequency of inflammatory comorbid diseases in a large FMF cohort. All patients were recruited from "FMF in Central Anatolia (FiCA) Cohort", comprising 971 (mean age 35.3 ± 12 years, 61.5% female) adult subjects. All patients fulfilled Tel Hashomer criteria. Demographic data, FMF disease characteristics, MEFV gene mutations, and comorbid inflammatory diseases were meticulously questioned, and laboratory features and genotype data were retrieved from hospital records. There were comorbid inflammatory diseases in 205 (21.1%) patients. The most common inflammatory disease was spondyloarthritis (12.9%). Other remarkable inflammatory disorders were psoriasis, immunoglobulin A vasculitis/Henoch-Schönlein purpura, Behçet's disease and inflammatory bowel diseases. Cryptogenic organizing pneumonia is a newly defined entity in our cohort which is seemed to be associated with FMF (0.3%). Number of patients with persistent inflammation was higher in those with comorbid diseases (p < 0.001). Our results suggest that FMF is commonly associated with other inflammatory diseases. Therefore, clinicians should be cautious about comorbid inflammatory diseases in FMF patients, particularly in those with persistent inflammation. Identification of pathogenic pathways linking FMF to these diseases warrants further investigations.

Colchicine intolerance in FMF patients and primary obstacles for optimal dosing

Background/aim: Colchicine is the mainstay of treatment in FMF. However, in daily practice it is not easy to maintain effective colchicine doses in a substantial number of patients due to its side effects. In this study, we aimed to investigate prevalence and risk factors for colchicine side effects that limit optimal drug dosing and cause permanent discontinuation. Materials and methods: All patients were recruited from "FMF in Central Anatolia" (FiCA) cohort, 915 adults with a minimum follow- up time of 6 months during which they had obeyed all treatment instructions. Demographic and anthropometric data, FMF disease characteristics, disease severity, complications, and treatment features were recorded on a web-based registry. Prevalence of colchicine intolerance and characteristics of intolerant patients were analyzed. Results: Effective colchicine doses cannot be maintained in 172 (18.7%) subjects. Main side effects that limit optimal dosing were as follows: diarrhea in 99 (10.8%), elevation in transaminases in 54 (5.9%), leukopenia in 10 (%1.1), renal impairment in 14 (1.3%), myopathy in five (0.5%), and allergic skin reaction in two. Colchicine had to be permanently ceased in 18 (2%) patients because of serious toxicity. Male sex and obesity were found to be associated with liver toxicity, and having a normal body weight was associated with diarrhea. Chronic inflammation and proteinuria were more common in colchicine-intolerant patients, and they had reported more frequent attacks compared to those tolerating optimal doses. Conclusion: Colchicine intolerance is an important problem in daily clinical practice, mainly due to diarrhea and liver toxicity. Suboptimal colchicine dosing is associated with complications.

Circulating endothelial cells in Behçet's disease: is there a relationship with vascular involvement?

OBJECTIVES: Circulating endothelial cells (CEC) are identified in conditions with vascular damage such as systemic vasculitis. Our aim was to investigate if EPC, CEC, and/or its subgroups activated CEC (aCEC) or resting CEC (rCEC) related with vascular involvement in Behçet's disease (BD). METHODS: In total 60 patients were included in this study, divided into 4 groups: 1) Behçet patients with a history of vascular involvement: vascular BD; 2) Behçet patients with mucocutaneus involvement: mucocutaneus BD; 3) patients with history of thrombosis due to other causes: thrombosis; 4) 20 healthy controls were also included: control group. Percentages of CEC, aCEC, rCEC and EPCs in peripheral blood mononuclear cells were measured by flow cytometry. RESULTS: CEC (3.75 (1.80-7.20), 1.80 (0.70-3.53), 3.50 (1.83-7.23), 2.45 (1.28- 4.60)) and aCEC (2.40 (1.28-4.28), 1.10 (0.77-2.20), 3.15 (1.48-7.20), 3.20 (1.15-9.80) levels were did not show a statistically significant difference between groups (p:0.077 and p:0.054, respectively). EPC and rCEC levels were higher in vascular BD and thrombosis groups than mucocutaneus BD and control groups (EPC:10.5 (7.20-18.3), 11.6 (7.30-20.9) vs. 7.15 (5.55-8.25), 10.2 (5.93-18.6), rCEC: 5.35 (3.13-7.90), 6.45 (4.60-10.8) vs. 4.95 (3.05-7.55), 3.40 (1.88-4.30), p:0.042 and p:0.007, respectively). CONCLUSIONS: CEC, EPC, aCEC and rCEC may have role in the assessment of vascular involvement in BD. Longitudinal studies would be needed to identify the utility of these cells for the follow up and risk stratification of BD patients with vascular involvement for recurrences or identify BD patients at risk of vascular involvement.

Prevalence of comorbid diseases in patients with fibromyalgia: A retrospective cross-sectional study.

OBJECTIVE: To examine the prevalence of comorbid conditions in patients diagnosed with fibromyalgia. METHODS: The retrospective cross-sectional study was conducted at Eskisehir Osmangazi University, Eskisehir, Turkey, and comprised data of fibromyalgia patients aged 18 years or more admitted between January 1, 2012 and August 15, 2016. Hospital's database was investigated using the International Classification of Diseases, 10th Revision codes to identify fibromyalgia cases and predetermined comorbid conditions. SPSS 21 was used for data analysis. RESULTS: Of 509 patients, 51(10%) were males and 458(90%) were females with an overall mean age of 50.24±12.32 years. Of the total, 345(67.8%) patients had at least one comorbid disease, while 164(32.2%) had no comorbid disease. The most prevalent condition was cardiovascular diseases in 187(36.7%) patients followed by endocrine diseases in 157(30.8%). CONCLUSIONS: Fibromyalgia is a disease that is seen to be increasing in frequency in recent years. It is useful to evaluate fibromyalgia patients with their comorbid conditions on their follow-up.

Methodology of a new inflammatory arthritis registry: TReasure

Background/aim: The TReasure registry, created in 2017, is an observational multicenter cohort that includes inflammatory arthritis patients. This article reviews the methodology and objectives of the TReasure registry established to collect data from rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients. Methodology: Fifteen rheumatology centers in Turkey will contribute data to the TReasure database. The actual proprietor of the database is the Hacettepe Rheumatology Association (HRD) and Hacettepe Financial Enterprises. Pharmaceutical companies that operate in Turkey (in alphabetical or er), Abbvie, Amgen, BMS, Celltrion Healthcare, Novartis, Pfizer, Roche, and UCB, support the TReasure registry. TReasure is a web-based database to which users connect through a URL (https://www.trials-network.org/treasure) with their unique identifier and passwords provided for data entry and access. TReasure records demographic and clinical features, comorbidities, radiology and laboratory results, measures of disease activity, and treatment data. Discussion: TReasure will provide us with various types of data, such as a cross-sectional view of the current nationwide status of the patients currently receiving these treatments, and retrospective data as much as allowed by the participating centers' records. Finally, a high-quality prospective dataset will be built over the ensuing years from patients with a new diagnosis of RA or SpA.

Comparison of methotrexate and azathioprine as the first-line steroid-sparing immunosuppressive agents in patients with Takayasu's arteritis.

BACKGROUND: Immunosuppressive (IS) agents are recommended for the first-line treatment of patients with active Takayasu's arteritis (TAK) together with glucocorticoids (GCs). However, there is limited data comparing the efficacy and outcomes of different IS agents for this purpose. OBJECTIVES: In this study, we aimed to compare the outcomes of two most frequently used first-line IS agents, namely methotrexate (MTX) and azathioprine (AZA) in TAK patients. METHODS: TAK patients who received any IS agent in addition to GCs as the initial therapy were included in this multicentre, retrospective cohort study. Clinical, laboratory and imaging data of the patients were assessed. In addition, a matched analysis (cc match) using variables 'age', 'gender' and 'diffuse aortic involvement' was performed between patients who received MTX or AZA as the first-line IS treatment. RESULTS: We recruited 301 patients (F/M: 260/41, mean age: 42.2 ± 13.3 years) from 10 tertiary centres. As the first-line IS agent, 204 (67.8 %) patients received MTX, and 77 (25.6 %) received AZA. Less frequently used IS agents included cyclophosphamide in 17 (5.6 %), leflunomide in 2 (0.5 %) and mycophenolate mofetil in one patient. The remission, relapse, radiographic progression and adverse effect rates were similar between patients who received MTX and AZA as the first-line IS agent. Vascular surgery rate was significantly higher in the AZA group (23% vs. 9 %, p = 0.001), whereas the frequency of patients receiving ≤5 mg/day GCs at the end of the follow-up was significantly higher in the MTX group (76% vs 62 %, p = 0.034). Similarly, the rate of vascular surgery was higher in AZA group in matched analysis. Drug survival was similar between MTX and AZA groups (median 48 months, MTX vs AZA: 32% vs 42 %, p = 0.34). IS therapy was discontinued in 18 (12 MTX, 6 AZA) patients during the follow-up period due to remission. Among those patients, two patients had a relapse at 2 and 6 months, while 16 patients were still on remission at the end of a mean 69.4 (±50.9) months of follow-up. CONCLUSIONS: Remission, relapse, radiographic progression and drug survival rates of AZA and MTX were similar for patients with TAK receiving an IS agent as the first-line f therapy. The rate of vascular surgery was higher and the rate of GC dose reduction was lower with AZA compared to MTX at the end of the follow-up.

Unveiling cancer risk in ANCA-associated vasculitis: result from the Turkish Vasculitis Study Group (TRVaS).

To investigate cancer incidence in patients with ANCA-associated vasculitis (AAV), compare it with the age/sex-specific cancer risk of the Turkish population, and explore independent risk factors associated with cancer. This multicenter, incidence case-control study was conducted using the TRVaS registry. AAV patients without cancer history before AAV diagnosis were included. Demographic and AAV-related data of patients with and without an incident cancer were compared. Standardized cancer incidence rates were calculated using age-/sex-specific 2017 Turkish National Cancer Registry data for cancers (excluding non-melanoma skin cancers). Cox regression was performed to find factors related to incident cancers in AAV patients. Of 461 AAV patients (236 [51.2%] male), 19 had incident cancers after 2022.8 patient-years follow-up. Median (IQR) disease duration was 3.4 (5.5) years, and 58 (12.6%) patients died [7 with cancer and one without cancer (log-rank, p = 0.04)]. Cancer-diagnosed patients were older, mostly male, and more likely to have anti-PR3-ANCA positivity. The cumulative cyclophosphamide dose was similar in patients with and without cancer. Overall cancer risk in AAV was 2.1 (SIR) ((1.3-3.2), p = 0.004); lung and head-neck [primary target sites for AAV] cancers were the most common. In Cox regression, male sex and ≥ 60 years of age at AAV diagnosis were associated with increased cancer risk, while receiving rituximab was associated with decreased cancer risk. Cancer risk was 2.1 times higher in AAV patients than the age-/sex-specific cancer risk of the Turkish population population, despite a high rate of rituximab use and lower dose of cyclophosphamide doses. Vigilance in cancer screening for AAV patients covering lung, genitourinary, and head-neck regions, particularly in males and the elderly, is vital.

Frequency and the effects of spondyloarthritis-spectrum disorders on the clinical course and management of Takayasu arteritis: an observational retrospective study.

OBJECTIVES: Extravascular findings of Takayasu arteritis (TAK) often share features with the spondyloarthritis (SpA) spectrum of disorders. However, the characteristics of this overlap and its effect on the vascular manifestations of TAK are not fully known. Therefore, we aimed to investigate the frequency of SpA-related features in TAK patients. MATERIAL AND METHODS: In this observational retrospective study, 350 patients with TAK classified according to ACR 1990 criteria, from 12 tertiary rheumatology clinics, were included and evaluated for the presence of axSpA, IBD, or psoriasis. Demographic, clinical features, angiographic involvement patterns, disease activity, and treatments of TAK patients with or without SpA were analyzed. RESULTS: Mean age was 45.5 ± 13.6 years and mean follow-up period was 76.1 ± 65.9 months. Among 350 patients, 31 (8.8%) had at least one additional disease from the SpA spectrum, 8 had IBD, 8 had psoriasis, and 20 had features of axSpA. In the TAK-SpA group, TAK had significantly earlier disease onset, compared to TAK-without-SpA (p = 0.041). SpA-related symptoms generally preceded TAK symptoms. Biological treatments, mostly for active vasculitis, were higher in the TAK-SpA group (70.9%) compared to TAK-without-SpA (27.9%) (p < 0.001). Vascular involvements were similar in both. CONCLUSION: Our study confirmed that diseases in the SpA spectrum are not rare in TAK. Vascular symptoms appeared earlier in such patients, and more aggressive therapy with biological agents was required in the TAK-SpA group, suggesting an association between TAK and SpA spectrum. Key Points • The pathogenesis of Takayasu arteritis is mediated by an MHC class I alelle (HLA-B*52), similar to spondyloarthritis-disorders. • Extravascular findings of Takayasu arteritis are in the spectrum of spondyloarthritis disease. • This frequent coexistence between Takayasu arteritis and spondyloarthritic disorders suggests a relationship rather than a coincidence.

Werner's syndrome may be lost in the shadow of the scleroderma.

We describe three patients with Werner's syndrome (WS), two of whom had been mistakenly diagnosed as having scleroderma. We would like to discuss briefly the importance of differentiation of these two disorders from each other.

Regulatory T cells in Behçet's disease: is there a correlation with disease activity? Does regulatory T cell type matter?

The aim of this study was to investigate the percentage of regulatory T cells and the correlation with clinical activity in Behçet's disease. Forty Behçet's disease (BD) patients, 18 males and 22 females, were included in the study. The patients were diagnosed according to the published BD criteria. Twenty age- and sex-matched volunteer healthy donors were also included. At the time of sampling, clinical activity was assessed for activity signs and symptoms according to the BD Current Activity Form. We considered active those patients with a clinical activity index equal to and/or above 2. Eleven patients had active disease and the remaining were considered as clinically inactive. We have studied the percentages of CD4+CD25+FOXP3+, CD4+CD25+ and CD4+FOXP3+regulatory T cells by flow cytometry and investigated the correlation with disease activity. Percentage of CD4+CD25+FOXP3+Treg in active patients was lower than clinically inactive patients and healthy controls. Percentage of CD4+CD25+Treg was not different between active and inactive patients and healthy controls. Percentage of CD4+FOXP3+Treg was lower than healthy controls in clinically active patients but was not different for inactive group and healthy controls. Patients were active when CD4+CD25+FOXP3+Treg was ≤1.19 %, CD4+CD25+Treg was ≤2.68 %, and CD4+FOXP3+Treg was ≤2.60. CD4+CD25+FOXP3+Treg and CD4+FOXP3+Treg were found negatively correlated with disease activity. Peripheral blood regulatory T cells are decreased in clinically active Behçet's disease patients. The advances in our understanding of the interactions between distinct subsets of Treg and clinical activity might help in modulating BD treatment.

Scoping beyond pulmonary artery involvement; pulmonary involvement in Behcet's disease; a retrospective analysis of 28 patients.

OBJECTIVES: Pulmonary involvement other than pulmonary artery involvement in Behcet's disease still remains an area of investigation. The aim of this study was to evaluate pulmonary involvement associated with Behcet's disease. METHOD: We retrospectively investigated all Behcet's disease patients in terms of pulmonary involvement. Twenty-eight patients, whose radiologic examinations were consistent with Behcet's disease-related involvement after excluding other possibilities, were included in this study. Data regarding demographic characteristics, other clinical components of Behcet's disease, treatment modalities, and types of pulmonary involvement were analyzed. RESULTS: Pulmonary involvement was seen more common in male (82.1% vs 17.9%). Mean age for Behcet's disease diagnosis was found 32 years (SD 10.9) and mean age for pulmonary involvement was calculated 37 years (SD 11.4). Deep vein thrombosis (DVT) was the most common associated vascular involvement (53.6%). In our study population, alveolar hemorrhage and/or ground glass appearance were seen in 46.4% (13/28) of BD patients with pulmonary involvement. Totally, pulmonary artery aneurysm (PAA), small-sized pulmonary vasculitis (sPV), and pulmonary thrombosis (PT) were seen in 7 (25%), 13 (46.3%), and 18 (64.4%) of patients, respectively. Intracardiac thrombosis (ICT) in the right ventricle was present in 5 patients. Cyclophosphamide (CYC) was the most common preferred agent (78%) followed by azathioprine (AZA) in the first line. Warfarin was used in 18 patients. Overall mortality was seen in 3 patients: 1 due to PAA bleeding and others with unknown causes. CONCLUSION: Despite the importance of pulmonary artery involvement and pulmonary thrombosis in Behcet's disease, small-sized pulmonary vasculitis in the form of small vessel involvement is generally overlooked. Our study findings have shown that alveolar hemorrhage and/or ground-glass appearance in the absence of pulmonary artery aneurysm and pulmonary thrombosis are seen commonly as well. Key Points • The characteristics of pulmonary small vasculature involvement in Behcet's disease which is still an area of investigation warrant further attention. • The clinician should bear in mind that the spectrum of pulmonary involvement in Behcet's disease may be variable, but an extensive work up is still of great importance especially in atypical cases.

Retrospective evaluation of 22 patients with Takayasu's arteritis.

Takayasu's arteritis (TA) is a rare, idiopathic, inflammatory, granulomatous vasculitis that affects the aorta and its primary branches. Clinical features and the pattern of arterial involvement show differences in different regions of the world according to ethnic influences. Our aim in this retrospective study was to evaluate the demographic, clinic, laboratory, and angiographic findings of 22 patients with TA followed by our clinic and also compare our results with series from the literature. The hospital files of the 22 patients followed by our clinic between 1998 and 2009 were retrospectively evaluated. We also compared our results with the series from the literature that we were able to reach by US National Library of Medicine, National Institute of Health. Gender distribution, age at diagnosis, and type of aortic involvement were similar with the study from Turkey. Different clinical manifestations of Takayasu's arteritis have been described in different ethnic groups. We also want to underline the coincidence of TA and other rheumatic diseases such as sarcoidosis, SLE, RA, and psoriatic arthritis, different from other published series.