Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study.

Takayasu arteritis is a rare inflammatory disease of large arteries. We performed a genetic study in Takayasu arteritis comprising 6,670 individuals (1,226 affected individuals) from five different populations. We discovered HLA risk factors and four non-HLA susceptibility loci in VPS8, SVEP1, CFL2, and chr13q21 and reinforced IL12B, PTK2B, and chr21q22 as robust susceptibility loci shared across ancestries. Functional analysis proposed plausible underlying disease mechanisms and pinpointed ETS2 as a potential causal gene for chr21q22 association. We also identified >60 candidate loci with suggestive association (p < 5 × 10-5) and devised a genetic risk score for Takayasu arteritis. Takayasu arteritis was compared to hundreds of other traits, revealing the closest genetic relatedness to inflammatory bowel disease. Epigenetic patterns within risk loci suggest roles for monocytes and B cells in Takayasu arteritis. This work enhances understanding of the genetic basis and pathophysiology of Takayasu arteritis and provides clues for potential new therapeutic targets.

Ocular manifestations of granulomatosis with polyangiitis: report from a tertiary eye care center.

PURPOSE: To report demographic characteristics and ophthalmological manifestations of patients with granulomatosis with polyangiitis (GPA) in a tertiary eye care center in Turkey. METHODS: Medical records of patients with GPA-related ocular manifestations evaluated between 2013 and 2023 were included. Demographic and clinical characteristics of the patients including nature of systemic involvement, ophthalmologic symptoms and signs, laboratory investigations and treatment modality were reviewed. RESULTS: Twelve eyes of 10 patients (5 female/5 male) were included. The mean age was 57.2 ± 12.2 (35-71) years. Five (50%) patients were already diagnosed with GPA. Ocular involvement was the first manifestation of GPA in 3 patients. The remaining 2 patients had simultaneous systemic and ocular symptoms at presentation. Conjunctival hyperemia (9 eyes) and pain (7 eyes) were the most frequent presenting symptoms followed by blurred vision (3 eyes). The frequencies of ocular manifestations were as follows:episcleritis (3 eyes), isolated peripheral ulcerative keratitis (PUK) (3 eyes), scleritis (3 eyes), simultaneous PUK and scleritis (2 eyes) and periorbital mass (1 eye). CONCLUSION: Ophthalmological manifestations can be the initial findings in GPA. Since GPA can affect different structures of the eye, it sometimes might be challenging for ophthalmologists. Therefore, it is crucial for ophthalmologists to be well-informed about GPA-related ocular findings and to have a high index of suspicion for GPA. Although PUK associated with scleritis is highly suggestive for GPA, isolated cases of PUK or scleritis can be seen in GPA. Therefore, it is important to adopt a multidisciplinary approach, consider GPA in differential diagnosis, and benefit from accurate diagnostic tests.

Low relapse rate in patients with giant cell arteritis in a multi-centre retrospective Turkish Registry.

OBJECTIVES: Glucocorticoids (GC) are widely accepted as the standard first-line treatment for giant cell arteritis (GCA). However, relapse rates are reported up to 80% on GC-only protocol arms in controlled trials of tocilizumab and abatacept in 12-24 months. Herein, we aimed to assess the real-life relapse rates retrospectively in patients with GCA from Turkey. METHODS: We assembled a retrospective cohort of patients with GCA diagnosed according to ACR 1990 criteria from tertiary rheumatology centres in Turkey. All clinical data were abstracted from medical records. Relapse was defined as any new manifestation or increased acutephase response leading to the change of the GC dose or use of a new therapeutic agent by the treating physician. RESULTS: The study included 330 (F/M: 196/134) patients with GCA. The mean age at disease onset was 68.9±9 years. The most frequent symptom was headache. Polymyalgia rheumatica was also present in 81 (24.5%) patients. Elevation of acute phase reactants (ESR>50 mm/h or CRP>5 mg/l) was absent in 25 (7.6%) patients at diagnosis. Temporal artery biopsy was available in 241 (73%) patients, and 180 of them had positive histopathological findings for GCA. For remission induction, GC pulses (250-1000 methylprednisolone mg/3-7 days) were given to 69 (20.9%) patients, with further 0.5-1 mg/kg/day prednisolone continued in the whole group. Immunosuppressives as GC-sparing agents were used in 252 (76.4%) patients. During a follow-up of a median 26.5 (6-190) months, relapses occurred in 49 (18.8%) patients. No confounding factor was observed in relapse rates. GC treatment could be stopped in only 62 (23.8%) patients. Additionally, GC-related side effects developed in 64 (24.6%) patients, and 141 (66.2%) had at least one Vasculitis Damage Index (VDI) damage item present during follow-up. CONCLUSIONS: In this first multi-centre series of GCA from Turkey, we observed that only one-fifth of patients had relapses during a mean follow-up of 26 months, with 76.4% given a GC-sparing IS agent at diagnosis. At the end of follow-up, GC-related side effects developed in one-fourth of patients. Our results suggest that patients with GCA had a low relapse rate in real-life experience of a multi-centre retrospective Turkish registry, however with a significant presence of GC-associated side effects during follow-up.

Does decision tree analysis predict oral ulcer activity-related factors in patients with Behçet's syndrome?

OBJECTIVES: The study aimed to identify the interactions among treatment protocols and oral ulcer activity related factors in patients with Behçet's syndrome (BS) using the Classification and Regression Tree (CART) algorithm. METHODS: In this cross-sectional study, 979 patients with BS were included from16 centres in Turkey, Jordan, Brazil and the United Kingdom. In the CART algorithm, activities of oral ulcer (active vs. inactive), genital ulcer (active vs. inactive), cutaneous involvement (active vs. inactive), musculoskeletal involvement (active vs. inactive), gender (male vs. female), disease severity (mucocutaneous and musculoskeletal involvement vs. major organ involvement), smoking habits (current smoker vs. non-smoker), tooth brushing habits (irregular vs. regular), were input variables. The treatment protocols regarding immunosuppressive (IS) or non-IS medications were the target variable used to split from parent nodes to purer child nodes in the study. RESULTS: In mucocutaneous and musculoskeletal involvement (n=538), the ratio of IS use was higher in patients with irregular toothbrushing (ITB) habits (27.1%) than in patients with regular toothbrushing (RTB) habits (14.2%) in oral ulcer activity. In major organ involvement (n=441), male patients with ITB habits were more likely treated with IS medications compared to those with RTB habits (91.6% vs. 77.6%, respectively). CONCLUSIONS: Male BS patients on IS who have major organ involvement and oral ulcer activity with mucocutaneous and musculoskeletal involvement have irregular toothbrushing habits. Improved oral hygiene practices should be considered to be an integral part for implementing patient empowerment strategies for BS.

Sex-specific analysis in Behçet's disease reveals higher genetic risk in male patients.

OBJECTIVES: Behçet's disease tends to be more severe in men than women. This study was undertaken to investigate sex-specific genetic effects in Behçet's disease. METHODS: A total of 1762 male and 1216 female patients with Behçet's disease from six diverse populations were studied, with the majority of patients of Turkish origin. Genotyping was performed using an Infinium ImmunoArray-24 BeadChip, or extracted from available genotyping data. Following imputation and extensive quality control measures, genome-wide association analysis was performed comparing male to female patients in the Turkish cohort, followed by a meta-analysis of significant results in all six populations. In addition, a weighted genetic risk score for Behçet's disease was calculated and compared between male and female patients. RESULTS: Genetic association analysis comparing male to female patients with Behçet's disease from Turkey revealed an association with male sex in HLA-B/MICA within the HLA region with a GWAS level of significance (rs2848712, OR = 1.46, P = 1.22 × 10-8). Meta-analysis of the effect in rs2848712 across six populations confirmed these results. Genetic risk score for Behçet's disease was significantly higher in male compared to female patients from Turkey. Higher genetic risk for Behçet's disease was observed in male patients in HLA-B/MICA (rs116799036, OR = 1.45, P = 1.95 × 10-8), HLA-C (rs12525170, OR = 1.46, P = 5.66 × 10-7), and KLRC4 (rs2617170, OR = 1.20, P = 0.019). In contrast, IFNGR1 (rs4896243, OR = 0.86, P = 0.011) was shown to confer higher genetic risk in female patients. CONCLUSIONS: Male patients with Behçet's disease are characterized by higher genetic risk compared to female patients. This genetic difference, primarily derived from our Turkish cohort, is largely explained by risk within the HLA region. These data suggest that genetic factors might contribute to differences in disease presentation between men and women with Behçet's disease.

Oral ulcer activity assessment with the composite index according to different treatment modalities in Behçet's syndrome: a multicentre study.

OBJECTIVES: The aim of this multicentre study was to understand patients' needs and to evaluate the oral ulcer activity with the Composite Index (CI), according to different treatment modalities in Behçet's syndrome (BS). METHODS: BS patients (n=834) from 12 centres participated in this cross-sectional study. Oral ulcer activity (active vs. inactive) and the CI (0: inactive vs. 1-10 points: active) were evaluated during the previous month. The effects of treatment protocols [non-immunosuppressive: non-IS vs. immunosuppressive: (ISs)], severity (mild vs. severe), disease duration (<5 years vs. ≥5 years) and smoking pattern (non-smoker vs. current smoker) were analysed for oral ulcer activity. RESULTS: Oral ulcer activity was observed in 65.1% of the group (n=543). In both genders, the activity was higher in mild disease course with non-IS treatment group compared to severe course with ISs (p<0.05). As a resistant group, patients with mild disease course whose mucocutaneous symptoms were unresponsive to non-IS medications were treated with ISs in a limited period and achieved the highest CI scores in females. Oral ulcer activity and poor CI score were associated with disease duration less than 5 years compared to others in male patients (p<0.05). CONCLUSIONS: Oral ulcer activity pattern is affected by both the combination of disease course, treatment protocols and disease duration. CI scores reflected the oral clinical activity and CI might be a candidate scale to evaluate the efficacy of treatments during the follow-up of oral ulcer activity in BS.

Diagnosis and differential diagnosis of large-vessel vasculitides.

There are no universally accepted diagnostic criteria for large-vessel vasculitides (LVV), including giant cell arteritis (GCA) and Takayasu arteritis (TAK). Currently, available classification criteria cannot be used for the diagnosis of GCA and TAK. Early diagnosis of these two diseases is quite challenging in clinical practice and may be accomplished only by combining the patient symptoms, physical examination findings, blood test results, imaging findings, and biopsy results, if available. Awareness of red flags which lead the clinician to investigate TAK in a young patient with persistent systemic inflammation is helpful for the early diagnosis. It should be noted that clinical presentation may be highly variable in a subgroup of GCA patients with predominant large-vessel involvement (LVI) and without prominent cranial symptoms. Imaging modalities are especially helpful for the diagnosis of this subgroup. Differential diagnosis between older patients with TAK and this subgroup of GCA patients presenting with LVI may be difficult. Various pathologies may mimic LVV either by causing systemic inflammation and constitutional symptoms, or by causing lumen narrowing with or without aneurysm formation in the aorta and its branches. Differential diagnosis of aortitis is crucial. Infectious aortitis including mycotic aneurysms due to septicemia or endocarditis, as well as causes such as syphilis and mycobacterial infections should always be excluded. On the other hand, the presence of non-infectious aortitis is not unique for TAK and GCA. It should be noted that aortitis, other large-vessel involvement or both, may occasionally be seen in various other autoimmune pathologies including ANCA-positive vasculitides, Behçet's disease, ankylosing spondylitis, sarcoidosis, and Sjögren's syndrome. Besides, aortitis may be idiopathic and isolated. Atherosclerosis should always be considered in the differential diagnosis of LVV. Other pathologies which may mimic LVV include, but not limited to, congenital causes of aortic coarctation and middle aortic syndrome, immunoglobulin G4-related disease, and hereditary disorders of connective tissue such as Marfan syndrome and Ehler-Danlos syndrome.

Discrepancies between vascular and systemic inflammation in large vessel vasculitis: an important problem revisited.

A lack of absolute correlation between systemic inflammation parameters and ongoing vascular disease activity is an important problem in some patients with large vessel vasculitis, especially Takayasu arteritis (TAK). Systemic and vascular wall inflammation in TAK are obviously interrelated, but sometimes they may act independently. There are clear discrepancies between these two types of inflammation, including cytokine patterns and responses to treatment. Vascular and systemic inflammation may also be discordant in two subgroups of giant cell arteritis. The first subgroup is mainly characterized by severe systemic inflammation mostly associated with IL-6-driven immunity, while in the second subgroup there is less systemic inflammation but prominent neuro-ophthalmic ischaemic complications characterized mostly by IFN-γ-mediated effects. Although no definite boundaries exist, it may be suggested that the IL-6/Th17/IL-17 pathway primarily drives systemic inflammation while the IL-12/Th1/IFN-γ pathway dominates in vascular wall inflammation both in TAK and giant cell arteritis. Immunosuppressive treatment of TAK (especially corticosteroids) initially suppresses systemic inflammation, while longer treatment duration is required for the suppression of vascular inflammation. Therefore, evaluating only the systemic inflammation may be misleading. Vascular wall inflammation is currently evaluated using expensive imaging methods, which are not feasible for repetitive use. Although pentraxin-3 is superior to erythrocyte sedimentation rate and CRP, we need more reliable biomarkers to reflect vascular wall inflammation in patients with TAK.

Takayasu arteritis: an update

Takayasu arteritis (TAK) is a challenging chronic, granulomatous, large-vessel systemic vasculitis, mostly due to difficulties in early diagnosis and assessing actual disease activity. Since there are no specific diagnostic laboratory tests, biomarkers, or autoantibodies, many patients experience considerable delay in diagnosis. Remembering the possibility of TAK together with the use of acute phase responses and appropriate imaging studies may be helpful for early diagnosis. Since there may be discrepancies between systemic and vascular wall inflammation, using only acute phase responses is not reliable in assessing current disease activity. Therefore, physical examination and new imaging findings should also be used to assess current disease activity. Despite its limitations, the Indian Takayasu Clinical Activity Score (ITAS2010) may also be helpful for this purpose. The rationale of medical treatment is to suppress both vascular and systemic inflammation with appropriate systemic immunosuppression, including corticosteroids and conventional immunosuppressive agents. In cases of refractory disease activity, leflunomide and biologic agents such as TNF inhibitors and tocilizumab may be tried. In selected cases with persistent lesions that cannot be reversed with medical treatment, endovascular interventions including balloon angioplasty, stent and stent graft replacement, or surgery may be tried. However, such procedures should be performed after suppression of inflammation, i.e. during inactive disease. Prognosis of TAK is probably getting better with lower mortality rates reported in recent years, probably due to the use of more effective medical treatments as well as the use of endovascular interventions when necessary and available.

Identification of multiple genetic susceptibility loci in Takayasu arteritis.

Takayasu arteritis is a rare inflammatory disease of large arteries. The etiology of Takayasu arteritis remains poorly understood, but genetic contribution to the disease pathogenesis is supported by the genetic association with HLA-B*52. We genotyped ~200,000 genetic variants in two ethnically divergent Takayasu arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform (Immunochip). Additional genetic variants and the classical HLA alleles were imputed and analyzed. We identified and confirmed two independent susceptibility loci within the HLA region (r(2) < 0.2): HLA-B/MICA (rs12524487, OR = 3.29, p = 5.57 × 10(-16)) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 × 10(-9); and rs189754752, OR = 2.47, p = 4.22 × 10(-9)). In addition, we identified and confirmed a genetic association between Takayasu arteritis and the FCGR2A/FCGR3A locus on chromosome 1 (rs10919543, OR = 1.81, p = 5.89 × 10(-12)). The risk allele in this locus results in increased mRNA expression of FCGR2A. We also established the genetic association between IL12B and Takayasu arteritis (rs56167332, OR = 1.54, p = 2.18 × 10(-8)).

Response rate of initial conventional treatments, disease course, and related factors of patients with adult-onset Still's disease: Data from a large multicenter cohort.

BACKGROUND: Adult-onset Still's disease (AOSD) is a rare condition, and treatment choices are frequently dependent on expert opinions. The objectives of the present study were to assess treatment modalities, disease course, and the factors influencing the outcome of patients with AOSD. METHODS: A multicenter study was used to reach sufficient patient numbers. The diagnosis of AOSD was based on the Yamaguchi criteria. The data collected included patient age, gender, age at the time of diagnosis, delay time for the diagnosis, typical AOSD rash, arthralgia, arthritis, myalgia, sore throat, lymphadenopathy, hepatomegaly, splenomegaly, pleuritis, pericarditis, and other rare findings. The laboratory findings of the patients were also recorded. The drugs initiated after the establishment of a diagnosis and the induction of remission with the first treatment was recorded. Disease patterns and related factors were also investigated. A multivariate analysis was performed to assess the factors related to remission. RESULTS: The initial data of 356 patients (210 females; 59%) from 19 centers were evaluated. The median age at onset was 32 (16-88) years, and the median follow-up time was 22 months (0-180). Fever (95.8%), arthralgia (94.9%), typical AOSD rash (66.9%), arthritis (64.6%), sore throat (63.5%), and myalgia (52.8%) were the most frequent clinical features. It was found that 254 of the 306 patients (83.0%) displayed remission with the initial treatment, including corticosteroids plus methotrexate with or without other disease-modifying antirheumatic drugs. The multivariate analysis revealed that the male sex, delayed diagnosis of more than 6 months, failure to achieve remission with initial treatment, and arthritis involving wrist/elbow joints were related to the chronic disease course. CONCLUSION: Induction of remission with initial treatment was achieved in the majority of AOSD patients. Failure to achieve remission with initial treatment as well as a delayed diagnosis implicated a chronic disease course in AOSD.

Plasma pentraxin-3 levels in patients with Takayasu's arteritis during routine follow-up.

OBJECTIVES: To date, no biomarker is universally accepted to be a surrogate for active disease being one of major difficulties in follow-up of Takayasu's arteritis (TAK). In this study, we aimed to investigate plasma pentraxin-3 (PTX-3) levels and its correlation with activity in patients with TAK. METHODS: This cross-sectional study included 94 patients (age: 43.3±13.6 years, F/M: 80/14) with TAK, 40 age-sex matched control donors (age: 41.5±9.3 years, F/M: 28/12). TAK patients were evaluated by physician's global assessment (PGA; active/inactive), as well as with the activity definition by Kerr et al. and with a new composite index of ITAS2010 (Indian Takayasu Clinical Activity Score). Plasma PTX-3 levels are measured with an enzyme linked immunosorbent assay kit. RESULTS: Thirty-three (35.5%) patients were clinically active with PGA, while 25 (31.6%) patients and 28 (31.8%) patients were accepted to have active disease according to Kerr activity criteria and ITAS2010, respectively. Plasma PTX-3 levels were significantly higher in TAK patients compared to healthy controls (3.5±2.5 ng/ml vs. 2.5±1.6 ng/ ml, p=0.029). However, PTX-3 levels were similar among active and inactive patients according to all three assessment tools. PTX-3 levels significantly correlated only with serum CRP levels. CONCLUSIONS: Although plasma PTX- 3 levels were higher in patients with TAK compared to healthy controls, we observed no association with disease activity, limiting the role of PTX-3 level as a biomarker for active disease in TAK.

Epidemiology of Takayasu's arteritis in Turkey.

OBJECTIVES: To estimate the prevalence and incidence of Takayasu arteritis (TA) among the residents of the city of Izmir, the third largest metropolis in Turkey. METHODS: Five tertiary care teaching hospitals, which were the only ones that provided rheumatology specialty care during the study period in the city of Izmir from 2006 through 2010, were invited to take part in the present study. A case search was performed electronically in the information systems of these hospitals using The International Classification of Diseases Tenth Revision (ICD-10) code for Takayasu arteritis (M31.4). The diagnosis was confirmed through chart review by a rheumatologist according to the 1990 American College of Rheumatology (ACR) criteria. Annual prevalence was calculated based on the number of patients that were alive at the end of 2010. Age- and sex-adjusted prevalence rates were standardised according to the 2010 Turkish population, based on 2010 Turkish Census. RESULTS: A total of 41 patients were confirmed to have TA and also to live within the targeted area. The annual prevalence was estimated as 12.8 (95% CI 12.0-13.6) per million; 23.5/million (95% CI 21.9-25.0) in females and 1.9/million (95% CI 1.5-2.4) in males. The prevalence was higher 8.8/million (95% CI 7.7-10.0) in the population >40 years of age. During the study period, the mean annual incidence of TA was estimated as 1.11/million (95% CI 0.54-1.67). CONCLUSIONS: The first epidemiologic study of TA in a Turkish population suggests that TA is a relatively common vasculitis in Turkey.

A relationship between spinal new bone formation in ankylosing spondylitis and the sonographically determined Achilles tendon enthesophytes.

Spinal new bone formation is a major but incompletely understood manifestation of ankylosing spondylitis (AS). We explored the relationship between spinal new bone formation and ultrasound (US)-determined Achilles enthesophytes to test the hypothesis that spinal new bone formation is part of a generalized enthesis bone-forming phenotype. A multicenter, case control study of 225 consecutive AS patients and 95 age/body mass index (BMI) matched healthy controls (HC) was performed. US scans of Achilles tendons and cervical and lumbar spine radiographs were obtained. All images were centrally scored by one investigator for US and one for radiographs, blinded to medical data. The relation between syndesmophytes (by modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) and the number of syndesmophytes) and enthesophytes (with a semi-quantitative scoring of the US findings) was investigated. AS patients had significantly higher US enthesophyte scores than HCs (2.1(1.6) vs. 1.6(1.6); p = 0.004). The difference was significant in males (p = 0.001) but not in females (p = 0.5). The enthesophyte scores significantly correlated with mSASSS scores (ρ = 0.274, p < 0.0001) with the association even stronger in males (enthesophyte scores vs. mSASSS ρ = 0.337, p < 0.0001). In multiple regression analysis, age, BMI, enthesophyte scores and disease duration were significantly associated with syndesmophytes in males, and keeping all other variables constant, increasing US enthesophyte scores increased the odds of having syndesmophytes by 67%. Male AS patients that have more severe US-determined Achilles enthesophyte also associated spinal syndesmophytes suggesting a bone-forming gender-specific phenotype that could be a useful marker predicting of new bone formation.

Plasma thiopurine S-methyltransferase levels and azathioprine-related adverse events in patients with Behçet's disease.

OBJECTIVES: Thiopurine S-methyltransferase (TPMT) is the key enzyme inactivating azathioprine (AZA), an immunosuppressive agent commonly used for treating inflammatory diseases including Behçet's disease (BD), systemic lupus erythematosus (SLE) and systemic vasculitis. Low TPMT levels facilitate occurrence of AZA-related adverse effects. We investigated TPMT levels in patients with BD, compared to healthy controls and patients with SLE or systemic vasculitis. METHODS: This cross-sectional study included 101 BD (77 using AZA), 74 SLE (35 using AZA), and 44 vasculitis (18 using AZA) patients and 101 healthy controls. Plasma TPMT levels were measured using ELISA. Student's t- and Kruskal-Wallis tests were used to compare TPMT levels according to possible risk factors. Receiver operating characteristic (ROC) analysis was used to determine whether a cut-off TPMT level could be found to predict AZA-related adverse effects. RESULTS: Plasma TPMT levels (mean± SD ng/mL) in BD (22.80±13.81) were comparable with healthy controls (22.71±13.49), but significantly lower than in SLE group (29.37±11.39) (p<0.001). TPMT levels in 130 patients receiving AZA were similar to the rest of the group. AZA-related adverse effects were identified in only 8 patients (5 with BD and 3 with SLE). TPMT levels were significantly lower in those 8 patients (14.08±9.49 vs. 25.62±12.68) (p=0.013), besides a cut-off value for predicting adverse effects was determined for the BD group with ROC analysis (area under the curve: 0.813). CONCLUSIONS: This is the first study to evaluate TPMT activity in a Turkish adult population. Although low plasma TPMT level is not the only factor determining AZA toxicity, a TPMT cut-off value may help to predict AZA-related adverse effects in BD.

Management of Takayasu arteritis: a systematic review.

Assessment of the pattern and extent of arterial involvement and measurement of current disease activity are essential for the management of Takayasu arteritis (TA). Since there is no completed, placebo-controlled, randomized clinical trial, the level of evidence for management of TA is low, generally reflecting the results of open studies, case series and expert opinion. The most commonly used agents include corticosteroids and conventional immunosuppressive agents such as MTX, AZA, MMF and LEF. In patients who remain resistant and/or intolerant to these agents, biologic drugs including TNF inhibitors, rituximab and tocilizumab seem to be promising. Antiplatelet treatment may also lower the frequency of ischaemic events in TA. In the presence of short-segment, critical arterial stenosis, balloon angioplasty or stent graft replacement may be useful. On the other hand, long-segment stenosis with extensive periarterial fibrosis or occlusion requires surgical bypass of the affected segment, which is clearly associated with superior results compared with endovascular intervention. As a general rule, both endovascular intervention and surgical procedures should be avoided during the active phase of the disease. Earlier diagnosis, better assessment of disease activity and future clinical trials will obviously improve the management of TA.

Impact of rheumatoid arthritis in Turkey: a questionnaire study.

OBJECTIVES: Unmet needs of rheumatoid arthritis (RA) patients regarding physician/patient communication, treatment preferences and quality of life issues were investigated in a Turkish survey study. METHODS: The study was conducted with the contribution of 33 rheumatologists, and included 519 RA patients. The study population included patients who had been on biologic therapy for >6 months and were still receiving biologic therapy (BT group), and those who were biologic naive, but found eligible for biologic treatment (NBT group). Of the RA patients, 35.5% initially had a visit to an internal disease specialist, 25.5% to a physical therapy and rehabilitation specialist, and 12.2% to a rheumatology specialist for their RA complaints. The diagnosis of RA was made by a rheumatologist in 48.2% of patients. RESULTS: The majority of RA patients (86.3%) visit their doctor within 15-week intervals. Most of the physician-patient communication focused on disease symptoms (99.0%) and impact of the disease on quality of life (61.8%). The proportion of RA patients who perceived their health status as good/very good/excellent was higher in the BT group than in the NBT group (74.3% vs. 51.5%, p<0.001). However, of those RA patients in the NBT group, only 24.8% have been recommended to start a biologic treatment by their doctors. With respect to dose frequency options, once-monthly injections were preferred (80%) to a bi-weekly injection schedule (8%). CONCLUSIONS: In conclusion, RA patients receiving biologic therapy reported higher rates of improved symptoms and better quality of life and seemed to be more satisfied with their treatment in our study.

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.

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.

Impaired quality of life, disability and mental health in Takayasu's arteritis.

OBJECTIVE: Patient-reported outcomes (PROs) are increasingly accepted to be among the major tools for outcome assessment in rheumatic disorders. In this study we aimed to assess quality of life (QoL), disability, anxiety and depression in patients with Takayasu's arteritis (TAK). METHODS: Patients followed with the diagnosis of TAK (n = 165) and healthy controls (HCs) (n = 109) were enrolled to the study. The 36-item Short Form Health Survey (SF-36) and hospital anxiety and depression scales (HADS) were used to assess QoL and mental status together with HAQ for disability. RESULTS: In SF-36 subscale assessment, all items were observed to be statistically lower in TAK patients; similarly HAQ scores were also higher (P < 0.001) in this group. In mental assessment, anxiety was found to be more common in TAK patients [90 (54.5%) vs 38 (34.9%), P = 0.001]. Depression also tended to be higher in TAK patients [70 (66.7%) vs 35 (33.3%)], without reaching significance (P = 0.086). Most of the SF-36 subgroup parameters were lower in TAK patients with active disease. Patients having anxiety and depression or with high HAQ scores reported worse SF-36 scores. In multivariate analysis, HADS-A, HADS-D and HAQ were associated with most SF-36 subscales. CONCLUSION: PROs demonstrate that not only general health but also physical and social functioning with physical role limitations and mental health parameters were impaired in TAK. Our results, especially in active disease, suggest that PROs such as SF-36 can be core domains of disease assessment in TAK, similar to ANCA-associated vasculitides.