Imaging is the major determinant in the assessment of disease activity in Takayasu's arteritis.

OBJECTIVES: There are no valid follow-up parameters in the assessment of disease activity in Takayasu's arteritis (TAK). We investigated the impact of vascular imaging in the assessment of disease activity. METHODS: Patients with TAK who fulfilled the ACR criteria were included. Physician global assessment (PGA), the criteria defined by Kerr et al. and the Indian Takayasu Clinical Activity Score (ITAS2010) were evaluated. Patients were followed up since 3-6 months B-mode/Doppler ultrasonography (US) and 6-12 monthly magnetic resonance imaging/angiography (MRI/MRA). Active disease according to vascular imaging (Rad-Active) was defined based on the presence of any of the 3 parameters: (1) new vessel involvement by any imaging technique; (2) an increase in vessel wall thickness on US compared to previous one; (3) the presence of mural contrast enhancement/oedema on MRI/ MRA. The agreement of Rad-Active with other disease activity indexes was studied. Furthermore, ITAS-A-Rad index was developed by combining the vascular imaging with ITAS-A. RESULTS: A total of 410 visits in 52 patients were evaluated. The agreement was found to be 76% (κ: 0.52) between Rad-Active and PGA; 83% (κ: 0.57) between Rad-Active and Kerr's criteria. Both the agreements of ITAS2010 and acute phase reactants with PGA (69%, κ:0.38 and 60%, κ:0.22, respectively) and also Kerr's criteria (78%, κ:0.49 and 42%, κ:0.05, respectively) were lower compared to those of Rad-Active. Mean ITAS-A-Rad scores were higher in visits with active disease according to PGA and Kerr's criteria. CONCLUSIONS: The results of this study suggest that the vascular imaging should be included in the assessment of disease activity in TAK.

Genome-wide association study in Turkish and Iranian populations identify rare familial Mediterranean fever gene (MEFV) polymorphisms associated with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a highly heritable immune-mediated arthritis common in Turkish and Iranian populations. Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disease most common in people of Mediterranean origin. MEFV, an FMF-associated gene, is also a candidate gene for AS. We aimed to identify AS susceptibility loci and also examine the association between MEFV and AS in Turkish and Iranian cohorts. We performed genome-wide association studies in 1001 Turkish AS patients and 1011 Turkish controls, and 479 Iranian AS patients and 830 Iranian controls. Serum IL-1ß, IL-17 and IL-23 cytokine levels were quantified in Turkish samples. An association of major effect was observed with a novel rare coding variant in MEFV in the Turkish cohort (rs61752717, M694V, OR = 5.3, P = 7.63×10(-12)), Iranian cohort (OR = 2.9, P = 0.042), and combined dataset (OR = 5.1, P = 1.65×10(-13)). 99.6% of Turkish AS cases, and 96% of those carrying MEFV rs61752717 variants, did not have FMF. In Turkish subjects, the association of rs61752717 was particularly strong in HLA-B27-negative cases (OR = 7.8, P = 8.93×10(-15)), but also positive in HLA-B27-positive cases (OR = 4.3, P = 7.69×10(-8)). Serum IL-1ß, IL-17 and IL-23 levels were higher in AS cases than controls. Among AS cases, serum IL-1ß and IL-23 levels were increased in MEFV 694V carriers compared with non-carriers. Our data suggest that FMF and AS have overlapping aetiopathogenic mechanisms. Functionally important MEFV mutations, such as M694V, lead to dysregulated inflammasome function and excessive IL-1ß function. As IL-1 inhibition is effective in FMF, AS cases carrying FMF-associated MEFV variants may benefit from such therapy.

Histopathological differences between primary Sjögren's syndrome and Sjögren's syndrome accompanied by scleroderma.

BACKGROUND: Investigation of morphological differences in relation with serological variables between primary versus secondary Sjögren's syndrome associated with systemic scleroderma (Scl-SS). MATERIALS AND METHODS: A total of 69 primary Sjögren's syndrome (pSS) and Scl-SS patients were grouped according to the American-European Consensus Group criteria. Serum autoantibody information was obtained from the patient records. Hematoxylin and eosin sections of the minor salivary gland biopsy were reevaluated, and the lymphocyte focus score (FS), plasma cell focus, and fibrosis rates were all evaluated. RESULTS: There were 43 pSS and 26 Scl-SS cases. Both biopsy and autoantibody were positive in 16 pSS cases while only biopsy was positive in 25 cases and only antibody in 1 case. Both biopsy and antibody were positive in 5 Scl-SS cases while only biopsy was positive in 18 and only antibody in 3 cases. The plasma cell focus was statistically significantly higher in pSS cases (P = 0.003). No difference was seen between Sjögren' syndrome (SS) subtypes in terms of lymphocyte FS, fibrosis, and autoantibody positivity. CONCLUSION: We found that plasma cell focuses could be found more frequently in pSS than Scl-SS. In addition, our study reveals that the coexistence of SS and systemic scleroderma decreases the incidence of FS value ≥1 compared to pSS.

Nationwide Experience With Off-Label Use of Interleukin-1 Targeting Treatment in Familial Mediterranean Fever Patients.

OBJECTIVE: Approximately 30-45% of patients with familial Mediterranean fever (FMF) have been reported to have attacks despite colchicine treatment. Currently, data on the treatment of colchicine-unresponsive or colchicine-intolerant FMF patients are limited; the most promising alternatives seem to be anti-interleukin-1 (anti-IL-1) agents. Here we report our experience with the off-label use of anti-IL-1 agents in a large group of FMF patients. METHODS: In all, 21 centers from different geographical regions of Turkey were included in the current study. The medical records of all FMF patients who had used anti-IL-1 treatment for at least 6 months were reviewed. RESULTS: In total, 172 FMF patients (83 [48%] female, mean age 36.2 years [range 18-68]) were included in the analysis; mean age at symptom onset was 12.6 years (range 1-48), and the mean colchicine dose was 1.7 mg/day (range 0.5-4.0). Of these patients, 151 were treated with anakinra and 21 with canakinumab. Anti-IL-1 treatment was used because of colchicine-resistant disease in 84% and amyloidosis in 12% of subjects. During the mean 19.6 months of treatment (range 6-98), the yearly attack frequency was significantly reduced (from 16.8 to 2.4; P < 0.001), and 42.1% of colchicine-resistant FMF patients were attack free. Serum levels of C-reactive protein, erythrocyte sedimentation rate, and 24-hour urinary protein excretion (5,458.7 mg/24 hours before and 3,557.3 mg/24 hours after) were significantly reduced. CONCLUSION: Anti-IL-1 treatment is an effective alternative for controlling attacks and decreasing proteinuria in colchicine-resistant FMF patients.

Do major histocompatibility complex tag single nucleotide polymorphisms accurately identify HLA-B27 in the Turkish population?

OBJECTIVE: To evaluate the performance of human leukocyte antigen (HLA)-B27 tag single nucleotide polymorphisms (SNPs) by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP). METHODS: We genotyped three SNPs (rs116488202, rs13202464 and rs4349859). The primers were designed using Primer3 algorithm via primer-BLAST interface. PCR products were digested by using NlaIII, BmrI and TaqαI enzymes. Quality control was performed by DNA sequence analysis. RESULTS: In total, 207 patients with ankylosing spondylitis and 32 healthy controls were included in the study. The sensitivity and specificity of SNPs rs116488202 and rs4349859 in identifying HLA-B27 were identical and adequate at 0.946 and 1.000, respectively. On the other hand, the sensitivity and specificity for rs13202464 was 0.878 and 0.934, respectively. The presence of another SNP (rs141774149) in close proximity to rs116488202 complicated the analysis for RFLP and required that we sequence all the T allele carrying samples. CONCLUSION: The SNPs rs116488202 and rs4349859 may have a place in the identification of HLA-B27 in the Turkish population; however, methods other than PCR-RFLP should be considered.

Minor salivary gland evaluation: Sjögren's syndrome.

BACKGROUND/AIM:  We aimed to analyze the value of 3 serial sections, spaced 200 µm apart, for quantification of lymphocyte and plasma cell foci in minor salivary gland biopsy (MSGB). MATERIALS AND METHODS:  Labial MSGBs from 69 patients with Sjögren's syndrome (SS) and scleroderma were used for this study. Each sample was prepared as 3 serial sections spaced 200 µm apart. Lymphocytic and plasma cell focus score (LFS, PFS) were determined for each section, and the diagnostic results were compared to those obtained from a single section. RESULTS: For 22 of the 69 patients, all 3 sections were scored at <1 and interpreted as inconclusive for the presence of SS. For 20 cases, all 3 sections were scored at ≥1 and interpreted as diagnostic for SS. In the remaining 27 cases, the score was found to vary between sections. Plasma cell foci were observed in 11 cases, with 5 cases exhibiting a PFS of ≥1. Of those 5 cases, 4 also had a LFS of ≥1. CONCLUSION:  Assessment of 3 serial sections in MSGB has the potential to improve accuracy of SS diagnosis by detecting specific features that may not have been detected in a single section. We concluded that data about the PFS require further evaluation.

Increased Frequency of Hand Osteoarthritis in Patients with Primary Sjögren Syndrome Compared with Systemic Lupus Erythematosus.

OBJECTIVE: In daily practice, we noticed that hand osteoarthritis (OA) was commonly associated with primary Sjögren syndrome (pSS). Therefore, we aimed to investigate its prevalence in patients with pSS in a controlled study. METHODS: The study included patients with pSS and controls with systemic lupus erythematosus (SLE). Standard hand/wrist radiographs were obtained and classified according to the Kellgren-Lawrence system. "Erosive hand OA" was defined according to the Verbruggen-Veys classification. RESULTS: There were 114 patients with pSS (110 women, 51.0 yrs) and 34 patients with SLE (33 women, 42.4 yrs). Among 114 patients with pSS, 42.7% had radiographic, 30.3% symptomatic, and 16.0% erosive hand OA. The prevalences of radiographic (45.5%) and erosive hand OA (14.4%) in 90 patients with pSS with age- and sex-matched patients with SLE were significantly higher than those in patients with SLE (14.7% and 0.0%, p = 0.007 and p = 0.012, respectively). Interobserver reliabilities for diagnosing radiographic and erosive OA were found to be good (ĸ = 0.780 and ĸ = 0.788, respectively). Intraobserver reliabilities for diagnosing radiographic and erosive OA were also good (ĸ = 0.784 and ĸ = 0.825 for FO, and ĸ = 0.722 and ĸ = 0.800 for AB, respectively). The frequency of hand OA in patients with pSS was found to be increased with increasing age (r = 0.513). The mean age of those with erosive hand OA was significantly higher than those without erosive OA (p < 0.001). CONCLUSION: This study suggests that pSS, conversely to SLE, is more frequently associated with hand OA.

Cross-cultural adaptation and validation of the Turkish version of the pain catastrophizing scale among patients with ankylosing spondylitis.

[Purpose] This study describes the cultural adaptation, validation, and reliability of the Turkish version of the Pain Catastrophizing Scale in patients with ankylosing spondylitis. [Methods] The validity of the Turkish version of the Pain Catastrophizing Scale was assessed by evaluating data quality (missing data and floor and ceiling effects), principal components analysis, internal consistency (Cronbach's alpha), and construct validity (Spearman's rho). Reproducibility analyses included standard measurement error, minimum detectable change, limits of agreement, and intraclass correlation coefficients. [Results] Sixty-four adult patients with ankylosing spondylitis with a mean age of 42.2 years completed the study. Factor analysis revealed that all questionnaire items could be grouped into two factors. Excellent internal consistency was found, with a Chronbach's alpha value of 0.95. Reliability analyses showed an intraclass correlation coefficient (95% confidence interval) of 0.96 for the total score. There was a low correlation coefficient between the Turkish version of the Pain Catastrophizing Scale and body mass index, pain levels at rest and during activity, health-related quality of life, and fear and avoidance behaviors. [Conclusion] The results of this study indicate that the Turkish version of the Pain Catastrophizing Scale is a valid and reliable clinical and research tool for patients with ankylosing spondylitis.

Prevalence of Inflammatory Back Pain and Axial Spondyloarthritis Among University Employees in Izmir, Turkey.

OBJECTIVE: To estimate the prevalence of inflammatory back pain (IBP) and axial spondyloarthritis (axSpA) using the Assessment of SpondyloArthritis International Society (ASAS) classification criteria among employees in a university. METHODS: In the first stage of the study, a face-to-face interview was done using a standard questionnaire to investigate IBP in 381 subjects randomly selected from 2894 employees at Dokuz Eylul University in Izmir, Turkey. In the second stage, subjects with back pain for ≥ 3 months and age at onset < 45 years were evaluated for axSpA using the ASAS criteria. Both the European Spondyloarthropathy Study Group (ESSG) criteria and Amor criteria were used for the classification of the whole group of spondyloarthritis (SpA). RESULTS: There were 131 male and 250 female subjects (mean age: 38.0 yrs). Twenty-five subjects (6.6%) were classified as having IBP according to the ASAS criteria. The prevalence of IBP according to the Berlin and Calin criteria was 7.1% and 21.5%, respectively. The prevalence of axSpA was estimated at 1.3% according to the ASAS classification criteria (0.5% for radiographic axSpA and 0.8% for nonradiographic axSpA). A total of 7 patients (1.8%) fulfilled both the Amor and ESSG criteria for the whole group of SpA. CONCLUSION: This is the first prevalence study of IBP and axSpA using ASAS classification criteria in the Turkish population. The prevalence estimates of IBP and axSpA reported here are within the upper range of other studies in European countries and the United States.

Efficacy of interleukin-1 targeting treatments in patients with familial mediterranean Fever.

Herein, we reported our experience in colchicine-resistant familial Mediterranean fever (FMF) patients who are treated with anti-interleukin-1 (IL-1) drugs. A retrospective review of medical records of anti-IL-1 recipients was performed. The main clinical characteristics of these patients and the evolution after anti-IL-1 were recorded. There were 20 patients (11 male [M] and 9 female [F]). Despite regular colchicine treatment, median number of attacks per month and per year was 1 (1-4) and 12 (4-50), respectively. Twelve patients were receiving anakinra, and eight patients were treated with canakinumab. The number of monthly and yearly attacks after IL-1 treatment was significantly decreased after the biologic agent (p < 0.05). One patient did not respond to the treatment, and one patient developed serious infection during anti-IL-1. We also observed a significant decrease in proteinuria in the amyloidosis complicated FMF patients. Anti-IL-1 targeting drugs seem safe and effective therapies in colchicine-resistant FMF.

Herpetic whitlow during immunosuppressive therapy for Wegener's Granulomatosis.

Skin involvement may occur in patients with Wegener's granulomatosis (polyangiitis with granulomatosis; WG) and is more frequent in the generalised form. However, when a patient with vasculitis develops digital ulceration, in addition to disease activation, other pathologies should be considered. One of them may be the herpetic whitlow mimicking paronychia. Here, we present a patient who developed herpetic whitlow during the course of immunosuppressive therapy due to WG. Just before the third course of cyclophosphamide therapy, she was re-admitted to the outpatient clinic with the above-mentioned ulcerated lesions. On physical examination, there was erythema and a painful, crusted ulceration in the distal phalanx of the right index finger involving the proximal nail fold. Similar lesions were also present in her lower lip. Due to the absence of clinical and laboratory findings suggesting the activation of WG and the Tzanck smear result, which is compatible with herpes virus infection, we do not believe that WG was responsible for our patient's complaints. All of the patient's lesions completely disappeared following the interruption of immunosuppressive therapy.

Bilateral intravitreal ranibizumab injection and panretinal photocoagulation in a 16-year-old girl with severe vaso-occlusive lupus retinopathy.

A 16-year-old girl with fever of unknown origin and bilateral vaso-occlusive retinopathy with retinal neovascularization, preretinal hemorrhage, and serous macular detachment was treated with single bilateral 0.5 mg intravitreal ranibizumab injection prior to aggressive PRP with success. No systemic steroids or immunosuppressive therapy was employed at that time. She received the diagnosis of "systemic lupus erythematosus" five years after this episode with further systemic symptoms. In certain cases with vaso-occlusive type of lupus retinopathy, anti-VEGF agents may be administered in addition to panretinal photocoagulation to achieve better visual and anatomic outcome.

Does immunosuppressive treatment ameliorate morphology changes in encapsulating peritoneal sclerosis?

Encapsulating peritoneal sclerosis (EPS) is a clinical syndrome associated with ileus symptoms and irreversible sclerosis of the peritoneal membrane. Inflammation, fibrosis, and neoangiogenesis are the main features of the pathophysiology. No evidence-based therapy is currently available for EPS. In recent years, anti-inflammatory and immunosuppressive (IS) treatment modalities have become more popular. The aim of the present study was to investigate the effects of various IS treatment strategies-glucocorticosteroid (GC), azathiopurine (AZT), and cyclosporin (CsA)- on regression of EPS. We divided 52 nonuremic Wistar albino rats into six groups: Control group-2 mL isotonic saline injected intraperitoneally (IP) daily for 3 weeks; CG group-2 mL/200 g 0.1% chlorhexidine gluconate (CG) and 15% ethanol dissolved in saline injected IP daily for 3 weeks; Resting group-CG (weeks 1 - 3), plus peritoneal rest (weeks 4 - 6); Corticosteroid (GC) group-CG (weeks 1 - 3), plus 10 mg/L prednisolone in drinking water (weeks 4 - 6); AZT group- CG (weeks 1 - 3), plus 100 mg/L azathioprine in drinking water (weeks 4 - 6); and CsA group-CG (weeks 1 - 3), plus cyclosporin 7.5 mg/kg by subcutaneous injection daily (weeks 4 - 6). At the end of the study, under ketamine HCl anesthesia, the rats were humanely killed by bleeding. Parietal peritoneal samples were then taken from same location (away from the injection site) and changes of parietal peritoneum morphology were examined by a single pathologist. The CG severely disturbed parameters of peritoneal morphology, increasing peritoneal thickness, inflammatory activity, vascularity, and fibrosis score as compared with the Control group (p < 0.05). No benefit was observed for any parameter in the Resting group as compared withthose parameters in the CG group (p < 0.05). We observed a lower fibrosis score and less peritoneal thickness in the GC group as compared with the Resting group (p < 0.05). No beneficial effects of AZT on peritoneal morphology were observed as compared with the effects of peritoneal rest or corticosteroid therapy. Treatment with cyclosporin resulted in more fibrosis, vascularity, and inflammation than was seen with corticosteroid therapy (p < 0.05). Immunosuppressive therapies, especially those that are corticosteroid-based, may have therapeutic value in the management of EPS. Patients treated with cyclosporin may have a risk for developing EPS.

The effects of renin-angiotensin system inhibition on regression of encapsulating peritoneal sclerosis.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a clinical syndrome associated with symptoms of ileus and irreversible sclerosis of both visceral and parietal peritoneum. Peritoneal dialysis (PD) patients rarely develop EPS, a severe life-threatening condition of unknown pathogenesis. Angiotensin II is known to promote fibrosis and inflammation in various tissues. Renin-angiotensin system (RAS) blockade provides advantages in the course of diseases such as hypertension, chronic kidney disease, and proteinuria. We have also previously shown that RAS blockade has beneficial effects on hypertonic (3.86%) PD solution-induced peritoneal alterations. Because it shares the same characteristics as other fibrotic processes, peritoneal fibrosis can benefit from RAS blockade. OBJECTIVE: To determine the advantages of RAS blockade in regression of EPS. METHODS: We divided 56 nonuremic albino Wistar rats into 6 groups: control group (n = 10), daily intraperitoneal (IP) injection of 2 mL isotonic saline for 3 weeks; CG group (n = 10), daily IP injection of 2 mL/200 g chlorhexidine gluconate (CG) for 3 weeks; resting group (n = 10), daily IP injection of CG (0 - 3 weeks) plus peritoneal rest (4 - 6 weeks). After 3 weeks of being injected with CG (0 - 3 weeks), a fourth group (n = 9) was treated with 100 mg/L enalapril (ENA group); a fifth group (n = 10) was treated with 80 mg/L valsartan (VAL group), and a sixth group (n = 7) was treated with 100 mg/L enalapril + 80 mg/L valsartan (ENA+VAL group) in drinking water for an additional 3 weeks (4 - 6 weeks). At the end, a 1-hour peritoneal equilibration test was performed with 25 mL 3.86% PD solution. Dialysate-to-plasma ratio of urea (D/P urea), dialysate WBC count, ultrafiltration volume (UF), and morphological changes of parietal peritoneum were examined. RESULTS: Exposure to CG for 3 weeks resulted in alterations in peritoneal transport (increased D/P urea, decreased UF volume; p < 0.05) and morphology (increased inflammation, neovascularization, fibrosis, and peritoneal thickness; p < 0.05). Peritoneal rest had some beneficial effect only on UF failure and dialysate cell count (p < 0.05). However, RAS blockade was more effective than peritoneal rest with respect to UF volume, vascularity (p < 0.05), and peritoneal thickness (p > 0.05). Dual blockade of RAS had no additional beneficial effects. CONCLUSION: We suggest that RAS blockade either with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may be a more effective option than resting in the management of EPS.