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Objective Behcet's disease is a complex systemic inflammatory vasculitis of incompletely understood etiology. This study was undertaken to investigate genetic associations with Behcet's disease in a diverse multiethnic population. Methods A total of 9,444 patients and controls from 7 different populations were included in this study. Genotyping was performed using an Infinium ImmunoArray-24 v.1.0 or v.2.0 BeadChip. Analysis of expression data from stimulated monocytes, and epigenetic and chromatin interaction analyses were performed. Results We identified 2 novel genetic susceptibility loci for Behcet's disease, including a risk locus in IFNGR1 (rs4896243) (odds ratio [OR] 1.25; P = 2.42 x 10(-9)) and within the intergenic region LNCAROD/DKK1 (rs1660760) (OR 0.78; P = 2.75 x 10(-8)). The risk variants in IFNGR1 significantly increased IFNGR1 messenger RNA expression in lipopolysaccharide-stimulated monocytes. In addition, our results replicated the association (P < 5 x 10(-8)) of 6 previously identified susceptibility loci in Behcet's disease: IL10, IL23R, IL12A-AS1, CCR3, ADO, and LACC1, reinforcing the notion that these loci are strong genetic factors in Behcet's disease shared across ancestries. We also identified >30 genetic susceptibility loci with a suggestive level of association (P < 5 x 10(-5)), which will require replication. Finally, functional annotation of genetic susceptibility loci in Behcet's disease revealed their possible regulatory roles and suggested potential causal genes and molecular mechanisms that could be further investigated. Conclusion We performed the largest genetic association study in Behcet's disease to date. Our findings reveal novel putative functional variants associated with the disease and replicate and extend the genetic associations in other loci across multiple ancestries., National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH) [R01AR070148]; NIH [U54GM104938, U19AI082714, UM1AI144292, P30AR053483, P30AR073750], Supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH) grant number R01AR070148 to Dr. Sawalha. Recruitment and genotyping of the EuropeanAmerican controls was supported by NIH grants number U54GM104938, U19AI082714, UM1AI144292, P30AR053483, and P30AR073750 to Drs. Guthridge and James. This work was supported by the use of study data downloaded from the dbGaP web site, under dbGaP accession phs000272. v1.p1.

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 x 10(-s)) 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., National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) [R01 AR070148]; National Institute of Arthritis and Musculoskeletal and Skin DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) [U54 AR057319, U01 AR51874 04]; National Center for Research ResourcesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Research Resources (NCRR) [U54 RR019497]; Office of Rare Diseases Research of the National Center for Advancing Translational Sciences; Imperial College, National Institute for Health Research, Biomedical Research Centre; Wellcome TrustWellcome TrustEuropean Commission [WT107881]; Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission [MC_UU_00002/4], This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health grant R01 AR070148 to A.H.S. The Vasculitis Clinical Research Consortium has received support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54 AR057319 and U01 AR51874 04), the National Center for Research Resources (U54 RR019497), and the Office of Rare Diseases Research of the National Center for Advancing Translational Sciences. J.C.M., A.P.K., and R.M.M. acknowledge support from the Imperial College, National Institute for Health Research, Biomedical Research Centre. C.W. and G.R. acknowledge support from The Wellcome Trust (WT107881) and the Medical Research Council (MC_UU_00002/4). This work was supported by the use of study data downloaded from the dbGaP website, under dbGaP: phs000272.v1.p1, phs000431.v2.p1, phs000583.v1.p1, and phs000444.v1.p1.

WOS: 000463722100007, PubMed ID: 30489254, Objective: Familial Mediterranean fever (FMF) is the most common autoinflammatory disease. Most of the identified disease-causing mutations are located on exon 10. As the number of studies about the effect of the exonal location of the mutation and its phenotypic expression is limited, we aimed to investigate whether the exonic location of the Mediterranean fever (MEFV) mutation has an effect on the clinical manifestation in patients with FMF. Methods: Study population was derived from the main FMF registry that included 2246 patients from 15 different rheumatology clinics. We categorized the mutations according to their exon locations and retrieved the clinical and demographic information from the database. Results: Patients having the MEFV mutations on exon 2 or 10 (n: 1526) were divided into three subgroups according to the location of the MEFV mutations: Group 1 (exon 2 mutations), Group 2 (exon 10 mutations), and Group 3 (both exon 2 and exon 10 mutations). Group 2 patients were of a significantly younger age at onset, and erysipel-like erythema, arthritis, amyloidosis, and a family history of FMF were more common in this group. Conclusion: Patients with FMF and exon 10 mutations show more severe clinical symptoms and outcome. Exon 2 mutations tend to have a better outcome.

Tezcan, Mehmet Engin/0000-0002-1753-4936; TUFAN, Abdurrahman/0000-0001-6244-9362; SARI, Ismail/0000-0001-7737-4180; YILMAZ, Sedat/0000-0002-4691-3417 WOS: 000436403100017 PubMed: 28992387 ObjectiveApproximately 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. MethodsIn 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. ResultsIn 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. ConclusionAnti-IL-1 treatment is an effective alternative for controlling attacks and decreasing proteinuria in colchicine-resistant FMF patients.

AIMS: In August 2015, FDA published a black box declaring that DPP-4 inhibitors may cause severe joint pains. The impact on autoimmunity marker positivity of these drugs has not been comprehensively evaluated. We compared the incidence of arthritis/arthralgia in patients with T2DM who were using DPP-4 inhibitors and patients who were not using. METHODS: A number of 93 DPP-4 inhibitor users and 107 non-users were included into the study. Arthritis/arthralgia were found in 41 of 93 (44.1%) DPP-4 inhibitor users and in 19 of 107 (17.8%) non-users (p0.05). After adjusting for gender the incidence for arthritis/arthralgia was significantly increased in the DPP-4 inhibitor user group (p value for any DPP-inhibitor

To investigate the choroidal thickness in patients with scleroderma and to compare them with healthy control subjects. Forty-six patients with scleroderma (3 male and 43 female) and 31 healthy controls (6 male and 25 female) were included in the study. Twenty-five patients had limited-type and 21 patients had diffuse-type scleroderma. Only left eyes of the patients and control subjects were used in the analysis. Demographic features of all the patients and control subjects were recorded. Each subject underwent ophthalmological examinations including refraction, visual acuity, intraocular pressure, axial length (AXL) measurement, slit-lamp biomicroscopy, and fundus examination. Body mass index (BMI) was estimated for all participants. There were no significant differences between the patients with scleroderma and the control subjects in terms of age, gender, BMI, mean AXL, and mean spherical equivalent refractive error (SE) (P=0.1, P=0.086, P=0.37, P=0.55, and P=0.072 respectively). The patients with scleroderma had significantly thinner nasal, temporal, and subfoveal choroid than the healthy control subjects (P1=0.012, P2=0.046, and P3 0.05). Choroidal thickness in patients with scleroderma was significantly less than healthy control subjects. Vasculopathy in scleroderma is characterized by obliteration of arterioles and reduced capillary density may cause atrophy of choroid in patients with scleroderma.

Background Viruses are common and are involved in the etiology of idiopathic rheumatological diseases. Hepatitis B virus (HBV), a member of the family Hepadnaviridae and hepatitis C virus (HCV), play an important role in the undetermined etiology of arthritis. The clinical manifestations of hepatitis B and C show similarities with various diseases, such as rheumatic diseases. Anti-cyclic citrullinated peptide (anti-CCP) is a specific serological marker for rheumatoid arthritis. Objectives The aim of this study was to analyze anti-CCP and rheumatoid factor (RF) levels in patients with a hepatitis B and C infection. Material and methods Forty-four patients with hepatitis B, 43 patients with hepatitis C, 25 patients with rheumatoid arthritis, and 46 healthy control serums and their RF and anti-CCP levels were compared. RF was measured by the nephelometer, which detects IgM-RF. Anti-CCP was measured using enzymelinked immunosorbent assay (ELISA) that is included in the second-generation anti-CCP antibody assays (anti-CCP2). Results The anti-CCP positivity levels were 20.5%, 32.5%, 72.4% and 10.9% for HBV, HCV and RA groups and healthy control group, respectively. When the groups were compared based on their RF positivity and anti-CCP positivity while the values for HBV and HCV group and healthy control group were the same, in RA group there is a significant difference to the rest of the groups (p Conclusions Anti-CCP may be positive for HBV and HCV as well, but it is a sensitive and specific immunological marker for RA diagnosis, especially in high-titres.

Objectives To examine associations between red blood cell distribution width (RDW) and organ involvement and disease activity in patients with Behçet’s disease. Methods Haematological and inflammatory parameters including RDW, high-sensitivity C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR) were examined in patients with Behçet’s disease and in healthy controls. Patients were divided into those with active or inactive disease. Results Data from 236 patients with Behçet’s disease (77 with active and 159 with inactive disease) and 72 controls were analysed. RDW, ESR and hsCRP were significantly higher in patients with Behçet’s disease than in controls, and in those with active disease compared with inactive disease or controls. In addition, ESR and hsCRP were significantly higher in those with inactive disease than controls. No correlations were found between hsCRP, ESR and RDW. No differences were observed in RDW, ESR or hsCRP between patients with or without ocular or vascular involvement. Multivariate logistic regression analysis revealed that RDW was significantly higher in active disease compared with inactive disease. Conclusions RDW was increased in active disease compared with inactive disease. No relationships were found between organ involvement and RDW. RDW may be a cost-effective, novel potential parameter to evaluate disease activity in Behçet’s disease.

RESUMO Objetivo A artrite gostosa e a febre familiar do Mediterrâneo (FFM) compartilham algumas características clínicas e patológicas, como ser classificada como uma doença autoimune inflamatória, ter associação com o inflamassoma, manifestar artrite intermitente de curta duração e boa resposta a tratamentos com colchicina e anti-interleucina-1. Como o gene da febre familiar do Mediterrâneo (MEFV) é o fator causador da FFM, este estudo teve como objetivo investigar a prevalência de mutações do gene MEFV e seu efeito sobre as manifestações da doença em pacientes turcos com artrite gotosa. Métodos Foram incluídos no estudo 97 pacientes com diagnóstico de artrite gotosa primária (93 M e 4 F; 54 [37-84] anos) e 100 controles saudáveis (94 M e 6 F; 57 [37-86] anos). Todos os indivíduos foram submetidos à análise do genótipo à procura de variações no MEFV. Também foi registrado o número de crises de gota, o uso de diuréticos e a história de nefrolitíase e presença de tofos. Resultados A frequência de portadores de mutações no MEFV em pacientes e controles foi de 22,7% (n = 22) e 24% (n = 24), respectivamente. A comparação entre os pacientes e os controles não produziu diferença estatisticamente significativa em termos de frequência de portadores de mutações no MEFV (p = 0,87). As frequências alélicas de mutações no MEFV nos pacientes foram de 11,9% (n = 23) e 14% (n = 28) nos controles (p = 0,55). A presença de variantes do MEFV não mostrou qualquer associação com as características clínicas da artrite gotosa. A análise por subgrupos de pacientes revelou que aqueles com artrite gotosa com mutações tinham frequências semelhantes de tofo, história de nefrolitíase e podogra em comparação com os indivíduos sem mutações (p > 0,05). Conclusões As mutações no gene MEFV não exercem um papel relevante em pacientes turcos com artrite gotosa. ABSTRACT Objective Gouty arthritis and familial Mediterranean fever share some clinical and pathological features such as being classified as auto-inflammatory disease, association with inflammasome, short-lived intermittent arthritis, and good response to colchicine and anti-interleukin-1 treatments. As Mediterranean fever gene is the causative factor of familial Mediterranean fever, we aimed to investigate the prevalence of Mediterranean fever gene mutations and their effect on disease manifestations in Turkish gouty arthritis patients. Methods Ninety-seven patients diagnosed with primary gouty arthritis (93 M and 4 F, 54 [37–84] years) and 100 healthy controls (94 M and 6 F, 57 [37–86] years) were included in the study. All subjects were genotyped for the Mediterranean fever gene variations. Number of gout attacks, diuretic use, history of nephrolithiasis and presence of tophus were also recorded. Results The carriage rate of Mediterranean fever mutations for patients and controls was 22.7% (n = 22) and 24% (n = 24), respectively. The comparison of the patient and control groups yielded no significant difference in terms of the Mediterranean fever mutations’ carriage rate (p = 0.87). The allelic frequencies of the Mediterranean fever mutations in patients were 11.9% (n = 23) and 14% (n = 28) in controls (p = 0.55). The presence of Mediterranean fever variants did not show any association with clinical features of gouty arthritis. The subgroup analysis of patients revealed that gouty arthritis patients with mutations had similar frequencies of tophus, history of nephrolithiasis and podagra compared to the ones without mutations (p > 0.05). Conclusions This study does not provide support for a major role of Mediterranean fever mutations in Turkish gouty arthritis patients.

Objective Takayasu arteritis is a rare large vessel vasculitis with incompletely understood etiology. This study was undertaken to perform the first unbiased genome-wide association analysis of Takayasu arteritis. Methods Two independent cohorts of patients with Takayasu arteritis from Turkey and North America were included in our study. The Turkish cohort consisted of 559 patients and 489 controls, and the North American cohort consisted of 134 patients and 1,047 controls of European ancestry. Genotyping was performed using the Omni1-Quad and Omni2.5 genotyping arrays. Genotyping data were subjected to rigorous quality control measures and subsequently analyzed to discover genetic susceptibility loci for Takayasu arteritis. Results We identified genetic susceptibility loci for Takayasu arteritis with a genome-wide level of significance in IL6 (rs2069837) (odds ratio [OR] 2.07, P = 6.70 × 10−9), RPS9/LILRB3 (rs11666543) (OR 1.65, P = 2.34 × 10−8), and an intergenic locus on chromosome 21q22 (rs2836878) (OR 1.79, P = 3.62 × 10−10). The genetic susceptibility locus in RPS9/LILRB3 lies within the leukocyte receptor complex gene cluster on chromosome 19q13.4, and the disease risk variant in this locus correlates with reduced expression of multiple genes including the inhibitory leukocyte immunoglobulin-like receptor gene LILRB3 (P = 2.29 × 10−8). In addition, we identified candidate susceptibility genes with suggestive levels of association (P < 1 × 10−5) with Takayasu arteritis, including PCSK5, LILRA3, PPM1G/NRBP1, and PTK2B. Conclusion Our findings indicate novel genetic susceptibility loci for Takayasu arteritis and uncover potentially important aspects of the pathophysiology of this form of vasculitis.

Background Although anti-tumour necrosis factor agents (anti-TNFs) are very effective in most patients with ankylosing spondylitis (AS) significant proportion of patients quit the treatment due to non-response or adverse events. The development of anti-drug antibodies (ADAs) and low serum drug levels might have a mechanistic role in loss of efficacy of or the development of adverse events in patients treated with anti-TNFs. There is limited data regarding the immunogenicity of anti-TNFs in patients with AS. Objectives Therefore the aim of this study was to evaluatethe relationship between the formation of ADAs, serum through drug levels and clinical response to anti-TNFs in patients with AS. Methods In total 350 AS patients with a new anti-TNF agent prescription in the last two weeks period were planned to include this multi-center prospective observational cohort study. Herein we are presenting the data of first 102 patients who had >3months follow-up. Clinical data and serum samples were collected at baseline and at every three months of treatment. Serum drug levels and ADAs were measured by ELISA in one center to avoid inter-assay variability. Results 102 biologic naive AS patients (75 [74%] male, mean (±SD) age; 37.2±10.7 years) who started anti-TNF agents (14 infliximab [13.7%], 27 adalimumab [26.5%], 33 etanercept [32.4%] and 28 golimumab [27.5%]) were included in the present analysis. In comparison to baseline values BASDAI, ASDAS-CRP and CRP values were significantly decreased in third months of follow-up ( P P P P P =0.012 and ASDAS-CRP values were 2.7±1.3 vs 1.9±1.0; P =0.015). Conclusions ADAs against anti-TNF agents might develop as early as 12 weeks of treatment. Our results confirm that ADA development may hinder the anticipated response to anti-TNF agents in patients with AS. Disclosure of Interest None declared

ResumoIntroduçãoColchicina é a viga‐mestra para o tratamento de FFM, que é uma doença autoinflamatória com polisserosite recidivante como principal manifestação. Apesar de doses diárias de 2mg ou mais/dia, aproximadamente 5%‐10% dos pacientes continuam a sofrer de seus ataques. Neste estudo, objetivamos investigar os aspectos da depressão e dos ataques em pacientes com FFM apresentando resistência à colchicina (RC).Pacientes e MétodosEm pacientes com FFM, RC foi definida como dois ou mais ataques nos últimos seis meses, quando em medicação com colchicina 2mg/dia. Dezoito pacientes (nove mulheres e nove homens) foram recrutados no grupo RC e 41 pacientes no grupo de controle (29 mulheres/12 homens). Foram avaliados os achados demográficos, clínicos e laboratoriais, a fidelidade ao tratamento e os escores do Beck Depression Inventory (BDI).ResultadosA idade de surgimento da FFM foi significativamente menor no grupo RC (12,3 anos vs. 16,9 anos, P=0,03). A duração da doença foi maior no grupo RC (p=0,01). Dores abdominais e nas pernas em decorrência do exercício foram significativamente mais frequentes no grupo RC versus controles (83% vs. 51%; p=0,02 e 88% vs. 60%; p=0,04, respectivamente). Pacientes com escores BDI>17 pontos foram mais frequentes no grupo RC versus controles (50% vs. 34,1%; p

Terlipressin is a synthetic vasopressin analogue that is used in the treatment of bleeding esophageal varices and hepatorenal syndrome in patients with cirrhosis. Hepatorenal syndrome is a form of renal failure seen in patients with cirrhosis, with fatal outcomes. Ischemic adverse effects related to terlipressin are rarely observed. Herein, two cases who developed ischemic skin necrosis due to terlipressin usage are presented. Terlipressin therapy was started in two cirrhotic patients with presumptive hepatorenal syndrome. During the therapy, ecchymotic and necrotic changes were observed on the scrotal regions of both patients. Skin lesions were relieved after terlipressin therapy. Biopsy results were consistent with ischemia. Even if seen rarely, possible emergence of ischemic complications must be considered.

Recent studies have shown that genetic factors involved in the host responses might determine the disease severity for both familial Mediterranean fever (FMF) and periodontitis. The present study aimed to investigate the relationship of FMF with periodontitis and to search for the potential association between periodontitis and MEFV gene missense variations in patients with FMF. The study consisted of 97 FMF patients and 34 healthy volunteers. FMF patients were classified according to the kind of MEFV gene mutation: (1) patients with homozygous M694V gene mutation, (2) patients with heterozygous M694V gene mutation, and (3) patients with MEFV gene different mutations. Gingival Index (GI), Plaque Index (PI), probing pocket depth (PD), and clinical attachment level (CAL) were measured in all participants. The results of multivariate logistic regression showed a highly significant association between homozygous M694V gene mutation and periodontitis in FMF patients (p

ResumoOs fármacos antifator de necrose tumoral (anti‐TNF) são frequentemente preferidos no tratamento de doenças reumatológicas e outras doenças inflamatórias. O desenvolvimento de miosite após o uso de anti‐FNT é uma condição clínica rara. Este estudo objetivou descrever casos de pacientes que desenvolveram miosite após o uso de anti‐TNF e fazer uma revisão da literatura atual. Descrevem‐se dois casos de artrite reumatoide (AR) e um caso de espondilite anquilosante (EA) que desenvolveram miopatia inflamatória idiopática após o tratamento com anti‐TNF. Em conclusão, pode haver desenvolvimento de miosite durante o tratamento com anti‐TNF, de modo que esses pacientes devem ser cuidadosamente avaliados inicialmente à procura de miosite e devem ser cuidadosamente monitorados em razão do potencial de desenvolvimento de miosite no processo de tratamentoAbstractAnti‐tumor necrosis factor (anti‐TNF) drugs are frequently preferred in the treatment of rheumatologic diseases and other inflammatory diseases. The development of myositis after using anti‐TNF is a rare clinical condition. Here we aimed to report cases who developed myositis after using anti‐TNF and review the current literature. We report two cases of rheumatoid arthritis (RA) and a case of ankylosing spondylitis (AS) developed idiopathic inflammatory myopathy following anti‐TNF therapy. In conclusion, myositis could develop during anti‐TNF therapy, so these patients should be evaluated carefully initially for myositis and should be closely monitored due to the potential for developing myositis in treatment process.

Çalışmada 24 yazar bulunmaktadır. Bu yazarlardan sadece Bursa Uludağ Üniversitesi mensuplarının girişleri yapılmıştır. In this multicenter, retrospective study, we evaluated the efficacy and safety of biologic therapies, including anti-TNFs, in secondary (AA) amyloidosis patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA). In addition, the frequency of secondary amyloidosis in RA and AS patients in a single center was estimated. Fifty-one AS (39M, 12F, mean age: 46.7) and 30 RA patients (11M, 19F, mean age: 51.7) with AA amyloidosis from 16 different centers in Turkey were included. Clinical and demographical features of patients were obtained from medical charts. A composite response index (CRI) to biologic therapy-based on creatinine level, proteinuria and disease activity-was used to evaluate the efficacy of treatment. The mean annual incidence of AA amyloidosis in RA and AS patients was 0.23 and 0.42/1000 patients/year, respectively. The point prevalence in RA and AS groups was 4.59 and 7.58/1000, respectively. In RA group with AA amyloidosis, effective response was obtained in 52.2 % of patients according to CRI. RA patients with RF positivity and more initial disease activity tended to have higher response rates to therapy (p values, 0.069 and 0.056). After biologic therapy (median 17 months), two RA patients died and two developed tuberculosis. In AS group, 45.7 % of patients fulfilled the criteria of good response according to CRI. AS patients with higher CRP levels at the time of AA diagnosis and at the beginning of anti-TNF therapy had higher response rates (p values, 0.011 and 0.017). During follow-up after anti-TNF therapy (median 38 months), one patient died and tuberculosis developed in two patients. Biologic therapy seems to be effective in at least half of RA and AS patients with AA amyloidosis. Tuberculosis was the most important safety concern.

Objective.Screening strategies for latent tuberculosis (TB) before starting tumor necrosis factor (TNF)-α inhibitors have decreased the prevalence of TB among patients who are treated with these agents. However, despite vigilant screening, TB continues to be an important problem, especially in parts of the world with a high background TB prevalence. The aim of this study was to determine the factors related to TB among a large multicenter cohort of patients who were treated with anti-TNF.Methods.Fifteen rheumatology centers participated in this study. Among the 10,434 patients who were treated with anti-TNF between September 2002 and September 2012, 73 (0.69%) had developed TB. We described the demographic features and disease characteristics of these 73 patients and compared them to 7695 patients who were treated with anti-TNF, did not develop TB, and had complete data available.Results.Among the 73 patients diagnosed with TB (39 men, 34 women, mean age 43.6 ± 13 yrs), the most frequent diagnoses were ankylosing spondylitis (n = 38) and rheumatoid arthritis (n = 25). More than half of the patients had extrapulmonary TB (39/73, 53%). Six patients died (8.2%). In the logistic regression model, types of anti-TNF drugs [infliximab (IFX), OR 3.4, 95% CI 1.88–6.10, p = 0.001] and insufficient and irregular isoniazid use (< 9 mos; OR 3.15, 95% CI 1.43–6.9, p = 0.004) were independent predictors of TB development.Conclusion.Our results suggest that TB is an important complication of anti-TNF therapies in Turkey. TB chemoprophylaxis less than 9 months and the use of IFX therapy were independent risk factors for TB development.

Rhupus is a rare syndrome characterized by overlap of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Previous reports mentioned that rhupus patients have prominent RA associated clinical manifestations and only mild organic damage related to SLE. Progressive or life-threatening manifestations are rare in rhupus patients. Our patient diagnosed as rhupus was a young women, presented with multi-organ involvement of systemic vasculitis. Rheumatologists should be aware of possibility that rhupus may be accompanied by progressive or life-threatening conditions such as vasculitis.

Systemic sclerosis (SSc) is an inflammatory disease characterized by vascular abnormalities and fibrosis. The aim of the present study was to investigate the possible role of transient receptor potential melastatin (TRPM) channel genes in the susceptibility and phenotype expression of SSc.A total of 339 patients with SSc and 302 healthy controls were studied. Genomic DNA was extracted from leukocytes of the peripheral blood, and 25 single nucleotide polymorphisms in the TRPM channel genes were analyzed by the BioMark HD dynamic array system.There were marked increases in the CC genotype (94.7% vs 81.8%, p0.0001) and C allele frequencies (97.0% vs. 90.1%, p0.0001) in the TRPM3 rs1328142, and TT genotype (19.0% vs. 7.8%, p=0.0002) in TRPM5 rs34551253 (Ala456Thr) polymorphism in SSc patients when compared to controls. TRPM3 gene rs1328142 polymorphism was also markedly associated with disease phenotype. However, no associations with the other 23 polymorphisms studied were found.This is the first study to examine the involvement of TRPM channel gene variations on the risk of SSc incidence. Our results suggest roles of TRPM3 and TRPM5 gene variants in the susceptibility to or clinical expression of SSc in the Turkish population.

Objective.Acne vulgaris is a chronic inflammatory disease involving the pilosebaceous unit of the skin. Isotretinoin is a systemic retinoid that is often used as an effective treatment option for severe and treatment-resistant acne. Isotretinoin may also cause rheumatologic symptoms. The aim of this prospective observational study was to present followup results regarding the rheumatologic symptoms of patients who received systemic therapy for the treatment of acne (isotretinoin and tetracycline).Methods.For inclusion in the study, all consecutive patients with acne who were aged > 18 years were evaluated by the same dermatologist. The first 42 consecutive patients were included in the isotretinoin group, and after matching for age and sex, 32 consecutive patients were included in the tetracycline group. Isotretinoin treatment was planned as an average dose of 30 mg daily and a total dose of 120–150 mg/kg for 4–6 months. The patients were administered a dose of 1 g/day of tetracycline as 2 equal doses for 3 months.Results.Forty-two patients diagnosed with acne vulgaris were treated with isotretinoin 20.6 ± 4.4 (male/female: 17/22), and 32 patients were treated with tetracycline 20.6 ± 2.7 (male/female: 8/24). There was no significant difference between the 2 groups with respect to age and sex. Unilateral Achilles enthesopathy developed in 3 patients, whereas both Achilles enthesopathy and unilateral sacroiliitis developed in 1 patient. Inflammatory back pain developed in 6 patients in the isotretinoin group.Conclusion.To our knowledge, this was the first prospective observational study that assessed the rheumatologic symptoms of isotretinoin treatment. The spondyloarthropathy findings were identified in 23.1% of the patients who used isotretinoin.

WOS: 000374567100016 PubMed ID: 26743213 Systemic sclerosis (SSc) is a chronic inflammatory disease characterized by widespread fibrosis of the skin and several visceral organs. The pro-fibrotic potential of interleukin (IL)-33 has been demonstrated by in both in vitro and in vivo settings; moreover, increased level of IL-33 has also been reported in patients with SSc. Therefore, the aim of the present study was to detect the potential association of IL-33 gene polymorphisms on the susceptibility of SSc. A total of 300 SSc patients and 280 healthy controls (HC) were enrolled in this multicentric preliminary candidate gene study. DNA samples were harvested using an appropriate commercial DNA isolation kit. Four single nucleotide polymorphisms (SNPs) of IL-33 gene (rs7044343, rs1157505, rs11792633 and rs1929992) were genotyped using the appropriate commercial primer/probe sets on real-time PCR. There was no significant difference in terms of the allelic distributions and minor allele frequencies of evaluated four IL-33 polymorphisms between the SSc and HC groups (P > 0.05 for all). Moreover, the genotypic distributions of rs1157505, rs11792633 and rs1929992 polymorphisms were not significantly different (P > 0.05 for all). However, CC genotype of rs7044343 SNP was significantly higher in the SSc group compared to the HC group (P = 0.013, OR 1.75, 95 % CI 1.12-2.72). This preliminary candidate gene study demonstrates that rs7044343 polymorphism of IL-33 gene is associated with the susceptibility to the SSc in Turkish population. It may be suggested that IL-33 gene may be a candidate gene to research in SSc.

Background: Recent recommendations have established clinical remission ideally or low disease activity (LDA) as therapeutic targets in all patients with rheumatoid arthritis (RA). Controlled studies of biologic agents have primarily assessed treatment effects in patients with severe RA; patients with moderate disease activity, whoconstitute a larger group, have received far less attention. In Period 1 of the PRESERVE trial, the proportion of subjects with moderately active RA achieving LDA or remission were evaluated after treatment with etanercept 50mg once weekly (QW) plus methotrexate for 36 weeks.Methods: Subjects with DAS28 >3.2 and ≤5.1 despite stable doses of oral methotrexate received open-label etanercept 50mg QW plus methotrexate (screening dose permitted to be titrated up to 25 mg/wk through week 28) for 36 weeks.Results: 834 subjects received treatment and were analyzed. Subjects were mostly female (83%), Caucasian (74%), RFþ (73%), and aCCPþ (78%), with a mean age of 48 years and disease duration of 7 years. Mean baseline DAS28 was 4.4; SDAI, 19.1; ESR, 22.2 mm/hr; and CRP, 12.3 mg/L. Efficacy results from Period 1 are shown in the table. The most commonly reported adverse events (AEs) were headache (6.1%), nasopharyngitis (5.4%), and upper respiratory tract infection (4.4%). Twenty-two subjects (2.6%) discontinued due to AEs.Conclusions: Substantial proportions of subjects with moderately active RA who received etanercept 50mg QW plus methotrexate for 36 weeks achieved LDA (85%-86%), DAS28 remission (67%), or SDAI remission (25%). Therefore, these ambitious goals can be achieved realistically in a high percentage of patients with moderate disease activity.

Objective Gouty arthritis and familial Mediterranean fever share some clinical and pathological features such as being classified as auto-inflammatory disease, association with inflammasome, short-lived intermittent arthritis, and good response to colchicine and anti-interleukin-1 treatments. As Mediterranean fever gene is the causative factor of familial Mediterranean fever, we aimed to investigate the prevalence of Mediterranean fever gene mutations and their effect on disease manifestations in Turkish gouty arthritis patients. Methods Ninety-seven patients diagnosed with primary gouty arthritis (93 M and 4 F, 54 [37–84] years) and 100 healthy controls (94 M and 6 F, 57 [37–86] years) were included in the study. All subjects were genotyped for the Mediterranean fever gene variations. Number of gout attacks, diuretic use, history of nephrolithiasis and presence of tophus were also recorded. Results The carriage rate of Mediterranean fever mutations for patients and controls was 22.7% (n = 22) and 24% (n = 24), respectively. The comparison of the patient and control groups yielded no significant difference in terms of the Mediterranean fever mutations’ carriage rate (p = 0.87). The allelic frequencies of the Mediterranean fever mutations in patients were 11.9% (n = 23) and 14% (n = 28) in controls (p = 0.55). The presence of Mediterranean fever variants did not show any association with clinical features of gouty arthritis. The subgroup analysis of patients revealed that gouty arthritis patients with mutations had similar frequencies of tophus, history of nephrolithiasis and podagra compared to the ones without mutations (p > 0.05). Conclusions This study does not provide support for a major role of Mediterranean fever mutations in Turkish gouty arthritis patients.

Objective.To assess bladder toxicity of cyclophosphamide (CYC) and uroprotective effect of mesna in rheumatic diseases.Methods.Data of 1018 patients (725 women/293 men) treated with CYC were evaluated in this retrospective study. All of the following information was obtained: the cumulative CYC dose, route of CYC administration, duration of therapy, concomitant mesna usage, and hemorrhagic cystitis. Cox proportional hazard model was used for statistics.Results.We identified 17 patients (1.67%) with hemorrhagic cystitis and 2 patients (0.19%) with bladder cancer in 4224 patient-years. The median time for diagnosis to hemorrhagic cystitis was 10 months (4–48) and bladder cancer was 8 years (6–10.9). There were 583 patients (57.2%) who received mesna with intravenous CYC therapy. We observed similar incidence rate for hemorrhagic cystitis in both patient groups concomitantly treated with or without mesna [9/583 (1.5%) vs 8/425 (1.8%) respectively, p = 0.08]. Cumulative CYC dose (HR for 10-g increments 1.24, p < 0.001) was associated with hemorrhagic cystitis.Conclusion.Cumulative dose was the only risk factor for hemorrhagic cystitis in patients treated with CYC. No proof was obtained for the uroprotective effect of mesna in our cohort.

WOS:000382751900010 Familial Mediterranean Fever (FMF) is a fairly common inflammatory disease in communities with mediterranean origin. It is characterized with autosomal recessive, recurrent short-term episodes of fever, peritoneal, pleural, synovial membrane involvement and skin lesions. The aim of the present study was to investigate possible associations between FMF and Ala-9Val polymorphism of MnSOD and Pro198Leu polymorphism of GPx1. The study included 129 FMF patients who has mutations (E148Q, P369S, F479L, M680I(G/C), M680I(G/A), I692del, M694V, M694I, K695R, V726A, A744S, R761H) in the heterozygous or homozygous form and 95 healthy subjects. To identify MnSOD Ala-9Val and GPx1 Pro198Leu SNPs, genotyping was performed using PCR amplification, and polymorphisms were detected with hybridization probes labeled with fluorescent dyes. Genotype and allele frequencies of Ala-9Val polymorphism of MnSOD and Pro198Leu polymorphism of GPx1 were detected. The MnSOD Val allele frequency is 132 (51.16%) in the FMF and 115 (60.52%) in the control group (p

WOS: 000365587100005, PubMed ID: 27708953, Objective: The reactivation of hepatitis B virus (HBV) infection is a well-known event in hepatitis B surface antigen (HbsAg)-positive patients receiving immunosuppressive therapy. The objective of this study was to assess the antiviral practice and course of HBV infection in inflammatory arthritis. Material and Methods: Nineteen rheumatology centers participated in this retrospective study. HbsAg-positive patients who were taking disease-modifying antirheumatic drugs and who were being tested for HBV viral load at a minimum of two different time points were included. The case report form (CRF) consisted of demographic data, rheumatic diseases, treatment profiles, transaminase levels, viral hepatitis serological markers, and HBV viral load. The reactivation of HBV was defined as the abrupt rise in HBV replication by an increase in serum HBV DNA levels in a patient with a previously inactive HBV infection. Results: In total, the data of 101 (female 50.5%) patients were included (76 patients with inactive HBV carriers and 25 patients with chronic HBV infection). The mean age of patients was 44 +/- 12 years, and the mean follow-up duration was 31 +/- 22 months. Of the 101 patients, 70 (69.3%) received antiviral treatment. HBV reactivation was detected in 13 of 76 (17.1%) patients with inactive HBV carriers. HBV reactivation was observed less frequently, not although significantly, in those patients receiving antiviral prophylaxis compared with those not receiving prophylaxis [5/41 (12.2%) vs. 8/33 (24.2%), p=0.17]. Forty-two patients (31 patients had inactive HBV carriers) were using anti-tumor necrosis factor agents. HBV reactivation was detected in 6 of the 31 (19.3%) patients. Twenty-five patients had chronic hepatitis, and five (20%) of them had not received antiviral prophylaxis. HBV viral loads were persistently elevated in 7 (28%) of 25 patients (three patients under and four patients not under antiviral treatment). Conclusion: HBV reactivation was observed in approximately 17% of patients under immunosuppressive treatments. HBV reactivation was more frequently observed in those who did not receive antiviral prophylaxis.

Yigit, Serbulent/0000-0002-1019-3964 WOS: 000308260400007 PubMed: 22771921 Objective: Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent attacks of fever and inflammation in the peritoneum, synovium, or pleura, accompanied by pain. The disease is associated with mutations in the Mediterranean fever (MEW) gene, which encodes for the pyrin protein. The aim of this study was to explore the frequency and clinical significance of the R202Q (c.605G>A) polymorphism in exon 2 of the MEFV gene in a cohort of Turkish patients with FMF. Methods: The study included 191 patients with FMF and 150 healthy controls. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) assay for the MEFV gene R202Qpolymorphism. Results: The genotype and allele frequencies of R202Q polymorphism showed a statistically significant difference between FMF patients and controls (p

Behcet’s disease (BD) is a systemic inflammatory disorder characterised by oral/genital ulcers, ocular lesions, and gastrointestinal, musculoskeletal, neurological and major vessel involvements. Venous manifestations are more common than arterial involvements. In this case report, we present a patient with internal jugular vein thrombosis, which is a very rare complication of BD.

Gouty arthritis and familial Mediterranean fever (FMF) share some clinical and pathological features such as being classified as auto inflammatory disease, association with inflammasome, short-lived intermittent arthritis, and good response to colchicine and anti-interleukin-1 treatments. As Mediterranean fever (MEFV) gene is the causative factor of FMF, we aimed to investigate the prevalence of MEFV gene mutations and their effect on disease manifestations in Turkish gouty arthritis patients.Ninety-seven patients diagnosed with primary gouty arthritis (93M and 4 F, 54 [37-84] years) and 100 healthy controls (94M and 6 F, 57 [37-86] years) included in the study. All subjects were genotyped for the MEFV variations. Number of gout attacks, diuretic use, and history of nephrolithiasis and presence of tophus were also recorded.The carriage rate of MEFV mutations for patients and controls were 22.7% (n=22) and 24% (n=24) respectively. The comparison of the patient and control groups yielded no significant difference in terms of the MEFV mutations carriage rate (p=0.87). The allelic frequencies of the MEFV mutations in patients were 11.9% (n=23) and 14% (n=28) in controls (p=0.55). The presence of MEFV variants did not show any association with clinical features of gouty arthritis. The subgroup analysis of patients revealed that gouty arthritis patients with mutations had similar frequencies of tophus, history of nephrolithiasis and podogra compared to the ones without mutations (p0.05).This study does not provide support for a major role of MEFV mutations in Turkish gouty arthritis patients.

To evaluate the effects of anti-tumor necrosis factor-alpha (TNF-a) therapy on the frequency of varicocele in patients with ankylosing spondylitis (AS) using color Doppler ultrasound. Materials and methods: The patients were divided into 2 groups: patients with AS who were on anti-TNF-a treatment and patients with AS who were not regularly taking any antiinflammatory drugs. Thirty-one healthy volunteers were included as controls. Results: Left-sided varicocele was determined in 14 patients of Group 1 (44%), 10 patients of Group 2 (33%), and 7 of the controls (23%). There was a statistically significant difference only between Group 1 and controls (P = 0.009). However, right-sided varicocele was determined in 12 patients of Group 1 (38%), 2 patients of Group 2 (6%), and 2 of the controls (6%) (P = 0.01 vs. Group 2, P = 0.005 vs. controls). Conclusion: The present study shows that patients with AS who were taking anti-TNF-a therapy had an increased prevalence of right-sided and bilateral varicocele compared to patients with AS who were not taking any disease-modifying antirheumatic drugs and the healthy control group.

WOS: 000333263500025, PubMed ID: 24369413, Methods. Fifteen centres from the different geographical regions of Turkey were included in the study. Detailed demographic and medical data based on a structured questionnaire and medical records were collected. The diagnosis of amyloidosis was based on histological proof of congophilic fibrillar deposits in tissue biopsy specimens. Results. There were 2246 FMF patients. The male/female ratio was 0.87 (1049/1197). The mean age of the patients was 34.5 years (s.d. 11.9). Peritonitis was the most frequent clinical finding and it was present in 94.6% of patients. Genetic testing was available in 1719 patients (76.5%). The most frequently observed genotype was homozygous M694V mutation, which was present in 413 (24%) patients. Amyloidosis was present in 193 patients (8.6%). Male sex, arthritis, delay in diagnosis, M694V genotype, patients with end-stage renal disease (ESRD) and family history of amyloidosis and ESRD were significantly more prevalent in patients with amyloidosis compared with the amyloidosis-negative subjects. Patients with homozygous M694V mutations had a 6-fold higher risk of amyloidosis compared with the other genotypes (95% CI 4.29, 8.7, P < 0.001). Conclusion. In this nationwide study we found that 8.6% of our FMF patients had amyloidosis and homozygosity for M694V was the most common mutation in these patients. The latter finding confirms the association of homozygous M694V mutation with amyloidosis in Turkish FMF patients.

A patient with primary Sjögren's syndrome complicated with primary biliary cirrhosis and lymphocytic interstitial pneumonia is presented. She was 38 years old and was admitted to our hospital for generalized pruritus, xerostomia, xerophthalmia, fatigue, and reticulonodular changes on her chest X-ray. With the findings of ground-glass attenuation and centrilobular nodules in high resolution computerized tomography, the diagnosis of lymphocytic interstitial pneumonia was made. Oral methylprednisolone 1 mg/kg/day and ursodeoxycholic acid 15 mg/kg/day were started. At the 6th month follow-up, she had no complaints, and pulmonary function tests and high resolution computerized tomography were normal. This is the first case of Sjögren's syndrome, primary biliary cirrhosis and lymphocytic interstitial pneumonia in the English literature.

20th National Gastroenterology Week Meeting -- SEP, 2003 -- Kusadasi, TURKEY WOS: 000227637600039 PubMed: 15749512 Objective: To describe the benefit of ursodeoxycholic acid (UDCA) for the initiation and completion of a successful pregnancy in a previously infertile woman with primary biliary cirrhosis. Design: Case report. Setting: A university hospital with relevant departments. Patient(s): A 29-year-old woman with primary biliary cirrhosis and failure to conceive for 6 years. Intervention(s): Establishment of diagnosis with a liver biopsy, pretreatment of patient with UDCA before conception, and continuation of UDCA after first trimester until term. UDCA was used in the second pregnancy again after the first trimester. Main Outcome Measure(S): Achievement of a safe conception and full-term pregnancy. Result(S): Two consecutive successful pregnancies, a healthy 3,250-g male infant and a healthy 3,000-g female infant. The second conception occurred in a period without the use of UDCA, implicating a latent beneficial effect of either UDCA orthe previous pregnancy via some possible immune mechanism. Conclusion(s): Ursodeoxycholic acid could help achieve conception in infertile women with primary biliary cirrhosis. The use of UDCA after the first trimester is shown to be safe in two consecutive pregnancies. Although it cannot be conclusive, the unintentional use of UDCA in the first 20 days after conception did not result in any teratogenicity in the first child. (c) 2005 by American Society for Reproductive Medicine. Turkish Journal Gastroenterol

Granulomatosis with polyangiitis (Wegener9s) (GPA) is a chronic disease of unknown aetiology that leads to necrotising vasculitis in small and medium-sized vessels characterised by respiratory system and kidney involvement. Intestinal involvement is rare and perforation is even rarer in GPA. In this study, we are presenting a literature review of related cases, and a 29-year-old man referred from the emergency department with a multiple distal ileal perforation that was diagnosed with GPA, and successfully treated with rituximab.

Systemic sclerosis (SSc) is a disease characterized by skin and internal organ involvement. There is progressive accumulation of extracellular matrix components in the skin and involved organs. Tissue fibrosis is the prominent reason for mortality, and still, there is no satisfactory treatment. The aim of this study was to evaluate the effects of urotensin-II (U-II) antagonist palosuran in an animal model of scleroderma. We also planned to measure U-II, endothelin-1 (ET-1), and transforming growth factor-beta 1 (TGF-beta 1) levels, as well as the association of these levels with dermal thickness. Twenty-four male mice were included in this study and they were divided into three groups-group 1: control group, group 2: fibrosis group, and group 3: fibrosis + palosuran treatment group. Fibrosis + palosuran treatment in group 3 reduced ET-1, U-II, and TGF-beta 1 levels. In total, the diminished values were statistically significant in the ET-1 and TGF-beta 1 levels (p < 0.05). Dermal thickness was higher in the fibrosis group, when compared with the other groups. There was no significant relationship between dermal thickness and ET-1, U-II, or TGF-beta 1 levels (p > 0.05). It is believed that U-II is an important mediator in SSc, and its antagonism with palosuran could be a new treatment choice in SSc.

Although it is known that ankylosing spondylitis (AS) is associated with cardiovascular complications, the extent of these complications has not been clearly demonstrated in young adult patients. We have therefore investigated myocardial diastolic functions, carotid intima-media thickness (CIMT), and aortic elastic properties of young adult patients diagnosed with AS. Sixty-six AS patients and 21 age/gender-matched healthy subjects were enrolled in the study. Spectral and tissue Doppler echocardiography, CIMT, aortic strain and distensibility, and serum B-type natriuretic peptide values were compared with disease activity indexes of AS, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and the role of other variables, such as anti-tumor necrosis factor-alpha (anti-TNF-α) treatment, lipid parameters, erythrocyte sedimentation rate, and C-reactive protein. Both mitral early diastolic flow speed (mE) and late diastolic flow speed (mA) scores were lower among patients than among the control subjects (p = 0.015 and p = 0.035, respectively). The Em ratio of the patients was remarkably lower than that of the control subjects (p = 0.044). BASDAI scores of >4 were used to identify patients with more active disease. The mA and mE/mA ratios were significantly different between patients with a BASDAI score of >4 and those with a BASDAI score of

The cyclin D1 gene (CCND1) is a proto-oncogene playing a critical role in the transition through the G1 to the S phase of the cell cycle and is overexpressed in many tumors. G870A polymorphism at the exon4/intron4 splicing region of the CCND1 gene may play a role in pituitary tumorigenesis and invasiveness. The objective of this study was to examine CCND1 polymorphism in patients with different types of sporadic pituitary adenomas.One hundred thirty patients (38 male, 92 female, mean age: 45.37+/-13.55 SD years) with sporadic pituitary adenomas (PA group) and 129 healthy controls (HC group) were included in the study. The CCND1 G870A polymorphism in PA and HC were genotyped by PCR-RFLP using peripheral blood samples. CCND1 expression was also evaluated with an immunohistochemical method in tumor tissues of 39 patients of the PA group.The genotype distribution in the PA [AA: 30 (23.1%), AG: 90 (69.2%), GG: 10 (7.7%)] was statistically different from the HC group [AA: 36 (27.9%), AG: 64 (49.6%), GG: 29 (22.5%), p=0.001]. Patients carrying the AG genotype were more frequent compared with the control group. Tumor type, volume, and invasion were not related to the genotype. Immunohistochemically, 21 of the 39 tumors showed nuclear positivity for CCND1, varying between 1 and 40% of tumor cells. Positive staining was observed more intense in patients carrying the AG genotype.CCND1 polymorphism may be an early event in tumorigenesis, but it is not a reliable prognostic criterion.

Rubinstein-Taybi syndrome (RTS) is characterized by typical facies, short stature, mental retardation, broad thumbs and broad great toes. The syndrome is at least in part caused by microdeletions at chromosome 16p13.3 or by mutations in the gene for the CREB binding protein (CBP), which is located at 16p13.3. Familial Mediterranean fever (FMF) is an autosomal recessive disease, caused by mutations in the FMF-gene [Mediterranean fever (MEFV)] and characterized by recurrent attacks of fever and peritonitis, arthritis and pleuritis. The FMF gene (MEFV) has recently been cloned by two consortia and 30 point mutations, causing the disease have been identified. MEFV maps to chromosome 16p and encodes a 781-amino-acid protein called pyrin or marenostrin, which is expressed mainly in neutrophils and myeloid bone marrow precursors. Herein, we report a case with RTS and FMF.

MASIF (Medication Adherence Scale in FMF) is an instrument designed to measure adherence to treatment in children with Familial Mediterranean Fever (FMF). We have developed this scale for children with FMF and found valid and reliable.

Demonstrating the efficiency and safety of rituximab (Rtx) in the treatment of active rheumatoid arthritis (RA) and tuberculosis (TB). Two cases of RA with active TB were followed up to 3 years following the initiation of Rtx. The former case presented with a history of concomitant diagnosis of both RA and TB and the latest one, also diagnosed with RA and reactivation of TB developed during the anti-tumour necrosis factor treatment. After a sufficient time of follow-up, we have observed that Rtx seems to be safer and efficient in the treatment of active RA and TB.

To the Editor: Despite the positive effects of isotretinoin on a number of cancers and severe skin conditions, several disorders of the musculoskeletal system have been reported in patients who are treated with it. Reactive seronegative arthritis and sacroiliitis are very rare side effects1,2,3. We describe 4 cases of inflammatory back pain without sacroiliitis after a month of isotretinoin therapy. We observed that after termination of the isotretinoin therapy, patients’ complaints completely resolved. Musculoskeletal system side effects reported from isotretinoin treatment include skeletal hyperostosis, calcification of tendons and ligaments, premature epiphyseal closure, decreases in bone mineral density, back pain, myalgia and arthralgia, transient pain in the chest, arthritis, tendonitis, other types of bone abnormalities, elevations of creatine phosphokinase, and rare reports of rhabdomyolysis. Musculoskeletal symptoms are common with isotretinoin therapy, but sacroiliitis is a very rare adverse … Address correspondence to Dr. Y. Pehlivan, Gaziantep Universitesi Sahinbey Arastirma Hastanesi, Romatoloji BD, Gaziantep 27310, Turkey. E-mail: drpehlivan{at}hotmail.com