Timuçin Kaşifoğlu

Amyloidosis and its related factors in Turkish patients with familial Mediterranean fever: a multicentre study

OBJECTIVE The primary aim of this study was to investigate the prevalence of amyloidosis and its related factors in a large number of FMF patients. 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.

Identification of Susceptibility Loci in IL6, RPS9/LILRB3, and an Intergenic Locus on Chromosome 21q22 in Takayasu Arteritis in a Genome-Wide Association Study

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.

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 Takayasus 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.

Cytomegalovirus-induced interstitial pneumonitis in a patient with dermatomyositis

Dermatomyositis (DM) patients might present with pulmonary involvement as the first manifestation or during the follow-up period. It is sometimes difficult to determine whether the clinical manifestations related with pulmonary involvement are due to DM or to an infectious process. We report a case of DM patient who developed interstitial pneumonitis induced by cytomegalovirus (CMV) while receiving immunosuppressive treatment. To the best of our knowledge, this is the second report in the literature of interstitial pneumonitis secondary to CMV infection in a patient with DM.

Incidence of Cyclophosphamide-induced Urotoxicity and Protective Effect of Mesna in Rheumatic Diseases

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.

Diagnostic dilemma of paraneoplastic arthritis: case series.

Paraneoplastic arthritis (PA) may mimic rheumatic diseases. While presenting the demographic and laboratory features of the patients diagnosed with PA, this study also aims to provide possible appropriate tools to differentiate the PA cases from early rheumatoid arthritis (ERA).

Retrospective evaluation of 22 patients with Takayasu’s arteritis

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

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 Stills 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.

PTU-induced ANCA-positive vasculitis: an innocent or a life-threatening adverse effect?

Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides are rare, but they can be triggered by chemicals, infections and drugs; among them, antithyroid drugs are common. Autoimmune disorders, such as vasculitis, are unusual, but serious complications of antithyroid therapy. Both propylthiouracil (PTU) and methimazole may induce ANCA-associated vasculitis. PTU-induced vasculitides may have different organ involvement patterns. Herein, we report four cases with ANCA-associated vasculitis with different clinical manifestations.

Disease-modifying antirheumatic drugs increase serum adiponectin levels in patients with rheumatoid arthritis.

Background:Adiponectin is an adipocyte-derived adipokine with immunosuppressive and anti-inflammatory properties. It also decreases expression of adhesion molecules. In terms of its relationship with acute-phase reactants, there are conflicting results in patients with rheumatoid arthritis (RA). Objectives:The objectives of this study were to evaluate the levels of adiponectin in RA patients before and after the treatment with disease-modifying antirheumatic drugs (DMARDs) and to evaluate whether there is a correlation between adiponectin levels and disease activity and acute-phase-response reactants (APRRs). Methods:Serum adiponectin levels, APRRs, total and high-density lipoprotein cholesterol (HDL-C), body mass index, and body fat mass were measured in 27 patients with RA before and after the treatment with DMARDs plus prednisolone. An inclusion criterion for RA patients was to be DMARD naive for at least 6 months or to have been newly diagnosed with RA. Twenty patients with osteoarthritis were included in this study as a disease control. Results:No significant difference was found between RA and osteoarthritis group in terms of baseline adiponectin level. Mean adiponectin level and mean HDL-C level increased significantly compared with mean baseline level after the treatment with DMARDs plus prednisolone (10 [SD, 4.9] vs. 13.9 [SD, 8.7] &mgr;g/mL; P < 0.001; 56.8 [SD, 19] vs. 65 [SD, 18] mg/dL, P < 0.004, respectively). APRRs and the 28-joint-count disease activity score decreased significantly at the end of the 3 months of therapy. The adiponectin levels tended to be negatively correlated with acute-phase reactants and disease activity, although no changes were significant. There was a positive correlation between HDL-C and adiponectin levels at 3 month (r = 0.53, P < 0.001). No correlation was found between erythrocyte sedimentation rate and adiponectin levels both at baseline and at 3 months. Conclusion:Adiponectin levels can be modified by effective treatment of rheumatoid arthritis. This suggests that active inflammation may decrease serum adiponectin levels. In consideration of the antiatherogenic and anti-inflammatory features of adiponectin, increased adiponectin levels in patients with RA may result in a more favorable cardiovascular profile.