L. Kilic

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.

Characteristics Predicting Tuberculosis Risk under Tumor Necrosis Factor-α Inhibitors: Report from a Large Multicenter Cohort with High Background Prevalence

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.

The Reporting of Patient-reported Outcomes in Studies of Patients with Rheumatoid Arthritis: A Systematic Review of 250 Articles

Objective. Patient-reported outcomes (PRO) in rheumatoid arthritis (RA) provide important information regarding disease effect. The study objective was to assess the frequency of PRO use in recent RA studies and compare results with a previous systematic review (SR) in 2005–2007. Methods. An SR was performed in PubMed MEDLINE (January 2015). Publications were identified using these MEdical Subject Headings terms: “arthritis, rheumatoid” with a limitation to “humans,” “all adults: 19+ years,” “English,” “published in the last 2 years,” and “clinical trials.” All studies were assessed, whatever their designs. All PRO reported in publications were classified according to general domains of health by 2 authors. Statistics were descriptive. Results. Two hundred fifty articles were analyzed. Of them, 113 (45.2%) were randomized controlled trials; 138 different PRO were reported. The most frequent PRO, similar to the 2007 SR, were function (68.0%), pain (40.0%), patient’s global assessment (49.2%), and health-related quality of life (18.4%). Fatigue (14.4%), morning stiffness (10.0%), psychological status (9.6%), productivity losses (6.4%), utility (5.2%), sleep disturbance (2.4%), and coping (2.0%) were rarely reported. Although frequent domains were reported using well-validated questionnaires, the others were reported using heterogeneous questionnaires. Conclusion. The PRO collected and reported in RA studies are remarkably consistent with those seen in 2005–2007, and reflect the existing RA Core Set measures. Other domains of health prioritized by patients including fatigue, psychological status, productivity losses, sleep disturbance, and coping remain rarely reported. Further, heterogeneity in outcome measures used presents challenges in interpreting true disease effect and response to therapy.

Assessment of the HScore for reactive haemophagocytic syndrome in patients with rheumatic diseases

Objectives: Reactive haemophagocytic syndrome (RHS) is a hyperinflammatory disorder often occurring in the background of several disorders such as infections, malignancies, and rheumatic diseases. Recently, a score known as the HScore was developed for the diagnosis of RHS. In the original study, most of the patients had underlying haematological malignancy or infection and the best cut-off value for the HScore was 169 (sensitivity 93%; specificity 86%). In this study we aimed to analyse the performance of the HScore in rheumatic disease-related RHS. Method: The patients with rheumatic disorders evaluated in the Departments of Rheumatology and Paediatric Rheumatology at Hacettepe University, Ankara, Turkey between 2002 and 2014 were reviewed retrospectively. The first group (n = 30) consisted of patients with RHS; the control group (n = 64) included patients with active rheumatic diseases without RHS. Results: In the RHS group, 14 (46.7%) had adult-onset Still’s disease (AOSD), 10 (33.3%) systemic juvenile idiopathic arthritis (SJIA), and six (20%) systemic lupus erythematosus (SLE). The control group (n = 64) consisted of 32 (50%) AOSD, 13 (20.3%) SJIA, and 19 (29.7%) SLE patients. Applying the HScore to the RHS patients, the best cut-off value was 190.5 with a sensitivity of 96.7% and specificity of 98.4%. When we excluded the patients from the control group who had not had bone marrow aspiration (n = 23), the same cut-off (190.5) performed best (sensitivity 96.7%; specificity 97.6%). Applying the 2004 haemophagocytic lymphohistiocytosis (HLH-2004) criteria gave a sensitivity of 56.6% and a specificity of 100% in the whole study group. Conclusions: In our study, a cut-off value for the HScore different from the original study performed better. Further studies are warranted to determine optimum cut-off values in different studies.

Pulmonary hypertension in systemic lupus erythematosus: pulmonary thromboembolism is the leading cause.

BackgroundPulmonary hypertension (PH) is a life-threatening complication of systemic lupus erythematosus (SLE). Pulmonary hypertension in SLE has a variety of causes. Diagnosing early and defining the cause of PH accurately can provide better clinical outcome in SLE. We investigated the causes and characteristics of PH in patients with SLE. MethodsOne hundred twenty-one patients with SLE who had a visit in a 6-month period were assessed retrospectively. Patients who ever had a systolic pulmonary arterial pressure of 40 mm Hg or greater by Doppler echocardiography were considered to have PH. ResultsAmong 122 patients, 65 had echocardiography for some reason, and 10 (8.2%) were diagnosed as having PH by echocardiographic examination. This number reduced to 9 (7.4%) when we excluded the patient with normal pulmonary artery pressure at right heart catheterization. Causes of PH were as follows: thromboembolic events in 4 patients (44.4%) (2 of them had chronic thromboembolic PH), left-sided heart disease in 2 patients (22.2%), pulmonary arterial hypertension in 1 patient (11.1%), high cardiac output state in 1 patient (11.1%), and transient elevation of systolic pulmonary artery pressure in 1 patient (11.1%) who had a history of venous thromboembolism. Venous thromboembolic disease was significantly higher in patients with SLE with PH in comparison to patients with SLE without PH (7 patients [6.3%] vs 5 patients [50.0%]; P = 0.001). All patients improved clinically during their short-term follow-up. ConclusionsPatients with SLE are at increased risk for PH. This study highlights the complexity of the differential diagnosis of PH in patients with SLE once again and emphasizes the importance of pulmonary thromboembolism as a cause of PH. One should investigate patients with SLE with unexplained symptoms and/or signs related to PH for possible treatable causes.

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.

Disease severity in adult patients of Turkish ancestry with familial mediterranean fever living in Germany or Turkey. Does the country of residence affect the course of the disease

BackgroundThe environment may affect the course of familial Mediterranean fever (FMF). ObjectiveThe objective of this study was to compare disease severity between adult FMF patients in Turkey (TR) and Germany (G). MethodsAdult FMF patients of Turkish ancestry on colchicine living in Turkey (n = 40) or G (n = 35) were compared. Disease severity, C-reactive protein (CRP), and erythrocyte sedimentation rate were assessed. ResultsGroups differed significantly in the following aspects: age at onset of disease (TR: 15.6, G: 10.8 years; P = 0.02), delay between onset and initiation of colchicine treatment (TR: 6.8 years, G: 14.9 years; P < 0.001), female gender (TR: 80%, G: 57.1%; P = 0.04), and duration of disease (TR: 14.4 years, G: 23.4 years; P < 0.001). There was no significant difference in colchicine treatment concerning average dosing and duration of therapy. No significant difference could be found between the 2 groups in CRP and disease severity as assessed by the score of Pras et al. (Am J Med Genet. 1998;75:216–219) even after adjusting for potential confounding variables. Mean erythrocyte sedimentation rate was significantly higher among patients living in G (TR: 13.2 mm/first hour, G: 26.3 mm/first hour; P < 0.001). Among patients living in Germany, there was a significant difference in age at FMF onset depending on their country of birth (born in TR: 14.9 years, born in G: 6.9 years; P = 0.0001). ConclusionsIn adult FMF patients living in Turkey or Germany, no difference in disease activity or CRP could be found. German patients were younger at onset of disease and had a longer delay between onset and initiation of colchicine treatment.

Inflammatory bowel diseases and Takayasu's arteritis: coincidence or association?

Takayasus arteritis (TA) and inflammatory bowel disease (IBD) are rare diseases but there are case reports presenting their co‐existence in the literature. The aim of this study was to investigate the relation between IBD and TA.

Aspirin resistance in systemic lupus erythematosus. A pilot study

Systemic lupus erythematosus (SLE) patients are at increased risk of thrombosis and cardiovascular diseases. Aspirin is an effective treatment option for these patients. The aim of this study was to investigate the presence of aspirin resistance in SLE patients. We studied aspirin resistance in 33 SLE patients and nine healthy controls by using a Multiplate® impedance aggregometer (Dynabyte GmbH, Munich, Germany). Twenty-six SLE patients were on regular aspirin treatment. Aspirin resistance was found in five (19.2%) out of 26 patients who were on aspirin treatment. When the tests were repeated by adding acetylsalicylic acid in the medium, all of these patients became responsive to the aspirin. SLE disease activity, body mass index, smoking status, and the presence of anticardiolipin antibodies or positive lupus anticoagulant test results were no different in patients with or without aspirin resistance. (p > 0.05 for all). Our results suggest that there may be a considerable number of SLE patients with aspirin resistance.

Assessment of cardiac autonomic nervous system involvement in systemic sclerosis via exercise heart rate recovery.

Objective: To assess exercise heart rate recovery (HRR) indices in patients with systemic sclerosis (SSc) for an assessment of their cardiac autonomic function. Subjects and Methods: Thirty-five patients with diffuse or limited SSc and 35 healthy controls were enrolled. All subjects underwent exercise testing and transthoracic echocardiography. The HRR indices were calculated by subtracting the first- (HRR1), second- (HRR2) and third-minute (HRR3) heart rates from the maximal heart rate. Results: The SSc and control groups were similar in age (45.2 ± 11.6 vs. 43.9 ± 10.0 years), had identical gender ratios (31 female/4 male in both groups) and similar left ventricular ejection fraction (66.5 ± 5.1 vs. 67.7 ± 5.9%). The mean HRR1 (21.8 ± 4.4 vs. 27.7 ± 4.3 bpm, p = 0.001), HRR2 (43.8 ± 6.3 vs. 47.6 ± 4.4 bpm, p = 0.004) and HRR3 (58.8 ± 10.3 vs. 63.6 ± 7.3 bpm, p = 0.031) values were significantly lower in the SSc group than in the healthy controls. HRR indices were similar in the limited and diffuse SSc subgroups. Conclusions: The patients with SSc had lower HRR indices than normal subjects. Cardiac autonomic functions might be involved in SSc, even in patients without cardiac symptoms.