Sukran Erten

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.

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).

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.

Evaluation of Left Ventricle Function by Strain Imaging in Patients with Familial Mediterranean Fever

Aim: Familial Mediterranean Fever (FMF) is a hereditary inflammatory disease characterized by recurrent fever and serositis. We aimed to evaluate cardiac involvement in FMF patients by using strain and strain rate echocardiographic imaging method in this study. Materials and Methods: Echocardiographic evaluation was performed in 23 FMF patients and 22 healthy controls. FMF diagnosis was based on Tell‐Hashomer diagnostic criteria. Conventional echocardiography, tissue Doppler echocardiography and longitudinal two‐dimensional (2D) strain and strain rate imaging were performed in patient and control groups. Results: There were no significant differences between patient and control groups in terms of 2D, M‐mode, conventional Doppler and tissue Doppler velocities. Left ventricle strain value was significantly lower in five out of eight segments in FMF patients than controls and left ventricle strain rate value was significantly lower in three out of eight segments in FMF patients than controls. Mean left ventricle strain value was significantly lower in FMF patients than controls (–21.1 ± 2.2% vs. –23.8 ± 2.2%; P < 0.001). No significant difference was noted between FMF patients and controls in mean left ventricle strain rate value (–1.61 ± 0.23 vs. –1.58 ± 0.21; P = 0.48). Conclusion: We have shown that although conventional echocardiography and tissue Doppler velocity data were similar, strain, strain rate values were significantly lower in FMF patients than controls. We know that strain and strain rate imaging method might be useful for evaluating subclinical cardiac involvement in case of normal conventional and tissue Doppler velocity data in patients with FMF. (Echocardiography 2010;27:1056‐1060)

Anti-interleukin-1 treatment in 26 patients with refractory familial mediterranean fever

Abstract Objective: To investigate the effect of anti-interleukin-1 (anti-IL-1) treatment on the frequency and severity of attacks and other disease-related clinical parameters and to evaluate the adverse effects associated with anti-IL-1 treatment in 26 patients with refractory familial mediterranean fever (FMF). Methods: The study included 26 FMF patients followed up in our centre using colchicine for 4 months to 30 years. The treatment was switched to anti-IL-1 treatment for various reasons; 20 cases were resistant to colchicine, 8 were intolerant to colchicine, and 3 had prolonged arthritis under colchicine. Clinical response was monitored through the number of attacks, and laboratory inflammation was monitored through erythrocyte sedimentation rate, C-reactive protein, and serum amyloid A concentrations. Colchicine resistance was defined as at least two attacks/month together with C-reactive protein and serum amyloid A levels above the normal range between attacks. The colchicine dose was increased to 2 mg/day before they were considered colchicine-resistant. Results: 24 patients used anakinra (100 mg/day), and 2 used canakinumab (150 mg/month), for –36 months. Sixteen patients with colchicine resistance had no attacks under anti-IL-1 treatment, and 4 had decreased frequency and duration of attacks. Seven of 8 patients intolerant to colchicine used anakinra, and 6 were attack-free under treatment, while 1 using canakinumab had attacks under treatment. One patient with prolonged arthritis used canakinumab but arthritis showed progression and the treatment was changed to IL-6 inhibitor. Three patients had injection site erythema and one had fatigue with anti-IL-1 treatment. Topical steroids with systemic antihistaminics were sufficient for symptom control in two cases, but canakinumab treatment was given due to severe injection site erythema in one case. Conclusion: Anti-IL-1 agents are rational treatment modalities in patients resistant or intolerant to colchicine. Anti-IL-1 agents can control FMF attacks quite effectively and they have a promising role in the treatment of FMF.

Assessment of left ventricular functions in patients with Sjögren's syndrome using tissue doppler echocardiography

In our study, we aimed to evaluate left ventricular function in patients with Sjögren syndrome (SS) using tissue Doppler echocardiography (TDE) and myocardial performance index (MPI) in addition to conventional echocardiographic methods.

Corneal Biomechanical Properties in Rheumatoid Arthritis.

Purpose: To investigate the variations in biomechanical properties of the cornea in rheumatoid arthritis (RA) patients. Methods: A total of 53 RA patients, and 25 healthy individuals (control group) were enrolled. Rheumatoid arthritis patients were classified as in active phase (group 1; n=24) or in remission phase (group 2; n=29). Corneal biomechanical parameters including corneal hysteresis (CH), corneal resistance factor (CRF), corneal compensated intraocular pressure (IOPcc), and Goldmann-correlated IOP (IOPg) were measured with the Reichert Ocular Response Analyzer. Topographical measurements, including central corneal thickness (CCT), anterior chamber depth, iridocorneal angle, and corneal volume were measured using a Sirius corneal topographer. Results: The mean CH was 9.43±1.17 mm Hg in group 1, 9.42±1.84 mm Hg in group 2, and 10.47±1.68 mm Hg in the control group (P=0.03). The mean IOPcc was 17.85±3.2 mm Hg in group 1, 17.95±3.49 mm Hg in group 2, and 15.36±3.11 mm Hg in the control group (P=0.008). The CH showed a significant positive correlation with CRF (P=0.000, r=0.809) and CCT (P=0.000, r=0.461), and a significant negative correlation with IOPcc (P=0.000, r=−0.469). Conclusions: Decrease in the mean CH measurements indicates that ultrastructural changes in the cornea may occur in the active phase, and these changes persist in the remission period. In addition, IOPcc is significantly affected by the corneal biomechanical properties. In RA patients, it is important to control the corneal parameters and IOP measurements against the irreversible changes on the optic nerve.

Two cases of familial Mediterranean fever associated with sarcoidosis (Lofgren's syndrome) and rheumatoid arthritis

Dear Editor, Familial Mediterranean Fever (FMF) is an autosomal recessive disease caused by mutations in the MEFV gene encoding for the pyrin protein which belongs to a class of proteins taking part in the regulation of apoptosis and inflammation. The role of the pyrin domain which provides an uninterrupted inflammatory cascade is blocked by mutations in the MEFV gene. The mutations in the MEFV gene may act as susceptibility factors for diseases with autoinflammatory characteristics through a state of more intense inflammatory response. The impact of MEFV mutations has been shown in inflammatory diseases, namely Henoch-Schonlein purpura, Behçet’s disease, rheumatic heart diseases and rheumatoid arthritis (RA). Sarcoidosis is a chronic, inflammatory disease of unknown etiology and is characterized by the formation of noncaseating granulomas in the affected organs, mostly in the lungs. In this letter, we report two cases of FMF, one of which was associated with sarcoidosis and the other one associated with RA. A 61-year-old woman was admitted to our rheumatology out-patient clinic with widespread bone pain and erythematous skin lesions on the upper and lower limbs. Twenty days prior to admission, she started to complain of chest pain and cough. She had a history of right hip surgery after a fall and was suffering from attacks of abdominal pain and fever for 3 years. On physical examination, she had diffuse, round, subcutaneous, painful, stiff and red nodules in her extremities which were compatible with erythema nodosum (EN). The laboratory test results were as follows: She had a severe acute phase response with erythrocyte sedimentation rate (ESR) 124 mm/h (normal 0–20), C-reactive protein (CRP) 215 mg/L (0–5) and rheumatoid factor (RF) 10.1 U/mL (0–14), angiotensin converting enzyme (ACE) 63.2 U/L (8–52), calcium 9.7 mg/dL (8.6–10), purified protein derivative (PPD) intradermal reaction 9 mm after 72 h. Human leukocyte antigen (HLA)-B27 and pathergy tests were also negative. A chest X-ray showed hilar lympadenopathy. Computed tomography (CT) scan revealed mediastinal lymphadenopathy (LAP) and ground-glass nodules in both lungs. Lung biopsy revealed noncaseified granuloma and epithelioid histiocytes scattered among inflammatory cells (Fig. 1). The patient was diagnosed as having Löfgren’s syndrome, which is a clinical subtype of acute sarcoidosis involving acute arthralgia, bilateral hilar LAP and erythema nodosum. Methylprednisolone 16 mg/day and methotrexate 10 mg/week were prescribed. Erythema nodosum had regressed on follow-up but the patient complained about fever, abdominal and ankle pain and skin rash on her face, neck and back. On genetic analysis, heterozygous mutation for E148Q was detected. Therefore, colchicine was added to methotrexate and steroid treatment. After initiation of colchicine treatment, fever and abdominal pain of the patient recovered. A 28-year-old woman was referred to our rheumatology out-patient clinic with joint pain and swelling in

A Nationwide Experience With The Off‐label Use of Interleukin‐1 Targeting Treatment in Familial Mediterranean Fever Patients

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.

Validity and reliability of medication adherence scale in FMF (adult version)

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.