Frequency, characteristics, and clinical determinants of 'prodrome' in familial Mediterranean fever patients.

Objective: Prodrome is defined by manifestations that precede a familial Mediterranean fever (FMF) attack and predict its emergence. We aimed to determine the frequency, characteristics, and clinical determinants of prodrome in patients with FMF.Method: This cross-sectional study was conducted in a tertiary rheumatology clinic. During the clinical interview, all patients completed a standardized questionnaire about the pre-attack period. Prodrome was defined as the presence of any recurrent pre-attack manifestation occurring at least 4 h before an attack. Patients were classified according to whether they had prodrome of any kind of attack.Results: The study enrolled 401 patients aged 37.7 ± 11.0 years (mean ± sd). Male gender, M694V/M694V, homozygous MEFV mutation, peritonitis, pleuritis, and arthritis were more frequent in prodrome-positive patients. Altogether, 141 patients (35.2%) had prodrome. Male gender and ever having attack types of peritonitis or arthritis were independent clinical determinants of prodrome [relative risk (95% confidence interval): 1.72 (1.07-2.76), p = 0.02; 4.27 (1.80-10.1), p = 0.001; 1.77 (1.04-3.04), p = 0.04, respectively]. Age, MEFV mutations, pleuritis, and erysipelas-like erythema were not clinical determinants.Conclusions: All FMF patients, particularly males and patients who had peritonitis or arthritis at any time, should be questioned about prodrome. Prodrome should be analysed in terms of elucidating the pathogenesis of FMF and as an opportunity for a secondary prevention strategy for impending attacks. This study may shed light on prodrome for future cytokine or drug studies with the purpose of developing new cost-effective treatment protocols irrespective of colchicine resistance.

Chronic inflammation in adult familial Mediterranean fever patients: underlying causes and association with amyloidosis.

Background: Chronic inflammation, as determined by persistently elevated acute-phase reactants in attack-free periods, can occasionally be observed in patients with familial Mediterranean fever (FMF) and is suggested to be a risk factor for the development of amyloidosis. We aimed to investigate the underlying causes of chronic inflammation in FMF patients and its association with amyloidosis in long-term follow-up. Method: Electronic medical records of FMF patients who had regular follow-up for ≥ 5 years in our cohort were utilized. As part of routine evaluation, detailed history, physical examination, and pertinent laboratory and radiographic investigations were performed in all patients to determine potential causes of elevated C-reactive protein (CRP) levels. Results: The study included 146 FMF patients who had no evidence of amyloidosis at baseline and had regular follow-up for ≥ 5 years. Thirty-seven patients (25.3%) were found to have chronic inflammation in the disease course. Twenty-five (67.5%) of them had either very frequent attacks or chronic manifestations of disease. In the entire study group, amyloidosis developed in five patients (3.42%) during the 5 year follow-up, four in the FMF with chronic inflammation group (10.8%), and only one of the 109 patients without chronic inflammation (odds ratio 13.09, 95% confidence interval 1.41-121.2). Conclusions: The results suggest that persistently high CRP levels during the attack-free periods may be a strong risk factor for the development of amyloidosis in patients with FMF. The vast majority of FMF patients with chronic inflammation had active FMF.