Background Familial Mediterranean fever (FMF) is the most frequent form of periodic fever syndromes which is characterized by recurrent febrile inflammatory attacks of serosal and synovial membranes. Attacks are usually preceded by a prodromal period with great inter-individual differences1. Colchicine reduces severity, frequency and duration of attacks, and prevents development of amyloidosis. Despite regular colchicine use, a considerable number of FMF patients continue to suffer from attacks which cause significant morbidity, impairment in quality of life and loss of work. Anti IL-1 agents are newly introduced and promising agents for the autoinflammatory diseases. Recently, on demand use of anakinra has been shown to be effective in mevolonate kinase deficiency2. Likewise, on demand use of IL-1 antagonists during prodromal period might halt or reduce the severity of attacks in patients with FMF. Therefore, it’s crucial to well-define the prodrom of FMF attacks.
Objectives To investigate the prodromal period in FMF and its clinical associations.
Methods Eighty-five patients with FMF (51 female, mean ± standart deviation age 36.2±9.9 years) who continued to have attacks despite colchicines theraphy were enrolled. Demographic data, disease characteristics and MEFV genotypes were retrieved from the medical records. Patients were meticulously questioned about the attack characteristics and the prodromal period preceding these attacks. Logistic regression analyzes were used to investigate clinical associations of prodroma. Age, sex, disease duration, MEFV genotypes, education level, attack severity, similarity, duration and presence of triggering factors are included in analyzes.
Results Fever, peritonitis, pleuritis, arthritis and erysipeloid-eruption (ELE) had been observed in 66 (77.6%), 82 (96.5%), 50 (58.8%), 58 (68.2) and 32 (37.6%) patients respectively. Sixty-three (76.8%) and 21 (42%) patients had well-characterized prodromata of peritonitis and pleuritis attacks, with a median duration of 4 hours (min 0.5- max 24). About half and one-third of the patients reported attack prodroma in arthritis and ELE with median duration of 3 hours (min 0.5- max 10), respectively. Similarity of attacks [odds ratio 13.6 (95%CI, 1.02-182)] and attack severity [odds ratio 1.62 (95%CI, 1.03-2.53] were found to be the clinical determinants of serosal attacks. Age, sex, disease duration, MEFV genotypes, education level and presence of triggering factors did not associate with attack prodroma.
Conclusions Majority of attacks in FMF are preceded with a prodromal period. Similarity and severity of attacks are the clinical predictors for having prodromal period. This period might be a window of opportunity for the acute treatment of an impending attack.
Lidar M, et al. The prodrome: a prominent yet overlooked pre-attack manifestation of familial Mediterranean fever. J Rheumatol. 2006;33:1089-92.
Bodar EJ, et al. On-demand anakinra treatment is effective in mevalonate kinase deficiency. Ann Rheum Dis. 2011;70:2155-8.
Disclosure of Interest None Declared