The prodrome: a prominent yet overlooked pre-attack manifestation of familial Mediterranean fever

Abstract

Objective: To identify and characterize pre-attack symptoms (prodrome) in patients with familial Mediterranean fever (FMF).

Methods: Forty-eight patients with FMF whose attacks are preceded by a prodromal period composed the study population. Clinical, demographic, and genetic characteristics of the study group were compared to those of a control group of 48 patients with FMF whose attacks begin without a premonitory phase. Patients of both groups were recruited consecutively, during their routine followup visit to the FMF clinic.

Results: A prodrome was found to be a common manifestation of FMF, experienced by about 50% of the patients. Overall, demographic, clinical, and genetic variables were comparable between study and control groups. In affected patients prodrome recurs in most attacks, lasts a mean of 20 hours, and manifests with either a mildly unpleasant sensation at the site of the forthcoming spell (discomfort prodrome), or with a spectrum of physical, emotional, and neuropsychological complaints (variant prodrome). The 2 types of prodromata are frequently accompanied by a host of constitutional symptoms.

Conclusions: A prodromal period heralding attacks is a newly defined and reliable FMF manifestation that reproducibly predicts attacks and may help prevent attacks and elucidate the pathogenesis of the disease.