Familial mediterranean fever (FMF) in Apulia: rare, or actually not? A 14 year experience as Internist

ABSTRACT

Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disorder characterized by recurrent attacks of fever and serosal inflammation. The clinical features consist of especially abdominal pain, chest pain and arthralgias, plus erysipelas-like manifestations. According to the available literature, most patients with FMF experience their first attack in early childhood, before the ages of 10 and 20 years in 65 and 90% of cases, respectively. Rarely, the initial attack can occur in individuals older than 50 years of age. We report our experience with FMF during the last 14 yrs [1], following case #1 aged 36 yrs. [2]. In the regions of Apulia and Basilicata, we could identify several family clusters due to historical and geographical roots. In the initial series of 60 cases, the five most frequent MEFV variants were E148Q/R761H (41.9%, compound heterozygosity), K695R (10.2%, heterozygosity), E148Q (8.2%, heterozygosity), E148Q/R761H/A744S (6.1% compound heterozygosity), and P369S (6.1%, heterozygosity). Notably, the mean disease onset was 22 yrs and the diagnostic delay was 15 yrs. The severity of symptoms was generally mild/intermediate but about 30% of this initial series had undergone unnecessary abdominal surgery. Females were significantly older than males (median 40 vs. 30 yrs., respectively, P = 0.03). Symptoms including fever were largely responsive to the average dose of colchicine 1 mg/day ad libitum. Only one case required canakinumab for resistance/intolerance to colchicine. We did not observe severe cases of secondary amyloidosis and kidney damage. Later, we extended our observations and concluded that the combination of available expert information with sensitive predictor tools could result in a more accurate interpretation of clinical consequences of MEFV gene variants, and a better genetic counselling and patient management, with respect to symptom severity as well [3, 4]. We recently reported the rare case of a very late onset of FMF symptoms in a patient aged 86 [5]. Further studies in FMF have focused the attention on environmental factors including intestinal microbiota [6], COVID-19 pandemic [7], blood-based test for diagnosis and functional subtyping of FMF by the ex vivo colchicine assay [8], and histopathological characteristics of synovitis in FMF [9]. Following these seminal observations, we conclude that the Apulia region represents a new endemic area for FMF, a puzzling inherited autoinflammatory disorder. Clinical presentation of FMF can be misleading and requires a complete and early workup to recognize the disease and avoid unjustified surgery. Colchicine remains the gold standard therapy to prevent FMF attacks and fatal long-term complications [10, 11].