Familial Mediterranean Fever in Japan

Abstract

Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease that is prevalent in Mediterranean populations. While it is considered a rare disease in the rest of world, a significant number of FMF patients have been reported in East Asia, including Japan. Our aim was to determine the prevalence of FMF in Japan and elucidate the clinical and genetic features of Japanese patients. A primary nationwide survey of FMF was conducted between January and December 2009. Hospitals specializing in pediatrics and hospitals with pediatric, internal medicine, and rheumatology/allergy departments were asked to report all patients with FMF during the survey year. The estimated total number of Japanese FMF patients was 292 (95% confidence interval, 187-398 people). We evaluated the clinical and genetic profiles of Japanese patients from the data obtained in a secondary survey of 134 FMF patients. High-grade fever was observed in 95.5%, chest pain (pleuritis symptoms) in 36.9%, abdominal pain (peritonitis symptoms) in 62.7%, and arthritis in 31.3%. Of the patients profiled, 25.4% of patients experienced their first attack before 10 years of age, 37.3% in their teens, and 37.3% after age 20 years. Colchicine was effective in 91.8% of patients at a relatively low dose (mean dose, 0.89 ± 0.45 mg/d). AA amyloidosis was confirmed in 5 patients (3.7%). Of the 126 patients studied, 109 (86.5%) were positive for 1 or more genetic mutations and 17 (13.5%) had no mutation detected. Common Mediterranean fever gene (MEFV) mutations were E148Q/M694I (19.8%) and M694I/normal (12.7%). The differences in the prevalence of peritonitis, pleuritis, and a family history of FMF were statistically significant between FMF patients with MEFV exon 10 mutations compared with those without exon 10 mutations.In conclusion, a significant number of patients with FMF exist in Japan. Although Japanese patients with FMF are clinically or genetically different from Mediterranean patients, the delay in diagnosis is an issue that should be resolved.

Three Patients with Familial Mediterranean Fever: A Possible Underdiagnosed Entity in Japan

“…In a nationwide study in Japan, the mean period from disease onset to diagnosis was 9.1±9.3 years, thus suggesting a delay in diagnosis (2). In the present three cases, the mean period from disease onset to diagnosis was 24 months.…”

“…In the nationwide study of FMF in Japan, the MEFV gene mutation was not identified in 17 of 126 patients (13.5%) (2). The present two patients without the MEFV gene mutation were the two elderly patients.…”

“…FMF is typically diagnosed in childhood or adolescence. In the nationwide survey in Japan, 25.4% of the patients experienced their first attack before 10 years of age, 37.3% in their teens, and 37.3% after age 20 (2).…”

“…FMF is distributed mainly in the Mediterranean region, and it is considered to be rare in East Asia, including Japan (1). The estimated total number of Japanese FMF patients was 292 according to a nationwide survey of FMF in 2009 (2). FMF is typically diagnosed in childhood or adolescence.…”

Acute Pericarditis as the First Manifestation of Familial Mediterranean Fever: A Possible Relationship with Idiopathic Recurrent Pericarditis

“…Although many mutations have been reported, the most frequent mutations are located in exon 10 (M694V, M680I, V726A and M694I) and exon 2 (E148Q) (12). Migita et al reported that among 142 Japanese FMF patients, they found 12 carrying a heterozygous E84K mutation and four carrying a heterozygous G304 mutation who presented with a heterogeneous clinical phenotype (13). Meanwhile, Brucato et al searched for MEFV mutations confined to exon 10 (using direct sequencing) and exon 2 E148Q (by restriction site analysis) in 23 Italian IRP patients; however, they found no mutations (14).…”