Familial Mediterranean Fever

Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease from MEFV (pyrin) gain of function mutations, causing recurrent self-limited febrile serositis.

• Prevalence 1 in 500 to 1000 in Turkish, Armenian, Arab and Jewish populations.

• Pyrin inflammasome activation leads to IL-1 beta release.

• Onset before 20 in 90%. Common mutations: M694V (severe, arthritis, amyloidosis), M680I, V726A, E148Q.

• Complications: AA amyloidosis (renal, nephrotic syndrome, ESKD) in untreated disease, infertility in women, chronic arthritis.

• Attacks lasting 12 to 72 hours: fever, peritonitis (severe abdominal pain, mimics acute abdomen), pleuritis, monoarticular arthritis, erysipelas-like erythema on the lower leg, scrotal pain, pericarditis.

• Attack-free intervals; precipitants include stress, menstruation, exertion.

• Protracted febrile myalgia, vasculitis (IgA vasculitis, polyarteritis nodosa).

• Amyloidosis: proteinuria, nephrotic syndrome.

• Tel Hashomer or Eurofever/PRINTO criteria; clinical diagnosis with response to colchicine.

• Acute phase: raised CRP, ESR, serum amyloid A, neutrophilia, fibrinogen; normal between attacks.

• MEFV gene analysis (two pathogenic variants confirm; single variants or exon 10 in compatible phenotype).

• Urinalysis and 24 hour protein for amyloidosis; biopsy if suspected.

• Exclude other autoinflammatory diseases (TRAPS, HIDS, CAPS), appendicitis, infection, Behçet.

• Colchicine lifelong: adults 1 to 2 mg daily (children under 5: 0.5 mg; 5 to 10 years: 0.5 to 1 mg; over 10: 1 to 1.5 mg), maximum 3 mg daily; controls attacks in 60% completely and 30% partially, and prevents amyloidosis.

• Monitor liver tests, creatinine, blood counts; reduce dose in renal impairment; avoid with strong CYP3A4/P-gp inhibitors (clarithromycin).

• Colchicine resistant (3 or more attacks over 6 months on maximum tolerated dose) or intolerant: anakinra 100 mg SC daily (2 to 8 mg/kg in children), canakinumab 150 mg (2 mg/kg in children) every 4 weeks, rilonacept.

• Amyloidosis: colchicine 2 mg daily, anti-IL-1 therapy, renal transplantation.

• Acute attack: NSAIDs for symptoms.

• Continue colchicine in pregnancy (safe) and breastfeeding; counsel regarding genetic risk.

• Monitor SAA and proteinuria every 6 months.