Familial Mediterranean fever

Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disorder (usually autosomal recessive) characterized by recurrent episodes of fever and serosal inflammation (peritonitis, pleuritis, arthritis).

• FMF is the most common monogenic periodic fever syndrome in Mediterranean populations (Jews, Armenians, Turks, Arabs). Untreated FMF causes chronic inflammation and AA amyloidosis (leading to renal failure), so early diagnosis and prophylactic colchicine are crucial.

• Recurrent short (1–3 day) fevers (38–40°C) with severe serosal pain: often peritonitis (abdominal pain) or pleuritic chest pain.
• Monoarthritis (typically hip, knee, or ankle) in one joint per attack is common.
• Occasional erysipelas-like rash on the legs or myalgia may occur with fever.
• Completely asymptomatic between episodes; most patients have first attack in childhood or adolescence (by age 20 in ~90%).
• Attacks often recur periodically (e.g. monthly); common triggers include stress or infection.

1. Think FMF in a young patient of Mediterranean/Middle Eastern descent with unexplained periodic fevers + serositis (abdomen, chest, joint).
2. During attacks: markedly elevated inflammatory markers (ESR/CRP/SAA) and neutrophils. Imaging or laparoscopy usually shows no permanent pathology.
3. Apply Tel Hashomer criteria (typical attacks or colchicine response with family history) for clinical diagnosis.
4. MEFV genetic testing can confirm diagnosis in atypical cases (although ~10% of patients have no identifiable mutation).
5. A therapeutic trial of colchicine (1–2 mg daily) that prevents attacks strongly supports the diagnosis.

1. Lifelong colchicine (1–2 mg/day) is first-line; it prevents attacks and AA amyloid deposition.
2. If colchicine resistance or intolerance occurs, add an IL-1 inhibitor (anakinra or canakinumab).
3. Ensure patient compliance; monitor SAA/CRP and adjust dose (up to 2.5 mg/day) to achieve complete control.
4. Symptomatic NSAIDs or analgesics can relieve pain during attacks. (Immunosuppressants/steroids are not effective except in specific cases.)

• FMF mnemonic: Fever in Mediterranean families with Periodic serositis.
• Tel-Hashomer criteria are useful: look for recurrent serositis + family history + colchicine response.
• AA amyloid clue: If young patient has unexplained nephrotic syndrome, think chronic FMF.
• Key exam hint: Teen of Jewish/Armenian descent with periodic abdominal pain and fever → think FMF.

• Proteinuria or renal failure – possible AA amyloidosis from untreated FMF.
• Failure to respond to colchicine – check compliance and consider other diagnoses.
• Repeated acute abdomen evaluations/negative surgeries – consider FMF to avoid unnecessary operations.
• Testicular pain/infertility – may indicate amyloid deposition in testes (complication of FMF).

1. Suspect FMF: recurrent fever + serositis in Mediterranean patient.
2. Order labs (ESR/CRP/SAA, CBC) – expect high inflammatory markers during attacks.
3. Rule out infection or surgical emergencies (imaging if peritonitis/pleuritis is severe).
4. Apply Tel-Hashomer criteria or do MEFV genetic test for confirmation.
5. If likely FMF, start colchicine immediately and monitor response.
6. If attacks or inflammation persist despite colchicine, add IL-1 blockade (anakinra/canakinumab).

• Armenian or Middle Eastern adolescent with recurrent peritonitis/fever and no other explanation.
• Periodic pleuritic chest pain or monoarthritis with fever (especially hip/knee) in a high-risk ethnicity.
• Young patient with recurrent fever and erysipelas-like rash on the legs.
• Early-onset renal amyloidosis (nephrotic syndrome) in a young adult suggests undiagnosed FMF.