Familial Mediterranean fever
Familial Mediterranean fever is an autosomal recessive autoinflammatory disease of pyrin, most common in Jewish, Arab, and Turkish populations, causing recurrent short attacks of fever with sterile peritonitis, pleuritis, monoarthritis, or an erysipelas-like leg rash. First-line treatment is lifelong daily colchicine, which both suppresses attacks and prevents secondary (AA) amyloidosis; colchicine-resistant disease escalates to interleukin-1 blockade.
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What this article covers
- Overview
Definition: familial Mediterranean fever (FMF), caused by mutations in the Mediterranean fever gene (MEFV), is an autosomal recessive autoinflammatory disease of pyrin producing recurrent…
- Epidemiology
Most common monogenic autoinflammatory disease: FMF is the most frequently encountered of the autoinflammatory syndromes (autoinflammatory diseases).
- Risk factors
Ancestry: Jewish, Arab, and Turkish ancestry carries the highest disease burden; eastern Mediterranean ancestry raises pretest probability.
- Pathophysiology
Pyrin dysregulation: MEFV mutations affect pyrin, a protein that normally regulates innate immune inflammasome activity; the mutated protein instead drives inflammasome activation.
- Clinical features
Fever with abdominal pain (sterile peritonitis): the dominant presentation, with diffuse abdominal pain and tenderness severe enough to mimic an acute surgical abdomen.
- Differential diagnosis
Acute appendicitis: shares fever and severe abdominal pain and has led to unnecessary appendectomy in FMF, but does not remit spontaneously within 12 to 72 hours nor recur as a stereotyped pattern…
- Diagnosis
The diagnosis is made clinically, based on the stereotyped pattern of recurrent, short, self-limited attacks of fever with serositis in a patient of compatible ethnicity, confirmed in most patients by MEFV genetic testing.
- Management
First-line, all patients, lifelong: colchicine, taken continuously rather than only during attacks: Start colchicine 0.6 mg PO once or twice daily.
- Complications
Secondary (AA) amyloidosis: the major long-term threat of FMF, arising from sustained serum amyloid A protein production during recurrent or subclinical inflammation, depositing most consequentially in the kidney (amyloidosis).
- Prognosis
Attacks are self-limited but recurrent: each resolves within 12 to 72 hours, but untreated patients accumulate frequent recurrences over a lifetime, as illustrated by patients with more than 20 lifetime episodes.
- Prevention
Continuous, lifelong colchicine adherence is the only proven prevention of renal amyloidosis: intermittent or attack-only dosing does not provide the same protection, since it depends on suppressing…
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Related articles
- Autoinflammatory diseases
Autoinflammatory diseases are monogenic disorders of enhanced inflammasome function that cause recurrent, stereotyped fever and multiorgan inflammation without autoantibodies or autoreactive T cells. The cryopyrin-associated periodic syndromes, tumor necrosis factor receptor-associated periodic syndrome, and familial Mediterranean fever are the core named entities; diagnosis rests on the attack pattern plus genetic confirmation, and treatment is built around interleukin-1 blockade with anakinra or canakinumab, or colchicine for familial Mediterranean fever.
- Amyloidosis
Amyloidosis is extracellular deposition of misfolded protein fibrils that stain apple-green with Congo red under polarized light, most often AL (clonal light chains, linked to plasma cell dyscrasias), AA (chronic inflammation), or ATTR (transthyretin, hereditary or wild-type). Diagnosis requires tissue biopsy for Congo red birefringence plus typing of the amyloid protein, and treatment targets the underlying source, plasma-cell-directed therapy for AL, inflammatory disease control for AA, and transthyretin stabilizers or silencers for ATTR.
- Acute appendicitis
Acute appendicitis is luminal obstruction and infection of the vermiform appendix presenting as migratory periumbilical-to-right-lower-quadrant pain, diagnosed by the classic history and exam plus confirmatory imaging (CT in adults, ultrasound or MRI in children and pregnancy), and treated with prompt appendectomy or, in selected uncomplicated cases, antibiotics alone.
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Adult-onset Still disease is a rare systemic autoinflammatory disorder marked by quotidian spiking fevers, an evanescent salmon-colored rash, arthritis, sore throat, and a markedly elevated ferritin. It is a diagnosis of exclusion confirmed by the Yamaguchi criteria, and treatment begins with NSAIDs, escalates to glucocorticoids, then to interleukin-1 blockade (anakinra or canakinumab) or interleukin-6 blockade (tocilizumab) for refractory disease.
- Behcet disease
Behcet disease is a variable-vessel vasculitis, the only vasculitis that can involve arteries and veins of any size, marked by recurrent oral and genital ulceration, uveitis, skin lesions, and pathergy. There is no confirmatory laboratory test; diagnosis is clinical. Treatment is organized by organ severity, from colchicine for mucocutaneous disease to urgent immunosuppression and tumor necrosis factor inhibitors for sight-, organ-, or life-threatening involvement.