Diagnosis
Familial mediterranean fever
A rare, hereditary, autoimmune disease characterized by brief (2–3 days) recurrent episodes of abdominal pain/peritonitis (95%), chest pain/pleuritis (40-60%), arthritis (60-75%), fever (78%), skin rashes (23%), headache/aseptic meningitis, and renal failure due to chronic inflammation and subsequent amyloidosis. FMF type 2 describes a phenotype where amyloidosis occurs as the first and only manifestation of the disease.
Also known as: Familial paroxysmal polyserositis, Periodic peritonitis, Reimann syndrome, Siegal-Cattan-Mamou disease, Wolff periodic disease
Etiology
Cause/Pathophysiology
Autosomal recessive mutations in the MEFV (MEditerranean FeVer) gene
MEFV produces a protein called pyrin, which is expressed mostly in neutrophils
Pyrin has a regulatory function of inflammation
Uninhibited activity causes episodes of inflammation in the peritoneum, pleura, and joints with accompanying dermatologic manifestations and fever lasting 48-96 hours
Chronic inflammation --> excess production of amyloid A protein from the acute phase and reactant serum amyloid A --> deposition in the kidneys --> amyloidosis
Dermatologic manifestations: urticaria, diffused erythema on the palms and soles, subcutaneous nodules, angioneurotic edema, pyoderma, Raynaud’s phenomenon [rs3]
Complications [zza]
Secondary AA amyloidosis (affecting GI, spleen, liver, testes, heart, lungs, kidneys)
Glomerulonephritis
Infertility
Bowel obstruction
Epidemiology
Incidence per 100.000 [hwn][kry]
Symptoms & findings
Symptoms
Arthralgia, Arthritis, Cervical motion tenderness, Constipation, Diarrhea, Fever, Headache, Hepatomegaly, Hypoactive bowel sounds, Infertility, Myalgia, Splenomegaly
Clinical findings
Air-fluid level, Elevated Creatinine, Elevated CRP, Elevated Fibrinogen, Elevated Sedimentation Rate, Friction rub, Joint effusion, Leukocytosis, Pericardial effusion, Peritonitis, Pleural effusion, Pleuritis, Proteinuria
Anamneses
None listed.
Localized findings
Approach
Blood test: leukocytosis, CRP, erythrocyte sedimentation rate, serum fibrinogen, IgD
Abdominal x-ray
Chest x-ray
Genetic testing
Skin biopsy
Renal biopsy
Diagnostic criteria of familial Mediterranean fever [rs3]
Definite diagnosis: 2 major or 1 major + 2 minor criteria
Probable diagnosis: 1 major + 1 minor criteria
Major criteria
Recurrent febrile episodes associated with peritonitis, pleuritis or synovitis
Amyloidosis of AA-type without a predisposing disease
Favourable response to daily colchicine
Minor criteria
Recurrent febrile episodes
Erysipelas-like erythema
A positive history of familial Mediterranean fever in a first-degree relative
Treatment
Avoid triggers: [zza]
Exercise
Infection
Menstruation
Stress
Colchicine 2.5 mg/day reduce the frequency/severity of attacks and prevent secondary systemic amyloidosis
NSAIDs
Analgetics
Corticosteroids (single-dose methylprednisolone at the start of episodes)
Thalidomide
Anakinra (interleukin-1 receptorantagonist)
Etanercept
Differential diagnoses
Acute intermittent porphyria, Acute pancreatitis, Amyloidosis, Angioedema, Ankylosing spondylitis, Appendicitis, Behcet's disease, Calcium pyrophosphate deposition disease, Cellulitis, Cholecystitis, Fibromyalgia, Gout, Henoch-Schönlein purpura, Juvenile rheumatoid arthritis, Leukemia, Lyme disease, Lymphoma, Pelvic inflammatory disease, Perforated ulcer, Pericarditis, Periodic fever syndromes, Peritonitis, Pleuritis, Polyarteritis nodosa, Renal failure, Rheumatoid arthritis, Systemic lupus erythematosus, Testicular torsion, Urolithiasis
References
[1] Sarı İ, Birlik M, Kasifoğlu T. Familial Mediterranean fever: An updated review. Eur J Rheumatol. 2014 Mar;1(1):21-33.
[2] Bhatt H, Cascella M. Familial Mediterranean Fever. [Updated 2023 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560754/
[3] Gallego E, Arias-Merino G, Sánchez-Díaz G, Villaverde-Hueso A, Posada de la Paz M, Alonso-Ferreira V. Familial Mediterranean Fever in Spain: Time Trend and Spatial Distribution of the Hospitalizations. Int J Environ Res Public Health. 2023 Feb 28;20(5):4374.
[4] Lainka E, Bielak M, Lohse P, Timmann C, Stojanov S, von Kries R, Niehues T, Neudorf U. Familial Mediterranean fever in Germany: epidemiological, clinical, and genetic characteristics of a pediatric population. Eur J Pediatr. 2012 Dec;171(12):1775-85.
[5] http://emedicine.medscape.com/article/330284 (2014-01-29); [Medscape]
[6] Ebrahimi-Fakhari D, Schönland SO, Hegenbart U, Lohse P, Beimler J, Wahlster L, Ho AD, Lorenz HM, Blank N. Familial Mediterranean fever in Germany: clinical presentation and amyloidosis risk. Scand J Rheumatol. 2013;42(1):52-8.