Familial Mediterranean Fever

Clinical Manifestation:

  • FMF classically presents with unprovoked, recurrent attacks of fever and painful polyserositis mainly affecting the peritoneum (most common), synovium, and pleura that usually (but not always) begin in childhood.
  • Acute episodes may last from 24 to 72 hours and have variable frequency, often without a recognized triggering event.
  • Commonly reported precipitating causes include viral illness, emotional stress, excessive/intense physical activity, high-fat diet, extremes of temperature, and menstruation in women.
  • Half of the affected individuals report experiencing a prodrome of discomfort and/or psychological uneasiness up to 24 hours before the actual attack.
  • Fevers are generally accompanied by abdominal (most common), chest, or joint pain; thus, the attacks resemble peritonitis, pleuritis, or synovitis (depending on the serous membrane involved) from other causes, which is the reason for frequent misdiagnosis, exploratory surgery, and unnecessary appendectomies.
  • Skin manifestations include erysipelas-like lesions that are reminiscent of cellulitis and cluster unilaterally on the extensor surfaces of the leg or over the ankles and/or dorsum of the foot.

Complications:

  • In untreated individuals, the risk of amyloidosis (SAA type) is arguably the most significant complication of this condition.
  • Decreased fertility by oligospermia/azoospermia in men or by peritoneal inflammatory exudate leading to fibrous abdominal and ovarian adhesions noted in some affected women.
  • Intermittent intestinal obstruction

Diagnosis:

  • The patient’s medical history, family history, ethnicity, and physical examination findings are the most salient entities.
  • Labs reveal an increase in acute phase reactants such as C-reactive protein, fibrinogen, erythrocyte-sedimentation rate, and increased white blood cell count with neutrophilia.
  • Molecular genetic diagnostic testing is used to provide a confirmation of the FMF diagnosis as it is obviously more specific than the other laboratory analytes such as erythrocyte-sedimentation rate and C-reactive protein.

Treatment: centered on prevention of painful attacks and the development of amyloidosis.

  • Colchicine is the gold standard and indeed the only recommended drug for treating FMF. It is thought to primarily concentrate in neutrophils and inhibit their increased chemotactic activity during FMF attacks.
  • NSAIDS: may be used to expectantly treat fever and pain, although it is not always effective. Before a definitive diagnosis, many patients with intractable pain are given steroids or narcotics; although these drugs do provide temporary relief, we do not recommend them for long-term use, for obvious reasons: aside from their well-known side effects, they are not useful in preventing the one fatal complication of FMF, amyloidosis.

Genetics in Medicine (2011) 13, 487–498; doi:10.1097/GIM.0b013e3182060456