Familial Mediterranean fever

Familial Mediterranean fever (FMF) (also known as recurrent polyserositis) is a genetic autoimmune condition that is notable for its spontaneous self-limiting acute episodes of fever and serositis, especially peritonitis and synovitis.

Epidemiology

Familial Mediterranean fever tends to be ethnic specific, the vast majority of patients being Turkish, Jewish, Arabic, and Armenian. The largest number of patients globally are found in Turkey, with a disease prevalence between 1 in 150 to 1 in 10,000 patients ¹. It is slightly more common in the male population ¹.

Clinical presentation

Familial Mediterranean fever is characterized by:

• spontaneous serial acute attacks

  • fever (typically >38°C), and

  • symptoms of serosal inflammation

    • abdominal pain (peritonitis) and joint pains (synovitis): most common

    • occasional pleuritis, pericarditis, etc.

  • flu-like symptoms common, e.g. arthralgia, myalgia, etc.

• episodes last minimum 12 hours, subsiding within 3-4 days

• in 90% the first episode occurs in patients <20 years old

  • in 60% the age of initial onset is <10 years of age

Laboratory markers

• mild C-reactive protein (CRP) and white cell count elevation during acute episodes is typical ⁶

Complications

• amyloidosis

  • development of this sequela, and associated amyloid-related chronic renal failure, is a major determinant of the long term prognosis of familial Mediterranean fever

Pathology

Etiology

Familial Mediterranean fever is a single gene defect disorder with an autosomal recessive pattern of inheritance. The MEFV gene is found on chromosome 16p13·3 and it encodes a protein named pyrine. Pyrine is important in the regulatory control of apoptosis and inflammation, however its physiology is still being unravelled. Point mutations in MEFV are typically found in those with familial Mediterranean fever.

Radiographic features

CT is the mainstay of investigation of familial Mediterranean fever. The findings are non-specific and only seen during an acute episode ^3,4:

• dilated mesenteric vessels with widened mesenteric folds ²

• mesenteric adenopathy

• ascites

• splenomegaly ^2,5

• hepatomegaly ⁵

• focal peritonitis ^2,5

The diagnosis of familial Mediterranean fever is usually not considered by radiologists/clinicians unless there is a known history of the condition.

Treatment and prognosis

Colchicine is the primary therapy and in the pre-colchicine era, the prognosis was very poor. In addition to colchicine, anti-interleukin-1 (anti-IL-1) agents, specifically canakinumab ^7,8, may be used in patients resistant or unresponsive to colchicine treatment.

Differential diagnosis

• familial Mediterranean fever is in the differential for an acute abdomen, and occasionally this results in inappropriate surgery ¹

See also

• autoinflammatory diseases with periodic fevers