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Familial Mediterranean fever

Familial Mediterranean fever (FMF) is a hereditary inflammatory disorder that affects groups of patients originating from around the Mediterranean Sea (hence its name). It is prominently present in the Armenian people (up to 1 in 7 affected), Sephardi Jews (and, to a much lesser extent, Ashkenazi Jews), people from Turkey, the Arab countries and Lebanon. more...

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Clinical symptoms


There are seven types of attacks. 90% of all patients have their first attack before they are 20 years old. All develop over 2-4 hours and last anytime between 6 hours and 4 days. Most attacks involve fever:

  1. Abdominal attacks, featuring abdominal pain affecting the whole abdomen with all signs of acute abdomen (e.g. appendicitis). They occur in 95% of all patients and may lead to unnecessary laparotomy. Incomplete attacks, with local tenderness and normal blood tests, have been reported.
  2. Joint attacks, occurring in large joints, mainly of the legs. Usually, only one joint is affected. 75% of all FMF patients experience joint attacks.
  3. Chest attacks with pleuritis (inflammation of the pleural lining) and pericarditis (inflammation of the pericardium). Pleuritis occurs in 40%, but pericarditis is rare.
  4. Scrotal attacks due to inflammation of the tunica vaginalis. This occurs in up to 5% and may be mistaken for acute scrotum (i.e. testicular torsion)
  5. Myalgia (rare in isolation)
  6. Erysipeloid (a skin reaction on the legs, rare in isolation)
  7. Fever without any symptoms (25%)


AA-amyloidosis with renal failure is a complication and may develop without overt crises. AA (amyloid protein) is produced in very large quantities during attacks and at a low rate between them, and accumulates mainly in the kidney, as well as the heart, spleen, gastrointestinal tract and the thyroid.

There appears to be an increase in the risk for developing particular vasculitis-related diseases (e.g. Henoch-Schoenlein purpura), spondylarthropathy, prolonged arthritis of certain joints and protracted myalgia.


The diagnosis is clinically made on the basis of the history of typical attacks, especially in patients from the ethnic groups in which FMF is more highly prevalent. An acute phase response is present during attacks, with high C-reactive protein levels, an elevated white blood cell count and other markers of inflammation. In patients with a long history of attacks, monitoring the renal function is of importance in predicting chronic renal failure.

A genetic test is also available now that the disease has been linked to mutations in the MEFV gene. Sequencing of exons 2, 3, 5, and 10 of this gene detects an estimated 97% of all known mutations.

Disease mechanism


Virtually all cases are due to a mutation in the MEFV gene, which codes for a protein called pyrin or marenostenin. This was discovered in 1997 by two different groups. Various mutations of this gene lead to FMF, although some mutations cause a more severe picture than others. Mutations occur in exons 2, 3, 5 and 10.


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