Familial Mediterranean Fever, FMF

Familial Mediterranean Fever, FMF 

FMF is a familial disease with high fever, abdominal pain, chest pain and joint pain. In the later period, signs and symptoms related to amyloid deposition may accompany. It develops in attacks.

Disease symptoms are caused by painful, non-infectious inflammation of the serous membranes. Attacks usually occur after a trigger such as cold, trauma, menstruation, vaccination. Between attacks does not give any symptoms. The time between attacks is not certain, it varies. Attacks develop suddenly, can last 6-72 hours.



Attacks often begin before the age of 20. Before the attacks, there are usually no symptoms (aura) and they start suddenly. Frequent attacks include fever, abdominal pain, and joint pain.

Genetic transmission in FMF: 

The gene responsible for the disease (MEFV) is on the short arm of chromosome 16. The most common mutations are exon 10 and exon 2. The disease is autosomal recessive (with recessive genes) inherited. In other words, a part of the society carries the disease but does not show any symptoms. According to this:

• If both parents carry an autosomal recessive gene, 25% of the children to be born are healthy, 50% are carriers, and 25% are FMF patients.
• If one of the parents has FMF and the other is healthy, all of the children are carriers.
• If one of the parents is a carrier and the other has FMF, 50% of the children are carriers and 50% are sick.

The disease is more common in some ethnic groups (Jews, Arabs, Armenians, Turks, etc.). However, recently, cases have been reported from different geographies apart from these ethnic groups. Especially in common ethnic groups, the disease can be seen in every 1000 people and carriers can be seen in every 5 people.

FMF symptoms: 

• Fever: A fever of up to 40 °C may be present throughout the attack, but resolves within the first 24 hours in most patients.
• Abdominal pain: Abdominal pain is seen in almost all patients during attacks. Severe, tender abdominal pain similar to acute abdomen.
• Joint attacks: It is mostly in the form of arthritis or joint pain involving only one joint. The knee is most commonly involved. There may be redness, swelling, pain, tenderness, limitation of movement.
• Chest pain: There may be severe pain that radiates to the shoulder, often on one side of the chest, making it difficult to breathe.
• Skin lesion: Most commonly, there may be redness and rash on the front of the legs, on the feet, on the ankles, and it resolves spontaneously within 2-3 days.
• Testicular tenderness: Recurrent swelling, redness, pain and tenderness may be seen in the testicles, especially in men under the age of 20.
• Muscle pain: Muscle pain is encountered in 25% of FMF patients.
• Vascular inflammation: Vascular diseases such as Henoch schönlein purpura or Polyarteritis nodosa can be seen.
• Nerve involvement: It is rare. It most often manifests itself in the form of headaches.
• Amyloid deposition: It is the most basic prognostic indicator and the most important complication of FMF. AA type amyloid deposition may develop especially in patients who are not followed up and treated regularly. Protein loss in the urine and renal failure may occur in the later period.

FMF diagnosis: 

There is no definitive diagnostic test for the disease. The diagnosis of the patient is made with a detailed anamnesis and a good physical examination and laboratory tests.

The characteristics of the patient’s attacks, their duration, presence of fever, etc. are questioned. Abdominal examination, joint and skin findings are investigated.

• Blood tests: Complete blood count may show an increase in white blood cells, increased fibrinogen, beta2 microglobulin, sedimentation and increased CRP.
• Urine tests: There may be proteinuria,
• Genetic analysis : Disease-specific genetic mutations are investigated.
• Imaging tests : Direct radiographs of the lungs and joints, abdominal ultrasound, etc. may be required.
• Biopsy : Renal biopsy and rectal biopsy can be tried, especially in patients with suspected amyloid deposition.

None of the tests may be sufficient for a definitive diagnosis. In this case, if FMF is suspected, colchicine treatment is started. If the time between attacks is getting longer and the attacks are getting lighter, it may be FMF.

There are some defined diagnostic criteria. Evaluation is made according to major or minor criteria. Presence of 2 major or 1 major and 2 minor criteria makes a definitive diagnosis. Presence of 1 major and 1 minor criteria is considered as probable FMF.

• Major Diagnostic Criteria:
  • Episodes of peritonitis, synovitis and pleuritis with fever
  • AA amyloidosis
  • Response to colchicine therapy
• Minor Diagnostic Criteria
  • recurrent fever attacks
  • Erysipelas-like rash
  • Having AAA in first degree relatives

FMF treatment: 

The main drug in treatment is colchicine.

• Colchicine: 1-2 mg/day is started according to the patient’s age, characteristics and complaint. It reduces the frequency and severity of attacks. The most important feature is the prevention of amyloid accumulation in regular use. It can be used during pregnancy. The most common side effect is diarrhea. It may need to be used for a lifetime. The dose is increased in patients who do not respond adequately to colchicine. If severe side effects develop or there is no response, treatment options such as interferon alpha, TNF alpha blocker, anakinra (IL-1 receptor antagonist) can be tried.
• Steroid treatment : It can be used in severe muscle pain.
• NSAID : It can be started as a part of the treatment for accompanying joint pain.