Familiar mediterranean fever (FMF)

Medicine 3

Head of Department:
Prof. Dr. med. univ. Georg Schett

Understanding causes

Numbers around the disease

Populations with high prevalence of the disease (1:200-1:1,000) are non-Ashkenazi Jews, Turks, Armenians and Arabs. The disease is also common in Italy, Greece, and Spain.

Usually the disease appears before the age of 30. An earlier start is often associated with more severe symptoms.

A distinction is made between 2 types in the FMF:

- Type 1 of the FMF is characterized by:

  • Attacks (once a week or every few years) with fever and serositis, which last 1 to 4 days and subside spontaneously. Possible triggers for these attacks are stress, exposure to cold, high-fat meals, infections, some drugs and menstruation
  • Mild symptoms (muscle pain, headache, nausea, dyspnoea, arthralgia, low back pain, asthenia and anxiety) precede the attacks and last for about 17 hours
  • Attacks manifest themselves as fever (38-40°C for 12-72 hours, which does not respond to antibiotics), diffuse or localised abdominal pain, constipation (diarrhoea in children), joint pain, arthritis (in the upper/lower limbs or knee joints) and chest pain caused by pleuritis and/or pericarditis
  • In 7-40% of patients there are also skin changes. A possible serious long-term complication is amyloidosis type AA

- Type 2 of the FMF is characterized by:

  •     occurrence of amyloidosis as the first and only sign

Typical symptoms

Clinical:

  • Peritonitis
  • Pleuritis (unilateral) or pericarditis
  • Monarthritis (hip, knee, OSG)
  • repeated, self-limiting fever attacks
  • Muscle aches
  • Good response to colchicine

Lab:

  • Increase of the C-reactive protein (CRP)
  • Increase of the blood sedimentation rate (BKS, ESR)
  • Increase of further so-called "acute phase proteins" (e.g. ferritin massively increased, S100 proteins increased).
  • Increase of serum amyloid (SAA)
  • Increase Fibrinogen

How does the physician make the diagnosis?

The Tel-Hashomer criteria require for diagnosis that two major criteria (fever and serositis, amyloidosis AA, efficacy of colchicine) and two minor criteria (recurrent fever attacks, erysipelas-like erythema, relatives with FMF) are present. The positive predictive value of a genetic analysis is only 70-80%.

Main criteria:

  • Peritonitis
  • Pleuritis (unilateral) or pericarditis
  • Monarthritis (hip, knee, upper ankle joint)
  • repeated, self-limiting fever attacks
  • Muscle aches
  • Good response to colchicine

Additional criteria

  • Positive family history
  • Suitable ethnic background
  • repeated Fever attacks
  • erysipelas-like exanthema
  • symptofree intervals
  • spontaneous remissions
  • Symptoms that require bed rest
  • Episodic proteinuria or haematuria

How is Familiar mediterranean fever treated?

  • Colchicine is the drug used to treat the FMF. It eliminates FMF attacks and prevents the occurrence of amyloidosis type AA. The dosage ranges from 0.03 mg/kg body weight/day to a maximum of 3 mg/day and must be taken regularly throughout life.
  • During an attack, non-steroidal anti-inflammatory drugs may be prescribed.
  • Anakinra, canakinumab, interferon-alpha and selective serotonin reuptake inhibitors (SSRIs) may be an alternative.
  • To prevent amyloidosis, patients should be examined annually and their serum amyloid A protein (SAA) should be controlled.

Practical tips for everyday life

  • Macrolides, diltiazem, grapefruit and cyclosporine should be avoided when taking colchicine! Serious toxicity may occur here.
  • Colchicine can increase B12 malabsorption and in rare cases cause alopecia and bone marrow insufficiency.
  • Renal amyloidosis may require dialysis and organ transplantation. Regular checks are necessary.
 
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