Familial Mediterranean fever

Overview

Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disorder that primarily affects people of Mediterranean descent, including those of Armenian, Turkish, Arab, and Sephardic Jewish origin. It is characterized by recurrent episodes of fever, abdominal pain, chest pain, joint inflammation, and skin rashes. These attacks are usually self-limiting, lasting 1 to 3 days. FMF is one of the most common periodic fever syndromes and can lead to serious complications such as amyloidosis if left untreated.

Causes

FMF is caused by mutations in the MEFV gene, which encodes a protein called pyrin. Pyrin plays a role in controlling inflammation in the body. Mutations in this gene result in excessive inflammation, leading to the characteristic symptoms of FMF. The condition is inherited in an autosomal recessive pattern, meaning a person must inherit two defective copies of the gene (one from each parent) to develop the disease. However, some individuals with only one mutated copy may also show symptoms.

Symptoms

Symptoms of Familial Mediterranean Fever typically begin in childhood or adolescence and include:

• Recurrent fever: Sudden episodes of fever that last 1–3 days.

• Abdominal pain: Severe pain due to inflammation of the peritoneum (peritonitis).

• Chest pain: Caused by inflammation of the pleura (pleuritis) or pericardium.

• Joint pain: Particularly in the knees and ankles; may resemble arthritis during attacks.

• Skin rash: Typically seen on the lower legs (erysipelas-like erythema).

• Muscle aches: Especially during or after attacks.

Diagnosis

Diagnosing FMF involves a combination of clinical evaluation, family history, and genetic testing. Key steps include:

• Clinical criteria: Diagnosis is based on the pattern and type of symptoms, especially recurrent fever with serosal inflammation.

• Family history: A history of similar symptoms in relatives can support the diagnosis.

• Genetic testing: Identification of mutations in the MEFV gene confirms the diagnosis.

• Laboratory tests: Elevated inflammatory markers such as CRP, ESR, and serum amyloid A during attacks.

Treatment

The primary treatment for FMF is aimed at preventing attacks and reducing the risk of long-term complications. Management strategies include:

• Colchicine: A daily oral medication that prevents attacks and significantly reduces the risk of amyloidosis.

• IL-1 inhibitors: Medications like anakinra or canakinumab may be used in patients who are unresponsive or intolerant to colchicine.

• NSAIDs: Used to manage pain during acute attacks.

• Monitoring for amyloidosis: Regular screening for proteinuria (urine protein) to detect early signs of kidney involvement.

Prognosis

With proper treatment, especially with lifelong use of colchicine, the prognosis for individuals with FMF is generally excellent. Most patients can lead normal, active lives with minimal disruptions. However, untreated FMF can result in serious complications, most notably amyloidosis, which may lead to kidney failure. Early diagnosis, adherence to treatment, and regular medical follow-up are essential to prevent complications and ensure long-term health.