familiar mediterranean fever

Familial Mediterranean fever (FMF) is a congenital, inherited disorder transmitted in an autosomal recessive manner. FMF is characterized by recurrent episodes of fever accompanied by abdominal and chest pain. The disease most commonly affects individuals originating from the Mediterranean region and the Middle East, particularly Jews, Turks, Arabs, and Armenians. The disease is not contagious.

Familial Mediterranean fever occurs with a frequency of approximately 1:1,000 in the above‑mentioned high‑risk populations, whereas it is very rare in other parts of the world. In recent years, the MEFV gene has been identified as responsible for proper regulation of inflammation in the body. When not mutated, this gene encodes a protein that suppresses inflammation. Mutations in this gene have also been identified among Italians, Greeks, and Americans. FMF most frequently affects children and adolescents, typically individuals under 20 years of age. Boys are affected more often than girls. Two types of FMF are recognized.

It causes attacks of fever and pain of the abdomen, joints, and lungs. Between episodes, patients are usually asymptomatic. These episodes may recur after days or even years. Several complications may develop and cause health problems, including kidney disease, abnormal protein levels in the body, female infertility, and joint pain.

Diagnosis

FMF is most commonly diagnosed in childhood. Diagnosis is based on the clinical symptoms listed above, and a definitive diagnosis of FMF is usually made after at least three febrile episodes. In recent years, genetic analysis and laboratory tests have been increasingly used to support the diagnosis.

Treatment

Treatment of familial Mediterranean fever is relatively straightforward and is based on lifelong administration of colchicine in preventive doses. Although colchicine does not treat the underlying cause of the disease, it prevents febrile attacks and amyloid deposition. With proper treatment, 60% of FMF patients experience complete resolution of symptoms, partial response occurs in about 30%, and treatment is ineffective in 5–10% of children.

Common adverse effects include diarrhea, in which case the dose must be reduced to a tolerated level. Temporary reduction of lactose intake for approximately three weeks may also help alleviate gastrointestinal symptoms.

Other side effects include nausea, vomiting, and cramping abdominal pain. Rarely, colchicine may cause muscle weakness. Blood cell counts (white blood cells, red blood cells, and platelets) may occasionally decrease but usually normalize after dose reduction.

• recurrent episodes of fever accompanied by abdominal, chest, and joint pain
• fever episodes usually last 1–4 days
• severe abdominal pain occurs in 90% of patients and may mimic acute appendicitis
• in other cases, only milder abdominal symptoms are present, associated with constipation or digestive disturbances
• chest pain is usually unilateral and associated with difficulty breathing; occurs in 20–40% of affected individuals
• typically one joint is affected (monoarthritis) – most commonly the ankle or knee
• the affected joint may develop red rash and swelling
• in 5–10% of cases, joint inflammation may progress to joint damage
• the rash in FMF is referred to as erysipelas‑like erythema
• in untreated cases, development of amyloidosis – amyloid is a protein that accumulates uncontrollably during inflammation in the kidneys, cardiac muscle, etc., leading to renal and/or cardiac damage
• rarely, recurrent pericarditis, myositis, periorchitis (inflammation around the testes), or meningitis may occur