Familial Mediterranean fever is a hereditary disorder characterized by episodes of high fever with abdominal pain or, less commonly, chest pain, joint pain, or a rash.
Familial Mediterranean fever is caused by a gene inherited from both parents.
Typically, most people have attacks of severe abdominal pain and a high fever.
The diagnosis usually is based on symptoms, but genetic testing is available.
This disorder may cause amyloidosis if not adequately treated.
Familial Mediterranean fever is the most common hereditary periodic fever syndrome across all age groups. It occurs most commonly among people of Mediterranean origin (such as people who have Sephardic Jewish, North African Arab, Armenian, Greek, Italian, or Turkish ancestry). However, this disorder has occurred among people of other origins (such as people who have Ashkenazi Jewish, Cuban, or Japanese ancestry).
Up to 50% of people who have familial Mediterranean fever have family members, usually siblings, who have the disorder (family history).
Familial Mediterranean fever is caused by an abnormal recessive gene. That is, to develop the disorder, people usually must have two copies of the abnormal gene, one from each parent. However, rarely, only one copy of the abnormal gene may be enough to cause some symptoms.
The abnormal gene results in the production of a defective form of pyrin, a protein that regulates inflammation. There are a number of different possible mutations of the gene, not all of which have been identified, which may explain why some people with typical familial Mediterranean fever are not found to have a mutation in the gene. Alternatively, there may also be nongenetic and environmental factors that play a role in how this syndrome develops.
Symptoms of Familial Mediterranean Fever
Symptoms of familial Mediterranean fever usually begin between the ages of 5 and 15 years.
The most common symptoms are
Abdominal pain and fever
Attacks of abdominal pain occur in about 95% of people. Attacks happen irregularly and are accompanied by fever as high as 104° F (40° C). The painful attacks usually last 12 to 72 hours but may last longer. Attacks may occur as often as twice a week or as seldom as once a year. The severity and frequency of the attacks may decrease during pregnancy and in people who develop amyloidosis. Sometimes the attacks stop completely for a number of years, only to resume afterwards.
The abdominal pain is caused by inflammation of the lining of the abdominal cavity (peritonitis). The pain usually starts in one part of the abdomen then spreads throughout the entire abdomen. The severity of the pain may vary with each attack.
Less common symptoms include
Chest pain: About 30% of affected people have chest pain. Chest pain, which is typically triggered by breathing, is caused by inflammation of the membranes surrounding the lungs (pleuritis) or, rarely, by inflammation of the sac surrounding the heart (pericarditis).
Arthritis: About 25% of people have inflammation of large joints (arthritis), such as the knees, ankles, and hips.
Rash: A painful red rash may appear near the ankles.
Scrotum pain: In males, the thick-skinned sac that surrounds and protects the testes (scrotum) may swell and be painful due to inflammation of a testis (testicle).
Despite the severity of symptoms during attacks, people rapidly recover and remain free of illness until their next attack.
Physical and emotional stress (for example, physical injury, infection, and menstruation) may trigger some attacks.
Complications of familial Mediterranean fever
If not treated adequately, some people with familial Mediterranean fever develop amyloidosis. In amyloidosis, an unusually shaped protein called amyloid is deposited in the kidneys and in many organs and tissues, impairing their function.
Amyloid deposits may damage the kidneys, eventually resulting in kidney failure. People may retain fluids, feel weak, and lose their appetite.
Up to one third of untreated women with familial Mediterranean fever have infertility or miscarry a pregnancy. The disorder can cause scar tissue to form in the pelvis. The scar tissue can interfere with conception.
People with familial Mediterranean fever have an increased risk of developing other inflammatory disorders, such as ankylosing spondylitis, immunoglobulin A–associated (IgA) vasculitis (formerly Henoch-Schönlein purpura), polyarteritis nodosa, and Behçet disease.
Diagnosis of Familial Mediterranean Fever
A doctor's evaluation
Genetic testing
A doctor usually bases the diagnosis of familial Mediterranean fever on typical symptoms. However, the abdominal pain of familial Mediterranean fever is virtually indistinguishable from that of other abdominal emergencies, particularly a ruptured appendix. Thus, some people with this disorder have urgent surgery before the correct diagnosis is made.
No routine laboratory test or imaging test is by itself diagnostic, but such tests can be useful in excluding other disorders. Blood tests can identify the abnormal gene that causes this disorder and can thus sometimes help with the diagnosis. Because some people with typical familial Mediterranean fever have only one rather than two copies of the gene or occasionally have no detectable mutations in the gene, genetic test results may be negative. In these cases, people should receive genetic counseling and care from specialists who are experienced with familial Mediterranean fever.
Treatment of Familial Mediterranean Fever
Taking colchicine daily by mouth eliminates or greatly reduces the number of painful attacks in about 95% of people. Also, colchicine greatly reduces the risk of kidney failure due to amyloidosis. In pregnant women, colchicine helps prevent attacks that might lead to a miscarriage.
