Familial Mediterranean Fever (FMF) Overview
Familial Mediterranean Fever is an inflammatory disorder that causes recurrent fevers and painful inflammation of your abdomen, lungs and joints.
Familial Mediterranean fever is an inherited disorder that usually occurs in people of Mediterranean origin including Sephardic Jews, Arabs, Italians, Armenians and Turks. But it may affect any ethnic group.
Familial Mediterranean fever is typically diagnosed during childhood. While there’s no cure for this disorder, you may be able to relieve signs and symptoms of familial Mediterranean fever or even prevent them altogether by sticking to your treatment plan.
Symptoms of Familial Mediterranean Fever (FMF)
The main symptoms of FMF are recurrent episodes of fever, accompanied by abdominal, chest or joint pain. Not all children will have all the symptoms, and symptoms may change over time. Episodes usually last 1-3 days and resolve without treatment. Most children look and feel healthy between episodes, but some children have such frequent episodes they do not fully recover or do not grow properly. Some of the episodes may be so painful that the patient or family seeks medical help in the emergency department.
Severe abdominal pain may look like appendicitis, and some patients may undergo surgery to remove the appendix. The chest pain may be so severe that it is difficult to breathe deeply. Joint pain may accompany the episodes of fever. Usually, only one joint is affected at a time, most commonly an ankle or a knee. The joint may be so swollen and painful that the child cannot walk.
One-third of patients may have a red rash over the lowerextremities, usually near the ankles and feet. In some children, the only finding of the disease may be episodes of joint pain and swelling, which can be misdiagnosed as acute rheumatic fever or juvenile idiopathic arthritis. Usually the joint swelling resolves over 5-14 days, but sometimes may become chronic. Some children report muscle pain in the legs, especially after physical exertion. Rarely, children have recurrent pericarditis (inflammation of the outer layer of the heart); myositis (muscle inflammation); meningitis (inflammation of the membrane surrounding the brain and spinal cord); or orchitis (testicular inflammation). Younger children (less than 5 years old) may present only with episodes of recurrent fever, without other symptoms.
How is Familial Mediterranean Fever (FMF) diagnosed?
In making a diagnosis of Familial Mediterranean Fever (FMF), doctors take all of these factors into account:
- Whether or not the patient has the clinical symptoms common for the disease and whether the symptoms are recurrent.
- How he or she responds to colchicine treatment (see “How is Familial Mediterranean Fever treated?” below).
- Usually a positive family history in people of Middle Eastern ancestry.
- The results of genetic testing.
Also helpful in establishing a correct diagnosis of FMF is the patient’s ancestry. Testing for the following can also be helpful:
- Elevated white blood cell count, which is an indication of an immune response.
- Elevated erythrocyte sedimentation rate (ESR), which is an indication of an inflammatory response.
- Elevated plasma fibrinogen, which helps stop bleeding. An elevated amount would indicate that something might be wrong with this mechanism.
- Elevated serum haptoglobin, which would indicate that red blood cells are being destroyed, a common occurrence in rheumatic diseases, such as FMF.
- Elevated C-reactive protein, which is a special type of protein, produced by the liver, that is only present during episodes of acute inflammation.
- Elevated albumin in the urine, which is demonstrated by urinalysis. The presence of the protein albumin in the urine can be a symptom of kidney disease, along with microscopic hematuria (very small – microscopic – amounts of blood or blood cells in the urine), during attacks.
Key Points
- Familial Mediterranean fever is caused by an autosomal recessive mutation in a protein that helps modulate the inflammatory response in neutrophils.
- People with genetic origins in the Mediterranean basin are more commonly (but not exclusively) affected.
- Patients have brief episodes of fever, abdominal pain, and sometimes other symptoms such as pleuritis, arthritis, and rash.
- Renal amyloidosis, sometimes causing renal failure, is the most common complication, but prophylactic colchicine provides protection against amyloidosis.
- Diagnose clinically, but consider genetic testing for atypical cases.
- Daily colchicine results in significant protection against attacks in most patients, but a few require an immunomodulator such as infliximab, anakinra, or rilonacept.
Causes of Familial Mediterranean Fever (FMF)
Familial Mediterranean fever is caused by a gene mutation that’s passed from parents to children. The gene mutation causes problems in regulating inflammation in the body.
In people with familial Mediterranean fever, the gene mutation occurs in a gene called MEFV. Many different mutations in MEFV are linked to familial Mediterranean fever. Some mutations may cause very severe cases, while others may be milder.
Familial Mediterranean fever is inherited as an autosomal recessive trait, meaning that you must inherit the mutated gene from both parents in order to develop the condition.
How is Familial Mediterranean Fever (FMF) treated?
At present, there is no known cure for Familial Mediterranean Fever (FMF). Physicians can only treat the symptoms of the disease.
A common therapy for FMF is daily use of the drug colchicine, a medicine that reduces inflammation. This therapy has been successful in preventing attacks of fever in 75 percent of patients who take the drug regularly, and over 90 percent of patients demonstrate a marked improvement. Even if colchicine does not prevent the fever attacks, it does prevent the amyloidosis. However, compliance in taking colchicine every day is very important. If a patient stops taking the drug, an attack can occur within a couple of days.
Since the gene that causes FMF codes for the protein pyrin, researchers hope that by studying how this protein works they will ultimately develop improved treatments for FMF, and possibly for other conditions involving excess inflammation.