Familial Mediterranean Fever (FMF)

Familial Mediterranean fever (FMF) is a disease that involves recurrent episodes of fever without an associated infection. Attacks of fever in FMF are usually accompanied by symptoms of inflammation in one or more sites. These may include abdominal pain, chest pain, joint pain, and skin rashes, among others. It is a life-long disease and there is no known cure. Fortunately, however, it can be controlled with treatment.

How common is FMF?

FMF is more common in certain ethnic groups, primarily those whose ancestry was around the Mediterranean Sea. These groups include Armenians, Turks, Arabs, and Jews, especially of Sephardic background. More recently, however, FMF has been diagnosed in people from many other ethnic backgrounds. Attacks of FMF begin before the age of 20 in 90% of patients. Attacks begin before age 10 in at least 50% of patients.

Symptoms of FMF

A typical attack of FMF starts with a sudden rise in temperature, often up to 104° F (40°C). Fever usually lasts from 1 to 3 days and in most cases is accompanied by severe abdominal pain. The pain comes from inflammation of the lining of the abdomen. Sometimes the pain is so bad that it seems as if the child has appendicitis​, even though the appendix itself is not inflamed. Severe chest pain, called pleuritis, occurs in about one-third of patients. Brief episodes of arthritis, usually involving the knee or ankle, can occur in about half of patients. About one-third of patients get painful red skin and swelling, called erysipelas. This typically occurs over the foot. These symptoms generally disappear as the fever resolves, although attacks of arthritis may last for up to one week. Rarely, arthritis affecting a single joint, including the joints of the back (sacroiliitis), may persist. Attacks may also be accompanied by severe muscle pain, called myalgia.​

Causes of FMF

FMF appears to be caused by failure of the body to control the inflammation system. A protein called pyrin is an important controller of inflammation in the body. Changes (mutations) in the gene that makes pyrin, called MEFV, are found in up to 80% of FMF cases. Most cases require two mutations (one from the mother and one from the father) in the MEFV gene to result in FMF. This type of disease is called “autosomal recessive,” meaning that parents are generally carriers. There is often, but not always, a history of another family member having a similar disease. Sometimes only one or even no mutations are found in typical cases of FMF.

Complications of FMF

Without treatment, attacks of FMF will occur frequently and can be disabling for the patient. If attacks of inflammation are not controlled, there is a risk of developing amyloidosis, the most serious complication of FMF. In amyloidosis, a protein of inflammation called SAA is deposited in multiple organ systems, particularly the kidney, heart, and gastrointestinal tract. Amyloidosis appears to be less common in patients born and raised in the northern hemisphere.

Treatment of FMF

Fortunately, amyloidosis can almost always be prevented by stopping attacks of inflammation with the drug colchicine. Taking colchicine every day reduces the frequency of the attacks as well as the severity of the attacks that do occur, and therefore prevents the development of amyloidosis. Colchicine is prescribed as a daily medication. In some patients, missing even one dose may result in an attack. You and your doctor will decide if your child needs colchicine and if so, for how long.​

Lab tests for children with FMF

During the attacks, blood tests will usually show very marked degrees of inflammation. The most commonly requested tests are a complete blood count (CBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). These levels return to normal or near normal between attacks.

Your doctor will check for the development of amyloidosis by performing a general physical examination and also a urine test to check for protein in the urine every six months.​

How you can help your child with FMF

Typical episodes of FMF should not be treated with ant​ibiotics. However, children with FMF may also get usual childhood infections. So, if you are concerned that a fever episode is not FMF, always contact your child’s doctor.

Also notify your child’s school about the diagnosis. Children with FMF are not contagious. They should not be excluded from school. Children with FMF should be encouraged to carry on with normal activities.

Follow-up care at a rheumatology clinic

Your child may be referred to a rheumatology clinic for follow-up care. Usually, a rheumatology clinic will have a team of doctors and nurses who have a lot of experience treating children with FMF.

Other members of the rheumatology team include:​

  • a social worker and a child life specialist to help with emotional and behavioural problems that might result from the disease
  • a dietitian to help with your child’s diet and nutrition

Preparing for visits to the rheumatology clinic

Your child may need a blood test during a clinic visit. This will help doctors monitor the disease. Blood tests also help check for side effects of the medicine your child may be taking. A urine test will usually be needed as well. If your child needs to prepare for clinic visits in any other way, a member of the rheumatology team will tell you before the visit.

After you have met the rheumatology team, you will know more about how to care for your child and how to plan for future clinic visits.

Key points

  • FMF is a disease that causes regular attacks of fever.
  • The attacks are accompanied by inflammation in areas such as the abdomen, chest, joints, and skin.
  • FMF can be treated and controlled with a medication called colchicine.

Ron Laxer, MD, FRCPC

Karyl S. Barron, MD (National Institutes of Health)​​