Familial Mediterranean fever

What causes familial Mediterranean fever?

Familial Mediterranean fever (FMF) usually is caused by changes in both copies of a person's MEFV gene. Changes in genes that are responsible for causing disease are also called pathogenic variants, or mutations.

Pathogenic variants are usually inherited from one or both parents. There is nothing either parent can do before or during a pregnancy to cause them. Over 80 different pathogenic variants in the MEFV gene are known to cause FMF.

The MEFV gene normally provides instructions for making a protein called pyrin, which is found in white blood cells called granulocytes. It is thought that this protein plays a role in keeping inflammation under control. Inflammation occurs when the immune system sends signaling molecules and white blood cells to a site of injury or disease, and pyrin may stop or slow down the inflammatory process once it is no longer needed.

When the MEFV gene is mutated and pyrin is not formed correctly or working properly, inflammation is not regulated as it should be. This is thought to result in the painful inflammation, rashes and fever that characterize FMF.

Last updated on 05-01-20

How is familial Mediterranean fever (FMF) diagnosed?

In making a diagnosis of FMF, doctors take several factors into account:

  • whether a person has symptoms of FMF and whether the symptoms are recurrent
  • how a person responds to colchicine treatment
  • family medical history and ancestry
  • results of genetic testing

Testing for the following may also be helpful to make a diagnosis of FMF:

  • 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 can be a symptom of kidney disease, along with microscopic hematuria (microscopic amounts of blood in the urine).

Last updated on 05-01-20

How is familial Mediterranean fever (FMF) inherited?

FMF is almost always inherited in an autosomal recessive manner. This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers. Carriers typically do not show signs or symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a:

  • 25% chance to have the condition
  • 50% chance to be a carrier like each of the parents
  • 25% chance to not have the condition and not be a carrier

As many as 1 in 5 people of Sephardic Jewish, Armenian, Arab and Turkish heritage is a carrier of FMF.

In rare cases, FMF appears to be inherited in an autosomal dominant manner. This means that to be affected, a person needs to have a mutation in only one copy of the responsible gene in each cell. In some cases, an affected person inherits the mutation from an affected parent. Other cases may result from new (de novo) mutations in the gene. A person with autosomal dominant FMF has a 50% chance to pass the mutated gene on to each child.

In some cases, FMF may appear to be autosomal dominant when it is actually autosomal recessive. This phenomenon is called pseudodominance.

Last updated on 05-01-20

What is the long-term outlook for people with familial Mediterranean fever (FMF)?

People with FMF who are compliant with daily colchicine can probably expect to have a normal lifespan, if colchicine is started before proteinuria develops. Even with amyloidosis, the use of colchicine, dialysis, and kidney transplantation should extend a patient's life beyond 50 years of age.

Last updated on 05-01-20

How might familial Mediterranean fever (FMF) be treated?

The goal of treatment for familial Mediterranean fever (FMF) is to control symptoms because there is no cure for the condition.

Treatment of an acute episode may include:

  • intravenous saline for hydration
  • nonsteroidal anti-inflammatory drugs (NSAIDs) for fever and inflammatory episodes
  • NSAIDs, paracetamol or dipyrone for pain relief
  • routine treatment of end-stage renal disease (kidney failure), including renal transplantation

Depending on disease severity or the presence of specific mutations, lifelong treatment with colchicine may be needed. Colchicine prevents inflammatory attacks and the deposition of amyloid. Those who are only mildly affected (with infrequent inflammatory attacks) may either be treated with colchicine or be monitored every six months for the presence of protein in the urine (proteinuria). Others may only be treated with colchicine if they develop severe inflammatory episodes and/or proteinuria as a result of amyloidosis. Those who are unresponsive to oral colchicine may respond to intravenous colchicine, or one of several other medications. Colchicine is not effective as treatment for an acute FMF attack.

Last updated on 05-01-20

Name: FMF & AID Global Association Schüracherstrasse 25a 8306 Brüttisellen
Phone: +41 76 415 4010 Email: info@fmfandaid.org Url: https://www.fmfandaid.org/

Note, these links are external searches against the National Laboratory of Medicine's drug database. You may need to adjust the search if there are no results found.

Drug Name Generic Name
Ilaris canakinumab

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