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Familial Mediterranean fever (FMF)


Related Terms
  • Abdomen inflammation, amyloidosis, anti-inflammatory, arthritis, autosomal disorder, autosomal recessive disorder, autosomal recessive trait, chromosomal disorder, chronic arthritis, colchicine, dialysis, genetic disorder, immune, immune defense system, immune deficiency, immune system, immunodeficiency, inflammation, inherited disorder, joint pain, kidney transplant, kidney transplantation, lung inflammation, Mediterranean ancestry, Mediterranean fever, nephrotic syndrome, polyserositis.

  • Familial Mediterranean fever (FMF), also called recurrent polyserositis, is an inherited disorder that causes swelling in the body, especially in the lungs and abdomen. Inherited disorders are passed down from parents to their children.
  • FMF primarily occurs in individuals of Mediterranean ancestry. Researchers estimate that the disorder occurs in one out 500 Armenians, one out of 1,000 Turks, one out of 2,600 Arabs, one out of 250-2,000 Sephardic Jews, and one out of 73,000 Ashkenazi Jews.
  • The disorder is more common in men than women; researchers estimate that males are 1.5-2 times more likely to develop the disorder than females.
  • Although patients are born with the disorder, symptoms generally do not appear until the individual is between five and 15 years old. Symptoms generally include recurrent fevers and painful inflammation of the abdomen, lungs, and joints. FMF is not considered a fatal disease, but it can be debilitating, especially if it is not properly managed with treatment.
  • While there is currently no cure for the disease, life-long treatment with a medication called colchicine has been shown to alleviate symptoms. Colchicine helps reduce inflammation associated with the disorder. Before colchicine was first used as a treatment for FMF in 1972, almost all patients died by age 50 from nephrotic syndrome (disorder that causes kidney dysfunction).
  • For some FMF patients, the frequency and the severity of symptoms may lessen with age or during pregnancy. It is unknown why symptoms may improve.

Author information
  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (

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  • Familial Mediterranean fever (FMF) is an inherited disorder that is passed down from parents to their children. Individuals who have FMF inherited a defective gene from their parents.
  • Each person has 46 chromosomes in 23 pairs. Chromosomes contain all of the genes inherited from an offspring's parents. FMF patients have a genetic defect (abnormality) on chromosome 16. However, researchers have not discovered exactly how this genetic defect causes FMF. It also remains unknown why the severity and duration of FMF attacks vary among patients.
  • The abnormal gene for FMF is inherited as an autosomal recessive trait. This means the patient must inherit one mutated gene from each parent in order to develop the disease. Individuals who only inherit one mutated gene and do not experience symptoms are called carriers. Although they do not have the disease, they can pass the mutated gene to their children.
  • Carriers have a 50% chance of passing the abnormal gene to each of their children. If both parents are carriers of FMF, there is a 25% chance that each of their children will have the disease and a 50% chance that each of their children will be a carrier.

  • General: Symptoms of familial Mediterranean fever (FMF) generally do not appear until the patient between five and 15 years old. Symptoms are collectively called attacks because they develop suddenly and only last about two to three days. Symptoms are typically the most intense within the first 12 hours of an attack. The length of time between attacks varies among patients. Sometimes the attacks are only a few weeks apart, while other times they are several months apart. In between attacks, patients do not experience any symptoms.
  • Common symptoms: Common symptoms of an attack include sudden fever (ranging from about 100-104 degrees Fahrenheit), chills, abdominal pain, chest pain, achy and swollen joints, rash on the legs, and constipation followed by diarrhea.
  • Less common symptoms: Less common symptoms include muscle aches, inflammation of the blood vessels, pelvic inflammatory disease in females (swollen female reproductive organs), and swollen and tender scrotum in males.

  • General: An estimated 80-95% of patients with familial Mediterranean fever (FMF) are diagnosed before the age of 20. There is currently no specific lab test to diagnosis FMF. Instead, a diagnosis is made after a physical examination and medical history are conducted along with blood tests. Genetic tests may also be performed.
  • Blood tests: Blood tests can be performed during an attack to help diagnose the disorder. During an attack, patients typically have elevated levels of white blood cells. Healthy individuals typically have 4,500-10,000 white blood cells per microliter of blood.
  • An erythrocyte sedimentation rate (ESR) test, which measures the rate that red blood cells settle in unclotted blood, may also be performed. Normal values for men younger than 50 years old are 15 millimeters/hour and less than 20 millimeters/hour for men older than 50. The normal values for women who are less than 50 years old are less than 20 millimeters/hour and less than 30 millimeters/hour for women older than 50. Patients with FMF will have elevated rates.
  • A fibrinogen blood test may also be performed. During the procedure, a small sample of blood is taken from the patient in order to measure the amount of fibrinogen (a coagulation factor) in the blood. Healthy individuals typically have 200-400 milligrams of fibrinogen per deciliter of blood. Elevated levels indicate FMF.
  • A C-reactive protein (CRP) test can be performed. A high or increasing amount of CRP in the blood suggests that the patient has inflammation. In a healthy patient, CRP is usually less than 10 milligrams/liter. Most inflammations result in CRP levels above 100 milligrams/liter.
  • Genetic test: The DNA (genetic makeup) from a sample of the patient's blood can be analyzed for mutations associated with FMF. However, genetic tests are not commonly used as a diagnostic tool because they do not identify all of the different gene mutations associated with the disorder. This procedure may be performed to determine whether a patient carries the gene. Although carriers do not have the disorder, they can pass the mutated gene on to their children.
  • Medical history: During a careful medical history, a healthcare provider will ask the patient if FMF has been diagnosed in family members. The patient's ethnicity should also be considered because patients of Mediterranean ancestry, including Sephardic Jews, Armenians, Turks, North Africans, Arabs, and less frequently, Greeks and Italians, are most likely to develop this disorder. However, FMF has also been diagnosed in other ethnic groups, including Ashkenazi Jews in the United States. Therefore, ethnicity alone cannot be used to diagnose or rule out the disorder.
  • Physical examination: During the physical examination, a healthcare provider will determine whether the patient's symptoms are characteristic of FMF. Such symptoms include recurrent fever, joint paint, abdominal pain, chest pain, and achy or swollen joints that occur in isolated episodes, lasting about two to three days.

  • General: There is currently no cure for familial Mediterranean fever (FMF). However, medications have shown to significantly reduce symptoms associated with the disorder. For some FMF patients, the frequency and the severity of symptoms may lessen with age or during pregnancy. It is unknown why symptoms may spontaneously improve.
  • Colchicine: Patients with FMF typically take a drug called colchicine for the rest of their lives. This drug, which is usually taken as a pill, reduces swelling in the body. Colchicine should be taken regularly to prevent FMF attacks from occurring. If the medication is taken after FMF symptoms of an episode appear, it will not be effective. Colchicine treatment also significantly reduces the risk of complications, such as amyloidosis or nephrotic syndrome.
  • The recommended dose of colchicine varies among patients. Some patients may only need to take one dose a day, while others may require multiple doses. Also, a patient's dose may change over time.
  • Colchicine is generally considered safe, even when taken long-term. Side effects of colchicine may include pain, tingling or numbness in the hands or feet, and muscle weakness. Long-term use of colchicine may cause lactose intolerance. Patients who experience bloating, abdominal pain, or cramping after consuming dairy products should consider a lactose-free diet.
  • Dialysis or kidney transplantation: Before colchicine therapy was introduced as a treatment for FMF in 1972, patients with the disorder commonly needed dialysis because they suffered from kidney dysfunction. During this procedure, waste is removed from the patient's blood at the hospital. The patient's blood is filtered through a machine outside of the body. In healthy individuals, the kidneys are responsible for filtering the blood. Patients who suffer from kidney failure often need to receive a kidney transplant. Dialysis and kidney transplantation are usually only needed in patients who do not take medication exactly as prescribed or who cannot tolerate colchicine.

Integrative therapies
  • Good scientific evidence:
  • Bromelain: Some physicians use bromelain, an enzyme derived from pineapple, to help reduce inflammation. It is sometimes recommended to be taken with turmeric (Curcuma longa), which may enhance the effects of bromelain.
  • Avoid if allergic to bromelain, pineapple, honeybee, venom, latex, birch pollen, carrots, celery, fennel, cypress pollen, grass pollen, papain, rye flour, wheat flour, or members of the Bromeliaceaefamily. Use cautiously with a history of bleeding disorders, stomach ulcers, or heart, liver, or kidney disease. Use caution before dental or surgical procedures or while driving or operating machinery. Avoid if pregnant or breastfeeding.
  • Comfrey: Comfrey may have anti-inflammatory effects. Clinical trials investigating topical application of comfrey-containing creams have found significant reductions in inflammation and pain associated with sprains and muscle injuries. Additional study is needed to confirm these results.
  • Avoid if allergic/hypersensitive to comfrey, its constituents, or members of the Boraginaceae family. Avoid oral comfrey. Avoid topical comfrey on broken skin. Avoid topical comfrey in individuals with or at risk for hepatic disorders, cancer, or immune disorders. Use topical creams containing comfrey cautiously if taking anti-inflammatory medications or cytochrome P450 3A4-inducing agents. Use extreme caution when using topical creams containing comfrey for extended periods. Avoid if pregnant or breastfeeding.
  • Unclear or conflicting scientific evidence:
  • Andrographis: While early studies suggest that a combination product containing andrographis may reduce the duration, frequency, and severity of Familial Mediterranean fever (FMF) attacks among children, more studies using andrographis alone are needed.
  • Cases of anaphylactic reactions, including shock, have been reported to the World Health Organization Collaborating Center for International Drug Monitoring as of June 2003. Avoid with infertility or patients actively trying to conceive. Use cautiously with diabetes, bleeding disorders, and high or low blood pressure. Use cautiously with blood sugar-altering medications, warfarin or other blood thinning medications, and blood pressure-altering medications. Avoid if pregnant or breastfeeding.
  • Cat's claw: Cat's claw may have anti-inflammatory effects. Large, high-quality human studies are needed comparing effects of cat's claw alone vs. placebo.
  • Avoid if allergic to cat's claw or Uncaria plants or plants in the Rubiaceae family such as gardenia, coffee, or quinine. Avoid with a history of conditions affecting the immune system (such as AIDS, HIV, some types of cancer, multiple sclerosis, tuberculosis, rheumatoid arthritis, lupus). Use cautiously with bleeding disorders or a history of stroke, or if taking drugs that may increase the risk of bleeding. Discontinue use two weeks before surgery/dental/diagnostic procedures with bleeding risk, and do not use immediately after these procedures. Cat's claw may be contaminated with other Uncaria species. Reports exist of a potentially toxic, Texan grown plant, Acacia gregii being substituted for cat's claw. Avoid if pregnant, breastfeeding, or trying to become pregnant.
  • Dandelion: Research in laboratory animals suggests that dandelion root may possess anti-inflammatory properties. There is a lack of well-conducted human studies currently available in this area.
  • Avoid if allergic to chamomile, feverfew, honey, yarrow, or any related plants such as aster, daisies, sunflower, chrysanthemum, mugwort, ragweed, or ragwort. Use cautiously with diabetes or bleeding disorders, gastroesophageal reflux disease (GERD), kidney or liver diseases, or a history of stroke or electrolyte disorders. Potassium blood levels should be monitored. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk and do not use immediately after these procedures. Avoid if pregnant or breastfeeding.
  • Euphorbia: Euphorbia balsamifera has been studied in patients with acute dental pulpitis, and may be comparable to that of pulpal nerve caustics. Additional study is necessary to make a recommendation for inflammation.
  • Avoid if allergic or hypersensitive to pollen from Euphorbia fulgens. Use cautiously with history of Epstein Barr virus infection or stomach conditions. Avoid if pregnant or breastfeeding.
  • Eyebright: Several iridoid glycosides isolated from eyebright, particularly aucubin, may possess anti-inflammatory properties comparable to those of indomethacin (a nonsteroidal anti-inflammatory drug). However, there is currently insufficient evidence to recommend for or against eyebright as an anti-inflammatory agent.
  • Avoid with a known allergy or hypersensitivity to eyebright. Hypersensitivity to members of the Scrophulariaceae family may lead to a cross-sensitivity reaction. Use cautiously as an eye treatment, particularly homemade preparations, due to the risk of infection if not sterile. Use cautiously with diabetes and drugs that are broken down by the liver. Avoid if pregnant or breastfeeding.
  • Licorice: Many medical conditions are marked by inflammation. Because licorice can affect the metabolism of steroids, licorice is sometimes used to help decrease inflammation. Additional study is needed to make a conclusion.
  • Early study of a multi-ingredient preparation containing licorice, called ImmunoguardT, suggests possible effects in managing Familial Mediterranean fever (FMF). Well-designed study of licorice alone is necessary before a recommendation can be made.
  • Avoid with a known allergy to licorice, any component of licorice, or any member of the Fabaceae (Leguminosae) plant family. Avoid with congestive heart failure, coronary heart disease, kidney or liver disease, fluid retention, high blood pressure, hormonal abnormalities or if taking diuretics. Licorice can cause abnormally low testosterone levels in men or high prolactin or estrogen levels in women. This may make it difficult to become pregnant and may cause menstrual abnormalities.
  • Schisandra: There is currently a lack of sufficient evidence to determine if schisandra is an effective treatment for Familial Mediterranean fever (FMF). Results from limited study using schisandra in combination with other herbs for this condition suggested a potential benefit. Further study is required before conclusions can be drawn.
  • Avoid if allergic or sensitive to schisandra. Skin rashes and hives have been reported.
  • Siberian ginseng: Preliminary study of a combination product containing Siberian ginseng (Eleutherococcus senticosus) suggests the potential for reduced symptoms in patients with Familial Mediterranean Fever (FMF). Due the presence of other ingredients in this product, the effect of Siberian ginseng cannot be determined, and further study is required.
  • Avoid in patients with a known allergy/hypersensitivity to Siberian ginseng, its constituents, related products, or members of the Araliaceae family. Use cautiously in patients with blood pressure disorders, bleeding disorders or in those using anticoagulant or antiplatelet agents, diabetes or in those using antidiabetic agents, autoimmune disorders, psychiatric disorders, or impaired gastrointestinal function. Use cautiously in patients taking digoxin, CNS depressants, or steroids. Avoid in children or pregnant and lactating women.
  • Turmeric: Turmeric is a perennial plant native to India and Indonesia, and it is often used as a spice in cooking. Laboratory and animal studies show activity against inflammation for turmeric and its constituent curcumin. Reliable human research is lacking.
  • Avoid if allergic or hypersensitive to turmeric (curcumin), yellow food colorings or plants belonging to the Curcuma or Zingiberaceae (ginger) families. Use cautiously with history of bleeding disorders, immune system deficiencies, liver disease or gallstones. Use cautiously with blood-thinners (e.g. warfarin). Use cautiously if pregnant or breastfeeding.
  • Traditional or theoretical uses lacking sufficient evidence:
  • Devil's claw root: Devil's claw root may help reduce inflammation and skin lesions. Additional research is needed regarding anti-inflammatory effects.
  • Avoid if allergic to devil's claw or to plants in the Harpagophytum procumbens family. Use caution with stomach ulcers or history of bleeding disorders, diabetes, gallstones, gout, heart disease, stroke, ulcers, or with prescription drugs used for these conditions. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk, and do not use immediately after these procedures. Avoid if pregnant or breastfeeding.
  • Ginkgo biloba: Ginkgo biloba extract has been used for inflammation. However, in rare cases, Ginkgo has been reported to cause an allergic reaction on the skin.
  • Avoid if allergic or hypersensitive to members of the Ginkgoaceaefamily. If allergic to mango rind, sumac, poison ivy or oak or cashews, then allergy to ginkgo is possible. Avoid with blood-thinners (like aspirin or warfarin (Coumadin®)). Ginkgo seeds are dangerous and should be avoided. Skin irritation and itching may also occur due to ginkgo allergies. Do not use ginkgo in supplemental doses if pregnant or breastfeeding.

  • Currently there is no known method of prevention for familial Mediterranean fever (FMF).
  • Patients who have the disorder may wish to speak with their healthcare providers about the risk of passing FMF to their children.
  • If a patient is a suspected carrier, they can undergo genetic testing to determine whether they have the mutated gene. Although carriers do not have the disorder, they may pass the mutated gene to their children.

  • General: Complications of familial Mediterranean fever (FMF) usually only occur in patients who are not receiving treatment or not following their treatment regimens. Therefore, patients should take medications exactly as prescribed by their healthcare providers to help prevent complications.
  • Amyloidosis: Amyloidosis is considered the most common complication of untreated FMF. This condition occurs when an abnormal protein called amyloid builds up in the body's tissues and organs, especially the kidneys. Amyloidosis that affects the kidneys may lead to a kidney disorder called nephrotic syndrome. Once the FMF is treated, symptoms of amyloidosis will begin to resolve.
  • Chronic arthritis: An estimated five percent of FMF patients develop chronic arthritis, which causes pain and inflammation of the joints. Chronic arthritis is typically treated with non-steroidal anti-inflammatories like celecoxib (Celebrex®). In sever cases, patients may need surgical hip or knee joint replacements.
  • General discomfort: If FMF is not properly treated, it can be extremely painful and may interfere with a patient's quality of life. Patients may be unable to perform normal daily activities when attacks occur.
  • Infertility: If inflammation associated with FMF is not properly treated, it can potentially lead to infertility, especially in women. Researchers estimate that about 33% of females are infertile, and 20-30% of women who become pregnancy have miscarriages.
  • Nephrotic syndrome: Nephrotic syndrome, a disorder in which the kidneys become damaged and do not function normally, may also occur if FMF is not properly treated. This occurs when abnormal levels of a protein called amyloid build up in the kidneys. Patients typically experience swollen hands and feet. Nephrotic syndrome is potentially life threatening because it may lead to blood clots in the kidneys or kidney failure. Patients with nephrotic syndrome typically receive different types of medications, including immunosuppressants, corticosteroids, and diuretics. Once FMF is adequately treated, patients will no longer need to receive additional treatment for nephrotic syndrome.

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The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.