Table of ContentsView AllTable of ContentsOverviewSymptomsComplicationsGenetics and InheritanceRisk FactorsDiagnosis
Table of ContentsView All
View All
Table of Contents
Overview
Symptoms
Complications
Genetics and Inheritance
Risk Factors
Diagnosis
PhotoAlto / Michele Constantini / Getty Images
As a chronic, recurrent disorder, FMF can cause short-term disability and significantly impair a person’s quality of life.Fortunately, newer anti-inflammatory drugs have all but eliminated many of the more severe manifestations of the disease.
FMF is a recessiveautosomal disorder, meaning that it is inherited from one’s parents. The disease is associated with mutations in the Mediterranean fever (MEFV) gene, of which there are more than 30 variations.For a person to experience symptoms, they would need to have inherited copies of the mutation from both parents. Even then, having two copies doesn’t always confer illness.
While rare in the general population, FMF is seen more frequently in Sephardic Jews, Mizrahi Jews, Armenians, Azerbaijanis, Arabs, Greeks, Turks, and Italians.
With FMF, the MEFV mutation almost always affects chromosome 16 (one of the 23 pairs of chromosomes thatmake up a person’s DNA). Chromosome 16 is responsible for, among other things, creating a protein called pyrin found in certain defensive white blood cells.
Of the 30-plus variations of the MEFV mutation, there are four that are closely linked to symptomatic disease.
Symptoms range in severity from mild to debilitating. The frequency of the attacks can also vary from every few days to every few years. While the signs of FMF can develop as early as infancy, it more commonly starts in one’s 20s.
Depending on the severity and frequency of attacks, FMF can cause long-term health complications. Even if symptoms are mild, FMF can trigger the overproduction of a protein known as serum amyloid A.These insoluble proteins can gradually accumulate in and cause damage to major organs, most predominately the kidneys.
Kidney failureis, in fact, the most serious complication of FMF. Prior to the advent of anti-inflammatory drug treatments, persons with FMF-associated kidney disease had an average life expectancy of 50 years.
Individuals with FMF also appear to have an increased incidence of other inflammatory diseases such as different forms of vasculitis and inflammatory bowel disease (Crohn’s disease and ulcerative colitis).
As with any autosomal recessive disorder, FMF occurs when two parents who don’t have the disease each contribute arecessive geneto their offspring. The parents are considered “carriers” because they each have one dominant (normal) copy of the gene and one recessive (mutated) copy. It is only when a person has two recessive genes that FMF can occur.
If both parents are carriers, a child has a 25 percent chance of inheriting two recessive genes (and getting FMF), a 50 percent chance of getting one dominant and one recessive gene (and becoming a carrier), and a 25 percent chance of getting two dominant genes (and remaining unaffected).
Because there are well over 30 variations of the MEFV mutation, different recessive combinations can end up meaning vastly different things. In some cases, having two MEFV mutations can confer severe and frequent bouts of FMF. In others, a person may be largely symptom-free and experience nothing more than an occasional unexplained headache or fever.
As rare as FMF is in the general population, there are groups in which the risk of FMF is considerably higher. The risk is largely constrained to so-called “founder populations” in which groups can trace the roots of a disease back to a common ancestor. Due to the lack of genetic diversity within these groups (often due to intermarriage or cultural isolation), certain rare mutations are more readily passed from one generation to the next.
By contrast, Ashkenazi Jews have a one in five chance of carrying the MEFV mutation but only a one in 73,000 chance of developing the disease.
The diagnosis of FMF is largely based on the history and pattern of the attacks. Key to the identification of the disease is the duration of the attacks, which is rarely longer than three days.
Blood tests may be ordered to evaluate the type and level of inflammation being experienced. These include:
A urine test may also be performed to assess whether there is excess albumin in the urine, an indication of chronic kidney impairment.
Based on these results, the healthcare provider may order agenetic testto confirm the MEFV mutation. In addition, the practitioner may recommend a provocation test in which a drug called metaraminol can induce a milder form of FMF, usually within 48 hours of an injection. A positive result can provide the healthcare provider with a high level of confidence in making the FMF diagnosis.
Treatment
There is no cure for FMF. Treatment is primarily directed at the management of acute symptoms, most often with nonsteroidal anti-inflammatory drugs like Voltaren (diclofenac).
To reduce the severity or frequency of attacks, the anti-gout drugColcrys (colchicine)is commonly prescribed as a form of chronic therapy. Adults are typically prescribed 1 to 1.5 milligrams a day, although up to 3 milligrams might be used in more severe disease. The dose is decreased for liver and kidney disease. No matter your condition, your healthcare provider will work to find the lowest effective dose.
So effective is Colcrys in treating FMF that 90 percent of sufferers report marked improvement. Moreover, the use of Colcrys is seen to greatly reduce the risk of FMF complications, including kidney failure.
Side effects of Colcrys can include nausea, diarrhea, and abdominal pain.Much more rare side effects include bone marrow suppression (causing low white blood cell count, low platelets, oranemia), liver toxicity, rash, muscle injury, andperipheral neuropathy(a numbness or pins-and-needles sensation of the hands and feet). Caution must be taken when using Colcrys in the presence of liver or kidney disease.
A Word From Verywell
If faced with a positive diagnosis of familial Mediterranean fever, it is important to speak with a disease specialist to fully understand what the diagnosis means and what your treatment options are.
If prescribed Colcrys, it is important to take the drug every day as directed, neither skipping nor increasing the frequency of doses. Persons who remain adherent to therapy can generally expect to have both a normal lifespan and a normal quality of life.
Even if treatment is started after kidney disease has developed, the twice-daily use of Colcrys can increase life expectancy well beyond the 50 years seen in persons with untreated disease.
14 SourcesVerywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.National Association of Rare Disorders.Familial Mediterranean Fever.Cengiz AK.SAT0514 Fatigue in Familial Mediterranean Fever.Ann Rheum Dis.2020;79:1213. doi:10.1136/annrheumdis-2020-eular.6085Özen S, Batu ED, Demir S.Familial mediterranean fever: recent developments in pathogenesis and new recommendations for management.Front Immunol. 2017;8. doi:10.3389/fimmu.2017.00253Journal of Clinical Medicine and Therapeutics.Familial Mediterranean Fever.Mukhin NA, Kozlovskaya LV, Bogdanova MV, Rameev VV, Moiseev SV, Simonyan AKh.Predictors of AA amyloidosis in familial Mediterranean fever.Rheumatol Int. 2015;35(7):1257-1261. doi:10.1007/s00296-014-3205-xTwig G, Livneh A, Vivante A, et al.Mortality risk factors associated with familial Mediterranean fever among a cohort of 1.25 million adolescents.Ann Rheum Dis. 2014;73(4):704-709. doi:10.1136/annrheumdis-2012-202932Bouomrani S, Masmoudi I, Teber SB.Familial Mediterranean fever: What associations to screen for?.Reumatologia. 2020;58(3):150-154. doi:10.5114/reum.2020.96688Gene Reviews, National Library of Medicine.Familial Mediterranean Fever.M. Milenković J, R. Stojanović D, G. Najdanović J.Adaptation to mediterranea. In: Trindade Maia R, de Araújo Campos M, eds.Genetic Variation. IntechOpen; 2021. doi:10.5772/intechopen.94081Manna R, Rigante D.Familial Mediterranean Fever: assessing the overall clinical impact and formulating treatment plans.Mediterr J Hematol Infect Dis. 2019;11(1):e2019027. doi:10.4084/MJHID.2019.027Sharkia R, Mahajnah M, Zalan A, et al.Comparative screening of FMF mutations in various communities of the Israeli society.European Journal of Medical Genetics. 2013;56(7):351-355.doi:10.1016/j.ejmg.2013.04.002Ozen S, Demirkaya E, Erer B, et al.EULAR recommendations for the management of familial Mediterranean fever.Annals of the Rheumatic Diseases2016;75:644-651.National Organization for Rare Disorders.Standard Therapies, Familial Mediterranean Fever.National Library of Medicine Medline Plus.Colchicine.Additional ReadingFujikura, H. “Global epidemiology of Familial Mediterranean fever mutations using population exome sequences.“Mol Genet Genomic Med.2015; 3(4):272-82.Padeh, S, and Yakov, B. “Familial Mediterranean fever.“Curr Opin Rheumatol. 2016; 28(5):523-29. DOI:10.1097/BOR.0000000000000315.Sonmez, H.; Batu, E.; and Ozen, S. “Familial Mediterranean fever: current perspective.“J Inflamm Res.2016; 9:13-20.
14 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.National Association of Rare Disorders.Familial Mediterranean Fever.Cengiz AK.SAT0514 Fatigue in Familial Mediterranean Fever.Ann Rheum Dis.2020;79:1213. doi:10.1136/annrheumdis-2020-eular.6085Özen S, Batu ED, Demir S.Familial mediterranean fever: recent developments in pathogenesis and new recommendations for management.Front Immunol. 2017;8. doi:10.3389/fimmu.2017.00253Journal of Clinical Medicine and Therapeutics.Familial Mediterranean Fever.Mukhin NA, Kozlovskaya LV, Bogdanova MV, Rameev VV, Moiseev SV, Simonyan AKh.Predictors of AA amyloidosis in familial Mediterranean fever.Rheumatol Int. 2015;35(7):1257-1261. doi:10.1007/s00296-014-3205-xTwig G, Livneh A, Vivante A, et al.Mortality risk factors associated with familial Mediterranean fever among a cohort of 1.25 million adolescents.Ann Rheum Dis. 2014;73(4):704-709. doi:10.1136/annrheumdis-2012-202932Bouomrani S, Masmoudi I, Teber SB.Familial Mediterranean fever: What associations to screen for?.Reumatologia. 2020;58(3):150-154. doi:10.5114/reum.2020.96688Gene Reviews, National Library of Medicine.Familial Mediterranean Fever.M. Milenković J, R. Stojanović D, G. Najdanović J.Adaptation to mediterranea. In: Trindade Maia R, de Araújo Campos M, eds.Genetic Variation. IntechOpen; 2021. doi:10.5772/intechopen.94081Manna R, Rigante D.Familial Mediterranean Fever: assessing the overall clinical impact and formulating treatment plans.Mediterr J Hematol Infect Dis. 2019;11(1):e2019027. doi:10.4084/MJHID.2019.027Sharkia R, Mahajnah M, Zalan A, et al.Comparative screening of FMF mutations in various communities of the Israeli society.European Journal of Medical Genetics. 2013;56(7):351-355.doi:10.1016/j.ejmg.2013.04.002Ozen S, Demirkaya E, Erer B, et al.EULAR recommendations for the management of familial Mediterranean fever.Annals of the Rheumatic Diseases2016;75:644-651.National Organization for Rare Disorders.Standard Therapies, Familial Mediterranean Fever.National Library of Medicine Medline Plus.Colchicine.Additional ReadingFujikura, H. “Global epidemiology of Familial Mediterranean fever mutations using population exome sequences.“Mol Genet Genomic Med.2015; 3(4):272-82.Padeh, S, and Yakov, B. “Familial Mediterranean fever.“Curr Opin Rheumatol. 2016; 28(5):523-29. DOI:10.1097/BOR.0000000000000315.Sonmez, H.; Batu, E.; and Ozen, S. “Familial Mediterranean fever: current perspective.“J Inflamm Res.2016; 9:13-20.
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
National Association of Rare Disorders.Familial Mediterranean Fever.Cengiz AK.SAT0514 Fatigue in Familial Mediterranean Fever.Ann Rheum Dis.2020;79:1213. doi:10.1136/annrheumdis-2020-eular.6085Özen S, Batu ED, Demir S.Familial mediterranean fever: recent developments in pathogenesis and new recommendations for management.Front Immunol. 2017;8. doi:10.3389/fimmu.2017.00253Journal of Clinical Medicine and Therapeutics.Familial Mediterranean Fever.Mukhin NA, Kozlovskaya LV, Bogdanova MV, Rameev VV, Moiseev SV, Simonyan AKh.Predictors of AA amyloidosis in familial Mediterranean fever.Rheumatol Int. 2015;35(7):1257-1261. doi:10.1007/s00296-014-3205-xTwig G, Livneh A, Vivante A, et al.Mortality risk factors associated with familial Mediterranean fever among a cohort of 1.25 million adolescents.Ann Rheum Dis. 2014;73(4):704-709. doi:10.1136/annrheumdis-2012-202932Bouomrani S, Masmoudi I, Teber SB.Familial Mediterranean fever: What associations to screen for?.Reumatologia. 2020;58(3):150-154. doi:10.5114/reum.2020.96688Gene Reviews, National Library of Medicine.Familial Mediterranean Fever.M. Milenković J, R. Stojanović D, G. Najdanović J.Adaptation to mediterranea. In: Trindade Maia R, de Araújo Campos M, eds.Genetic Variation. IntechOpen; 2021. doi:10.5772/intechopen.94081Manna R, Rigante D.Familial Mediterranean Fever: assessing the overall clinical impact and formulating treatment plans.Mediterr J Hematol Infect Dis. 2019;11(1):e2019027. doi:10.4084/MJHID.2019.027Sharkia R, Mahajnah M, Zalan A, et al.Comparative screening of FMF mutations in various communities of the Israeli society.European Journal of Medical Genetics. 2013;56(7):351-355.doi:10.1016/j.ejmg.2013.04.002Ozen S, Demirkaya E, Erer B, et al.EULAR recommendations for the management of familial Mediterranean fever.Annals of the Rheumatic Diseases2016;75:644-651.National Organization for Rare Disorders.Standard Therapies, Familial Mediterranean Fever.National Library of Medicine Medline Plus.Colchicine.
National Association of Rare Disorders.Familial Mediterranean Fever.
Cengiz AK.SAT0514 Fatigue in Familial Mediterranean Fever.Ann Rheum Dis.2020;79:1213. doi:10.1136/annrheumdis-2020-eular.6085
Özen S, Batu ED, Demir S.Familial mediterranean fever: recent developments in pathogenesis and new recommendations for management.Front Immunol. 2017;8. doi:10.3389/fimmu.2017.00253
Journal of Clinical Medicine and Therapeutics.Familial Mediterranean Fever.
Mukhin NA, Kozlovskaya LV, Bogdanova MV, Rameev VV, Moiseev SV, Simonyan AKh.Predictors of AA amyloidosis in familial Mediterranean fever.Rheumatol Int. 2015;35(7):1257-1261. doi:10.1007/s00296-014-3205-x
Twig G, Livneh A, Vivante A, et al.Mortality risk factors associated with familial Mediterranean fever among a cohort of 1.25 million adolescents.Ann Rheum Dis. 2014;73(4):704-709. doi:10.1136/annrheumdis-2012-202932
Bouomrani S, Masmoudi I, Teber SB.Familial Mediterranean fever: What associations to screen for?.Reumatologia. 2020;58(3):150-154. doi:10.5114/reum.2020.96688
Gene Reviews, National Library of Medicine.Familial Mediterranean Fever.
M. Milenković J, R. Stojanović D, G. Najdanović J.Adaptation to mediterranea. In: Trindade Maia R, de Araújo Campos M, eds.Genetic Variation. IntechOpen; 2021. doi:10.5772/intechopen.94081
Manna R, Rigante D.Familial Mediterranean Fever: assessing the overall clinical impact and formulating treatment plans.Mediterr J Hematol Infect Dis. 2019;11(1):e2019027. doi:10.4084/MJHID.2019.027
Sharkia R, Mahajnah M, Zalan A, et al.Comparative screening of FMF mutations in various communities of the Israeli society.European Journal of Medical Genetics. 2013;56(7):351-355.
doi:10.1016/j.ejmg.2013.04.002
Ozen S, Demirkaya E, Erer B, et al.EULAR recommendations for the management of familial Mediterranean fever.Annals of the Rheumatic Diseases2016;75:644-651.
National Organization for Rare Disorders.Standard Therapies, Familial Mediterranean Fever.
National Library of Medicine Medline Plus.Colchicine.
Fujikura, H. “Global epidemiology of Familial Mediterranean fever mutations using population exome sequences.“Mol Genet Genomic Med.2015; 3(4):272-82.Padeh, S, and Yakov, B. “Familial Mediterranean fever.“Curr Opin Rheumatol. 2016; 28(5):523-29. DOI:10.1097/BOR.0000000000000315.Sonmez, H.; Batu, E.; and Ozen, S. “Familial Mediterranean fever: current perspective.“J Inflamm Res.2016; 9:13-20.
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