Familial Mediterranean fever

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Familial Mediterranean Fever
Classification and external resources
ICD-10 E85.0
ICD-9 277.31
OMIM 249100 608107
DiseasesDB 9836
MedlinePlus 000363
eMedicine med/1410
Patient UK Familial Mediterranean fever
MeSH D010505

Familial Mediterranean fever (FMF), also known as Armenian disease,[1][2] is a hereditary inflammatory disorder.[3]:149 FMF is an autoinflammatory disease caused by mutations in MEFV, a gene which encodes a 781–amino acid protein denoted pyrin.[4]

The disorder has been given various names including familial paroxysmal polyserositis, periodic peritonitis, recurrent polyserositis, benign paroxysmal peritonitis, periodic disease or periodic fever, Reimann periodic disease or Reimann's syndrome, Siegal-Cattan-Mamou disease, and Wolff periodic disease.[5][6][7] Note that "periodic fever" can also refer to any of the Periodic fever syndromes.

Signs and symptoms[edit]



  1. Abdominal attacks, featuring abdominal pain, affect the whole abdomen with all signs of peritonitis (inflammation of abdominal lining), and acute abdominal pain like appendicitis. They occur in 95% of all patients and may lead to unnecessary laparotomy. Incomplete attacks, with local tenderness and normal blood tests, have been reported.
  5. Myalgia (rare in isolation)


AA-amyloidosis with kidney failure is a complication and may develop without overt crises. AA amyloid protein is produced in very large quantities during attacks, and at a low rate between them, and accumulates mainly in the kidney, as well as the heart, spleen, gastrointestinal tract and thyroid.[8]








A specific and highly sensitive test for FMF is the "Metaraminol Provocative Test (MPT)," whereby a single 10 mg infusion of Metaraminol is administered to the patient. A positive diagnosis is made if the patient presents with a typical, albeit milder, FMF attack within 48 hours. As MPT is more specific than sensitive, it does not identify all cases of FMF. Although a positive MPT can be very useful.[9][10]


Familial Mediterranean fever has an autosomal recessive pattern of inheritance.

The MEFV gene is located on the short arm of chromosome 16 (16p13). The disorder is inherited in an autosomal recessive fashion. Therefore, two asymptomatic carrier parents have a 25% chance of a child with the disorder, a 50% chance of a child who is an asymptomatic carrier and a 25% chance of a child who does not carry the disorder. FMF patients who have children with a carrier or another FMF patient have a 50% and 100% chance, respectively, of having a child with FMF.[11][12]

There is one known case of an affected patient with only one parent who is a carrier. This is caused by a unique mutation on the sixteenth chromosome.


Attacks are self-limiting, and require analgesia and NSAIDs (such as diclofenac).[8]


Approximately 5–10% of FMF cases are resistant to colchicine therapy alone. In these cases, adding anakinra to the daily colchicine regimen has been successful.[14]


FMF affects groups of people originating from around the Mediterranean Sea (hence its name). It is prominently present in the Armenians, Sephardi Jews (and, to a much lesser extent, Ashkenazi Jews), Cypriots, Turks, and Arabs.[8][15]


A New York allergist, Dr Sheppard Siegal, first described the attacks of peritonitis in 1945; he termed this "benign paroxysmal peritonitis", as the disease course was essentially benign.[16] Dr Hobart Reimann, working in the American University in Beirut, described a more complete picture which he termed "periodic disease".[17][18]

In 1972, colchicine was discovered to prevent attacks.[19]

The link to the MEFV gene was discovered in 1997 by two different groups, each working independently - the French FMF Consortium,[11] and the International FMF Consortium.[12]

See also[edit]


  1. ^ Oxford Textbook of Medicine (4th ed.). Oxford: Oxford University Press. 2003. p. 159. ISBN 9780192629227. 
  2. ^ Unsal, Erbil (2006). Current Opinions in Pediatric Rheumatology. Hauppauge, N.Y.: Nova Science Publishers. p. 276. ISBN 9781594548710. 
  4. ^ Chae JJ; Wood G; Richard K et al. (September 2008). "The familial Mediterranean fever protein, pyrin, is cleaved by caspase-1 and activates NF-kappaB through its N-terminal fragment". Blood 112 (5): 1794–1803. doi:10.1182/blood-2008-01-134932. PMC 2518886. PMID 18577712. 
  5. ^ Dugdale III, David C; Jatin Vyas (2010-09-15). "Familial Mediterranean fever - PubMed Health". PubMed Health. National Centre for Biotechnology Information. Retrieved 2011-04-24. 
  6. ^ Siegal-Cattan-Mamou syndrome at Who Named It?
  7. ^ "Familial Mediterranean fever - Genetics Home Reference". Genetics Home Reference. U.S. National Library of Medicine. 2011-04-14. Archived from the original on 2011-04-24. Retrieved 2011-04-24. 
  9. ^ Barakat MH, El-Khawad AO, Gumaa KA, El-Sobki NI, Fenech FF (1984). "Metaraminol provocative test: a specific diagnostic test for familial Mediterranean fever". Lancet 1 (8378): 656–7. PMID 6142351. 
  10. ^ Huppertz HI, Michels H (1988). "[The metaraminol provocation test in the diagnosis of familial Mediterranean fever]". Monatsschr Kinderheilkd 136 (5): 243–5. PMID 3405225. 
  13. ^ Michael O, Goldman RD, Koren G (August 2003). "Safety of colchicine therapy during pregnancy". Can Fam Physician 49: 967–9. PMC 2214270. PMID 12943352. 
  14. ^ Calligaris L, Marchetti F, Tommasini A, Ventura A (2008). "The efficacy of anakinra in an adolescent with colchicine-resistant familial Mediterranean fever". European Journal of Pediatrics 167 (6): 695–696. doi:10.1007/s00431-007-0547-3. PMC 2292480. PMID 17588171. 
  15. ^ Sinha, Chandrasen K.; Davenport, Mark (2010). Handbook of Pediatric Surgery. New York: Springer. p. 192. ISBN 9781848821323. 
  16. ^ Siegal S (1945). "Benign paroxysmal peritonitis". Ann Intern Med 23 (2): 234–47. doi:10.7326/0003-4819-23-1-1. PMID 18124924. 
  17. ^ Reiman HA (1948). "Periodic disease. Probable syndrome including periodic fever, benign paroxysmal peritonitis, cyclic neutropenia and intermittent arthralgia". J Am Med Assoc 136 (4): 239–44. doi:10.1001/jama.1948.02890210023004. PMID 18920089. 
  18. ^ synd/2503 at Who Named It?
  19. ^ Goldfinger, S.E. (1972-12-21). "Colchicine for familial Mediterranean fever". New England Journal of Medicine 287 (25): 1302. doi:10.1056/NEJM197212212872514. PMID 4636899. 

External links[edit]