Familial Mediterranean fever
Familial Mediterranean fever | |
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Familial Mediterranean fever has an autosomal recessive pattern of inheritance | |
Specialty | Rheumatology, Immunology |
Familial Mediterranean fever (FMF) is a
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 syndrome, Siegal-Cattan-Mamou disease, and Wolff periodic disease.[9][10][11] Note that "periodic fever" can also refer to any of the periodic fever syndromes.
Signs and symptoms
Attacks
There are seven types of attacks. Ninety percent of all patients have their first attack before they are 18 years old. All develop over 2–4 hours and last anywhere from 6 hours to 5 days. Most attacks involve fever.[12]
- 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.
- Joint attacks mainly occur in large joints, especially in the legs. Usually, only one joint is affected. 75% of all FMF patients experience joint attacks.
- Chest attacks include pleura) and pericarditis (inflammation of the pericardium). Pleuritis occurs in 40% of patients and makes it difficult to breathe or lie flat, but pericarditis is rare.
- Scrotal attacks due to inflammation of the tunica vaginalis are somewhat rare but may be mistaken for testicular torsion.
- Myalgia (rare in isolation)
- Erysipeloid rashes (a skin reaction on the legs that can mimic cellulitis, rare in isolation)
Diagnostic criteria
Various diagnostic criteria have been set, but the Tel-Hashomer clinical criteria is widely recognized for the diagnosis of FMF. It has more than 95% and 97% sensitivity and specificity, respectively.[13]
For the criteria, typical attacks consist of all the following: recurrent (three or more episodes), febrile (
Incomplete attacks (must be recurrent) are differing from typical attacks in at least one feature as follows:
Complications
There appears to be an increase in the risk for developing particular
Genetics
The
Pathophysiology
Virtually all cases are due to a mutation in the Mediterranean Fever (MEFV) gene on the chromosome 16, which codes for a protein called pyrin or marenostrin. Various mutations of this gene lead to FMF, although some mutations cause a more severe picture than others. Mutations occur mainly in exons 2, 3, 5 and 10.[12]
The function of pyrin has not been completely elucidated, but in short, it is a protein that binds to the adaptor
The pathophysiology of familial Mediterranean fever has recently undergone significant advances: at basal state,
It is not conclusively known what exactly sets off the attacks, and why overproduction of IL-1 would lead to particular symptoms in particular organs (e.g. joints or the peritoneal cavity).[12] However, steroid hormone catabolites (pregnanolone and etiocholanolone) have been shown to activate the pyrin inflammasome, in vitro, by interacting with the B30.2 domain (coded by exon 10).[22]
Diagnosis
The diagnosis is clinically made on the basis of the history of typical attacks, especially in patients from the ethnic groups in which FMF is more highly prevalent. An
A genetic test is also available to detect mutations in the MEFV gene. Sequencing of exons 2, 3, 5, and 10 of this gene detects an estimated 97% of all known mutations.[12]
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.[23][24]
Treatment
Attacks are self-limiting, and require
Approximately 5–10% of FMF cases are resistant to colchicine therapy alone. In these cases, adding
Epidemiology
FMF affects groups of people originating from around the Levant or Eastern Mediterranean (hence its name); it is thus most prominent among those from or with ancestry from the regions including Arabs, Armenians, Jews (particularly Sephardi, Mizrahi, and to a lesser degree Ashkenazi Jews), and Turks.[3][12][28][29]
History
A New York City allergist, Sheppard Siegal, first described the attacks of peritonitis in 1945; he termed this "benign paroxysmal peritonitis", as the disease course was essentially benign.[30] Dr Hobart Reimann, working in the American University in Beirut, described a more complete picture which he termed "periodic disease".[31][32] French physicians Henry Mamou and Roger Cattan described the complete disease with renal complications in 1952.[33][34]
See also
- List of cutaneous conditions
- Urticarial syndromes
References
- ISBN 0-7216-2921-0.
- PMID 18577712.
- ^ PMID 10854115.
- ^ PMID 11528510.
- ^ "Familial Mediterranean fever". Mayo Clinic.
- S2CID 7306747.
- ^ Saeed D, Mortaza B, Tooba M (15 December 2010). "The Prevalence of Genetic Disorders in East Azerbaijan Province". Urmia Medical Journal. 21 (4): 339–346.
- PMID 10854115.
- ^ Dugdale III DC, Vyas J (2010-09-15). "Familial Mediterranean fever - PubMed Health". PubMed Health. National Centre for Biotechnology Information. Archived from the original on 2012-09-10. Retrieved 2011-04-24.
- ^ "Siegal-Cattan-Mamou syndrome". Retrieved February 19, 2021.
- ^ "Familial Mediterranean fever - Genetics Home Reference". Genetics Home Reference. U.S. National Library of Medicine. 2011-04-14. Archived from the original on 2011-06-05. Retrieved 2011-04-24.
- ^ PMID 10985982.
- PMID 9336425.
- PMID 18035151.
- S2CID 51606430.
- ^ Ratner D (May 11, 2016). Activation and Inhibition of Multiple Inflammasome Pathways by the Yersinia Pestis Type Three Secretion System (Ph.D. thesis). University of Massachusetts Medical School.
- PMID 21600797.
- PMID 29718184.
- PMID 27270401.
- PMID 31589380.
- PMID 27911804.
- PMID 36223753.
- S2CID 23211155.
- PMID 3405225.
- PMID 12943352. Archived from the originalon 2009-01-30.
- PMID 17588171.
- PMID 29768139.
- PMID 25649364.
- ISBN 9781848821323.
- PMID 18124924.
- PMID 18920089.
- Who Named It?
- ^ Mamou H, Cattan R (1952). "Semaine Des Hôpitaux de Paris". La Maladie Périodique. 28: 1062–1070.
- PMID 26318474.
External links
- Proteopedia 2wl1 information about the MEFV gene.
- GeneReview/NIH/UW entry on Familial Mediterranean Fever
- Familial Mediterranean Fever (FMF) - US National Institute of Arthritis and Musculoskeletal and Skin Diseases