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| {{Infobox_Disease |
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| Name = {{PAGENAME}} |
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| Image = |
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| Caption = |
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| DiseasesDB = 9836 |
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| ICD10 = {{ICD10|E|85|0|e|70}} |
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| ICD9 = |
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| ICDO = |
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| OMIM = 249100 |
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| OMIM_mult = {{OMIM2|608107}} |
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| MedlinePlus = |
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| MeshID = D010505 |
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| }}
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| {{SI}}
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| {{CMG}}
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| {{SK}} Familial Mediterranean fever, autosomal recessive; FMF; polyserositis, recurrent; polyserositis, familial paroxysmal; recurrent hereditary polyserositis; Siegal-Cattan-Mamou disease; Wolff periodic disease; Periodic fever syndrome; hereditary periodic fever syndrome; Mediterranean fever, familial; periodic disease, periodic disease, Wolff's; periodic fever syndromes, hereditary; Wolff's periodic disease
| | '''For patient information on this topic, click [[Familial mediterranean fever (patient information)|here]].''' |
| ==Overview==
| | {{Familial mediterranean fever}} |
| '''Familial Mediterranean fever''' (FMF) is a [[genetic disorder|hereditary]] [[inflammation|inflammatory]] disorder that affects groups of patients originating from around the Mediterranean Sea (hence its name). It is prominently present in the Armenian people (up to 1 in 7 affected), Sephardi Jews (and, to a much lesser extent, Ashkenazi Jews), people from Turkey, the Arab countries and Lebanon.<ref name=Livneh>Livneh A, Langevitz P. Diagnostic and treatment concerns in familial Mediterranean fever. ''Baillieres Best Pract Res Clin Rheumatol'' 2000;14(3):477-98. PMID 10985982.</ref> | | {{CMG}} {{AE}} {{Sahar}} |
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| ==Historical Perspective==
| | {{SK}} [[Familial paroxysmal polyserositis]]; [[periodic peritonitis]]; [[recurrent polyserositis]]; [[benign paroxysmal peritonitis]]; [[Reimann periodic disease]]; [[Reimann's syndrome]]; [[Siegal-Cattan-Mamou disease]]; [[Wolff periodic disease]]; [[recurrent hereditary polyserositis]] |
| 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.<ref>Siegal S. Benign paroxysmal peritonitis. ''Ann Intern Med'' 1945;23:1-21.</ref> Dr Hobart Reimann, working in the American University in Beirut, described a more complete picture which he termed "periodic disease".<ref>Reiman HA. Periodic disease. Probable syndrome including periodic fever, benign paroxysmal peritonitis, cyclic neutropenia and intermittent arthralgia. ''[[Journal of the American Medical Association|JAMA]]'' 1948;136:239-44.</ref>
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| ==Pathophysiology== | | ==[[Familial mediterranean fever overview|Overview]]== |
| Virtually all cases are due to a mutation in the ''MEFV'' gene, which codes for a protein called ''pyrin'' or ''marenostenin''. This was discovered in 1997 by two different groups, each working independently - the French FMF Consortium,<ref name=FConsort>The French FMF Consortium. A candidate gene for familial Mediterranean fever. Nat Genet 1997;17:25-31. PMID 9288094</ref> and the International FMF Consortium<ref name=IConsort>The International FMF Consortium. Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell 1997;90:797-807. PMID 9288758.</ref> Various mutations of this gene lead to FMF, although some mutations cause a more severe picture than others. Mutations occur in [[exon]]s 2, 3, 5 and 10.<ref name=Livneh/>
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| The function of pyrin has not been completely elucidated, but it appears to be a suppressor of the activation of [[caspase 1]], the [[enzyme]] that stimulates production of [[IL-1|interleukin 1β]], a [[cytokine]] central to the process of [[inflammation]]. 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).<ref name=Livneh/>
| | ==[[Familial mediterranean fever historical perspective|Historical Perspective]]== |
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| ===Genetics=== | | ==[[Familial mediterranean fever pathophysiology|Pathophysiology]]== |
| The ''[[MEFV]]'' gene is located on the short arm of [[chromosome 16 (human)|chromosome 16]] (16p13). The disease inherits in an [[autosomal recessive]] fashion. Therefore, two asymptomatic carrier parents have a 25% chance of a child with the disorder. FMF patients who marry a carrier or another FMF patient have a 50% and 100% chance, respectively, in having a child with FMF.<ref name=FConsort/><ref name=IConsort/>
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| ==Natural History, Complications and Prognosis== | | ==[[Familial mediterranean fever causes|Causes]]== |
| [[amyloidosis|AA-amyloidosis]] with [[renal 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 the [[thyroid]].<ref name=Livneh/> | |
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| There appears to be an increase in the risk for developing particular [[vasculitis]]-related diseases (e.g. [[Henoch-Schönlein purpura]]), [[spondylarthropathy]], prolonged [[arthritis]] of certain joints and protracted myalgia.<ref name=Livneh/>
| | ==[[Familial mediterranean fever differential diagnosis|Differentiating Familial Mediterranean Fever from other Diseases]]== |
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| | ==[[Familial mediterranean fever epidemiology and demographics|Epidemiology and Demographics]]== |
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| | ==[[Familial mediterranean fever risk factors|Risk Factors]]== |
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| | ==[[Familial mediterranean fever natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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| ==Diagnosis== | | ==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.
| | ===[[Familial Mediterranean fever diagnostic study of choice|Diagnostic study of choice]]=== |
| ===Symptoms===
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| There are seven types of attacks. 90% of all patients have their first attacks before they are 20 years old. All develop over 2-4 hours and last anytime between 6 hours and 4 days. Most attacks involve [[fever]]:<ref name=Livneh/>
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| # Abdominal attacks, featuring [[abdominal pain]] affecting the whole abdomen with all signs of [[acute abdomen]] (e.g. [[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.
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| # Joint attacks, occurring in large joints, mainly of the legs. Usually, only one joint is affected. 75% of all FMF patients experience Joint attacks.
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| # Chest attacks with [[pleuritis]] (inflammation of the [[pleura]]l lining) and [[pericarditis]] (inflammation of the [[pericardium]]). Pleuritis occurs in 40%, but pericarditis is rare.
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| # [[Scrotum|Scrotal]] attacks due to inflammation of the [[tunica vaginalis]]. This occurs in up to 5% and may be mistaken for acute scrotum (i.e. [[testicular torsion]])
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| # [[Myalgia]] (rare in isolation)
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| # [[Erysipelas|Erysipeloid]] (a skin reaction on the legs, rare in isolation)
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| # [[Fever]] without any symptoms (25%)
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| ===Laboratory Findings===
| | [[Familial mediterranean fever history and symptoms|History and Symptoms]] | [[Familial mediterranean fever physical examination|Physical Examination]] | [[Familial mediterranean fever laboratory findings|Laboratory Findings]] | [[Familial Mediterranean fever echocardiography and ultrasound|Echocardiography and ultrasound]] | [[Familial mediterranean fever x ray|X-Ray Findings]] | [[Familial mediterranean fever CT scan|CT-Scan Findings]] | [[Familial mediterranean fever MRI|MRI Findings]] | [[Familial mediterranean fever other imaging studies|Other Imaging Studies]] | [[Familial mediterranean fever other diagnostic studies|Other Diagnostic Studies]] |
| An [[acute phase response]] is present during attacks, with high [[C-reactive protein]] levels, an elevated [[white blood cell]] count and other markers of [[inflammation]]. In patients with a long history of attacks, monitoring the [[renal function]] is of importance in predicting [[chronic renal failure]].<ref name=Livneh/>
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| A genetic test is also available now that the disease has been linked to mutations in the ''MEFV'' gene. Sequencing of exons 2, 3, 5, and 10 of this gene detects an estimated 97% of all known mutations.<ref name=Livneh/>
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| ==Treatment== | | ==Treatment== |
| Attacks are self-limiting, and require [[analgesia]] and [[non-steroidal anti-inflammatory drug]]s (such as [[diclofenac]]).<ref name=Livneh/>
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| Since the 1970s, [[colchicine]], a drug otherwise mainly used in [[gout]], has been shown to decrease attack frequency in FMF patients. The exact way in which colchicine suppresses attacks is unclear. While this agent is not without side-effects (such as [[abdominal pain]] and [[myalgia|muscle pains]]), it may markedly improve quality of life in patients. The dosage is typically 1-2 mg a day. Development of amyloidosis is delayed with colchicine treatment. [[Interferon]] is being studied as a therapeutic modality.<ref name=Livneh/>
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| ==References==
| | [[Familial mediterranean fever medical therapy|Medical Therapy]] | [[Familial mediterranean fever prevention|Prevention]] | [[Familial mediterranean fever cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Familial mediterranean fever future or investigational therapies|Future or Investigational Therapies]] |
| {{Reflist|2}}
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| | ==Case Studies== |
| | [[Familial mediterranean fever case study one|Case #1]] |
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| {{Endocrine, nutritional and metabolic pathology}} | | {{Endocrine, nutritional and metabolic pathology}} |
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| [[Category:Genetic disorders]] | | [[Category:Genetic disorders]] |
| [[Category:Inborn errors of metabolism]] | | [[Category:Inborn errors of metabolism]] |
| | [[Category:Disease]] |
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| [[de:Mittelmeerfieber]] | | [[de:Mittelmeerfieber]] |