Familial Mediterranean fever - Revision history

Prab: CSV import

2025-04-06T16:07:56Z

CSV import

Prab at 04:31, 30 March 2025

2025-03-30T04:31:41Z

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-== Familial Mediterranean fever ==
+{{Infobox medical condition (new)
+| name          = Familial Mediterranean fever
 [[File:Erysipeloid skin rashes in Familial Mediterranean Fever.jpg|thumb|600px|Erysipeloid skin rashes in Familial Mediterranean Fever]]
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 #[[Myalgia]] (rare in isolation)
 #[[Erysipelas|Erysipeloid]] (a skin reaction on the legs that can mimic [[cellulitis]], rare in isolation)
-#Fever without any of the other symptoms listed above (25%). Fever may be the only symptom during the childhood. It may vary from a mild fever to 38–40&nbsp;°C. It nearly always accompanies to episodes.<ref name="Kucuk 2014 97–104">{{Cite journal|last=Kucuk|first=Adem|last2=Gezer|first2=Ilknur Albayrak|last3=Ucar|first3=Ramazan|last4=Karahan|first4=Ali Yavuz|date=2014|title=Familial Mediterranean Fever|journal=Acta Medica (Hradec Kralove, Czech Republic)|language=en|volume=57|issue=3|pages=97–104|doi=10.14712/18059694.2014.47|pmid=25649364|issn=1211-4286}}</ref>
+#Fever without any of the other symptoms listed above (25%). Fever may be the only symptom during the childhood. It may vary from a mild fever to 38–40&nbsp;°C. It nearly always accompanies to episodes.
 ===Complications===
@@ Line 56: / Line 77: @@
 ==Treatment==
-Attacks are self-limiting, and require [[analgesia]] and [[non-steroidal anti-inflammatory drug|NSAID]]s (such as [[diclofenac]]).<ref name="Livneh">{{cite journal |vauthors=Livneh A, Langevitz P |title=Diagnostic and treatment concerns in familial Mediterranean fever |journal=Best Practice & Research Clinical Rheumatology |volume=14 |issue=3 |pages=477–498 |year=2000 |pmid=10985982 |doi=10.1053/berh.2000.0089}}</ref> [[Colchicine]], a drug otherwise mainly used in [[gout]], decreases 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&nbsp;mg a day. Development of amyloidosis is delayed with colchicine treatment. [[Interferon]] is being studied as a therapeutic modality.Some advise discontinuation of colchicine before and during pregnancy, but the data are inconsistent, and others feel it is safe to take colchicine during pregnancy.
+Attacks are self-limiting, and require [[analgesia]] and [[non-steroidal anti-inflammatory drug|NSAID]]s (such as [[diclofenac]]). [[Colchicine]], a drug otherwise mainly used in [[gout]], decreases 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&nbsp;mg a day. Development of amyloidosis is delayed with colchicine treatment. [[Interferon]] is being studied as a therapeutic modality.Some advise discontinuation of colchicine before and during pregnancy, but the data are inconsistent, and others feel it is safe to take colchicine during pregnancy.
 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.[[Canakinumab]], an anti-interleukin-1-beta [[monoclonal antibody]], has likewise been shown to be effective in controlling and preventing flare-ups in patients with colchicine-resistant FMF and in two additional autoinflammatory recurrent fever syndromes: mevolonate kinase deficiency (hyper-[[immunoglobulin D]] syndrome, or [[Hyperimmunoglobulinemia D with recurrent fever|HIDS]]) and tumor necrosis factor receptor-associated periodic syndrome ([[TNF receptor associated periodic syndrome|TRAPS]]).
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 FMF affects groups of people originating from around the Mediterranean Sea (hence its name). It is prominently present in the [[Armenians]], [[Sephardic Jews|Sephardic]] Jews (and, to a much lesser extent, [[Ashkenazi]] Jews), [[Cyprus|Cypriots]], Turks and Arabs.
 ==See also==
 *[[List of cutaneous conditions]]
 *[[Urticarial syndromes]]
 {{Amyloidosis}}
 {{DEFAULTSORT:Familial Mediterranean Fever}}
 [[Category:Arthritis]]

Kondreddy Naveen at 19:40, 19 November 2023

2023-11-19T19:40:09Z

New page

== Familial Mediterranean fever ==

[[File:Erysipeloid skin rashes in Familial Mediterranean Fever.jpg|thumb|600px|Erysipeloid skin rashes in Familial Mediterranean Fever]]

'''Familial Mediterranean fever''' ('''FMF''') is a [[genetic disorder|hereditary]] [[inflammation|inflammatory]] disorder. FMF is an autoinflammatory disease caused by mutations in [[MEFV|Mediterranean fever]] gene, which encodes a 781–amino acid protein called [[pyrin]]. While all ethnic groups are susceptible to FMF, it usually occurs in people of [[Mediterranean Sea|Mediterranean]] origin—including [[Sephardic Jews]], [[Mizrahi Jews]], [[Ashkenazi Jews]], [[Armenians]], [[Azerbaijanis]], [[Arab]]s, [[Kurds]], [[Greeks]], [[Turkish people|Turks]], and [[Italians]].

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.Note that "periodic fever" can also refer to any of the [[periodic fever syndrome]]s.

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==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 4 days. Most attacks involve [[fever]].

#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 [[pleuritis]] (inflammation of the [[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.
#[[Scrotum|Scrotal]] attacks due to inflammation of the [[tunica vaginalis]] are somewhat rare but may be mistaken for [[testicular torsion]].
#[[Myalgia]] (rare in isolation)
#[[Erysipelas|Erysipeloid]] (a skin reaction on the legs that can mimic [[cellulitis]], rare in isolation)
#Fever without any of the other symptoms listed above (25%). Fever may be the only symptom during the childhood. It may vary from a mild fever to 38–40 °C. It nearly always accompanies to episodes.<ref name="Kucuk 2014 97–104">{{Cite journal|last=Kucuk|first=Adem|last2=Gezer|first2=Ilknur Albayrak|last3=Ucar|first3=Ramazan|last4=Karahan|first4=Ali Yavuz|date=2014|title=Familial Mediterranean Fever|journal=Acta Medica (Hradec Kralove, Czech Republic)|language=en|volume=57|issue=3|pages=97–104|doi=10.14712/18059694.2014.47|pmid=25649364|issn=1211-4286}}</ref>

===Complications===
[[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]], [[Human gastrointestinal tract|gastrointestinal tract]], and [[thyroid]].

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.

==Genetics==

The ''[[MEFV]]'' gene is located on the short arm of [[chromosome 16 (human)|chromosome 16]] (16p13). Many different mutations of the ''[[MEFV]]'' gene can cause the disorder. Having one mutation is unlikely to cause the condition. Having two mutations either a copy from both parents, or two different mutations, one from each parent is the threshold for a genetic diagnosis of FMF. However, most individuals who comply with the genetic diagnosis of FMF remain asymptomatic or undiagnosed. Whether this is due to modifier genes or environmental factors remains to be established.

==Pathophysiology==

Virtually all cases are due to a mutation in the ''Mediterranean Fever (MEFV)'' gene on the [[Chromosome 16 (human)|sixteenth chromosome]], 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 [[exon]]s 2, 3, 5 and 10.

The function of pyrin has not been completely elucidated, but in short, it is a protein that binds to the adaptor ASC and the pro form of the enzyme caspase-1 to generate multiprotein complexes called inflammasomes in response to certain infections. In healthy individuals, pyrin-mediated inflammasome assembly (which leads to the caspase 1) dependent processing and secretion of the pro-inflammatory cytokines (such as interleukin-18 (IL-18) and IL-1β) is a response to enterotoxins from certain bacteria.The gain-of-function mutations in the MEFV gene render Pyrin hyperactive, and subsequently, the formation of the inflammasomes becomes more frequent.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).

==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 [[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 [[kidney function]] is of importance in predicting [[chronic kidney failure]].

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.

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.

==Treatment==

Attacks are self-limiting, and require [[analgesia]] and [[non-steroidal anti-inflammatory drug|NSAID]]s (such as [[diclofenac]]).<ref name="Livneh">{{cite journal |vauthors=Livneh A, Langevitz P |title=Diagnostic and treatment concerns in familial Mediterranean fever |journal=Best Practice & Research Clinical Rheumatology |volume=14 |issue=3 |pages=477–498 |year=2000 |pmid=10985982 |doi=10.1053/berh.2000.0089}}</ref> [[Colchicine]], a drug otherwise mainly used in [[gout]], decreases 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.Some advise discontinuation of colchicine before and during pregnancy, but the data are inconsistent, and others feel it is safe to take colchicine during pregnancy.

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.[[Canakinumab]], an anti-interleukin-1-beta [[monoclonal antibody]], has likewise been shown to be effective in controlling and preventing flare-ups in patients with colchicine-resistant FMF and in two additional autoinflammatory recurrent fever syndromes: mevolonate kinase deficiency (hyper-[[immunoglobulin D]] syndrome, or [[Hyperimmunoglobulinemia D with recurrent fever|HIDS]]) and tumor necrosis factor receptor-associated periodic syndrome ([[TNF receptor associated periodic syndrome|TRAPS]]).

==Epidemiology==

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

==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.Dr Hobart Reimann, working in the [[American University of Beirut|American University in Beirut]], described a more complete picture which he termed "periodic disease".

In 1972, colchicine was discovered to prevent attacks. The link to the ''MEFV'' gene was discovered in 1997 by two different groups, each working independently - the French FMF Consortium,and the International FMF Consortium.

==See also==

*[[List of cutaneous conditions]]
*[[Urticarial syndromes]]

==External links==
{{Medical resources
| DiseasesDB = 9836
| ICD10 = {{ICD10|E|85|0|e|70}}
| ICD9 = {{ICD9|277.31}}
| ICDO =
| OMIM = 249100
| OMIM_mult = {{OMIM2|608107}}
| MedlinePlus = 000363
| eMedicineSubj = med
| eMedicineTopic = 1410
| MeshID = D010505
| GeneReviewsNBK = NBK1227
| GeneReviewsName= Familial Mediterranean Fever
}}

*{{Proteopedia|2wl1}} information about the [[MEFV]] gene.
*[https://www.ncbi.nlm.nih.gov/books/NBK1227/ GeneReview/NIH/UW entry on Familial Mediterranean Fever]
*[http://niams.nih.gov/Health_Info/Autoinflammatory/default.asp#2 Familial Mediterranean Fever (FMF)] - US National Institute of Arthritis and Musculoskeletal and Skin Diseases

{{Amyloidosis}}

{{DEFAULTSORT:Familial Mediterranean Fever}}
[[Category:Arthritis]]
[[Category:Rheumatology]]
[[Category:Immune system disorders]]
[[Category:Autosomal recessive disorders]]
[[Category:Autoinflammatory syndromes]]
{{stub}}