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Familial Mediterranean Fever

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Textbook of Autoinflammation

Abstract

Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease characterized by recurrent, sporadic, self-limited episodes of fever accompanied by peritonitis, pleuritis, arthritis, and/or erysipelas-like erythema. The disease is prevalent among populations surrounding the Mediterranean Sea, however, in recent years, more cases have been reported in countries not related or close to this region. The frequency of episodes varies from once every week to several times a year, and unlike the term “periodic disease”, the attacks are at random and not cyclic. A typical attack of FMF lasts 0.5–3 days, and between attacks patients are mostly asymptomatic. One of the devastating outcomes of FMF is the development of AA amyloidosis, which mostly affects the kidneys but may involve other organs. Since 1972, life-long prophylactic colchicine has been the treatment of choice for FMF, which reduces the number of acute attacks and prevents the development of amyloidosis. Several sets of diagnostic criteria and several severity scores have been proposed. The disease is caused by gain-of-function mutations in the MEFV gene, encoding pyrin, a protein which by binding to additional proteins form the pyrin inflammasome. Mutated pyrin is associated with activation of caspase-1 and the release of interleukin (IL)-1ß, resulting in inflammation. Unraveling the molecular mechanisms of FMF led to the understanding of the potential of IL1ß blockade as a novel treatment in patients with colchicine-resistant FMF. However, colchicine remains the main treatment of FMF.

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Abbreviations

ADDI:

Autoinflammatory Disease Damage Index

AIDAI:

Autoinflammatory Disease Activity Index

ANCA:

Antineutrophil cytoplasmic antibodies

ASC:

Apoptotic speck protein containing a caspase recruitment domain

CARD:

Caspase recruitment domain

CRP:

C-reactive protein

ESR:

Erythrocyte sedimentation rate

EULAR:

European League Against Rheumatism

FAVOR:

FMF Arthritis Vasculitis and Orphan Disease Research group

FMF:

Familial Mediterranean fever

IL:

Interleukin

ISSF:

International Severity Score for FMF

JIA:

Juvenile idiopathic arthritis

LPS:

Lipopolysaccharide

MEFV:

MEditerranean FeVer gene

NET:

Neutrophil extracellular traps

PAAND:

Pyrin-associated autoinflammation with neutrophilic dermatosis

PFAPA:

Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis

PFMS:

Protracted febrile myalgia syndrome

PKN:

Protein kinase N

PRINTO:

Pediatric Rheumatology International Trials Organization

PYD:

Pyrin domain

SAA:

Serum amyloid A

SHARE:

Single Hub and Access point for paediatric Rheumatology in Europe

TNF:

Tumor necrosis factor

TRAPS:

Tumor necrosis factor receptor-associated periodic syndrome

TRIM:

Tripartite motif

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Authors and Affiliations

  1. Department of Pediatrics A, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel Hashomer, Israel

    Shai Padeh

  2. Department of Pediatric Rheumatology, Hacettepe University, Ankara, Turkey

    Yelda Bilginer & Seza Ozen

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  1. Shai Padeh
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  2. Yelda Bilginer
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  3. Seza Ozen
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Correspondence to Seza Ozen .

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Editors and Affiliations

  1. Pediatric Rheumatology Unit, Shaare Zedek Medical Center and Hebrew University, Jerusalem, Israel

    Philip J. Hashkes

  2. Department Paediatrics, Division of Rheumatology, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada

    Ronald M. Laxer

  3. Department of Internal Medicine, Radboudumc Expertisecenter for Immunodeficiency and Autoinflammation, Radboud University Medical Center, Nijmegen, The Netherlands

    Anna Simon

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Padeh, S., Bilginer, Y., Ozen, S. (2019). Familial Mediterranean Fever. In: Hashkes, P., Laxer, R., Simon, A. (eds) Textbook of Autoinflammation. Springer, Cham. https://doi.org/10.1007/978-3-319-98605-0_16

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