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Familial Mediterranean Fever

  • Shai Padeh
  • Yelda Bilginer
  • Seza OzenEmail author
Chapter

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.

Keywords

Familial Mediterranean fever Pyrin Colchicine Interleukin 1 Treatment Canakinumab, anakinra, rilonacept Autoinflammatory disease 

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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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Pediatrics AEdmond and Lily Safra Children’s Hospital, Sheba Medical CenterTel HashomerIsrael
  2. 2.Department of Pediatric RheumatologyHacettepe UniversityAnkaraTurkey

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