Diagnostic and therapeutic algorithms for monogenic autoinflammatory diseases presenting with recurrent fevers among adults

Marion Delplanque; Antoine Fayand; Guilaine Boursier; Gilles Grateau; Léa Savey; Sophie Georgin-Lavialle

doi:10.1093/rheumatology/keac712

Diagnostic and therapeutic algorithms for monogenic autoinflammatory diseases presenting with recurrent fevers among adults

Rheumatology (Oxford). 2023 Aug 1;62(8):2665-2672. doi: 10.1093/rheumatology/keac712.

Authors

Marion Delplanque^{1

2}, Antoine Fayand^{1

2}, Guilaine Boursier^{2

3}, Gilles Grateau^{1

2}, Léa Savey^{1

2}, Sophie Georgin-Lavialle^{1

2}

Affiliations

¹ Sorbonne University, Internal Medicine Department, AP-HP, Tenon Hospital, Paris, France.
² French National Reference Center for Autoinflammatory Diseases and AA Amyloidosis (CEREMAIA) France.
³ Department of Molecular Genetics and Cytogenomics, Rare and Auto Inflammatory Diseases Unit, CHU Montpellier, University of Montpellier, Montpellier, France.

PMID: 36575989
DOI: 10.1093/rheumatology/keac712

Abstract

Autoinflammatory diseases (AIDs) are defined as disorders of innate immunity. They were initially defined in contrast to autoimmune diseases because of the lack of involvement of the adaptive immune system and circulating autoantibodies. The four monogenic AIDs first described are called the 'historical' AIDs and include FMF (associated with MEFV mutations), cryopyrinopathies (associated with NLRP3 mutations), TNF receptor-associated periodic syndrome (associated with TNFRSF1A mutations) and mevalonate kinase deficiency (MKD; associated with MVK mutations). In the last 10 years, >50 new monogenic AIDs have been discovered due to genetic advances. The most important discovery for adult patients is VEXAS syndrome associated with somatic UBA1 mutations leading to an AID affecting mostly elderly men. Diagnosis of monogenic AIDs is based on personal and family history and detailed analysis of symptoms associated with febrile attacks in the context of elevated peripheral inflammatory markers. This review proposes a practical approach for the diagnosis of the main monogenic AIDs among adult patients.

Keywords: VEXAS syndrome; autoinflammation; familial Mediterranean fever; monogenic autoinflammatory disease; recurrent fever.

Publication types

Review

MeSH terms

Adult
Aged
Cryopyrin-Associated Periodic Syndromes* / diagnosis
Cryopyrin-Associated Periodic Syndromes* / drug therapy
Cryopyrin-Associated Periodic Syndromes* / genetics
Familial Mediterranean Fever* / diagnosis
Familial Mediterranean Fever* / drug therapy
Familial Mediterranean Fever* / genetics
Fever / etiology
Fever / genetics
Hereditary Autoinflammatory Diseases* / diagnosis
Hereditary Autoinflammatory Diseases* / genetics
Humans
Male
Mevalonate Kinase Deficiency* / diagnosis
Mevalonate Kinase Deficiency* / genetics
Pyrin

Substances

MEFV protein, human
Pyrin

Supplementary concepts

VEXAS syndrome