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


 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: Familial Mediterranean Fever (associated with MEFV mutations), cryopyrinopathies (associated with NLRP3 mutations), Tumor Necrosis Factor Receptor-associated Periodic Syndrome (associated with TNFRSF1A mutations) and Mevalonate Kinase Deficiency (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 autoinflammatory disease 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 of the diagnosis of the main monogenic AIDs among adult patients to guide the clinician.