Clinical Approach to Systemic Autoinflammatory Disorders: Classification, Disease Phenotypes and Management

Autoinflammatory Disorders (AIDs) can be either systemic or organ-specific. Systemic AIDs are associated with a primary dysfunction of the innate immunity that results in clinical signs of inflammation and/or elevated serum levels of acute-phase reactants. AIDs often present with rash, serositis, arthritis and/or aphthosis. Hereditary periodic fever syndromes, such as Familial Mediterranean Fever (FMF) and Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS), constitute the prototype of systemic AIDs. However, these also include many other disorders that do not follow the typical relapse-remitting pattern of unprovoked recurrent febrile episodes with intercalated periods of general well-being that can also result in severe complications such as amyloidosis. In this review, previous classification systems of AIDs, either clinical or pathophysiological/functional-based, have been revised and systemic AIDs are individually described. Also, a simplified classification based on clinical phenotypes that differentiates systemic from organ-specific AIDs is discussed.