Autoinflammatory Disorders: A Review and Update on Pathogenesis and Treatment

Abstract

The autoinflammatory diseases comprise a broad spectrum of disorders characterized by unchecked activation of the innate immune system. Whereas aberrations in adaptive immunity have long been identified in 'autoimmune' disorders, the concept of 'autoinflammation' emerged relatively recently, first describing a group of clinical disorders characterized by spontaneous episodes of systemic inflammation without manifestations typical of autoimmune disorders. Improved knowledge of innate immune mechanisms, coupled with remarkable progress in genomics and an expanding number of clinical cases, has since led to an increasing number of disorders classified as autoinflammatory or containing an autoinflammatory component. Biologic therapies targeting specific components of the innate immune system have provided immense clinical benefit, and have further elucidated the role of innate immunity in autoinflammatory disorders. This article reviews the basic mechanisms of autoinflammation, followed by an update on the pathophysiology and treatment of the monogenic and multifactorial autoinflammatory diseases, and the common dermatologic conditions in which autoinflammation plays a major role.