Acquired autoinflammatory disorders: a dermatologist's perspective.

Abstract

Autoinflammatory disorders are characterized by a dysregulated and disproportionately heightened response by the innate immune system to PAMPs and DAMPs (pathogen- and damage-associated molecular patterns, respectively), with a crucial role played by neutrophils and macrophages in disease pathogenesis. Autoinflammatory disorders closely resemble connective tissue diseases (CTDs); however, tests for antinuclear antibodies, typically considered a marker of CTDs, are negative in autoinflammatory disorders. Many autoinflammatory disorders are monogenic and arise from inherited genetic mutations, resulting in autoinflammation. This is especially true for disorders presenting in childhood or early adulthood. However, with the relatively recent identification of VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, the recognized genetic spectrum of these disorders has expanded, especially in the adult population, emphasizing that these mutations could either be inherited or acquired later in life. Additionally, many of the acquired autoinflammatory disorders, for example, adult-onset Still disease and Schnitzler syndrome, have a multifactorial pathogenesis and are typically polygenic. Many novel disorders are being described in this category, and the majority of them have prominent cutaneous manifestations - either at onset or during the course of disease - that are particularly important from a diagnostic point of view. In this review, we discuss the cutaneous findings of a few acquired autoinflammatory disorders, with a specific focus on adult-onset Still disease, VEXAS syndrome, Schnitzler syndrome, Kikuchi-Fujimoto disease and haemophagocytic lymphohistiocytosis.