Acquired autoinflammatory disorders: A dermatologist's perspective.

Abstract

Autoinflammatory disorders are characterized by dysregulated and disproportionately heightened response of innate immune system (IIS) to molecular patterns associated with damage and pathogens/microbes (DAMPs/PAMPs) with crucial role played by neutrophils and macrophages in disease pathogenesis. They closely resemble connective tissue diseases (CTDs). However, anti-nuclear antibodies (ANA), typically considered a marker of CTDs, are negative in autoinflammatory disorders. Many autoinflammatory disorders are monogenic and arise due to inherited genetic mutations resulting in autoinflammation. This is especially true for disorders presenting in childhood or early adulthood. However, with advent of VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, the genetic spectrum of these disorders has expanded, especially in adult population, emphasizing that these mutations could either be inherited or acquired later during one's lifetime. Additionally, many of the acquired autoinflammatory disorders, for example, adult-onset Still's disease (AOSD), and Schnitzler syndrome have a multifactorial pathogenesis and are typically polygenic. Many new disorders are being described in this category, and majority of them have prominent cutaneous manifestations, either at onset or during the course of disease, which are particularly important from diagnostic point of view. In this review, we discuss the cutaneous findings of a few acquired autoinflammatory disorders, with specific focus on AOSD, VEXAS syndrome, Schnitzler syndrome, Kikuchi-Fujimoto disease and hemophagolymphohistiocytosis (HLH).