Immunopathogenesis of skin injury in systemic lupus erythematosus

Abstract

Purpose of review: Skin injury is the most common clinical manifestation of SLE and is disfiguring, difficult to treat, and incompletely understood. We provide an overview of recently published articles covering the immunopathogenesis of skin injury in SLE.

Recent findings: Skin of SLE has an inherent susceptibility to apoptosis, the cause of which may be multifactorial. Chronic IFN overexpression leads to barrier disruption, infiltration of inflammatory cells, cytokine production, and release of autoantigens and autoantibody production that result in skin injury. Ultraviolet light is the most important CLE trigger and amplifies this process leading to skin inflammation and potentially systemic disease flares.

Summary: The pathogenesis of skin injury in CLE is complex but recent studies highlight the importance of mechanisms driving dysregulated epidermal cell death likely influenced by genetic risk factors, environmental triggers (UV light), and cytotoxic cells and cellular signaling.

Figure 1:. Inflammatory loop of skin injury and response in SLE.

IgG and immune complex deposition are found in both lesional and nonlesional skin of patients with SLE. Additional triggers (such as UV exposure or smoking) are required for inflammation and rash to develop. Chronically elevated levels of type I IFN, specifically IFNκ, are required for the exaggerated UV induced keratinocyte apoptosis and drive the pro-inflammatory loop by stimulating resident dendritic cells and keratinocytes to release signals to stimulate T cell activation. The inflammatory loop is completed by T cell activation of B cells to further produce autoantibodies potentially leading to spread of the rash and to systemic disease flare.