Cutaneous lupus erythematosus: updates on pathogenesis and associations with systemic lupus

Abstract

Purpose of review: Cutaneous lupus erythematosus (CLE) is a common manifestation among systemic lupus patients. There are no U.S. Food and Drug Administration approved therapies for CLE, and these lesions are frequently disfiguring and refractory to treatment. The present review will cover the recent inroads made into understanding the mechanisms behind CLE lesions and discuss promising therapeutic developments.

Recent findings: The definition of cutaneous lupus is being refined to facilitate diagnostic and research protocols. Research into the pathogenesis of CLE is accelerating, and discoveries are now identifying genetic and epigenetic changes which may predispose to particular disease manifestations. Furthermore, unique features of disease subtypes are being defined. Murine work supports a connection between cutaneous inflammation and systemic lupus disease activity. Importantly, human trials of type I interferon blockade hold promise for improving our treatment armamentarium for refractory CLE lesions.

Summary: Continued research to understand the mechanisms driving CLE will provide new methods for prevention and treatment of cutaneous lesions. These improvements may also have important effects on systemic disease activity, and thus, efforts to understand this link should be supported.

Figure 1. Summary of CLE pathogenesis

Triggers for skin inflammation, including UV light, stimulate innate cytokine production from keratinocytes and trigger cell death which can activate nucleic acid signaling pathways. Increased autoantigen exposure on the cell surface encourages immune complex deposition, which can lead to antibody dependent cell-mediated cytotoxicity. Cytokine and chemokine production promotes inflammatory infiltrates which damage tissues, perpetuate the inflammatory cycle and lead to chronic TGFβ signaling which promotes damage and scar. The links between skin inflammation and systemic disease require further study. DC=dendritic cell