Current Insights in Cutaneous Lupus Erythematosus Immunopathogenesis

Abstract

Cutaneous Lupus Erythematosus (CLE) is a clinically diverse group of autoimmune skin diseases with shared histological features of interface dermatitis and autoantibodies deposited at the dermal-epidermal junction. Various genetic and environmental triggers of CLE promote infiltration of T cells, B cells, neutrophils, antigen presenting cells, and NK cells into lesional skin. In this mini-review, we will discuss the clinical features of CLE, insights into CLE immunopathogenesis, and novel treatment approaches.

Keywords: CLE; UV light; autoantibodies; autoimmune; cutaneous; interface dermatitis; lupus; lupus band.

Figure 1

Posterior view of the trunk in a Hispanic patient with Cutaneous Lupus Erythematosus (CLE). (A) Arrows point to two lupus patches on the upper back and lower back. (B) Closer view of the upper back patch in the intrascapular area showing scaling, erythema, dyspigmentation, and scarring.

Figure 2

Initiation, immunopathogenesis, and histopathologic features of CLE. (A) Environmental triggers of CLE include UV light and drugs which may become photoconverted to induce translocation of autoantigens, DAMP release and keratinocyte death. UV damage is sensed by LHC, which protect surrounding keratinocytes through release of EGFR-L; however, LHC are decreased or absent in CLE lesional skin. Keratinocytes from CLE patients also exhibit a hyper IFN loop via JAK/STAT signaling to release IFNs. Keratinocytes and skin resident immune cells upregulate cytokines and chemokines in response to IFN and other signals to promote lesion formation. (B) Histopathological features of CLE lesions include mild hyperkeratosis, keratinocyte death and debris, lymphocytic infiltrates, interface dermatitis, and mucin deposition. Dyspigmentation occurs in some CLE subtypes. Perivascular pDC clusters and fibrosing alopecia occur primarily in DLE lesions. CLE interface dermatitis is comprised of lymphomonocytic infiltrates with “clockface” plasma cells. Neutrophils, which may form NETs, are also present in CLE lesions and may activate pDCs through release of DNA and other autoantigens. Resident memory T and B cells likely form in CLE lesions. Inflammatory mediators drive continued recruitment and damage in the lesion, including IFNκ (yellow, associated with keratinocytes), IFNγ (orange, associated with the infiltrating immune cells), CXCL9 (red, amplified by keratinocytes and immune cells), and CXCL10 (blue, amplified by keratinocytes and immune cells).