Rethinking the Pathogenesis of Cutaneous Lupus

Abstract

Knowledge of the etiology of cutaneous lupus is rapidly evolving. Dissection of the pathologic events in lesional skin has led to knowledge of important cell populations and transcriptional changes contributing to disease. Recently, the study of nonlesional skin in patients with systemic lupus has also identified key abnormalities that likely contribute to a propensity for inflammation. These include an elevated type I IFN signature, overproduction of IFNs, and an absence of Langerhans cells. These changes promote aberrant inflammation in response to known triggers of disease, such as UV light. Further research will undoubtedly accelerate our understanding of this disfiguring disease.

E-Cadherin Expression and Blunted Interferon Response in Blastic Plasmacytoid Dendritic Cell Neoplasm

“…Our data point to a defective IFN-I response in BPDCN, at variance with CLE lesions, the latter representing active inflammatory lesions sustained by the action of Teffector cells. 24,30,31 Production of IFN-I, 32 together with the extent of recruitment and activation of innate and/or adaptive immune cells at sites of neoplastic growth, dictates the outcome of anti-cancer immune responses. [33][34][35][36][37][38] To start exploring the immune contexture of BPDCN, we analyzed the distribution and proliferation status of CD8 + T cells.…”

Current concepts of photosensitivity in cutaneous lupus erythematosus

“…Cutaneous lupus erythematosus (CLE) represents a chronic recurrent autoimmune disease with multiple clinical manifestations ranging from isolated cutaneous lesions to systemic disease with systemic involvement ( 2 , 3 ). UV light can cause a deterioration of skin lesions as well as flares of systemic lupus erythematosus (SLE) ( Figures 1A,B ) ( 4 ).…”

Lymphatic dysfunction in lupus contributes to cutaneous photosensitivity and lymph node B cell responses

“…Photosensitive skin inflammation, the accompanying risk of systemic disease flares, and the lifestyle modifications needed to prevent these all contribute to disrupting patients' quality of life [4][5][6]. Advances have begun to delineate the mechanisms that contribute to photosensitivity [7][8][9]. However, how skin sensitivity to UVR is connected to increased autoimmunity remains poorly understood.…”