Chronic Inflammation Promotes Skin Carcinogenesis in Cancer-Prone Discoid Lupus Erythematosus

Anniek Zaalberg, Sara Moradi Tuchayi, Amir H. Ameri, Kenneth H. Ngo, Trevor J. Cunningham, Jean Pierre Eliane, Maia Livneh, Thomas D. Horn, Ilana S. Rosman, Amy Musiek, Milan J. Anadkat, Shadmehr Demehri

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

High-risk skin cancer is a rare, but severe, complication associated with discoid lupus erythematosus (DLE). Chronic scar, inflammation, UVR, and immunosuppressive medications are proposed explanations for this heightened skin cancer risk; however, the exact mechanism driving skin carcinogenesis in DLE is unknown. The distinct co-localization of multiple independent skin cancers with areas of active inflammation in two DLE patients followed over 8 years strongly suggested that lupus inflammation promotes skin carcinogenesis in DLE. To investigate this clinical observation, we subjected lupus-prone MRL/lpr and control (MRL/n) mice to a skin carcinogenesis protocol. Skin tumors developed preferentially within the cutaneous lupus inflammation without scarring in MRL/lpr mice (P < 0.01). The inflammation in MRL/lpr skin was characterized by the accumulation of regulatory T cells, mast cells, M2 macrophages, and markedly elevated transforming growth factor-β1 and IL-6 levels, which have been linked to tumor promotion. Tacrolimus treatment reduced skin inflammation and blocked cancer development in MRL/lpr mice (P = 0.0195). A similar tumor-promoting immune environment was detected in SCCs and the perilesional skin of cancer-prone DLE patients. Therefore, discoid lupus inflammation promotes skin cancer in high-risk DLE patients, and blocking the inflammation may be critical for preventing this life-threatening complication of DLE.

Original languageEnglish
Pages (from-to)62-70
Number of pages9
JournalJournal of Investigative Dermatology
Volume139
Issue number1
DOIs
StatePublished - Jan 2019

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    Zaalberg, A., Moradi Tuchayi, S., Ameri, A. H., Ngo, K. H., Cunningham, T. J., Eliane, J. P., Livneh, M., Horn, T. D., Rosman, I. S., Musiek, A., Anadkat, M. J., & Demehri, S. (2019). Chronic Inflammation Promotes Skin Carcinogenesis in Cancer-Prone Discoid Lupus Erythematosus. Journal of Investigative Dermatology, 139(1), 62-70. https://doi.org/10.1016/j.jid.2018.06.185