Ashes to Rashes: An Exploration of the Intersection Between Smoking and Cutaneous Lupus Erythematosus.

Cutaneous lupus erythematosus is an autoimmune skin disorder with a known association with cigarette smoking. Smokers with cutaneous lupus have a worse disease course and may be refractory to treatments. Despite many studies documenting this association, minimal work exists examining the molecular drivers of these clinical differences. This review delves into how cigarette smoke may influence key immunopathogenic pathways in cutaneous lupus, including oxidative stress, interferon signaling, inflammatory cell recruitment, extracellular vesicles, and immune regulation. Additionally, factors such as epigenetics and heat injury are considered as well. Here, we integrate the existing and emerging literature on the pathophysiology of cutaneous lupus with known effects of cigarette smoke on the skin and immune system and propose hypotheses that may explain clinical differences in smokers. Understanding the molecular underpinnings of these differences may yield a clearer picture of the disease and more effective treatment strategies.