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

Area of Science:

• Dermatology
• Immunology
• Toxicology

Background:

• Cutaneous lupus erythematosus (CLE) is an autoimmune skin disease.
• Smokers with CLE often experience a more severe disease course and treatment resistance.
• The molecular mechanisms linking smoking to worse CLE outcomes are not well understood.

Purpose of the Study:

• To review the molecular pathways through which cigarette smoke may exacerbate CLE.
• To integrate existing literature on CLE pathophysiology and smoking's effects on the skin and immune system.
• To propose hypotheses explaining clinical differences in CLE patients who smoke.

Main Methods:

• Literature review integrating studies on CLE immunopathogenesis.
• Analysis of known effects of cigarette smoke on skin and immune cells.
• Examination of molecular drivers including oxidative stress, interferon signaling, and epigenetics.

Main Results:

• Cigarette smoke impacts key CLE pathways: oxidative stress, interferon signaling, inflammatory cell recruitment, extracellular vesicles, and immune regulation.
• Factors like epigenetics and heat injury may also play a role.
• Hypotheses are proposed linking smoking-induced molecular changes to clinical severity in CLE.

Conclusions:

• Understanding the molecular impact of smoking on CLE is crucial for explaining clinical variations.
• Identifying these molecular underpinnings may lead to more effective treatment strategies for CLE patients who smoke.