The impact of air pollution on the progression of cutaneous lupus erythematosus from a cellular and molecular perspective

Summary: Air pollution accelerates cutaneous lupus erythematosus (CLE) progression through oxidative stress, immune dysregulation, and epigenetic alterations. Fine particulate matter (PM2.5), nitrogen dioxide (NO2), and polycyclic aromatic hydrocarbons (PAHs) penetrate the skin barrier, inducing reactive oxygen species (ROS), mitochondrial dysfunction, and DNA damage in keratinocytes and fibroblasts. Oxidative stress disrupts autophagy, promotes apoptosis, and enhances immune activation via damage-associated molecular patterns (DAMPs). The aryl hydrocarbon receptor (AhR) becomes activated, driving the transcription of pro-inflammatory mediators which perpetuate cell infiltration and further tissue inflammation. Epigenetic modifications, including DNA methylation and histone acetylation shifts, further prime autoreactive responses. A PubMed-based literature review synthesizes molecular, epidemiological, and clinical data to elucidate the mechanistic link between air pollution and CLE disease progression. Clinical studies suggest that patients residing in urban environments with high pollution indices exhibit increased CLE disease severity and heightened photosensitivity, potentially linked to pollutant-driven alterations in UV-induced skin damage responses. Environmental toxins may alter immunosuppressive drug metabolism, affecting treatment efficacy. Findings highlight air pollution as a modifiable disease driver, warranting targeted interventions and public health strategies. Hafsa F. Hassan¹, Nicholas Jianu², Edward Shao³, Amal Umerani⁴, Kristina Mueller⁵, Alexandra I. Jianu⁶, Jonique Depina⁷, Kelly Frasier⁸ 1. Medicine, Northeast Ohio Medical University, Rootstown, OH, United States. 2. Medicine, Lake Erie College of Osteopathic Medicine, Erie, PA, United States. 3. Environmental Science and Forestry, SUNY The State University of New York, Albany, NY, United States. 4. Medicine, Georgetown University School of Medicine, Washington, DC, United States. 5. Medicine, Philadelphia College of Osteopathic Medicine, Philadelphia, PA, United States. 6. Medicine, University of Nevada Las Vegas Kirk Kerkorian School of Medicine, Las Vegas, NV, United States. 7. Medicine, Kansas City University College of Osteopathic Medicine, Kansas City, MO, United States. 8. Dermatology, Northwell Health, New Hyde Park, NY, United States. Adaptive and Auto-Immunity