Pathogenesis of skin damage in lupus: recent advances and future directions

Lupus erythematosus (LE) encompasses a spectrum of autoimmune diseases with significant heterogeneity, ranging from cutaneous lupus erythematosus (CLE), confined to the skin, to systemic lupus erythematosus (SLE), which affects multiple internal organs. The underlying pathogenesis of lupus skin lesions and the heterogeneity among various subtypes remain elusive and require further investigation. This review synthesizes recent progress in elucidating the mechanisms of lupus skin injury, providing novel perspectives on diagnosis and therapeutic strategies, while also outlining promising avenues for future investigation.

Key insights include the active pathogenic role of keratinocytes, essential involvement of neutrophils, the central role of type I interferon (IFN-I) signaling, and a preactivated molecular state in nonlesional skin. Emerging distinctions between CLE and SLE lesions, as well as the role of photosensitivity, are also examined. These findings highlight modifiable environmental factors as critical parts for LE prevention and establish a new paradigm for future precision medicine in LE.

These novel findings enrich the complex pathogenic network underlying lupus skin injury, accelerating the transition toward precision medicine. Rational prevention, early diagnosis, and targeted treatment represent the core principles and a promising vision for the future evolution of lupus management.