Persistent Cutaneous Lupus Erythematosus: A Pathway Toward Systemic Disease?

Cutaneous lupus erythematosus (CLE) is an inflammatory autoimmune disease characterized by specific skin lesions, differing from systemic lupus erythematosus (SLE) which affects multiple organs widely. Although CLE has traditionally been regarded as a cutaneous-limited disorder, increasing evidence suggests that a subset of CLE patients—particularly those with persistent, refractory, or relapsing disease courses—face a heightened risk of systemic progression. The heterogeneous transition rates among CLE subtypes and the increasing frequency of treatment-resistant cases highlight unmet needs in predicting disease evolution and refining therapeutic strategies. This review synthesizes current knowledge on the clinical characteristics and management challenges of refractory and recurrent CLE, while analyzing epidemiological evidence and risk factors associated with progression to SLE. We further delineate shared and distinct immunopathogenic pathways linking CLE and SLE, emphasizing the roles of type I interferon signaling, neutrophils, autoreactive B cells and T cell–mediated immunity. By integrating clinical insights with emerging mechanistic data, this review highlights the importance of early risk stratification and targeted immunomodulation to prevent systemic involvement in high-risk CLE patients, offering new perspectives for improving long-term outcomes.