Abstract
Cutaneous lupus erythematosus (CLE) comprises dermatologic manifestations that may occur independently or with systemic lupus erythematosus (SLE). Despite advancements in refining CLE classification, establishing precise subtype criteria remains challenging due to overlapping presentations and difficulty in distinguishing morphology. Current treatments encompass preventive measures, topical therapies, and systemic approaches. Hydroxychloroquine and glucocorticoids are the sole US Food and Drug Administration (FDA)-approved medications for CLE, with numerous off-label treatments available. However, these treatments are often not covered by insurance, imposing a significant financial burden on patients. The exclusion of most CLE patients, particularly those without concurrent SLE, from trials designed for SLE has resulted in a lack of targeted treatments for CLE. To develop effective CLE treatments, validated outcome measures for tracking patient responsiveness are essential. The Cutaneous Lupus Erythematosus Disease Area and Severity Index is widely utilized for its reliability, validity, and ability to differentiate between skin activity and damage. In contrast, the FDA mandates the use of the Investigator's Global Assessment, a five-point Likert scale related to lesion characteristics, for skin-related therapeutic trials. It requires the disease to resolve or almost completely resolve to demonstrate improvement, which can be difficult when there is residual erythema or incomplete clearance that is meaningfully improved from a patient perspective. Various classes of skin lupus medications target diverse pathways, allowing tailored treatment based on the patient's lupus inflammatory profile, resulting in improved outcomes. Promising targeted therapeutic drugs include anifrolumab (anti-type 1 interferon), deucravacitinib (allosteric tyrosine kinase 2 inhibitor), litifilimab (plasmacytoid dendritic cell-directed therapy), iberdomide (cereblon-targeting ligand), and belimumab (B-cell directed therapy). Despite the significant impact of CLE on quality of life, therapeutic options remain inadequate. While promising treatments for cutaneous lupus are emerging, it is crucial to underscore the urgency for skin-focused treatment outcomes and the implementation of validated measures to assess therapeutic effectiveness in clinical trials.