Date of Award

January 2026

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Alicia J. Little

Abstract

Cutaneous lupus erythematosus (CLE) produces lifelong morbidity through visible, functionally consequential skin disease and accrued damage. In discoid lupus erythematosus (DLE), alopecia and dyspigmentation at hair-bearing and cosmetically sensitive sites are frequently cited as major drivers of reduced quality of life1,2. Despite this burden and the risk of progression to systemic lupus erythematosus (SLE), CLE has no FDA-approved therapy, and treatment evidence remains limited by the small number of CLE-specific datasets and trials focused on CLE-trials. Many therapeutic decisions for CLE are extrapolated from SLE despite the fact that CLE subtypes differ in morphology, histopathology, and reported immune signatures3,4. We leveraged a large dermatology-based CLE cohort to address two linked gaps: phenotyping a high-burden DLE manifestation (alopecia) with serologic correlates and describing real-world treatment utilization and dermatologist-documented cutaneous outcomes across CLE subtypes.We conducted a retrospective electronic health record review of patients with CLE seen in dermatology clinics at an academic medical center between 2018 to 2023, identified by ICD-10 codes with diagnosis confirmed by manual confirmation in dermatology visit records. After exclusions for age <18 years, insufficient information for CLE subtype classification, those with multiple CLE subtypes documented, the analytic cohort included 300 patients with single classifiable CLE subtypes. Analyses were restricted to subtypes with 30 patients, yielding a final cohort of 243 patients: discoid lupus erythematosus (DLE, n = 209) and subacute CLE (SCLE, n = 34). DLE patients were categorized by alopecia status and compared across demographic, clinical, and serologic features using descriptive and bivariate analyses, with SLE-stratified Mantel-Haenszel applied for selected comparisons. Alopecia cases were further characterized by subtype, distribution, and histopathology. Treatment utilization and dermatologist-documented cutaneous outcomes were evaluated in patients with at least one CLE-directed therapy and at least 3 months of follow-up, stratified by CLE subtype and SLE status. Alopecia was common among patients with DLE (111/209, 53.1%). Compared with patients without alopecia, those with alopecia more frequently had head and neck involvement of DLE skin lesions (96.4% vs 75.5%) and dyspigmentation (94.5% vs 83.3%) and identified as Black; the higher prevalence of alopecia among Black patients compared with non-Black patients persisted after adjusting for concomitant SLE. Among patients with available serologic testing, anti-U1 RNP positivity was more frequent in those with alopecia than without (48.7% vs.13.0%; p = 0.003); this association remained significant after stratification by SLE status. Anti-Smith autoantibodies also trended towards an increase in patients with alopecia than those without (29.2% vs. 12.8%; p = 0.054) but did not reach statistical significance. In the treatment analysis, DLE patients with concomitant SLE received a greater cumulative number of therapies than those with skin-limited disease; however, higher-therapy utilization did not reliably translate into cutaneous improvement, with worsening cutaneous disease documented in up to 26% of DLE patients with concurrent SLE. By contrast, SCLE showed high rates of improvement across therapy strata, with no documented worsening in SCLE with concomitant SLE. Alopecia was common and clinically burdensome manifestation of DLE, occurring more frequently among Black patients and among those anti-U1 RNP positivity. Patterns of real-world treatment utilization suggested that greater escalation of systemic therapy in DLE-SLE-overlap did not correspond to more favorable outcomes. While these treatment approach findings support the need for CLE and CLE subtype-specific studies to better define tailored therapeutic approaches, the alopecia-associated clinical and serologic findings warrant validation in larger cohorts and further mechanistic study to inform strategies to prevent irreversible scarring and dyspigmentation, major contributors to disease burden in DLE.

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This is an Open Access Thesis.

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