Drug-Associated Risk of Subacute Cutaneous Lupus Erythematosus: A Pharmacovigilance Study of the FDA Adverse Event Reporting System

To the Editor,

Subacute cutaneous lupus erythematosus (SCLE) is a subtype of cutaneous lupus erythematosus, primarily affecting the skin and mucous membranes. Approximately 23% of patients with SCLE may progress to systemic lupus erythematosus, with notable disease progression over several years. ¹ While drug-induced SCLE has been documented, the full range of associated drugs is not yet fully understood. To address this, we conducted a retrospective review of the FDA’s Adverse Event Reporting System (FAERS) from 2012 to 2022, focusing on drug-related SCLE reports.

We extracted FAERS data from the first quarter of 2013 to the second quarter of 2024 and identified SCLE cases using the Important Medical Event list from MedDRA version 26.1. Disproportionality analysis was performed using 4 methods: Reporting Odds Ratio (ROR), Proportional Reporting Ratio, Bayesian Confidence Propagation Neural Network, and Empirical Bayes Geometric Mean. Only drugs that achieved statistical significance across all 4 methods were considered. Duplicate reports were excluded according to FDA guidelines.

During the study, FAERS collected 15,027,984 adverse event reports, identifying 1424 SCLE-related cases. The majority of patients were female (65.6%), predominantly aged 18 to 65 years (40.7%). Most reports originated in the United States (30.4%), with physicians as primary reporters (40.9%). Gastroesophageal reflux disease was the most commonly reported indication (4.6%) (Supplemental Table 1).

Among drugs with more than 5 reports, proton pump inhibitors (PPIs) constituted the highest proportion of SCLE cases (42.66%), with omeprazole, lansoprazole, and pantoprazole contributing 16.88%, 12.66%, and 9.17%, respectively. Despite having fewer reports (5.87%), terbinafine showed a strong association with SCLE (ROR 81.5, 95% CI: 63.48-104.86) (Supplemental Tables 2 and 3). The top drug subclasses were PPIs (42.66%), antihypertensive agents (15.87%), and chemotherapeutic agents (14.86%) (Supplemental Figure 1).

This study highlights a higher prevalence of SCLE among females, which may be influenced by the role of sex hormones. Since hydrochlorothiazide was first reported to induce SCLE, ² PPIs and chemotherapeutic agents have gradually replaced traditional agents like calcium channel blockers and antifungal drugs, such as terbinafine, as leading contributors to SCLE. ³ Our study further substantiates this trend, with PPIs (42.66%) and chemotherapeutic agents (14.86%) representing a significant proportion of SCLE cases. This shift may reflect the widespread use of PPIs as the first-line treatment for gastroesophageal reflux disease, as well as the increasing use of chemotherapeutic agents in cancer treatment, potentially contributing to higher SCLE incidence across diverse populations.

This study utilizes FAERS data, which is based on voluntary reporting and may be prone to bias, limiting causal inferences. The absence of detailed drug dosage and duration data restricts dose-response analysis, and the limited reports for some drugs may weaken the observed associations. Future prospective studies are essential to validate these findings.

Our results demonstrate that PPIs and chemotherapeutic agents play a dominant role in SCLE development, further emphasizing the evolving spectrum of drug-induced SCLE. Terbinafine remains a key factor in SCLE pathogenesis. We recommend enhanced monitoring of these drugs, especially in high-risk populations, and future research should focus on elucidating their pathogenic mechanisms to improve clinical management.

Supplemental Material

sj-docx-1-cms-10.1177_12034754241303082 – Supplemental material for Drug-Associated Risk of Subacute Cutaneous Lupus Erythematosus: A Pharmacovigilance Study of the FDA Adverse Event Reporting System

Supplemental material, sj-docx-1-cms-10.1177_12034754241303082 for Drug-Associated Risk of Subacute Cutaneous Lupus Erythematosus: A Pharmacovigilance Study of the FDA Adverse Event Reporting System by Liu Yang, Han-Zhang Xie, Yi-Xuan Yang, Bing-Nan Cui and Zhan-Shuo Xiao in Journal of Cutaneous Medicine and Surgery