Pharmacovigilance and Multi-Omics Analysis of Potential Drug Signals and Mechanisms in Oral Lichen Planus

Background Oral lichen planus (OLP) is a chronic inflammatory condition of uncertain cause, yet the role of drug exposure in its development remains largely unexplored. Objectives To identify drugs with disproportionate OLP reporting signals and explore their potential biological mechanisms. Methods We systematically screened for drugs with disproportionate OLP reporting signals via disproportionality analysis of FDA Adverse Event Reporting System (FAERS) data. To explore the potential mechanistic basis, we conducted network toxicology analysis and further assessed potential mechanistic inference for overlapping targets using summary-based Mendelian randomization (SMR) integrated with cis-protein quantitative trait loci (pQTL) data. Cell type-specific expression was evaluated through single-cell RNA sequencing of oral mucosa tissue from OLP patients. Results FAERS screening identified 14 drugs with significantly elevated OLP reporting risks. Network toxicology showed that overlapping drug-OLP targets were mainly enriched in pathways related to chemical carcinogenesis, drug/xenobiotic metabolism (cytochrome P450), arachidonic acid metabolism, interleukin-17 (IL-17), and tumor necrosis factor (TNF) signalling. Among the overlapping drug-OLP targets, programmed cell death 1 (PDCD1) and TNF exhibited genetically predicted associations with OLP in SMR, and single-cell transcriptomics further revealed their preferential expression in T/natural killer (NK) cells. Conclusion This study systematically identified drugs with disproportionate OLP reporting signals and generated putative mechanistic hypotheses, providing a potential reference for pharmacovigilance monitoring and clinical assessment of OLP.