Exploration of Drugs Associated With the Development of Bullous Pemphigoid: A Nationwide Study

Bullous pemphigoid (BP) is an autoimmune blistering skin disorder with an increasing incidence, particularly among older adults. Given the role of medications in developing drug-associated BP (DABP), exploring drugs that cause DABP is crucial for prescribing appropriate drugs to prevent BP development. This study aimed to identify drugs associated with DABP. In this nationwide retrospective cohort study, we compared 5066 patients newly diagnosed with BP with 10 132 matched controls. We first established a comprehensive drug list of all medications used in our country and conducted a case-control study to identify candidate drugs associated with DABP. To validate these associations, we performed a separate cohort study, enrolling patients with a confirmed diagnosis of BP and matched controls. In the screening stage, 88 drugs were associated with an increased risk of DABP, while 27 drugs were linked with a reduced risk. Validation confirmed that 78 drugs increased the risk of DABP, whereas 22 drugs lowered it. Among the candidate drugs, anti-diabetic medications, including dipeptidyl peptidase-4 (DPP4) inhibitors and sulfonylureas, neuropsychiatric drugs such as benserazide and carbidopa (used for Parkinson's disease) and donepezil and memantine (for Alzheimer's disease), increased the risk of DABP. Conversely, several anti-inflammatory medications, including meloxicam and celecoxib and lipid-lowering agents, such as rosuvastatin and atorvastatin, have been found to lower the risk of DABP. Lastly, diazepam, diltiazem, and Ginkgo biloba extracts exhibited protective effects against DABP development. This nationwide study, employing an unbiased analysis of all medications in our country, highlights a substantial number of medications linked to the development of DABP. Our study provides practical insights for drug selection to prevent the development of DABP in elderly patients.