005 Association between prescription drugs and vaccines commonly prescribed to older people and bullous pemphigoid: a UK population-based study
Authors: Swiderski Mikolaj , Vinogradova Yana , Knaggs Roger , Harman Karen , Harwood Rowan , Prasad Vibhore , Persson Monica S M , Figueredo Grazziela , Layfield Carron , Gran Sonia 
Published: June 2023

Abstract
Bullous pemphigoid (BP) is the most common autoimmune blistering skin disease, manifested by painful itching of the skin and mucous membranes. Despite high mortality, poor quality of life and increasing incidence in older people, BP can be overlooked due to its rarity in the general population. The cause of BP is unknown, but there are reports of drug-induced BP and remission after the withdrawal of suspected drugs. Systematic reviews have found prescription drugs such as gliptins and loop diuretics to be associated with BP. However, previous studies did consider multiple drug exposures and had selected populations. Our UK population-based study aimed to determine whether drugs/vaccines prescribed between 1998 and 2021 for common conditions in older people are associated with BP. We conducted a population-based nested case–control study using the UK Clinical Practice Research Datalink (representing 8% of the UK population). Each person with BP (case) was matched by age, sex and general practice to up to five controls at the diagnosis time of their case. Multivariable conditional logistic regression was used to determine adjusted odds ratios (aOR) of developing BP within 1 year of taking at least one prescription for the following therapeutic groups: antibiotics, antidiabetics and insulin, antihypertensives, antithrombotics, lipid modifiers, analgesics, dementia drugs, antiepileptics, antipsychotics, antidepressants and influenza vaccine. Where possible, we report results for classes of drugs or subclasses. The results were adjusted for multiple exposures and corrected for multiple testing. We also explored potential confounders: ethnicity, deprivation, stroke, Parkinson disease and dementia. Six months of antibiotics prescriptions before the BP diagnosis was excluded to account for treating undiagnosed BP symptoms. We identified 16 844 patients with BP and 79 493 controls (mean age 76 years; 44% male). The drugs associated with an increased risk of BP were penicillinase-resistant penicillins [aOR 2.6, 95% confidence interval (CI) 2.4–2.8]; macrolides (aOR 1.5, 95% CI 1.4–1.7); gliptins (aOR 2.8, 95% CI 2.4–3.3); centrally acting anticholinesterases (aOR 2.3, 95% CI 2.0–2.7); N-methyl-D-aspartate receptor antagonists (aOR 2.2, 95% CI 1.7–2.9); antiepileptics (aOR 2.4, 95% CI 2.3–2.6); influenza vaccine (aOR 1.4, 95% CI 1.4–1.5) and loop diuretics (aOR 1.3, 95% CI 1.2–1.4). Reduced BP risk was associated with nonsteroidal anti-inflammatory drugs (aOR 0.8, 95% CI 0.8–0.9) and opioids (aOR 0.8, 95% CI 0.8–0.9). Potential confounders did not affect odds ratio estimates. All P values were &lt; 0.001. No association was found for broad-spectrum penicillins, lipid-modifying drugs, anticoagulants, beta blockers, calcium channel blockers and potassium-sparing diuretics with another diuretic. Clinicians need to be aware of BP risk in older people following administration of penicillinase-resistant penicillins, gliptins, dementia and epilepsy drugs, in order to recognize BP early and consider withdrawal of the suspect drug.