P136 Dose–response association between antibiotic use and the risk of bullous pemphigoid: a UK population-based case–control study

Abstract

Bullous pemphigoid (BP) is a rare, autoimmune blistering skin disease primarily affecting older adults. Recent evidence suggests an association between antibiotics and BP risk. This study focused on assessing a dose–response association. A population-based nested case–control study was conducted using the Clinical Practice Research Datalink Aurum (1998–2021). Adults with an incident BP diagnosis were matched with up to five controls by age, sex and general practice. Antibiotic prescriptions within 6–12 months before diagnosis were considered, excluding the preceding 6 months to reduce protopathic bias. Exposures (by group, classes, subclasses and substances) included the number of prescriptions, cumulative number of defined daily doses (cDDDs), cumulative durations (days) and time since last prescription (days). Reference groups were people not exposed to specific antibiotics. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were estimated using multivariable conditional logistic regression, accounting for confounders. There were 11 156 cases and 52 201 controls. Most antibiotics (except clarithromycin and oxytetracycline) showed dose–response associations with BP risk, peaking 6–8 months after exposure. Strong associations (aOR > 2, P < 0.001) were observed for flucloxacillin and trimethoprim. For flucloxacillin, the aOR increased from 2.22 (95% CI 1.96–2.50) for one prescription to 3.44 (2.80–4.23) for at least two prescriptions, consistent with cDDDs ≤ 7 (2.28, 2.02–2.57), > 7–14 (3.26, 2.54–4.19) and > 14 (2.97, 2.11–4.19); and cumulative durations ≤ 7 (2.14, 1.89–2.43), > 7–14 (3.56, 2.84–4.46) and > 14 (3.13, 2.28–4.30). BP risk remained elevated throughout 1 year after the last flucloxacillin prescription (aOR 1.97, 95% CI 1.60–2.43). Trimethoprim also showed elevated risk with at least two prescriptions (aOR 1.98, 95% CI 1.58–2.49), and higher risk for > 7–14 cDDDs (2.25, 1.65–3.06) and cumulative durations > 7–14 (2.00, 1.47–2.73) and > 14 (2.03, 1.50–2.75). These findings highlight the need for mindful antibiotic prescribing, especially repeated or prolonged courses, in people at risk of BP, while acknowledging confounding by indication as a limitation.