Identifying characteristics of people with bullous pemphigoid prior to diagnosis using clustering analysis: a UK population-based case-control study

Abstract Background Bullous pemphigoid (BP) is a rare, serious autoimmune skin disease that is more common in older people. Numerous drugs and conditions have been previously associated with BP, but no study has explored patterns of risk factors. It is important to identify characteristics of people at risk of BP to help raise clinical suspicion. Diagnostic delay can lead to serious symptoms and poor quality of life. Objectives To identify patterns of drug prescriptions, comorbidities and sociodemographic characteristics of people with BP prior to diagnosis. Methods We conducted a 1:1 case-control study (1998-2021) using routinely collected primary care data from Clinical Practice Research Datalink. Cases were matched to controls by age, sex, and clinical practice. We ran clustering analysis to identify groups of cases with similar characteristics. We repeated the analysis for controls to verify whether these characteristics are unique or more common in cases. Results There were 16 624 cases/controls (median age, 80 years; 55.6% women). Eight case/control clusters were identified. Four case clusters included people who were all prescribed penicillinase-resistant penicillins. Statins were prescribed in six BP and four control clusters. Multiple sclerosis was rare (1-2% people) but unique in case clusters (5/8). Conclusions Penicillinase-resistant penicillins and statins were more often prescribed prior to BP diagnosis. Healthcare professionals should be vigilant for skin reactions in older people following these medications, particularly penicillinase-resistant penicillins. Due to low BP prevalence, we do not suggest preventative discontinuation of highlighted drugs. We also propose checking for skin reactions following a multiple sclerosis diagnosis.