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. 2025 Feb 18;192(3):440-449.
doi: 10.1093/bjd/ljae416.

Association between drugs and vaccines commonly prescribed to older people and bullous pemphigoid: a case-control study

Mikolaj Swiderski  1 , Yana Vinogradova  1 , Roger D Knaggs  2 , Karen Harman  3 , Rowan H Harwood  4 , Vibhore Prasad  1   5   6 , Monica S M Persson  7 , Grazziela Figueredo  8 , Carron Layfield  1 , Sonia Gran  1
Affiliations

Association between drugs and vaccines commonly prescribed to older people and bullous pemphigoid: a case-control study

Mikolaj Swiderski et al. Br J Dermatol. .

Abstract

Background: Bullous pemphigoid (BP) is an autoimmune skin disease that mainly affects older people. Based on case series and small hospital-based studies, a number of drugs have been associated with BP. More reliable and precise estimates of associations between a broad selection of drugs/vaccines and BP will enable greater awareness of any potential increased risk of BP following the administration of certain medicines and help identify clinical, histological and genomic characteristics of drug-induced BP for different culprit drugs. Greater awareness could lead to earlier recognition or suspicion of BP and referral to a dermatologist for diagnosis. Earlier diagnosis may lead to less aggressive treatment and improved wellbeing.

Objectives: To determine the association between drugs/vaccines commonly prescribed to older people and the risk of developing BP.

Methods: We conducted a population-based nested case-control study between 1998 and 2021 using electronic primary care records from the Clinical Practice Research Datalink. We matched patients with BP with up to five controls. Exposures were drugs/vaccines commonly prescribed to older people. We used multivariable conditional logistic regression adjusting for multiple drug use. For antibiotics, in a sensitivity analysis, we considered that drugs may be prescribed for undiagnosed symptoms of BP that resemble skin infection (protopathic bias).

Results: Antibiotics were associated with the highest risk of BP [odds ratio (OR) 4.60, 95% confidence interval (CI) 4.40-4.80]. However, after adjusting for protopathic bias, the OR decreased to 2.08 (95% CI 1.99-2.17). Also, after adjusting for protopathic bias, of all the antibiotic classes and subclasses, penicillins [OR 3.44, 95% CI 3.29-3.60 (sensitivity analysis OR 1.74, 95% CI 1.66-1.84)] and penicillinase-resistant penicillins [OR 7.56, 95% CI 7.15-8.00 (sensitivity analysis OR 2.64, 95% CI 2.45-2.85)] had the strongest associations with BP risk. Other drugs strongly associated with increased risk were gliptins (OR 2.77, 95% CI 2.37-3.23) and second-generation antipsychotics (OR 2.58, 95% CI 2.20-3.03).

Conclusions: Healthcare professionals need to be aware of BP risk in older people, particularly when prescribing penicillinase-resistant penicillins, gliptins and second-generation antipsychotic drugs, to recognize and manage BP early. Owing to the low disease prevalence, we do not suggest avoiding certain drugs/vaccines to prevent BP. Further research should consider recency, dosage and duration of antibiotic treatments.

Plain language summary

Bullous pemphigoid (or ‘BP’ for short) is a serious and rare skin condition. It mainly affects older people. About 8 in every 100,000 people in the UK will develop BP for the first time each year. The initial symptoms are often very itchy skin and a red rash that can develop into painful blisters and open sores. Although we do not know which factors trigger BP, it has been suggested that certain medications may cause it. However, these findings have mainly been from small studies and specialist hospitals. It is important to provide reliable estimates of the risk of BP following medication use from a population that is representative of the whole of the UK. This study was carried out in the UK, and may help GPs to suspect BP early on. This may allow them to refer patients to a dermatologist who will diagnose and treat symptoms. We used routinely collected data from more than 2,000 GP surgeries in the UK to find out the risk of BP. We also took into consideration that older people can take many medications at the same time. We found that some antibiotic, anti-diabetic and anti-psychotic drugs are associated with an increased risk of BP. Our findings highlight how important it is to look for skin reactions after using certain medications, and to recognize and manage BP quickly. We advise against avoiding these medications, as most people taking them do not develop BP. Future research could explore how the dosage, treatment duration and recency of antibiotics affect the risk of BP.

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Conflict of interest statement

Conflicts of interest: During the course of this work V.P. received salary funding via King’s College London from the National Institute for Health and Care Research’s (NIHR) academic clinical lecturer scheme, University of Nottingham as Associate Professor, via the NIHR East Midlands scholarship scheme (hosted by NHS Nottingham and Nottinghamshire and the University of Nottingham) and via University of Nottingham as Clinical Associate Professor via the NIHR Senior Clinical and Practitioner Research Award. V.P. reports associations with King’s College London and the University of Nottingham. The other authors declare no conflicts of interest.