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Original Investigation
June 17, 2020

Association Between Medication Use and Bullous Pemphigoid: A Systematic Review and Meta-analysis

Author Affiliations
  • 1Department of Pharmacy, New Taipei Municipal TuCheng Hospital (Built and Operated by Chang Gung Medical Foundation), New Taipei City, Taiwan
  • 2Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
  • 3Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
  • 4College of Medicine, Chang Gung University, Taoyuan, Taiwan
  • 5Department of Dermatology, Xiamen Chang Gung Memorial Hospital, Fujian, China
JAMA Dermatol. Published online June 17, 2020. doi:10.1001/jamadermatol.2020.1587
Key Points

Question  Is there an association between use of medications and the development of bullous pemphigoid?

Findings  In this systematic review and meta-analysis of 13 case-control studies, 1 cohort study, and 1 randomized clinical trial with 285 884 participants, there was a significant association of the development of bullous pemphigoid with the prescribed use of aldosterone antagonists, dipeptidyl peptidase 4 inhibitors, anticholinergics, and dopaminergic medications.

Meaning  The findings of this systematic review and meta-analysis suggest that medications should be prescribed judiciously, particularly in high-risk patients who are elderly and have disabling neurologic disorders.

Abstract

Importance  The association between the use of medications and the development of bullous pemphigoid (BP) is unclear.

Objective  To assess the associations between previous exposure to certain medications and BP.

Data Sources  For this systematic review and meta-analysis, PubMed, the Cochrane Central Register of Controlled Trials, and Embase were searched for relevant studies from inception to February 20, 2020.

Study Selection  Case-control or cohort studies and randomized clinical trials that examined the odds or risk of BP in patients with previous medication use were included. No geographic or language limitations were imposed.

Data Extraction and Synthesis  The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guideline was followed. The Newcastle-Ottawa Scale was used to evaluate the risk of bias of included observational studies; Cochrane Collaboration’s tool was used for randomized clinical trials. Aggregate data were used to conduct a random-effects model meta-analysis if the included studies were sufficiently homogenous. Subgroup analyses were performed for use of various medications of the same category.

Main Outcomes and Measures  Odds ratio (OR), hazard ratio, and risk ratio of bullous pemphigoid in association with medication use.

Results  This meta-analysis included 13 case-control studies, 1 cohort study, and 1 randomized clinical trial with a total of 285 884 participants. The meta-analysis of case-control studies showed a significant association of BP with previous use of aldosterone antagonists (pooled OR, 1.75; 95% CI, 1.28-2.40), dipeptidyl peptidase 4 inhibitors (pooled OR, 1.92; 95% CI, 1.55-2.38), anticholinergics (pooled OR, 3.12; 95% CI, 1.54-6.33), and dopaminergic medications (pooled OR, 2.03; 95% CI, 1.34-3.05). One cohort study found an increased risk of BP among patients receiving dipeptidyl peptidase 4 inhibitors (hazard ratio, 2.38; 95% CI, 1.16-4.88; P = .02). One trial found a higher occurrence of BP in patients with diabetes receiving linagliptin (0.2% in diabetes group vs 0% in the placebo group).

Conclusions and Relevance  The findings of this systematic review and meta-analysis suggest that aldosterone antagonists, dipeptidyl peptidase 4 inhibitors, anticholinergics, and dopaminergic medications are associated with BP. These medications should be judiciously prescribed, particularly in high-risk patients who are elderly and have disabling neurologic disorders.

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