Are omeprazole and enalapril associated with bullous pemphigoid?

Drug-Induced Bullous Pemphigoid: Omeprazole and Enalapril

Yes, both omeprazole and enalapril have been associated with bullous pemphigoid, though the evidence quality differs between the two drugs.

Enalapril Association with Bullous Pemphigoid

Enalapril has documented case reports demonstrating drug-induced bullous pemphigoid with immunological confirmation. A case report identified IgG antibody directed against the 230 kd bullous pemphigoid antigen in a patient who developed the condition after receiving enalapril for hypertension, with the autoantibody showing identical characteristics to spontaneous bullous pemphigoid 1. Additionally, enalapril has been implicated in lichen planus pemphigoides (a related bullous condition), with complete resolution occurring within 12 weeks after drug discontinuation 2.

Related ACE Inhibitor Evidence

• Captopril, another ACE inhibitor in the same drug class, has been associated with bullous pemphigoid in a 77-year-old patient who developed bullous eruptions approximately 50 days after starting therapy, with resolution after drug discontinuation and corticosteroid treatment 3
• This class effect suggests ACE inhibitors as a group may trigger bullous pemphigoid through similar mechanisms 3

Omeprazole and Proton Pump Inhibitor Association

Proton pump inhibitors, including omeprazole, are recognized triggers for drug-associated bullous pemphigoid. A systematic review of drug-induced pemphigoid identified 89 drugs implicated in drug-associated bullous pemphigoid (DABP), though the specific strength of evidence for omeprazole individually was not detailed 4. However, lansoprazole (another PPI) has documented cases of inducing bullous pemphigoid, with improvement following PPI cessation and corticosteroid use 5.

Guideline Recognition of Drug-Induced Bullous Pemphigoid

The British Association of Dermatologists' 2012 guidelines acknowledge drug associations with bullous pemphigoid, noting:

• Multiple anecdotal case reports suggest associations between BP and various drugs 6
• Three epidemiological studies have examined BP and drug relationships, with two French case-control studies finding significant associations with spironolactone and neuroleptics, and one UK study finding association only with furosemide after adjusting for cardiovascular and neurological disease 6
• The mechanism by which drugs induce BP has not been studied 6

Clinical Implications and Management

When drug-induced bullous pemphigoid is suspected, early recognition and prompt discontinuation of the offending medication is essential. The case of enalapril-induced lichen planus pemphigoides demonstrated that medication given for the condition alone, without cessation of the offending drug, may not change the disease course 2.

Key Clinical Considerations:

• Drug-associated bullous pemphigoid demonstrates clinical, histological, and immunopathological features identical or similar to idiopathic bullous pemphigoid 4
• The strongest evidence for DABP exists with gliptins, PD-1/PD-L1 inhibitors, loop diuretics, and penicillin derivatives, though PPIs and ACE inhibitors are also implicated 4
• Bullous pemphigoid typically develops in elderly patients (mean age around 80 years) and is associated with neurological diseases including cerebrovascular disease, dementia, Parkinson disease, epilepsy, and multiple sclerosis 6

Treatment Approach After Drug Discontinuation:

• First-line treatment remains superpotent topical corticosteroids (clobetasol propionate) for localized disease 7
• For generalized disease, apply clobetasol propionate 20g per day over the entire body except the face 7
• If topical corticosteroids fail, consider oral prednisone at 0.5 mg/kg/day 7
• Adjunctive azathioprine may allow steroid dose reduction by approximately 45% 7

Common Pitfalls to Avoid

• Do not continue the suspected offending medication while treating the bullous pemphigoid, as this may prevent resolution despite appropriate immunosuppressive therapy 2
• Avoid higher doses of oral prednisone (>0.75 mg/kg/day), as they do not confer additional benefit and are associated with significant mortality 7
• Consider drug-induced etiology in all new-onset bullous pemphigoid cases, particularly in patients recently started on ACE inhibitors, PPIs, diuretics, or other implicated medications 6, 4