Usefulness of patch tests for diagnosing selective allergy to captopril

Captopril, enalapril, and lisinopril are angiotensin-converting enzyme (ACE) inhibitors widely prescribed for hypertension and heart failure. Cutaneous side effects of captopril include angio-edema, anaphylactoid reactions, maculopapular eruptions, pitiryasis rosea-like rash, toxic erythema, and exfoliative dermatitis. Some of the immunological captopril-induced cutaneous adverse reactions have been diagnosed in recent years by patch tests. A case of a cutaneous immune adverse reaction to captopril with tolerance to enalapril and lisinopril demonstrated both by patch tests and double-blind challenge tests is reported for the first time. A 71-year-old nonatopic woman suffered a generalized pruriginous maculopapular rash. Two months earlier, she had started oral treatment with captopril 50 mg t.i.d and glibenclamide 5 mg daily. After the rash appeared, she stopped both drugs and the reaction cleared. A skin biopsy from one of the lesions showed perivascular lymphocytic infiltrate of the upper dermis. Skin prick tests with captopril and glibenclamide and patch tests with enalapril, lisinopril, and glibenclamide at 1% and 10% pet., and with mercaptobenzothiazole (a sulfhydryl group-containing chemical at 1% pet were negative. Only patch tests with captopril at 1% and 10% concentrations were positive at 48 h. Oral double-blind challenge tests with glibenclamide, enalapril, lisinopril, and placebo showed good tolerance. The patient was advised to avoid only captopril. Because captopril is the only ACE inhibitor containing a sulfhydryl group and has occasionally been implicated in complex immunological diseases, this chemical group has been considered the culprit of allergic reactions to captopril. The lack of cross-reactivity between captopril, enalapril, and benazepril has been demonstrated in a few patients by patch tests. In our patient, patch tests identified captopril as the drug responsible for a probably immune adverse reaction not due to the sulfhydryl group. Patch tests are useful and safe in the diagnostic work-up of allergic drug reactions and in studies of cross-sensitivity among ACE inhibitors.