Characterization of clopidogrel hypersensitivity reactions and management with oral steroids without clopidogrel discontinuation

Objectives: The purpose of this study was to characterize clopidogrel hypersensitivity and describe its successful management with oral steroids without clopidogrel discontinuation.

Background: Hypersensitivity reactions to clopidogrel are poorly understood and present difficulty in management.

Methods: Patients diagnosed with clopidogrel hypersensitivity after percutaneous coronary intervention underwent evaluation and received oral prednisone without clopidogrel discontinuation. Cutaneous testing was performed after completion of clopidogrel therapy for diagnosis and assessment of cross-reactivity.

Results: Sixty-two patients representing 1.6% of the percutaneous coronary intervention population developed clopidogrel hypersensitivity during the study period. The mean age was 62 ± 11 years, 71% of patients were male, and 35% reported prior adverse drug reaction. Clopidogrel hypersensitivity manifested as generalized exanthema in 79%, localized skin reaction in 16%, and angioedema or urticaria in 5% of patients. Biopsy of affected areas demonstrated a lymphocyte-mediated delayed hypersensitivity reaction. Complete resolution of hypersensitivity reaction was observed in 61 patients (98%) with a short course of oral prednisone. Cutaneous testing confirmed delayed hypersensitivity reaction to clopidogrel in 34 (81%) and immediate hypersensitivity in 3 of 42 patients (7%) tested. Allergenic cross-reactivity was observed for ticlopidine in 10 (24%), prasugrel in 7 (17%), and both ticlopidine and prasugrel in 3 patients (7%). Histological examination showed lymphocyte-mediated hypersensitivity in abnormal patch test areas.

Conclusions: Clopidogrel hypersensitivity is manifested as generalized exanthema and is caused by a lymphocyte-mediated delayed hypersensitivity in most patients. This can be managed with oral steroids without clopidogrel discontinuation. Allergenic cross-reactivity with ticlopidine, prasugrel, or both is present in a significant number of patients with clopidogrel hypersensitivity.