A 50-year-old male with past medical history of ischemic heart disease and prasugrel hypersensitivity in the form of generalized rash underwent elective PCI with one drug-eluting stent (DES) to the left anterior descending artery (LAD). He was subsequently started on dual antiplatelet therapy with aspirin 81 mg daily and ticagrelor 90 mg twice a day.\nTwo days following discharge, the patient was complaining of severe shortness of breath with minimal exertion, and occasionally at rest. He denied any fevers, chills, productive cough, orthopnea, paroxysmal nocturnal dyspnea or lower limb edema. The patient’s dyspnea was heavily investigated with basic labs, cardiac biomarkers, imaging of the chest, and repeat transthoracic echocardiogram. All results came back within normal limits. The patient’s dyspnea was deemed secondary to ticagrelor use and the drug was discontinued, with subsequent improvement of his symptoms. Given his history of prasugrel hypersensitivity and current intolerance to ticagrelor, the patient was started on clopidogrel. Three days later, he presented to the emergency department (ED) with a rash that started on his chest and spread to his arms and face (Figure ).\nThe patient was diagnosed with cutaneous hypersensitivity to clopidogrel. Given the patient’s need for dual antiplatelet therapy and previously documented prasugrel hypersensitivity as well as intolerance to ticagrelor, shifting to any of them was not an option.\nReviewing the literature, three management strategies have been described for clopidogrel hypersensitivity, including switching to another agent, implementing a desensitization protocol, and a six-day course of steroids without clopidogrel discontinuation. A shared decision was made to implement the latter approach however with a slow taper over a three-week period. The patient was started on oral prednisone 30 mg twice a day for five days, followed by a decrease of 5 mg/day every three days for 15 days. On his one-week follow-up, the patient was well-tolerating clopidogrel with complete resolution of his symptoms and no significant side effects from steroids. The patient showed no side effects related to steroids on his one-month follow-up.
A 57-year-old man with significant history of ischaemic heart disease underwent elective percutaneous coronary intervention to the proximal left anterior descending artery with insertion of two drug-eluting stents in February 2014. He was commenced on dual antiplatelet therapy with the addition of clopidogrel to his regular aspirin. His other past medical history included hypertension and hypercholesterolaemia. He had no previous history of drug allergy or atopy.\nEleven days after commencement of clopidogrel he developed a generalised urticarial rash including his scalp and palms, with associated peripheral paraesthesia. He was treated with antihistamines and his clopidogrel was changed to ticagrelor.\nThirty-six hours after the introduction of ticagrelor, he represented with facial angioedema associated with left sided chest pain and dysphagia without respiratory compromise. Following the cessation of ticagrelor, the symptoms resolved with intramuscular adrenaline and intravenous corticosteroids and he was discharged home after a period of observation.\nFurther cardiology consultation recommended the trial of prasugrel under close supervision. Within two hours, he developed an urticarial reaction involving the hands, feet and groin, which initially resolved with antihistamine. After the third dose of prasugrel, he experienced chest, left arm and abdominal discomfort, with periorbital and lip angioedema. Although haemodynamically stable, he was diaphoretic and required oxygen therapy. Again, he improved with intramuscular adrenaline, intravenous f luid and oral and intravenous antihistamines. All investigations were unremarkable including the tryptase level which was only collected 36 hours post symptom onset.\nThe idea of trialling a fourth antiplatelet agent, ticlopidine, was briefly considered. Given his reaction to three antiplatelet agents, and after reviewing the molecular structure of all four drugs (), as well as available literature on clopidogrel sensitisation and its cross-reactivity towards ticlopidine and prasugrel, there was significant concern about the risk of similar but more severe and rapid onset hypersensitivity reaction. The patient ultimately underwent clopidogrel desensitisation with prednisolone cover. He successfully completed the programme without complication and was maintained on strict daily dose afterwards. He continues to take clopidogrel without adverse effects four months post desensitisation.