A 44-year-old South Asian male with no significant medical or family history presented to the emergency department with typical chest pain and shortness of breath. He did not report any significant social history, and his review of systems was unremarkable. His vital signs indicated systolic blood pressures of 156/92 mmHg, heart rate of 108 beats per minute, respiratory rate of 20 breaths per minute, with an oxygen saturation of 97% on room air. The brief physical examination was normal. An emergency 12-lead electrocardiogram revealed marked, 6-millimeter ST-segment elevation in leads V1-V6 with reciprocal ST-depressions in the inferior leads, II, III, and aVF.\nHe was immediately administered oral aspirin, ticagrelor load, high-intensity rosuvastatin in addition to an intravenous nitroglycerin infusion and subsequently proceeded for primary PCI. During cardiac catheterization, it was discovered that the patient had the much dreaded "widow-maker" lesion - a proximal left anterior descending (LAD) artery occlusion with high-grade thrombus burden. He successfully underwent transfemoral drug-eluting stent (DES) implantation after thrombus aspiration with a Boston Scientific Corporation (Marlborough, Massachusetts) SYNERGY® everolimus DES.\nPost-procedure, the patient developed translucent bullous lesions with surrounding erythema on the distal flexor aspect of the right forearm, for which he promptly received intravenous hydrocortisone and chlorphenamine. At this juncture, the tentative diagnosis was a contrast-media reaction (Ultravist®️ 370, Bayer AG, Leverkusen, Germany). During the subsequent hospitalization, the patient was hemodynamically stable. He was subsequently discharged on guideline-directed medical therapy on DAPT with ticagrelor, high-intensity statin, low-dose beta-blocker, and angiotensin-receptor neprilysin inhibitor, and mineralocorticoid receptor antagonist, in addition to oral antihistamine and topical steroid cream therapies. A skin biopsy was not performed, as there were no available dermatologists during the coronavirus disease 2019 (COVID-19) pandemic.\nThe patient contacted the interventional cardiologist one-week post-procedure and alerted him that the lesions were worsening despite the therapies. At that time, a measured decision was taken to transition him to clopidogrel (loading dose of 300 milligrams, followed by daily maintenance dose, 75 milligrams) and rivaroxaban 2.5 milligrams twice daily. Over the following four days, the bullous lesions spontaneously ruptured, with resolving erythema and induration. After a further three-day period, the lesions almost fully healed with areas of hyperpigmentation. There was no generalized body or mucosal involvement. Provocation tests with ticagrelor were not performed (Figure ).
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.