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 68-year-old male developed pruritic and exanthematous eruptions over a 24-hour period. He had a history of angina for the past 6 months, and he underwent elective percutaneous coronary intervention in the left anterior descending artery and left circumflex artery on June 24, 2015. Three drug-eluting stents were inserted (2 paclitaxel eluting stents, YINYI Biomedical Materials R&D Center Co., Ltd., Liaoning, China; and 1 sirolimus eluting stent, Lepu Medical Technology Co., Ltd., Beijing, China). All 3 stents were made of 316L stainless steel. Moreover, he also had a previous history of hypertension and hypercholesterolaemia. He had no history of prior drug allergy.\nDrugs included aspirin, ticagrelor, bisoprolol, and rosuvastatin. He has taken aspirin, bisoprolol, and rosuvastatin for the last 5 months, showing a good tolerance. After taking ticagrelor for 2 days, he developed pruritic and maculopapular rash on his bilateral costal margin, which was then generalized to the trunk (predominantly affected the chest and abdomen). His extremities were not affected, with no angioedema, no fever, and no arthralgia.\nThe laboratory test result showed an elevation in the leukocyte count (11.4 ×109/L) and in the neutrophil count (8.21 ×109/L). The lymphocyte count was 1.72 ×109/L and the eosinophil count was 0.58 ×109/L. The liver function test results were as follows: alanine aminotransferase, 14 U/L; aspartate aminotransferase, 27 U/L; total protein, 61.9 g/L; albumin, 40.2 g/L; total bilirubin, 36.8 µmol/L; direct bilirubin, 5.59 µmol/L; γ-glutamyltranspetidase, 61 U/L; total bile acid, 0.9 µmol/L; and lactate dehydrogenase, 380 U/L.\nHe showed to have a hypersensitive reaction to ticagrelor, and he was treated with antihistamines. Ticagrelor was switched to clopidogrel. Soon thereafter, his rash was gradually improved.\nHowever, 10 days later, he developed severe chest pain and received emergency coronary angiogram. Subacute definite stent thrombosis was confirmed, and thrombectomy was performed. After the procedure, a platelet function test was conducted, revealing a low response to clopidogrel.\nTo achieve therapeutic platelet aggregation inhibition, ticagrelor was reused under close supervision. Within approximately 2 hours, he developed generalized maculopapular rash in the whole trunk, which was resolved with intravenous corticosteroids. Ticagrelor was discontinued to avoid further hypersensitive reaction. Our patient showed delayed-type hypersensitivity reaction from the use of ticagrelor, represented in the form of generalized maculopapular rashes. Ticagrelor desensitization might not be appropriate for this patient.\nSwitching to other kinds of P2Y12 receptor antagonist antiplatelet drug was considered. Drugs that are structurally different from ticagrelor may be a good substitute for those with ticagrelor hypersensitivity. The chemical class of ticagrelor is cyclopentyl-triazolo-pyrimidine, and the other chemical class consists of thienopyridines (clopidogrel, prasugrel, ticlopidine) []. This patient presented a low response to clopidogrel and had suffered subacute in-stent thrombosis. Currently, prasugrel has not been approved for use in China. Ticlopidine has been associated with toxic side effects, such as rash, severe neutropenia, diarrhea, and thrombocytopenic purpura. Therefore, antithrombotic therapy was significantly difficult in this patient.\nThe patient ultimately received aspirin and warfarin as an antithrombotic treatment. He was given subcutaneous injection of low molecular weight heparin for 7 days. The regulated dose of warfarin was maintained in between 2 and 3 of the international normalized ratio (INR). During the follow-up period, our patient did not report any discomfort.