key: cord-0698746-n5sovcey authors: Korekawa, Ayumi; Nakajima, Koji; Fukushi, Karen; Nakano, Hajime; Sawamura, Daisuke title: Three cases of drug‐induced hypersensitivity syndrome associated with mRNA‐based coronavirus disease 2019 vaccines date: 2022-03-03 journal: J Dermatol DOI: 10.1111/1346-8138.16347 sha: 1c7ef2a21d7dcf867c0196c924dddb97cc683ebd doc_id: 698746 cord_uid: n5sovcey Drug‐induced hypersensitivity syndrome (DiHS) is a severe drug eruption that can induce reactivation of herpesviruses such as human herpesvirus 6, resulting in symptom flare‐up and organ damage. DiHS is known as drug reaction with eosinophilia and systemic symptoms (DRESS) in Europe. We report three cases of DiHS that could have been triggered by mRNA‐based coronavirus disease 2019 (COVID‐19) vaccines. In these three patients, symptoms of DiHS developed 2–6 days after the first dose of an mRNA‐based COVID‐19 vaccine. Although there have been no reports of DiHS/DRESS induced by mRNA‐based COVID‐19 vaccines in domestic and international journals despite the progress in vaccination worldwide, we speculate that mRNA‐based COVID‐19 vaccines might have triggered the development of DiHS/DRESS in our patients. In the current coronavirus epidemic, it might be important to assess mRNA‐based COVID‐19 vaccination status and date of vaccination when evaluating a patient with DiHS/DRESS. (1.69 mg/dL), aspartate aminotransferase (AST; 35 U/L), aspartate aminotransferase (ALT; 94 U/L), and C-reactive protein (CRP; 8.37 mg/dL). HHV-6 reactivation was detected on hospital day 10. The serum level of thymus and activation-regulated chemokine (TARC) on the second day of hospitalization was 73 200 pg/mL. Computed tomography did not reveal findings indicating an infectious lesion. Blood cultures did not show any bacteria or fungi. We performed skin biopsy from an erythematous area. Histopathological findings included an infiltration of lymphocytes surrounding the vessels and hemorrhage in the dermis and mild vacuolar changes and lymphocytic infiltration in the epidermis (Figure 1f) . A diagnosis of typical DiHS induced by carbamazepine was made. Oral prednisolone (1 mg/kg/day) was administered. His skin rash, high fever, and laboratory test abnormalities decreased gradually over 5 weeks. The steroid dose is still being tapered. A 31-year-old Japanese man was transferred to our hospital with fever, erythroderma, and liver dysfunction. His past medical history was unremarkable. He started taking allopurinol for a diagnosis of gout 38 days before being transferred to our hospital. He The TARC level on the fourth day after transfer was 33 800 pg/mL. Oral prednisolone (1 mg/kg/day) was administered. His skin rash, high fever, and liver dysfunction decreased gradually over 6 weeks. The steroid dose is still being tapered. A 72-year-old Japanese man was hospitalized with fever and erythroderma. He started taking carbamazepine for a diagnosis of facial nerve paralysis 58 days before hospitalization. He received the first We performed skin biopsy from an erythematous area. Histopathological findings in the dermis included an infiltration of lymphocytes and eosinophils surrounding the vessels with hemorrhage. In the epidermis, there were mild vacuolar changes and lymphocytic infiltration (Figure 2f,g) . A diagnosis of atypical DiHS was made. Oral prednisolone (30 mg/day) was administered. His skin rash and high fever decreased within 1 week. However, he had cough, respiratory discomfort, high fever (38°C), formation of new skin rashes, elevated blood eosinophil count, and oxygen desaturation on hospital day 9. We consulted a respiratory physician. The patient was diagnosed with acute exacerbation of interstitial pneumonia. Steroid pulse therapy was given. Respiratory symptoms, laboratory test abnormalities, fever, and skin rashes decreased within 3 days after the start of steroid pulse therapy. The steroid dose is still being tapered. Drug-induced hypersensitivity syndrome is a severe drug eruption associated with rash along with high fever, organ dysfunction (e.g., liver), and lymphadenopathy. [1] [2] [3] It is characterized by prolonged symptoms even after discontinuation of the causative drug. DiHS is known as DRESS in Europe. [1] [2] [3] A diagnosis of atypical DiHS or DRESS was made for case 3 because HHV-6 reactivation was not detected. However, we thought that the timing of examination was inappropriate. In these three patients, In conclusion, although accumulation of more cases is needed, we emphasize that it might be important to assess mRNA-based COVID-19 vaccination status and date of vaccination when evaluating a patient with DiHS/DRESS during the current coronavirus epidemic. We thank Zenis for English-language editing. None declared. Ayumi Korekawa https://orcid.org/0000-0002-4534-8313 Koji Nakajima https://orcid.org/0000-0003-0652-9338 Drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS): An update in 2019 Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms severity score: A useful tool for assessing disease severity and predicting fatal cytomegalovirus disease A retrospective study of DRESS -drug reaction with eosinophilia and systemic symptoms DRESS syndrome potentially induced by allopurinol and triggered by influenza vaccine Drug reaction with eosinophilia and systemic symptoms associated with H1N1 vaccination A case of severe cutaneous adverse reaction following administration of the Janssen Ad26.COV2.S COVID-19 vaccine Comment on 'Drug reaction with eosinophilia and systemic symptoms syndrome in a patient with COVID-19′: involvement of herpesvirus reactivations and adverse drug reactions in diverse cutaneous manifestations and overall disease severity of COVID-19