Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 3 2024 05 27 339 346 Amin Tajerian Department of Pediatrics, School of Medicine, Arak University of Medical Sciences, Arak, Iran Ali Pourvali Department of Pediatrics, School of Medicine, Arak University of Medical Sciences, Arak, Iran Masoud Movahedi Division of Allergy and Clinical Immunology, Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran Maryam Mohammadi Department of Pediatrics, School of Medicine, Arak University of Medical Sciences, Arak, Iran Behzad Khansarinejad 3 Department of Microbiology and Immunology, Arak University of Medical Sciences, Arak, Iran Matin Pourmatin National Forensic Medicine Organization, Arak, Iran Yazdan Ghandi Department of Pediatrics, School of Medicine, Arak University of Medical Sciences, Arak, Iran Mohammad Ali Daneshmand Daneshmand Pathology Laboratory, Arak, Iran 2023 10 29 2024 02 12 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a complex and potentially fatal hypersensitivity condition. We present a unique case report and literature review focusing on DRESS syndrome-associated myocarditis resulting from reactivated viral infections in a 21-year-old female. 3 weeks after 5-day oral co-trimoxazole consumption due to acne, she developed symptoms consistent with DRESS syndrome, including a generalized maculopapular rash. Despite prednisolone treatment, the patient developed fatal fulminant myocarditis linked to HHV-6 and CMV reactivation. The patient's death highlights the importance of early recognition and careful management of DRESS syndrome, especially considering the potential viral reactivation that can lead to severe complications. Postmortem investigations revealed that viral reactivation caused myocarditis. Careful consideration must be given to corticosteroid usage in DRESS treatment, as inappropriate prescribing may promote viral reactivation and subsequent complications. While high-dose corticosteroids initiated within the first week effectively suppress HHV-6 reactivation. Conversely, low-dose or late-start high-dose corticosteroids prove ineffective in preventing HHV-6 viremia. Late- onset or low- dose corticosteroids may lead to fatal complications following the primary viral reactivation. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3940 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3940/2042