Abstract Introduction Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe hypersensitivity syndrome characterized by rash, fever, hematologic abnormalities, and multi-organ involvement. Mortality approaches 10%, most often due to organ failure. While frequently reported in medical wards, severe cases requiring intensive care unit (ICU) management remain challenging, particularly when complicated by shock and multi-organ dysfunction. Emerging evidence suggests that genetic and mitochondrial factors may influence disease severity. Case Presentation A 61-year-old female with coronary artery disease, ischemic cardiomyopathy, and oxygen-dependent COPD presented with shock and a diffuse non-blanchable rash. She had recently undergone aortic valve replacement for Enterococcus faecium endocarditis and was completing a six-week vancomycin course. After five weeks, she developed confusion, dyspnea, and rash. In the emergency department, she was hypotensive and hypoxic, improving transiently with steroids and antihistamines. Despite antibiotic switch to Linezolid, she deteriorated with fever, hypotension, radiographic evidence of pneumonia, acute kidney injury, leukocytosis, and marked eosinophilia. She required ICU admission, vasopressors, and stress-dose steroids. Peripheral smear showed transient RBC membrane abnormalities (Fig.1). Work-up excluded infectious and autoimmune causes. Genetic testing revealed an SDHA mutation, and coenzyme Q10 was initiated. With continued steroids and supportive care, she improved and was transitioned to oral prednisone prior to discharge. Discussion This case highlights the potential role of mitochondrial dysfunction in amplifying the severity of DRESS. The SDHA gene encodes a succinate dehydrogenase subunit essential for oxidative phosphorylation 1, 2. Pathogenic variants impair electron transport and increase reactive oxygen species (ROS). In DRESS, where immune activation and cytokine release are already heightened, excess ROS may drive immune dysregulation, cellular injury, and systemic inflammation. Such mechanisms could explain the disproportionate severity of our patient’s presentation and persistence of eosinophilia despite corticosteroids. Antibiotics with known mitochondrial toxicity (e.g., vancomycin, daptomycin) may exacerbate this vulnerability. Recognition of genetic predispositions like SDHA mutations could eventually guide antibiotic choice and support early consideration of adjunctive antioxidant therapy such as coenzyme Q10 in ICU settings. Conclusion We describe a severe case of DRESS complicated by shock and multi-organ dysfunction in a patient with an SDHA mutation. This raises the hypothesis that mitochondrial dysfunction and oxidative stress may predict more severe outcomes. Further study is warranted to evaluate whether genetic testing can inform prognosis, antibiotic selection, and targeted adjunctive therapy in DRESS, especially in ICU settings. This abstract is funded by: None
Bleik et al. (Fri,) studied this question.