S2437 DRESSed Up: A Rare Case of Aspirin-Induced DRESS Without Eosinophilia

Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe drug-induced hypersensitivity reaction with significant hepatic implications, often presenting with acute liver injury alongside multi-organ involvement, fever, rash, and hematologic abnormalities. While eosinophilia is traditionally associated with DRESS, cases lacking eosinophilia pose a unique challenge in hepatology, as liver dysfunction may dominate the clinical picture. Methods: A 33-year-old man with a history of Gilbert’s syndrome was hospitalized after a week of nausea, malaise and intermittent fevers up to 100.4°F. A few days prior, he developed a maculo-papular rash coalescing into patches, where tests showed abnormal aminotransferases (alanine aminotransferase [ALT] 755 U/L, aspartate aminotransferase 520 U/L, alkaline phosphatase 204 U/L, and total bilirubin (TB) 14.0 mg/dL) but normal blood counts. He reported taking azithromycin and acetaminophen-Aspirin-Caffeine combination for an upper respiratory infection which had since resolved. Infectious workup including viral hepatitis, HSV, EBV, CMV, HHV-6, HHV-7 and measles serologies, as well as autoimmune and fungal causes were ruled out. A liver doppler ultrasound was unremarkable. Patient's TB continued to rise up to a peak of 22.2. A skin biopsy showed vacuolar interface dermatitis compatible with DRESS syndrome. A subsequent liver biopsy identified acute hepatitis representing a likely drug-induced liver injury (DILI). Aspirin was thought to be the culprit of injury, with LiverTox Likelihood score: A[HD] (well-known cause of clinically apparent liver injury when given in high doses). Treatment with cyclosporine was initiated leading to improvement in aminotransferases (ALT 531, aspartate aminotransferase 169 and TB at 9.7) and resolution of the rash at time of discharge. Conclusion: This case highlights the difficulty in diagnosing DRESS syndrome given the absence of peripheral eosinophilia, which emphasizes the need for heightened clinical suspicion in cases of unexplained hepatic dysfunction. Biopsy findings were critical in distinguishing DRESS-related hepatic injury from other causes of acute hepatitis. Emerging evidence supports cyclosporine as an effective immunomodulator in DRESS syndrome with liver involvement and hepatologists should consider early intervention with immunosuppressive agents to mitigate disease progression. This case underscores the complex interplay between drug hypersensitivity and hepatic injury, reinforcing the need for multidisciplinary collaboration.