A diagnostic dilemma: Differentiating hepatic sarcoidosis from DRESS syndrome in a patient with acute liver injury

If unexplained acute liver injury symptoms imply several overlapping etiologies, diagnostic difficulty can ensue. Less frequent diseases like hepatic sarcoidosis and DRESS syndrome need to be included in differential diagnosis, but drug-induced liver injury and viral hepatitis are frequent etiologies. A 28-year-old woman patient presented with pruritic rash, jaundice, and right upper quadrant pain for one month. Laboratory tests showed eosinophilia (520 cells/μL), hyperbilirubinemia (6.20 mg/dL), hepatocellular injury (AST 401 U/L, ALT 351 U/L), and highly raised ACE levels (216 U/L). Imaging revealed mediastinal lymphadenopathy. The patient's liver enzymes and symptoms significantly improved with corticosteroid treatment. Because DRESS syndrome and hepatic sarcoidosis share clinical and biochemical characteristics, the diagnostic challenge of differentiating between the two conditions is brought about in this case. While temporal drug association and eosinophilia predisposed towards drug hypersensitivity, the raised ACE levels and lymphadenopathy pushed in the direction of granulomatous disease. The shared immune-mediated pathophysiology of the two diseases was emphasized by the steroid response. In the assessment of acute liver injury with systemic manifestations, this case emphasizes the need to rule out both drug hypersensitivity and granulomatous disease. It draws attention towards the need for improved diagnostic markers while also recognizing the utility of serum ACE testing and imaging in these situations. The case highlights the advantage of interdisciplinary management in difficult hepatology patients and the effectiveness of corticosteroids. This case demonstrates the difficulty of making a distinction between hepatic sarcoidosis and drug-induced liver damage in cases where the two diseases mimic each other. Both etiologies must be considered in cases of unexplained acute liver injury with systemic symptoms. Although corticosteroids can be an effective treatment of immune-mediated disease, prolonged follow-up is indicated. Interdisciplinary collaboration enhances the treatment of such complex cases and the validity of diagnoses. • Rare overlap of hepatic sarcoidosis and DRESS syndrome presenting as acute liver injury with fulminant transaminitis and hyperbilirubinemia. • Diagnostic challenge due to overlapping features rash, eosinophilia, elevated ACE levels, and mediastinal lymphadenopathy complicated differentiation from DILI and viral hepatitis. • Multidisciplinary approach (hepatology, rheumatology, dermatology) was crucial for diagnosis and management. • Rapid clinical and biochemical improvement with corticosteroids, supporting immune-mediated liver injury as the shared mechanism. • Case underscores the need for sensitive biomarkers and long-term follow-up in patients with overlapping immune-mediated liver diseases.