S2695 A Rare Drug Reaction: A Case of Dapsone Hypersensitivity Syndrome

Abstract

INTRODUCTION: Dapsone is used to treat a variety of infectious and inflammatory disorders, and can be associated with a number of adverse side effects and events including a rare clinical entity known as dapsone hypersensitivity syndrome (DHS). This is a case of a 22-year-old female presenting with fever, hemolytic anemia, and acute hepatitis, found to have DHS. CASE DESCRIPTION/METHODS: A 22-year-old female with macular lymphocytic arteritis presented to the ED with one week of abdominal pain and fevers. She had been initiated on dapsone one month prior for her arteritis, but had stopped taking dapsone when her symptoms began. Prior to therapy, her G6PD level was normal. On presentation, she was febrile and tachycardic, with exam notable for diffuse abdominal tenderness. Her mental status was intact. Her admission labs were notable for hemolytic anemia and transaminitis with a hepatocellular injury pattern. Her INR was normal and Coomb’s test was negative. A right upper quadrant ultrasound showed gallbladder wall thickening and mild intrahepatic biliary ductal dilation. She remained febrile despite a negative infectious workup and empiric antibiotic therapy. A broad workup for causes of acute and chronic liver injury revealed no obvious etiology. Five days into her admission, her eosinophil count increased from 0.6 to 15, and she developed a new rash on her upper extremities. Given the concern for DRESS syndrome, specifically a variant known as DHS, she was started on prednisone and underwent liver and skin biopsies, which were consistent with DHS. Her labs and symptoms improved after a prolonged taper of prednisone. A RUCAM (Roussel Uclaf Causality Assessment Method in DILI) final score was calculated in this case to be eight, suggesting probable causality. DISCUSSION: DHS is a severe idiosyncratic reaction and variant of DRESS that occurs in 0.5 to 3.6% of patients treated with dapsone, and is associated with a fatality rate of 10%. Symptoms of DHS include fever, rash and lymphadenopathy, and typically arise within weeks of initiating dapsone, but can present as late as six months after its use. The mechanism by which DHS occurs remains unclear, although there is evidence that variability in the production of reactive metabolites plays a role in sulfonamide hypersensitivity reactions. Due to the rarity of DHS and the potentially fatal associated organ dysfunction, it is important to make an early diagnosis in order to promptly withdraw dapsone and administer glucocorticoids.Figure 1.: Magnification 10x. Severe acute hepatitis with mixed triaditis, interface and lobular hepatitis, and cholestasis, consistent with drug-induced liver injury.Figure 2.: Magnification 30x. Hepatic parenchyma shows zone 3 inflammation associated with prominent cholestasis and scattered single cell necrosis.