P3889 - Rifampin-Induced Multi-Organ Toxicity With Hepatic, Hematologic, and Renal Involvement: A Case Report in the Era of Intermittent TB Prophylaxis

Hiwot G. Tebeje, MD, MPH¹, Michael G. Tebeje, MD, MPH², Gedion Yilma Amdetsion, MD³, Yonas Fetle, MD⁴
1Washington University in St. Louis, Saint Louis, MO; 2Washington University in St. Louis, St. Louis, MO; 3Cook County Health, Chicago, IL; 4Marshall University Joan C. Edwards School of Medicine, Huntington, WV

Introduction: Rifampin remains a cornerstone of latent tuberculosis (TB) treatment and prophylaxis. Rifampin-induced hypersensitivity syndrome is rare but can result in severe hepatic, hematologic, and renal toxicity. We present a case of a patient who developed acute multi-organ injury after inconsistent rifampin use for latent TB.

Case Description/

Methods: A 60-year-old male with a history of type 2 diabetes and latent TB presented with an acute onset of shortness of breath, chest pain, nausea, vomiting, and transient visual changes. He reported inconsistent adherence with rifampin, having last taken two pills on the day of admission and a prior dose eight days earlier. On exam, he was hemodynamically stable and asymptomatic except for midline back pain. Laboratory evaluation revealed a significantly elevated transaminase (434AST/243ALT) with direct hyperbilirubinemia (total bilirubin 3.6–8.9 mg/dL), acute kidney injury (creatinine 0.9–2.3 mg/dL), anemia (Hgb 13.4–6.4 g/dL), leukocytosis (WBC 17.6 ×10⁹/L), and thrombocytopenia. Infectious workup including HIV, hepatitis markers, and STIs was negative. Imaging showed mild sigmoid colonic wall thickening without evidence of obstruction or mass. Further investigation confirmed a hemolytic process, with undetectable haptoglobin (< 6 mg/dL), elevated LDH (426 U/L), and a reticulocyte count of 6%. A comprehensive workup, including acute liver failure etiology screening, Liver Ultrasound, and further evaluation for Coombs-negative hemolysis, was entirely unremarkable. In the absence of any alternative etiology, and given the rapid normalization of hemolytic markers after rifampin discontinuation. At two weeks post-discharge, liver function tests and creatinine had begun to downtrend, with full normalization observed by one month.

Discussion: Rifampin-induced multi-organ toxicity is an under-recognized syndrome characterized by hepatic dysfunction, hemolytic anemia, thrombocytopenia, and acute kidney injury. The mechanism is thought to involve type II and III hypersensitivity reactions leading to intravascular hemolysis and immune-mediated hepatotoxicity. This case underscores the importance of clinical vigilance in patients with inconsistent rifampin adherence or intermittent dosing when they present with unexplained systemic manifestation apart from DILI. Given the increasing use of short-course and intermittent TB prophylaxis, clinicians should be aware of this potentially life-threatening adverse drug reaction.

Disclosures:
Hiwot Tebeje indicated no relevant financial relationships.
Michael Tebeje indicated no relevant financial relationships.
Gedion Yilma Amdetsion indicated no relevant financial relationships.
Yonas Fetle indicated no relevant financial relationships.

Hiwot G. Tebeje, MD, MPH¹, Michael G. Tebeje, MD, MPH², Gedion Yilma Amdetsion, MD³, Yonas Fetle, MD⁴. P3889 - Rifampin-Induced Multi-Organ Toxicity With Hepatic, Hematologic, and Renal Involvement: A Case Report in the Era of Intermittent TB Prophylaxis, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.