Characteristics of liver injury in drug-induced systemic hypersensitivity reactions

J Am Acad Dermatol. 2013 Sep;69(3):407-15. doi: 10.1016/j.jaad.2013.03.024. Epub 2013 Apr 28.

Abstract

Background: The liver is the most commonly involved internal organ in drug-induced systemic hypersensitivity. However, data obtained from these patients have yet to be analyzed in depth with respect to liver injury.

Methods: The medical records of 136 patients who developed delayed-type drug hypersensitivity were reviewed at a tertiary referral hospital. Culprit drugs, the pattern and degree of liver injury, and the effect of systemic corticosteroids were evaluated in the group of patients with drug-induced systemic hypersensitivity and liver dysfunction (aspartate aminotransferase or alanine aminotransferase ≥80 IU/L). Clinical characteristics of patients with drug-induced systemic hypersensitivity and liver injury were analyzed.

Results: Among the 61 patients with drug-induced systemic hypersensitivity and liver dysfunction, the clinical phenotypes were drug reaction with eosinophilia and systemic symptoms (n = 29, 48%), Stevens-Johnson syndrome/toxic epidermal necrolysis (n = 11, 18%), and maculopapular rash (n = 17, 28%). Antibiotics (n = 27, 44%) were the most common cause of drug-induced systemic hypersensitivity with liver dysfunction. Whereas patients with Stevens-Johnson syndrome/toxic epidermal necrolysis had mild hepatocellular-type liver injury of relatively brief duration, those with drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome had more severe and prolonged hepatocellular injury in addition to moderate to severe cholestatic-type liver injury. The use of systemic corticosteroids did not significantly affect either recovery from liver injury or mortality.

Limitations: This study was retrospective and the number of subjects was small.

Conclusion: The results suggest that the severity, pattern, and duration of liver injury differ according to the drug-hypersensitivity phenotype. Further studies are needed to evaluate the role of systemic corticosteroids in drug-induced systemic hypersensitivity and liver injury.

Keywords: ADR; ALT; AST; DRESS; DiHS; SJS; Stevens-Johnson syndrome; TEN; adverse drug reaction; alanine aminotransferase; aspartate aminotransferase; corticosteroid; drug hypersensitivity; drug reaction with eosinophilia and systemic symptoms; drug-induced hypersensitivity syndrome; drug-induced liver injury; toxic epidermal necrolysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use*
  • Adult
  • Aged
  • Alanine Transaminase / blood
  • Allopurinol / adverse effects
  • Anti-Bacterial Agents / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anticonvulsants / adverse effects
  • Aspartate Aminotransferases / blood
  • Chemical and Drug Induced Liver Injury / blood
  • Chemical and Drug Induced Liver Injury / complications*
  • Chemical and Drug Induced Liver Injury / drug therapy
  • Drug Hypersensitivity / complications*
  • Drug Hypersensitivity / drug therapy
  • Enzyme Inhibitors / adverse effects
  • Eosinophilia / chemically induced
  • Eosinophilia / complications*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Stevens-Johnson Syndrome / complications*
  • Stevens-Johnson Syndrome / drug therapy
  • Stevens-Johnson Syndrome / etiology

Substances

  • Adrenal Cortex Hormones
  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Anticonvulsants
  • Enzyme Inhibitors
  • Allopurinol
  • Aspartate Aminotransferases
  • Alanine Transaminase