Drug-Induced Liver Injury Associated With Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: Patient Characteristics, Causes, and Outcome in 36 Cases

The liver and skin are the organs most commonly involved in serious adverse drug reactions. Rarely a drug reaction can affect both organs concurrently. The association of drug-induced liver injury (DILI) and Stevens-Johnson syndrome (SJS) or toxic epidermal necrosis (TEN) is even rarer and not well studied. We describe our experience of DILI occurring in association with SJS/TEN including the etiologic agents, clinical and biochemical characteristics, and outcome. We identified patients who developed DILI in association with SJS/TEN from a registry of DILI patients from a single center. Causality assessment for DILI and SJS/TEN was carried out with the Roussel Uclaf Causality Assessment Method and the Algorithm for Drug Causality for Epidermal Necrolysis, respectively. Among 748 consecutive patients with DILI from 1997 to March 2015, 36 (4.8%) had associated features of SJS/TEN. The mean age was 32 years (females 19). Children and patients with human immunodeficiency virus constituted 25% (n=9) and 22% (n=8), respectively. Only a small number of "high-risk" drugs such as antiepileptic agents, sulfonamides, and antiretroviral drugs accounted for the majority of cases. Overallmortality was 36% (n=13), which rose to 45.5% in the presence of jaundice. Mortality was less in children 11% (n=1) and human immunodeficiency virus patients 12.5% (n=1). Conclusions: DILI associated with SJS/TEN is rare and associated with a high death rate, particularly in those with jaundice; however, children and human immunodeficiency virus-infected individuals have a favorable outcome; a small group of drugs contributed to a disproportionate number of cases, and causality with Roussel Uclaf Causality Assessment Method and the Algorithm for Drug Causality for Epidermal Necrolysis was highly probable or probable in all cases.