Drug‐induced liver injury associated with severe cutaneous adverse drug reactions: A nationwide study in Taiwan

Abstract

Background & Aims: Severe cutaneous adverse drug reactions (SCARs) including Stevens‐Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP) are high‐mortality adverse drug reactions. The risk factors and prognosis of drug‐induced liver injury (DILI) concomitant with SCAR warrant clarification. We aimed to evaluate the characteristics and outcomes of DILI with SCAR. Methods: We analysed the database of a 10‐year multi‐centre prospective study in Taiwan from 2011 to 2020. Results: A total of 1415 patients with DILI were enrolled, including 81 cases combined with SJS/TEN, 74 with DRESS, 3 with AGEP and 1257 with pure DILI. Approximated 11.2% of patients had SCAR, of which allopurinol was the leading incriminated drug, followed by sulphonamides and carbamazepine. The SJS/TEN group had the highest mortality (34.6%). Jaundice, acute kidney injury and SJS/TEN were independent risk factors of mortality (odds ratio: 29.54, 4.43 and 4.86, respectively, P < .003). Chronic kidney disease with high‐dose allopurinol also contributed to high mortality (78.9%) in cases of allopurinol‐induced DILI with SCAR. The HLA‐B*5801 was associated with a high risk and mortality of allopurinol‐induced DILI with SCAR. Likewise, the HLA‐B*1502 was closely related to carbamazepine‐induced DILI with SCAR. Conclusions: DILI patients combined with SCAR are common and have a high mortality in Taiwan. Allopurinol is the leading incriminated drug. Jaundice, acute kidney injury and SJS/TEN are risk factors of mortality. HLA‐B*5801, chronic kidney disease and high drug dosage also contribute to high mortality in allopurinol‐induced DILI with SCAR.