Drug-induced hypersensitivity syndrome associated with reactivation of human herpesvirus 6 presenting with severe hepatic injury

Abstract

Little is known about the pathophysiology of liver complication seen in drug-induced hypersensitivity syndrome (DIHS). We describe herein a 32-year-old Japanese man with DIHS due to salazosulfapyridine (SASP) associated with reactivation of human herpesvirus 6 (HHV-6) presenting with severe acute hepatic injury. The patient, with a 1-year history of ulcerative colitis (UC), presented with high fever and abnormally elevated liver enzymes. Six weeks prior to his symptoms, prednisolone (PSL) and SASP had been started because of UC aggravation. Besides fever and liver dysfunction, the appearance of atypical lymphocytes together with eosinophils and generalized erythematous maculopapular skin rash developed sequentially, and a diagnosis of DIHS was established. Despite cessation of SASP and increased dose of PSL, his initial abnormalities continued, and biphasic second alanine aminotransferase (ALT) flare with deep jaundice worsened. Based on the significant increase in the titer of HHV-6 IgG antibodies at the second peak of ALT level without HHV-6 IgM antibody elevation, strongly suggesting reactivation of the virus, HHV-6 was first considered to directly contribute to the deterioration of liver function. However, extensive histological analysis of the liver led to the realization that the cause of the DIHS liver injury was essentially drug-related hepatotoxicity induced by SASP, causing wide-ranging damage to both the hepatocytes and cholangiocytes.

A 51-Year-Old Woman with Drug-Induced Hypersensitivity Syndrome Associated with Carbamazepine, Reactivation of Human Herpesvirus 6, and Acute Liver Failure: A Case Report

“…Drugs are commonly associated with DIHS. Symptoms of DIHS occur 2–5 weeks after initiating treatment with the causal agent, such as carbamazepine, phenobarbital, allopurinol, or salazosulfapyridine [ 5 , 7 – 11 ]. Our patient had received numerous drugs before and after admission to our hospital.…”

Drug Rash with Eosinophilia and Systemic Symptoms Syndrome in a Patient on Sulfasalazine for Ulcerative Colitis

“…To our knowledge, only two cases of sulfasalazine-induced DRESS have been reported in IBD in the literature that had clinical features similar to ours. 7,8 In patients with DRESS, hepatitis, lymphadenopathy, and hematological abnormalities are observed to varying degrees. These diverse presentations emphasize the need for a set of diagnostic criteria that are easily applicable in the clinical setting.…”

“…These findings make our case unique, since two cases of sulfasalazine-induced DRESS in IBD did not exhibit the above-mentioned results. 7,8 Indeed, it is difficult to demonstrate whether viral infection is a prerequisite for DRESS or an outcome of immune dysfunction in DRESS. Therefore, a large prospective study is necessary to investigate the role of the HHV family.…”

“…4 While many studies have described experiences of sulfasalazine-induced DRESS in rheumatic diseases, 5,6 few such reports have examined in relation to IBD. 7,8 We herein describe a case of DRESS on sulfasalazine treatment of UC for 6 weeks and present a short review of the literature.…”