Reactivation of Human Herpes Virus-6 in the Renal Tissue of a Patient with Drug-induced Hypersensitivity Syndrome/Drug Rash with Eosinophilia and Systemic Symptoms (DIHS/DRESS)

Abstract

A 74-year-old man who had been administered trimethoprim-sulfamethoxazole for three weeks suffered from drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms (DIHS/ DRESS). In the early stage of the clinical course, he developed renal dysfunction. A renal biopsy showed granulomatous tubulointerstitial nephritis accompanying the proliferation of human herpes virus (HHV)-6 in tubular epithelial cells. With corticosteroid therapy, the systemic rash and renal function gradually improved. The present patient is the second case of DIHS/DRESS demonstrating a possible reactivation of HHV-6 in the renal tissue. The clinical role of viral reactivation in DIHS/DRESS must be further elucidated.

Lymphoproliferative Syndromes Associated With Human Herpesvirus-6a and Human Herpesvirus-6b

“…Perhaps the deleterious effects of HHV-6-mediated lymphocytic infiltration are exemplified best by severe DIHS/DRESS, a condition that can mimic malignant lymphoma 140 – 142 characterized by erythematous rash, organ dysfunction, and occasionally organ failure. 143 High level HHV-6 viremia is often found in these patients, and HHV-6 DNA and antigen has been detected in the CSF of patients with encephalitis and hemophagocytosis, 143 , 144 the livers of patients with hepatitis and liver failure, 143 , 145 the kidneys of patients with renal dysfunction and failure, 146 , 147 and the bone marrow of patients with hemophagocytic syndrome. 148 , 149 HHV-6 is thought to contribute to the clinical manifestations of DIHS/DRESS, especially the atypical lymphocytosis, 150 lymphadenitis, 141 and multiorgan involvement, and viremia is predictive of a more severe course and flaring of symptoms, including hepatitis and fever, 151 as is hemophagocytosis.…”

“… 140 Additionally, administration of valganciclovir has improved the condition of patients with severe DIHS/DRESS. 143 , 147 , 149 HHV-6 has been found in hepatocytes 143 , 145 , 152 and tubular epithelial cells of the kidney, 146 , 147 as well as in infiltrating lymphocytes, often atypical. 141 , 148 , 152 Notably, the detection of HHV-6 in these cells has corresponded to severe necrosis and dysfunction in the related organs.…”

Lamotrigine Induced DRESS Syndrome in a Child: A Case Report and Literature Review

“…The incidence of DRESS has been estimated to be between 1/1000 and 1/10,000 exposures to anticonvulsant drugs [4]. Furthermore, DRESS has previously been reported to be associated with herpesviruses, although existing explanations of how viral infections contribute to the pathogenesis of DRESS remain speculative [5].…”

Lamotrigine induced DRESS syndrome in a child: a case report and literature review

“…4 Furthermore, DRESS has previously been reported to be associated with herpesviruses, although existing explanations of how viral infections contribute to the pathogenesis of DRESS remain speculative. 5 There are two sets of diagnostic criteria for the diagnosis of DRESS; one set consists of the RegiSCAR criteria (Table 1) and the other consists of the SCAR-J criteria developed by Japanese investigators (Table 2). [6][7][8] The treatment for DRESS consists of immediate withdrawal of the culprit drug followed by the initiation of systemic steroids.…”