Drug-Induced Hypersensitivity Syndrome Associated with Transient Hypogammaglobulinaemia and Increase in Serum IgE Level

Abstract

Drug-induced hypersensitivity syndrome (DIHS) is a rare but severe disease with multiorgan failure. Recently, the association of the human herpesvirus (HHV) family, particularly of HHV-6, with DIHS has been reported. We report a 43-year-old female diagnosed as having DIHS based on the clinical course and laboratory examinations. The HHV-6 reactivation was demonstrated by significantly increased levels of the specific antibody in her paired sera and by polymerase chain reaction of HHV-6 DNA. Notably, transient hypogammaglobulinaemia was detected in the early stage of the disease, which was associated with the disease activity. By contrast, the serum IgE level and eosinophils were increased 2 or 3 weeks later. In addition, serum levels of interferon γ, interleukin (IL)-4 and soluble IL-2 receptor, which were increased in the early phase of the disease, decreased gradually after the corticosteroid therapy.

Are Viral Infections Responsible for the Development of Drug-Induced Hypersensitivity Syndrome as well as Graft-versus-Host Diseases?

“…In support of this hypothesis, we found that patients with DIHS/DRESS display several immune system defects at the onset of the rash, which allow reactivation of herpesviruses: our recent retrospective study demonstrates that the mean serum IgG levels and circulating B cells at the onset of the rash are dramatically decreased compared with control groups [7] . In this issue, Nakashima et al [8] confi rm these observations. In addition, our recent observations indicate that not only HHV-6, but also other herpesviruses (Epstein-Barr virus, cytomegalovirus and HHV-7) become reactivated from latency probably in obligate sequential order during the course of DIHS/DRESS [9] , a fi nding that can often be observed in the setting of bone marrow transplantation [10] .…”

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

“…It has been postulated that HHV-6 reactivation contributes to the decrease in B-cell count or immunoglobulin level [24,25]. In addition, SASP is known to have a direct immunosuppressive effect on B cells [26].…”

TrimethoprimSulfamethoxazoleInduced Hypersensitivity Syndrome Associated with Reactivation of Human Herpesvirus6

“…3) α (18-20); suppression of IL-12 production (21, 22); modulation of the interferon (IFN)-γeffect on the production of cytokines such as IL-1β, IL-6, IL-10, IL-12, and TNF-α (23,24); and increases in serum levels of IFN-γ, IL-4, IL-5, and IL-6 in DIHS associated with HHV-6 reactivation (25,26). From these findings, we speculated that the pathogenesis of DIHS is as follows: a latent virus is reactivated in a T lymphocyte-dependent manner involving proinflammatory cytokine, and the reactivated virus influences the production or regulation of these cytokines, which may be involved in the development of systemic symptoms of DIHS.…”

“…Hypogammaglobulinemia was reported as a risk factor for the reactivation of HHV-6 in DIHS (25)(26)(27) to be involved in the development of DIHS. At present, the use of systemic steroid should be limited in cases with severe symptoms such as internal organ damage (2).…”