Carbamazepine-induced hypersensitivity syndrome associated with transient hypogammaglobulinaemia and reactivation of human herpesvirus 6 infection demonstrated by real-time quantitative polymerase chain reaction

Abstract

Drug-induced hypersensitivity syndrome (HS) is a rare but severe disease with multiorgan failure. Many different precipitating factors have been reported, but the pathophysiology of HS remains unknown. However, the association of the human herpesvirus (HHV) family, particularly of HHV-6, has recently been reported in patients with HS. We report a 14-year-old boy who was diagnosed as having carbamazepine-induced HS based on the clinical course, laboratory data and results of drug-induced lymphocyte stimulation tests. In addition, the reactivation of HHV-6 was demonstrated by real-time quantitative polymerase chain reaction and by significantly increased levels of the specific antibody in his paired sera. Furthermore, transient hypogammaglobulinaemia was detected in the early stage of the disease. In addition, serum levels of interferon-gamma, interleukin (IL)-6, IL-5 and eosinophil cationic protein, which were increased on admission, decreased dramatically after steroid therapy. This is the first report of carbamazepine-induced HS associated with reactivation of HHV-6, transient hypogammaglobulinaemia, increased serum levels of inflammatory cytokines and activated eosinophils. This case might contribute to the understanding of the pathophysiology of HS.

Activation of Human Herpesvirus Replication by Apoptosis

“…Some of these have been associated with HHV activation. These associations range from advanced age and the activation of varicella-zoster virus (VZV) as shingles, to stress and UV radiation and the activation of HSV-1, to cancer chemotherapy or neoplastic diseases themselves, bone marrow transplantation, drug-induced hypersensitivity syndrome/drug reaction/rash with eosinophilia and systemic symptoms (DIHS/DRESS) (21)(22)(23)(24)41), and the activation of cytomegalovirus (CMV), EBV, HHV-6, and HHV-7. Our findings would suggest that some, if not many, of the HHV activation phenomena observed in association with these disorders result from a caspase-3-dependent activation of a herpesvirus ARP.…”

“…In addition to the fact that these viruses represent a cross-section of human herpes-virus families, we also chose these herpesviruses because good latently infected cell line model systems exist for them and because they cause close to universal infections in humans by an early age (14)(15)(16)(17), making the clinical and translational implications of the studies more compelling. These viruses have been associated with significant adverse clinical outcomes in clinical situations in which substantial numbers of cells may be undergoing apoptosis, such as treatment with cytotoxic cancer chemotherapeutic agents, solid organ and bone marrow transplantation (18,19), and severe hypersensitivity and autoimmune disorders (20)(21)(22)(23)(24), and in patients critically ill from a variety of causes (25). Human herpesviruses have been implicated in a variety of incompletely understood clinical disorders (26), some of which may be associated with apoptosis.…”

TrimethoprimSulfamethoxazoleInduced Hypersensitivity Syndrome Associated with Reactivation of Human Herpesvirus6

“…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).…”

“…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.…”

Infections caused by herpes virus type 6: modern features

“…Так, по данным литературы, реактивация хронической ВГЧ6B-инфекции реги-стрируется у 30% реципиентов костного мозга и со-провождается при этом длительной виремией [10]. Реактивация может провоцироваться некоторыми лекарственными средствами (амоксициллин, ванко-мицин, габапентин, дапсон, карбамазепин, фенобар-битал, ибупрофен, аллопуринол, дексаметазон, ко-три мо кса зол) [11][12][13][14][15][16]. Эпидемиология и клинические проявления ин-фекции ВГЧ6А сравнительно мало изучены, и его роль в патологии человека до настоящего времени не очень понятна.…”