Differences in immunological alterations and underlying viral infections in two well-defined severe drug eruptions

Abstract

The difference in the pattern of immune responses shaped in part by previous and underlying viral infections at the time of drug exposure could cause a marked deviation in the pathological phenotype of severe drug eruptions. Elucidating these host factors may provide a basis for therapeutic approaches in patients with severe drug reactions.

The dynamics of herpesvirus reactivations during and after severe drug eruptions: their relation to the clinical phenotype and therapeutic outcome

“…The most obvious explanation is that the observed increase in viral loads could reflect expansions of EBV‐infected memory cells such as B cells. However, not consistent with this view, patients with SJS revealed a dramatic decrease in circulating T‐ and B‐cell numbers at the acute stage 26. Alternatively, it is possible that the increase could be the result of destruction of EBV‐specific CD4 + and CD8 + T cells during the active stage, thereby facilitating EBV persistence.…”

Severe Cutaneous Adverse Reactions

“…Failure to eradicate the antigenic stimulus, in this instance due to the continued ingestion of the drug, causes persistent cytokine release and promotes differentiation of macrophages into epithelioid cells, which secrete large amounts of TNF promoting their fusion to form multinucleate giant cells [210]. Analogous to that observed in GVHD, longitudinal real-time PCR analyses of viral loads in blood samples drawn from patients with DIHS show that various herpetic viruses are sequentially activated as a result of massive T cell stimulation, B cell loss and hypogammaglobulinemia [213]; Activation of Epstein-Barr virus or HHV-6 extends to the sequential activation of HHV-7, cytomegalovirus and varicella-zoster virus [189]. The frequent deterioration or several exacerbations that occur despite continuation of the drug may at least be partly explained by sequential reactivation of herpetic viruses and the immune response to viral replication.…”

Antibiotic Induced Cutaneous Rash in Infectious Mononucleosis: Overview of the Literature

“…The role of previous and/or present, acute or chronic viral infection, in the development of drug induced reactions has received more attention recently [40]. Molecular mimicry between amoxicillin and viral molecules, or high affinity of betalactams for viral proteins cannot be excluded as potential mechanisms for skin reactions in some patients.…”

“…Viral infection may be a co-activating factor for drug specific T cells and without the acute viral infection these drug specific T cells could apoptose, therefore we could not detect a long lasting hypersensitivity in these patients. It is recognized that Human Herpesvirus 6 (HHV-6), EBV and CMV reactivation appears in drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome or in other severe cutaneous adverse drug reactions, resulting in a marked deviation in the pathological phenotype of severe drug eruptions [40][41][42]. Mardivirin et al investigated the influence of amoxicillin on HHV-6 replication by in vitro methods.…”