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

• Published in: Allergy (Copenhagen) Vol. 69; no. 6; pp. 798 - 805
• Main Authors: Ishida, T., Kano, Y., Mizukawa, Y., Shiohara, T.
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.06.2014; Wiley-Blackwell
• Subjects: Adult; Aged; Clinical outcomes; Cytomegalovirus; DNA, Viral; Drug Eruptions - complications; Drug Eruptions - diagnosis; Drug Eruptions - drug therapy; drug‐induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms; Epstein-Barr virus; Female; Follow-Up Studies; Genotype & phenotype; Herpes viruses; Herpesviridae - drug effects; Herpesviridae - genetics; Herpesviridae Infections - complications; Herpesviridae Infections - virology; Human cytomegalovirus; Human herpesvirus 6; Humans; Immunosuppressive Agents - pharmacology; Immunosuppressive Agents - therapeutic use; Male; Middle Aged; Original; Outcome Assessment, Health Care; Phenotype; Retrospective Studies; Side effects; Steroids; Stevens-Johnson Syndrome - complications; Stevens-Johnson Syndrome - diagnosis; Stevens–Johnson syndrome/toxic epidermal necrolysis; Time Factors; Viral Load; Virus Activation - drug effects; human herpesvirus 6; drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms; Epstein-Barr virus; Stevens-Johnson syndrome/toxic epidermal necrolysis; cytomegalovirus
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/all.12410

Background Drug‐induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms (DIHS/DRESS) and Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) represent contrasting poles of severe drug eruptions, and sequential reactivations of several herpesviruses have exclusively been demonstrated in the former. No previous studies, however, were extended beyond the acute stage. We sought to investigate whether herpesvirus reactivations could also be observed in SJS/TEN and beyond the acute stage of both diseases. Methods Patients with SJS (n = 16), SJS/TEN overlap (n = 2), TEN (n = 10), and DIHS/DRESS (n = 34) were enrolled. We performed a retrospective analysis of Epstein–Barr virus (EBV), human herpesvirus 6 (HHV‐6), and cytomegalovirus (CMV) DNA loads sequentially determined by real‐time polymerase chain reaction during a 2‐year period after onset. Results Persistently increased EBV loads were detected in SJS during the acute stage and long after resolution, but not in others. In contrast, high HHV‐6 loads were exclusively detected in DIHS/DRESS during the acute stage. The dynamics of herpesvirus reactivation varied in DIHS/DRESS according to the use of systemic corticosteroids: While EBV loads were higher in patients not receiving systemic corticosteroids, CMV and HHV‐6 loads were higher in those receiving them. Conclusions Distinct patterns of herpesvirus reactivation according to the pathological phenotype and to the use of systemic corticosteroids were observed during the acute stage and follow‐up period, which may contribute, at least in part, to the difference in the clinical manifestations and long‐term outcomes. Systemic corticosteroids during the acute stage may improve the outcomes in DIHS/DRESS.