title: Drug-induced severe adverse reaction enhanced by human herpes virus-6 reactivation.
abstract: Reactivation of certain latent viruses has been linked with a more severe course of drug-induced hypersensitivity reaction (HSR). For example, reactivation of human herpes virus (HHV)-6 is associated with severe organ involvement and a prolonged course of disease. The present study discusses an HSR developed in a previously healthy male exposed to ceftriaxone, doxycycline, vancomycin, and trimethoprim/sulfamethoxazole (co-trimoxazole; TMP/SMX). Initially, the patient presented clinical manifestations of HSR, as well as clinical and laboratory measurements compatible with liver and renal failure. Moreover, the patient presented skin desquamation compatible with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis. During the reaction, it was observed HHV-6 reactivation. The severity of clinical symptoms is correlated with HHV-6 titer, as well as with results of the in vitro lymphocyte toxicity assay (LTA). Serum levels of a large panel of cytokines are compared between the patient, a large population of SJS patients, and a cohort of healthy controls, using data collected by our laboratory over the years. HHV-6 was measured in the cell culture media from lymphocytes incubated with each of the 4 drugs. Moreover, we describe a new assay using cytokines released by patient lymphocytes following in vitro exposure to the incriminated drugs as biomarkers of HSR. Based on LTA results, HHV-6 reactivation and cytokine measurements, we establish that only doxycycline and TMP/SMX were involved in the HSR. As result of this analysis, the patient could continue to use the other 2 antibiotics safely.
authors: In Vitro Drug Safety and Biotechnology, Toronto, Ontario, Canada. manuela.neuman@utoronto.ca
authors: Manuela G
authors: MG
authors: Neuman
authors: Kristi K
authors: KK
authors: McKinney
authors: Radu M
authors: RM
authors: Nanau
authors: Vincent
authors: V
authors: Kong
authors: Izabella
authors: I
authors: Malkiewicz
authors: Tony
authors: T
authors: Mazulli
authors: George
authors: G
authors: Moussa
authors: Lawrence B
authors: LB
authors: Cohen
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology / Q000821:virology; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004318:Doxycycline / Q000009:adverse effects; D003875:Drug Eruptions / Q000276:immunology / Q000821:virology; D004342:Drug Hypersensitivity / Q000276:immunology / Q000821:virology; D015654:Herpesvirus 6, Human / Q000187:drug effects* / Q000472:pathogenicity*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D019349:Roseolovirus Infections / Q000209:etiology / Q000276:immunology; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced / Q000276:immunology / Q000821:virology; D057170:Translational Research, Biomedical; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects; D014775:Virus Activation / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D004318:Doxycycline