Drug-Induced Hypersensitivity Syndrome due to Mexiletine Hydrochloride Associated with Reactivation of Human Herpesvirus 7

Abstract

It has been suggested that reactivation of human herpesvirus 6 (HHV-6) infection may be involved in the pathogenesis of drug-induced hypersensitivity syndrome. We report a 45-year-old Japanese man who developed a generalized papuloerythematous rash, fever, hepatitis, lymphadenopathy and lymphocytosis with an increased number of atypical lymphocytes. He was diagnosed with DIHS due to mexiletine hydrochloride based on laboratory data, results of a patch test and the clinical course of his complaint, and was treated with systemic steroids. In order to determine whether HHV-6 or -7 was associated with the patient’s disease, serological assays and PCR were carried out. Significant increases in antibody titers against HHV-6 and -7 were observed from day 12 to 24. From PCR analysis, none of the peripheral blood mononuclear cells or skin tissue samples contained HHV-6 DNA. All samples, however, were found to contain HHV-7 DNA. Reactivation of HHV-7 could be responsible for drug-induced hypersensitivity syndrome.

Occupational Trichloroethylene Hypersensitivity Syndrome with Human Herpesvirus-6 and Cytomegalovirus Reactivation

“…Recently, we observed a patient who developed a severe generalised rash with liver dysfunction, associated with the reactivation of HHV-6 and cytomegalovirus (CMV), after exposure to TCE. In addition, the characteristics of this patient, including the clinical findings and period of reactivation of these two viruses after onset, closely resembled those of drug-induced hypersensitivity syndrome (DIHS) [4,5,6,7], also referred to as drug rash with eosinophilia and systemic symptoms (DRESS) [8,9]. This is the first report describing the reactivation of both HHV-6 and CMV in HS caused by TCE.…”

“…DIHS [4,5,6,7], which is also referred to as DRESS [8,9], is characterised by a serious adverse systemic reaction that usually appears after 3–6 weeks of exposure to certain drugs such as anticonvulsants and allopurinol [4,5,6,7]. DIHS is frequently associated with the reactivation of HHV-6 [4,5,6,7,9], and the reactivation of HHV-7, CMV or Epstein-Barr virus has also been reported [7,21,22].…”

“…The prednisolone was tapered off with the improved clinical symptoms. Given the onset, and because the clinical findings including the facial oedema, scales and crusts around the nose and lips, maculopapular eruptions and relapse during the course were quite similar to those of DIHS/DRESS [4,5,6,7,8,9,10], we examined whether certain herpesviruses had been reactivated. As shown in table 1, serum HHV-6 DNA measured by using real-time PCR, as described previously [4,10], was detected 4 weeks after the onset (and only at this point).…”

Carbamazepine Hypersensitivity Syndrome Triggered by a Human Herpes Virus Reactivation in a Genetically Predisposed Patient

“…Moreover, among patients receiving penicillins and other antimicrobial agents, the incidence of rashes is significantly higher in those with infectious mononucleosis [3]. For carbamazepine and other anticonvulsants, the association between reactivation of HHV, in particular HHV 6 and 7, and the development of hypersensitivity syndrome has been previously reported [15]; the reactivation of HHV has been associated even with hypersensitivity syndromes caused by other molecules like cyanamide [16] or mexiletine hydrochloride [17]. For all these drug-related hypersensitivity reactions, virus-induced immune modulation has been proposed as the triggering factor [5].…”

Hypereosinophilia Associated with Increased Serum Levels of Carcinoembryonic Antigen

“…The most common reported drugs that cause DIHS are anticonvulsants, sulfasalazine, dapsone, minocycline, and mexiletine chloride (11)(12)(13). The main symptoms of DIHS are generalized exanthematous eruption, sometimes with small pustules, facial edema, high fever, systemic lymphadenopathy, leukocytosis, eosinophilia, atypical lymphocytosis and liver dysfunction (11,14,15 (17).…”