The Link between Hypersensitivity Syndrome Reaction Development and Human Herpes Virus-6 Reactivation

Pritchett, Joshua C.; Nanau, Radu M.; Neuman, Manuela G.

doi:10.1155/2012/723062

Cited by 33 publications

(30 citation statements)

References 92 publications

(213 reference statements)

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“…Among those negative for HHV6, 20 patients were treated with systemic corticosteroids (median total dose 5 mg kg À1 , range 1-16) and five patients were managed with supportive therapy alone. All four patients positive for HHV6 were treated with systemic corticosteroids (median total dose 6Á5 mg kg À1 , range [2][3][4][5][6][7][8][9][10][11][12][13][14]. Systemic corticosteroids were administered either intravenously or orally.…”

Section: Resultsmentioning

confidence: 99%

“…Some authors have raised concern that HHV6 positivity in the context of DHS might influence disease severity in affected patients. [6][7][8] In addition, it has been speculated that systemic corticosteroid treatment of those with DHS and concomitant expression of HHV6 may prolong the drug reaction, although it remains unclear whether the presence of HHV6 is pathogenic or only a nonpathogenic marker for disease severity. 5,6,9 Although systemic corticosteroids have been the mainstay of treatment, their efficacy remains controversial.…”

Section: What Does This Study Add?mentioning

confidence: 99%

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Human herpesvirus 6 involvement in paediatric drug hypersensitivity syndrome

et al. 2015

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Background HHV6-positivity in context of drug hypersensitivity syndrome (DHS) may influence disease severity. Systemic corticosteroid treatment of those with DHS, testing positive for HHV6, has been speculated to prolong the duration of disease. Objectives This study's objectives are to: (1) Evaluate whether DHS patients with HHV6-positivity develop a more severe illness compared to DHS patients without presumed reactivation in the pediatric population, and (2) Evaluate the response to systemic corticosteroid treatment. Methods Retrospective case series of 29 pediatric inpatients treated for DHS and tested for HHV6. HHV6-positive and -negative patients were identified and stratified to groups treated with and without systemic corticosteroids to examine their disease severity on the basis of hospital length-of-stay (LOS), total number of febrile days (Tfeb), and days until cessation of progression (CTP). Results HHV6-positive patients had similar demographic characteristics as HHV6-negative patients, but had significantly longer hospital LOS (11.5 days v 5 days, p=0.0386), Tfeb (12.5 days v 3 days, p=0.0325), and CTP (4 days v 2 days, p=0.0141). All HHV6-positive patients and most (80%) of the HHV6-negative patients received systemic corticosteroids. Among the HHV6-negative patients, those who received corticosteroids showed significantly shorter CTP than those who did not receive corticosteroids (3 days v 2 days, p=0.043). Additionally, there was a trend towards shorter hospital LOS and Tfeb among HHV6-negative patients who received corticosteroids when compared with those who did not, though these differences were not statistically significant. The most common inciting drugs included trimethoprim-sulfamethoxazole (33%), phenytoin (10%), and amoxicillin (10%). Conclusions HHV6-positivity with DHS is associated with a more severe disease course. Treatment with systemic corticosteroids was associated with a non-statistical trend toward reduced hospital LOS and febrile days, and a statistically reduced number of days until cessation of progression.

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Section: Resultsmentioning

confidence: 99%

Section: What Does This Study Add?mentioning

confidence: 99%

Human herpesvirus 6 involvement in paediatric drug hypersensitivity syndrome

et al. 2015

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“…HHV-6B reactivation causes encephalitis in immunosuppressed patients. HHV-6B reactivation is also associated with drug-induced hypersensitivity syndrome, and recent studies have suggested that it could be related to the severity of this disease (8,9).…”

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confidence: 99%

CD134 is a cellular receptor specific for human herpesvirus-6B entry

Tang

Serada

Kawabata

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

145

139

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Human herpesvirus-6B (HHV-6B) is a T lymphotropic β-herpesvirus that is clearly distinct from human herpesvirus-6A (HHV-6A) according to molecular biological features. The International Committee on Taxonomy of Viruses recently classified HHV-6B as a separate species. The primary HHV-6B infection causes exanthem subitum and is sometimes associated with severe encephalopathy. More than 90% of the general population is infected with HHV-6B during childhood, and the virus remains throughout life as a latent infection. HHV-6B reactivation causes encephalitis in immunosuppressed patients. The cellular receptor for HHV-6A entry was identified as human CD46, but the receptor for HHV-6B has not been clear. Here we found that CD134, a member of the TNF receptor superfamily, functions as a specific entry receptor for HHV-6B. A T-cell line that is normally nonpermissive for HHV-6B infection became highly susceptible to infection when CD134 was overexpressed. CD134 was down-regulated in HHV-6B-infected T cells. Soluble CD134 interacted with the HHV-6B glycoprotein complex that serves as a viral ligand for cellular receptor, which inhibited HHV-6B but not HHV-6A infection in target cells. The identification of CD134 as an HHV-6B specific entry receptor provides important insight into understanding HHV-6B entry and its pathogenesis.H uman herpesvirus-6B (HHV-6B) is a T lymphotropic β-herpesvirus (1) and is clearly distinct from human herpesvirus-6A (HHV-6A) according to their genetic and antigenic differences and their cell tropism (2-5). Recently the International Committee on Taxonomy of Viruses classified HHV-6B as a separate species.The primary HHV-6B infection causes exanthem subitum (6) and is sometimes associated with severe encephalopathy, whereas the diseases caused by HHV-6A are still unknown. More than 90% of the general population is infected with HHV-6B during childhood, and the virus remains throughout life as a latent infection (7). HHV-6B reactivation causes encephalitis in immunosuppressed patients. HHV-6B reactivation is also associated with drug-induced hypersensitivity syndrome, and recent studies have suggested that it could be related to the severity of this disease (8, 9).HHV-6A can infect a broader variety of human cells than HHV-6B (10), although the homology between HHV-6A and -6B is almost 90% over their entire genome (11-13). Human CD46 has been shown to be a cellular receptor of , and its viral ligand is a glycoprotein (g) complex made up of viral glycoprotein H (gH)/glycoprotein L (gL)/glycoprotein Q1 (gQ1)/ glycoprotein Q2 (gQ2) (15). However, the HHV-6A gH/gL/gQ1/ gQ2 complex binds to its human cellular receptor, CD46, whereas the corresponding complex of HHV-6B does not bind to it (10, 15). Moreover, anti-CD46 antibody does not block HHV-6B infection into the cells, whereas it does HHV-6A infection, indicating that the cellular receptor exists specific for HHV-6B infection. Because HHV-6B remains as a lifelong latent infection in more than 90% of the population and causes severe disease, it is...

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“…Then, transient alteration in immune responses may induce reactivation of viral infections. The latter explains why the clinical findings continue after the patient stops taking the medication 2 3…”

Section: Discussionmentioning

confidence: 99%

DRESS syndrome potentially induced by allopurinol and triggered by influenza vaccine

et al. 2016

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Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, also known as drug-induced hypersensitivity syndrome (DHIS), is an acute, potentially life-threatening disease that includes skin rash, fever, haematological abnormalities and multiorgan involvement. Although its aetiopathogenesis is not exactly known, it is thought that inefficient drug detoxification leading to the accumulation of drug reactive metabolites causes autoimmune responses in skin and some internal organs, alters immune responses and induces reactivation of viral infections in people who have genetic predisposition. To the best of our knowledge, only one case of DRESS syndrome has been reported after delivery of the influenza vaccine, but the drug that induced the reaction in that case was sulfasalazine. We report a case of a 64-year-old woman, receiving allopurinol, who developed DRESS syndrome after taking the influenza vaccine.

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The Link between Hypersensitivity Syndrome Reaction Development and Human Herpes Virus-6 Reactivation

Cited by 33 publications

References 92 publications

Human herpesvirus 6 involvement in paediatric drug hypersensitivity syndrome

Human herpesvirus 6 involvement in paediatric drug hypersensitivity syndrome

CD134 is a cellular receptor specific for human herpesvirus-6B entry

DRESS syndrome potentially induced by allopurinol and triggered by influenza vaccine

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