Understanding the Pathogenesis of HSV-Associated Erythema multiforme

Aurelian, Laure; Kokuba, Hisashi; Burnett, Joseph W.

doi:10.1159/000018000

Cited by 46 publications

(31 citation statements)

References 9 publications

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“…HSV DNA fragments with an intact pol gene are deposited at different anatomical skin sites where pol is expressed. Activated T cells are recruited to the site of pol expression resulting in an inflammatory cascade [12]. We had done a preliminary study earlier [unpubl.…”

Section: Discussionmentioning

confidence: 99%

Detection of Herpes simplex Virus Genomic DNA in Various Subsets of Erythema multiforme by Polymerase Chain Reaction

Sun

Tan

et al. 2003

Dermatology

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Background: The wide variation in the detection of herpes simplex virus (HSV) DNA (36–75%) by polymerase chain reaction (PCR) in erythema multiforme (EM) may be partly attributed to differences in case selection in terms of subsets of EM studied. Objective: To determine the frequencies of detection of HSV DNA in specific subsets of EM. Methods: Nested PCR was used to detect HSV DNA in skin biopsies with histologically proven EM. Results: PCR was performed on skin biopsies from 63 patients with EM. HSV DNA was detected in 3/11 (27.2%) of single-episode HSV-associated EM (HAEM), 6/10 (60%) of recurrent HAEM, 1/4 (25%) of single-episode idiopathic EM and 6/12 (50%) of recurrent idiopathic EM. HSV DNA was not detected in atypical EM (0/11), suspected drug-induced EM (0/9) or Stevens-Johnson syndrome (0/6). Conclusion: The overall PCR positive rates of HAEM (42.9%) and idiopathic EM (43.8%) were comparable suggesting that idiopathic EM is likely to be related to a subclinical HSV infection.

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Section: Discussionmentioning

confidence: 99%

Detection of Herpes simplex Virus Genomic DNA in Various Subsets of Erythema multiforme by Polymerase Chain Reaction

Sun

Tan

et al. 2003

Dermatology

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“…Infiltration of HAEM lesional skin by Vβ2 (but not Vβ3) cells in contrast to the presence of both Vβ2 and Vβ3 cells in HSV lesional skin is consistent with this interpretation. It also suggests that an immunological component directed against viral antigens is involved in HAEM pathogenesis [30]. Presumably, the reappearance of the broader TCR repertoire after lesion resolution reflects down-regulation of gene expression and the absence of Vβ2 cells in the skin [23, 24].…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Study of a Patient with Herpes-simplex-Virus-Associated Erythema multiforme: Viral Gene Expression and T Cell Repertoire Usage

Kokuba

Imafuku

et al. 1999

Dermatology

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Background: Erythema multiforme is a polymorphous self-limited, often recurrent eruption that can follow herpes simplex virus (HSV) infection, hereby designated HAEM. Studies of relatively large groups of patients during one recurrent episode indicated that HAEM pathogenesis is associated with HSV gene expression, Vβ2 T cell infiltration of lesional skin and altered T cell receptor (TCR) repertoire usage by HSV-stimulated peripheral blood mononuclear cells (PBMC). However, HAEM recurrences are not always preceded by overt HSV eruptions and virus cannot be isolated from HAEM lesional skin. Therefore, it is unknown whether all HAEM recurrences experienced by a given patient are HSV related. Objective: The studies described in this report were designed to examine whether all HAEM recurrences experienced by a given patient are HSV related. Methods: We describe one patient who was studied longitudinally during 6 HAEM recurrences and in the intervening lesion-free periods. Lesional skin from all HAEM episodes was studied for HSV gene expression and infiltration by Vβ2 and Vβ3 T cells. PBMC obtained at these times were assayed for TCR repertoire usage upon HSV stimulation. Results: Lesional skin from all HAEM episodes was positive for HSV gene expression (RNA and protein) as well as Vβ2 T cell infiltration. HSV-stimulated PBMC obtained at these times had an altered TCR repertoire characterized by a predominance of Vβ2 cells. The duration of viral gene expression, Vβ2 cell infiltration and altered TCR repertoire usage correlated with the duration of clinical symptoms. Conclusion: The data suggest that HSV and a virus-specific immunopathology component are involved in the causation of all HAEM episodes experienced by the patient.

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“…However, live HSV has seldom been recovered in culture (131), and inclusions typical of lytic HSV replication are not seen. If immunity to HSV proteins is involved in the pathogenesis of HAEM, as implied by some data (17,130,131,204), caution is warranted in therapeutic or prophylactic vaccination of individuals with a history of this disorder Corneal HSK is a serious HSV-1-related ocular disorder.…”

Section: Potential Toxicities Of Vaccinesmentioning

confidence: 99%

Recent Progress in Herpes Simplex Virus Immunobiology and Vaccine Research

2003

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Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) cause prevalent, chronic infections that have serious outcomes in some individuals. Neonatal herpes may occur when the infant traverses the cervix during maternal genital herpes. Genital herpes is a major risk factor for human immunodeficiency virus type 1 transmission. Considerable efforts have been made to design and test vaccines for HSV, focusing on genital infection with HSV-2. Several protein subunit vaccines based on HSV-2 envelope glycoproteins have reached advanced-phase clinical trials. These antigens were chosen because they are the targets of neutralizing-antibody responses and because they elicit cellular immunity. Encouraging results have been reported in studies of treatment of HSV-seronegative women with a vaccine consisting of truncated glycoprotein D of HSV-2 and a novel adjuvant. Because most sexual HSV transmission occurs during asymptomatic shedding, it is important to evaluate the impact of vaccination on HSV-2 infection, clinically apparent genital herpes, and HSV shedding among vaccine recipients who acquire infection. There are several other attractive formats, including subunit vaccines that target cellular immune responses, live attenuated virus strains, and mutant strains that undergo incomplete lytic replication. HSV vaccines have also been evaluated for the immunotherapy of established HSV infection

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Understanding the Pathogenesis of HSV-Associated Erythema multiforme

Cited by 46 publications

References 9 publications

Detection of Herpes simplex Virus Genomic DNA in Various Subsets of Erythema multiforme by Polymerase Chain Reaction

Detection of Herpes simplex Virus Genomic DNA in Various Subsets of Erythema multiforme by Polymerase Chain Reaction

Longitudinal Study of a Patient with Herpes-simplex-Virus-Associated Erythema multiforme: Viral Gene Expression and T Cell Repertoire Usage

Recent Progress in Herpes Simplex Virus Immunobiology and Vaccine Research

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