Erythema multiforme lesions are associated with expression of a herpes simplex virus (HSV) gene and qualitative alterations in the HSV-specific T-cell response

Abstract

A common form of erythema multiforme, herpes-associated erythema multiforme (HAEM), occurs following infection with herpes simplex virus (HSV). Here we report that HSV gene expression and the qualitative nature of the virus-specific T-cell responses are related to HAEM lesion development. Skin from HAEM lesions and 1-3 months healed HAEM lesional skin were positive for the viral DNA polymerase gene (Pol) by polymerase chain reaction. However, gene expression as determined by immunohistochemistry with Pol-specific antibody was seen only in HAEM lesions, suggesting that lesion development is associated with Pol gene expression. Similar HSV-specific T-cell lymphoproliferative responses were seen in peripheral blood mononuclear cells (PBMCs) from patients with acute or healed HAEM lesions or HSV lesions and from HSV-seropositive patients with unrelated inflammatory diseases. However, the T-cell receptor variable (V beta) chain repertoire of HSV-stimulated PBMCs obtained from HAEM lesions was altered; the prevalence of some families of variable chain (namely V beta 16 and V beta 19) was reduced, whereas the prevalence of others was increased (namely V beta 2 and V beta 7). V beta 2 cells were found in HAEM lesional skin positive for Pol antigen, suggesting that these cells home to viral antigen-positive skin.

Erythema Multiforme-Oral Variant: Case Report and Review of Literature

“…In one study, it has been reported that 71% of the EMm/EMM attacks were precipitated by a preceding HSV infection [9], particularly herpes labialis [10]. Typically, EMm/EMM lesions develop 10-14 days following clinical manifestations of HSV infection [11].…”

Erythema Multiforme Minor: A Revision

“…However, it was not seen in uninvolved skin, adjacent to the HAEM lesions. The skin from 1-3 months healed HAEM also were PCR positive for the viral Pol gene [32] . In agreement with Imafuku et al [34] the viral DNA is cleared from the skin within 1-1,5 months of HSV lesion resolution, whereas HAEM lesional skin is still positive 1-3 months after healing.…”

“…Suggesting an explanation for the physiopathology of these lesions, some authors hypothesized that HSV is engulfed by macrophages at the site of the HSV lesion that precedes HAEM development. These phagocyte cells are non-permissive for HSV replication, resulting in a degradation of the viral DNA and dissemination of fragments to peripheral skin [31,32] . HSV DNA fragments with an intact DNA polymerase gene (Pol) are deposited at different anatomical skin sites where Pol is expressed.…”

“…The CD4 lymphocytes are the main cells involved in the lesional skin. There are also the contribution of non-specific effectors cells (neutrophils, basophils, natural killer cells, lymphokine-activated killer cells and macrophages) activated and recruited to the skin by cytokines generated by the antigen-activated T cells [20,32] . Generally, HSV-1 infections and acute diseases of the upper respiratory tract, two recognized triggers of EM, mostly of the minor type, occur in infancy and in the preschool years.…”

Ulcerative Lesions of the Mouth: An Update for the General Medical Practitioner

“…The ulcers comprise a few small superficial ulcers of the oral mucosa. EBV is more typically associated with the ulcers of some non-Hodgkin's lymphomas 19 or white patches termed oral hairy leukoplakia (OHL) that may arise in cases of immunodeficiency (e.g. HIV, or with corticosteroid or other systemic immunosuppressant therapy, etc.).…”