An immunopathological study of herpes‐associated erythema multiforme

Abstract

Any pathogenetic mechanism proposed for erythema multiforme (EM) must account for the prominent mononuclear cell infiltrate in the skin lesions. The purpose of this study was to characterize immunopathologically, with monoclonal antibodies to human leukocyte antigens, the inflammatory cells in early target lesions of recurrent herpes-associated EM. Cryostat sections of snap-frozen skin biopsies were studied by the avidin-biotin immunoperoxidase technique with use of the following monoclonal antibodies: anti-HLA-DR, anti-Leu M5, anti-Leu 4 + 5b, anti-Leu 3a + 3b, anti-Leu 2a, anti-Leu 14, and anti-Leu 6. The dermal mononuclear inflammatory infiltrate in the EM biopsies consisted of monocyte-macrophages and T-lymphocytes, with both helper and suppressor T cells present. Both the dermal inflammatory infiltrate and the overlying keratinocytes were strongly HLA-DR positive. No definite alteration of Langerhans cell number or distribution was noted. These findings are consistent with the characteristics seen in cell-mediated immune reactions in the skin and point to this as a likely immune mechanism for the tissue damage of EM.

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

“…However, HSV-specific immune responses are similar in HAEM and HSV patients [6, 7, 8, 9]. Indeed, our patient had HSV neutralizing antibody (data not shown) and his PBMC proliferated in response to HSV antigen (22,377 ± 6,011 cpm) at levels similar to those seen for HSV patients [6, 11, 14].…”

“…Indeed, HSV DNA was identified in HAEM lesional skin by polymerase chain reaction (PCR), and viral gene expression was associated with lesion development [1, 2, 3, 4, 5, 6]. Monocytes/ macrophages, plasma cells and T cells were seen in lesional skin, with CD4+ lymphocytes outnumbering CD8+ lymphocytes [7, 8, 9], a distribution significantly different from that in normal skin and buccal mucosa [8]. However, HSV-specific antibody, T cell responses and the CD phenotype of HSV-responding T cells was similar in HAEM and HSV patients [6, 7, 8, 9].…”

“…Monocytes/ macrophages, plasma cells and T cells were seen in lesional skin, with CD4+ lymphocytes outnumbering CD8+ lymphocytes [7, 8, 9], a distribution significantly different from that in normal skin and buccal mucosa [8]. However, HSV-specific antibody, T cell responses and the CD phenotype of HSV-responding T cells was similar in HAEM and HSV patients [6, 7, 8, 9]. More recent studies of relatively large numbers of patients during one recurrent episode and after its resolution indicated that HSV-stimulated peripheral blood mononuclear cells (PBMC) from patients with acute, but not healed, HAEM lesions have a qualitatively altered T cell receptor (TCR) repertoire which is not seen in patients with HSV alone or with drug-induced EM [6].…”

Understanding the Pathogenesis of HSV-Associated Erythema multiforme

“…CD4+ T cells outnumbered the CD8+ cells, a distribution significantly different from that in normal skin [10]. Also, lesional keratinocytes expressed HLA class II antigen which may be induced by immune interferon (IFNγ) resulting from a cell-mediated immune reaction in the skin [11]. …”

“…The mononuclear cell infiltrate and the epidermal damage that characterize the HAEM histopathology are consistent with an immunologically mediated attack by cytotoxic T lymphocytes and/or natural killer cells and monocytes directed against antigenic targets located in epidermal cells. Evidence in support of a cell-mediated immune reaction includes a report of a circulating lymphokine and the presence of helper (CD4+) and suppressor/cytotoxic (CD8+) T cells and macrophages in lesional skin [10, 11, 12]. CD4+ T cells outnumbered the CD8+ cells, a distribution significantly different from that in normal skin [10].…”