Examination of non‐involved skin, previously involved skin, and peripheral blood for herpes simplex virus DNA in patients with recurrent herpes‐associated erythema multiforme

Abstract

The association between infection with HSV and the subsequent development of erythema multiforme is well established, although the role that the virus plays in the pathogenesis of this disorder is not known. HSV DNA has been detected in cutaneous lesions of herpes-associated erythema multiforme (HAEM), and it has been suggested that the tissue damage seen in these lesions is virus-specific. In the current, prospective study, we examined biopsies of lesional, non-involved, and previously involved but healed skin, in addition to specimens of peripheral blood, from patients with HAEM, for HSV DNA by using the polymerase chain reaction. HSV DNA was detected in lesional skin of 10 of 11 patients compared to 2 of 11 non-involved skin biopsies obtained at the same time. HSV was present in 4 of 6 blood specimens obtained during the acute episode. Five patients returned 3 months after the acute episode resolved for biopsies of previously involved skin. HSV was detected in 4 of these 5 biopsies. Thus, the presence of HSV DNA in the skin of patients with HAEM appears to be predominantly in areas of clinical involvement; the virus remains in those cutaneous sites for up to 3 months without evidence of clinical disease; and HSV DNA may be detected in the peripheral blood cells during acute HAEM. Based on these findings, we suggest that the virus plays a role in lesion development, that the skin may function as a site of viral persistence, and that hematogenous spread of viral DNA may be an important factor in the development of HAEM.

Understanding the Pathogenesis of HSV-Associated Erythema multiforme

“…and (2); what role does HSV play in HAEM pathogenesis? We conclude that the virus does not persist in the skin because: (1) it cannot be isolated from HAEM lesional skin, even by cocultivation which results in virus isolation from latently infected ganglia [6, 7, 9], and (2) HSV DNA is cleared from healed HAEM lesional skin [4, 6, 8]. The virus could reach the periphery by axonal or vascular transport.…”

“…obs.]. By contrast, HSV DNA was detected in circulating leukocytes from HAEM patients [8], suggesting that viral genetic material (not the whole virus) is transported by the vascular route. We associate HAEM pathogenesis with viral DNA fragments transported to peripheral skin sites, because in PCR with equally sensitive primers for HSV genes that span the entire viral genome, only one gene (DNA polymerase [Pol]) was present and expressed in HAEM lesional skin [5, 6, 7].…”

“…Clearance of HSV DNA from the skin could result from flushing by the vascular system or extrusion by natural epidermal desquamation. It was delayed in HAEM as compared to HSV patients [4, 6, 8]. …”

“…Specimens obtained from the proximal area of the same dermatome as acute HAEM lesional skin were free of HSV DNA, arguing against axonal transport [Kokuba et al, submitted]. Vascular transport of the virus is also unlikely as the virus was never recovered from the blood, even during relatively frequent consecutive sampling of the same patient beginning at the time of HSV episodes and throughout HAEM development [7, 8unpubl. obs.].…”

Systemic Lupus Erythematosus Associated with Rowell's Syndrome

“…This cell-mediated response in classical EM is elicited by T cells responding to a limited triggering antigenic epitope, which include infections (herpes simplex, Mycoplasma pneumoniae) or drugs (antibiotics, antiepileptics, non-steroid antiinflammatory, and sulfonamides). Keratinocytes become antigenic through drug-hapten binding to keratinocytes or in the setting of viral infections molecular mimicry or possible incorporation of viral DNA into the cell rendering it antigenic [2,8].…”