The association between
erythema multiforme (EM) and herpes simplex virus (HSV)
infection has long been appreciated, although the exact role which HSV may play in the pathogenesis of this herpes-associated EM (
HAEM), is unknown. Previous studies have suggested, but not definitively demonstrated, the presence of HSV in lesions of
HAEM. The presence of HSV would support the hypothesis that an immune-mediated response directed against HSV-specific
antigens in the skin is central to lesion development in
HAEM. The purpose of this study was to examine lesions of EM for the presence of HSV
DNA by using the polymerase chain reaction (PCR). In addition, in situ hybridization using an HSV-specific
RNA probe was performed to further localize the HSV
nucleic acids within the skin.
DNA was extracted from
formalin-fixed,
paraffin-embedded specimens of cutaneous lesions of
HAEM and also from EM for which no precipitating factor could be documented, otherwise known as idiopathic EM (
IPEM).
DNA from lesions of
bullous pemphigoid served as a negative control. Using PCR to specifically amplify HSV sequences which might be present, and then performing Southern analysis, we demonstrated HSV
DNA in 9/13
HAEM and 6/9
IPEM biopsies. No HSV was detected in six lesions of
bullous pemphigoid. In situ hybridization of three cutaneous
HAEM lesions using an 35S-labeled HSV-specific
RNA probe localized the HSV
nucleic acids predominantly to the epidermis. Three biopsies of chronic
dermatitis, used as negative controls, did not demonstrate this specific hybridization. These findings confirm the presence of HSV in lesions of
HAEM and are consistent with the concept of an HSV-specific immune-mediated pathogenesis for this disease. In addition, most cases of
IPEM appear to be herpes associated despite the absence of clinically apparent HSV
infection.