An immunopathological study of herpes-associated erythema multiforme

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.     

Oral acyclovir prevents herpes simplex virus-associated erythema multiforme

A young woman suffering from recurrent erythema multiforme associated with relapsing gluteal herpes simplex is presented, in whom long-term treatment with oral acyclovir prevented herpes episodes as well as erythema multiforme.     

Complement deposition in the skin of patients with herpes-associated erythema multiforme

Granular staining for C3 by direct immunofluorescence is a frequent finding along the dermoepidermal junction and in papillary blood vessels in the early skin lesions of erythema multiforme. In order to evaluate whether the complement cascade is activated by the classical or alternative pathway, ten biopsies from patients with herpes-associated erythema multiforme, which were positive for granular C3 along the dermoepidermal junction, were stained by an immunofluorescence technic for other complement components. Staining for the components of classical pathway, C1q and C4, were found in none of the ten biopsies. However, in nine of ten biopsies, granular staining for properdin was present along the dermoepidermal junction. These findings suggest complement activation by the alternative complement pathway in herpes-associated erythema multiforme.     

阿昔洛韦治疗多形红斑疗效观察

用阿昔洛韦口服０．２ｇ,每日５次治疗了２１例多形红斑患者,与对照组相比,痊愈时间明显缩短。此结果说明阿昔洛韦是治疗多形红斑的有效药物,并提示多形红斑的发生可能与疱疹病毒感染有关。     

Oral manifestations of erythema multiforme

Erythema multiforme is a reactive mucocutaneous disorder in a disease spectrum that comprises a self-limited, mild, exanthematic, cutaneous variant with minimal oral involvement (EM minor) to a progressive, fulminating, severe variant with extensive mucocutaneous epithelial necrosis (SJS and TEN). Significant differences exist among EM minor, EM major, SJS, and TEN with regards to severity and clinical expression; however, all variants share two common features: typical or less typical cutaneous target lesions and satellite-cell or more widespread necrosis of the epithelium. These features are considered to be sequelae of a cytotoxic immunologic attack on keratinocytes expressing non-self-antigens. These antigens are primarily microbial (viruses) or drugs and in rare instances histocompatibility antigens [5]. Although the precise pathogenesis is unknown, there is a tendency to consider EM both minor and major as part of one spectrum that is most often triggered by viral infections, and SJS and TEN as a separate one most often elicited by drugs with EM major and SJS representing a bridge in the continuum of EM. The oral manifestations of the spectrum of EM range from tender superficial erythematous and hyperkeratotic plaques to painful deep hemorrhagic bullae and erosions. Other mucosal surfaces including ocular, nasal, pharyngeal, laryngeal, upper respiratory, and anogenital may be involved. Scarring sequelae from ocular and pharyngeal involvement cause morbidity. The oral EM variant is an underrecognized form of EM. Most patients have chronic or recurrent oral lesions only, but one third have oral and lip lesions and one quarter have oral, lip, and skin lesions. This variant is a reaction pattern similar to EM minor, EM major, SJS, and TEN. The diagnosis of oral EM is one of exclusion. Careful clinical evaluation for other chronic mucocutaneous diseases, such as pemphigus, paraneoplastic pemphigus, mucous membrane pemphigoid, and lichen planus, is a necessary component of the diagnosis. The value of a biopsy specimen studied by both routine histopathologic and immunopathologic methods is fundamental to excluding the other causes for this variant of EM.     

Oral terbinafine and erythema multiforme

Two patients developed classical erythema multiforme while taking oral terbinafine. A case of Stevens-Johnson syndrome occurring after terbinafine therapy has recently been described, but there have been no published reports of an association with erythema multiforme until now.     

A double-blind, placebo-controlled trial of continuous acyclovir therapy in recurrent erythema multiforme

Twenty patients who suffered from more than four attacks of erythema multiforme (EM) per year were enrolled in a 6-month double-blind, placebo-controlled trial of acyclovir 400 mg twice daily. Fifteen patients had disease precipitated by recurrent herpes simplex. In the acyclovir-treated group the median number of EM attacks during the treatment period was zero, compared with three in the placebo-treated group (P < 0.0005, Wilcoxon rank sum test). Seven of the 11 patients treated with continuous acyclovir did not have any attacks of EM while taking the drug, and one showed almost complete disease suppression. Following treatment with acyclovir, two patients went into complete remission, whereas all individuals in the placebo group continued to have attacks. In the acyclovir-treated group nine of the 11 patients had herpes simplex-precipitated disease. One of the two patients with idiopathic disease showed complete disease suppression while on acyclovir, lending support to the view that idiopathic recurrent EM may be related to subclinical herpetic infection. In this study, we have shown that continuous acyclovir therapy can completely suppress attacks of recurrent EM and, in some cases, may induce disease remission.     

The herpes-specific immune response of individuals with herpes-associated erythema multiforme compared with that of individuals with recurrent herpes labialis

Infection with herpes simplex virus (HSV) is the most common precipitating factor in the development of erythema multiforme (EM). It is not known why only a few of the many individuals who experience recurrent HSV infection also develop herpes-associated EM (HAEM), although a difference in the HSV-specific immune response has been postulated. The purpose of this study was to compare the HSV-specific immune response of individuals with HSV infection alone with that of individuals with HAEM. There were 21 patients in each of the two groups. Four parameters of the HSV-specific immune response were examined: (1) anti-HSV IgG titers were measured by ELISA; (2) antibody neutralization was assessed using a plaque assay; and (3) antibody-dependent complement-mediated cytotoxicity, and (4) antibody-dependent cellular cytotoxicity were investigated using a previously described in vitro HSV-specific cytotoxicity assay. No statistically significant differences were detected between the two patient groups. Thus, a difference in these HSV-specific immune mechanisms does not explain the development of HAEM in some individuals with recurrent HSV infection.Grant support: AI 16637 from the National Institutes of Allergy and Infectious Disease     

Histiocytic erythema multiforme

Erythema multiforme is histologically characterized by liquefactive degeneration along the dermal-epidermal junction, necrotic keratinocytes and a lymphocytic infiltrate. We report a 10-year-old boy with recurrent erythema multiforme major of undetermined etiology with unusual histologic findings. A skin biopsy taken at day 2 of his eruption revealed histologic features otherwise characteristic of erythema multiforme, but mediated instead by a CD68-positive infiltrate, resembling cutaneous Kikuchi's disease. To the best of our knowledge this is the first reported case of 'histiocytic' erythema multiforme.