Shiohara T, Nickoloff B J, Sagawa Y, Gomi T, Nagashima M
Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan.
Arch Dermatol. 1989 Oct;125(10):1371-6. doi: 10.1001/archderm.125.10.1371.
The pathogenic mechanism of preferential localization to certain skin sites of fixed drug eruption lesions has remained unknown. Skin biopsy specimens were obtained from four patients with fixed drug eruptions at various time points after final exposure to the causative drug and were studied immunohistologically using monoclonal antibodies to intercellular adhesion molecule-1 (ICAM-1), lymphocyte function-associated antigen-1, and HLA-DR. The expression of ICAM-1 by keratinocytes was confined exactly to the involved epidermis. In contrast, the expression of HLA-DR by keratinocytes was observed not only in the involved epidermis but also in the uninvolved epidermis, although to a lesser extent. In general, the intensity of expression of ICAM-1 by keratinocytes correlated well with the degree of epidermal invasion of lymphocytes but not with the degree of dermal lymphocytic infiltration. Interestingly, in fixed drug eruption lesions, basal keratinocytes still showed intense reactivity for ICAM-1 6 to 10 days after final exposure to the causative drug, at which time the expression of HLA-DR was already down-modulated. Such a strong dissociation between the expression of ICAM-1 and HLA-DR on lesional keratinocytes was never observed at any time in the normal skin of control patients challenged with dinitrochlorobenzene. These results suggest that localized misregulated expression of ICAM-1 by the keratinocytes may be one factor that explains the preferential site-specificity characteristic of fixed drug eruptions.
固定性药疹皮损优先定位于某些皮肤部位的致病机制尚不清楚。从4例固定性药疹患者末次接触致病药物后的不同时间点获取皮肤活检标本，并用抗细胞间黏附分子-1（ICAM-1）、淋巴细胞功能相关抗原-1和HLA-DR的单克隆抗体进行免疫组织学研究。角质形成细胞ICAM-1的表达严格局限于受累表皮。相比之下，角质形成细胞HLA-DR的表达不仅在受累表皮中可见，在未受累表皮中也有表达，不过程度较轻。一般来说，角质形成细胞ICAM-1的表达强度与淋巴细胞的表皮浸润程度密切相关，而与真皮淋巴细胞浸润程度无关。有趣的是，在固定性药疹皮损中，末次接触致病药物6至10天后，基底角质形成细胞对ICAM-1仍表现出强烈反应，而此时HLA-DR的表达已下调。在用二硝基氯苯激发的对照患者的正常皮肤中，任何时候都未观察到皮损角质形成细胞上ICAM-1和HLA-DR表达之间如此强烈的分离。这些结果表明，角质形成细胞ICAM-1的局部表达失调可能是解释固定性药疹优先位点特异性特征的一个因素。
