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Fixed drug eruption. Expression of epidermal keratinocyte intercellular adhesion molecule-1 (ICAM-1)
T Shiohara1, B J Nickoloff, Y Sagawa
1Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan.
Abstract:
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.
Insights
Localized misregulated expression of intercellular adhesion molecule-1 (ICAM-1) by keratinocytes may explain why fixed drug eruptions reappear in the same skin sites. This finding offers insight into the pathogenesis of this condition.
Area of Science:
- Dermatology
- Immunohistology
- Pathogenesis of Skin Diseases
Background:
- The pathogenic mechanism behind the specific localization of fixed drug eruption (FDE) lesions remains unclear.
- Understanding FDE pathogenesis is crucial for managing recurrent drug reactions.
Purpose of the Study:
- To investigate the role of intercellular adhesion molecule-1 (ICAM-1) and HLA-DR expression in the site-specificity of FDE.
- To elucidate the immunohistological features of FDE lesions at the keratinocyte level.
Main Methods:
- Skin biopsy specimens from four FDE patients were analyzed immunohistologically.
- Monoclonal antibodies against ICAM-1, lymphocyte function-associated antigen-1, and HLA-DR were utilized.
- Expression patterns were studied at various time points post-drug exposure.
Main Results:
- ICAM-1 expression by keratinocytes was strictly localized to involved epidermis in FDE lesions.
- HLA-DR expression was observed in both involved and uninvolved epidermis.
- Persistent ICAM-1 expression on basal keratinocytes, even after HLA-DR down-modulation, was noted in FDE.
Conclusions:
- Localized, misregulated ICAM-1 expression by keratinocytes is a potential factor in the site-specificity of FDE.
- The distinct expression patterns of ICAM-1 and HLA-DR in FDE keratinocytes differentiate it from normal skin responses.