Cytotoxic T lymphocytes and phenotypically abnormal epidermal dendritic cells in fixed cutaneous eruptions.
Fixed cutaneous eruptions are erythematous plaques or bullae that recur, often after drug ingestion, at precisely the same cutaneous sites. The study of this condition may provide insight into the mechanisms responsible for regionally localized, immunologically mediated dermatoses. Biopsy specimens from both advancing borders and established centers of fixed eruptions were studied by immunofluorescence microscopy, light microscopy (1-micron sections), and transmission electron microscopy, and with a panel of monoclonal antibodies to Langerhans cells and subsets of T lymphocytes. The dermal inflammatory infiltrates of the advancing edges of the lesions were composed predominantly of OKT4/Leu-3a-positive lymphoid cells in perivascular array. In more established regions (the centers of the lesions), the majority of mononuclear cells were OKT8-positive lymphocytes disposed along the dermal-epidermal junction and migrating into the epidermis through focal defects in the basement membrane. In these areas, keratinocyte reactivity for anti-HLA-DR antibody and the apposition of intraepidermal lymphocytes to degenerating keratinocytes were observed. T6-positive epidermal dendritic cells were observed in normal numbers in the epidermis, although extensive study failed to reveal characteristic Langerhans cell granules within these cells. It is concluded that fixed cutaneous eruptions are characterized by an early vascular phase involving lymphocytes with helper/inducer phenotypes, and a later epidermal phase involving cytotoxic/suppressor cells. Potential effector cells with the phenotypic characteristics of cytotoxic T cells appear to represent important mediators of the epidermal damage characteristic of fixed cutaneous eruptions. Morphologically abnormal epidermal dendritic cells may contribute to regionally altered antigen presentation and may thus be relevant to the recurrence of lesions at identical cutaneous sites.
G F
GF
Murphy
F J
FJ
Guillén
T C
TC
Flynn
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D003875:Drug Eruptions / Q000276:immunology / Q000473:pathology*; D004817:Epidermis / Q000276:immunology / Q000473:pathology*; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D006801:Humans; D007120:Immunochemistry; D007633:Keratins / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology*; D008297:Male; D010641:Phenotype; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology*
D000911:Antibodies, Monoclonal; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D007633:Keratins