Adhesion molecule expression and endothelial cell activation in cutaneous leukocytoclastic vasculitis. An immunohistologic and clinical study in 42 patients.

OBJECTIVES

To investigate the sequential expression of adhesion molecules on endothelium and inflammatory cells in cutaneous leukocytoclastic vasculitis, and the relation of these adhesive molecules with clinical and histologic variables.

DESIGN

An immunohistochemical analysis (streptavidin-biotin-peroxidase technique) of 42 vasculitic lesions of up to 96 hours was performed using a panel of monoclonal antibodies specific for different adhesion molecules. Twenty normal skin samples and 3 perilesional specimens served as control samples. A clinical protocol was also performed, and patients were followed up for 1 to 5 years.

SETTING

A clinicopathologic research unit of a university hospital.

PATIENTS

Forty-two patients, 21 women and 21 men, aged 22 to 79 years, with cutaneous leukocytoclastic vasculitis.

INTERVENTIONS

Three skin biopsy specimens of vasculitic lesions from each patient were obtained for histopathologic examination on paraffin, direct immunofluorescence, and immunohistochemical analysis on cryostatic tissue sections.

MAIN OUTCOME MEASURES

The histologic characteristics and the immunohistochemical-stained specimens were evaluated by 3 independent investigators, using a semiquantitative method.

RESULTS

Increased endothelial expression of very late activation antigen-1, HLA-DR, and intercellular adhesion molecule-1 was observed. The induction of E-selectin expression was more marked in recent lesions (P < .001) and correlated with the proportion of infiltrating neutrophils (P = .03). Endothelial expression of vascular cell adhesion molecule-1 was restricted to developed lesions. Most infiltrating cells were neutrophils expressing Mac-1. In 1 patient, lymphocyte function associated antigen-1 expression was also up-regulated. No significant increase in CD3, CD8, or CD71 immunoreactivity was found. An up-regulation of perivascular cells expressing HLA-DR and vascular cell adhesion molecule-1 was observed in vasculitic lesions. This cellular staining correlated with long-term evolution of the disease (P = .04).

CONCLUSIONS

Adhesion molecules are sequentially upregulated in cutaneous leukocytoclastic vasculitis. The results of this study support the possible involvement of E-selectin in mediating recruitment of neutrophils expressing Mac-1.