Erythema elevatum diutinum - evidence for disease-dependent leucocyte alterations and response to dapsone

Erythema elevatum diutinum (EED) is a type of leucocytoclastic vasculitis o f unknown aetiology. We report a patient with unusually widespread and disa bling EED that had been unresponsive to corticosteroids and antibiotics, bu t resolved on dapsone. Biopsies of fresh lesions showed typical features of leucocytoclastic vasculitis, with prominent neutrophil infiltration, marke d expression of the beta(2)-integrins CR3 and LFA-1, and increased mast cel l numbers. Older lesions exhibited granulation tissue and fibrosis, macroph ages were more dominant, beta(2)-integrins were expressed less markedly, an d mast cell numbers were lower. In vitro chemotaxis of the patient's periph eral blood neutrophils prior to treatment showed increased random migration and directed migration towards interleukin-8 (by 424%), but a profoundly d ecreased responsiveness towards the bacterial peptide analogue N-formyl-met hionyl-leucyl-phenylalanine (fMLP) (by 98%). These values returned to norma l after dapsone treatment and clinical improvement 5 months later. These fi ndings support the concept that in EED, activation via cytokines such as in terleukin-8 allows a selective recruitment of leucocytes to tissue sites, w hile immune complexes and bacterial peptides sustain the persistent local i nflammatory infiltrate and the leucocytoclastic vasculitis.