Haemorrhagic cellulitis: a syndrome associated with tumour necrosis factor-α

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Abstract
A newly defined clinical syndrome, haemorrhagic cellulitis, is described in 12 patients. The syndrome consists of an acute onset of extremely painful erythema affecting dependent areas, followed by dermal haemorrhage and sloughing of the overlying epidermis, and requiring both antibiotics and systemic corticosteroids for complete resolution. The patients usually have demonstrable Gram-negative or Gram-positive infection, of non-cutaneous origin, and underlying systemic disease. Vacuolopathic necrosis of epidermal keratinocytes, and damaged vascular endothelium of the dermal blood vessels can be demonstrated by light and electron microscopy, as well as by lectin studies. Immunocytochemical studies reveal the presence of activated macrophages and T lymphocytes. We believe the syndrome is due to lipopolysaccharide-induced or bacterial mitogen-induced tumour necrosis factor-alpha (TNF-alpha), secreted by previously primed activated macrophages in a second-set response. TNF-alpha characteristically injures endothelial cells and epidermal keratinocytes. It is thought to induce its cytotoxic effects partly via neutrophil degranulation, and partly via DNAase activation, with resultant DNA fragmentation and cell lysis. Corticosteroids have been shown not only to inhibit TNF-alpha secretion by activated macrophages, but also to block its cytotoxicity, thus accounting for the extremely rapid clinical response to this drug in conjunction with adequate and appropriate antibiotic therapy.