Tumor necrosis factor–alfa in nonhealing venous leg ulcers

BackgroundVenous leg ulcers are responsible for more than half of all lower extremity ulcerations, affecting more than one million Americans annually. Studies have demonstrated alterations in levels of proinflammatory cytokines in patients with chronic wounds, including tumor necrosis factor–alfa (TNFα), which may be implicated in wound chronicity.ObjectiveTo test the hypothesis that recalcitrant venous leg ulcers have increased local tissue TNFα as compared to normal skin.MethodsFive patients with nonhealing healing chronic venous leg ulcers were recruited. Two 4-mm punch biopsy specimens were obtained: one from the wound margin and one from noninvolved, non–sun exposed normal skin on the flexor aspect of the forearm. Tissue samples were processed using fixed with formalin stained by immunohistochemistry for TNFα. Qualitative and quantitative comparisons were made for the presence of TNFα receptor in all tissue samples, specifically comparing the presence of TNFα in nonhealing venous leg ulcer samples versus normal skin.ResultsThe overall staining score for nonhealing venous leg ulcers was significantly higher compared to respective normal skin samples (P = .01). In addition, immunostaining for TNFα was significantly less in the two nonhealing venous leg ulcers that were present for the shortest duration compared to the other ulcers of longer duration (P = .048).LimitationsThe small sample size may mitigate the clinical implications of findings.ConclusionsIncreased levels of TNFα in nonhealing venous leg ulcers, especially those of longer duration, implies that excessive inflammation may be causal in wound chronicity and suggests potential therapeutic alternatives.