Tumor necrosis factor-alfa in nonhealing venous leg ulcers

Background: Venous 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 (TNF alpha), which may be implicated in wound chronicity. Objective: To test the hypothesis that recalcitrant venous leg ulcers have increased local tissue TNF alpha as compared to normal skin. Methods: Five 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 TNF alpha. Qualitative and quantitative comparisons were made for the presence of TNF alpha receptor in all tissue samples, specifically comparing the presence of TNF alpha in nonhealing venous leg ulcer samples versus normal skin. Results: The overall staining for nonhealing venous leg ulcers was significantly higher compared to respective normal skin samples (P = .01). In addition, immunostaining for TNF alpha 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). Limitations: The small sample size may mitigate the clinical implications of findings. Conclusions: Increased levels of TNF alpha 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. (J Am Acad Dermatol 2009;60:951-5).