Deficient functional wound closure as measured by elevated trans-epidermal water loss predicts chronic wound recurrence: An exploratory observational study

Abstract

A single-center, prospective, observational pilot study was performed to evaluate wound healing endpoint and recurrence by measuring transepidermal water loss (TEWL) post-closure at the site of wound repair. Patients with clinically-defined chronic wounds (such as pressure ulcers, diabetic ulcers, and trauma wounds) who visited the Plastic Surgery outpatient department or were in-patients at the All India Institute of Medical Sciences, Rishikesh, India, and were referred for chronic wound management, were enrolled. Non-invasive point-of-care TEWL measurements were obtained, from closed wound-site and contralateral healthy skin site, starting from confirmation of closure (post-closure, V0) continuing every 2 weeks for a maximum of five visits or until the wound recurred. Statistical analyses of the data involved logistic regression and likelihood ratio chi-square tests to assess differences in TEWL at visit 0 (V0) between the closed wound site and reference skin, with the TEWL score as the sole predictor of recurrence. Of the 72 subjects that completed the study, 44 (61%) showed no recurrence and 28 (39%) had wounds that recurred over a period of 12 weeks. A significant association was found between the V0 (post-closure) TEWL score and the odds of wound recurrence, both in univariate analysis (OR [95%CI] = 1.26[1.14,1.42] (p < 0.001) and after adjusting for covariates in multivariable analysis (OR [95%CI] = 1.34[1.19,1.61] (p < 0.001). The likelihood ratio chi-square analysis demonstrated that the V0 TEWL score is a significant universal predictor of recurrence across all wound types studied. Cases of closed wounds with subsequent recurrence showed an overall higher post-closure V0 TEWL score, compared to those who did not have a wound recurrence, across visits. The TEWL score cut-off value predictive of recurrence was 24.1 g.m^-2.h^-1 (AUC = 0.967). The outcome of this pilot study on a wide range of chronic wounds leads to the hypothesis that post-closure TEWL at the site of wound healing is a reliable biomarker of wound recurrence. It also raises the question whether the clinical endpoint of wound closure should include re-establishment of skin barrier function as additional criterion. The current standard of care wound closure endpoint calls for re-epithelialization of the wound with no discharge for two consecutive weeks disregarding the functional parameter of restoration of skin barrier function at the wound-site.

Keywords: Transepidermal water loss measurement (TEWL); Wound healing; Wound recurrence.

Fig. 1

Study enrollment flowchart and design.

Fig. 2

Increased Difference Between Healed and Reference Site TEWL Values is Associated with Wound Recurrence. (A) Line plot, each line is a separate patient and (B) box plot showing wound/reference TEWL at each visit post-closure of wound. **P < 0.001; Wilcoxon Rank sum test.

Fig. 3

Difference Between Healed Wound and Reference Site TEWL at First Visit Post-Closure is a Good Predictor of Wound Recurrence. (A) Plot showing estimated recurrence probability based on the difference between wound site and reference site TEWL at visit 0. (B) Chart exhibited increase in probability of recurrence for incremental difference of 10 TEWL values (C) Optimal cut point difference in TEWL for wound site vs reference site at visit 0 post-closure using Youden’s J statistics.