Clinical Measurement of Transepidermal Water Loss

Abstract

Significance: Recent reports recognize transepidermal water loss (TEWL) as a critical objective parameter measuring clinical wound healing endpoint. At the site of wound repair, TEWL measures functional wound closure as marked by re-establishment of barrier function at the wound site. This review article addresses recent developments in clinical TEWL measurement in the context of human skin health and wound care. To that end, emphasis is placed on the review of registered clinical studies reported in ClinicalTrials.gov for which TEWL results have been posted or published. Recent Advances: The U.S. Food and Drug Administration (FDA) defines complete wound closure as the achievement of 100% re-epithelialization of the wound surface, with no detectable exudate, drainage, or need for wound dressing, as verified during two sequential clinical assessments conducted at least 14 days apart. Clinically, wounds may meet this current FDA-recommended clinical criteria for wound closure, yet not achieve functional wound closure which requires the re-establishment of barrier function at the site of repair. Such wounds are likely to recur. High TEWL posthealing predicts wound recurrence. Thus, TEWL measurement at the site of repair posthealing is emerging as a significant measurement of wound healing endpoint. Critical Issues: Appropriate clinical measurement of TEWL requires a basic understanding of the related technologies and their appropriate use. Such understanding will help achieve the necessary rigor and reproducibility in clinical measurement. Future Directions: Recent reports on the critical significance of TEWL in wound care open new horizons wherein TEWL is likely to have broader applications involving altered skin barrier functions, such as during aging and other factors that determine skin health. Evidence to support revisiting the FDA definition of wound closure to include restoration of barrier function at the site of closure is strong. Widespread adoption of TEWL in wound care practices to determine functional wound closure is anticipated.

Keywords: TEWL; clinical trials; device; skin barrier function; transepidermal water loss.

Figure 1.

TEWL (g·m⁻²·h⁻¹) at different anatomical locations in healthy adult humans. A search was conducted in the PubMed database using the keywords “TEWL” OR “Transepidermal Water Loss,” with the “Article Type” field set to “Clinical Trial” to identify relevant articles related to TEWL (last accessed: March 16th, 2025). The initial search yielded 784 articles, of which 726 were excluded by filtering out studies published before 2024, leaving 58 studies for screening. After manual screening, seven studies^,– were included that met our predefined inclusion criteria by reporting baseline TEWL values (g·m⁻²·h⁻¹) on healthy adult skin (between 18–65 years of age), with both the anatomical measurement site and the TEWL measuring device specified. These studies were categorized based on the type of TEWL measurement device used: open chamber, closed chamber, or condenser chamber. An additional nine studies^,–, identified through targeted searches and examination of reference lists that fulfilled the same inclusion criteria and were incorporated into the final review. Reported values represent the average baseline TEWL, and standard deviations are provided in parentheses where available. TEWL, transepidermal water loss.

Figure 2.

Systematic review flow diagram searched on ClinicalTrials.gov registers. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) were used to guide the literature search and study selection process. A search was conducted on ClinicalTrials.gov to find studies relevant to TEWL. The search used the keywords “TEWL” OR “Transepidermal Water Loss” to identify studies incorporating TEWL measurements and last accessed on March 16th, 2025. Initially, 435 studies were identified (Table 2). Subsequently, the “Study Results” field was used as a filter to eliminate studies that had not posted their results, resulting in the exclusion of 385 studies and leaving 50 studies with results for further screening. During the initial screening, two clinical studies were found to be terminated and were therefore not included in the final analysis. In addition, seven studies were excluded for not including TEWL outcome measurements, leaving a total of 41 studies for full-text review. Below is the list of NCT numbers of the studies that are included in the review (n = 41): NCT06415292, NCT06034340, NCT05085730, NCT04718870, NCT04606134, NCT04559022, NCT04477187, NCT04447417, NCT04040933, NCT03927404, NCT03901144, NCT03804710, NCT03803059, NCT03743038, NCT03507036, NCT03370757, NCT03365934, NCT03332628, NCT03216265, NCT03197883, NCT03180645, NCT03119688, NCT03103906, NCT02930590, NCT02906566, NCT02839772, NCT02557698, NCT02216526, NCT02173054, NCT01963793, NCT01909713, NCT01856764, NCT01787461, NCT01375205, NCT01065714, NCT01015638, NCT00974480, NCT00964366, NCT00926367, NCT00819507, and NCT00097253. *To conduct the search for studies, the ClinicalTrials.gov register was used, using the search term “TEWL” or “Transepidermal Water Loss”. A total of 435 studies were identified and last accessed on March 16th, 2025. A supplementary list containing all NCT numbers for the total studies searched in ClinicalTrials.gov and the studies included in the review is provided. **After download, the study status was sorted and a two studies with the “TERMINATED” designator were excluded.

Figure 3.

ClinicalTrial.gov studies categorized by type of (a) skin studies and by type of TEWL measuring devices used in clinical studies. (a) Illustrates the distribution of studies across five main skin study groups, namely (1) Wounded Skin (3), (2) Healthy Skin (20), (3) Atopic Dermatitis (8), (4) Acneiform Skin (9), and (5) Infant Skin (1). These divisions were made manually based on the information provided in the Study Details and Results Overview sections of each study, resulting in a total of 41 studies categorized. (b) Categorizes the studies by device type used in measuring TEWL into three categories: (1) Open Chamber System (21), (2) Closed Chamber System (1), and (3) Condenser Chamber System (8), including the device names. Among the 41 studies, 30 studies specified the TEWL measuring device type and name, and 11 studies have not reported their device type (NCT06415292, NCT06034340, NCT04718870, NCT04559022, NCT04447417, NCT03743038, NCT03365934, NCT03332628, NCT02906566, NCT01963793, NCT01909713). TEWL, transepidermal water loss.

Figure 4.

Post-closure wound TEWL measurement. The wound shown is where the wound was pre-closure based on historical clinical photo records. Each individual point and four equidistant points were subject to three consecutive TEWL measurements. These points were marked at 12 o’clock (blue), 3 o’clock (red), 6 o’clock (green), and 9 o’clock (yellow), with an extra measurement conducted at the midpoint of the wound, indicated by gray. Consistency in the lag-time between measurements was maintained to ensure uniformity. Illustrated using BioRender.com. TEWL, transepidermal water loss.