ETD

• Actinic keratosis
• Cancer
• SCC
• TEWL
• Treatment

Actinic keratoses (AKs) are one of the most common cutaneous keratinocyte dysplasia in the overall population. AKs are characterized by the abnormal proliferation of atypical epidermal keratinocyte, and it is classified as keratinocyte intraepidermal neoplasia (KIN). AK may progress to invasive cutaneous squamous cell carcinoma. Patients commonly present multiple lesions alongside signs of chronic sun damage in surrounding skin, a condition often termed field cancerization. Several topical therapies for field cancerizations are available including topical drugs such as 5-fluorouracil, imiquimod and tirbanibulin. Transepidermal water loss (TEWL) is a non-invasive diagnostic tool that not only has been used evaluate skin maceration for ulcerative lesions but can also give objective measurements for evaluating skin barrier function by measuring the quantity of condensed water loss by the stratum corneum. Standardized conditions are essential to ensure reliable results, as TEWL is highly sensitive to the surrounding microclimate. Higher values can be associated with higher skin damage reflecting increased water loss and heightened percutaneous permeability. In the context of AK, TEWL may serve as a non-invasive tool for assessing barrier dysfunction, aiding in risk stratification and treatment monitoring. In AK, elevated TEWL reflects barrier dysfunction due to histopathological changes, such as parakeratosis and reduced corneocyte cohesion. This observational study included 103 patients and sought to compare the clinical outcome of topical 5-Fluorouracil, Imiquimod and Tirbanibulin to a field cancerization < 25 cm2. The outcome was measured in terms of actinic keratosis area and severity index (AKASI) and TEWL values. The TEWL values of the field cancerization were assessed at week 0, 2, 4, 8 and 24 alongside the AKASI score for actinic keratosis severity. The adverse events for each drug were carefully evaluated and compared as well. A TEWL value more than 15 was considered pathological and values over 23 were considered highly pathological. The patient outcomes were stratified for high pathological TEWL values (>23) and pathological TEWL values (>15 but < 23). Our results show that each field therapy can be a valid option for the treatment of an affected area < 25 cm2. Nonetheless, when our population sample were stratified for TEWL > 23, we have reported a success rate of only 45% for the tirbanibulin group while 76% and 85% success rate for imiquimod and 5-fluorouracil were obtained respectively. The success rate was comparable among these drugs in the subgroup of TEWL < 23. These data might suggest a potential role for TEWL to decide which is the best field therapy for AKs. As of today, each topical drug evaluated in this study remains a viable option for treating field cancerization areas <25 cm², including grade I and II actinic keratosis. However, no clear objective measurement exists to guide the initial choice of agent based on patient characteristics. Furthermore, high actinic keratosis area and severity index (AKASI) did not always correlate with high TEWL values possibly indicating that the severity of field cancerization in some subset of patients may be missed with only clinical evaluation. In conclusion, this study shed some light on the possible use of TEWL for the management of actinic keratoses and prompt the use of other non-invasive devices for better understanding the severity of field cancerization.