154. Non-invasive Detection of Subclinical Skin Changes in Lymphedema: A Promising Screening Method for Early Stage Disease

PURPOSE: Current diagnostic measures for lymphedema are limited in detesting subclinical disease. The purpose of this study was to quantify early skin changes in lymphedematous skin and evaluate their correlation with indocyanine-green (ICG) lymphography findings and patient-reported symptoms. METHODS: Trans-epidermal-water-loss (TEWL), a skin-barrier function marker, tonometry (fibrosis), and percentage-water-content (PWC) were prospectively measured under ICG lymphography in patients with unilateral breast-cancer-related-lymphedema. Both dermal-backflow areas and areas not impacted by dermal-backflow were assessed using three non-invasive devices. Respective skin sites of the contralateral arm were used as controls. Matched biopsies were collected and analyzed using histology and immunofluorescence. RESULTS: 39 patients were included. TEWL, PWC, and tonometry were significantly increased in dermal-backflow areas. Dermal-backflow intensity was highly correlated with PWC (r=.90, p<0.0001), TEWL (r=.42, p=0.002) and higher symptom scores (r=.78, p<0.0001). These findings were confirmed on histological analysis, demonstrating epidermal spongiosis, nuclear polarity, and increased epidermal-thickness, hyperkeratosis, and inflammatory markers in dermal-backflow areas. High correlations were demonstrated between the non-invasive skin measurements and histological findings. CONCLUSION: Early-stage lymphedema is characterized by a localized increase in tissue water content, fibrosis, and skin-barrier dysfunction. This is the first study to show that early detection of localized skin changes using simple, non-invasive methods applicable for clinical adaptation, could be a valuable tool in the screening of subclinical-lymphedema. These findings represent a major shift in current clinical practice paradigms, putting an emphasis on prevention rather than symptomatic relief.