Safety and Efficacy of Photodynamic Therapy with Aminolevulinic Acid 10% Topical Gel Activated by Red Light versus Aminolevulinic Acid 20% Topical Solution Activated by Blue Light for the Treatment of Actinic Keratosis on the Upper Extremities: A Blinded Randomized Study

Abstract

Introduction: Actinic keratoses (AKs) are common precancerous skin lesions resulting from chronic sun exposure and carry the potential to progress into squamous cell carcinoma if left untreated. Photodynamic therapy (PDT) is a well-established, non-invasive treatment option for AKs. Currently, PDT with 10% aminolevulinic acid (ALA) gel activated by red light is FDA-approved for the treatment of AKs on the face and scalp, while PDT with ALA 20% solution activated by blue light is FDA-approved for AKs on the face, scalp, and upper extremities. Although both PDT treatment regimens have demonstrated clinical effectiveness for treating AKs on the upper extremities, no head-to-head studies have directly compared their relative efficacy and safety using the recommended incubation times and light sources. The purpose of this study was to compare the safety, tolerability, and efficacy of both therapeutic combinations for PDT treatment of AKs on the upper extremities. 

Methods: This was a prospective, single-center, split-arm randomized clinical trial involving 30 adults, each with 4-17 clinically confirmed mild-to-moderate AKs on both distal upper extremities (graded by Olsen criteria). Each participant received PDT with 10% ALA gel plus red light on one arm and 20% ALA solution plus blue light on the contralateral arm, with side assignment randomized. The primary endpoint was total lesion clearance rate (TLCR) at 12 weeks after the first PDT. Secondary endpoints included TLCR for moderate grade 3 lesions, TLCR at 6- and 12-months after the last PDT, investigator-assessed cosmetic outcomes, and patient-reported satisfaction.

Results: Of the 30 enrolled patients, 27 completed the study. Mixed-effects statistical analysis showed significant improvement in TLCR for both treatment arms (p<0.0001). At 6 months post-2 PDT treatments, TCLR was 87.6% with 10% ALA gel and 84.5% with 20% ALA solution. At 12-months, TLCR was 90.5% for 10% ALA gel and 86.9% for 20% ALA solution. Although differences were not statistically significant, 10% ALA gel demonstrated a trend toward higher clearance of grade 3 AK lesions (94.12%) compared with 20% ALA (88.24%). No statistical differences were observed between groups in patient-reported pain or satisfaction ratings. Moderate erythema occurred more frequently in the 10% ALA gel group (41.5%) than with the 20% ALA solution group (23.6%), though this difference was not statistically significant. All erythema resolved, and no serious adverse events were reported.

Conclusion: This study represents the first direct, head-to-head comparison of 10% ALA gel with red light and 20% ALA solution with blue light for the treatment of AKs on the upper extremities. Both regimens were safe, well tolerated, and achieved high lesion clearance rates. A trend toward greater efficacy was observed with 10% ALA gel in the management of grade 3 lesions, potentially related to a stronger post-PDT inflammatory response, as indicated by higher rates of erythema. Overall, both regimens were effective treatment options, with 10% ALA gel offering additional advantages in ease of application as a field therapy and potentially higher clearance rates in patients with more severe AKs.