The Comparison Between Conventional Photodynamic Therapy and “Painless”TM Photodynamic Therapy in the Treatment of Actinic Keratosis: A Mini Review
May 2025 | Volume 24 | Issue 5 | 502 | Copyright © May 2025
Published online April 27, 2025
Faraz Yousefian DOa,b, Ameije Ismaili MMSc, Shireen Sachdeva DOa,b, Josh Hammel MDa,b, Marcus Goodman DOa,b, Leon Kircik MDd,e
aPhiladelphia College of Osteopathic Medicine- Department of Dermatology and Mohs Surgery, Roswell, GA
bGoodman Dermatology, Roswell, GA
cLake Erie College of Osteopathic Medicine, Bradenton, FL
dIcahn School of Medicine at Mount Sinai, Department of Dermatology, New York, NY
ePhysicians Skin Care, Louisville, KY
Abstract
Actinic keratosis is a prevalent skin condition associated with prolonged exposure to ultraviolet radiation and serves as a precursor to squamous cell carcinoma. This condition arises from DNA mutations and abnormal cell growth triggered by ultraviolet rays. While uncertainties persist regarding the progression rate of actinic keratosis (AK) to squamous cell carcinoma, the significance of nonmelanoma skin cancers underscores the need for safe, efficient, cost-effective, and accessible treatment options. Factors such as number of lesions, skin type, and sun exposure increase the risk of progression into squamous cell carcinoma. Available therapeutics include cryosurgery, topical medications, laser ablation, field ablative treatments, and photodynamic therapy (PDT). PDT has emerged as a frontline choice for addressing widespread damage, demonstrating its effectiveness in impeding the carcinogenic progression of actinic keratosis. PDT utilizes topical photosensitizers such as 5-aminolevulinic acid or methyl aminolevulinate, followed by an incubation period and subsequent exposure to either red or blue light. Both light sources exhibit similar efficacy in treating actinic keratosis and are likely to possess distinct advantages and disadvantages. Conventional PDT presents the challenge of causing significant pain and inflammation. In contrast, 'painless' PDT minimizes incubation time and extends light exposure, showing similar efficacy and improved patient comfort. Insights into pain management during photodynamic therapy reveal a correlation to protoporphyrin IX tissue accumulation. Limiting the incubation time has demonstrated a decrease in protoporphyrin IX accumulation, thus reducing pain. Further research through larger trials is imperative to establish standardized protocols and validate the potential of 'painless' PDT in reducing patient discomfort during AK treatment while preserving effectiveness.
Citation: Yousefian F, Ismaili A, Sachdeva S, et al. The comparison between conventional photodynamic therapy and ‘painless’ photodynamic therapy in the treatment of actinic keratosis: a mini review. J Drugs Dermatol. 2025;24(5):502-506. doi:10.36849/JDD.8638
BACKGROUND
Actinic keratosis (AK) is a prevalent skin lesion induced by ultraviolet (UV) radiation, serving as a precursor to squamous cell carcinoma (SCC). Ultraviolet A (UVA) rays constitute approximately 95% of the radiation reaching the Earth's surface, while ultraviolet B (UVB) rays make up only about 5%, largely absorbed by the ozone layer.1 UVA radiation penetrates the skin more deeply, giving rise to reactive oxygen species that contribute to DNA mutations, specifically from guanine to thymine, and abnormal cellular proliferation. UVB radiation is absorbed by cellular DNA creating the characteristic cytosine-thymine DNA substitutions, thus promoting abnormal cell proliferation.1 These mechanisms underlie the development of AK, marked by nuclear pleomorphism, dysregulated maturation, increased mitoses, and mutations in the p53 protein. AKs originate from the proliferation of keratinocytes with varying degrees of dysplasia in the epidermis.1 Despite uncertainties regarding the progression of AKs to SCC, it is crucial to recognize the significance of effective AK management, given that nonmelanoma skin cancers in the United States result in 2,000 to 8,000 annual deaths.2 Although limited literature exists on the nationwide financial healthcare costs of nonmelanoma skin cancers, cost-per-person estimates range from $360 to $426, contingent on the cancer cell type, lesion site, and geographic location of treatment.3
While multiple factors influence the transformation of AK into SCC, studies suggest that patients with over 10 AKs face a 14% cumulative probability of developing SCC within 5 years.4 Historically, transformation rates of AK to SCC have been reported at 0.1% per lesion per year, however, there has been significant controversy regarding the rate at which AKs
