Aminolevulinic Acid 20% Solution Combined With Photodynamic Therapy for Treatment of Actinic Keratoses: A Review

November 2021 | Volume 20 | Issue 11 | Original Article | 1239 | Copyright © November 2021

Published online November 1, 2021

Joe Gorelick MSN FNP-C,a Scott Freeman MCMS PA-Cb

aCalifornia Skin Institute, San Jose, CA
bAdvanced Dermatology, St. Petersburg, FL

Actinic keratoses (AK) are lesions with potential to transform into nonmelanoma skin cancers. Numerous methods are available for treatment of AK. Here, we review clinical trial data on the use of photodynamic treatment combined with the sensitizing agent aminolevulinic acid 20% solution (ALA-PDT) for AK management. Although treatment guidelines for AK vary in their specific recommendations, efficacy of ALA-PDT is considered comparable or better relative to other FDA-approved treatments for AK. It is generally well tolerated and has a very acceptable long-term safety profile. ALA-PDT is typically recommended for patients who have multiple AKs and is associated with improved cosmetic outcomes compared with cryotherapy. Patients who undergo treatment with ALA-PDT should receive thorough education regarding the risks and benefits of treatment, the treatment regimen and the importance of adhering to it, how to manage local reactions, and signs and symptoms that warrant further evaluation.

J Drugs Dermatol. 2021;20(11):1239-1244. doi:10.36849/JDD.6166


Actinic keratoses (AK) are dysplastic epidermal lesions resulting from long-term sun exposure that have potential to progress to nonmelanoma skin cancer (NMSC), particularly squamous cell carcinoma (SCC).1,2 They are a manifestation of abnormal keratinocyte proliferation and differentiation.3

AKs may be considered visible evidence of a photo-damaged field with changes predisposing the patient to development of NMSC.4 However, AKs may also spontaneously resolve or remain stable without malignant transformation.3 In one study of 169 patients with 7784 AKs, 5.6% of patients progressed to develop SCC or basal cell carcinoma (BCC) within 5 years.4,5 Another study predicted that patients with an average of 7.7 AKs had a 10% risk of developing SCC within 10 years.3 Further, roughly two-thirds of primary SCCs, one-third of primary BCCs, and 60% to 80% of invasive SCCs arose in AK lesions.4,5

The prevalence of AK varies from 6% to 60% among populations and appears to be increasing.2 Factors increasing risk for AK include age, skin phototype, lifestyle, and occupation (eg, working outdoors), geographical location, history of skin cancer, and immunosuppressed status.2 Development of AK is more likely in patients whose skin burns easily (eg, phototype I) compared with those who rarely burn (eg, phototype VI).6

They primarily occur on areas of skin that experience chronic sun exposure, particularly the head and neck, followed by the upper extremities.3 The total direct costs associated with AK in 2004 were estimated at $1.2 billion, with the majority of these costs resulting from outpatient visits to health care providers for treatment.4

Although some AKs are associated with sensations of itching or tenderness, most are generally asymptomatic.3 Patients often describe the lesions as rough “sandpaper”-like patches. AKs are graded using a 3-point scale: grade 1 lesions are visible and palpable, grade 2 lesions are usually red and scaly, and grade 3 lesions are thicker, hyperkeratotic lesions that can be difficult to differentiate from early SCCs.3 Presence of a single lesion may be associated with development of multiple lesions in the future.3 When multiple AKs are present, they are considered to be evidence of “field change,” ie, an area of skin with extensive actinic damage.3

Overview of Treatment Options for Actinic Keratoses
The goals of AK treatment are to eliminate existing AKs and minimize risk of recurrence and progression to SCC.2 Available treatment options include photodynamic therapy (PDT) with photosensitizing agents; topical agents such as 5-fluorouracil, imiquimod, diclofenac, and topical retinoids; cryosurgery;