The Interventions to Minimize Pain During Photodynamic Therapy With 5-Aminolevulinic Acid for the Treatment of Cutaneous Diseases

Photosensitization with 5-aminolevulinic acid (ALA) combined with photodynamic therapy (PDT) is approved in the United States for the treatment of actinic keratosis (AK) and is used off-label for other indications including acne treatment and photo rejuvenation. However, pain, particularly during the initial illumination period, limits the utility of this highly efficacious therapy. Although modifications to conventional ALA-PDT protocols that improve tolerability without diminishing efficacy have been identified, few have been evaluated in randomized, controlled trials, and the number of variables involved in ALA incubation (eg, duration, occlusion, ALA formulation, and strength) and PDT illumination (eg, light source, fluence rate, irradiance, and duration) confounds standardization.  Perhaps the most promising modifications to date involve continuous activation of low levels of protoporphyrin IX, the photoactive metabolite of ALA, as well as using shorter incubation times (with or without prolongation of illumination), lower irradiance, and daylight or combined (daylight and conventional) PDT. However, reimbursement of PDT with alternative light sources in the US is hampered by the US Food and Drug Administration (FDA) labeling, which specifies the blue or red light devices approved for use with corresponding marketed ALA 20% solution and 10% gel, respectively. This review summarizes the existing evidence with respect to pain control in patients undergoing ALA-PDT, recommendations from clinical experience, and goals for future research. J Drugs Dermatol. 2023;22(11):1082-1087   doi:10.36849/JDD.7637.