INTRODUCTION
Actinic keratosis (AK) is a common skin lesion that classically presents as a rough, scaly papule on an erythematous base; AKs typically arise in areas chronically exposed to ultraviolet light and may progress to squamous cell carcinoma if untreated.1 Photodynamic therapy (PDT) is conditionally recommended for the treatment of AK by the American Academy of Dermatology (AAD).1
In the United States, ALA 20% solution is approved by the Food and Drug Administration (FDA) in combination with blue light illumination (BLU-U) for lesion-directed treatment of minimally to moderately thick AKs of the face, scalp, and upper extremities,2 whereas ALA 10% gel is approved in combination with BF-RhodoLED® red light for lesion-directed and field-directed treatment of AKs of mild-to-moderate severity on the face and scalp.3 ALA is also used -- off-label in the US -- for the treatment of nonmelanoma skin cancers (NMSC; ie, squamous cell carcinoma in situ/Bowen's disease and superficial or nodular basal cell carcinoma [BCC]) and acne vulgaris.4
Pain during treatment is a drawback of ALA-PDT. Local skin reactions, including stinging/burning and erythema, are common during and shortly after illumination and can be severe.2,3 Patients may have difficulty tolerating multiple treatments or even a full treatment session.5 Furthermore, adjunctive measures to improve efficacy or decrease required incubation time may increase pain; these include skin preparation by curettage4,6 or microneedling7 and incubation with occlusion.8 Despite these considerations, the 2021 AAD guidelines devote little attention to pain mitigation during ALA-PDT.1 This review summarizes the available medical literature on attempts to reduce pain associated with ALA-PDT, focusing on
Conventional PDT involves the application of a photosensitizing compound (usually 5-aminolevulinic acid [ALA] or methyl-5-aminolevulinate [MAL]) to the affected skin and incubation for 3 or more hours. During incubation, ALA and MAL are metabolized to protoporphyrin IX (PpIX), a photoactive compound that can be activated by light in the presence of oxygen to form reactive oxygen species that damage cellular components and cause cell death.2-4 Although abundant literature supports the use of MAL-PDT for the treatment of AKs,1 MAL is not FDA approved or commercially available in the US.
In the United States, ALA 20% solution is approved by the Food and Drug Administration (FDA) in combination with blue light illumination (BLU-U) for lesion-directed treatment of minimally to moderately thick AKs of the face, scalp, and upper extremities,2 whereas ALA 10% gel is approved in combination with BF-RhodoLED® red light for lesion-directed and field-directed treatment of AKs of mild-to-moderate severity on the face and scalp.3 ALA is also used -- off-label in the US -- for the treatment of nonmelanoma skin cancers (NMSC; ie, squamous cell carcinoma in situ/Bowen's disease and superficial or nodular basal cell carcinoma [BCC]) and acne vulgaris.4
Pain during treatment is a drawback of ALA-PDT. Local skin reactions, including stinging/burning and erythema, are common during and shortly after illumination and can be severe.2,3 Patients may have difficulty tolerating multiple treatments or even a full treatment session.5 Furthermore, adjunctive measures to improve efficacy or decrease required incubation time may increase pain; these include skin preparation by curettage4,6 or microneedling7 and incubation with occlusion.8 Despite these considerations, the 2021 AAD guidelines devote little attention to pain mitigation during ALA-PDT.1 This review summarizes the available medical literature on attempts to reduce pain associated with ALA-PDT, focusing on
