Journal of photochemistry and photobiology. B, Biology · 2026
Topical and oral chemical pretreatments for photodynamic therapy in actinic keratoses: A scoping review.
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Androus Maya, Williams Avery, Boostani Mehdi, Paragh Gyorgy
Аннотация
BACKGROUND: Photodynamic therapy (PDT) is an established field-directed treatment for actinic keratoses (AKs). PDT efficacy is reduced in thicker, treatment-resistant lesions. Pharmacologic pretreatment has been explored as a strategy to improve photosensitizer penetration, protoporphyrin IX (PpIX) accumulation, and lesion clearance.
OBJECTIVE: To systematically review the evidence on topical and oral chemical pretreatments used before PDT for AKs.
METHODS: PubMed, Embase, and Scopus were searched for English-language human studies evaluating pharmacologic pretreatment before PDT for AKs. Interventional studies reporting clearance, recurrence, fluorescence, or adverse outcomes were included.
RESULTS: Nineteen studies published from 2009 to 2025 met the inclusion criteria. Pretreatments included oral vitamin D (VD), and topical VD-analogs, 5-fluorouracil (5-FU), retinoids, urea, salicylic acid, corticosteroids, diclofenac, and ingenol mebutate. The most consistent improvements in PDT response were observed with oral VD, and topical VD-analog or 5-FU pretreatments, particularly in grade II and thicker lesions. Several studies also demonstrated increased PpIX fluorescence after pretreatments. Retinoids showed mixed results. Urea and salicylic acid generally increased efficacy to a level comparable to curettage. Corticosteroid pretreatment did not appear to improve efficacy, whereas diclofenac showed limited short-term benefit but possible longer-term reduction in lesion burden. Ingenol mebutate pretreatment only showed a statistically nonsignificant reduction in AKs.
CONCLUSIONS: Pharmacologic pretreatments can enhance PDT response, especially in thicker, more resistant AKs. Currently, oral VD and topical VD analogs, as well as 5-FU, have the strongest supporting evidence. The heterogeneity in study design, pretreatment regimens, and outcome measures limits direct comparison.
OBJECTIVE: To systematically review the evidence on topical and oral chemical pretreatments used before PDT for AKs.
METHODS: PubMed, Embase, and Scopus were searched for English-language human studies evaluating pharmacologic pretreatment before PDT for AKs. Interventional studies reporting clearance, recurrence, fluorescence, or adverse outcomes were included.
RESULTS: Nineteen studies published from 2009 to 2025 met the inclusion criteria. Pretreatments included oral vitamin D (VD), and topical VD-analogs, 5-fluorouracil (5-FU), retinoids, urea, salicylic acid, corticosteroids, diclofenac, and ingenol mebutate. The most consistent improvements in PDT response were observed with oral VD, and topical VD-analog or 5-FU pretreatments, particularly in grade II and thicker lesions. Several studies also demonstrated increased PpIX fluorescence after pretreatments. Retinoids showed mixed results. Urea and salicylic acid generally increased efficacy to a level comparable to curettage. Corticosteroid pretreatment did not appear to improve efficacy, whereas diclofenac showed limited short-term benefit but possible longer-term reduction in lesion burden. Ingenol mebutate pretreatment only showed a statistically nonsignificant reduction in AKs.
CONCLUSIONS: Pharmacologic pretreatments can enhance PDT response, especially in thicker, more resistant AKs. Currently, oral VD and topical VD analogs, as well as 5-FU, have the strongest supporting evidence. The heterogeneity in study design, pretreatment regimens, and outcome measures limits direct comparison.