Increased protoporphyrin IX accumulation does not improve the effect of photodynamic therapy for actinic keratosis: a randomized controlled trial

Background: Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is highly effective for treating actinic keratosis (AK) on the face/scalp, but less effective on the extremities. Insufficient accumulation of protoporphyrin IX (PpIX) may cause these inferior efficacy rates. However, it is possible to increase PpIX accumulation by extending the MAL application time and/or pretreating the skin with curettage. Objectives: To investigate whether increased PpIX accumulation improves the effect of MAL-PDT for AKs in a randomized intra-individual study. Methods: Twenty-two patients with 533 AKs on both hands were treated with MAL-PDT. To obtain different concentrations of PpIX, four symmetrical areas on each patient were randomly allocated to different regimens: (i) 3-h MAL application without prior curettage (3hC−); (ii) 3 h with curettage (3hC+); (iii) 21 h without curettage (21hC−); and (iv) 21 h with curettage (21hC+). Treatment efficacy was evaluated after 3 months, whereas PpIX fluorescence, pain and erythema were assessed during and after PDT. Results: Extended MAL application with and without curettage increased PpIX accumulation significantly compared with the standard 3hC+ regimen (P = 0·001 and P = 0·002, respectively). However, the median total clearance rates did not improve accordingly: 3hC+ (55·0%), 21hC− (55·0%) and 21hC+ (53·6%). Conversely, insufficient PpIX accumulation in the 3hC− regimen led to a significantly lower clearance rate (33·3%) than the other regimens (P < 0·045). Furthermore, pain and erythema were correlated to PpIX accumulation. Conclusions: Increased PpIX accumulation does not improve the effect of MAL-PDT for AKs on the hands, but leads to worse adverse events. Different strategies are needed to improve PDT on the extremities.