Pain Associated With Photodynamic Therapy Using 5-Aminolevulinic Acid or 5-Aminolevulinic Acid Methylester on Tape-Stripped Normal Skin

Abstract

Background: Pain during and after topical photodynamic therapy (PDT) is one of the few severe adverse effects of the new treatment of skin diseases.Objective: To compare the pain experienced in normal skin treated with 5-aminolevulinic acid (ALA) PDT and 5-aminolevulinic methylester (ALA-ME) PDT.Design: Double-blind randomized trial.Interventions: Twenty healthy volunteers were treated randomly with ALA-PDT on one forearm and ALA-ME-PDT on the other forearm after tape stripping of the sunexposed skin areas.Main Outcome Measures: Pain was scored using a numerical scale ranging from 0 to 10 during illumination, immediately after illumination, and each day in the following week. In addition, we measured erythema, pigmentation, and protoporphyrin IX (PpIX) fluorescence.Results: ALA-PDT generated significantly more pain than ALA-ME-PDT during and after illumination (P=.001 and P = .05, respectively). ALA-PDT induced a larger decrease in PpIX fluorescence than ALA-ME-PDT (P=.009). There was no correlation between pain and peak PpIX fluorescence or absolute decrease in peak PpIX fluorescence. Both treatments lead to erythema immediately after illumination and increased pigmentation 1 week after PDT. There was no correlation between pain and degree of erythema or pigmentation.Conclusions: ALA-ME-PDT was less painful than ALA-PDT when performed on tape-stripped normal skin. The pain scores did not correlate with the intensity of peak PpIX fluorescence in the skin or with the degree of erythema after illumination, suggesting that pain was not caused by activation of PpIX alone. The theory that ALA and not ALA-ME is transported by ␥-aminobutyric acid receptors into the peripheral nerve endings may explain the higher pain scores in ALA-PDT-treated areas.

Consensus recommendations on the use of daylight photodynamic therapy with methyl aminolevulinate cream for actinic keratoses in Australia

“…In one clinical trial, a small but significant association ( P  = 0.02, r 2  = 0.17) was found between the first sensation of pain and a delay greater than 30 min in exposure to daylight after the application of MAL cream 16. Together with anecdotal evidence from a retrospective case series,20 these findings suggest that patients who remain indoors for longer than 30 min after applying MAL cream may be at risk of increased pain, presumably arising from the greater accumulation of PpIX before sun exposure 23…”

Clinical investigation of the novel iron-chelating agent, CP94, to enhance topical photodynamic therapy of nodular basal cell carcinoma

“…Irradiation-induced pain is thought to be associated with an effective PDT treatment taking place. Previous studies however have shown that pain scores do not correlate with the intensity of PpIX fluorescence either during ALA-PDT of tape stripped normal skin 20 or during ALA-PDT of skin cancer 22 . This suggests that pain associated with ALA-PDT is not simply due to the These findings are in contrast to studies using other iron chelating agents particularly DFO, where the addition of DFO to the higher ALA dose being employed in clinical treatment did not significantly enhance PpIX levels, when examined in matched lesions in the same patient 21 .…”

Photodynamic Therapy and Skin Cancer

“…In a previous study it could be shown that MAL-PDT induces less pain in comparison to ALA-PDT which can be partially explained due to the differences in selectivity between the two substances [44].…”