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Stine Regin Wiegell, MD; Ida-Marie Stender, MD; Renhua Na, MD; Hans Christian Wulf, MD

Arch Dermatol. 2003;139:1173-1177.

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 sun-exposed 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.

From the Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Denmark. The authors have no relevant financial interest in this article.

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