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Thermo-Mechanical Fractional Injury Enhances Skin Surface- and Epidermis- Protoporphyrin IX Fluorescence: Comparison of 5-Aminolevulinic Acid in Cream and Gel Vehicles.

  • Foged, Camilla1
  • Haedersdal, Merete1
  • Bik, Liora1, 2
  • Dierickx, Christine3
  • Phillipsen, Peter A1
  • Togsverd-Bo, Katrine1
  • 1 Department of Dermatology, Copenhagen University Hospital Bispebjerg and Frederiksberg, Nielsine Nielsens Vej 17, entrance 9, 2. floor, Copenhagen, Nordvest, DK-2400, Denmark. , (Denmark)
  • 2 Department of Dermatology, Erasmus MC University Medical Center Rotterdam, Dr. Molewaterplein 40, Rotterdam, 3015, The Netherlands. , (Netherlands)
  • 3 Skinperium, Private Dermatology Clinic, Rue Charles Martel 52, Luxembourg, 2134, Luxembourg. , (Luxembourg)
Published Article
Lasers in Surgery and Medicine
Wiley (John Wiley & Sons)
Publication Date
Jul 01, 2021
DOI: 10.1002/lsm.23326
PMID: 33001491


Thermo-mechanical fractional injury (TMFI) impacts the skin barrier and may increase cutaneous drug uptake. This study investigated the potential of TMFI in combination with 5-aminolevulinic acid (ALA) cream and gel formulations to enhance Protoporphyrin IX (PpIX) fluorescence at the skin surface and in the skin. In healthy volunteers (n = 12) a total of 144 test areas were demarcated on the upper back. Test areas were randomized to (i) TMFI (6 milliseconds, 400 µm at a single pass) or no pretreatment and (ii) 20% ALA in cream or gel formulations. Skin surface PpIX fluorescence was quantified by PpIX fluorescence photography and photometry in 30-minute intervals until 3 hours. PpIX fluorescence microscopy quantified separate PpIX fluorescence in the epidermis, and in superficial-, mid-, and deep- dermis from punch biopsies sampled after 3 hours of ALA incubation. Local skin reactions (LSR) and pain intensities (numerical rating scale 0-10) were evaluated immediately, at 3 hours and 14 days after the intervention. TMFI exposure before photosensitizer application significantly increased skin surface PpIX fluorescence, both for ALA cream (TMFI-ALA-cream 7848 arbitrary units [AU] vs. ALA-cream 5441 AU, 3 hours, P < 0.001) and ALA gel (TMFI + ALA-gel 4591 AU vs. ALA-gel 3723 AU, 3 hours, P < 0.001). The TMFI-mediated increase in PpIX fluorescence was similar for ALA-cream and -gel formulations (P = 0.470) at the skin surface. In the epidermis, PpIX fluorescence intensities increased from combination treatment with TMFI and ALA-cream (TMFI + ALA-cream 421 AU vs. ALA-cream 293 AU, P = 0.034) but not from combination with TMFI and ALA-gel (TMI + ALA-gel 264 AU vs. ALA-gel 261 AU, P = 0.791). Dermal fluorescence intensities (superficial-, mid-, or deep dermis) were unaffected by TMFI pretreatment in both ALA-cream and ALA-gel exposed skin (P = 0.339). ALA-cream generally induced higher PpIX fluorescence intensities than ALA-gel (skin surface P < 0.001 and epidermis P < 0.03). TMFI induced low pain intensities (median 3) and mild LSR that were resolved at 14 days follow-up. Given the present study design, TMFI, in combination with the standardized application of 20% ALA cream and gel formulations, significantly enhanced skin surface PpIX fluorescence compared to no pretreatment. Additionally, TMFI increased epidermal PpIX fluorescence combined with 20% ALA cream vehicle. Thus, TMFI pretreatment and formulation characteristics exert influence on PpIX fluorescence intensities in normal skin. Lasers Surg. Med. © 2020 Wiley Periodicals LLC. © 2020 Wiley Periodicals LLC.

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