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Original Investigation
February 1, 2017

Comparison of Physical Pretreatment Regimens to Enhance Protoporphyrin IX Uptake in Photodynamic TherapyA Randomized Clinical Trial

Author Affiliations
  • 1Department of Dermatology D92, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
JAMA Dermatol. Published online February 1, 2017. doi:10.1001/jamadermatol.2016.5268
Key Points

Question  What is the relative potential of curettage, microdermabrasion, microneedling, and fractional laser pretreatment to enhance methyl aminolevulinate hydrochloride–induced protoporphyrin IX formation in photodynamic therapy?

Findings  This randomized clinical trial of 12 healthy participants demonstrates that pretreatment with an ablative fractional laser significantly intensifies protoporphyrin IX fluorescence to a larger extent than curettage, microdermabrasion, microneedling, and nonablative fractional laser. Moreover, increasing laser densities (2%-6%) and the number of pretreatment passes (1-3) did not further enhance protoporphyrin IX fluorescence.

Meaning  Ablative fractional laser treatment has a higher potential than curettage, microdermabrasion, microneedling, and nonablative fractional laser to enhance the PDT response in normal skin.


Importance  Skin pretreatment is recommended for adequate penetration of topical photosensitizing agents and subsequent protoporphyrin IX (PPIX) accumulation in photodynamic therapy (PDT).

Objective  To compare the relative potential of different physical pretreatments to enhance PPIX fluorescence in normal skin.

Design, Setting, and Participants  This intraindividual, randomized clinical trial was performed from November 28 to December 20, 2014, at Bispebjerg Hospital, Copenhagen, Denmark, among 12 healthy volunteers 18 years or older. Analysis was based on intention to treat. All participants completed the study protocol.

Interventions  Participants were each exposed to standardized skin preparation with curettage, microdermabrasion with abrasive pads, microneedling with dermarollers, ablative fractional laser (AFXL), non-AFXL, and no pretreatment, followed by 3 hours of methyl aminolevulinate hydrochloride incubation and subsequent red light illumination.

Main Outcomes and Measures  The primary outcome measure was methyl aminolevulinate–induced PPIX fluorescence accumulation. Secondary outcome measures were PPIX photobleaching and clinical local skin reactions, supported by noninvasive reflectance measurements of percentage of skin redness, transepidermal water loss, and participant-assessed pain.

Results  Among the 12 healthy study participants (8 men; 4 women; mean [SD] age, 33 [15] years), histologic findings confirmed standardization of interventions with partial removal of the stratum corneum after curettage and microdermabrasion and similar vertical penetration depths for microneedling, AFXL, and non-AFXL (median, 125 μm). PPIX fluorescence reached highest intensities in skin pretreated with AFXL (median, 8661 arbitrary units [AU]) compared with microdermabrasion (median, 6731 AU), microneedling (median, 5609 AU), and curettage (median, 4765 AU) (P < .001), among which similar enhancement was shown. Comparatively lower fluorescence levels were demonstrated for skin pretreated with non-AFXL (median, 2898 AU), methyl aminolevulinate–treated controls (median, 2254 AU), and untreated controls (median, 239 AU) (P < .03). Increasing laser densities (2% vs 4% vs 6%) and the number of pretreatment passes (1, 2, and 3 passes) did not enhance PPIX fluorescence. Local skin reactions were most intensified in AFXL-pretreated skin and correlated with PPIX fluorescence and degree of PPIX photobleaching.

Conclusions and Relevance  Under standardized conditions, PPIX accumulation was most enhanced after AFXL pretreatment, followed by microdermabrasion, microneedling, and curettage. Increasing the number of pretreatment passes and laser densities did not further augment PPIX accumulation. These results may indicate relatively enhanced PDT response by AFXL pretreatment in diseased skin.

Trial Registration  clinicaltrials.gov Identifier: NCT02372370