TY - JOUR
T1 - Comparison of Physical Pretreatment Regimens to Enhance Protoporphyrin IX Uptake in Photodynamic Therapy
T2 - A Randomized Clinical Trial
AU - Bay, Christiane
AU - Lerche, Catharina Margrethe
AU - Ferrick, Bradford
AU - Philipsen, Peter Alshede
AU - Togsverd-Bo, Katrine
AU - Haedersdal, Merete
PY - 2017/4/1
Y1 - 2017/4/1
N2 - 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 trialwas 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 measurewasmethyl 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 accumulationwas 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.
AB - 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 trialwas 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 measurewasmethyl 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 accumulationwas 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.
KW - Adolescent
KW - Adult
KW - Aminolevulinic Acid/administration & dosage
KW - Curettage/methods
KW - Denmark
KW - Dermabrasion/methods
KW - Female
KW - Fluorescence
KW - Humans
KW - Laser Therapy/methods
KW - Male
KW - Middle Aged
KW - Photochemotherapy/methods
KW - Photosensitizing Agents/administration & dosage
KW - Protoporphyrins/metabolism
KW - Skin/metabolism
KW - Young Adult
U2 - 10.1001/jamadermatol.2016.5268
DO - 10.1001/jamadermatol.2016.5268
M3 - Journal article
C2 - 28146245
SN - 2168-6068
VL - 153
SP - 270
EP - 278
JO - JAMA Dermatology
JF - JAMA Dermatology
IS - 4
ER -