Microneedling Prior to Levulan PDT for the Treatment of Actinic Keratoses: A Split-Face, Blinded Trial
September 2016 | Volume 15 | Issue 9 | Original Article | 1072 | Copyright © 2016
James M. Spencer MD MSa,b and Scott A. Freeman PAb
aDepartment of Dermatology, Mt Sinai School of Medicine, New York, NY
bSpencer Dermatology & Skin Surgery Center, St Petersburg, FL
INTRODUCTION: Photodynamic Therapy (PDT) with topical Levulan is an approved and efficacious method for treating actinic keratoses. This therapy depends on the ability of the Levulan (delta amino levulinic acid) to penetrate the stratum corneum and enter the cells of the epidermis. Microneedling is an increasing popular cosmetic therapy in which an array of tiny needles is used to make holes in the epidermis and presumably induce a wound healing cascade that leads to cosmetic improvement of the skin. We were interested to know if prior microneedling would enhance the penetration of topical Levulan and thus enhance the PDT treatment, and if a cosmetic improvement beyond the PDT alone would be seen when it is used in conjunction with microneedling.
METHODS: 20 patients each with at least 4 non hyperkeratotic AKs on each side of their face were enrolled. All patients were randomized to receive multiple passes with a microneedling device to ½ of their face, left or right, followed by application of Levulan to the entire face. The Levulan was allowed to incubate 1 hour followed by exposure to blue light (Blu U) for 1000 seconds.
RESULTS: 19 patients completed the study with 4-month follow up. The mean percentage reduction in AKs was 89.3% on the microneedling side versus 69.5% on the PDT alone side, a significant difference. A physician’s global cosmetic assessment was performed based on Canfield Visia photographs: 15 of the 19 patients had a noticeable improved cosmetic appearance on one side of the face versus the other, and in 13 of these patients the improved side was the microneedled side.
DISCUSSION: Prior microneedling significantly enhances the effect of Levulan PDT. It also seems to provide a cosmetic benefit above and beyond the PDT alone. It was safe and well tolerated in this study.
J Drugs Dermatol. 2016;15(9):1072-1074.
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Photodynamic therapy refers to the application of a light sensitizing compound followed by light of the appropriate wavelength to destroy premalignant and malignant cells. The use of a 20% solution of delta amino levulinic acid followed by exposure to blue light with a peak at 417 ±5 nm has been shown to be highly effective for the treatment of premalignant Actinic Keratoses (AK). Multiple studies have proven efficacious, and a large phase III study suggested 77% of patients had complete clearing of 75% of lesions in 8 weeks following PDT.1
Despite the excellent efficacy rates, the drug must penetrate to the lower epidermis to work, and therefore must cross the stratum corneum, which represents a barrier to drug absorption. Microneedling refers to a series of devices that have in common a series of tiny needles either on a roller or a mechanical stamp with the intention of creating a series of tiny holes into the epidermis, and dermis if set with the needles longer. The idea is that this creates a wound healing cascade the leads to cosmetic improvement in the skin. From a drug delivery point of view, these tiny holes allow a passage way for topical medications to reach the epidermis or dermis. It has been proposed that microneedling would allow deeper/better penetration of mal Levulinic acid and give an enhanced cosmetic improvement, either due to the microneedling itself or deeper penetration of the mal Levulinic acid.2 A full face microneedling treatment of several passes was performed, followed by mal Levulinic acid, red light, and broadband pulsed light. A global improvement in cosmetic facial assessment was seen, but no control was performed and the effect on the PDT could not be assessed as there was no control group. A more recent study3 again looked at mal PDT in 10 patients who received gentle curettage followed by mal levulinic acid PDT on 1 side of the face and microneedling with mal PDT to the other. The microneedling side was judged to be cosmetically superior, but no difference in AK clearance rates between the two sides was noted with each being 83.3%. Of note, curettage was only performed on the control side, which may explain why the microneedling did not make AK reduction greater, and the number of patients was small at 10.
We were interested to see if microneedling does in fact enhance the effectiveness of Levulan PDT due to increased absorption of the drug. Therefore, a split face trial was conducted to assess the efficacy of Levulan PDT with and without microneedling.