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    Photodynamic photorejuvenation

    Waikoloa, Hawaii - Intense pulsed light (IPL) and lasers used in combination with 5-aminolevulinic acid (ALA) on the full face can achieve photorejuvenation as well as treat actinic keratoses (AK), according to Mitchel P. Goldman, M.D.

    IPL has been used to achieve photorejuvenation by heating collagen fibers and causing inflammation that tightens the skin. Lasers have been used to achieve a peel similar to multiple microdermabrasions.

    "What's new is that we're adding ALA," Goldman said. Several recent studies show that photodynamic treatment with ALA significantly reduces AK lesions with less pain than cryosurgery, chemical peeling, or topical 5 flurouracil.

    Used together, IPL or lasers with ALA, can achieve both a therapeutic and an aesthetic effect, Dr. Goldman said at the Skin Disease Education Foundation's 28th Hawaii Dermatology Seminar. As well as clinical AK lesions, the full-face treatment can improve subclinical AK lesions, solar lentigos, wrinkles, sallow complexion, and telangiectasia, said Dr. Goldman, an associate clinical professor of dermatology,University of California, San Diego, and medical director of La Jolla Spa.

    ALA works by penetrating the stratum corneum into tumors, including basal and squamous cell carcinomas and solar keratoses, as well as sebaceous glands. There, it can be transformed into a highly photoactive endogenous porphyrin derivative, protoporphyrin IX (PpIX). Red or blue light sources can activate PpIX, which destroys cells by generating singlet oxygen molecules.


    Dr. Goldman
    Apply, then expose to blue lightIn the United States, ALA is marketed by DUSA Pharmaceuticals as Levulan. It is used with the company's applicator, the Kerastick. In the original clinical trial protocols, investigators applied the ALA individually to AK lesions, allowed it to dry, and then applied more ALA. They let the ALA incubate on the skin for 14 to 18 hours before exposing the lesions to a 10 J/cm2 dose of visible blue light with a 417 nm wavelength for 1,000 seconds. They repeated the treatment eight weeks later for those lesions that had not responded.

    For Phase III trials, 243 patients with nonhyperkeratotic AK of the face and scalp were randomly assigned to receive either 20 percent ALA and blue light, or to receive vehicle and blue light. At the conclusion of these trials, 88 percent of the ALA-treated patients had at least 75 percent response, vs 20 percent of the control group.

    Patients reported a range of transient adverse reactions, including stinging, burning, itching, erythema, and edema. Many of the patients required a healing period of up to one week following the treatment, but fewer than 3 percent dropped out of the study because of such symptoms. Ninety-four percent were pleased with the cosmetic results. In other studies, a majority of patients have reported that photodynamic therapy is less painful than cryosurgery.

    For the past two years, Dr. Goldman and other investigators have been trying ALA in confluent application over the face and chest. "Instead of just putting it on the AKs, I put it on the entire face," Dr. Goldman said. In this way, "the ALA treats AKs that are both clinical and subclinical."

    Lesions vanishFor a study reported in the 2003 Journal of Cosmetic and Laser Therapy (5:1-4), Dr. Goldman and his colleague Deborah Atkins at Dermatology/Cosmetic Laser Associates of San Diego County applied ALA selectively to lesions of 19 patients and over the entire faces of 13 patients, then exposed them with blue light. Almost all the lesions were cleared in both groups, and two thirds of the patients receiving confluent therapy also reported that their skin was smoother afterwards.

    The confluent application does appear to be more painful, however. The investigators found that only 31 percent of patients who had the full-face application would repeat the treatment, compared to 79 percent of those who had the ALA applied to individual lesions.

    IPL appears less painful than blue light, Dr. Goldman pointed out, and is more effective in treating hyperpigmentation and telangiectasia.

    Cancer preventive?Dr. Goldman thinks the confluent treatment may prevent skin cancer.

    "In studies on hairless mice, this reduced the appearance of skin cancer. We will know in humans in a few years."

    In addition, Dr. Goldman and others are experimenting with ALA incubation times of 0.5 to 1 hour, followed by exposure to blue light, vascular wavelength lasers in the 585nm to 600 nm range, or IPL in the 550 nm to 1,200 nm range. These shorter incubation times appear just as effective, Dr. Goldman reported, "and that's good because the patient can be treated in one day."

    Lasting effects uncertainIt remains to be seen how long the benefits of photodynamic photorejuvenation with ALA will last, Dr. Goldman says. "The truth is that we don't know. We've only been doing this for about 21 months. But I have been seeing my patients after a year, and they look really good," he said.

    He added that any lesions that return after photodynamic therapy might be something other than AK and a biopsy should be considered.

    As a consultant to DUSA and to Lumenis, which makes IPL equipment, Dr. Goldman has received equipment discounts, honoraria, and research support.

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