WAIKOLOA, HAWAII – Using EMLA or lidocaine cream in conjunction with topical 5-aminolevulinic acid photodynamic therapy may boost uptake of the photosensitizer, but the clinical outcomes can be unpredictable, according to Dr. E. Victor Ross.
"Our worst scenarios have been when we’ve used EMLA on the skin. We’ve stopped using EMLA or lidocaine cream on the skin in ALA-PDT because of the very pronounced, enhanced photodynamic effects. You get great long-term results, but such a bad short-term result that lots of people didn’t want to go through it," said Dr. Ross of Scripps Clinic Laser and Cosmetic Dermatology Center in Carmel Valley, Calif.
Bruce Jancin/Elsevier Global Medical News
Dr. E. Victor Ross
Using a topical numbing agent seemed to be an attractive option because patients often complain that photodynamic therapy (PDT) is painful. Plus, there seemed to be an added benefit: The anesthetic cream increased aminolevulanic acid (ALA) uptake by the skin, such that ALA incubation times before application of the light source could be greatly compressed. But clinical outcomes were too unpredictable, he said at the seminar sponsored by Skin Disease Education Foundation (SDEF). After several patients had unintended florid full photopeels involving 1½ weeks of downtime, it was time to abandon the practice.
When ALA-PDT first appeared about 10 years ago, the indication was for the treatment of actinic keratoses (AKs). Today this approved indication remains the No. 1 reason Dr. Ross utilizes the therapy, he said. But PDT’s role has expanded off label to include cosmetic procedures and the treatment of warts, nonmelanoma skin cancer, nevus sebaceous, as well as acne, which he considers "one of the great opportunities for PDT." In addition, in Asia, dermatologists are now refining the use of PDT with hematoporphyrin derivatives for the treatment of port wine stains and other vascular lesions.
Many U.S. dermatologists have incorporated PDT into their practices, with ALA being more widely used as a photosensitizer than methyl aminolevulinate (MAL). Yet PDT is a therapy that hasn’t been fully optimized; it is still fraught with side effects and suboptimal results, he said. Moreover, some fundamental issues regarding PDT remain unanswered: For example, the optimal duration of photosensitizer incubation time for various indications is still controversial.
Dr. Ross said he opts for what he considers a middle-of-the-road approach, with ALA application times of about 90-120 minutes, which he views as having an optimal balance between side effects and effectiveness. Even so, he noted that among the 8-10 patients per week he treats with ALA-PDT on average, 1 or 2 experience mild side effects.
"I don’t think we’re quite ‘there’ yet with PDT, although we’re getting closer. There are still so many tricks involved in making it work without side effects. We’ve still got some work to do," he said.
In addition to advising his colleagues to stay away from topical anesthetic creams, he offered additional tips for the use of ALA-PDT. Among them:
• Sending acne into long-term remission via PDT remains the Holy Grail, he said. The objective is to enhance the fluorescence of protoporphyrin 9 at the sebaceous gland while sparing the epidermis.
Some investigators are using low-intensity blue light at the skin surface while the photosensitizer is incubating in order to bleach it out of the epidermis, or, alternatively, warming and cooling the skin.
The best results Dr. Ross said he has seen have come through an arduous regimen involving three 3-hour-long ALA applications scheduled a month apart. There’s a delayed effect, with significant improvement coming at 3-6 months.
"It’s a tough, tough therapy to get through. There are lots of pustules and papules, and the acne invariably gets worse before it gets better. This doesn’t play into the hands of the typical teenager, who wants to get better right away," Dr. Ross said.
• A creamy solution of ALA will create more protoporphyrin 9 than an aqueous solution will.
• A red light source should be considered for deeper structures, such as basal cell carcinomas or sebaceous glands, and blue light for treating more superficial skin lesions. Although continuous blue light is 40 times more potent per photon than red light in exciting protoporphyrin 9, it doesn’t penetrate as deeply.
• Performing low-density fractional CO2 ablative laser therapy prior to application of the photosensitizing agent is "an exciting advance" in PDT, he said.
The innovation was developed by an international team led by investigators at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, who published a split-face randomized study involving 15 patients with a total of 212 facial AKs. At the 3-month follow-up, the complete response rate of grade II-III lesions treated with MAL-PDT preceded by fractional ablative laser therapy was 87.5%, vs. 58.8% with conventional MAL-PDT. The complete response rate of grade I AKs was 100% with fractional laser/MAL-PDT, vs. 79% for MAL-PDT alone.