WAILEA, HAWAII — Aggressively dosed red light photodynamic therapy effectively destroys sebaceous glands, resulting in prolonged inhibition of sebum output and lasting cure of moderate-to-severe acne, according to Dr. R. Rox Anderson said.
"I don't use the word 'cure' lightly. I think there really are patients you can cure with high-dose aggressive photodynamic therapy. In my experience, it's more effective than oral retinoids. It's something you want to reserve for patients who have more severe acne, though," said Dr. Anderson, professor of dermatology at Harvard Medical School, Boston, and director of the Wellman Center for Photomedicine at Massachusetts General Hospital.
High-dose red light PDT needs to be employed selectively because it is a time consuming office-based procedure with substantial side effects. These include marked pain, several days of erythema and edema, crusting, sterile pustules, and sensitivity to light that keeps patients indoors for 48 hours post-treatment; because of their daunting appearance, they actually welcome being temporarily shut in. Complete healing is typical a week after treatment, he explained at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).
This therapy is different from the low-dose version of PDT that improves acne temporarily via its anti-inflammatory effect. High-dose red light PDT is akin to a necrotizing folliculitis that results in histologically confirmed destruction of many of the deeply placed sebaceous glands.
Having first demonstrated that high-dose red light PDT is capable of curing acne in a small clinical trial 11 years ago (J. Invest. Dermatol. 2000;15:183-92), lately, Dr. Anderson has focused on optimizing the treatment. He is varying the topical photosensitizer agent and dose, contact time, light fluence, and other factors in an effort to make a faster therapy with fewer side effects, while preserving the unmatched effectiveness.
"We're not done with this yet. We're still tweaking," he said. "This work is not funded by any drug or device company. I'm doing it because I just want to help people with severe acne. It's still the number-one disease we face. We're losing Accutane [isotretinoin] because of medicolegal issues and we need to come up with an alternative."
An important step has been the discovery in his laboratory that low-level blue light, shined on the skin during incubation with the photosensitizing agent, appears to inhibit porphyrin synthesis selectively in the epidermis. This turns off unwanted epidermal photosensitization and greatly lessens the epidermal inflammatory reaction responsible for many of the most florid treatment side effects. At the same time, the dim blue light, which cannot penetrate far into the skin, allows continued production of porphyrin deep into the sebaceous follicles, where the red light is aimed.
"Pain scores go from 7 or 8 on a 10-point scale down to 1 or 2 with blue light," according to Dr. Anderson.
The only Food and Drug Administration-approved dermatologic indication for the two topical PDT photosensitizing agents—aminolevulinic acid (Levulan) and methyl aminolevulinate (Metvixia)—is treatment of actinic keratoses.
For physicians interested in using high-dose red light PDT off-label to treat severe acne, Dr. Anderson provided several practical tips. First degrease the skin, then apply the photosensitizing agent under plastic wrap occlusion for 1-3 hours with low-level blue light, and apply 5%-7% topical lidocaine 30 minutes before putting on the red PDT light for 10-30 minutes. Use a red light LED array having a 635-nm wavelength and a fluence of at least 50 J/cm2. The topical lidocaine has the side benefit of greatly enhancing the PDT response for reasons that are not understood.
Also, keep the treatment room warm. Porphyrin is the target in PDT, and porphyrin synthesis varies tremendously depending upon skin temperature. A chilly room will essentially shut it down. Dr. Anderson said he keeps the room warm and dimly lit with a low-level blue LED light source. The optimal features of the blue light in terms of wavelength and output level are still under study.
The two available photosensitizing agents appear to be essentially equivalent for this form of therapy, although methyl aminolevulinate tends to be more selective for the sebaceous glands.
The treatment course consists of four sessions at roughly 2-week intervals. The first two sessions elicit the big inflammatory reaction. The third and fourth generate only a mild sunburn-like reaction.
Asked if he is concerned about possible long-term adverse health consequences resulting from destroying sebaceous glands, Dr. Anderson said he used to be until he asked the late Dr. Albert Kligman for his thoughts.
"He said if you want to know what skin is like with no sebaceous gland function, look at any child. The glands are there but they're turned off because they haven't yet seen the androgen of puberty," recalled Dr. Anderson. "So, I think functionally, the sebaceous gland is just there as God's curse on teenagers."