Treatment of a broad area, occluding extremities, and the use of antihistamines are among the measures that can help optimize the results of treating actinic keratoses (AKs) with topical photodynamic therapy (PDT) using aminolevulinic acid (ALA), according to Dr. Brian Berman.

For many patients with AKs, ALA-PDT can be an effective and well-tolerated option, Dr. Berman said in a presentation at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

ALA-PDT is a two-step process, Dr. Berman explained. The first step involves the application of ALA with presumed selective cellular uptake, followed by conversion to protoporphyrin IX (PpIX). Next, the light activation of PpIX causes cell death via high-energy oxygen molecules.

Histamines play a role in the topical response to ALA-PDT, which generally involves some edema and erythema, he noted. “The edema component is generated by mast cell degranulation and can be uncoupled using selective H1 antihistamines,” he said. However, the erythema response is not affected by H1 blockade, he added.

Dr. Berman’s recommendations for optimizing ALA-PDT to treat AKs include a shorter ALA incubation time; treatment of a broad area, not just the baseline visible AKs; occlusion of ALA for AKs on the arms and legs; increased skin temperature during ALA incubation; and moderate cooling during light exposure. To reduce pain, he recommended a very short ALA incubation time with a longer time of light exposure.

He referred to a 2004 study of 18 patients, which found that AK reductions were not significantly different at 1 month post treatment with ALA incubation times of 1, 2, or 3 hours ( Arch Dermatol. 2004 Jan;140[1]:33-40 ). As for occlusion, a 2012 study found that AK clearance was significantly greater for extremities that were occluded during incubation in patients undergoing blue light ALA-PDT, compared with areas that were not occluded ( J Drugs Dermatol. 2012 Dec;11[12]:1483-9 ).

Skin cooling can be useful in reducing patients’ pain, said Dr. Berman of the department of dermatology and cutaneous surgery, University of Miami. Data from a retrospective study showed that cooling pain relief, with an air-cooling device during treatment, resulted in lower PpIX photobleaching in AK lesions, compared with no cooling ( J Photochem Photobiol B. 2011 Apr 4;103[1]:1-7 ). But cooling was associated with decreased efficacy of the PDT treatment in terms of complete AK response (68% for the cooling device group vs. 82% for controls without cooling), he said.

Increasing skin temperature has been shown to reduce AK lesions significantly, compared with no heat, Dr. Berman pointed out. “PpIX synthesis is temperature dependent,” he said. The median difference in AK lesion counts was significantly greater on a heated extremity side than a control side in an unpublished study, he noted.

Finally, when it comes to facial AKs, less may be more in terms of treatment time. In a split face study, a “painless PDT” protocol of 15 minutes of ALA incubation with 1 hour of blue light yielded a 52% reduction in AKs at 8 weeks post treatment, vs. a 44% reduction with a standard treatment of 75 minutes of ALA incubation with 16 minutes, 45 seconds of blue light, Dr. Berman said.

Dr. Berman disclosed relationships with multiple companies including Ferndale, LEO, Halscion, Sensus, Exeltis, Dermira, Celumigen, Sun, DUSA, Biofrontera, and Berg. He holds stock in Halscion, Dermira, Celumigen, and Berg.

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