A new form of photodynamic therapy remains controversial

A new approach to photodynamic therapy (PDT) – where patients expose their skin to daylight after application of a photosensitizing agent – is gaining traction in Europe, and dermatologists in the United States could soon see more patients inquiring about daylight PDT.

While proponents of daylight PDT point to less pain and greater convenience for patients who have when acne or precancerous actinic keratosis (AK) lesions or are trying to improve the appearance of their skin, not everyone is convinced this approach is safe.

A man's scalp is prepared before daylight PDT treatment.

In terms of evidence-based medicine, there is a continental divide on this issue, with the majority of research coming from Europe. It’s not unusual for a new dermatology procedure or agent to debut in Europe and later come to the United States, but, in the case of daylight PDT, several factors make a direct comparison difficult, including disparate formulations of aminolevulinic acid (ALA) approved on either side of the Atlantic. Another factor is that the degree of sun exposure in studies conducted in Northern European climates may be quite different than the exposure in some parts of the United States, especially in Southern states.

The European experience

Italy is among the European countries where daylight PDT has been evaluated in quality studies. In one Italian study, a split-face study of 35 patients with multiple grade 1 AKs of the face and scalp, no statistically significant difference in the complete response rate of grade 1 AKs at 3 months emerged between the side of the face treated with daylight PDT (87%) and the side treated with conventional PDT (91%). Most of the patients preferred the treatment with daylight PDT, reported the investigators, from the University of L’Aquila (Italy) and the University of Milan (J Eur Acad Dermatol Venereol. 2015 Oct;29[10]:1926-32).

“Daylight photodynamic therapy is an advantage for patients with multiple grade 1 or 2 actinic keratoses because it is as effective as conventional PDT, but [with] virtually no pain and inflammation,” Piergiacomo Calzavara-Pinton, MD, chairman of the department of dermatology at the University of Brescia (Italy), said in an interview.

Another advantage of daylight PDT is the ability to treat a larger surface area, he said, pointing out that it is possible to treat half of the face (200 cm²) in only one session. “The drawback is the cost, but, if you compare this with Picato [ingenol mebutate] and Aldara [imiquimod], you must calculate that they are approved for 25 cm2. Therefore, if you need to treat 200 cm², you need eight packages,” added Dr. Calzavara-Pinton, who is also the president of the Italian Society of Dermatology.

“Daylight PDT with methyl aminolevulinate ... has proven to be efficacious in the treatment of mild to moderate actinic keratoses on the face and scalp,” agreed Rolf-Markus Szeimies, MD, PhD, head of the department of dermatology and allergology at Klinikum Vest, Recklinghausen, Germany.

Typically, after a patient applies a chemical sunscreen to block unwanted components of ultraviolet exposure, he or she applies methyl aminolevulinate. Within 30 minutes, patients should begin exposure to daylight, lasting for 2 hours, with light ranging from fully cloudy to a clear blue sky, Dr. Szeimies said in an interview. The outside temperature should not be below 50° F, he noted.

He cited two randomized, controlled, split-face studies conducted in Australia and Europe, the COMET-1 and COMET-2 trials in patients with mild to moderate AKs of the face and scalp, which found that cure rates with daylight PDT “were not statistically inferior to conventional PDT with red light.” The biggest advantages “are the single-treatment setting, the possibility to treat large areas in one step, the excellent cosmesis, and the almost total lack of pain during the procedure,” he said in an interview.

While it is not approved by the Food and Drug Administration for use in the United States, daylight PDT is a registered treatment modality in Europe, Australia, and South America, said Dr. Szeimies, who presented an update on daylight PDT during a session on PDT at the 2017 annual meeting of the American Academy of Dermatology in Orlando.

U.S. dermatologists urge caution

James Spencer, MD, is among those who believe daylight PDT is a bad idea. “There is a real potential for misadventure – people getting too much light and getting a severe sunburn reaction,” he said in an interview.