Applications of Photodynamic Therapy in Pediatric Age

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Photodynamic therapy (PDT) has long been considered an attractive, non-invasive therapeutic procedure widely used in adult patients for treatment of tumoral, inflammatory, and infectious skin diseases. PDT is a photochemotherapy based on local application of a photosensitive compound and subsequent exposure to a light source of adequate wavelength.

Researchers at the University of Messina in Italy, led by Luca Di Bartolomeo, department of clinical and experimental medicine in dermatology, wanted to explore the applications of PDT in pediatric ages, as well as look toward future applications.

In their paper¹, the authors explained that the most common photosensitizers utilized in dermatology are the 5-aminolaevulinic acid (ALA, an intermediate of the heme biosynthetic pathway) and its methyl ester 5-aminolevulinate (MAL), which are converted inside the target cells to photo-active protoporphyrin IX (PpIX).

“After an incubation period of around three hours, PpIX is activated by an artificial light source (conventional PDT) or by sunlight (daylight PDT), thus leading to the production of reactive oxygen species (ROS), triggering both apoptosis and necrosis of target cells as well as stimulation of an immune modulating response,” Di Bartolomeo said.

While different light sources with varying wavelengths can be used in PDT, past studies have revealed that the absorption spectrum of protoporphyrin IX shows maximal absorption peaks at approximately 410 nm—the wavelength of blue light. However, it also shows smaller absorption peaks at 506, 532, 580, and 630 nm as well, namely within the red light wavelength.

Therefore, the impact of red light seems to be stronger than what is observed with blue light due to the greater depth of penetration of red light into dermis, thus explaining its diffuse use worldwide with respect to blue light.

For its data, the researchers utilized the PubMed database using the terms “photodynamic therapy” and “skin.” Parameters were English-only research, and a systematic literature search was led based on the PRISMA flowchart.

Di Bartolomeo was one of two dermatology experts who critically examined clinical trials, retrospective studies, case series, and case reports. In total, 44 articles were identified with 33 studies exclusively focusing on pediatric patients.

“We included only studies on patients treated with topical ALA-PDT or MAL-PDT, the photosensitizers widely available and therefore most commonly used by dermatologists,” Di Bartolomeo said.

Among the parameters for those studies were patients’ features, type of topical photosensitizers and light sources used, conditions of treatment, number of treatments, and outcomes and adverse events.

The researchers noted that the onset of skin cancers in pediatric age is a rare event, however, some genetic syndromes, such as Gorlin syndrome or xeroderma pigmentosum, may predispose them to the development of skin tumors.

“Clinical trials focusing on PDT treatment in children are rare,” the authors wrote. “There is a general reluctance about involving children in trials by parents and adults, especially because of fears of unpredictable side effects in the pediatric population. Moreover, trials on children involve more ethical concerns because children lack the capacity to understand the risks underlying trials and informed consent is difficult to obtain by parents.”

Even so, the authors discovered promising results in the available data.

“It appears as a safe therapeutic procedure,” Di Bartolomeo said. “Pain may limit the compliance of pediatric patients but previous local analgesia or more tolerable PDT settings, for example, daylight PDT, lower PS concentration, shorter incubation times or lower light fluences, may be useful in more sensitive patients.”

A challenge is that it’s time-consuming because patients need to wait several hours at the hospital between PS application and illumination. Therefore, daylight PDT may be useful to reduce waiting times and it better fits pediatric patients who would rather spend time outside than within the walls of a hospital.

The authors noted that data on efficacy of DL-PDT in pediatric patients are still limited, and further comparison between C-PDT and DL-PDT is needed for more accurate conclusions.

What they did conclude is that PDT has an advantage in that it can combine easily with other therapies, thereby increasing its effectiveness rates. The majority of local combination therapies, such as curettage, microneedling, fractional micro-plasma radiofrequency, radiant infrared or surgical debulking, were used to improve penetration of photosensitizer in the skin. So, other therapies with mechanism of action other than PDT, such as cryotherapy for viral warts or oral antibiotics for juvenile acne, can also be associated without increased risk of adverse effects.

Reference

1. Di Bartolomeo, Luca et al. “Photodynamic therapy in pediatric age: Current applications and future trends.” Frontiers in pharmacology vol. 13 879380. 16 Aug. 2022, doi:10.3389/fphar.2022.879380