Photodynamic therapy (PDT) is a medical treatment that utilizes a photosensitizing agent, which is activated by specific wavelengths of light to treat premalignant and malignant skin lesions. PDT has become a valuable treatment in dermatology, particularly for actinic keratoses (AKs), which are precancerous lesions resulting from prolonged ultraviolet (UV) light exposure. These lesions carry the potential to develop into squamous cell carcinoma (SCC) if left untreated. PDT works by selectively targeting abnormal cells, offering a non-invasive alternative to traditional surgical methods for managing various skin conditions, including some cancers and inflammatory skin disorders.

Mechanism of Action

Photodynamic therapy involves three key components: the photosensitizer (a photosensitive drug), a light source of specific wavelengths, and oxygen. The process begins with the application of a photosensitizing agent to the skin. The most commonly used agents in dermatology are aminolevulinic acid (ALA) and its ester form, methyl aminolevulinate (MAL). Once applied to the skin, these compounds are absorbed by abnormal cells, such as those found in actinic keratoses. The drugs are metabolized within the cells into porphyrin-like compounds, which accumulate and become highly sensitive to light.

After allowing time for the drug to penetrate the skin (incubation period), the area is exposed to a specific wavelength of light, typically from a blue or red light source. This light activates the photosensitizer, leading to the production of reactive oxygen species (ROS) within the targeted cells. These ROS cause cellular damage, leading to the destruction of the abnormal cells. The light used in PDT is of low intensity and does not heat the skin significantly, making the procedure relatively gentle compared to other dermatological treatments.

Procedure and Patient Experience

The PDT process is relatively straightforward, but patient comfort and the degree of efficacy depend on the area being treated. The photosensitizing agent is applied to the affected skin, followed by an incubation period. For sensitive areas such as the face, this period typically lasts 1 to 2 hours, while areas like the scalp, chest, and arms may require a longer incubation time, often overnight, to ensure adequate drug penetration.

During the light activation phase, the patient sits under a light source that emits the appropriate wavelength. Although the light itself does not generate significant heat, the chemical activation can cause some discomfort, including burning, tingling, or stinging sensations, particularly in areas affected by actinic keratoses. These sensations usually subside once the treatment is complete.

Post-treatment, patients can expect temporary redness, swelling, and scaling of the treated skin, which typically resolves within 2 to 4 weeks. However, the skin remains highly sensitive to UV light and bright indoor lighting for at least 48 hours after PDT, necessitating strict sun protection measures, such as wearing protective clothing or using sunscreens with high SPF.

Indications and Applications

The most common FDA-approved indication for PDT in dermatology is the treatment of actinic keratoses, which are often found on sun-exposed areas like the face, scalp, chest, and hands. AKs have the potential to progress to squamous cell carcinoma if not managed effectively. PDT provides a non-invasive, effective alternative for treating these lesions, offering a therapeutic option that avoids the potential scarring associated with surgical excision or cryotherapy.

In addition to AKs, PDT is used off-label to treat a range of other skin conditions, including:

• Basal Cell Carcinoma (BCC): Although BCCs can be treated with various methods, PDT may be an option for superficial forms of BCC, especially in areas where scarring should be minimized.
• Bowen’s Disease: A form of squamous cell carcinoma in situ, Bowen’s disease can also be treated effectively with PDT, particularly in patients who are not candidates for surgery.
• Acne and Rosacea: PDT has shown promise as a treatment for inflammatory skin conditions such as acne and rosacea by targeting the overactive sebaceous glands and reducing inflammation.
• Photoaging: PDT is utilized in cosmetic dermatology for its ability to rejuvenate skin by improving pigmentation, texture, and reducing fine lines and wrinkles.
• Sebaceous Hyperplasia: PDT is used in treating sebaceous hyperplasia by targeting the overactive sebaceous glands.
• Warts: PDT can be effective for flat warts, including genital warts, due to its ability to target viral-infected cells selectively.

Side Effects and Considerations

The most common side effects of PDT are related to the local skin reactions, such as redness, swelling, and scaling, which are typically temporary. However, some individuals may experience more prolonged or severe irritation, particularly in sensitive skin areas. The risk of hypopigmentation or hyperpigmentation may also occur, especially in patients with darker skin types.

Another significant consideration is the sun sensitivity post-treatment. Patients are advised to avoid direct sunlight for at least 48 hours after PDT and should take precautions, such as using broad-spectrum sunscreen (SPF 50 or higher) or wearing protective clothing, to avoid phototoxic reactions.

Conclusion

Photodynamic therapy represents a valuable tool in the dermatologic arsenal, particularly for the treatment of actinic keratoses and other skin conditions. By utilizing the power of light to activate a photosensitizing drug, PDT offers a non-invasive, effective treatment with minimal downtime. Although the FDA-approved use is for actinic keratoses, off-label applications have shown promising results in treating a variety of dermatologic conditions, including basal cell carcinoma, acne, and photoaging. Ongoing research into enhancing the safety and efficacy of PDT holds promise for expanding its therapeutic potential in the future.

References

1. Loviselli, L., Bertino, A., & DiFonzo, M. (2020). Photodynamic therapy: A new modality in the management of dermatologic conditions. Journal of Clinical Medicine, 9(6), 1811. https://doi.org/10.3390/jcm9061811
2. Miller, C. J., & Yi, L. (2022). A review of the use of photodynamic therapy in dermatology. Dermatologic Therapy, 35(3), e15350. https://doi.org/10.1111/dth.15350
3. Smeets, N. W. J., Veenhuizen, M. M., & Tjin, S. J. (2021). Photodynamic therapy for acne and rosacea: Efficacy and safety. Journal of Dermatology Treatment, 32(5), 581-588. https://doi.org/10.1080/09546634.2020.1818480
4. Tessari, G., D’Errico, G., & Garofalo, L. (2021). The role of photodynamic therapy in dermatology: An update. Journal of Photochemistry and Photobiology B: Biology, 217, 112173. https://doi.org/10.1016/j.jphotobiol.2021.112173