Photodynamic therapy

Coined by O. Raab in 1900, this is a form of photochemotherapy in which a photosensitizer (e.g., 5-aminolevulinic acid, porphyrin derivatives) reacts with visible light to produce cyto- or tissue-toxic products. The basic prerequisite for this reaction is the presence of oxygen. Redox processes and radical chain reactions produce reactive singlet oxygen, which reacts cytotoxically and can destroy tissue structures as well as amino acids, nucleic acids and fatty acids. The method exploits the affinity of certain porphyrin derivatives on tumor cells. Tumor cells, as well as macrophages, take up LDL-bound photosensitizers by endocytosis. Subsequent irradiation with polychromatic light sources leads to the destruction of the cells while sparing the surrounding tissue. Irradiation doses range from 25 to 300 J/cm².

see also antimicrobial photodynamic therapy, aPDT, PACT

According to the guidelines of the European Dermatology Forum on topical photodynamic therapy, approval has been granted in Europe for the following indications:

• Actinic keratoses
• squamous cell carcinoma in situ, Bowen's disease
• superficial basal cell carcinoma
• nodular basal cell carcinoma
• Field carcinomatization

Recommendation grade A for: actinic keratoses, squamous cell carcinoma in situ, Bowen's disease, superficial basal cell carcinoma, nodular basal cell carcinoma and photorejuvenation

According to the guidelines of the European Dermatology Forum for topical photodynamic therapy, not approved in Europe, but recommendation grade B for photodynamic therapy exists for the treatment of non-melanocytic skin carcinomas in organ transplant patients, acne, therapy-resistant genital and plantar warts, skin leishmaniasis and onychomycosis

Also not approved, but still recommendation grade C is given by the European Dermatology Forum in its guidelines for superficial fungal infections, deep cutaneous tinea and hypertrophic scars and keloids.

For cutaneous T-cell lymphoma, the European Dermatology Forum recommends the use of topical PDT only for localized diseases with recommendation grade C.

PDT with porphyrin derivatives: Also as second-line therapy in patients with advanced squamous cell carcinoma of the head or neck (after failure of previous therapies and impracticability of X-ray therapy), excision and systemic chemotherapy.

• Preliminary results, which require further clinical confirmation, have been reported in the following diseases (Balakirski G et al. 2024):
  • Verrucae planae juveniles
  • psoriasis vulgaris
  • cutaneous sarcoidosis
  • lichen planus
  • pseudolymphomas
  • acne vulgaris
  • circumscribed scleroderma.

For actinic keratoses, one session, for basal cell carcinomas two (or more) sessions at an interval of one week: first, removal of scales and crusts on the lesion to be treated.

Application of the photosensitizing ointment (1 mm thick) by spatula on the lesion to be treated and overlapping 1 cm on the surrounding clinically healthy skin. Occluding and light-tight dressing. Therapy time over 3 hours if the methyl ester of aminolevulinic acid is applied (commercial preparation Metvix); over 6 hours if ALA is administered magistrally (usually 20%). Subsequently, irradiation (e.g. with red light, wavelength 570-670 nm in a dose of 75 J/cm²).

• Photosensitizers: e.g. Metvix® (methyl aminolevulinate; Galderma Laboratorium GmbH, Düsseldorf) 160 mg/g cream, this cream is approved as a ready-to-use preparation, or e.g. Ameluz® (5-aminolevulinate; Biofrontera AG, Leverkusen) 78 mg/g gel, also approved as a ready-to-use preparation.
• As an alternative to the cream base, a patch containing the active ingredient, Alacare® (5-aminolevulinate; photonamic GmbH & Co. KG, Reinbek) with 8 mg active ingredient per 4 cm² can be used on the face and hairless areas of the scalp.
• Lamps: e.g. Aktilite (wavelength 630 nm, especially when using Metvix); alternatively: BF-RhodoLEDZ. Wavelength 635 nm, or e.g. Hydrosun.

The treatment can only be performed by medical colleagues who have acquired sufficient experience in this therapy. Since these are so-called blind therapy procedures, histological clarification before the start of treatment, as well as a close clinical follow-up, is absolutely necessary!

The photodynamic therapy of actinic keratoses can also be performed as photodynamic daylight therapy.

1. Balakirski G et al. (2024)* Photodynamic therapy in dermatology: established and new indications. J Dtsch Dermatol Ges 22:1651-1662.

2. Bickers R (1995) Photodynamic therapy. Z Hautkr 70: 328-331

3. Braathen L et al. (2007) Guidelines on the use of photodynamic therapy (PDT) for the non-melanoma skin cancer - an international consensus. J Am Dermatol 56: 125-143
4. Cairduff F et al. (1994) Superficial photodynamic therapy with 5-aminolevulinic acid for superficial primary and secondary skin cancer. Br J Cancer 69: 605-608
5. Cather J, Menter A (2002) Novel therapies for psoriasis. Am J Clin Dermatol 3: 159-173
6. Gniazdowska B et al. (2007) Allergic contact dermatitis from delta-aminolevulinic acid used for phtodynamic therapy. Contact Dermatitis 38: 348-349
7. Hopper C (2000) Photodynamic therapy: a clinical reality in the treatment of cancer. Lancet Oncol 1: 212-219
8. Landthaler M et al. (1993) Photodynamic therapy of tumors of the skin. Dermatologist 44: 69-74
9. Leman J et al. (2002) Topical 5-ALA photodynamic therapy for the treatment of cutaneous T-cell lymphoma. Clin Exp Dermatol 27: 516-518
10. Pariser DM et al. (2003) Photodynamic therapy with topical methyl aminolevulinate for actinic keratosis: results of a prospective randomized multicenter trial. J Am Acad Dermatol 48: 227-232
11. Raab O (1900) On the effect of fluorescent substances on infusoria. Z Biol 19: 524-564
12. Szeimies RM et al. (1994) Topical photodynamic therapy in the treatment of superficial skin tumors. Dermatologist 46: 315-318
13. Szeimies RM et al. (2002) Photodynamic therapy using topical methyl 5-aminolevulinate compared with cryotherapy for actinic keratosis: A prospective, randomized study. J Am Acad Dermatol 47: 258-262
14. Valenta C et al. (2005) Skin permeation and stability studies of 5-aminolevulinic acid in a new gel and patch formulation. J Contr Rel 107: 495-501

15. Morton CA et al. (2020) European Dermatology Forum guidelines on topical photodynamic therapy 2019 Part 2: emerging indications - field cancerization, photorejuvenation and inflammatory/infective dermatoses. JEADV 34: 17-29