Photodynamic Therapy

Photodynamic therapy involves the use of photochemical reactions with the interaction of photosensitising agents, light energy and oxygen, for the treatment of malignant and benign diseases. Photodynamic therapy includes two stages.During the first stage, the photosensitiser is administered to the patient in one or more ways (topical, intravenous, orally), and is absorbed by the target cells. The second stage includes the activation of the photosensitiser in the presence of oxygen through a light of specific wavelength at the area where the photodynamic therapy is applied. Since the photosensitising agent is absorbed more by cells that proliferate faster, the treatment is selective, minimising healthy tissue damage.

Photosensitisers

The most commonly used photosensitisers in Photodynamic therapy (PDT) are ALA (amino-levulinic acid) and MAL (methyl-amino-levulinic acid). In Greece METVIX is available, which is available in a 2 g tube of MAL. It is used for the treatment of actinic keratosis on the face and scalp, for superficial and nodular basal cell carcinoma (BCC), and for Bowen’s disease.

Any light source, laser or not, with the adequate wavelength and high absorption in the spectrum of the photosensitising agent, can be used in Photodynamic therapy.

Laser

The purpose of Lasers in Photodynamic therapy is to initiate a photochemical reaction as opposed to photothermal or photomechanical reactions observed in other dermatological applications. Almost any laser device with a wavelength between 400-800 nm (visible light) can be used as the light source, with higher effect in cases that the wavelength of the light source overlaps with the drug absorption curve.

Light Sources for ALA and MAL

According to the current dermatological practice, the use of MAL (Metvix) involves exposure to 37J / cm2 or 75J / cm2 of red light using the relevant devices.

The use of Photodynamic Therapy in Dermatology

The only official use of Photodynamic Therapy is for the treatment of actinic keratosis. Other common applications that are not included in the indications are basal cell carcinomas, photo-ageing, acne and Bowen’s disease, among other conditions.

Photodynamic therapy in Actinic keratosis

For the treatment of Actinic Keratosis with MAL, the cream must be applied on the lesions after skin preparation. This includes removal of the keratosis and scales to allow better absorption of the drug. Following this, MAL (Metvix) is applied under occlusion for approximately 3 hours and then the area is exposed to 37J/cm2 or 75J/cm2 red light. Photodynamic therapies are repeated in 3-month or weekly intervals according to the treatment protocol.

Photodynamic therapy in Basal Cell Carcinoma

Metvix is the only substance that has been approved for use in basal cell carcinomas, in superficial or nodular basal cell carcinoma on the head or scalp. The relapses and the effectiveness are comparable to that of surgical excision, cryotherapy and other forms of treatment, however the aesthetic result is clearly superior.

Photodynamic therapy for Photo-ageing

Photodynamic therapy is widely used for the treatment of photo-ageing, although this use is not included in the indications. The parameters concerning the application time of the photosensitiser, the light energy and the duration of the treatment vary.

Photodynamic therapy for Acne

Photodynamic therapy (PDT) with use of Metvix has been used successfully for the treatment of acne, achieving clinical reduction of both sebum production and the size of the sebaceous glands. Biopsies have demonstrated the destruction of the sebaceous glands, which proves the long-term remission of the condition thanks to photodynamic therapy. The fact that red light penetrates deeper because of its wavelength makes it more suitable than blue light for the treatment of acne.

Photodynamic therapy for Bowen’s disease

The use of MAL (Metvix) is indicated in Europe for the treatment of Bowen’s disease, in cases where surgical excision is not appropriate. Bowen’s disease is one of the best indications for photodynamic therapy because the lesions are big and surgical excision can lead to scarring.

Other Applications of Photodynamic therapy

The use of ALA andphotodynamic therapyafter the application of Pulse -Dye Laser 565 nm is more effective in comparison to Laser alone for the hyperplasia of the sebaceous glands. Photodynamic therapy is applied in many other skin conditions, such as actinic cheilitis, flat warts, genital warts etc.

Phototoxic reactions – Desired and excessive

After the application of photodynamic therapy, a burning sensation or pruritus (itching) is often observed. These sensations usually decrease rapidly once the treatment session is completed. A phototoxic reaction on Actinic Keratoses and Basal Cell Carcinomas is characterised by erythema, oedema, crusting, vesiculation, pustules or erosion in most patients. These are considered normal and desirable reactions to achieve the therapeutic effect. Patients should be protected from sun exposure, especially during the first 2 days after Photodynamic therapy.

Pigmentary abnormalities and hypersensitivity reactions

Hyperpigmentation is sometimes seen after photodynamic therapy, which tends to fade over a few months. Hypopigmentation at treated sites has also been observed. Cases of allergic contact dermatitis and urticaria due to MAL (Metvix) have been rarely reported.

Contraindications

Metvix is contraindicated in persons with porphyria, cutaneous hypersensitivity, allergy to porphyrins, or known sensitivity to any component of the cream. The medicinal product contains peanut and almond oils.

Photodynamic therapy is not indicated for the treatment of pigmented or morpheaform BCC as no relevant studies have been conducted.

The use of both medicines during pregnancy is controversial. In addition, their use in children is contraindicated; although they have been used in persons with Gorlin syndrome, experience with treating patients younger than 8 years is very limited.

The major limitation of photodynamic therapy is its depth of treatment, which appears to be mainly the result of the failure to achieve adequate drug penetration, rather than light penetration. Greater uptake and a greater effective depth for photodynamic therapy could be obtained by increasing the application or occlusion times or by adding penetration enhancers, such as cleaning with acetone. Iontophoresis and electroporation constitute interesting alternatives. As improved photosensitisers and less expensive light sources are developed, photodynamic therapy will undoubtedly become an important alternative therapeutic option for the treatment of a many disorders in the near future.

Photodynamic therapywith methyl amino levulinate

The following procedure is used with Metvix:

  • Before applying the cream, the surface of the actinic keratosis is prepared by removing scales and crusts.
  • A spatula is used to apply a 1-mm thick layer of methyl amino levulinate cream to the lesion and surrounding 5 mm of normal skin. Ideally, nitrile gloves should be sued for the application and removal of the cream, because vinyl and latex gloves do not provide adequate protection. The area on which Photodynamic therapy will be applied should be covered with an occlusive dressing.
  • The same cream may be used for the second session, as long as it is performed within 7 days and the cream is stored in the fridge.
  • Patients should avoid sun exposure or exposure to artificial light on the area(s) of application, as well as exposure to cold temperatures between cream application and phototherapy.
  • 3 hours after the application of Metvix cream, the dressing should be removed and the treatment area should be cleaned with normal saline. The area is then exposed to red light at 37J/cm2, which is applied for approximately 9 minutes, keeping a distance of 5-8 cm between the device and skin. The patient, the operator, and any other person in the room should wear special protective goggles.
  • After the end of treatment, patients should not be exposed to sun or other artificial sources of intense light for at least 48 hours. Non-compliance may lead to intense phototoxic reactions.