Practical Photodynamic Therapy (PDT) made simple (For Professionals)

PDT: HOW DOES IT WORK ?

• PDT= photosensitizer + light + oxygen

• It was discovered in early 1900’s by a medical student (the professor claimed it first as his own !)
• Its action is through the generation of a singlet oxygen by using drugs and light.
• Porphyrin sensitizer* + light + porphyrin thus generates an excited porphyrin molecule who passes the energy to oxygen. Singlet oxygen is the consequence of this.
• Singlet oxygen has the follwing actions:

1. induces necrosis
2. induces apoptosis
3. kills microbes

Important to understand: Porphyrin are huge molecules (unable to penetrate intact skin) whereas ALA (and methyl-ALA) is small. ALA combines with a porphyrin to generate protoporphyrin 9 (PPIX which is photosensitizing).

*ALA= aminolevulinic acid, Methy-ALA=methyl-aminolevulinic acid

HOW TO DO IT ?

1. Administer photosensitizer
2. Wait
3. Apply light

1. Administer photosensitizer (Photosensitizers: ALA or methyl-ALA).

• ALA:

1. open application
2. easier to apply.

• Methyl-ALA:

1. occluded application
2. easier to see.

1. Off label preparation:

1. 20% ALA in a solution, lotion or cream.
2. Prepare it fresh as not stable

A patch is being developed (Szelmies et al, BJD 2010)

2. Wait

• One hour up to overnight.
• Lots of variability
• Photoprotection: just using sunscreens is NOT enough.

Tip: Show lesion to patient with Wood’s lamp as it fluoresces !

3. Apply light

• Non-laser sources:

1. sunlight
2. incandescent light
3. arc lamp
4. LED lamp
5. Intense Pulsed Light (IPL)
6. Fluorescent light (FDA-approved):
   1. blue lamp: application time 16 minutes (10J/cm2)
   2. red: application time 9minutes (27J/cm2)

Red lamp goes deeper than blue lamp. Blue light is superficial and is only adequate for conditions such as Actinic Keratosis

• Laser sources:

1. tunable dye
2. diode

• Pain management: probably the most important thing

1. pre-op education
2. dedicated PDT staff
3. verbal reinforcement and reassuraance
4. Actions to do:
   1. ice
   2. water spritz
   3. fans
   4. cold air
   5. interruption of treatment

Remark: PPIX photobleaches: the red fluorescence is visible on Wood’s lamp. It fades after light exposure. An hour later, the fluorescence comes back (because New PPIX is generated).
In the pipeline: Studies in Scandinavia show that natural daylight would be a solution. It is less pianful as light is shone over a longer time (an hour and a half).
Do not forget: Warn the patient of strong reaction (erythema) which can last up to a week after the treatment.

INDICATIONS:

• FDA approved:

1. Actinic Keratosis (AK) treated with the following methods:
2. ALA + blue fluorescent light
3. Methyl-ALA + red light

• Off-label uses:

1. Cancerous:
   1. Non-Melanoma Skin Cancer (not FDA approved in the US):
   2. Superficial BCC (Basal Cell Carcinoma)
   3. Bowen’s Disease
2. Genodermatosis (Gorlin’s syndrome)
3. Prevention of AK (Apola et al, BJD 2010)

1. Non oncologic:
   1. Psoriasis plaques (Bissonette et al, JID 2002) : it works but it is limited by extreme pain.
   2. Acne Vulgaris: it works but it depends on the tolerance to pain
   3. Hair removal (Grossman et al, Lasers Surg Med 1995): it depends on the tolerance to pain; further studies are still needed to show efficacy.
   4. Photorejuventation

• Potential indications:

1. Herpes Virus (Stender et al, Lancet 1995)
2. Antibiotic resistance
3. Warts (and genital warts)
4. Onychomycosis
5. Leishmaniasis

Studies done for portwine stains (intraveinous systemic administraion; Chinese study)

Contributors:

Dr Christophe Hsu – dermatologist. Geneva, Switzerland

Source of Information: Liu H. Update on Photodynamic Therapy. 71st Annual Meeting of the AAD (American Academy of Dermatology) – Miami, Florida, United States of America (USA)