1. Mechanism of Action
1.1. Exogenous ALA Applicaion
1.2. Incubation (Metabolism & Accumulation)
1.2.1. Metabolism
1.2.1.1. Exogenous ALA
1.2.1.1.1. Heme synthesis
1.2.2. Accumulation
1.2.2.1. Porphyrin levels peak in 12 hours
1.2.2.2. Optimal Incubation time for Acne treatment?
1.2.2.2.1. 3 hours
1.3. Light Exposure
1.3.1. ALA
1.3.1.1. Porphyrins (Ground Energy State)
1.3.1.1.1. Porphyrins (Excited Energy State)
1.4. Photobleaching
1.4.1. Irreversible oxidation of porphyrins
1.4.2. Starts at the onset of light exposure
1.5. Metabolism and Re-accumulation of Porphyrins
1.5.1. Occurs after therapeutic light exposure is completed
1.5.2. Instruct patients to have strict photoprotection for?
1.5.2.1. 48 hours
2. Porphyrins
2.1. ALA itself is not a photosensitizer
2.2. Accumulation of Protoporphyrin IX depends on?
2.2.1. Cytoplasmic ALA concentration
2.2.2. Expression and Activity of heme-synthesis enzymes (e.g., Porphyrias)
2.2.3. Peripheral Benzodiazapine Receptors
2.2.3.1. PBRs are overexpressed in neoplastic cells, enhancing ALA-PDT efficacy in cancer treatment
2.2.4. Iron Stores
2.3. Peripheral Benzodiazapine Receptors are overexpressed in cancers
2.3.1. PBRs are overexpressed in neoplastic cells, enhancing ALA-PDT efficacy in cancer treatment
3. Light Sources
3.1. Porphyrin Absorption Spectrum (300-650 nm)
3.1.1. Blue Light
3.1.2. Green Light
3.1.2.1. KTP, Nd:YAG
3.1.3. Yellow Light
3.1.3.1. PDL (e.g., LP-PDL 595 nm)
3.1.4. Red Light
3.1.5. IPL
4. Indications
4.1. FDA Approved
4.1.1. Compounds
4.1.1.1. Methyl Aminolevulinate (MAL)
4.1.1.2. 5 Aminolevulinate (ALA)
4.1.2. Actinic Keratoses
4.1.3. Pregnancy Category: C
4.1.4. Not approved for children
4.2. Off-Label
4.2.1. Acne Vulgaris
4.2.1.1. UV light is not therapeutic
4.2.1.2. Blue Light is antiinflammatory
4.2.1.3. Red light alone is not therapeutic
4.2.1.4. Glass-filtered sunlight may be helpful (UVA)
4.2.1.5. Propionibacterium acnes
4.2.1.5.1. Coproporphyrin III
4.2.1.5.2. Protoporphyrin IX
4.2.1.6. Mechanism of Action
4.2.1.6.1. Sebaceous gland destruction (ROS)
4.2.1.6.2. Reduction of follicular obstruction and hyperkeratosis
4.2.1.6.3. Immunological changes
4.2.1.7. Longer incubation times (3 hours or more) > long-term acne remission (ALA-PDT and MAL-PDT)
4.2.1.8. Red light is deeper penetrating > more likely to activate porphyrins in sebaceous glands in PDT
4.2.2. Basal Cell Carcinoma
4.2.3. Bowen's Disease
4.2.4. Actinic Cheilitis
4.2.5. Hidradenitis Suppurativa
4.2.6. Cosmetics
4.2.6.1. Photo-Aging
4.2.7. CTCL
4.2.8. Viral Infections of the skin
4.2.8.1. HPV
4.2.8.2. Molluscum
4.2.8.3. HSV
5. Contraindications
5.1. Photosensitivity at 400-450 nm
5.1.1. Caution to other wavelengths