Phototherapeutic Agents

Phototherapeutic Agents - Ray Foundations

• Light Basics: Phototherapy utilizes specific UV & visible light wavelengths.
• UV Radiation (UVR) Types:
  • UVA (320-400 nm): Deeper penetration. 📌 Think Aging.
    • UVA1: 340-400 nm
    • UVA2: 320-340 nm
  • UVB (290-320 nm): More erythemogenic. 📌 Think Burning, Vitamin B (D synthesis).
    • Broadband (BB-UVB): 290-320 nm
    • Narrowband (NB-UVB): 311-313 nm
  • UVC (100-290 nm): Germicidal, mostly ozone-filtered.
• Mechanism: DNA damage, immunomodulation, antiproliferative effects.
• Principle: Grotthuss-Draper law (light must be absorbed for effect).

⭐ The optimal therapeutic range for Narrowband UVB (NB-UVB) is 311-313 nm.

Phototherapeutic Agents - Psoralen Power Play

• Psoralens: Photosensitizing furocoumarins (e.g., 8-MOP, 5-MOP).
• PUVA Therapy: Psoralen + UVA radiation (320-400 nm).
  • Mechanism: Psoralens intercalate DNA. UVA activates → covalent DNA photoadducts (cross-links) with pyrimidines → inhibits DNA replication, cell division.
  • Administration: Oral 8-MOP (0.4-0.6 mg/kg) 1.5-2 hrs pre-UVA. Topical forms available.
  • Indications: Severe psoriasis, vitiligo, CTCL, severe atopic dermatitis.
• Side Effects:
  • Acute: Nausea (oral), phototoxicity (erythema, blisters), pruritus.
  • Chronic: Premature skin aging (PUVA lentigines), pigment changes, cataracts.

⭐ Long-term PUVA therapy significantly increases the risk of squamous cell carcinoma (SCC), particularly in fair-skinned individuals.

Phototherapeutic Agents - Spectrum Specifics

• UVB Therapy: Utilizes ultraviolet B light; no systemic photosensitizer needed, unlike PUVA.
  • Broadband UVB (BB-UVB): Wavelength 290-320 nm.
    • Effective for psoriasis, atopic dermatitis.
    • Higher risk of erythema, burning compared to NB-UVB.
  • Narrowband UVB (NB-UVB): Wavelength 311-313 nm.
    • More effective for psoriasis, vitiligo; deeper penetration.
    • Lower erythemogenic potential, allowing higher doses.
    • Preferred UVB modality for many conditions.

⭐ The Goeckerman regimen, combining crude coal tar application with UVB phototherapy, is a highly effective treatment for severe psoriasis.

Phototherapeutic Agents - Targeted Light Strike

Photodynamic Therapy (PDT): Photosensitizer + Light + O₂ → Reactive Oxygen Species (ROS) → Selective cell kill.

• Mechanism: Photosensitizer (drug) activated by light → Energy transfer to O₂ → ROS (e.g., singlet oxygen $^1O_2$) → Targeted cell destruction.
• Photosensitizers:
  • Pro-drugs: Aminolevulinic acid (ALA), Methyl aminolevulinate (MAL).
  • Direct: Porphyrins (e.g., Photofrin®), Chlorins.
• Light Sources: Lasers, LEDs. Wavelength matched to photosensitizer (e.g., Blue light ~417 nm for superficial; Red light ~630-635 nm for deeper).
• Indications: Actinic keratoses, Bowen's disease, superficial BCC, acne.

⭐ Aminolevulinic acid (ALA) used in PDT is a pro-drug that is preferentially converted to the photosensitizer Protoporphyrin IX in neoplastic cells.

Phototherapeutic Agents - Guarding the Glow

• PUVA (Psoralen + UVA):
  • 8-MOP + UVA → DNA adducts, ↓cell division.
  • Uses: Psoriasis, vitiligo, Mycosis Fungoides (MF).
  • SE: Phototoxicity, nausea, ↑Squamous Cell Carcinoma (SCC) risk.
• UVB Therapy:
  • NB-UVB (311-313 nm): Preferred for psoriasis, vitiligo, atopic dermatitis.
  • Action: Induces DNA damage, immunosuppression.
  • SE: Erythema, sunburn.
• Excimer Laser: 308 nm (XeCl) for targeted therapy of localized lesions.

⭐ Patients undergoing PUVA therapy must use UV-blocking eye protection for at least 24 hours post-treatment due to psoralen photosensitivity.

High‑Yield Points - ⚡ Biggest Takeaways

• PUVA (Psoralen + UVA) treats psoriasis, vitiligo, CTCL; high photocarcinogenesis risk.
• NB-UVB (311-313 nm) is first-line for psoriasis, vitiligo; safer than PUVA.
• BB-UVB (290-320 nm) is less effective than NB-UVB for psoriasis.
• Acute side effects: Erythema, pruritus, blistering. Chronic: Skin cancer.
• 8-Methoxypsoralen (8-MOP) is the standard psoralen for PUVA.
• Photodynamic Therapy (PDT): Photosensitizer + light for actinic keratoses, superficial BCCs.
• UVA1 (340-400nm) for atopic dermatitis, localized scleroderma.