Photochemotherapy

How Photochemotherapy Works: Biology and Pharmacology

Light-Dependent DNA Intercalation and Cross-Linking

Psoralens (such as 8-methoxypsoralen, or methoxsalen) are naturally occurring furocoumarins. In the dark, free psoralen molecules pass through the cell membrane and slip between the pyrimidine bases (mainly thymine) of double-stranded DNA without yet causing any harm:

• Absorbing UVA photons (320–400 nm): when UVA light is applied, the psoralen molecule absorbs photon energy, becomes excited and reacts through its furan or coumarin ring with thymine, forming single-strand covalent bonds (mono-adducts).
• Forming interstrand cross-links: when a second UVA photon is absorbed, the psoralen molecule also bonds covalently to a thymine on the opposite DNA strand. These cross-links block DNA unwinding and replication completely, so the cell cannot divide and promptly triggers programmed cell death (apoptosis).

Suppressing Infiltrating Immune Cells and Keratinocytes

PUVA reaches the superficial and deep dermis, where UVB cannot penetrate. It acts directly on abnormal CD4+ and CD8+ T lymphocytes infiltrating the skin (as in mycosis fungoides), destroying the diseased T-cell clones. PUVA also reduces the number of Langerhans cells and disables their antigen-presenting function, damping down chronic inflammation.

Clinical Types of Photochemotherapy

• Systemic (oral) PUVA:
  • Method: the patient takes 8-methoxypsoralen (8-MOP) at 0.6 mg/kg body weight with a light snack or milk 1.5–2 hours before entering a full-body UVA cabin.
  • Indications: extensive, treatment-resistant plaque psoriasis; cutaneous T-cell lymphoma (CTCL/mycosis fungoides, stages IA–IIA); large-plaque parapsoriasis; systemic sclerosis.
• Topical PUVA / bath PUVA:
  • Method:
    • Bath PUVA: the patient soaks the whole body, or just the hands and feet, in warm water containing 8-MOP (0.5–1 mg/L) for 15–20 minutes, followed immediately by UVA exposure.
    • Cream/gel PUVA: a 0.1% 8-MOP cream is applied to localized lesions 30 minutes before UVA exposure.
  • Advantages: largely avoids gastrointestinal side effects (nausea) and does not make the eyes or the rest of the body sensitive to light, making it very suitable for psoriasis or eczema of the hands and feet.
• Re-PUVA (oral retinoid plus PUVA):
  • Method: acitretin (0.25–0.5 mg/kg/day) is taken for 7–14 days before PUVA begins.
  • Advantages: acitretin thins the thick scale of psoriasis, allowing UVA to penetrate better, improving results and cutting the total cumulative UVA dose for the course by up to 50%.

Comparing Photochemotherapy Methods

Clinical Safety, Toxicity Management and Contraindications

• Eye protection: after oral 8-MOP, the drug reaches the lens of the eye and can react with ambient light to cause cataracts. Patients must wear UVA-blocking eye protection from the time they take the medication until 24 hours afterward whenever they are exposed to daylight or artificial light.
• Skin cancer risk from cumulative dose: PUVA is strongly mutagenic. Long-term use with a high cumulative dose (more than 150–200 sessions or a large total UVA dose) clearly increases the risk of squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and melanoma.
• Gastrointestinal toxicity and acute erythema: oral 8-MOP often causes nausea and stomach discomfort. This can be eased by splitting the dose, taking it with milk or using an antiemetic. PUVA-induced redness appears later than UVB redness, usually peaking 48–72 hours after exposure.
• Absolute contraindications:
  • Pregnancy and breastfeeding.
  • Inherited photosensitivity syndromes (xeroderma pigmentosum, Bloom syndrome).
  • Systemic lupus erythematosus (SLE), porphyria.
  • A history of melanoma or cutaneous squamous cell carcinoma.
  • Severe liver or kidney failure (psoralen cannot be metabolized and cleared).

Treatment Process at Haute-Derma

Assessment and Minimal Phototoxic Dose (MPD) Testing

• Full assessment of liver and kidney function, blood count and a specialist eye exam before treatment.
• MPD (minimal phototoxic dose) test: after taking 8-MOP, the patient receives increasing UVA doses on small test areas of the back or buttocks to find the lowest dose that produces clear redness after 48–72 hours.

Treatment in a Dedicated Light Cabin

• The patient takes 8-MOP (or has a bath PUVA soak) at exactly the prescribed time.
• The starting UVA dose is set at 70% of the MPD (or based on Fitzpatrick skin type if MPD is not measured).
• The patient wears dedicated UV goggles in the cabin, and the face (if unaffected) and genitals are shielded.
• Frequency: twice a week, at least 48 hours apart, so the peak erythema response can be assessed.

Cumulative Dose Monitoring and Maintenance

• The UVA dose is increased by 10–20% after each session if there is no redness.
• Once lesions have improved by more than 80–90%, the patient moves to a maintenance schedule, with sessions tapered (once a week, then every 2 weeks) over several weeks before stopping.
• The total number of sessions and cumulative UVA dose are recorded precisely in the electronic medical record so the maximum safe threshold is never exceeded.