What does PUVA (psoralen plus ultraviolet‑A) treatment involve?

What PUVA Treatment Means

PUVA is an acronym for Psoralen plus Ultraviolet A light photochemotherapy—a combined treatment where patients take or apply a photosensitizing medication (psoralen) followed by controlled exposure to UVA radiation (320-400 nm wavelength). 1

Core Components of PUVA

PUVA consists of two essential elements that work synergistically:

• Psoralen (P): A photosensitizing medication that makes skin dramatically more reactive to UVA light 1, 2
• Ultraviolet A radiation (UVA): Long-wave UV light (320-400 nm) delivered in a controlled light box 1

The psoralen is necessary to minimize time in the light box while maximizing therapeutic effect of the UVA 1

Forms of Psoralen Administration

PUVA can be delivered through multiple routes, each with distinct protocols:

Oral PUVA (Most Common in UK/US)

• 8-methoxypsoralen (8-MOP): Standard formulation taken 2 hours before UVA exposure 1
• Oxsoralen-Ultra: Microcrystalline formulation taken 1-1.5 hours before UVA exposure 1, 2
• 5-methoxypsoralen (5-MOP): Alternative used when excessive nausea occurs with 8-MOP 1
• Dosing is weight-based, requiring adjustment if patient weight changes 1

Topical PUVA

• Bath PUVA: Whole-body soaking (excluding head/neck) in bathwater containing psoralen liquid 1
• Cream/gel/lotion: Applied directly to affected areas, typically 0.1% 8-methoxypsoralen applied 30 minutes before UVA exposure 3
• Topical forms have superior safety profile with no increased skin cancer risk demonstrated 3

Treatment Protocol

Frequency and Timing

• Treatments given 2-3 times weekly with minimum 48-hour intervals between sessions 1, 3
• The 48-hour gap is critical because phototoxic "sunburn" reactions take this long to manifest 1

Time to Response and Duration

• Initial response typically seen within 1 month of starting treatment 1
• Treatment continues at initial frequency until clearance, then gradually tapered 1
• Topical PUVA may require 30-40 treatments for complete response 3

Light Box Positioning

• Patients must expose all affected areas by assuming specific positions for underarms, trunk sides, inner thighs, under breasts, and tops of feet 1
• Standing on a short platform may be needed to better treat lower legs 1

Mechanism of Action

PUVA works primarily through DNA photochemistry and immunosuppression:

• Methoxsalen, upon photoactivation, conjugates with DNA forming covalent bonds that create both monofunctional and bifunctional adducts (DNA crosslinking) 2, 4
• This leads to suppression of DNA synthesis and cell cycle arrest 2, 4
• Acts as skin-targeted immunosuppressive treatment, reducing Langerhans cells, cutaneous T lymphocytes, and mast cells 1, 4
• Alters cytokine expression and cytokine receptor profiles 4
• Stimulates melanogenesis (important for vitiligo treatment) 4

Clinical Indications

First-Line Phototherapy (Preferred Over NB-UVB)

• Mycosis fungoides beyond patch stage 1
• Pustular psoriasis 1
• Pompholyx 1
• Hand and foot eczema 1
• Adult generalized pityriasis rubra pilaris 1

Second-Line Phototherapy (After NB-UVB Failure)

• Chronic plaque psoriasis when NB-UVB ineffective 1
• Atopic eczema when NB-UVB ineffective 1
• Failure to respond to NB-UVB does not predict PUVA failure—PUVA is often successful 1

Critical Safety Measures

Absolute Contraindications

• Lupus erythematosus 3
• Porphyria 3
• Xeroderma pigmentosum 3

Extreme Caution Required

• Skin types I and II (burn easily) 3
• History of arsenic intake or ionizing radiation 3, 5
• History of melanoma or multiple nonmelanoma skin cancers 3, 5
• Pregnancy (Category C) 3

Protective Measures During Treatment

• Men must shield genitals with athletic supporter or sock due to increased risk of genital squamous cell carcinomas 1, 5
• Women should shield nipples with SPF 50 sunscreen or zinc oxide paste 1
• Shield areas of recent skin cancer or surgical scars 1
• UVA-opaque sunglasses required during entire period of photosensitivity after psoralen ingestion to prevent cataracts 5

Sun Protection Requirements

• No sun tanning or tanning beds during or after PUVA therapy 1
• SPF 30 sunscreen on non-treatment days and after phototherapy 1
• Minimize purposeful sun exposure after completing PUVA 1

Long-Term Risks and Monitoring

Carcinogenicity Threshold

• 200 treatments or cumulative UVA dose of 1200 J/cm² appears to be threshold for nonmelanoma skin cancer development 5
• Dose-dependent increase in squamous cell carcinoma incidence with oral PUVA 5
• Topical PUVA has no demonstrated increased skin cancer risk 3

Monitoring Requirements

• Annual dermatological skin examinations to detect skin cancer early 1, 5
• Regular evaluation during active treatment 1
• No routine screening required for topical PUVA (unlike oral PUVA) 3

Common Pitfalls to Avoid

• Never use PUVA as first-line therapy in children—use topical calcineurin inhibitors or narrowband UVB instead, with bath PUVA strongly preferred over oral/topical if phototherapy needed 3
• Never combine PUVA with cyclosporine due to accelerated skin cancer risk 3
• Never apply topical PUVA over large body surface areas without considering systemic absorption risk 3
• Food affects psoralen absorption—patients should take with same food (milk, crackers, meal) each time to maintain consistent blood levels 1
• Nausea management: Take psoralen with food or use antinausea medication 30-60 minutes before psoralen if needed 1

Pharmacokinetics (Oral Formulations)

• Peak drug levels: 0.5-4 hours (mean 1.8 hours) for Oxsoralen-Ultra; 1.5-6 hours (mean 3.0 hours) for regular hard gelatin capsules 2
• Peak photosensitivity: 1.5-2.1 hours for soft gelatin vs. 3.9-4.25 hours for hard gelatin 2
• Drug half-life: Approximately 2 hours 2
• Excretion: 95% excreted as metabolites in urine within 24 hours 2
• Protein binding: Reversibly bound to serum albumin, preferentially taken up by epidermal cells 2