Residency · Residency · Dermatology

Phototherapy: NB-UVB, PUVA, and Targeted Phototherapy

Introduction

Phototherapy harnesses specific wavelengths of ultraviolet radiation for therapeutic benefit in a wide range of dermatologic conditions. It remains one of the most effective, cost-efficient, and safe treatment modalities in dermatology when properly administered. This lecture reviews the mechanisms, indications, protocols, and safety considerations for the major phototherapy modalities: narrowband UVB, PUVA (photochemotherapy), and targeted phototherapy devices.

Narrowband UVB (NB-UVB)

Physics and Mechanism

Narrowband UVB has a peak emission at 311 to 312 nm, a narrow band within the UVB range of 280 to 320 nm, and is delivered via fluorescent lamps (Philips TL-01) in full-body or panel units. It is more effective and safer than broadband UVB (BB-UVB, 280 to 320 nm broad emission) and has largely replaced BB-UVB for most indications. Its mechanisms of action include immunomodulation (inducing keratinocyte and T-cell apoptosis, shifting Th1/Th17 to Th2 cytokine profile, inducing regulatory T cells, and depleting Langerhans cells), antiproliferative effects (inhibiting keratinocyte DNA synthesis and proliferation), pro-melanogenic effects (stimulating melanocyte proliferation, melanin synthesis, and melanocyte migration from the hair follicle reservoir, particularly relevant in vitiligo), and antimicrobial effects (reducing Staphylococcus aureus colonization, relevant in atopic dermatitis).

Indications

The most common indication is psoriasis, where NB-UVB is effective for moderate-to-severe plaque psoriasis, with 60 to 80% of patients achieving PASI 75 within 20 to 30 treatments. In vitiligo, it stimulates repigmentation but requires prolonged treatment (12 to 24 months), with the face and trunk responding best. It is effective for moderate-to-severe atopic dermatitis, reducing inflammation and pruritus. In mycosis fungoides (early-stage CTCL), it is effective for patch-stage disease (T1a to T2a). Additional indications include pityriasis rosea, pityriasis lichenoides, chronic pruritus (idiopathic, uremic, hepatic), polymorphic light eruption (prophylactic hardening courses before spring/summer), morphea, lichen planus, graft-versus-host disease, and prurigo nodularis.

Treatment Protocol

The initial dose is based on minimal erythema dose (MED) determination or Fitzpatrick skin type: skin types I to II start at 200 to 300 mJ/cm2, skin types III to IV at 300 to 500 mJ/cm2, and skin types V to VI at 400 to 600 mJ/cm2. Dose escalation increases by 10 to 20% per treatment if no erythema, with holding or reducing if symptomatic erythema occurs. The optimal frequency is 3 times per week, with a minimum of 2 times per week for efficacy. The target is a sub-erythemogenic dose that is therapeutically effective, where asymptomatic faint pink erythema at 24 hours is acceptable. Once clearing is achieved, maintenance involves gradually reducing frequency (twice weekly, then once weekly) before discontinuation, with some conditions requiring ongoing maintenance.

Practical Considerations

UV-blocking goggles must be worn during treatment for eye protection. Genital shielding is appropriate in males unless treating genital lesions. The medication list should be reviewed for photosensitizing medications, with dose adjustment if needed. Home phototherapy with handheld or panel units is increasingly prescribed, improving adherence and requiring patient education on proper use and dose tracking.

<image>Diagram showing the electromagnetic spectrum with the narrowband UVB peak at 311 nm highlighted, alongside a photograph of a full-body NB-UVB phototherapy cabinet with a patient in protective goggles, and a graph comparing the action spectra of NB-UVB and broadband UVB with the erythema action spectrum</image>

PUVA (Psoralen + UVA)

Physics and Mechanism

PUVA combines a photosensitizing psoralen (most commonly 8-methoxypsoralen [8-MOP] or 5-MOP) with UVA radiation (320 to 400 nm). Psoralens are furocoumarins that intercalate between DNA base pairs. UVA activation causes psoralens to form monoadducts and interstrand cross-links with DNA, which are more potent antiproliferative lesions than UVB-induced CPDs. Additional mechanisms include direct immunosuppression, induction of apoptosis in pathogenic T cells, and melanocyte stimulation.

Administration Routes

Oral PUVA involves 8-MOP (0.4 to 0.6 mg/kg) taken 1 to 2 hours before UVA exposure and is the most common route. Bath PUVA uses immersion in dilute 8-MOP solution (0.5 to 1 mg/L) for 15 to 20 minutes before UVA exposure, avoiding systemic side effects and preferred in Europe. Topical PUVA (paint PUVA) involves 0.1 to 0.3% 8-MOP solution applied to localized lesions 20 to 30 minutes before UVA, useful for palmoplantar disease. PUVA soak involves immersion of hands or feet in psoralen solution before UVA, effective for hand and foot dermatoses.

Indications

PUVA is indicated for severe or recalcitrant plaque psoriasis unresponsive to NB-UVB and palmoplantar psoriasis (bath/soak PUVA). In vitiligo, it was historically the standard treatment but has been largely replaced by NB-UVB due to a better safety profile. For mycosis fungoides, it is effective for thicker plaques and patch/plaque stage CTCL, and may be combined with retinoids (Re-PUVA) or IFN-alpha for enhanced efficacy. Morphea and scleroderma benefit from UVA1 phototherapy specifically. Chronic hand eczema responds to bath/soak PUVA. Graft-versus-host disease is managed with extracorporeal photopheresis using PUVA.

Treatment Protocol

The initial dose is based on minimal phototoxic dose (MPD) or skin type, beginning at 50 to 70% of MPD. Treatment frequency is 2 to 3 times per week, never on consecutive days (psoralen effects persist 12 to 24 hours). The UVA dose is increased by 0.5 to 1 J/cm2 per treatment as tolerated. Clearing typically requires 20 to 30 sessions, followed by a maintenance taper.

Adverse Effects and Safety

Acute

Phototoxic erythema and burns have a delayed onset (24 to 48 hours after treatment) and are the dose-limiting side effect. Nausea is common with oral psoralens and can be mitigated by taking medication with food or using bath PUVA. Pruritus during the treatment course is managed with emollients and antihistamines.

Chronic/Long-Term

Photoaging is accelerated with cumulative PUVA exposure (greater than with NB-UVB). Cataract risk exists because psoralens can enter the lens; UVA-blocking sunglasses must be worn for 12 to 24 hours after oral PUVA, even on cloudy days. Skin cancer risk shows a dose-dependent increase in SCC risk (particularly with cumulative UVA doses above 200 treatments or above 1000 J/cm2), with lower but still increased BCC risk. Genital SCC risk is significantly elevated, making genital shielding mandatory. The SCC risk persists even after PUVA discontinuation. PUVA lentigines are irregular, dark macules on PUVA-treated skin that are benign but cosmetically concerning and must be distinguished from melanoma. Overall, PUVA carries a higher carcinogenic risk than NB-UVB, which is the primary reason NB-UVB has become the first-line phototherapy for most conditions.

UVA1 Phototherapy

UVA1 phototherapy uses an emission spectrum of 340 to 400 nm (long-wave UVA) and does not require psoralens. Its mechanism involves deep penetration into the dermis, inducing T-cell apoptosis and collagenase production by fibroblasts. Its primary indication is morphea/localized scleroderma, where medium-to-high dose UVA1 is the most effective phototherapy. Other indications include atopic dermatitis (medium dose), CTCL, systemic sclerosis, and graft-versus-host disease. Dosing is classified as low (below 20 J/cm2), medium (20 to 70 J/cm2), or high (above 70 J/cm2), with medium dose providing the best balance of efficacy and safety. UVA1 is less widely available than NB-UVB due to equipment costs.

Targeted Phototherapy

Excimer Laser (308 nm)

The xenon chloride (XeCl) excimer laser delivers monochromatic 308 nm UVB. Its advantages include targeted delivery of high-fluence UVB directly to lesional skin while sparing surrounding normal skin, requiring fewer cumulative UV sessions and producing faster responses. Indications include localized vitiligo (superior to conventional NB-UVB for limited patches, allowing supraerythemogenic doses to lesional skin), localized psoriasis (scalp, elbows, knees, palms, soles, and other areas difficult to treat with conventional phototherapy), alopecia areata (localized patches), and atopic dermatitis, lichen planus, and granuloma annulare. Treatments are given 2 to 3 times per week at doses 2 to 4 times higher than NB-UVB MED, typically over 10 to 20 sessions. Adverse effects include blistering (phototoxic) from high fluences and hyperpigmentation of treated sites (expected and sometimes desired in vitiligo).

Excimer Lamp (308 nm)

The excimer lamp is a non-coherent, filtered light source emitting 308 nm UVB. It covers a larger treatment area than the excimer laser at lower cost and has similar efficacy for most indications. Handheld devices are available for home use.

LED-Based Phototherapy

LED-based phototherapy is an emerging modality using light-emitting diodes at specific wavelengths. Blue light (400 to 470 nm) has antimicrobial properties (anti-P. acnes) and is approved for acne vulgaris. Red light (620 to 700 nm) is anti-inflammatory, promotes wound healing, and is used for photodynamic therapy in combination with ALA/MAL. Low-level light therapy (LLLT) uses red and near-infrared LED for hair loss (androgenetic alopecia), with FDA-cleared devices available.

<image>Comparison panel showing different phototherapy modalities: a full-body NB-UVB cabinet treating widespread psoriasis, a PUVA hand-soak unit for palmoplantar disease, an excimer laser delivering targeted 308nm light to a vitiligo patch, and a UVA1 panel treating morphea on the trunk</image>

Extracorporeal Photopheresis (ECP)

Extracorporeal photopheresis is a modified PUVA technique in which the patient's blood is drawn, leukocytes are separated and exposed to 8-MOP plus UVA ex vivo, and then reinfused. The mechanism induces apoptosis of pathogenic T cells and promotes tolerogenic dendritic cells and regulatory T cells. Indications include erythrodermic CTCL (Sezary syndrome), chronic GVHD, and solid organ transplant rejection. It is typically administered on 2 consecutive days every 2 to 4 weeks. The procedure is very well-tolerated and carries no increased skin cancer risk because UV exposure is extracorporeal.

Combination Phototherapy Regimens

NB-UVB plus topical agents (TCS, calcipotriol, tazarotene, ruxolitinib) enhances efficacy and reduces the total UV dose needed. Re-PUVA combines PUVA with an oral retinoid (acitretin), achieving a 50% reduction in UVA dose needed, and is used for severe psoriasis and CTCL. NB-UVB plus biologics combines phototherapy with TNF inhibitors or IL-17/IL-23 inhibitors for severe psoriasis with additive efficacy. NB-UVB plus oral mini-pulse corticosteroids is used for rapidly progressive vitiligo to stabilize disease while promoting repigmentation.

Phototherapy Safety Summary

Key Clinical Pearls

NB-UVB has replaced PUVA as first-line phototherapy for most conditions due to comparable efficacy with a superior safety profile. PUVA remains valuable for conditions requiring deeper penetration (thick plaques, CTCL) and palmoplantar disease (bath/soak PUVA). Excimer laser allows targeted, high-dose treatment of localized disease, making it ideal for vitiligo patches, scalp psoriasis, and small plaques. Cumulative PUVA exposure must be tracked meticulously because SCC risk is dose-dependent and persistent even after discontinuation. Home phototherapy with NB-UVB significantly improves adherence and outcomes, particularly for vitiligo and atopic dermatitis requiring long-term treatment.

References

1. Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis — Section 5: guidelines for phototherapy and photochemotherapy. J Am Acad Dermatol. 2010;62(1):114-135.
2. Stern RS. The risk of squamous cell and basal cell cancer associated with psoralen and ultraviolet A therapy: a 30-year prospective study. J Am Acad Dermatol. 2012;66(4):553-562.
3. Hamzavi IH, Lim HW, Syed ZU. Ultraviolet-based therapy for vitiligo: what's new? Indian J Dermatol Venereol Leprol. 2012;78(1):42-48.
4. Musters AH, Mashayekhi S, Harvey J, et al. Phototherapy for vitiligo. Cochrane Database Syst Rev. 2021;(4):CD013478.

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