Phototherapy is a first-line option for the treatment of moderate to severe psoriasis. Systematic reviews indicate near comparable efficacy of the different forms of phototherapy. Localized phototherapy can be an adjunctive treatment of recalcitrant plaques during systemic treatment of psoriasis. More than 200 psoralen–UV-A therapy treatment sessions is associated with an increased risk of keratinocytic cancers, whereas no increased risk has been demonstrated for narrow-band UV-B therapy. The mechanism of action of phototherapy in psoriasis is via inhibition of keratinocyte proliferation; induction of apoptosis in keratinocytes, dendritic, and T cells; and inhibition of Th1 and Th17 pathways, but activation of Th2.
Key points
- •
Phototherapy of psoriasis is efficacious.
- •
Phototherapy of psoriasis is relatively cost-effective.
- •
Phototherapy may be combined with topical agents and systemic therapies.
- •
More than 200 PUVA therapy treatments is associated with an increased risk of keratinocytic cancers.
- •
The mode of action of phototherapy is via inhibition of keratinocyte proliferation, induction of apoptosis in immunocytes, and inhibition of Th1 and Th17 cells and stimulation of Th2.
Introduction
Phototherapy is a standard treatment option for psoriasis, generally applied if topical treatment modalities fail or are contraindicated or not practical, such as in extensive guttate psoriasis. Phototherapy may lead to the clearance of psoriasis in 5 to 8 weeks and has one of the highest treatment satisfaction rates compared with other treatment modalities. The development of phototherapy for psoriasis was based on the observation that sunlight improves the symptoms of the disease. Natural light in combination with herbal extracts has been in use for the treatment of skin disease from the era of the Ancient Egyptians. Artificial light sources have been used for the treatment of psoriasis since the 1920s. The most frequently applied regimen for psoriasis was the combination of topical coal tar and subsequent UV-B radiation, introduced by Göckerman in 1925.
Broad-band (BB) UV-B alone (wavelengths between 280 and 320 nm) has been used since the 1970s. Narrow-band (NB) UV-B phototherapy using Philips (Eindhoven, The Netherlands) TL-01 fluorescent lamps, emitting between 311 and 313 nm, was introduced in 1988 for the treatment of psoriasis. BB-UV-B and NB-UV-B were shown to have common, but also different biologic effects, because NB-UV-B radiation did not suppress contact hypersensitivity responses in mice, even at seven times higher doses than effective BB-UV-B doses.
In the 1970s psoralen–UV-A therapy (PUVA; 320–400 nm) was introduced. Psoralens, plant-derived photosensitizers, can be applied topically or taken orally. Subsequent UV-A irradiation causes a therapeutically beneficial phototoxic reaction in the skin. PUVA therapy has anti-inflammatory and antiproliferative effects, and is highly efficacious in the treatment of psoriasis, inducing response rates from 74% to 100%. PUVA is thereby one of the most effective treatment options in psoriasis; however, it is less well tolerated than UV-B phototherapy, and there is more evidence on its carcinogenic potential.
Further forms of UV phototherapy for psoriasis are climatotherapy and balneotherapy. Climatotherapy involves daily bathing in Dead Sea water and graduated exposure to natural sunlight. Treatment is usually for 4 weeks and results in reductions in Psoriasis Area and Severity Index (PASI) scores by 75% or more. Most of the benefit of climatotherapy at the Dead Sea has been attributed to the specific sunlight spectrum at the Dead Sea. Balneophototherapy, which involves salt water baths and artificial UV radiation, can be used as an alternative to climatotherapy at the Dead Sea. However, the clinical effect of adding salt water to BB-UV-B was negligible. Therefore, because of the heavy burden of salt on sewage and the environment, salt water baths are not recommended for home use.
For the treatment of chronic localized psoriatic plaques, localized phototherapy is available in the form of hand-held nonlaser UV-B (light-emitting diode) lamps, and the 308-nm excimer laser. The excimer laser emits monochromatic light equivalent to that of NB-UV-B with similar biologic and clinical effects. Localized phototherapy was shown to be less efficacious than total body irradiation, but is a practical solution for adjunctive home treatment of localized psoriasis, such as scalp, hand, or foot psoriasis.
Photochemotherapy can also be applied locally by using psoralen-containing gels or solutions (topical PUVA); this form of treatment is most often used for the treatment of psoriasis of the palms and soles.
Discussed next are the practical aspects of phototherapy of psoriasis and the mode of action as currently understood.
Introduction
Phototherapy is a standard treatment option for psoriasis, generally applied if topical treatment modalities fail or are contraindicated or not practical, such as in extensive guttate psoriasis. Phototherapy may lead to the clearance of psoriasis in 5 to 8 weeks and has one of the highest treatment satisfaction rates compared with other treatment modalities. The development of phototherapy for psoriasis was based on the observation that sunlight improves the symptoms of the disease. Natural light in combination with herbal extracts has been in use for the treatment of skin disease from the era of the Ancient Egyptians. Artificial light sources have been used for the treatment of psoriasis since the 1920s. The most frequently applied regimen for psoriasis was the combination of topical coal tar and subsequent UV-B radiation, introduced by Göckerman in 1925.
Broad-band (BB) UV-B alone (wavelengths between 280 and 320 nm) has been used since the 1970s. Narrow-band (NB) UV-B phototherapy using Philips (Eindhoven, The Netherlands) TL-01 fluorescent lamps, emitting between 311 and 313 nm, was introduced in 1988 for the treatment of psoriasis. BB-UV-B and NB-UV-B were shown to have common, but also different biologic effects, because NB-UV-B radiation did not suppress contact hypersensitivity responses in mice, even at seven times higher doses than effective BB-UV-B doses.
In the 1970s psoralen–UV-A therapy (PUVA; 320–400 nm) was introduced. Psoralens, plant-derived photosensitizers, can be applied topically or taken orally. Subsequent UV-A irradiation causes a therapeutically beneficial phototoxic reaction in the skin. PUVA therapy has anti-inflammatory and antiproliferative effects, and is highly efficacious in the treatment of psoriasis, inducing response rates from 74% to 100%. PUVA is thereby one of the most effective treatment options in psoriasis; however, it is less well tolerated than UV-B phototherapy, and there is more evidence on its carcinogenic potential.
Further forms of UV phototherapy for psoriasis are climatotherapy and balneotherapy. Climatotherapy involves daily bathing in Dead Sea water and graduated exposure to natural sunlight. Treatment is usually for 4 weeks and results in reductions in Psoriasis Area and Severity Index (PASI) scores by 75% or more. Most of the benefit of climatotherapy at the Dead Sea has been attributed to the specific sunlight spectrum at the Dead Sea. Balneophototherapy, which involves salt water baths and artificial UV radiation, can be used as an alternative to climatotherapy at the Dead Sea. However, the clinical effect of adding salt water to BB-UV-B was negligible. Therefore, because of the heavy burden of salt on sewage and the environment, salt water baths are not recommended for home use.
For the treatment of chronic localized psoriatic plaques, localized phototherapy is available in the form of hand-held nonlaser UV-B (light-emitting diode) lamps, and the 308-nm excimer laser. The excimer laser emits monochromatic light equivalent to that of NB-UV-B with similar biologic and clinical effects. Localized phototherapy was shown to be less efficacious than total body irradiation, but is a practical solution for adjunctive home treatment of localized psoriasis, such as scalp, hand, or foot psoriasis.
Photochemotherapy can also be applied locally by using psoralen-containing gels or solutions (topical PUVA); this form of treatment is most often used for the treatment of psoriasis of the palms and soles.
Discussed next are the practical aspects of phototherapy of psoriasis and the mode of action as currently understood.
Treatment regimens
Phototherapy is mostly applied in a clinical setting, in light cabinets where patients stand from a few seconds to a few minutes, two to five times a week. The starting dose of phototherapy is ideally based on the minimal erythema dose (MED) in the case of UV-B treatment, or the minimal phototoxic dose in the case of PUVA ( Table 1 ).
| UV-B | PUVA | |||
|---|---|---|---|---|
| Oral | Bath | |||
| Initial dose determination | Reading after 24 h | Reading after 72–96 h | Reading after 96–120 h | |
| Initial dose | 70% of MED | 75% of minimal phototoxic dose | 30% of minimal phototoxic dose | |
| Treatment frequency | 2–5 times weekly | 2–4 times weekly | ||
| Dose adjustment during treatment | No erythema | Increase by 30%–40% | Increase by 30% max. 2 times weekly | |
| Minimal erythema | Increase by 20% | No increase | ||
| Persistent asymptomatic erythema | No increase | No increase | ||
| Painful erythema | Break in therapy | Break in therapy | ||
| Resume therapy after symptoms fade | Reduce last dose by 50%, further increase by 10% | |||
MED is defined as the lowest radiation dose that produces just perceptible erythema on exposed skin after 24 hours. Common MEDs reported for NB-UV-B and BB-UV-B are shown in Table 2 . Thus, at least five-times higher doses of NB-UV-B, compared with BB-UV-B, are needed for the induction of erythema. NB-UV-B doses required for the induction of hyperplasia, edema, sunburn cell formation, and Langerhans cell depletion are 5 to 10 times higher than equally effective BB-UV-B doses. A more convenient approach is to base the starting dose on the skin type of the patient, although MED-based therapy is thought to be the safest regimen for the patient.
| Study | Skin Type | MED BB-UV-B (mJ/cm 2 ) | MED NB-UV-B (mJ/cm 2 ) |
|---|---|---|---|
| Van Weelden et al, 1988 | II | 76 | 410 |
| Johnson et al, 1988 | II | 100 | 500 |
| Karvonen et al, 1989 | II | 230 | 970 |
| Storbeck et al, 1993 | II | 114 | 1034 |
| Srinivas, 2002 | IV | 21 | 300 |
| Tejasvi et al, 2007 | III–V | — | 1000 |
| Youn et al, 2003 | III–V | — | 750–1075 |
| Morita et al, 2009 | IV | — | 700 |
Maintenance of a slight, asymptomatic erythema throughout the treatment results in optimal clinical efficacy. Treatments are continued until total remission is reached or until no further improvement can be obtained with continued phototherapy. The median number of treatments needed for clearance with UV-B is between 25 and 30 and for PUVA between 17 and 19.
Efficacy, duration of remission
The European S3 guideline on the treatment of psoriasis presents clearance rates for the different types of phototherapy ( Table 3 ). A few studies reported a superior clinical efficacy of NB-UV-B compared with BB-UV-B ; however, other studies found that BB-UV-B and NB-UV-B were equally effective. A recent Cochrane review reports on only one randomized controlled trial (RCT) comparing NB-UV-B with selective BB-UV-B (none that compares NB-UV-B with conventional BB-UV-B), showing no significant differences between these two treatments in terms of clearance rate and withdrawals because of adverse events.
| BB-UV-B | NB-UV-B | Balneotherapy | Oral PUVA | Bath PUVA | |
|---|---|---|---|---|---|
| Psoriasis Area and Severity Index 75 | 50–75 | 38–100 | 73–83 | 75–100 | 64–100 |
The Cochrane review also compared the efficacy of NB-UV-B with oral PUVA for psoriasis. The three RCTs they found show inconsistent results on the clearance rate, with one RCT showing equal efficacy and two a statistically significant higher clearance rate of oral PUVA. In terms of PASI 75 and withdrawals caused by adverse events no significant differences were found.
A recent European systematic review concluded that PUVA cleared psoriasis more often and in fewer treatment sessions than NB-UV-B alone, and that PUVA also resulted in longer lasting remission of the disease. The number of sessions to clear was lower for PUVA (17 sessions) than for NB-UV-B (approximately 25 sessions); these conclusions are in accordance with those of the Cochrane review. The median duration of remission was studied by Markham and colleagues ; this study reported 288.5 days for NB-UV-B group, and 231 days for PUVA. However, according to the European systematic review, more patients are still in remission 6 months after completing PUVA therapy than after NB-UV-B therapy. The duration of remission correlates with the PASI score at the end of the treatment.
Contraindications and precautions
Before treatment with phototherapy it is necessary to evaluate the skin type of the patient and his or her reaction to sunlight, and the age and the history of skin cancer ( Box 1 ). A total body check and an objective evaluation of psoriasis using the PASI should be performed before starting treatment. The contraindications for phototherapy are summarized in Box 2 (based on the European S3 Guideline and the American Academy of Dermatology Guideline on the treatment of psoriasis ).
Skin type
Age
History of skin cancer
Sunlight tolerance
Ability to stand in light cabin
History of previous phototherapy sessions, including clinical response and cumulative UV dose
Absolute
Gene defects with an increased sensitivity to light or an increased risk of skin cancer
Lupus erythematosus
PUVA: pregnancy or lactation
Relative
Epilepsy
Necessary use of photosensitizing medication
Skin type I
Dysplastic melanocytic nevi
History of skin cancer
Noncompliance
Physical or psychological inability to adhere to therapy (eg, claustrophobia)
Photodermatosis, photosensitive disease
PUVA: high cumulative UV-A dose (>150–200 individual sessions)
Prior therapy with arsenic or ionizing radiation
Severe liver damage
Adverse effects and their management
Acute adverse effects of UV-B therapy include redness, itch, and blistering, all symptoms of sunburn reaction. These effects are temporary and generally manageable with adjustment of the frequency and dose of irradiation. A frequent adverse effect of PUVA therapy is nausea. Carcinogenicity is the most concerning long-term serious adverse effect of phototherapy and photochemotherapy. Sufficient evidence supports the increased risk of nonmelanoma skin cancer after more than 200 sessions of PUVA therapy. The risk is most pronounced for squamous cell carcinomas, which may develop also on low exposures and on nonexposed skin, including penile tumors. The risk of basal cell carcinoma is also increased in patients receiving more than 100 PUVA sessions. A large US prospective follow-up study also identified an at least doubled incidence of melanoma (invasive and in situ) among patients exposed to at least 200 PUVA sessions. This increased risk began 15 years after first exposure to PUVA. This has not been shown in European studies.
Although in mice NB-UV-B was more carcinogenic than BB-UV-B at equally erythemogenic doses, follow-up of patients receiving extensive UV-B treatments did not demonstrate an increase in skin cancer incidence. However, most of the available studies had an observation time shorter than 5.6 years, which might be too short to detect skin cancer as a long-term risk of phototherapy. It is essential that the total number of treatments and the cumulative UV dose is recorded, because these are the factors that influence the skin cancer risk. Most commercially available UV cabinets are equipped with software for registration of the number of treatments and the cumulative dose.
Photoaging is induced by long-term phototherapy of patients with psoriasis, exacerbating the injury caused by natural sunlight. An increased risk of cataract can be expected in patients undergoing PUVA or NB-UV-B therapy based on animal studies. Therefore, eye protection is essential during irradiation, and additional UV-blocking glasses are recommended during daytime in patients who take oral psoralens. However, a recent systematic review found no evidence for an increased incidence of cataract in patients who have been treated with PUVA or NB-UV-B. Box 3 outlines the prevention of complications.
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
