Traditional Therapies in the Management of Moderate to Severe Chronic Plaque Psoriasis: An Assessment of the Benefits and Risks

L. Naldi; C.E.M. Griffiths

Disclosures

The British Journal of Dermatology. 2005;152(4):597-615. 

In This Article

Narrowband Ultraviolet B

The beneficial effects of UVB exposure for patients with psoriasis have long been known.[13] UVB wavelengths between 300 and 313 nm appear to have the greatest antipsoriatic activity, and introduction of the narrowband (311-312 nm) Philips TL-01 fluorescent lamp in 1984 represented a significant advance in psoriasis phototherapy. NBUVB phototherapy has multiple mechanisms of action which have not been fully elucidated; however, UVB is known to inhibit DNA synthesis and epidermal keratinocyte hyperproliferation, induce T-cell apoptosis, and induce immunosuppressive and anti-inflammatory cytokines.[14] Each of these effects may contribute to its antipsoriatic activity.

NBUVB phototherapy has been used primarily in Europe as narrowband lamps only became available in the U.S.A. in 1998;[15] its usage in the U.K. is now believed to exceed that of PUVA.[14] NBUVB phototherapy is considered appropriate for patients with moderate to severe psoriasis that does not respond adequately to topical therapies.[14,16] Current British guidelines recommend pretreatment evaluation of each patient's minimal erythema dose (MED) and initiation of NBUVB phototherapy at 50% of the MED. Treatment should continue two or three times weekly with incremental dose increases of 20% then 10% of the MED until the patient's maximal dose is reached.[14] Treatment courses of limited duration are recommended due to the likely increased risk of skin cancer associated with UVB,[14] and phototherapy is usually discontinued upon psoriasis clearance.[17]

The efficacy of NBUVB phototherapy for psoriasis has been demonstrated in clinical trials; however, most studies to date have involved patients with caucasian skin types I-III.[14,15] Between 15 and 20 treatments are generally required to achieve more than 50% improvement in psoriasis,[15] and approximately 63-80% of all patients achieve clearance with NBUVB phototherapy.[14] A recent systematic review identified 21 randomized controlled trials of NBUVB and BBUVB phototherapy for psoriasis.[11] There was considerable heterogeneity among the trials with respect to disease severity, psoriasis subtype, skin type, phototherapy regimens, treatment compliance and outcome measures.[11] None of the trials compared NBUVB phototherapy with placebo, and there were insufficient data to compare the efficacy of NBUVB with BBUVB or PUVA for psoriasis.[11] Nevertheless, NBUVB was found to be effective as monotherapy and to be preferred by patients over PUVA as no additional drug treatment is involved.[11] Although more research is required,[14] a separate meta-analysis that incorporated some of the same studies identified in the systematic review strongly suggested that NBUVB phototherapy was more effective than BBUVB in patients with mainly plaque-type psoriasis and type I-III skin.[18]

Analysis of several more recent comparative clinical trials suggested that the efficacy of NBUVB was slightly lower than but approached that of PUVA in patients with skin types I-III.[14] Available data suggest that concomitant use of systemic retinoids or topical therapy does not increase the efficacy of NBUVB; however, combination therapy may reduce patients' cumulative UVB dose, leading to improved long-term safety.[14] There is some evidence that concomitant treatment with topical corticosteroids may reduce remission times; therefore, this combination should be avoided.[17]

UVB phototherapy is associated with several well-characterized acute and chronic adverse effects that cannot be separated from the beneficial effects of treatment.[19] The primary NBUVB treatment-limiting acute adverse effect is erythema,[15] reported in 10-94% of patients depending on the treatment regimen and definition of erythema utilized.[14] The NBUVB dose necessary to produce erythema varies widely among patients;[15] therefore, careful dosimetry is required.[20] Topical corticosteroids may be used to treat painful erythema, and nonsteroidal anti-inflammatory drugs and systemic corticosteroids have been used in severe cases.[17] Other short-term adverse effects of NBUVB phototherapy for psoriasis include blistering of plaques, dry skin with pruritus (often due to the underlying disease) and increased frequency of herpes simplex reactivation.[14,17]

Long-term adverse effects of NBUVB phototherapy include photodamage and a possible dose-related increase in the incidence of skin cancer.[14,17,20] The incidence of skin cancer in patients with psoriasis treated with NBUVB has not been precisely quantified. However, one systematic review estimated that the excess annual risk of nonmelanoma skin cancer associated with UVB radiation is likely to be less than 2%.[21]

Current guidelines recommend administration of limited treatment courses and optimization of efficacy to reduce total UVB exposure, as well as general precautions such as shielding the face and genitalia.[14,22] Attempts have been made to estimate a maximum safe number of UVB treatments for psoriasis; however, the accuracy and usefulness of such estimates are limited at present.[14]

The safety of NBUVB phototherapy for psoriasis may be maximized by appropriate patient selection. Due to the risk of carcinogenesis, NBUVB should be reserved for patients with moderately severe disease who cannot tolerate or do not respond to topical treatments. NBUVB phototherapy is contraindicated in patients with xeroderma pigmentosum or systemic lupus erythematosus, and should be avoided in patients with a history of skin cancer.[14,20] Current guidelines recommend careful monitoring of patients considered to be at risk of skin cancer, and particular caution for patients with skin types I-II, and blonde or red hair.[14]

The principal monitoring requirements for patients receiving NBUVB phototherapy relate to erythema and skin cancer. Trained staff should perform pretreatment MED testing to establish a safe starting dose and to detect possible photosensitivity. In rare cases, photoactive medications such as nonsteroidal anti-inflammatory drugs, calcium channel antagonists and phenothiazines may increase photosensitivity.[14]

NBUVB phototherapy is an effective antipsoriatic treatment with a favourable safety profile for patients with moderate to severe disease. There are few contraindications for NBUVB, and unlike PUVA and systemic therapies it can be used relatively safely in children and pregnant women.[20] When treatment guidelines are followed, NBUVB phototherapy appears to have relatively few adverse effects; however, the long-term risk of skin cancer is yet to be precisely quantified. Until such time as it is better defined, patients at high risk of skin cancer may prefer to avoid NBUVB phototherapy.

Although slightly less effective than PUVA, current guidelines suggest that NBUVB phototherapy may be considered as the first-line phototherapy option due to the safety and convenience of avoiding psoralen therapy.[14] However, NBUVB may be insufficiently aggressive to clear severe psoriasis,[15] and may be unsuitable for some patients because of the inconvenience and cost of travelling to the phototherapy clinic for the frequent and numerous UV exposures involved.[14,20] Home delivery of NBUVB phototherapy may be suitable for some patients where there is a geographical need; however, appropriate training and support are required.[14,23]

While there is no convincing evidence that combination therapy enhances the efficacy of NBUVB, concomitant use of systemic retinoids may improve the benefit/risk profile of phototherapy by reducing cumulative UVB exposure.[14,24] However, caution is required as retinoid therapy causes thinning of the stratum corneum and may increase the risk of phototoxicity.[24] Oral retinoid therapy is also associated with several unique safety issues (see 'Oral retinoids') that must be taken into account when considering combination therapy.

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