Phototherapy for Psoriasis

Introduction

Phototherapy is the oldest form of psoriasis therapy and is still likely the most commonly used. From prescribing exposure to various wavelengths of ultraviolet light, to applying salts and tars at the Dead Sea, to sitting in the sun on vacation, almost all psoriasis patients use the power of ultraviolet light to improve their skin. Here, we focus on the forms of ultraviolet light that are most commonly prescribed by dermatologists, in-office or home ultraviolet light therapy (Table 10-1). However, we should never lose sight of the common use of the easiest and cheapest form of phototherapy, the sun.

Phototherapy traditionally has been classified in two forms, based on the wavelength of emitted light. Ultraviolet A (UVA) has a wavelength from 360 nm to 400 nm. Ultraviolet B has a wavelength from 290 to 360 nm. In general, UVA has deeper penetration into the skin but disperses less local energy. UVB is higher energy but is limited to the top layers of the skin. The earth’s atmosphere, particularly the ozone layer, is generally quite efficient at reducing the amount of UVB getting to the surface of the earth.

Phototherapy was one of the earliest treatments discovered for extensive psoriasis and remains an important part of therapy today. In the past century, it has progressed from simple sun exposure to treatment in a photo booth with or without exposure to photosensitizing agents. Today, narrowband Ultraviolet B (NB-UVB), whether given diffusely or locally, has the dominant role in psoriasis phototherapy, with psoralen plus Ultraviolet A (PUVA) being reduced to relatively specific uses. It is clear, however, that a good understanding of phototherapy and its availability are central to any comprehensive treatment approach to cutaneous psoriasis.

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Ultraviolet B Therapy

Ultraviolet B (UVB) therapy has been used as a therapeutic modality for a number of decades. Initially, UVB was given as a broad spectrum within the wavelength wave. However, with the identification of the most specific active spectrum for the treatment of the disease, narrowband UVB (NB-UVB) that uses a more specific wavelength of 309 nm to 313 nm has been the predominant modality of treatment. UVB has been combined with many other topical and systemic treatments to improve the efficacy of the treatment.

UVB works primarily as a local immunosuppressant. In vitro and in vivo data suggest that the light diminishes activity and induces apoptosis of local T cells that may be involved in the pathophysiologic process of psoriasis. This induction of apoptosis includes Th17 T cells. Likewise, phototherapy can decrease the concentration of local dendritic cells that may also act as pro-inflammatory.

Initial treatment with UVB, both broadband and narrowband, requires exposure to the light source frequently at increasing doses to be able to tolerate a therapeutically effective dose. The proper protocol for a patient is based on their Fitzpatrick skin type (I-VI) based on the ease with which they burn. Too rapid exposure to higher doses can lead to burning that can actually make psoriasis worse. Thus, with both narrowband and broadband treatment, patients are usually exposed two to three times per week. Older protocols with broadband frequently called for more frequent treatment but this is generally considered too inconvenient for most patients. One interesting difference between the two types of UVB is that patients with broadband therapy frequently benefit from small amounts of erythema after treatment, while this redness seems unnecessary with narrowband. Many different protocols for treatment have been published. Excellent protocols published by the American Academy of Dermatology Guidelines project are listed in Table 10-2 and Table 10-3.

The efficacy of UVB treatment is well accepted among dermatologists. Various studies have shown that monotherapy with NB-UVB gives a psoriasis area and severity index (PASI) 75 rate of about 60% to 80%. NB-UVB is generally significantly better than broadband UVB (BB-UVB) and approaches the efficacy of psoralen plus UVA (PUVA) therapy (see below). Since UVB can be used for sustained benefit, the efficacy of this treatment is considered the equal to or superior to many of the systemic medications available. UVB phototherapy can be delivered in the office or at home. In general, data suggest that while home UVB can be given safely, initial response is better with office-based units. This benefit in efficacy, however, needs to be balanced by the much greater convenience for the patient in getting treatment at home. Units are also available for the treatment of specific areas for the scalp, hands and feet. These have somewhat smaller rates of response than whole-body UVB but can be of benefit for many patients.

The addition of topical or systemic treatment to UVB in order to increase its efficacy has been controversial. The addition of emollients and/or mineral oil to decrease the amount of visible scale prior to treatment seems to increase efficacy by decreasing the reflective properties of scale. Likewise, low-grade evidence exists for the addition of topical corticosteroids and vitamin A and D derivatives in conjunction with UVB phototherapy. The traditional association of tar and anthralin to UVB is somewhat more controversial with existing low-grade data both supporting and denying the claim that these preparations have significant benefit when used in conjunction with phototherapy. Nonetheless, intense procedures associated with the use of tar-based topicals including Goeckerman therapy (intensive UVB and overnight tar therapy) and Ingram therapy (intensive UVB and anthralin treatment), both are considered highly effective, if inconvenient, treatments for psoriasis. The use of these protocols has decreased significantly due to difficulties in hospitalizing patients for psoriasis along with newer treatment modalities.

The safety of UVB is controversial. While acute events such as burning clearly take place and must be considered prior to every treatment with UVB, data on more significant side effects, including long-term photoaging and skin cancer, are less clear. There is general consensus, although with few data, that photoaging is among the risks of UVB phototherapy based on the patient’s exposure. Moreover, some authors suggest that there is a small, but real, increase in the risk of non-melanoma skin cancer with UVB phototherapy based on the number of treatments to which the patient has been exposed. However, the predominance of evidence is that there is no statistically or clinically significant increase in this risk.

This controversy concerning the risk of skin cancer with UVB is critical for clinicians in answering two important questions. The first is the use of UVB in patients at high risk, particularly those with a history of non-melanoma skin cancer or melanoma. In all the data bases evaluated in determining the risk of UVB, there is likely a bias toward not treating patients at higher risk. Thus, this bias may suggest that it would be preferable to avoid treating patients, if possible, who have had a prior skin cancer or have multiple pre-skin cancers.

The second question is whether one should consider long-term maintenance therapy with UVB for those patients who respond well. Since there is no consensus on whether the number of treatments is associated with skin cancer risk, there is considerable disagreement on the concept of maintenance therapy. At this time, the American Academy of Dermatology Guidelines on phototherapy for psoriasis suggest that less frequent maintenance therapy is a reasonable approach, while published European and German Guidelines suggest that UVB maintenance should not be used. While alternative therapy should always be considered at every patient visit, the recommendation of whether to use long-term maintenance UVB depends on the risk of alternative approaches. Thus, when these are considered, since the risk of UVB as maintenance therapy is clinically relatively small, it is often safer than other long-term approaches for this chronic therapy.

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Targeted Phototherapy With UVB

One of the more promising newer treatment phototherapy modalities is targeted Ultraviolet B (UVB). The most commonly used of these target treatments is the excimer laser. The excimer laser is monochromatic UVB at a wavelength of 308 nm, very near the peak of the action spectrum of phototherapy, given through a laser as a concentrated spot. The direct application of the UVB at a specific wavelength provides a number of advantages. Most importantly, controlled local application precludes the need to treat normal skin that does not require treatment. This, in turn, allows the overall light intensity to be increased for the psoriatic plaques, increasing the efficacy and allowing fewer treatments and greater patient convenience. Thus, the effectiveness in local treatment effect is significantly increased while long-term side effect considerations are minimized.

Unfortunately, with the increased intensity of local treatment, there are more acute treatment-emergent side effects. These include local burning, blistering and hyperpigmentation that can be of significant short-term distress to the patient. It is important to properly educate a patient prior to starting excimer laser therapy about potential short-term concerns even while considering the long-term safety benefit and local efficacy benefits. Most importantly, it is critical to remember that excimer laser treatment is for localized disease treatment. Patients wishing to have laser therapy for psoriasis that covers large areas should be given alternatives to this treatment.

Psoralen Plus Ultraviolet A (PUVA) Therapy

When psoralen plus Ultraviolet A (PUVA) therapy was first developed, it was considered to be one of the great advances in treatment for psoriasis. It was discovered that psoralen, a naturally occurring substance, could be activated by UVA light and be of tremendous benefit in diminishing cutaneous inflammatory disease. Later, it was determined that orally or topically applied 8-methoxypsoralen (8-MOP) or 5-methoxypsoralen (5-MOP) could intercalate into local DNA and when exposed to appropriate wavelengths of UVA, create abnormalities in the DNA, particularly in the formation of thymidine dimers, decreasing local keratinocyte proliferation and lymphocyte activity. Unfortunately, it was only after many years of study that it became clear that PUVA therapy had significant untoward effects making its use significantly less desirable. Thus, despite its great efficacy, PUVA therapy is rapidly decreasing around the world.

Since its inception, there has been little question of the efficacy of whole-body PUVA therapy. Patients using oral PUVA therapy take either 8-MOP or 5-MOP about 1 to 1.5 hours prior to exposure to UVA light and would receive treatment three times every week. While studies in Europe and the United States varied in the protocol for initiation of treatment, almost all studies of oral PUVA showed an almost 90% clearance rate. While this cannot be directly compared with more recent studies of systemic medications, these are among the highest response rates in any clinical studies of psoriasis. Moreover, patients were able to maintain their responses at a high level when decreasing their exposure to once weekly or even every other week. Further, alternative methods of exposure to psoralen, including application by soaking in a bath, showed equivalent efficacy results. PUVA has been shown to be superior to both forms of UVB phototherapy, although narrowband ultraviolet B (NB-UVB) may approach its efficacy. These results produced a world-wide acceptance of PUVA as an excellent treatment for patients with extensive psoriasis.

Unfortunately, despite the outstanding efficacy, as more patients were treated with PUVA, a very significant side effect profile began to emerge that has lessened the enthusiasm for PUVA. By far, the greatest concern for PUVA use is skin cancer. Multiple reports have made it clear that PUVA raises the rate of non-melanoma skin cancer. Although the magnitude of this increase varies by study, it is most identifiable in patients who have had > 200 treatments in their lifetime. The rate of increase is particularly prominent in squamous cell carcinoma and has been clearly shown in patients who are also taking cyclosporine. Of even greater concern, although still somewhat more controversial, is that PUVA also seems to increase the rate of melanoma. Again, the increase seems to be associated with > 200 treatments and may have a delayed onset that could make it difficult to detect. Clearly, based on the skin cancer results alone, PUVA should not be used for more than 200 treatments in any patient.

There are other side effects, both short- and long-term, that can have an impact on PUVA therapy. After taking psoralen orally, patients often have significant nausea that can be a major limitation of therapy. Additionally, due to ocular photosensitivity, patients are required to wear eye protection. Photosensitivity due to exposure to psoralen also exists with sun exposure so patients are at risk for sunburn after ingesting the medication. Finally, post-treatment erythema and sunburn can be a particular problem with PUVA therapy and great care must be taken in dosing.

Photoaging of the skin often is viewed as a minor long-term consequence of PUVA therapy compared with skin cancer but this, too, can have devastating results. Patients often have significant skin fragility to go along with wrinkles and multiple neoplasia, particularly lentigos. While these lesions are of cosmetic importance to the patient, their presence in light of concerns for melanoma can be confusing and lead to frequent excisional procedures since they often have an atypical appearance. While there is concern that PUVA treatment could increase the risk of cataract formation, long-term studies do not seem to bear out this concern.

Despite concerns for safety, PUVA therapy remains useful in special situations. Patients can be treated on short-term protocols but should not be treated for > 200 treatments. Certain specific treatment modalities, including topical treatment for hand and foot disease, are still in widespread use and minimize the safety concerns associated with PUVA therapy. Yet, as new treatment approaches continue to be discovered, PUVA therapy will likely continue to diminish as an alternative for patients with psoriasis.

Climatotherapy

One specific variant of phototherapy deserves special note due to, if nothing else, its historic significance. For many years, psoriasis patients have gone to Israel or Jordan to soak in the Dead Sea and apply mud or salts from the area, then have intense sun exposure due to the depth below sea level of the surrounding area. While psoriasis patients have been going to the Dead Sea for many years and products from this area are sold around the world, little in terms of critical study has been performed.

A few studies have suggested that the efficacy rate is quite good, with a 4-week psoriasis area and severity index (PASI)-75 rate of about 75%. Interestingly, a study comparing Dead Sea phototherapy alone against phototherapy with soaking strongly suggests that most of the improvement associated with climatotherapy is due to the sun exposure component rather than exposure to the various salts in the Dead Sea. While trips to the Dead Sea area are not feasible for most patients in the United States and Europe, some psoriasis guidelines suggest that it can be helpful for certain patients with chronic disease.