1. Health

Psoriasis

Description

An in-depth report on the causes, diagnosis, treatment, and prevention of psoriasis.

Alternative Names

PUVA therapy

Phototherapy

Ultraviolet B (UVB) and ultraviolet A (UVA) radiation are primary components of sunlight. UVB is the primary cause of sunburn and primarily affects the outer skin layers. UVA penetrates more deeply and efficiently.

When sunlight penetrates the top layers of the skin, this ultraviolet radiation bombards the genetic material, the DNA, inside skin cells and injures it. It also impairs immune function in the skin. Such effects are the cause of wrinkles, aging skin, and skin cancers. These same damaging effects, however, can also destroy the skin cells that form psoriasis patches.

Phototherapy for psoriasis can be administered as UVA in combination with medications or as variations of UVB radiation with or without medications. Not everyone is a candidate. For example, it may not be appropriate for patients who should avoid sunlight or those with very severe psoriasis.

UVB Therapy. UVB radiation reduces the abnormally rapid skin cell growth that occurs with psoriasis. The current standard treatments using this radiation are either broadband UVB or a newer approach--narrow-band UVB (NB-UVB). Both treatments involve exposure to a light source for a set length of time at regular schedules. Either treatment can be administered at home. Another recent option is the excimer laser that emits a precise wavelength for local areas.

  • Broadband UVB is radiation measured at 290 to 350 nm and has been the standard UVB phototherapy treatment in the US. It can be used with or without the aid of medications. It is not as potent as the treatments that use narrow-band UVB or PUVA and are not useful for chronic psoriasis.
  • Narrowband UVB (NB-UVB) is radiation in a specific range between 310 and 312 nm, which, theoretically, is the most beneficial component of sunlight. NB-UVB is used without medications and is very potent. It may be safer than other approaches, and some experts now believe it should be the first option for patients with chronic plaque psoriasis. Whether it has any affect, however, on the disease process itself is unclear.
  • The excimer laser emits precise UVB wavelength of 308 nm. It is proving to be more effective for treating local areas of psoriasis than many standard treatments.

UVA Therapy (PUVA). The treatment using UVA requires a photosensitizing medication (usually psoralen) in combination with UVA radiation to be effective (and therefore the treatment is referred to as PUVA. This approach is very potent and is effective in more than 85% of patients that use it. However, it also poses a higher risk for skin cancers, including melanoma, than UVB.

Psoralens and Ultraviolet A Radiation (PUVA)

PUVA treatments cause inflammation and redness in the skin to develop within two to three days after treatment. Such damage inhibits skin cell proliferation and reduces psoriasis plaque formation. PUVA employs a combination of a psoralen drug and ultraviolet A (UVA) radiation. Forms of psoralen include methoxsalen, 8-methoxypsoralen (8-MOP), or bergapten (5-MOP). The effectiveness of the treatment is based on a chemical reaction in the skin between the psoralen and light, which creates redness and inflammation that prevents the psoriasis disease process.

People should avoid this treatment if they are taking drugs or have conditions that cause them to be light sensitive. They should also take protective measures before, during, and after each treatment.

Initial PUVA Treatment Phase. The initial phase typically follows these steps:

  • Psoralen is typically taken orally in the form of 8-methoxypsoralen (e.g., Oxsoralen) 75 minutes to two hours before the treatment starts. Psoralen reaches the skin through the bloodstream, where it increases the skin's sensitivity to UVA radiation.
  • Topical preparations of psoralen are alternatives to oral forms. They can be "painted on" or applied to the affected areas by soaking or bathing in a psoralen solution. PUVA-bath therapy may be especially useful for persistent psoriasis on the palms and soles or for patients with liver disease or severe nausea from the oral form. UVA should be administered within 15 minutes of these procedures.
  • The patient then enters the "light box" (a unit lined with ultraviolet lamps, in which patients typically stand up). Initial time is very short (seconds to several minutes) and then increases to 20 minutes or longer. The amount of time a person is exposed to UVA rays depends on the skin type, with the shortest times recommended for fair-skinned patients.
  • Treatments may be repeated two or three times a week. They should never be performed more frequently than once every other day, since the full effects of the treatments are not evident for 48 hours.

It takes an average of about 25 PUVA treatments for full effect, but during that period, treatment intensity may vary:

  • If there is no response after 10 treatments, the physician may increase the UVA energy.
  • If there is still no response after 15 treatments, then the psoralen dosage may be increased.
  • If a patient's skin does not improve at all or worsens after these changes, then the treatment is temporarily stopped. PUVA may be causing a toxic response in such cases, and, often, the condition gradually improves over the following two weeks.
  • If the skin does not improve, then PUVA treatment is considered to have failed. If skin improves during this resting period, then treatment resumes.

Maintenance Phase. Once the psoriasis has improved by about 95%, the patient may be put on a maintenance schedule. Often only one or two treatments a month are needed, but some people may need more frequent treatments. As maintenance continues and the interval between treatments lengthens, the patients may become more susceptible to tanning and sunburn. They should reduce exposure to natural sunlight during this time.

Success Rates. Nearly 90% of patients achieve marked improvement or clearing within 20 to 30 treatment sessions.

Combinations. Effectiveness may be enhanced or response hastened by combining PUVA with oral retinoids, such as acitretin, or drugs such as calcipotriene, methotrexate, or tazarotene gel. In addition, combinations may allow for lower doses of radiation or medications to be used, minimizing side effects. Retinoids may also help protect against skin cancers. On the other hand, methotrexate may increase the risk. In some cases, patients resistant to PUVA or UVB may respond when the phototherapies are combined.

Side Effects and Complications of PUVA. Adverse side effects include the following:

  • The psoralen methoxsalen causes malaise and nausea in 20% of patients. Dividing up the dose and taking it in 15-minute intervals with food or taking the herb ginger 20 minutes before taking the drug may be helpful.
  • Skin reactions, including itching, sunburn, and blistering, are common. These can generally be avoided with careful administration of PUVA therapy and protective measures. Antihistamines, baths with special oatmeal preparations (Aveeno), and capsaicin (Zostrix)--an ointment prepared from the active ingredient in hot chili peppers--may be helpful.
  • After treatment, white spots commonly develop where psoriasis plaques had been, particularly in people with naturally darker skin. If they are troublesome, tanning products may help darken them. Small, dark raised spots called PUVA lentigines may also develop in affected areas with long-term treatment
  • Prolonged standing may trigger fainting in people with certain heart or blood pressure problems.
  • People with liver disease should discuss using topical psoralens, since oral forms may have adverse effects on the liver.
  • UVA penetrates the skin more deeply than UVB, so there is a greater danger of deep skin damage, accelerated skin aging, and skin cancers. Anyone who needs to avoid sunlight should not undertake this treatment.
  • The procedure increases the risk for cataracts if eyes are not protected for up to 24 hours after treatment.

Special Warning on PUVA and Skin Cancers. It has been known for some time that PUVA can modify DNA and cause genetic mutations. PUVA is known to increase the risk for squamous cell skin cancer and slightly increases the risk for basal cell skin cancer, both of which are nearly always curable. The risk for skin cancers is higher in the following patients:

  • Patients who have had over 200 treatments.
  • Patients with a family or personal history of skin cancer.
  • Patients with light skin and fair or red hair.
  • Patients who have had radiation or x-ray treatments or taken immunosuppressant drugs.

Even more worrisome was a study reporting an increased risk of melanoma, a very serious skin cancer. Discussions are under way, in fact, about discontinuing PUVA for psoriasis. The arguments generally are as follows:

  • Opponents of PUVA argue that studies suggest a long-term risk for melanoma, starting about 15 years after treatment, particularly in people who receive more than 250 treatments. Of note, in one 15-year study only nine out of 1,380 patients developed melanoma. However, seven of these cases occurred in the last five years of the study, indicating that the danger persists and more patients in this study are likely to develop this serious skin cancer as time goes on.
  • Supporters of PUVA argue that it is not yet known if the people who developed melanoma experienced sunburn during the procedures or if they already had risk factors for skin cancers. If so, then properly administered treatments could still be considered safe for patients without risk factors. They also argue that PUVA is still the most effective treatment for severe psoriasis, and the alternatives are usually very powerful and relatively new drugs that may have even more serious side effects. Furthermore, the addition of retinoids may protect against skin cancers while proving to be a very effective combination.

Protective Measures with PUVA Therapy

The side effects from UVA radiation can be severe and protective measures are needed during, before, and after treatment.

Protective Measures Before Treatment. Patients should avoid prolonged exposure to the sun for 24 hours before the oral treatment starts.

Protective Measures During Treatment. During PUVA therapy, the patient should take the following precautions:

  • They need to wear specially designed goggles to protect the eyes from UVA radiation.
  • Sensitive areas, such as genitals, abdominal skin, and breasts, are covered until tanning occurs in the exposed areas, after about a third of the treatment period. (Of note: PUVA is associated with a high risk for genital skin cancers and male genitals must be covered throughout the process.)

The following safety features should be available in the PUVA chamber:

  • Lamps with protective shields.
  • A viewing window so that a health professional can check the patient periodically.
  • A door that can be opened by the patient easily and with little pressure.
  • A timer that terminates the session automatically.
  • An accessible alarm device.

Protective Measures After Treatment. The drugs used in PUVA increase susceptibility for a natural sunburn for hours after treatment. The patient should take the following precautions:

  • Patients should wear UVA absorbing wrap-around sunglasses that are designed to completely block out stray radiation. They should begin wearing them as soon as the drug has been taken and for at least 12 hours after the treatment. This is important to prevent a PUVA reaction around the eyes that can cause cataracts. (They do not need to be taken after sundown.)
  • For about eight hours after taking the drug, patients must also avoid exposure to daylight, even if the day is cloudy or through windows.
  • Patients who must go out should wear heavy opaque clothing, including hats and gloves.
  • Sunblocks should be applied over all exposed areas, including the lips. The sunblock should have an SPF (sun protection factor) of more than 15 and include ingredients that block both UVB and UVA radiation.
  • No patient should spend any prolonged time in sunlight for at least two days after the combined treatment.

Broadband Ultraviolet B (UVB) Radiation

Broad spectrum UVB is radiation measured at 290 to 350 nm and has been the standard UVB phototherapy treatment in US. It may be administered with or without medications. When used without medication (known as selective ultraviolet phototherapy), UVB treatment generally is administered as follows:

  • Treatment is typically first administered in the physician's office or another medical setting. Once the disease has stabilized, the patient can obtain a prescription for equipment that can be used at home. Even at home, treatment must always be supervised, however.
  • In preparation, the patient fully undresses, although unaffected areas may be covered to avoid overexposure.
  • The initial session may last as little as a few seconds, depending on whether the patient has a lighter or darker skin, with the lightest skin exposed to the briefest session. The duration increases with each treatment until the skin clears or the patient experiences itching or irritation. (It should be noted that the condition may worsen initially.)
  • UVB therapy usually requires about 20 to 40 treatments (about three per week). Full results take about three weeks.
  • Patients should avoid natural sunlight on treatment days, since they risk becoming seriously sunburned at these times.
  • Maintenance treatment is sometimes required--usually twice weekly for one to two months and then once a week for about four months. This is generally effective in preventing relapse. Individuals vary, however, in their response.

Use of Medication. UVB was commonly used with coal tar (the Goeckerman regimen) in past decades and then with anthralin (the Ingram regimen). Other medications are being investigated with some success and may prove to be more tolerable.

The Goeckerman regimen requires daily treatments for up to four weeks. The coal tar or anthralin are applied once or twice each day and then washed off before the procedure. Studies indicate that a low-dose (1%) coal tar preparation is as effective as high-dose (6%). Such regimens are unpleasant, but still useful for some patients with severe psoriasis, since they can achieve long-term remission (up to six to 12 months).

Some evidence suggests that by using a simple emollient (e.g., Vaseline, mineral oil) that enhanced UVB light penetration can be effective. (This increases the risk for sunburning, however, and care must be taken.)

Combinations of other topical and oral medications are being tried. For example, combining UVB with methotrexate or retinoids, such as a tazarotene gel or oral acitretin, is producing positive results. Combinations with any of these agents, however, must be supervised carefully to avoid adverse reactions.

Side Effects of UVB. The treatment can cause itching and redness. UVB radiation from sunlight is known to increase the risk for skin cancers. There is no strong evidence, however, that UVB treatments pose any risk for skin cancers except on male genitalia, which can be significant (4.5%) at high doses.

Narrow Band Ultraviolet B (NB-UVB) Radiation

Narrow band NB-UVB radiation uses fluorescent lighting that emits radiation in a specific range between 310 and 312 nm, which, theoretically, is the most beneficial component of sunlight. Exposure times are shorter but of higher intensity than with broadband UVB.

Clearance of 75% typically occurs after 10 to 12 treatments. NB-UVB treatments performed three times a week achieve results that are equal to twice-weekly PUVA treatments. (Weekly NB-UVB treatments are not effective.) It is also probably less likely than PUVA to cause skin cancers. Studies are mixed on whether its remissions rates are equal to those of PUVA, but the weight of evidence is currently positive.

Patients prefer this approach over other PUVA treatments because they do not have to wear protective eyewear, take medications, or experience unpleasant side effects, notably nausea. It is also safe for pregnant women and children.

Some experts, then, believe that NB-UVB should be the first choice for patients with chronic plaque, with PUVA reserved for patients who fail.

According to one 2002 study, however, NB-UVB does not have any affect on the disease process itself. In the study NB-UVB radiation only affected the specific areas of skin that it targeted. Given these results, it is not clear, then, if this approach has any significant long-lasting value for treating chronic psoriasis. Combinations with topical agents, such as tazarotene or psoralens, may improve its effectiveness.

Laser Treatments

Laser UVB Treatment. A recent variation of a device called an excimer laser (Xtrac) delivers a precise UVB wavelength of 308 nm. The excimer laser is more effective than narrow-band UVB (NV-UVB) for localized psoriasis, since it allows targeting of very specific areas of skin. (It is not suitable for the scalp, however.) Generally, eight to 10 treatments administered twice a week are needed to clear psoriasis. Remission rates are similar to NB-UVB, but the excimer laser can clear the psoriasis faster and at lower doses. It also spares the healthy skin around it. Blistering is a common side effect. More comparison studies are needed to determine risk and benefits compared to NB-UVB, particularly any long-term risk for skin cancer.

Pulsed-Dye Lasers. Pulsed-dye lasers emit high-intensity yellow light, which destroy the tiny blood vessels that make up psoriatic plaques. (This treatment has been used for years to remove birthmarks, such as port wine stains, and unsightly blood vessels on the skin.) Some studies have reported significant (but not complete) improvement and remissions that have lasted up to 13 months. Treatments last up to 30 minutes and can feel uncomfortable (similar to being repeatedly snapped with a rubber band). It typically takes up to six sessions to clear the target areas. Bruising is common and there is a small risk for scarring.

Commercial Tanning Units

Home tanning devices and tanning salons are not ordinarily recommended, but they may be helpful for patients without access to a medical unit. In a 2003 study, many patients achieved a significant reduction in symptoms with a combination of acitretin and exposure to a UV-B commercial tanning unit (A Wolff tanning bed). It should be noted, however, that tanning bed and salon standards and UV outputs vary widely. Some units emit UVA radiation, which poses a higher risk for skin cancers. Adverse effects of tanning salons that use UVA or UVB radiation are the same as with any UV phototherapies, including a risk for skin cancer. Experts then do not recommend them except in consultation with a physician or as part of a clinical trial.

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