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NEWS > Publications
| Advances in Psoriasis Treatment |
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Source:
Advances in Psoriasis Treatment
Steven Feldman,M.D.,Ph.D
Dermatology Online Journal 6(1): 4
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Abstract
Psoriasis is a complex disorder that negatively impacts quality of life. Treatment strategies must address both psychosocial and physical aspects of the disease. Psoriasis can be categorized into localized and generalized forms for treatment purposes. In either case, the treatment plan should include obtaining rapid control of the disease and maintaining that control. For localized disease, recent data support the combined use of topical corticosteroids with a noncorticosteroid agent (topical calcipotriene or tazarotene). For generalized disease, UVB phototherapy is an effective treatment that permits both rapid control and long-term maintenance. Use of low doses of acitretin (25mg qd or qod) potentiates both UVB and PUVA therapy. For patients unresponsive to phototherapy or who are not able to come on a regular basis, methotrexate is an effective alternative. Cyclosporine is useful, especially for short-term use in settings of acute exacerbation, but should be replaced by other modalities for long-term maintenance. Other agents that have a place in treatment of generalized psoriasis include hydroxyurea and mycophenolate mofetil.
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UVB Phototherapy
UVB treatments are generally performed 3 to 5 or more times weekly. They are extremely safe. There are some risks of causing phototoxicity, but the sunburn reactions of UVB typically are not severe. Chronic adverse effects include photoaging, so the face should not be treated if there is no psoriasis there. Skin cancer is another potential risk, but this risk must be small because the long-term studies of patients who received Goeckerman (UVB + tar) for years were unable to detect an increased risk. If a patient has already had skin cancer, alternative therapies should be considered, but even so, the risks of UVB are probably still small. If patients have had melanoma, acitretin should be considered as an alternative.
Combining UVB with topical or oral treatments makes UVB more effective. Generally, patients have some heterogeneity to their lesions. Typically, the legs have thicker plaques and these lesions are slower to clear. Extra light can be given to these areas, but adjunctive topical therapy with calcipotriene or tazarotene may be helpful. The use of corticosteroids during phototherapy should generally be avoided to prevent shortening of remission periods though this belief has been refuted in one study. Outpatient day treatment regimens that utilize the Goeckerman (UVB plus tar under occlusive wraps) or Ingram (UVB plus anthralin paste) methods may be used for severe disease unlikely to clear with UVB alone. These day treatment regimens are very effective and very safe. Oral therapies such as acitretin or methotrexate may also enhance the effect of UVB.
UVB phototherapy is a very gratifying means of obtaining long-term control of psoriasis. If initial control of psoriasis is obtained with one of the variations of UVB phototherapy, then long-term control of the disease will usually be achieved either because the patient will have a long-term remission of their disease or by giving the patient maintenance UVB phototherapy, either in the form of sun exposure or with a home UVB phototherapy device. Patients generally love home UVB phototherapy, perhaps in part because of the sense of control that it gives them over their disease. Several arguments against home UVB phototherapy have been made:
- It is too much like giving a patient an unlimited prescription for a treatment that has potential side effects and that should be monitored. Only prescribe home UVB phototherapy devices that have incorporated timers.
- Patients may not be compliant with appropriate use of UVB. Prescribe patients home UVB units only after they have had a course of office UVB treatments. First make sure that UVB works for them and that they are aware of and compliant with genital protection and UVB dosing.
- The dose of home UVB phototherapy cannot be adequately controlled. Many dermatologists recommend sun exposure for patients with psoriasis. There is much better control of UVB dose with home UVB phototherapy compared with sun exposure.
Another way to obtain phototherapy is the use of a commercial tanning bed. Tanning beds are available in even the smallest towns in the U.S. and are probably a very useful treatment for patients who live in areas inaccessible to office UVB phototherapy treatments. One study found that use of one particular tanning bed resulted in improvement in >90% of patients. Tanning bed treatments are not a replacement for office phototherapy. It is not known if it is the UVA tanning light that is effective or a contaminant of UVB; moreover there is probably tremendous heterogeneity between tanning bed units in the community. Moreover, tanning bed treatments would not be medically supervised as was the case in the published trial. Nevertheless, for somebody who cannot get office UVB phototherapy, tanning beds may be a helpful option. Psoralens should not be used in combination with tanning bed light as there may be severe, life threatening burns!
Psoralen plus UVA photochemotherapy (PUVA)
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Table 6: Psoralen plus UVA photochemotherapy (PUVA)
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- 2-3 x/week treatment
- High risk of cutaneous carcinogenesis, should not be done in combination with tanning bed use
- Combination with low dose acitretin improves efficacy and may reduce long-term side effects
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PUVA is a very effective treatment for psoriasis, but the side effects are greater than for UVB. There is more risk for sunburn-like photoreactions, and they are more severe than the burns that occur with UVB. There is a well-documented increase in the risk for future development of squamous cell carcinomas. Moreover, patients who have been on PUVA for years get unusual appearing pigmented lesions, PUVA lentigines. One long-term follow-up study suggests there is an increased risk of melanoma. An advantage of PUVA is it can be used for maintenance (treatments given 1x/wk to 1x/month as needed) after the initial clearing phase (2-3x/wk). Acitretin improves the efficacy of PUVA, helping to reduce the number of treatments needed (and hopefully, therefore, the long-term risk of carcinogenesis). If any psoriasis treatment reduces the risk of skin cancer, it is probably oral retinoid.
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Table 7: Acitretin (Soriatane)
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- Oral retinoid, associated with high risk of teratogenesis and other retinoid side effects!
- Most effective for pustular psoriasis (including palmoplantar psoriasis)
- Monotherapy dose 25-50 mg/day
- Very effective in combination with UVB and PUVA, use low dose (25 mg/day or every other day) to minimize retinoid side effects
- Check liver function tests and triglycerides at baseline and at 2-4 week intervals
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Acitretin is modestly effective for plaque psoriasis. It is more effective as a monotherapy for pustular and erythrodermic psoriasis. Acitretin may be the safest systemic treatment for psoriasis except for the associated teratogenic risk that lasts two to three years after discontinuing treatment. Acitretin can be converted in vivo in the presence of ethanol to etretinate (Tegison), which has an even longer half-life. Therefore, if a woman of childbearing potential requires oral retinoid therapy, consider a course of isotretinoin (Accutane) instead of acitretin. While both drugs are potent teratogens, pregnancy can be safely initiated one month after discontinuing isotretinoin.
Other adverse effects of acitretin include hypertriglyceridemia and hepatotoxicity. Monitoring should include liver function tests and triglyceride levels at baseline and at 2-4 week intervals until stable levels are achieved. If hypertriglyceridemia does occur, use of a lipid-lowering agent may be helpful. Pancreatitis can occur with extremely high triglyceride levels. Acitretin may cause alopecia and other bothersome retinoid side effects. Low dose therapy (25mg/day or 25mg every other day) is well tolerated and is usually sufficient to improve the efficacy of phototherapy. Such doses of acitretin are also helpful in the treatment of palmoplantar psoriasis.
Summary
Psoriasis is a multifaceted disease and its treatment generally requires the expertise of dermatologists. The National Psoriasis Foundation is a tremendous resource for patient education and advocacy in psoriasis care. To plan for acute and long-term control of localized psoriasis, combinations of topical corticosteroids and either calcipotriene or tazarotene are the most effective approaches. For generalized disease, UVB treatment provides the safest means of achieving long-term control of the disease. Acitretin is a very helpful adjunct for improving the efficacy of phototherapy. For patients with severe, refractory disease, methotrexate may be most effective, while cyclosporine may be most valuable for patients needing rapid, short-term improvement.
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| Ultraviolet light for psoriasis |
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Source:
Ultraviolet light for psoriasis
Rona M Mackie
BMJ 1997;315 (12 July)
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Where does the balance of advantage lie in the effect of ultraviolet light for people with psoriasis?
Approximately 80% of people with psoriasis will observe that their psoriatic plaques are improved by exposure to natural sunlight, 10% notice no difference, and 10% report deterioration. This observation has led to the widespread use of artificial ultraviolet radiation as one method of treating psoriasis either singly or in combination. Broad band ultraviolet B (290-320 nm) has been widely used for many years either as monotherapy or to augment the effects of topical agents such as topical tar and dithranol. Several studies of large populations of patients with psoriasis have failed to find an increased incidence of any type of cutaneous or systemic malignancy in patients with psoriasis treated in this way compared with local controls.
A new addition to treatment with ultraviolet B is the narrow band TLO1 lamp emitting radiation at 312 nm. This wavelength clears psoriatic plaques more rapidly than older broad band ultraviolet B sources but not enough data are available to report on the ratio of risk and benefit of this approach. Ultraviolet A or longwave artificial ultraviolet sources (320-360 nm) may benefit some patients with psoriasis who use sunbeds which are usually equipped with tubes emitting this wavelength, but for greater benefit a systemic photosensitising agent, a psoralen (PUVA), is usually added. While PUVA is effective in clearing stubborn psoriasis it is teratogenic and full contraceptive precautions must be taken by young women. There is now also evidence that high total cumulative doses of ultraviolet A given with a psoralen photosensitiser lead to an increased incidence of squamous cell carcinoma, but not of other malignancies. The risk is greater in those who have used other carcinogenic agents as part of their treatment, such as methotrexate, but is still seen in patients who have used only PUVA.
Traditional broad band ultraviolet B sources are safe and non-carcinogenic if used in controlled conditions for intermittent courses (commonly three exposures a week for six weeks). There are no data on the new narrow band source or on ultraviolet A used alone.
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Source:
Update on phototherapy
By John Y. Koo, M.D. and Khanh D. Nguyen, M.S.
Skin & Aging Vol. 10 (Feb 02 2002)
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The reimbursement issue with phototherapy has been resolved, but a few other issues remain. Does narrow-band UVB work as well as PUVA phototherapy? Are you putting patients at risk for melanoma with PUVA phototherapy?
As of January 1, Medicare increased the reimbursement rate of UVB therapy and of phototherapy by 117%, thanks to work spearheaded by the National Psoriasis Foundation, which was represented by Mark Lebwohl, M.D., the chairman of dermatology at the Mount Sinai School of Medicine. The work was endorsed by the AAD. However, there are still a few other issues regarding UVB therapy and phototherapy that need to be discussed.
PUVA Versus Narrow-Band UVB
Results of earlier, small studies comparing the efficacy of narrow band UVB phototherapy to PUVA phototherapy were mixed. However, in a recent British randomized study of 100 patients, where 51 were treated with narrow-band UVB and 49 were treated with PUVA, the efficacy and duration of remission with PUVA phototherapy proved to be significantly superior to that of narrow-band UVB phototherapy.1 For this clinical trial, phototherapy was conducted for up to 16 weeks. PUVA phototherapy showed an 84% overall improvement of psoriasis as opposed to a 63% improvement seen with narrow-band UVB phototherapy. After 6 months, 35% of PUVA phototherapy patients remained in remission, while only 12% of narrow-band UVB patients stayed in remission. The results show that this is a valuable treatment for psoriasis, but do you increase melanoma risk as a result or is this a safe form of treatment?
PUVA and Melanoma Risk
Most of us are aware of the report of a U.S. 16-center PUVA cohort that demonstrated increased risk of melanoma among long-term PUVA patients.2-3 However, many are not aware of the fact that no less than 22 studies have been published world-wide specifically examining the melanoma risk of PUVA phototherapy showing no increased risk of melanoma. In fact, the U.S. 16-center study is the only cohort to date showing increased risk of melanoma with PUVA phototherapy. Among the 22-plus negative studies, the most comprehensive is a Swedish, long-term PUVA-melanoma study involving 4,799 patients of which 1,876 patients were followed for 15 to 21 years.4 When compared to the general Swedish population, neither the entire cohort nor the 1,876 patients followed for 15 to 21 years showed any increased melanoma risk. A separate analysis for the 1,876 patients was conducted specifically to determine whether the findings of the U.S. 16-center study could be replicated. The result was negative.
These diametrically opposite findings suggests that either there was a serious difference in the methodology on how the studies were conducted or that the relationship between PUVA and melanoma is much more complicated than the U.S. study suggests. There was a significant difference in the quality of the comparison group used to calculate the melanoma risk. Neither cohort had a control group. The U.S. study used the surveillance, epidemiology, and end results (SEER) data collected from hospital inpatients by the National Institute of Cancer. Many publications have criticized the use of this data as a comparison group because melanoma is often treated on an outpatient basis, not inpatient. Also, there is no legal requirement to report melanoma in the United States, so the SEER data might have underestimated the prevalence of melanoma in the general population, which automatically inflated the calculated risk of PUVA phototherapy. In contrast, both dermatologists and pathologists in Sweden are legally required to report melanoma.
Other Possible Explanations for the Discrepancy
Another possibility for the contradicting results is that increase in melanoma risk in the U.S. study is real, but simply not due to long-term exposure to PUVA phototherapy. If the increase is simply due to the fact that these patients were exposed to PUVA over that period of time, there is no way to explain the negative finding from the Swedish study. The true culprit might be more complicated in that it may have to do with how PUVA phototherapy was used or what it was used with. The discrepancy may be explained by the fact that, initially, PUVA phototherapy was conducted extremely aggressively in the U.S. 16-center study, where investigators tried to obtain visible erythema on research subjects. This protocol was later modified when it was realized that such aggressiveness was not necessary with PUVA (as opposed to UVB therapy) and often counterproductive. This aggressive protocol was never utilized in any of the other European studies. The more widespread use of bathPUVA and RePUVA in some European cohorts may also help explain the discrepancy.
In order to really understand the cause of the increased melanoma risk in the U.S. 16-center study and understand the discrepancies with all other published studies, open dialogue between the investigators is still needed. This is the only way the true nature of the risk factor(s) responsible for the melanoma risk can be elucidated.
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