Excimer laser for psoriasis: a review of theories regarding enhanced efficacy over traditional UVB phototherapy

BACKGROUND: Fiber-optically targeted ultraviolet B (UVB) therapy has been shown to clear plaques of psoriasis in a significantly fewer number of treatments and reduce overall cumulative UVB dose than traditional UVB phototherapy. OBJECTIVE: This article reviews existing theories in the literature attempting to explain the superior efficacy of targeted UVB. METHODS: Medline was used to perform a comprehensive review of the literature from 1965 to present. Only information from the English language journals are reported in this study. RESULTS: The theories proposed to explain the higher efficacy of the excimer (XeCl) laser relative to traditional UVB include the ability to use higher intensities of ultraviolet (UV) light and a more efficient induction of T cell apoptosis. CONCLUSION: The possible explanations for the superior efficacy of the excimer laser over traditional UVB therapy for psoriasis include: 1) a higher intensity UV light to plaques, which is more effective in clearing psoriasis; 2) penetration into the dermis where it may induce T cell apoptosis, potentially to a greater extent than the wavelength or given energy level predicts; and 3) the difference in the delivery of UVB light may result in cell death and skin immune system suppression more effectively than traditional UVB.     

Tazarotene: therapeutic strategies in the treatment of psoriasis, acne and photoaging

Tazarotene is a member of the new generation of receptor-selective, synthetic retinoids for the topical treatment of mild to moderate plaque psoriasis, acne vulgaris and photoaging. Though they are effective in monotherapy, clinical studies with a focus on novel combination treatments and a comparison of different agents for these skin disorders are accumulating. The concomitant use of tazarotene with a mid-potency or high-potency corticosteroid enhances the efficacy in psoriatic plaques and reduces the risk of steroid-induced skin atrophy. Combining phototherapy with adjunctive tazarotene accelerates the clinical response and reduces the cumulative UVB or PUVA exposure load. Tazarotene applied once daily is superior to adapalene monotherapy in acne vulgaris and is efficacious in the treatment of photodamage. Novel therapeutic regimens such as short-contact therapy have been developed for both acne and psoriasis in order to diminish the major adverse events like pruritus, burning, local skin irritation and erythema.     

A review of acitretin for the treatment of psoriasis

Background: Acitretin is an oral retinoid that is approved for the treatment of psoriasis. It is unique compared to other systemic therapies for psoriasis such as methotrexate and cyclosporine in that it is not immunosuppressive. It is, therefore, safe for use in psoriasis patients with a history of chronic infection such as HIV, hepatitis B, hepatitis C or malignancy who have a contraindication to systemic immunosuppressive therapy and require systemic therapy because topical therapy is inadequate and they are unable to commit to phototherapy. Acitretin is one of the treatments of choice for pustular psoriasis. Even though acitretin is less effective as a monotherapy for chronic plaque psoriasis, combination therapy with other agents, especially UVB or psoralen plus UVA phototherapy, can enhance efficacy. Objective: To provide an updated review of the safety and efficacy of acitretin in the treatment for psoriasis. Methods: Literature review of journal articles from 2008 to 2009 since the last review of acitretin evaluated medical literature from 2005 to 2008. Results/conclusion: Acitretin is an effective systemic therapy for psoriasis and is generally well tolerated at low doses for long-term use. If monotherapy with acitretin is inadequate, it can be used in combination with other treatments, particularly UVB phototherapy, to increase efficacy.     

维A酸在银屑病患者中的应用

银屑病为常见的慢性复发性皮肤病,维A酸已成功应用于该疾病的治疗。本文重点介绍两种代表性药物——阿维A酸与他扎罗汀在银屑病临床治疗中的有关情况。口服阿维A酸对脓疱型及红皮病型银屑病最为有效,与光疗联合对中、重度斑块性银屑病疗效显著;而他扎罗汀作为第一个受体选择性外用维A酸,不论单用或联合治疗,对寻常型银屑病均有显著疗效。     

Disease and treatment burden of psoriasis: examining the impact of biologics

Plaque psoriasis is a chronic, inflammatory skin disease that can be difficult to treat. Traditional systemic agents, topical agents, phototherapy and biologic therapies can be used for patients with psoriasis. The authors reviewed published results from a variety of sources in order to better understand the effects of psoriasis treatments on patient satisfaction, patient adherence, healthcare resource utilization and productivity. Patients with psoriasis consider many factors when evaluating therapies, including the time for the therapy to be effective, cosmetic issues common with topical therapies and travel to and from phototherapy centers. Satisfaction with and adherence to biologic therapies appears to be greater than for traditional therapies. Although biologic therapies are generally more expensive than are traditional, these agents may contribute to decreased healthcare utilization and increased productivity.     

Calcipotriol monotherapy versus calcipotriol plus UVA1 versus calcipotriol plus narrow-band UVB in the treatment of psoriasis

The purpose of this study was to evaluate the efficacy of calcipotriol ointment as monotherapy versus calcipotriol in combination with narrow-band ultraviolet (UV)-B or UVA1 phototherapy and to determine whether calcipotriol in combination with UVA1 is an alternative to calcipotriol with narrow-band UVB phototherapy. Forty-five patients with plaque psoriasis were divided into three treatment groups with no significant differences in Psoriasis Area and Severity Index (PASI) scores, mean age, sex or skin type. The total duration of the treatment was 3 months. Regarding PASI score, psoriasis regression was statistically significant between the groups. The response to UVA1 and narrow band UVB with calcipotriol was superior to calcipotriol monotherapy. UVA1 phototherapy with calcipotriol could be an alternative to narrow-band UVB phototherapy with calcipotriol.     

Medical backgrounder: psoriasis

Psoriasis is a chronic skin disorder that affects approximately 2% of the US and European populations. Psoriatic lesions are extremely characteristic of the disease, which allows for simple diagnosis. A clear understanding of the pathogenesis of psoriasis does not yet exist. Hyperproliferation of keratinocytes is a further characteristic feature. Studies have depicted that the epidermal cell cycle of psoriatic lesions is shortened by approximately eight-fold more than normal. The lesions are classified as erythrosquamous, due to the erythema which develops asa result of involvement of the vasculature, and the involvement of the epidermis with scale formation. The diagnosis of psoriasis can usually be established on clinical grounds. If the clinician is in doubt, a small cutaneous punch biopsy and subsequent histopathological examination can be performed. There are multiple therapeutic options for psoriasis. First-line therapy for patients with moderate to severe psoriasis is the application of topical agents, followed by phototherapy (UVB) for more extensive disease. If extensive disease does not respond to UVB, second-line agents include psoralen plus UVA (PUVA), methotrexate, cyclosporine or other systemic agents, including novel biologic therapies. New psoriasis treatment regimens have been developed and include combination, rotational and sequential therapy.     

Non-invasive evaluation of tacalcitol plus puva versus tacalcitol plus UVB-NB in the treatment of psoriasis: "right-left intra-individual pre/post comparison design"

Photochemotherapy with psoralen plus ultraviolet A(PUVA) and phototherapy with UVB narrow band (UVB-NB) are used in the treatment of psoriasis. Numerous studies have shown that the additional administration of either topical or systemic antipsoriatic agents may effectively increase the efficacy of these therapies. This study aimed to compare through objective data the efficacy of topical tacalcitol in combination with PUVA or UVB-NB versus PUVA and UVB-NB monotherapy in the treatment of mild to moderate chronic plaque psoriasis. Modified Psoriasis Area and Severity Index (PASI) score, transepidermal water loss (TEWL) and stratum corneum hydration were used to monitor the restoration of skin barrier in the psoriatic plaques of 40 patients during photochemotherapy. The study was a right-left, intra-individual, pre/post comparison trial. PUVAand UVB-NB treatments were given three times a week. On those plaques localized on the right side of the body tacalcitol ointment was applied once a day, in the evening. Corneometry, TEWL and modified PASI score were used to evaluate the response to the treatment at baseline, one month and two months. Thirty-six of the forty enrolled subjects completed the study. The comparison between combination treatments and the PUVA/UVB-NB monotherapy showed no significant differences with regard to modified PASI index. However, significant differences were recorded with regard to TEWL and corneometry. The combination of tacalcitol plus PUVA or tacalcitol plus UVB-NB restored epidermal barrier functions as well as skin hydration faster than PUVA or UVB-NB monotherapy (TEWL: p=0.0050 and corneometry: p=0.003). The combination of tacalcitol plus UVB-NB allowed a better restoration of skin barrier functions than tacalcitol plus PUVA (p=0.013). In conclusion, the combination of tacalcitol plus PUVA or plus UVB-NB improves the therapeutic result. In addition, the data from TEWL and skin hydration suggest a means in which tacalcitol plus UVB-NB induces a better normalization of skin biophysical parameters.     

国产卡泊三醇软膏联合308nm准分子激光治疗斑块状银屑病的疗效观察

目的探讨国产卡泊三醇软膏联合308 nm准分子激光治疗斑块状银屑病的疗效与安全性。方法 60例寻常性斑块状银悄病患者随机分为治疗组和对照组,每组30例。治疗组外用卡泊三醇软膏2次/d,联合308 nm准分子激光照射3次/周;对照组单照射308 nm准分子激光3次/周。治疗8周后,观察疗效。结果治疗组总有效率（90.00%）与对照组总有效率（63.33%）相比,差异有统计学意义（P〈0.05）,且治疗效果好,疗程缩短,不良反应少。结论国产卡泊三醇软膏联合308 nm准分子激光治疗斑块状银屑病比单用308 nm准分子激光更安全有效。     

Established treatments of psoriasis

Psoriasis is a complex disease with a spectrum of clinical manifestations. Psoriasis may express as a few coin-sized erythemato-squamous plaques up to widespread disease covering the entire body surface (erythrodermic psoriasis). Psoriasis may present as a few stable plaques or unstable disease, rapidly relapsing after treatment. Some patients may respond excellently to topical treatments whereas other patients may be difficult to manage, showing treatment resistance even to the systemic treatments. Therefore, a spectrum of treatments is available to individualize care of psoriasis. In this chapter the available treatments are presented. The vast majority of patients is treated with topical treatments, with vitamin D(3)analogs and topical corticosteroids as the first line treatments. Tazarotene is an alternative for vitamin D(3) treatment if this treatment fails. In some special cases, dithranol and tar treatment may be used. Phototherapy with UVB and photochemotherapy (PUVA) are indicated in patients not responding sufficiently to topical treatment. However, chronic exposure, in particular to photochemotherapy implies an increased risk for photo- carcinogenicity. Systemic treatments including methotrexate, cyclosporin, acitretin and fumarates are indicated in patients who cannot be managed with topical treatments or phototherapy, either for treatment resistance or cumulative toxicity. In this article the opportunities and limitations of the available treatments are presented.     

Strategy to manage the treatment of severe psoriasis: considerations of efficacy,safety and cost

Psoriasis is a common, unpredictable, chronic immune-mediated disease characterised by skin lesions and frequently associated with arthritis. Although rarely fatal, psoriasis has a tremendous impact on a patients' quality of life. Traditional therapies for severe psoriasis include phototherapy, methotrexate, oral retinoids and cyclosporin. New biological agents add to the treatment options for psoriasis; however, they raise the already considerable cost of managing the disease. In considering efficacy, safety and cost-effectiveness, ultraviolet Type B (UVB) phototherapy appears to be the best first-line agent for the control of psoriasis. Methotrexate, psoralen plus UVA, alefacept, etanercept and infliximab are appropriate second-line agents, the choice of which requires considerable patient input and physician judgement. Developing rational, effective and acceptable strategies to manage psoriasis treatments would encourage cost-effective psoriasis management.     

Strategy to manage the treatment of severe psoriasis: considerations of efficacy,safety and cost

Psoriasis is a common, unpredictable, chronic immune-mediated disease characterised by skin lesions and frequently associated with arthritis. Although rarely fatal, psoriasis has a tremendous impact on a patients’ quality of life. Traditional therapies for severe psoriasis include phototherapy, methotrexate, oral retinoids and cyclosporin. New biological agents add to the treatment options for psoriasis; however, they raise the already considerable cost of managing the disease. In considering efficacy, safety and cost-effectiveness, ultraviolet Type B (UVB) phototherapy appears to be the best first-line agent for the control of psoriasis. Methotrexate, psoralen plus UVA, alefacept, etanercept and infliximab are appropriate second-line agents, the choice of which requires considerable patient input and physician judgement. Developing rational, effective and acceptable strategies to manage psoriasis treatments would encourage cost-effective psoriasis management.     

New vitamin D analogs in psoriasis

Psoriasis is a common inflammatory and hyperproleferative skin disease characterized by infiltrated plaques of the skin and may involve nails, scalp and intertreginous areas. Recent years of research has shown that psoriasis can be treated topically with analogs of vitamin-D(3). Impaired differentiation and increased proliferation of epidermal keratinocytes are key features in psoriatic lesions together with a local activation of T lymphocytes. Evidence has accumulated that analogs of vitamin D(3) increase differentiation and inhibit proliferation of keratinocytes. Topical treatment with analogs of vitamin D(3) have in a number of trials shown improvement of psoriasis. Vitamin D analogs show the same efficacy as potent topical corticosteroids and do not produce skin atrophy during long-term therapy. Vitamin D analogs can be used both as monotherapy and in combination with topical corticosteroids, UVB, PUVA, acitretin, methotrexate and cyclosporine. The vitamin D(3) analog calcipotriol has been investigated in most detail and is available as an ointment, a cream and as a scalp solution. From clinical studies involving several thousands of patients, it can be concluded that calcipotriol is efficacious, safe and well-tolerated even on a long term basis.     

The efficacy of topical tazarotene monotherapy and combination therapies in psoriasis

Tazarotene (Tazorac, Allergan, Inc.) is the first topical retinoid approved for the treatment of plaque psoriasis. It has a similar onset of action compared to potent topical steroids and has the advantage of a longer remission. The common side effects associated with the drug include skin irritation (including pruritus), erythema and a burning sensation. To overcome some of these shortcomings, it has been used in combination with steroids, calcipotriene and phototherapy. Combination therapy not only results in a decrease in adverse side effects, but also enhanced efficacy. Clinical study data have shown that combination therapy is just as important as tazarotene monotherapy, if not more.     

Association of cyclosporine and 311 nM UVB in the treatment of moderate to severe forms of psoriasis: a new strategic approach

Psoriasis is a T-lymphocyte mediated autoimmune disease. The response to therapies targeting T-lymphocytes suggest that the latter is a key cell in the pathogenesis of the disease. Cyclosporine (CsA) inhibits the proliferation and the IL-2 dependent expansion of T-lymphocytes. Ultraviolet radiation is an effective treatment for psoriasis. Several studies have demonstrated a significant improvement of the therapeutic response when narrow-band radiation is issued by TL-01 fluorescent lamp compared to broad- band UVB issued by other fluorescent sources. The effects of UVB on the immune system appear to be limited to the cell-mediated compartment of the immune response. In order to reduce the cumulative dose of UVB and limit the toxicity of drugs in the therapy of psoriasis, phototherapy with UVB has been used as treatment in association with other standard therapies. The purpose of the study is to evaluate, in patients with moderate to severe psoriasis a combined therapy with Cyclosporine A and 311 nm UVB phototherapy.     

Emerging topical treatments for psoriasis

Introduction: Psoriasis is an immune-mediated chronic inflammatory skin disease which classically presents as erythematous, scaly plaques affecting extensor surfaces of the limbs, scalp and trunk. Approximately 80% of patients have a mild-to-moderate form routinely treated with topical medications, whereas phototherapy, systemic and biological therapies are typically reserved for treatment of moderate-to-severe psoriasis.

Areas covered: The major advances in psoriasis therapy in the past 15 years have been in new immunomodulatory and biological molecules, with a significant unmet need to have new, efficient and safe topical treatment options for the large percentage of patients for whom systemic therapy is not indicated. The available topical therapies (corticosteroids and vitamin D3 analogs) have remained relatively unchanged over the past several decades. This article reviews emerging topical drugs and formulations currently under evaluation in clinical trials.

Expert opinion: The time is right for a revolution in our topical therapy armamentarium. It has lagged significantly behind the systemic biological evolution of new drug development. Our large psoriasis population with mild-to-moderate psoriasis certainly deserves potent but safe and innovative topical agents with a new mode of action as well as with long-lasting clinical efficacy.     

The efficacy of topical tazarotene monotherapy and combination therapies in psoriasis

Tazarotene (Tazorac^®, Allergan, Inc.) is the first topical retinoid approved for the treatment of plaque psoriasis. It has a similar onset of action compared to potent topical steroids and has the advantage of a longer remission. The common side effects associated with the drug include skin irritation (including pruritus), erythema and a burning sensation. To overcome some of these shortcomings, it has been used in combination with steroids, calcipotriene and phototherapy. Combination therapy not only results in a decrease in adverse side effects, but also enhanced efficacy. Clinical study data have shown that combination therapy is just as important as tazarotene monotherapy, if not more.     

Classical to current approach for treatment of psoriasis: a review

Psoriasis is a genetic predisposition with T-cell mediated autoimmune inflammatory skin disorder, characterized by cutaneous inflammation, increased epidermal proliferation, hyperkeratosis, angiogenesis, and abnormal keratinization that affects up to 2 - 3% of the population worldwide. Common therapies that are used for the treatment of psoriasis include topical, systemic, phototherapy, combination, herbal therapy and novel molecules. Topically used agents include Vit D, calcipotriol, corticosteroids, dithranol and retinoids etc. Systemically used agents include methotrexate and cyclosporine etc. Phototherapy includes UV-B, Psoralen plus ultraviolet therapy and excimer laser etc. These therapies have a number of potential problems, such as limited in efficacy, inconvenience, organ toxicity, carcinogenic and broadband immunosuppression. In natural treatment a variety of natural agents such as methanolic extracts of duzhong (Eucommia ulmoides Oliv.), yerba mate (Ilex paraguariensis,) linseed oil, fish oil, and Indigo naturalis etc., that modulates T cell and cytokine action at various steps along with the pathogenic sequence have been developed. But till now there is no more in vivo, dose and its efficacy data has been established. Current therapy includes biologicals, small molecules inhibitor and enzyme inhibitors etc, which serve as novel therapeutic options for psoriasis treatment. All these avoid the side effects of the prebiologically developed systemic agents including hepatotoxicity, nephrotoxicity, and bone marrow suppression. Currently, Denilukin diftitox, Efalizumab, Alefacept, Ustekinumab and Etanercept are approved by the FDA, and others molecules are at clinical stage. Patents issued by the US office are also included in current psoriasis treatment scenario. In the United States, biologicals are widely used for moderate-to-severe psoriasis. But because of the high cost of medication and their availability in injection form, it remains to be seen how widely these agents will be utilized worldwide. Still, developing countries prefer conventional drugs.     

阿维A联合窄谱中波紫外线对银屑病患者炎症细胞因子的影响

目的探讨阿维A联合窄谱中波紫外线（NB—UVB）治疗寻常性银屑病的疗效及其对炎症细胞因子白介素-6（IL-6）、肿瘤坏死因子（TNF-α）表达的影响。方法A组口服阿维A联合NB—UVB治疗,B组单纯口服阿维A,C组单纯用NB—UVB照射全身,14周后评价疗效并测定患者治疗前后血清中IL-6及TNF-α水平。结果A组总有效率明显高于其他组（P〈0．05）,血清中IL-6及TNF-α水平明显降低（P〈0．05）。结论阿维A联合NB—UVB治疗银屑病,可提高疗效、缩短疗程,且能降低患者血清中IL-6及TNF-α水平。     

Safety considerations with combination therapies for psoriasis

ABSTRACT

Introduction: Psoriasis is a chronic inflammatory skin disease that waxes and wanes, and long-term remission can be difficult to achieve regardless of disease severity. Currently, numerous treatment options are available for psoriasis including steroid and non-steroid topical agents, phototherapy, oral systemic agents, and biologics, with many more therapeutic agents under development.

Areas covered: This article will review various combination therapy strategies such as rotational therapy and sequential therapy and describe a variety of safe and effective combination therapies for the treatment of psoriasis. Two or more agents with different mechanisms of action and safety profiles can be used to achieve and/or maintain adequate disease control while minimizing the toxicity of treatments. Combination therapy can also be used when a single agent is not enough for treating recalcitrant disease. Choosing a combination regimen that maximizes safety and efficacy while considering patient usability and compliance can be a challenge.

Expert opinion: Given the various treatment options currently available for psoriasis and more agents under development, combination therapy will continue to be a valuable treatment strategy for any patient with psoriasis. It is crucial for clinicians to carefully consider the fine balance between safety and efficacy when combining various therapeutic agents.