JAK抑制剂在银屑病治疗中的研究进展

Janus激酶/信号转导与转录激活子(The Janus kinase/signal transducer and activator of tran-i-ons,JAK/STAT)信号通路作为常见的信号通路之一,在银屑病的发病机制中起到重要的调控作用,因此抑制JAK/STAT通路成为治疗银屑病的有效方法.本文通过对J...     

Topical methotrexate therapy for psoriasis

In vitro percutaneous penetration of methotrexate is enhanced with 1-dodecylazacycloheptan-2-one (laurocapram [Azone]). Laurocapram-containing methotrexate formulations provide effective local inhibition of epidermal DNA synthesis in the in vivo hairless mouse and minipig models, providing the biochemical rationale for topical use in the treatment of psoriasis. Topical methotrexate (0.1%, 0.5%, and 1%) in a laurocapram-containing formulation was tested in a two-center double-blind pilot clinical study of 42 patients with plaque psoriasis. Drugs were applied twice a day for six weeks, and lesions were scored weekly for erythema, scale, and elevation. An overall improvement of 50% or more in the combined scores for erythema, scale, and elevation was obtained with 0.1% methotrexate (64% of patients), 0.5% methotrexate (59%), and 1% methotrexate (56%) vs the vehicle alone (25%). These preliminary findings suggest that methotrexate preparations that provide adequate percutaneous absorption may have a beneficial effect in the treatment of psoriasis.     

Topical tacrolimus: an effective therapy for facial psoriasis

We evaluated twenty-one cases of facial psoriasis lesions treated with topical tacrolimus ointment. Patients were 15 males and 6 females with a mean age of 51.1 years old. Mean duration of the disease was 10.1 years. 0.1% tacrolimus ointment was applied twice a day for 4 weeks without occlusion. A complete or good response was obtained in 10 (47.6%) and 9 (42.9%) patients, respectively. The mean score of erythema decreased from 1.76 to 0.62, that of infiltration decreased from 1.33 to 0.43, and that of desquamation decreased from 0.95 to 0.24, respectively. These data demonstrate that topical tacrolimus is effective for facial lesions of psoriasis without occlusion. We conclude that topical tacrolimus is an effective treatment for facial psoriasis.     

Topical salicylic acid interferes with UVB therapy for psoriasis.

Salicylic acid has been widely used in the topical treatment of psoriasis. Chemically it is closely related to paraaminobenzoic acid. Following in vitro studies indicating that salicylic acid might exhibit relevant UVB absorption, we found that salicylic acid had a clinically pronounced filter effect when applied prior to UVB exposure. The duration of photoprotection after application was more than 12 h, sometimes exceeding 24 h. In a prospective, randomized, double-blind, left-right comparison study in patients with psoriasis between emollients with and without salicylic acid, salicylic acid was shown to decrease the clearing rate significantly.     

Topical 6-aminonicotinamide plus oral niacinamide therapy for psoriasis.

Ninety-nine patients with psoriasis were treated topically with 6-aminonicotinamide (6-AN) in four years. In a double-blind study, 1% 6-AN gel was superior to 0.1% triamcinolone acetonide in 29 comparisons, equal in three, and inferior in one when applied without occlusion for four weeks. In an open study, 1% 6-AN was better than four "potent" steroid creams in 34 comparisons, equal in four, and inferior in one. Substantial improvement or complete clearing of plaques occurred in 85 of 99 patients. Tachyphylaxis occurred in ten, but was not permanent. Mucocutaneous toxicity appeared in 25% but was usually easily controlled. Tinnitus occurred in four, but none had deterioration of audiogram readings. The combination of topical 6-AN and oral niacinamide therapy gives promise of an effective and safe treatment for psoriasis. One of three patients with pityriasis rubra pilaris improved considerably with 6-AN.     

Treatment of psoriasis. Part 1. Topical therapy and phototherapy

New developments in the topical therapy and phototherapy of psoriasis have greatly improved our ability to safely and effectively treat this debilitating disease. Topical corticosteroids remain the most commonly prescribed agents for psoriasis, but they are frequently prescribed with other agents. Investigations of corticosteroids claiming an improved benefit/risk ratio have yielded promising results, but more work is needed. Use of anthralin and tar has declined with the availability of the noncorticosteroids calcipotriene and tazarotene. Other experimental topical therapies are in various stages of development. Broadband ultraviolet B (UVB) remains the most commonly used phototherapy light source, but many patients are being treated with a new form of ultraviolet light, narrowband UVB. Although PUVA remains one of the most effective psoriasis treatments, its use is declining because of its association with cutaneous malignancies. New radiation sources such as lasers have been added to our armamentarium of available therapies and even newer light source-based treatments are being examined. LEARNING OBJECTIVE: At the conclusion of this learning activity, participants should be familiar with the varying topical treatments for psoriasis as well as the different modalities of phototherapy. Participants should also have a better understanding of side effects associated with each treatment, which should help in determining options for therapy.     

Topical sodium metabisulfite for the treatment of calcinosis cutis: a promising new therapy

Calcinosis cutis is a chronic calcium‐mediated disease that causes significant morbidity. Multiple treatments have been tried, with varying results; indeed, to date, no standard treatment has been generally accepted. Sodium metabisulfite is an inorganic compound that, when it reacts with oxygen, becomes sodium sulfate, a metabolite of sodium thiosulfate that has a similar ability to inhibit calcium oxalate agglomeration. Four women diagnosed with calcinosis cutis, secondary to dermatomyositis, systemic sclerosis and radiodermatitis after breast cancer, were evaluated for their response to topical 25% sodium metabisulfite. In all patients a decrease in lesion size, erythema and pain from injuries was shown, with complete resolution of the associated ulcers. One patient had a complete response. None experienced adverse effects. Topical sodium metabisulfite is a promising emerging therapy that should be considered as a valid alternative treatment in calcinosis cutis. Randomized prospective studies are required to evaluate its true efficacy.     

Topical therapy for the management of childhood psoriasis: part I

Psoriasis represents a potentially life-altering disease that can profoundly impact physical, emotional and social functioning, and overall quality of life. The majority of cases are mild and managed adequately with topical medications. A minor subset of children present with severe, rapidly evolving disease that requires systemic therapy. The choice of treatment in children, as in adults, is determined by disease acuity, morphology, distribution, severity and the presence of comorbidities such as psoriatic arthropathy. Practical considerations such as ease of use, patient acceptability, accessibility, risk to benefit ratio, cost and individual perceptions of disease and quality of life are factored into treatment decisions. Part I of this 2-part series will focus on topical agents, their varying degrees of effectiveness, potential side-effects and applications in clinical practice.     

Topical calcipotriol therapy in nail psoriasis: a study of 24 cases

There are few reports regarding the treatment of nail psoriasis with topical calcipotriol. We undertook a case series study to evaluate the efficacy and safety of calcipotriol ointment (50 microg/g) in the treatment of nail psoriasis in 24 patients. This study involved 19 women and 5 men with nail psoriasis referred to Dermatology clinics of Razi hospital. The duration of trial was from October 2002 to September 2004. Informed consent was obtained from all patients before entering into the study. The patients applied calcipotriol ointment to the affected nails twice daily without occlusion for 3 months. Patients were seen by two academic dermatologists initially, after 2 weeks, and then at monthly intervals. The efficacy and safety were clinically assessed and any side effect was recorded. Patients who showed 50 percent or greater reduction in the baseline subungual thickness in at least one nail were considered to be responders and were offered continuation of therapy for an additional 2 months. After discontinuation of therapy, followup visits were performed at 1 and 2 months. After 3 months of therapy, fourteen patients showed significant clinical improvement, two of them were completely free from nail lesions after 5 months. Calcipotriol was particularly effective in subungual hyperkeratosis, onycholysis, and discoloration. In four patients fingertip tenderness and in one case the pain of involved distal phalanx were significantly reduced. No clinical response was observed in four patients. Only two cases showed adverse reactions. Topical Calcipotriol is an effective treatment for nail psoriasis and can be considered to be a safe topical treatment in chronic cases; its high tolerability allows prolonged usage without severe side effects.     

外用磷酸二酯酶4抑制剂软膏治疗斑秃一例附文献复习

斑秃既往治疗包括局部外用药物治疗(糖皮质激素、米诺地尔等)、系统药物治疗(口服糖皮质激素、甲氨蝶呤、环孢素等)以及物理疗法(如光化学疗法PUVA、308 nm准分子激光等)。磷酸二酯酶4(PDE-4)抑制剂通过增加细胞内环磷酸腺苷(cAMP)水平,进而调节一系列细胞因子发挥免疫调节作用。国外曾有口服PDE-4抑制剂治疗斑秃的动物模型研究和病例报道,但存在较多的不良反应。克立硼罗软膏是近年来新研发的外用磷酸二酯酶4(PDE-4)抑制剂,曾报道用于特应性皮炎、银屑病和白癜风等皮肤病的治疗,其治疗斑秃的二期临床试验正在开展,目前国内外尚无治疗斑秃的正式报道。我们报道一例外用磷酸二酯酶4抑制剂治疗斑秃的患者,取得良好治疗效果,未见明显不良反应。     

Topical tazarotene therapy for psoriasis,acne vulgaris,and photoaging

Psoriasis, acne vulgaris and photoaging are common conditions. Tazarotene is a pro-drug of tazarotenic acid, a receptor-selective retinoid, which has shown efficacy in the treatment of these disorders. In the treatment of acne vulgaris, it has greater comedolytic activity than the currently available topical retinoids. In psoriasis, tazarotene normalizes keratinocyte differentiation, reverses keratinocyte hyperproliferation and has better anti-inflammatory effects than any of the currently available topical retinoids. It is most commonly used as combination therapy with a topical corticosteroid or phototherapy in psoriasis, or with an antibiotic in acne.     

Topical corticosteroid therapy in psoriasis vulgaris: update and new strategies

This is an update of a previous report on the use of topical steroids in the management of psoriasis vulgaris. The current focus is on new combination therapies that enhance the efficacy of corticosteroids while diminishing their potential side effects.     

Systemic methotrexate therapy for psoriasis: past,present and future

Methotrexate (MTX) has remained the backbone of the treatment for moderate to severe psoriasis ever since its first use nearly half a century ago. Over the years, its high efficacy, low cost, relative ease of administration and usefulness in concomitant psoriatic arthritis have contributed in making MTX the drug of choice in managing severe psoriasis. Although the majority of patients achieve remission of disease activity with MTX, a significant proportion may experience mild and transient adverse effects. From time to time, various guidelines on the use of MTX have correctly and adequately stressed the need for strict monitoring of haematological and hepatic adverse events. Over the years, the safe total cumulative dose of MTX (above which the risk of developing liver fibrosis is significantly increased) has been raised. Simultaneously, there has been an increased emphasis on developing noninvasive tests such as scanning and serum biomarker assays for detecting early liver fibrosis, in order to obviate the need for liver biopsy. However, the recent discovery and subsequent proliferating use of biological response modifiers has gradually shifted the focus away from MTX, despite it still being the most commonly prescribed drug for psoriasis worldwide. The aim of this review is to present a detailed account of MTX therapy and its use in psoriasis, along with its current relevance in disease management in the evolving era of biological drugs.     

Topical 5-aminolaevulinic acid photodynamic therapy for intractable palmoplantar psoriasis

Photodynamic therapy (PDT) has been reported to be useful in treating non-melanoma skin cancers and a variety of benign skin conditions including psoriasis. However, only two reports of palmoplantar pustular psoriasis (PPP) treated with PDT have been reported. We treated three intractable cases of PPP with PDT, using 20% 5-aminolaevulinic acid and a 630+/-50 nm light-emitting diode device. The power density was 30 mW/cm2 and the fluence was 15 J/cm2. After treatment, all cases showed mild to marked improvement. Topical PDT may be an alternative therapy in the treatment of PPP, but further study is necessary to confirm the effectiveness of topical PDT in PPP.     

Topical treatment of psoriasis: a systematic update

Classical topical treatment regimens in psoriasis including dithranol and corticosteroids are widely used and have been supplemented in recent years by topical vitamin D preparations, by vitamin D analogues and topical retinoids.The combination of these preparations with each other, with UV light or with systemic drugs often lead to improved effectiveness and tolerability when compared with the respective monotherapy. In private offices, the combination of calcipotriol with various corticosteroids is very commonly prescribed for patients with mild to moderate psoriasis. This combination can be sequentially applied twice daily or--in a newly introduced fixed preparation--once daily. In severe psoriasis requiring systemic treatment a concomitant effective topical treatment regimen can greatly improve the overall longtime management in affected patients.     

Topical rapamycin for angiofibromas in paediatric patients with tuberous sclerosis: Follow up of a pilot study and promising future directions

One of the most visible and potentially disfiguring cutaneous manifestations of tuberous sclerosis complex is the development of multiple facial angiofibromas, present in over 80% of patients. Topical rapamycin has been shown in many reports to be a safe and effective treatment for facial angiofibromas. In February 2012 we reported the results of a pilot study of four patients undertaken at a paediatric tertiary hospital in Australia. Since then, we have continued to refine the optimal formulation and concentration of topical rapamycin and expanded our selection of patients. We present an update on our current cohort of treated patients, discuss the optimal formulation of topical rapamycin and include a literature review on all published cases to date. Although topical rapamycin is not a curative treatment, we have demonstrated that its early institution significantly reduces both the vascularity and palpability of angiofibromas and prevents their progression with age. It is well tolerated and now a cost effective option.     

Topical management of psoriasis - corticosteroids and sparing corticosteroid therapy

Psoriasis is a complex disease that requires safe, long-term treatment. Topical steroid therapy, topical non-steroid therapy only, and a combination of various topical therapies in the treatment of mild to moderate forms of psoriasis are presented. Topical therapy includes corticosteroids, vitamin D3 analogs, retinoids, tars, anthralin, keratolytics, and topical immunomodulators. While most medications are approved for use as a single agent in the treatment of psoriasis, some of these drugs are most effective when used in combination with topical corticosteroids. Topical therapy is generally administered for mild and localized forms of psoriasis, whereas phototherapy and systemic therapy are reserved for extensive lesions and more severe forms of the disease. Individual approach is absolutely necessary in each patient with psoriasis.