甲银屑病治疗的系统性评价

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银屑病是一种常见皮肤疾病,常累及指甲和甲周皮肤组织。甲银屑病的发病率随着银屑病的病程增加而增加。虽然甲银屑病治疗困难,但是现在已有多种治疗方法问世。本文就甲银屑病的治疗方法的有效性和安全性作一系统性评价。最后发现英夫利昔(Infliximab)、高利单抗(golimumab)、表面放射治疗(superficial radiotherapy,SRT)、跨界射线(grenz rays)以及电子束(electron beam )可以明显的改善甲银屑病的病情。当然这些临床研究的质量相对稍差,但是本文对于临床上治疗甲银屑病还是有所裨益。

虽然系统性治疗对于甲银屑病有较明显的治疗效果,但是其副作用也很严重。因此系统性治疗并不是甲银屑病的优先选择,除非患者周身银屑病或者银屑病关节炎,或甲银屑病很严重,对于其它治疗效果很不理想时才考虑应用系统性治疗方法。甲银屑病的局部治疗效果不定或效果较差,但是这并不能否定局部治疗的治疗效果。

甲银屑病概述

银屑病是一种皮肤科常见的慢性皮肤疾病,据欧洲的研究发现其患病率在2%-3%之间。现在多认为银屑病是由CD4+T淋巴细胞与角质形成细胞及其它皮肤细胞相互作用而导致的自身免疫性皮肤和关节疾病。银屑病中重度时可以累及甲。有些人可以单纯有甲银屑病或者甲银屑病是主要的临床表现。银屑病患者中,40%的有甲银屑病改变,而Salomon等人研究发现银屑病的甲改变则更高达78%。甲银屑无性别差异性。银屑病关节炎时甲银屑病发病率更高。随着银屑病病程的增加,甲银屑病的发病率也随之增加。

甲银屑病的病因和发病机制现在尚未完全清楚。现在发现位于6号染色体上的MHC-Ⅰ附件的HLA-Cw6基因是主要的易感基因。HLA-Cw*0602阳性者点滴型银屑病发病率较高,Cw*0602阴性者银屑病更易累及指甲。另外,外界轻度损伤也在甲银屑的发病中重要的作用。指甲相对于趾甲更易发病。甲板和甲床都可受累。临床上观察到如果甲发生不规则性的凹点,甲床发生鲑肉色斑(橙红色或浅橙色,salmon),甲板与甲床伴有甲沟炎可以有助于诊断甲银屑病。另外,还可能会观察到甲床出血,甲下角化过度,甲板增厚,甲碎屑等表现。但是最常见的是甲凹点和甲下角化过度。甲凹点是由于远端甲床微小的角化不全点而引起的。鲑肉色斑或者「油点(oil spots)」反应白细胞外渗到甲析下。毛细血管脆性增加会导致甲床出血。甲下角化过度和远端甲分离是远端甲床角化不全的结果。

甲银屑病主要与甲真菌病、扁平苔藓、角化不全性脓疱(parakeratosis pustulosa)、连续性肢端皮炎(acrodermatitis continua of Hallopeau)以及湿疹相鉴别。由于甲银屑病患者的甲真菌病的患病率较高,因此甲银屑病患者排除甲真菌感染就很重要。

现在认为银屑病的严重程度与患者的生活质量成反比。De Jong等人发现甲银屑病同样影响患者的生活质量。一半甲银屑病的患者在工作、生活中受到影响。超过90%的患者因美容方面的原因有社交障碍。超过50%的甲银屑病患者因甲改变而感到疼痛。

甲银屑病治疗概述

虽然甲银屑病治疗困难,但是治疗也可能有效果。如果甲板没有永久性的损伤,治疗一般效果较好。但是治疗起效较慢,有时治疗效果并不理想,且易反复。治疗包括局部外用或者注射糖皮质激素,局部外用卡铂三醇、环孢素、5-氟脲嘧啶和他扎罗汀(tazarotene)。Forleo等人一篇综述发现局部外用卡铂三醇是较好的治疗方法,尤其是甲下角化过度和甲分享的患者。

系统性治疗多用口服,如口服甲氨喋呤和环孢素,可能效果尚佳,但是迄今仅推荐用于泛发性皮肤或关节银屑病患者,因为其副作用太大。其它的疗法还有口服维甲酸类药物,光疗或者放射疗法,跨界射线疗法,UVB和光化学疗法。

生物治疗相对是一种较新治疗银屑病的方法,现在常规用于治疗中重度斑块型银屑病和银屑病型关节性患者对于常规的系统性治疗疗效不佳或有禁忌者。基于其治疗银屑病的有效性和安全性,现研究发现对甲银屑病也有效果。现在临床应用的有TNF-α抑制剂:依那西普(etanercept)、英夫利昔(Infliximab)以及阿达木单抗(adalimumab);T淋巴细胞阻滞剂阿法赛特(etanercept)。

甲银屑病严重程度评价

现有多种方法来测量甲银屑病的严重程度。除了临床描述甲银屑病的表现和病情进展情况,还有几种不同的评分系统,但结果并不一致。

1994年,Jones等人发明了一种评分系统银屑病甲严重程度评分(Psoriasis Nail Severity Score ,PNSS)。本评分利用双手指甲的凹点、甲分离、角化过度以及甲变形程度评分。每个指甲的每个表现表现为1分,最高40分。之后Williamson又利用该评分方法用于趾甲的评分,因此最大评分达到80分。

另外一个评分方法叫甲域严重(Nail Area Severity , NAS)评分,包含了甲凹点面积、甲凹点数量、甲下角质的数量、甲分享和油点等参数。

Rich等人发明了一个更复杂的评分方法,叫甲银屑病严重指数(Nail
Psoriasis Severity Index, NAPSI)。本评分基于每个甲每个区域的总分,并甲床和甲板分别计分。甲板银屑病包括以下甲表现和任何一个都要计娄:凹点、灰甲、甲半月的红点、油点、甲床出血和甲床角化过度。

由于本评分的复杂性,Parrish等人认为NAPSI评分方法敏感性并不佳,因此,他们提出了一个修正方法,每个象限的分数0-3之间。

Baran等人建议甲银屑病的症状计分为0-3,但是甲床出血常由外伤引起,因此不应当算入席计分之中,甲脱落也是如此。

甲银屑病系统性评价结果

有2个生物制剂的研究和3个放射治疗研究表明甲银屑病的治疗效果和计分有明显的改善。

5mg/kg的英夫利昔相比安安慰剂甲银屑病症状和评分都有明显的改善,且中长期治疗效果更佳。高利单抗50mg和100mg中期治疗(12-24周)能分别改善评分33%和54%,而安慰剂无明显效果。

放射疗法中,只有表面放射治疗有较好的效果,短期治疗后可以改善评分20%。

有7个研究使用了1%的5-氟脲嘧啶乳膏、2.5mg/kg环孢素,0.1%的他扎罗汀软膏、50ug/g的卡铂三醇、0.005%的卡铂三醇、甲氨喋呤和优特克单抗(ustekinumab)治疗甲银屑病,但是与分别与belanyx乳膏、依曲替酯、丙酸氯倍他索、倍他米松水杨酸复合软膏、倍他米松软膏、环孢素和安慰剂相比,发现就症状和评分改善都没有明显的治疗效果。

有人研究发现70%的环孢素乳剂、0.1%的他扎罗汀软膏、0.05%的氯倍他索短期治疗与治疗前可以改善75%的病情。

局部外用药物多用于治疗皮肤疾病,因此治疗甲银屑病并非最佳选择。因其很难渗透甲板。为了提高局部药物的渗透性,有些外用疗法使用了增效剂或者封包治疗,但是结果并不一定。

Abstract

BACKGROUND:

Psoriasis is a common skin disease that can also involve the nails. All parts of the nail and surrounding structures can become affected. The incidence of nail involvement increases with duration of psoriasis. Although it is difficult to treat psoriatic nails, the condition may respond to therapy.

OBJECTIVES:

To assess evidence for the efficacy and safety of the treatments for nail psoriasis.

SEARCH METHODS:

We searched the following databases up to March 2012: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 1946), EMBASE (from 1974), and LILACS (from 1982). We also searched trials databases and checked the reference lists of retrieved studies for further references to relevant randomised controlled trials (RCTs).

SELECTION CRITERIA:

All RCTs of any design concerning interventions for nail psoriasis.

DATA COLLECTION AND ANALYSIS:

Two authors independently assessed trial risk of bias and extracted the data. We collected adverse effects from the included studies.

MAIN RESULTS:

We included 18 studies involving 1266 participants. We were not able to pool due to the heterogeneity of many of the studies.Our primary outcomes were 'Global improvement of nail psoriasis as rated by a clinician', 'Improvement of nail psoriasis scores (NAS, NAPSI)', 'Improvement of nail psoriasis in the participant's opinion'. Our secondary outcomes were 'Adverse effects (and serious adverse effects)'; 'Effects on quality of life'; and 'Improvement in nail features, pain score, nail thickness, thickness of subungual hyperkeratosis, number of affected nails, and nail growth'. We assessed short-term (3 to 6 months), medium-term (6 to 12 months), and long-term (> 12 months) treatments separately if possible.Two systemic biologic studies and three radiotherapy studies reported significant results for our first two primary outcomes. Infliximab 5 mg/kg showed 57.2% nail score improvement versus -4.1% for placebo (P < 0.001); golimumab 50 mg and 100 mg showed 33% and 54% improvement, respectively, versus 0% for placebo (P < 0.001), both after medium-term treatment. Infliximab and golimumab also showed significant results after short-term treatment. From the 3 radiotherapy studies, only the superficial radiotherapy (SRT) study showed 20% versus 0% nail score improvement (P = 0.03) after short-term treatment.Studies with ciclosporin, methotrexate, and ustekinumab were not significantly better than their respective comparators: etretinate, ciclosporin, and placebo. Nor were studies with topical interventions (5-fluorouracil 1% in Belanyx® lotion, tazarotene 0.1% cream, calcipotriol 50 ug/g, calcipotriol 0.005%) better than their respective comparators: Belanyx® lotion, clobetasol propionate, betamethasone dipropionate with salicylic acid, or betamethasone dipropionate.Of our secondary outcomes, not all included studies reported adverse events; those that did only reported mild adverse effects, and there were more in studies with systemic interventions. Only one study reported the effect on quality of life, and two studies reported nail improvement only per feature.

AUTHORS' CONCLUSIONS:

Infliximab, golimumab, SRT, grenz rays, and electron beam caused significant nail improvement compared to the comparative treatment. Although the quality of trials was generally poor, this review may have some implications for clinical practice.Although powerful systemic treatments have been shown to be beneficial, they may have serious adverse effects. So they are not a realistic option for people troubled with nail psoriasis, unless the patient is prescribed these systemic treatments because of cutaneous psoriasis or psoriatic arthritis or the nail psoriasis is severe, refractory to other treatments, or has a major impact on the person's quality of life. Because of their design and timescale, RCTs generally do not pick up serious side-effects. This review reported only mild adverse effects, recorded mainly for systemic treatments. Radiotherapy for psoriasis is not used in common practice. The evidence for the use of topical treatments is inconclusive and of poor quality; however, this does not imply that they do not work.Future trials need to be rigorous in design, with adequate reporting. Trials should correctly describe the participants' characteristics and diagnostic features, use standard validated nail scores and participant-reported outcomes, be long enough to report efficacy and safety, and include details of effects on nail features.

本文摘译于:de Vries ACQ et al.Interventions for nail psoriasis. Cochrane Database Syst Rev.2013 Jan 31;1

翻译过程中因本人水平的限,难免会有错误或不当的地方,请指正。

附上全文下载地址:

Summary (64K): http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007633.pub2/pdf/abstract
Standard (1692K): http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007633.pub2/pdf/standard
Full (1769K): http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007633.pub2/pdf

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