Chen Xiaomei, Jiang Xia, Yang Ming, González Urbà, Lin Xiufang, Hua Xia, Xue Siliang, Zhang Min, Bennett Cathy
Department of Dermatology & Venereology, West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, Sichuan, China, 610041.
Cochrane Database Syst Rev. 2016 May 12;2016(5):CD004685. doi: 10.1002/14651858.CD004685.pub3.
Tinea capitis is a common contagious fungal infection of the scalp in children. Systemic therapy is required for treatment and to prevent spread. This is an update of the original Cochrane review.
To assess the effects of systemic antifungal drugs for tinea capitis in children.
We updated our searches of the following databases to November 2015: the Cochrane Skin Group Specialised Register, CENTRAL (2015, Issue 10), MEDLINE (from 1946), EMBASE (from 1974), LILACS (from 1982), and CINAHL (from 1981). We searched five trial registers and checked the reference lists of studies for references to relevant randomised controlled trials (RCTs). We obtained unpublished, ongoing trials and grey literature via correspondence with experts in the field and from pharmaceutical companies.
RCTs of systemic antifungal therapy in children with normal immunity under the age of 18 with tinea capitis confirmed by microscopy, growth of fungi (dermatophytes) in culture or both.
We used standard methodological procedures expected by Cochrane.
We included 25 studies (N = 4449); 4 studies (N = 2637) were new to this update.Terbinafine for four weeks and griseofulvin for eight weeks showed similar efficacy for the primary outcome of complete (i.e. clinical and mycological) cure in three studies involving 328 participants with Trichophyton species infections (84.2% versus 79.0%; risk ratio (RR) 1.06, 95% confidence interval (CI) 0.98 to 1.15; low quality evidence).Complete cure with itraconazole (two to six weeks) and griseofulvin (six weeks) was similar in two studies (83.6% versus 91.0%; RR 0.92, 95% CI 0.81 to 1.05; N = 134; very low quality evidence). In two studies, there was no difference between itraconazole and terbinafine for two to three weeks treatment (73.8% versus 78.8%; RR 0.93, 95% CI 0.72 to 1.19; N = 160; low quality evidence). In three studies, there was a similar proportion achieving complete cured with two to four weeks of fluconazole or six weeks of griseofulvin (41.4% versus 52.7%; RR 0.92, 95% CI 0.81 to 1.05; N = 615; moderate quality evidence). Current evidence for ketoconazole versus griseofulvin was limited. One study favoured griseofulvin (12 weeks) because ketoconazole (12 weeks) appeared less effective for complete cure (RR 0.76, 95% CI 0.62 to 0.94; low quality evidence). However, their effects appeared to be similar when the treatment lasted 26 weeks (RR 0.95, 95% CI 0.83 to 1.07; low quality evidence). Another study indicated that complete cure was similar for ketoconazole (12 weeks) and griseofulvin (12 weeks) (RR 0.89, 95% CI 0.57 to 1.39; low quality evidence). For one trial, there was no significant difference for complete cure between fluconazole (for two to three weeks) and terbinafine (for two to three weeks) (82.0% versus 94.0%; RR 0.87, 95% CI 0.75 to 1.01; N = 100; low quality evidence). For complete cure, we did not find a significant difference between fluconazole (for two to three weeks) and itraconazole (for two to three weeks) (82.0% versus 82.0%; RR 1.00, 95% CI 0.83 to 1.20; low quality evidence).This update provides new data: in children with Microsporum infections, a meta-analysis of two studies found that the complete cure was lower for terbinafine (6 weeks) than for griseofulvin (6-12 weeks) (34.7% versus 50.9%; RR 0.68, 95% CI 0.53 to 0.86; N = 334; moderate quality evidence). In the original review, there was no significant difference in complete cure between terbinafine (four weeks) and griseofulvin (eight weeks) in children with Microsporum infections in one small study (27.2% versus 60.0%; RR 0.45, 95% CI 0.15 to 1.35; N = 21; low quality evidence).One study provides new evidence that terbinafine and griseofulvin for six weeks show similar efficacy (49.5% versus 37.8%; RR 1.18, 95% CI 0.74 to 1.88; N = 1006; low quality evidence). However, in children infected with T. tonsurans, terbinafine was better than griseofulvin (52.1% versus 35.4%; RR 1.47, 95% CI 1.22 to 1.77; moderate quality evidence). For children infected with T. violaceum, these two regimens have similar effects (41.3% versus 45.1%; RR 0.91, 95% CI 0.68 to 1.24; low quality evidence). Additionally, three weeks of fluconazole was similar to six weeks of fluconazole in one study in 491 participants infected with T. tonsurans and M. canis (30.2% versus 34.1%; RR 0.88, 95% CI 0.68 to 1.14; low quality evidence).The frequency of adverse events attributed to the study drugs was similar for terbinafine and griseofulvin (9.2% versus 8.3%; RR 1.11, 95% CI 0.79 to 1.57; moderate quality evidence), and severe adverse events were rare (0.6% versus 0.6%; RR 0.97, 95% CI 0.24 to 3.88; moderate quality evidence). Adverse events for terbinafine, griseofulvin, itraconazole, ketoconazole, and fluconazole were all mild and reversible.All of the included studies were at either high or unclear risk of bias in at least one domain. Using GRADE to rate the overall quality of the evidence, lower quality evidence resulted in lower confidence in the estimate of effect.
AUTHORS' CONCLUSIONS: Newer treatments including terbinafine, itraconazole and fluconazole are at least similar to griseofulvin in children with tinea capitis caused by Trichophyton species. Limited evidence suggests that terbinafine, itraconazole and fluconazole have similar effects, whereas ketoconazole may be less effective than griseofulvin in children infected with Trichophyton. With some interventions the proportion achieving complete clinical cure was in excess of 90% (e.g. one study of terbinafine or griseofulvin for Trichophyton infections), but in many of the comparisons tested, the proportion cured was much lower.New evidence from this update suggests that terbinafine is more effective than griseofulvin in children with T. tonsurans infection.However, in children with Microsporum infections, new evidence suggests that the effect of griseofulvin is better than terbinafine. We did not find any evidence to support a difference in terms of adherence between four weeks of terbinafine versus eight weeks of griseofulvin. Not all treatments for tinea capitis are available in paediatric formulations but all have reasonable safety profiles.
头癣是儿童常见的头皮传染性真菌感染。治疗及预防传播均需采用全身治疗。这是对原Cochrane系统评价的更新。
评估全身用抗真菌药物治疗儿童头癣的效果。
我们将以下数据库的检索更新至2015年11月:Cochrane皮肤组专业注册库、Cochrane系统评价数据库(2015年第10期)、MEDLINE(1946年起)、EMBASE(1974年起)、LILACS(1982年起)及CINAHL(1981年起)。我们检索了五个试验注册库,并检查了纳入研究的参考文献列表以查找相关随机对照试验(RCT)的参考文献。我们通过与该领域专家通信及向制药公司索取,获取未发表的、正在进行的试验及灰色文献。
针对18岁以下免疫功能正常、经显微镜检查确诊为头癣、真菌(皮肤癣菌)培养阳性或二者均阳性的儿童进行全身用抗真菌治疗的RCT。
我们采用Cochrane期望的标准方法程序。
我们纳入了25项研究(N = 4449);本更新纳入4项新研究(N = 2637)。在3项涉及328例毛癣菌属感染患者的研究中(84.2% 对比79.0%;风险比(RR)1.06,95%置信区间(CI)0.98至1.15;低质量证据),特比萘芬治疗4周和灰黄霉素治疗8周对完全(即临床和真菌学)治愈这一主要结局显示出相似疗效。在2项研究中(83.6% 对比91.0%;RR 0.92,95% CI 0.81至1.05;N = 134;极低质量证据),伊曲康唑(2至6周)和灰黄霉素(6周)的完全治愈率相似。在2项研究中,伊曲康唑和特比萘芬治疗2至3周无差异(73.8% 对比78.8%;RR 0.93,95% CI 0.72至1.19;N = 160;低质量证据)。在3项研究中,氟康唑治疗2至4周或灰黄霉素治疗6周实现完全治愈的比例相似(41.4% 对比52.7%;RR 0.92,95% CI 0.81至1.05;N = 615;中等质量证据)。目前酮康唑与灰黄霉素对比的证据有限。一项研究支持灰黄霉素(12周),因为酮康唑(12周)在完全治愈方面似乎效果较差(RR 0.76,95% CI 0.62至0.94;低质量证据)。然而,当治疗持续26周时,二者效果似乎相似(RR 0.95,95% CI 0.83至1.07;低质量证据)。另一项研究表明酮康唑(12周)和灰黄霉素(12周)的完全治愈率相似(RR 0.89,95% CI 0.57至1.39;低质量证据)。在一项试验中,氟康唑(2至3周)和特比萘芬(2至3周)在完全治愈方面无显著差异(82.0% 对比94.0%;RR 0.87,95% CI 0.75至1.01;N = 100;低质量证据)。对于完全治愈,我们未发现氟康唑(2至3周)和伊曲康唑(2至3周)之间存在显著差异(82.0% 对比82.0%;RR 1.00,95% CI 0.83至1.20;低质量证据)。本更新提供了新数据:在小孢子菌感染儿童中,两项研究的荟萃分析发现,特比萘芬(6周)的完全治愈率低于灰黄霉素(6 - 12周)(34.7% 对比50.9%;RR 0.68,95% CI 0.53至0.86;N = 334;中等质量证据)。在原系统评价中,一项小型研究显示,小孢子菌感染儿童中,特比萘芬(4周)和灰黄霉素(8周)在完全治愈方面无显著差异(27.2% 对比60.0%;RR 0.45,95% CI 0.15至