Dupire Gwendy, Droitcourt Catherine, Hughes Carolyn, Le Cleach Laurence
Department of Immuno-Allergology, CHU Brugmann, Place A.Van Gehuchten 4, Brussels, Belgium, 1020.
Cochrane Database Syst Rev. 2019 Mar 5;3(3):CD011571. doi: 10.1002/14651858.CD011571.pub2.
Psoriasis is a chronic skin disease that affects approximately two per cent of the general population. Plaque psoriasis is the most common form: it usually appears as raised, red patches of inflamed skin, covered with silvery white scales. The patches often occur in a symmetrical pattern. Guttate psoriasis is a particular form of psoriasis with widespread, small erythematosquamous lesions. Streptococcal infection is suspected to be a triggering factor for the onset of guttate psoriasis, and flare-up of chronic plaque psoriasis. The previous Cochrane Review on this topic was published in 2000; it required an update because antistreptococcal treatment continues to be used to treat psoriasis, especially for the acute form of guttate psoriasis.
To assess the effects of antistreptococcal interventions for guttate and chronic plaque psoriasis.
We searched Cochrane Skin Specialised Register, Cochrane Register of Studies Online, CENTRAL, MEDLINE, Embase, LILACS, and five trials registers (January 2019). We checked the reference lists of included and excluded studies and searched conference proceedings from the American Academy of Dermatology, Society for Investigative Dermatology, and European Academy of Dermatology and Venereology.
We considered randomised controlled trials (RCTs) assessing antistreptococcal interventions (tonsillectomy or systemic antibiotic treatment) in people with clinically diagnosed acute guttate and chronic plaque psoriasis compared with placebo, no intervention, or each other.
We used standard methodological procedures expected by Cochrane. Primary outcome measures were: 1) time-to-resolution; achieving clear or almost clear skin (Physician Global Assessment (PGA) 0 or 1 or Psoriasis Area and Severity Index (PASI) 90 or 100); 2) proportion of participants with adverse effects and severe adverse effects. Secondary outcomes were: 1) proportion of participants achieving clear or almost clear skin; 2) proportion of participants achieving PASI 75 or PGA 1 to 2; 3) risk of having at least one relapse at long-term follow-up. Short-term assessment was defined as within eight weeks of the start of treatment; long-term was at least one year after the start of treatment.
We included five trials (162 randomised participants); three were conducted in a hospital dermatology department. One study declared funding by a pharmaceutical company. Participants' ages ranged from 12 to 77 years; only two participants were younger than 15 years. Mean PASI score at baseline varied from 5.7 (i.e. mild) to 23 (i.e. severe) in four studies. Twenty-three of 162 participants had streptococcus-positive throat swab culture. We did not perform a meta-analysis due to heterogeneity of participants' characteristics and interventions.None of the trials measured our efficacy primary outcome, time-to-resolution, or the secondary outcome, risk of having at least one relapse at long-term follow-up.We rated the quality of the results as very low-quality evidence, due to high risk of bias (absence of blinding of participants and caregivers, and high risk of outcome reporting bias) and imprecision (single study data with a low number of events). Hence, we are very uncertain about the results presented.Guttate psoriasisOne three-armed trial (N = 43) assessed penicillin (50,000 international units (IU)/kg/day in three doses) versus erythromycin (250 mg four times per day) versus no treatment (treatment for 14 days, with six-week follow-up from start of treatment). Adverse events and the proportion of participants achieving clear or almost clear skin were not measured.One trial (N = 20) assessed penicillin (1.6 MU (million units) intramuscularly once a day) versus no treatment (six weeks of treatment, with eight-week follow-up from start of treatment). At six-week (short-term) follow-up, no adverse events were observed in either group, and there was no statistically significant difference between the two groups in the proportion of participants with clear or almost clear skin (risk ratio (RR) 2.00, 95% confidence interval (CI) 0.68 to 5.85).One trial (N = 20) assessed rifampicin (300 mg twice daily) versus placebo (14-day treatment duration; six-week follow-up from start of treatment); none of the review outcomes were measured.These trials did not measure the proportion of participants achieving PASI 75 or PGA 1 to 2.Chronic plaque psoriasisOne trial (N = 50) assessed long-term azithromycin treatment (500 mg daily dose) versus vitamin C. Adverse events were reported in the azithromycin group (10 out of 30 had nausea and mild abdominal upset), but not in the vitamin C group. The proportion of participants who achieved clear or almost clear skin was not measured. In the azithromycin group, 18/30 versus 0/20 participants in the vitamin C group reached PASI 75 at the end of 48 weeks of treatment (RR 25.06, 95% CI 1.60 to 393.59).One trial (N = 29) assessed tonsillectomy versus no treatment, with 24-month follow-up after surgery. One participant in the tonsillectomy group had minor bleeding. At eight-week follow-up, 1/15 in the tonsillectomy group, and 0/14 in the no treatment group achieved PASI 90; and 3/15 participants in the tonsillectomy group, and 0/14 in the no treatment group achieved PASI 75 (RR 6.56, 95% CI 0.37 to 116.7).
AUTHORS' CONCLUSIONS: We found only five trials (N = 162), which assessed the effects of five comparisons (systemic antibiotic treatment (penicillin, azithromycin) or tonsillectomy). Two comparisons (erythromycin compared to no treatment, and rifampicin compared to placebo) did not measure any of the outcomes of interest. There was very low-quality evidence for the outcomes that were measured, Therefore, we are uncertain of both the efficacy and safety of antistreptococcal interventions for guttate and chronic plaque psoriasis.The included trials were at unclear or high risk of bias and involved only a small number of unrepresentative participants, with limited measurement of our outcomes of interest. The studies did not allow investigation into the influence of Streptococcal infection, and a key intervention (amoxicillin) was not assessed.Further trials assessing the efficacy and tolerance of penicillin V or amoxicillin are needed in children and young adults with guttate psoriasis.
银屑病是一种慢性皮肤病,约影响2%的普通人群。斑块状银屑病是最常见的类型:通常表现为凸起的、红色的炎症性皮肤斑块,覆盖有银白色鳞屑。这些斑块常呈对称分布。点滴状银屑病是银屑病的一种特殊类型,有广泛的小的红斑鳞屑性损害。链球菌感染被怀疑是点滴状银屑病发病以及慢性斑块状银屑病发作的触发因素。之前关于该主题的Cochrane系统评价发表于2000年;由于抗链球菌治疗仍被用于治疗银屑病,尤其是急性点滴状银屑病,因此需要更新。
评估抗链球菌干预措施对点滴状和慢性斑块状银屑病的疗效。
我们检索了Cochrane皮肤专科注册库、Cochrane在线研究注册库、CENTRAL、MEDLINE、Embase、LILACS以及五个试验注册库(2019年1月)。我们检查了纳入和排除研究的参考文献列表,并检索了美国皮肤病学会、皮肤病研究学会以及欧洲皮肤病与性病学会的会议论文集。
我们纳入了评估抗链球菌干预措施(扁桃体切除术或全身抗生素治疗)对临床诊断为急性点滴状和慢性斑块状银屑病患者疗效的随机对照试验(RCT),并与安慰剂、不干预或相互之间进行比较。
我们采用了Cochrane预期的标准方法程序。主要结局指标为:1)症状消退时间;皮肤达到清除或几乎清除(医师整体评估(PGA)为0或1或银屑病面积和严重程度指数(PASI)为90或100);2)出现不良反应和严重不良反应的参与者比例。次要结局为:1)皮肤达到清除或几乎清除的参与者比例;2)达到PASI 75或PGA为1至2的参与者比例;3)长期随访时至少有一次复发的风险。短期评估定义为治疗开始后八周内;长期评估为治疗开始后至少一年。
我们纳入了五项试验(162名随机参与者);三项在医院皮肤科进行。一项研究声明由一家制药公司资助。参与者年龄在12至77岁之间;只有两名参与者年龄小于15岁。四项研究中基线时的平均PASI评分从5.7(即轻度)到23(即重度)不等。162名参与者中有23名咽喉拭子培养为链球菌阳性。由于参与者特征和干预措施的异质性,我们未进行荟萃分析。没有一项试验测量我们的疗效主要结局指标症状消退时间,或次要结局指标长期随访时至少有一次复发的风险。由于存在高偏倚风险(参与者和护理人员未设盲,以及结局报告偏倚风险高)和不精确性(单个研究数据且事件数量少),我们将结果质量评为极低质量证据。因此,我们对所呈现的结果非常不确定。
点滴状银屑病
一项三臂试验(N = 43)评估了青霉素(50,000国际单位(IU)/kg/天,分三次给药)与红霉素(250 mg,每日四次)与不治疗(治疗14天,从治疗开始随访六周)的效果。未测量不良事件以及皮肤达到清除或几乎清除的参与者比例。
一项试验(N = 20)评估了青霉素(160万单位(MU),每日一次肌肉注射)与不治疗(治疗六周,从治疗开始随访八周)的效果。在六周(短期)随访时,两组均未观察到不良事件,两组中皮肤达到清除或几乎清除的参与者比例无统计学显著差异(风险比(RR)2.00,95%置信区间(CI)0.68至5.85)。
一项试验(N = 20)评估了利福平(300 mg,每日两次)与安慰剂(治疗持续14天;从治疗开始随访六周)的效果;未测量本综述的任何结局指标。这些试验未测量达到PASI 75或PGA为1至2的参与者比例。
慢性斑块状银屑病
一项试验(N = 50)评估了长期阿奇霉素治疗(每日剂量500 mg)与维生素C的效果。阿奇霉素组报告了不良事件(30名中有10名出现恶心和轻度腹部不适),而维生素C组未报告。未测量皮肤达到清除或几乎清除的参与者比例。在阿奇霉素组中,治疗48周结束时,30名中有18名达到PASI 75,而维生素C组20名中无一人达到(RR 25.06,95% CI 1.60至393.59)。
一项试验(N = 29)评估了扁桃体切除术与不治疗的效果,术后随访24个月。扁桃体切除组有一名参与者出现轻微出血。在八周随访时,扁桃体切除组15名中有1名达到PASI 90,不治疗组14名中无一人达到;扁桃体切除组中3/15参与者达到PASI 75,不治疗组14名中无一人达到(RR 6.56,95% CI 0.37至116.7)。
我们仅发现五项试验(N = 162),评估了五种比较(全身抗生素治疗(青霉素、阿奇霉素)或扁桃体切除术)的效果。两项比较(红霉素与不治疗,利福平与安慰剂)未测量任何感兴趣的结局指标。对于所测量的结局指标,证据质量极低。因此我们不确定抗链球菌干预措施对点滴状和慢性斑块状银屑病的疗效和安全性。所纳入的试验存在不明确或高偏倚风险,仅涉及少量缺乏代表性的参与者,对我们感兴趣的结局指标测量有限。这些研究无法探究链球菌感染的影响,且未评估一项关键干预措施(阿莫西林)。需要进一步开展试验评估青霉素V或阿莫西林对点滴状银屑病儿童和青年患者的疗效和耐受性。