组胺球蛋白在过敏性疾病中的疗效：一项对过敏性鼻炎具有启示意义的系统评价与Meta分析

文献信息

中文摘要

组胺球蛋白（组胺/免疫球蛋白复合物）作为非过敏原特异性免疫疗法，已用于过敏性疾病（包括过敏性鼻炎、慢性荨麻疹和特应性皮炎）数十年。尽管临床兴趣日益增长，但尚无Meta分析综合现有证据。本系统评价与Meta分析旨在评估组胺球蛋白在过敏性疾病中的疗效和安全性，特别强调其对过敏性鼻炎管理的启示。检索了PubMed、Embase、Web of Science和Cochrane Library，从建库至2026年3月。纳入评估皮下注射组胺球蛋白治疗过敏性疾病患者的研究。对于报告荨麻疹活动评分（UAS）为均值±标准差的慢性荨麻疹研究，采用随机效应Meta分析，使用标准化均数差（Hedges' g）。过敏性鼻炎研究进行叙述性综合。使用美国国立卫生研究院（NIH）质量评估工具评估偏倚风险。方案已在国际前瞻性系统评价注册库（PROSPERO）注册。14项研究（N=754）符合纳入标准：6项具有定量数据的慢性荨麻疹研究（N=190）、3项过敏性鼻炎研究（N=165）、2项特应性皮炎/慢性自发性荨麻疹病例系列（N=8）以及3项数据不完整的慢性荨麻疹研究。对6项慢性荨麻疹研究的Meta分析（均采用非对照前后设计）显示较大的合并组内效应量（Hedges' g=2.82；95%置信区间[CI] 1.75-3.88；p<0.00001），异质性高（I2=98.2%）。各研究中UAS降低范围为44%至89%。完全缓解率为30%至89%。排除一项存在报告问题的研究后的敏感性分析得出一致结果（g=2.34；95% CI 1.83-2.85；I2=90.2%）。所有3项过敏性鼻炎研究均报告症状显著改善（应答率57-90%），血清免疫球蛋白E（IgE）和嗜酸性粒细胞计数正常化。现有文献中未发现严重不良事件；然而，累积样本量（N=754）仍不足以排除罕见或长期不良效应。现有证据提示组胺球蛋白可能降低慢性荨麻疹的疾病活动度；由于合并估计主要来自异质性大的非对照前后研究，它反映的是治疗后的组内改善而非对照的治疗效果估计，对效应的信心仍然有限。初步证据提示组胺球蛋白也可能对过敏性鼻炎患者有益；然而，现有数据有限且异质性大，需要更大规模、设计良好的对照研究来证实其有效性。需要设计良好的随机对照试验，特别是针对过敏性鼻炎，以确立组胺球蛋白在循证耳鼻咽喉科实践中的作用。

英文摘要

Histaglobulin (histamine/immunoglobulin complex) has been used for decades as a non-allergen-specific immunotherapy for allergic diseases including allergic rhinitis, chronic urticaria, and atopic dermatitis. Despite growing clinical interest, no meta-analysis has synthesized the available evidence. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of histaglobulin across allergic diseases, with particular emphasis on implications for allergic rhinitis management. PubMed, Embase, Web of Science, and Cochrane Library were searched from inception to March 2026. Studies evaluating subcutaneous histaglobulin in patients with allergic diseases were included. For chronic urticaria studies reporting Urticaria Activity Score (UAS) as mean ± standard deviation, a random-effects meta-analysis was performed using the standardized mean difference (Hedges' g). Allergic rhinitis studies were synthesized narratively. Risk of bias was assessed using the National Institutes of Health (NIH) Quality Assessment Tools. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO). Fourteen studies (N = 754) met the inclusion criteria: six chronic urticaria studies with quantitative data (N = 190), three allergic rhinitis studies (N = 165), two atopic dermatitis/chronic spontaneous urticaria case series (N = 8), and three chronic urticaria studies with incomplete data. Meta-analysis of six chronic urticaria studies, all of which used an uncontrolled before-after design, demonstrated a large pooled within-group effect size (Hedges' g = 2.82; 95% confidence interval [CI] 1.75-3.88; p < 0.00001), with high heterogeneity (I2 = 98.2%). UAS reduction ranged from 44% to 89% across studies. Complete remission rates ranged from 30% to 89%. Sensitivity analysis excluding one study with reporting concerns yielded consistent results (g = 2.34; 95% CI 1.83-2.85; I2 = 90.2%). All three allergic rhinitis studies reported significant symptom improvement (response rates 57-90%) with normalization of serum immunoglobulin E (IgE) and eosinophil counts. No serious adverse events were identified within the available literature; however, the cumulative sample size (N = 754) remains insufficient to exclude rare or long-term adverse effects. Available evidence suggests that histaglobulin may reduce disease activity in chronic urticaria; because the pooled estimate derives predominantly from uncontrolled before-after studies with substantial heterogeneity, it reflects within-group improvement following treatment rather than a controlled estimate of treatment efficacy, and confidence in the effect remains limited. Preliminary evidence suggests that histaglobulin may also provide benefit in patients with allergic rhinitis; however, the available data are limited and heterogeneous, and larger, well-designed controlled studies are needed to confirm its effectiveness. Well-designed randomized controlled trials are needed, particularly for allergic rhinitis, to establish histaglobulin's role in evidence-based otorhinolaryngology practice.