Department of Pediatric Immunology and Rheumatology, Wilhelmina Children's Hospital, Utrecht, Netherlands.
Department of Immunology and Rheumatology, University Medical Center Utrecht, Utrecht, Netherlands.
Front Immunol. 2021 Apr 15;12:606099. doi: 10.3389/fimmu.2021.606099. eCollection 2021.
Besides recurrent infections, a proportion of patients with Common Variable Immunodeficiency Disorders (CVID) may suffer from immune dysregulation such as granulomatous-lymphocytic interstitial lung disease (GLILD). The optimal treatment of this complication is currently unknown. Experienced-based expert opinions have been produced, but a systematic review of published treatment studies is lacking.
To summarize and synthesize the published literature on the efficacy of treatments for GLILD in CVID.
We performed a systematic review using the PRISMA guidelines. Papers describing treatment and outcomes in CVID patients with radiographic and/or histologic evidence of GLILD were included. Treatment regimens and outcomes of treatment were summarized.
6124 papers were identified and 42, reporting information about 233 patients in total, were included for review. These papers described case series or small, uncontrolled studies of monotherapy with glucocorticoids or other immunosuppressants, rituximab monotherapy or rituximab plus azathioprine, abatacept, or hematopoietic stem cell transplantation (HSCT). Treatment response rates varied widely. Cross-study comparisons were complicated because different treatment regimens, follow-up periods, and outcome measures were used. There was a trend towards more frequent GLILD relapses in patients treated with corticosteroid monotherapy when compared to rituximab-containing treatment regimens based on qualitative endpoints. HSCT is a promising alternative to pharmacological treatment of GLILD, because it has the potential to not only contain symptoms, but also to resolve the underlying pathology. However, mortality, especially among immunocompromised patients, is high.
We could not draw definitive conclusions regarding optimal pharmacological treatment for GLILD in CVID from the current literature since quantitative, well-controlled evidence was lacking. While HSCT might be considered a treatment option for GLILD in CVID, the risks related to the procedure are high. Our findings highlight the need for further research with uniform, objective and quantifiable endpoints. This should include international registries with standardized data collection including regular pulmonary function tests (with carbon monoxide-diffusion), uniform high-resolution chest CT radiographic scoring, and uniform treatment regimens, to facilitate comparison of treatment outcomes and ultimately randomized clinical trials.
除了反复感染，一部分普通变异性免疫缺陷病（CVID）患者可能患有免疫失调，如肉芽肿性淋巴细胞间质性肺病（GLILD）。目前尚不清楚这种并发症的最佳治疗方法。已经提出了基于经验的专家意见，但缺乏对已发表的治疗研究的系统评价。
总结和综合已发表的关于 CVID 患者 GLILD 治疗效果的文献。
我们按照 PRISMA 指南进行了系统评价。纳入了描述 CVID 患者有影像学和/或组织学证据的 GLILD 患者的治疗和结局的研究。总结了治疗方案和治疗结果。
共确定了 6124 篇论文，其中 42 篇共报道了 233 例患者的信息，被纳入综述。这些论文描述了糖皮质激素或其他免疫抑制剂、利妥昔单抗单药或利妥昔单抗联合硫唑嘌呤、阿巴西普或造血干细胞移植（HSCT）的单药治疗的病例系列或小型非对照研究。治疗反应率差异很大。由于使用了不同的治疗方案、随访期和结局测量，跨研究比较变得复杂。根据定性终点，与包含利妥昔单抗的治疗方案相比，糖皮质激素单药治疗的患者 GLILD 复发更频繁。HSCT 是治疗 GLILD 的一种有前途的药物替代疗法，因为它不仅有控制症状的潜力，而且还有可能解决潜在的病理学问题。然而，死亡率，特别是免疫功能低下患者的死亡率很高。
由于缺乏定量、对照良好的证据，我们无法从当前文献中得出关于 CVID 患者 GLILD 最佳药物治疗的明确结论。虽然 HSCT 可能被认为是 CVID 患者 GLILD 的一种治疗选择，但该手术的风险很高。我们的研究结果强调需要进一步研究，采用统一、客观和可量化的终点。这应包括国际登记处，进行标准化数据收集，包括定期肺功能检查（一氧化碳弥散）、统一的高分辨率胸部 CT 放射性评分和统一的治疗方案，以促进治疗结果的比较，并最终进行随机临床试验。
