Da Silva Rafael C, Adhikari Prakash
School of Medicine, University Center for the Development of the Alto Vale of Itajai (UNIDAVI), Rio do Sul, BRA.
Internal Medicine, Piedmont Athens Regional Medical Center, Athens, USA.
Cureus. 2022 Oct 4;14(10):e29909. doi: 10.7759/cureus.29909. eCollection 2022 Oct.
Granulomatosis with polyangiitis (GPA) is a systemic disease that has variable clinical expression. GPA is the most common antineutrophilic cytoplasmic antibody(ANCA)-associated vasculitis (AAV). Diffuse alveolar hemorrhage (DAH) is one of the least common pulmonary manifestations in patients with GPA. DAH is clinically marked by hemoptysis, anemia, and diffuse alveolar infiltrates on imaging as well as hypoxemic respiratory failure. The diagnosis and treatment are challenging. Recommendations for ANCA-associated vasculitis, in general, are already established; however, there is a knowledge gap that addresses the association of GPA and DAH. The aim of this systematic review is to focus on the main clinical aspects and treatment of patients with GPA who present with DAH. Thorough research of available literature was performed, including studies published in the last 10 years, following the Preferred Items for Systematic Review and Meta-Analysis (PRISMA) 2020 recommendations. The following databases were included: PubMed, Medline, Embase, ClinicalTrials.com, Google Scholar, and Prospero. The search terms included: [granulomatosis] AND [polyangiitis] AND [diffuse alveolar hemorrhage] OR [diffuse pulmonary hemorrhage] NOT [microscopic polyangiitis] NOT [eosinophilic granulomatosis]. NOS was used to assess the internal validity of the study in four domains, including selection, ascertainment, causality, and reporting. Our initial search identified 8989 studies. After excluding duplicated data and using our predetermined inclusion and exclusion criteria, we were able to retrieve 18 studies. Twelve out of 18 (67%) studies were case reports. Five were retrospective cohorts and one controlled trial. The average age of patients with GPA with DAH was 49.55 ± 17.54 years (18 - 76). Male individuals had a slight predominance (59%) in comparison to female individuals (41%). The hemoglobin level at the time of presentation was 8.86 mg/dL ± 1.43. The majority of patients (61.5%) reported hemoptysis. Renal involvement was present in 66.7%. Patients who required mechanical ventilation represented 61.5%. Plasmapheresis was used in 71.4%. Mortality was 20%, and gender was not associated with mortality (p = 0.822). Hemoptysis was not associated with the need for mechanical ventilation (p = 0.928). Renal impairment was not a predictor of mechanical ventilation (p = 0.207). In summary, patients with GPA and DAH were severely ill, frequently had renal impairment upon admission, and frequently required mechanical ventilation. Steroids, rituximab, and cyclophosphamide are the first-line treatment, and plasmapheresis is still in use. Eventually, extracorporeal membrane oxygenation (ECMO) can be the salvage therapy. Randomized controlled clinical trials (RCTs) are needed to address the best therapeutic options for this population.
肉芽肿性多血管炎（GPA）是一种临床表现多样的全身性疾病。GPA是最常见的抗中性粒细胞胞浆抗体（ANCA）相关性血管炎（AAV）。弥漫性肺泡出血（DAH）是GPA患者中最不常见的肺部表现之一。DAH的临床特征为咯血、贫血、影像学上的弥漫性肺泡浸润以及低氧性呼吸衰竭。其诊断和治疗具有挑战性。一般来说，关于ANCA相关性血管炎的诊疗建议已经确立；然而，在GPA与DAH的关联方面存在知识空白。本系统评价的目的是聚焦于出现DAH的GPA患者的主要临床特征和治疗。按照系统评价和Meta分析的首选报告项目（PRISMA）2020声明，对现有文献进行了全面检索，包括过去10年发表的研究。纳入了以下数据库：PubMed、Medline、Embase、ClinicalTrials.com、谷歌学术和国际系统评价注册库（Prospero）。检索词包括：[肉芽肿病] AND [多血管炎] AND [弥漫性肺泡出血] 或 [弥漫性肺出血] NOT [显微镜下多血管炎] NOT [嗜酸性肉芽肿性多血管炎]。采用纽卡斯尔-渥太华量表（NOS）在四个领域评估研究的内部效度，包括选择、确定、因果关系和报告。我们最初的检索识别出8989项研究。在排除重复数据并应用预先设定的纳入和排除标准后，我们能够获取18项研究。18项研究中有12项（67%）为病例报告。5项为回顾性队列研究，1项为对照试验。出现DAH的GPA患者的平均年龄为49.55±17.54岁（18 - 76岁）。男性略占优势（59%），女性占41%。就诊时的血红蛋白水平为8.86mg/dL±1.43。大多数患者（61.5%）有咯血症状。66.7%的患者有肾脏受累。需要机械通气的患者占61.5%。71.4%的患者使用了血浆置换。死亡率为20%，性别与死亡率无关（p = 0.822）。咯血与是否需要机械通气无关（p = 0.928）。肾功能损害不是机械通气的预测因素（p = 0.207）。总之，患有GPA和DAH 的患者病情严重，入院时经常有肾功能损害，且经常需要机械通气。类固醇、利妥昔单抗和环磷酰胺是一线治疗药物，血浆置换仍在使用。最终，体外膜肺氧合（ECMO）可能是挽救性治疗方法。需要进行随机对照临床试验（RCT）来确定针对该人群的最佳治疗方案。
