Abstract：
BACKGROUND: Biological disease-modifying anti-rheumatic drugs (bDMARDs) targeting interleukin (IL)-6 and IL-1β represent a steroid-sparing first-line therapy used in systemic-onset juvenile idiopathic arthritis (sJIA). Recently, the occurrence of pulmonary alveolar proteinosis (PAP) in sJIA patients was reported with early-onset and exposure to bDMARDs as potential risk factors. We report on a new case with longitudinal immunomonitoring successfully treated by Janus Kinase inhibitors (JAKi) and review past clinical descriptions of this new entity.
METHODS: We report one case of pulmonary alveolar proteinosis and macrophage activation syndrome (PAP-MAS) with longitudinal immunomonitoring. We then conducted a review of the literature of seven publications reporting 107 cases of PAP-MAS sJIA, and included the main characteristics and evolution under treatment.
RESULTS: Of the seven articles analyzed, the incidence of PAP-MAS among sJIA patients varied from 1.28% to 12.9%. We report here a single case among a cohort of 537 sJIA patients followed in the pediatric department of the Hospices Civils de Lyon over the last 15 years. This child presented with all clinical and immunological characteristics of PAP-MAS. After several lines of treatment, he benefited from JAKi and improved with respect to both systemic symptoms and lung disease. In the literature, strategies with monoclonal antibodies targeting either INF-γ or IL-1β/IL-18 have been tested with variable results. Orally taken JAKi presents the advantage of targeting multiple cytokines and avoiding parenteral injections of monoclonal antibodies that may contribute to the pathogenesis.
CONCLUSIONS: JAKi represent a promising option in the treatment of lung disease associated with sJIA.
METHODS: We report one case of pulmonary alveolar proteinosis and macrophage activation syndrome (PAP-MAS) with longitudinal immunomonitoring. We then conducted a review of the literature of seven publications reporting 107 cases of PAP-MAS sJIA, and included the main characteristics and evolution under treatment.
RESULTS: Of the seven articles analyzed, the incidence of PAP-MAS among sJIA patients varied from 1.28% to 12.9%. We report here a single case among a cohort of 537 sJIA patients followed in the pediatric department of the Hospices Civils de Lyon over the last 15 years. This child presented with all clinical and immunological characteristics of PAP-MAS. After several lines of treatment, he benefited from JAKi and improved with respect to both systemic symptoms and lung disease. In the literature, strategies with monoclonal antibodies targeting either INF-γ or IL-1β/IL-18 have been tested with variable results. Orally taken JAKi presents the advantage of targeting multiple cytokines and avoiding parenteral injections of monoclonal antibodies that may contribute to the pathogenesis.
CONCLUSIONS: JAKi represent a promising option in the treatment of lung disease associated with sJIA.
摘要：
背景：针对白细胞介素（IL）-6和IL-1β的生物疾病缓解抗风湿药（bDMARDs）代表了一种保留类固醇的一线治疗，用于全身性发作的幼年特发性关节炎（sJIA）。最近,据报道,sJIA患者发生肺泡蛋白沉积症(PAP),早期发病和暴露于bDMARDs是潜在危险因素.我们报告了通过Janus激酶抑制剂（JAKi）成功治疗的纵向免疫监测新病例，并回顾了该新实体的过去临床描述。
方法：我们报告1例肺泡蛋白沉积和巨噬细胞活化综合征（PAP-MAS）的纵向免疫监测。然后，我们对7篇报告107例PAP-MASsJIA的文献进行了综述，并包括治疗下的主要特征和进化。
结果：在分析的七篇文章中，sJIA患者中PAP-MAS的发生率从1.28%到12.9%不等。我们在此报告了在过去15年中，在里昂公民医院儿科随访的537名sJIA患者中的一例。该孩子具有PAP-MAS的所有临床和免疫学特征。经过几行治疗，他受益于JAKI,在全身症状和肺部疾病方面均有所改善.在文学中,已经测试了靶向INF-γ或IL-1β/IL-18的单克隆抗体的策略，结果可变。口服JAKi具有靶向多种细胞因子并避免可能导致发病机理的单克隆抗体的肠胃外注射的优点。
结论：JAKi是治疗与sJIA相关的肺部疾病的一种有希望的选择。
方法：我们报告1例肺泡蛋白沉积和巨噬细胞活化综合征（PAP-MAS）的纵向免疫监测。然后，我们对7篇报告107例PAP-MASsJIA的文献进行了综述，并包括治疗下的主要特征和进化。
结果：在分析的七篇文章中，sJIA患者中PAP-MAS的发生率从1.28%到12.9%不等。我们在此报告了在过去15年中，在里昂公民医院儿科随访的537名sJIA患者中的一例。该孩子具有PAP-MAS的所有临床和免疫学特征。经过几行治疗，他受益于JAKI,在全身症状和肺部疾病方面均有所改善.在文学中,已经测试了靶向INF-γ或IL-1β/IL-18的单克隆抗体的策略，结果可变。口服JAKi具有靶向多种细胞因子并避免可能导致发病机理的单克隆抗体的肠胃外注射的优点。
结论：JAKi是治疗与sJIA相关的肺部疾病的一种有希望的选择。
