Two cases of autoimmune pulmonary alveolar proteinosis with rheumatoid arthritis
Two cases of autoimmune pulmonary alveolar proteinosis with rheumatoid arthritis
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类风湿性关节炎自身免疫性肺泡蛋白沉积症二例
DOI：
10.1016/j.alit.2017.02.002
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发表时间：
2017
影响因子：
6.8
通讯作者：
and Hasegawa Y.
中科院分区：
文献类型：
--
作者：
Ito S;Wakahara K;Kojima T;Takahashi N;Nishiwaki;K;Yamaguchi E;and Hasegawa Y.
肺泡蛋白沉积症（PAP），首次描述于1958年，1是一种罕见的疾病，表面活性剂成分的积累在肺泡和终端气道。2根据病因，PAP可分为遗传性、继发性和自身免疫性PAP。3自身免疫性PAP（aPAP）患者血清中抗粒细胞巨噬细胞集落刺激因子（GMCSF）IgG抗体的出现对诊断具有高度的敏感性和特异性。3 e5继发性PAP的发生与恶性肿瘤、传染病、药物和吸入二氧化硅或有毒烟雾以及可能的自身免疫性疾病有关。2，6虽然有报告称aPAP患者患有自身免疫性疾病，如风湿性多肌痛、溶血性贫血、肉芽肿伴多血管炎和皮肌炎，但aPAP与类风湿性关节炎（RA）的相关性尚不清楚。在这里，我们报告了两个日本的RA发病前的aPAP谁是阳性血清抗GM-CSF抗体和有效的治疗相结合的GM-CSF吸入治疗和全肺灌洗。2例患者的临床特征和实验室检查结果总结见表1。图1显示了基线和GM-CSF治疗及全肺灌洗前后的胸部计算机断层扫描（CT）图像。病例1是一名65岁女性，在名古屋大学医院接受甲氨蝶呤（4 mg/天，每周一次）和柳氮磺胺吡啶（1 g/天）治疗RA。由于干咳和用力时呼吸困难而进行的胸部计算机断层扫描（CT）成像显示双侧磨玻璃样阴影伴小叶间隔增厚，称为“疯狂铺路模式”（图1A）。Krebs von den Lungen-6（KL-6）（1233 U/mL）和表面活性蛋白-D（336 ng/mL）的血清水平升高，类风湿因子（29.3 IU/mL）呈弱阳性，但抗环瓜氨酸肽（CCP）抗体（0.3 U/ml）呈阴性（表1）。她的肺功能，包括肺活量（VC）、1秒用力呼气量（FEV 1）和肺一氧化碳弥散量（DLCO）得到保留（表1）。疑似RA相关间质性肺炎、甲氨蝶呤诱导的肺损伤、继发性PAP或这些异常的复合物。在她停止服用甲氨蝶呤后，她入院并接受了支气管镜检查和支气管肺泡灌洗（BAL）和经支气管活检。BALF检查显示肺泡内有高碘酸-希夫阳性渗出物和淋巴细胞增多（表1）。首先，怀疑继发性PAP与RA有关。全身皮质类固醇治疗
Pulmonary alveolar proteinosis (PAP), first described in 1958, 1 is a rare disorder with accumulation of surfactant components in the alveoli and terminal airways. 2 According to the etiology, PAP is classified into three groups: hereditary, secondary, and autoimmune PAP. 3 In patients with autoimmune PAP (aPAP), the appearance of IgG anti-granulocyte-macrophage colony-stimulating factor (GMCSF) is highly sensitive and specific for the diagnosis. 3 e5 Secondary PAP develops in association with malignancy, infectious diseases, drugs, and inhalation of silica or toxic fumes, and possibly as well as autoimmune diseases. 2, 6 Although cases of aPAP who had autoimmune diseases such as polymyalgia rheumatica, hemolytic anemia, granulomatosis with polyangiitis, and dermatomyositis have been reported, 4, 7 an association of aPAP with rheumatoid arthritis (RA) is not known. Here, we report two Japanese cases of RA preceding the onset of aPAP who were positive for serum anti-GMCSF antibody and effectively treated with combination of GM-CSF inhalation therapy and whole lung lavage. A summary of the clinical characteristics and laboratory findings of the two patients is shown in Table 1. Chest computed tomography (CT) images of baseline and before and after the GM-CSF therapy and whole lung lavage are shown in Figure 1.Case one was a 65-year-old female who had been treated with methotrexate (4 mg/day, once a week) and salazosulfapyridine (1 g daily) for RA at Nagoya University Hospital. Chest computed tomography (CT) imaging, which was performed because of dry cough and dyspnea on effort, revealed bilateral ground-glass opacities with interlobular septal thickening called “crazy-paving pattern”(Fig. 1 A). The serum levels of Krebs von den Lungen-6 (KL-6)(1233 U/mL) and surfactant protein-D (336 ng/mL) were elevated, and rheumatoid factor (29.3 IU/mL) was weakly positive, but anti-cyclic citrullinated peptide (CCP) antibody (0.3 U/ml) was negative (Table 1). Her pulmonary function, including vital capacity (VC), forced expiratory volume in 1 s (FEV1), and diffusion capacity of the lung for carbon monoxide (DLCO), was preserved (Table 1). RA-related interstitial pneumonia, methotrexate-induced lung injury, secondary PAP, or a complex of these abnormalities was suspected. After she stopped taking methotrexate, she was admitted to the hospital and underwent bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy. Examination of BAL fluid (BALF) revealed periodic acid-Schiff-positive intraalveolar exudate and increased lymphocytes (Table 1). First, secondary PAP related to RA was suspected. Systemic corticosteroid therapy