PDF(Pubmed)
Abstract：
BACKGROUND: Autoimmune pulmonary alveolar proteinosis (APAP) is a diffuse lung disease that causes abnormal accumulation of lipoproteins in the alveoli; however, its pathogenesis remains unclear. Recently, APAP cases have been reported during the course of dermatomyositis. The combination of these two diseases may be coincidental; however, it may have been overlooked because differentiating APAP from a flare-up of interstitial pneumonia associated with dermatomyositis is challenging. This didactic case demonstrates the need for early APAP scrutiny.
METHODS: A 50-year-old woman was diagnosed with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatitis and interstitial pneumonia in April 2021. The patient was treated with corticosteroids, tacrolimus, and cyclophosphamide pulse therapy for interstitial pneumonia complicated by MDA5 antibody-positive dermatitis, which improved the symptoms and interstitial pneumonia. Eight months after the start of treatment, a new interstitial shadow appeared that worsened. Therefore, three additional courses of cyclophosphamide pulse therapy were administered; however, the respiratory symptoms and interstitial shadows did not improve. Respiratory failure progressed, and 14 months after treatment initiation, bronchoscopy revealed turbid alveolar lavage fluid, numerous foamy macrophages, and numerous periodic acid-Schiff-positive unstructured materials. Blood test results revealed high anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody levels, leading to a diagnosis of APAP. The patient underwent whole-lung lavage, and the respiratory disturbance promptly improved. Anti-GM-CSF antibodies were measured from the cryopreserved serum samples collected at the time of diagnosis of anti-MDA5 antibody-positive dermatitis, and 10 months later, both values were significantly higher than normal.
CONCLUSIONS: This is the first report of anti-MDA5 antibody-positive dermatomyositis complicated by interstitial pneumonia with APAP, which may develop during immunosuppressive therapy and be misdiagnosed as a re-exacerbation of interstitial pneumonia. In anti-MDA5 antibody-positive dermatomyositis, APAP comorbidity may have been overlooked, and early evaluation with bronchoalveolar lavage fluid and anti-GM-CSF antibody measurements should be considered, keeping the development of APAP in mind.
METHODS: A 50-year-old woman was diagnosed with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatitis and interstitial pneumonia in April 2021. The patient was treated with corticosteroids, tacrolimus, and cyclophosphamide pulse therapy for interstitial pneumonia complicated by MDA5 antibody-positive dermatitis, which improved the symptoms and interstitial pneumonia. Eight months after the start of treatment, a new interstitial shadow appeared that worsened. Therefore, three additional courses of cyclophosphamide pulse therapy were administered; however, the respiratory symptoms and interstitial shadows did not improve. Respiratory failure progressed, and 14 months after treatment initiation, bronchoscopy revealed turbid alveolar lavage fluid, numerous foamy macrophages, and numerous periodic acid-Schiff-positive unstructured materials. Blood test results revealed high anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody levels, leading to a diagnosis of APAP. The patient underwent whole-lung lavage, and the respiratory disturbance promptly improved. Anti-GM-CSF antibodies were measured from the cryopreserved serum samples collected at the time of diagnosis of anti-MDA5 antibody-positive dermatitis, and 10 months later, both values were significantly higher than normal.
CONCLUSIONS: This is the first report of anti-MDA5 antibody-positive dermatomyositis complicated by interstitial pneumonia with APAP, which may develop during immunosuppressive therapy and be misdiagnosed as a re-exacerbation of interstitial pneumonia. In anti-MDA5 antibody-positive dermatomyositis, APAP comorbidity may have been overlooked, and early evaluation with bronchoalveolar lavage fluid and anti-GM-CSF antibody measurements should be considered, keeping the development of APAP in mind.
摘要：
背景：自身免疫性肺泡蛋白沉积症（APAP）是一种弥漫性肺部疾病，会导致肺泡中脂蛋白的异常积累；但是，其发病机制尚不清楚。最近,在皮肌炎过程中已经报道了APAP病例。这两种疾病的结合可能是巧合；然而，这可能被忽视了,因为区分APAP和与皮肌炎相关的间质性肺炎发作具有挑战性.这个说教的案例表明需要及早进行APAP审查。
方法：一名50岁女性于2021年4月被诊断患有抗黑色素瘤分化相关基因5（抗MDA5）抗体阳性皮炎和间质性肺炎。患者接受了皮质类固醇治疗，他克莫司,环磷酰胺冲击治疗间质性肺炎并发MDA5抗体阳性皮炎，改善了症状和间质性肺炎。治疗开始八个月后，出现了一个新的间隙阴影，恶化了。因此,另外三个疗程的环磷酰胺脉冲治疗;然而,呼吸道症状和间质性阴影没有改善.呼吸衰竭进展,治疗开始后14个月，支气管镜检查显示混浊的肺泡灌洗液，大量的泡沫巨噬细胞，和许多高碘酸席夫正非结构化材料。血液检测结果显示高抗粒细胞-巨噬细胞集落刺激因子（GM-CSF）抗体水平，导致APAP的诊断。病人接受了全肺灌洗,呼吸障碍迅速改善。从抗MDA5抗体阳性皮炎诊断时收集的冷冻保存的血清样品中测量抗GM-CSF抗体,10个月后,两个值都显著高于正常值.
结论：这是首次报道抗MDA5抗体阳性皮肌炎并发间质性肺炎的APAP，可能在免疫抑制治疗期间发展，并被误诊为间质性肺炎的再加重。在抗MDA5抗体阳性皮肌炎中，APAP合并症可能被忽视了，应考虑使用支气管肺泡灌洗液和抗GM-CSF抗体测量进行早期评估，牢记APAP的发展。
方法：一名50岁女性于2021年4月被诊断患有抗黑色素瘤分化相关基因5（抗MDA5）抗体阳性皮炎和间质性肺炎。患者接受了皮质类固醇治疗，他克莫司,环磷酰胺冲击治疗间质性肺炎并发MDA5抗体阳性皮炎，改善了症状和间质性肺炎。治疗开始八个月后，出现了一个新的间隙阴影，恶化了。因此,另外三个疗程的环磷酰胺脉冲治疗;然而,呼吸道症状和间质性阴影没有改善.呼吸衰竭进展,治疗开始后14个月，支气管镜检查显示混浊的肺泡灌洗液，大量的泡沫巨噬细胞，和许多高碘酸席夫正非结构化材料。血液检测结果显示高抗粒细胞-巨噬细胞集落刺激因子（GM-CSF）抗体水平，导致APAP的诊断。病人接受了全肺灌洗,呼吸障碍迅速改善。从抗MDA5抗体阳性皮炎诊断时收集的冷冻保存的血清样品中测量抗GM-CSF抗体,10个月后,两个值都显著高于正常值.
结论：这是首次报道抗MDA5抗体阳性皮肌炎并发间质性肺炎的APAP，可能在免疫抑制治疗期间发展，并被误诊为间质性肺炎的再加重。在抗MDA5抗体阳性皮肌炎中，APAP合并症可能被忽视了，应考虑使用支气管肺泡灌洗液和抗GM-CSF抗体测量进行早期评估，牢记APAP的发展。
