感染性疾病与肺泡出血综合征

1　概念　　肺泡出血综合征是临床特点为呼吸困难、咯血、Ｘ线胸片为双侧弥漫性肺泡浸润以及贫血的一组疾病。通常在发病之初不能被早期诊断 ,典型的咯血和肺泡浸润有时被认为是肺水肿或肺炎。对早期肺泡出血综合征错误的诊断和治疗将导致两种严重后果 :(1)疾病迅速进展导致呼吸衰竭 ,(2 )肺泡出血常常是一种全身系统疾病的早期表现 ,这种疾病会导致肺外器官的损害 ,尤其是肾脏。2　肺泡出血综合征病因　　在肺泡出血的疾病中 ,主要包括严重的免疫性疾病、特发性疾病、感染性疾病、凝血功能障碍疾病和急性肺损伤等原因。二尖瓣狭窄、骨髓移…     

自身免疫性疾病相关的弥漫性肺泡出血

弥漫性肺泡出血综合征(diffuse alveolar hemorrhage syn-drome,DAHs)指在病因作用下,肺微血管血液进入肺泡,发生弥漫性肺泡出血(DAH),临床出现呼吸困难、咯血、贫血等症状,胸部X线片示双侧弥漫性肺泡浸润.该综合征是发生在一系列疾病过程中的严重并发症,并非一独立疾病,多来势凶险,危及生命,症状复杂.目前对于DAH尤其是自身免疫性疾病相关的DAH认识不足,常导致诊断及治疗延误,应引起临床医生高度重视.     

肺泡出血综合征

肺泡出血综合征（Alveolar Haemorrhage SyndromesAHS）为一危及生命的严重并发症，多发生在一系列疾病过程中，在不同病因作用下，导致肺微血管的血液进入肺泡，即弥漫性肺泡出血（DAH）。当血液聚集于肺实质内，临床可发生呼吸困难、咯血、X线胸片为双侧弥漫性肺泡浸润以及贫血等临床特征。     

弥漫性肺泡出血与自身免疫性疾病

弥漫性肺泡出血 (diffusealveolarhemorrhage ,DAH)是以咯血、呼吸困难、缺铁性贫血和X线胸片呈弥漫性肺泡浸润或实变为特征的临床综合征[1] 。DAH临床少见 ,但病情凶险 ,常威胁患者生命。凡引起广泛的肺泡 毛细血管损伤 ,导致肺泡腔内出血的任何病因 ,均可引起DAH(表 1)。然而 ,不同疾病采取的治疗措施不同 ,其预后也截然不同。由于引发DAH的多样性、免疫机制的复杂性 ,目前对于DAH尤其是自身免疫相关DAH在诊断方面存在认识上不足并常延误治疗。本文就自身免疫性疾病相关DAH诊断及治疗进行综述。表 1　弥漫性肺泡出血的常见病因…     

免疫性肺泡出血

免疫反应引起肺损伤已越来越受到临床学家的关注。免疫性肺泡出血是免疫性疾病导致的肺泡弥漫性出血,本文描述其病因、发病机理、临床表现、诊断及治疗。     

浅析弥漫性肺泡出血

弥漫性肺泡出血（Diffuse Alveolar Hemorrhage,DAH）屡见于临床,多数病例经历了漫长的延误诊断。此症大多来势凶险,死亡率高。不典型的多系统受累,迷惑了不少临床医生。及时诊断,正确抢救治疗,才能挽救生命。对其研究较前有长足进步。本病是以咯血、呼吸困难、缺铁性贫血和X线胸片呈弥漫性肺泡浸润为特征的临床综合征。     

药物相关性弥漫性肺泡出血综合征2例报道及文献复习

目的提高对药物相关性弥漫性肺泡出血综合征（DAHS）临床特点的认识。方法对我院确诊的2例药物性弥漫性肺泡出血综合征患者的临床资料进行分析。结果 2例确诊患者均为成人,均有明确的药物暴露史,起病急,临床表现为：咯血、贫血、呼吸困难和双肺弥漫性浸润影,相关感染、心衰、免疫学指标阴性,肺部HRCT、肺功能检查和支气管肺泡灌洗是诊断的主要手段,糖皮质激素治疗效果良好。结论 DAHS是一种多种原因导致的少见的临床综合症,药物也是引起DAHS的重要病因。药物相关性DAHS为除外性诊断,需与其他原因的DAHS鉴别,强调本病的早期诊断和及时、正规的治疗。     

成人呼吸窘迫综合征并发上消化道出血

呼吸窘迫综合征是一种尚未完全明瞭的疾病,其特征是肺毛细血管内皮和肺泡弥漫性损害,进而导致肺水肿和动脉低氧血症。近来人们已注意到,成人呼吸窘迫综合征并发上消化道出血者逐渐增多。有人报道13例成人呼吸窘迫综合征患者中有11例发生胃肠道出血。作者认为:此类并发症多见于危重病人,且大多数病例的出血是发生在胃体与胃底的应激性溃疡所引起的。其     

闭塞性细支气管炎伴机化性肺炎1例

闭塞性细支气管炎伴机化性肺炎（Bronchiolitis obliterans organizing penumonia，BOOP）由Epler和Colby于1985年提出，是一种以细支气管、肺泡管及泡内肉芽组织形成为病理特点的临床病理综合征，应用皮肤类固醇激素治疗反应良好，属弥漫性间质性肺疾病的一种特殊类型。我们首次诊断1例，报道如下。     

干燥综合征伴弥漫性肺泡出血1例

弥漫性肺泡出血是SS的一种罕见而危险的肺部表现, 具有病情凶险、进展迅速的特点, 国内外鲜有报道。本文报道1例SS伴弥漫性肺泡出血的青年女性患者, 既往有视神经脊髓炎病史, 表现为反复咯血、气促、晕厥, 予甲泼尼龙40 mg治疗后肺泡出血控制欠佳, 后经甲泼尼龙0.5 g/d冲击等治疗后病情缓解, 随访3年无明显疾病进展。CTD伴弥漫性肺泡出血需注意早期识别、尽早足量激素及免疫抑制剂治疗。     

Antiphospholipid antibodies-associated diffuse alveolar hemorrhage

ObjectivesTo describe the clinical features and outcomes of 17 patients with primary antiphospholipid syndrome (PAPS) or antiphospholipid antibodies (aPL) and diffuse alveolar hemorrhage (DAH).MethodsWe reviewed the medical records of all patients diagnosed with PAPS-associated DAH and aPL-associated DAH between January 1, 1997, and December 31, 2013, for clinical features, laboratory and radiographic findings, management, and outcomes.ResultsA total of 17 patients met the criteria for DAH and had aPL and 10 patients met the criteria for PAPS. The mean age at DAH diagnosis was 57.6 years. Secondary causes of DAH were ruled out. Surgical lung biopsy was performed in 6 cases, 5 of whom had bland hemorrhage. Pulmonary capillaritis was present in only 1 case. Four patients (3 with aPLs and 1 with PAPS) achieved complete remission despite receiving no treatment. The majority of patients treated received initial corticosteroids. Additionally, cyclophosphamide (2 cases), rituximab (1 case), plasma exchange (2 cases), methotrexate (1 case), azathioprine (1 case), and hydroxychloroquine (2 cases) were used. In total, 10 patients (59%) achieved complete and sustained remission with a median length of follow-up of 48 months. Four patients (23%) died (2 with PAPS and 2 with aPLs), all from uncontrolled DAH. Three patients (18%) relapsed after achieving complete remission.ConclusionsDAH is a rare complication of PAPS that can also arise de novo in aPL-positive individuals. Lung pathology shows either bland hemorrhage or capillaritis. Recognition of this unusual but known complication is important, since early diagnosis and therapy could potentially affect outcomes.     

弥漫性结缔组织病并发弥漫性肺泡出血32例临床分析

目的 通过分析总结弥漫性结缔组织病(CTD)合并弥漫性肺泡出血(DHA)的临床资料,提高对其的认识.方法 回顾分析北京协和医院2004年4月-2007年6月确诊的32例弥漫性CTD并发DAH的临床特点和诊疗方法.结果 弥漫性CTD合并DAH的患者中,显微镜下多血管炎(MPA)发病率为58.8%(10/17),系统性红斑狼疮(SLE)为1.5%(19/1267),韦格纳肉芽肿(WG)为3.6%(2/56),类风湿关节炎(RA)为0.2%(1/570);诊断DAH时的年龄:SLE(27.3±13.1)岁,MPA(50.1±20.7)岁;诊断DAH时的病程:SLE(16.7±18.3)个月,MPA(10.6士18.7)个月;SLE合并DAH时SLE疾病活动指数(SLEDAI)评分为(17.1 4±6.7)分,抗双链DNA抗体呈高滴度,补体c3为(41.8±25.2)ms/dl.WG、MPA、RA患者ESR、C反应蛋白均明显升高,MPA/WG患者髓过氧化物酶抗体(MPO)/丝氨酸蛋白酶抗体(PR3)呈高滴度阳性;DAH主要表现是咯血、胸闷、呼吸困难、Hb下降;X线胸片、高分辨率CT可出现异常.多肺段支气管肺泡灌洗诊断DAH阳性率为100%.20例患者(20/32,62.5%)发生肺部感染,其中真菌感染10例(10/20,50%),混合性感染10例(10/20,50%).死亡19例(19/32,59.4%),其中SLE 12例(12/19,63.2%),MPA 5例(5/10),WG 2例(2/2);直接死于呼吸衰竭12例(12/19,63.2%).结论 弥漫性CTD患者出现咯血、呼吸困难,不明原因的Hb下降,胸部x线和高分辨率CT出现弥漫性浸润影,应警惕DAH,支气管肺泡灌洗有助于确诊.DAH与弥漫性CTD原发病的活动性密切相关,容易导致呼吸衰竭和肺部感染.弥漫性CTD合并DAH病死率较高,应早期诊断,早期治疗.     

Diffuse pulmonary alveolar hemorrhage after allogeneic bone marow transplantation

Summary Diffuse pulmonary alveolar hemorrhage (DAH) is a life-threatening complication following bone marrow transplantation (BMT). So far it has been seen preferentially after autologous BMT. Here, we describe a patient who presented with the picture of DAH after allogeneic BMT. We draw attention to the fact that the syndrome may occur after allogeneic BMT, too.     

Hemorragia alveolar difusa en pacientes con lupus eritematoso sistémico. Manifestaciones clínicas,tratamiento y pronóstico

Diffuse alveolar hemorrhage (DAH) in patients with systemic lupus erythematosus is a rare but potentially fatal condition. Although the pathogenesis of this condition is unknown, high disease activity is the main characteristic; moreover, histopathology in some studies showed alveolar immune complex deposits and capillaritis. Clinical features of DAH include dyspnea, a drop in hemoglobin, and diffuse radiographic alveolar images, with or without hemoptysis. Factors associated with mortality include mechanical ventilation, renal failure, and infections. Bacterial infections have been reported frequently in patients with DAH, but also invasive fungal infections including aspergillosis. DAH treatment is based on high dose methylprednisolone; other accepted therapies include cyclophosphamide (controversial), plasmapheresis, immunoglobulin and rituximab.     

Antiphospholipid antibodies as a cause of pulmonary capillaritis and diffuse alveolar hemorrhage: a case series and literature review

OBJECTIVES: To discuss the clinical manifestations and possible pathogenic mechanisms of the unusual syndrome of diffuse alveolar hemorrhage (DAH) and pulmonary capillaritis without thrombosis in the setting of the primary antiphospholipid antibody syndrome (PAPS). METHODS: Four men with DAH and capillaritis in the setting of PAPS are identified. Their clinical presentations, laboratory, radiographic, and pathologic findings are reviewed as is their clinical course and response to therapy. In addition, the literature regarding DAH and pulmonary capillaritis in the setting of PAPS is reviewed. RESULTS: The patients presented with dyspnea, hemoptysis, fever, hypoxia, and diffuse alveolar infiltrates; none had evidence of acute thromboembolic disease. All secondary causes of DAH were ruled out. All patients had positive testing for the lupus anticoagulant and high-titer anticardiolipin antibodies, including antibodies against the beta-2-glycoprotein I antigen. Three cases had lung biopsies that revealed pulmonary capillaritis and DAH with no evidence of thrombosis. All patients improved with high-dose corticosteroids. Recurrent disease in the setting of aggressive immunosuppression responded to intravenous immunoglobulin. Antiphospholipid antibody-mediated endothelial cell activation in the absence of thrombosis may induce capillaritis as seen in these cases. CONCLUSIONS: The syndrome of DAH and pulmonary capillaritis is further defined. Evidence supports a causative relationship between PAPS, pulmonary capillaritis, and DAH in the absence of thromboembolic disease. Further elucidation of a possible nonthrombotic mechanism of antiphospholipid antibody-mediated pathology is needed to guide future therapies for this unusual manifestation of PAPS.     

Plasmapheresis in Diffuse Alveolar Hemorrhage as Perinuclear Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Relapse on Hemodialysis

Unlike Goodpasture's syndrome with diffuse alveolar hemorrhage (DAH), there are scarce reports on the use of plasmapheresis for patients with a recurrence of DAH associated with antineutrophil cytoplasmic antibody (ANCA)-associated small vessel vasculitis (AAV) on hemodialysis. We report a case of a relapse of perinuclear-AAV with DAH, five months after starting hemodialysis. The patient received apheresis and induction immunosuppressive therapy, added to a short course of daily hemodialysis treatments. The DAH resolved with seven apheresis procedures and there were no adverse effects. We suggest that patients on hemodialysis with a relapse of AAV and DAH would benefit from the prompt initiation of apheresis in combination with aggressive immunosuppressive therapy. Pulmonary hemorrhage is not included in the current guidelines for therapeutic apheresis; therefore, we report this case and, if warranted, propose this condition to be included in the guidelines.     

Diffuse alveolar hemorrhage in Colombian patients with systemic lupus erythematosus

Diffuse alveolar hemorrhage (DAH) is a rare life-threatening complication seen in patients with systemic lupus erythematosus (SLE). This paper describes the clinical features and outcome of seven SLE patients with DAH admitted to a medical intensive care unit (ICU) in a referral center. Of a total of 122 SLE patients, seven patients presented this complication (5.7%). Five patients were women (71.4%). Mean age was 24.3 (range 4–51 years). Mean duration of SLE before clinical DAH was 15.7 months (range 0–48 months). DAH was the initial manifestation of SLE in two patients (29%). DAH recurrence was seen in two patients (29%). Active lupus was present in all seven patients. Fever, glomerulonephritis, arthritis, myositis, and peripheral neuropathy were observed in six, four, four, three, and two patients, respectively. Five patients who underwent to bronchoscopy had positive findings of DAH (71.4%; i.e., bloody return on bronchoalveolar lavage—with hemosiderin-laden macrophages). Treatment options included intravenous methylprednisolone (10 mg kg⁻¹ day⁻¹—3 days) following by prednisolone 1 mg kg⁻¹ day⁻¹ and pulse cyclophosphamide (750 mg/m²). Plasmapheresis was added in four patients (57.1%) because of the persistence of DAH. All patients were treated in an ICU, six of them requiring mechanical respiratory support (85.1%). Mortality rate during ICU stay was 12% (one patient). Our results show that DAH is an uncommon complication in SLE patients, requiring a prompt and aggressive recognition and treatment with high-dose steroid, intravenous cyclophosphamide, and plasmapheresis. With all of these treatments, there is a trend to a low mortality rate in patients with SLE presenting DAH.     

Diffuse Alveolar Hemorrhage Associated with Dilated Cardiomyopathy and Sleep Apnea Syndrome

We herein report a case of diffuse alveolar hemorrhage (DAH) associated with dilated cardiomyopathy (DCM) and sleep apnea syndrome (SAS) in a 47-year-old man. The patient exhibited recurring dyspnea and bloody sputum. Chest radiography showed bilateral diffuse infiltrative opacities without pleural effusion. A bronchoscopic analysis of bronchoalveolar lavage fluid revealed hemosiderin-laden macrophages. Based on these findings, he was diagnosed with DAH. Laboratory and pathological findings ruled out the possibility of collagen diseases and vasculitis. Overnight polysomnography revealed concomitant severe obstructive SAS. Treatment with continuous positive-pressure ventilation and pharmacological therapy for DCM prevented recurrence of DAH.     

Plasma Exchange Therapy to Reduce Mortality in Japanese Patients With Diffuse Alveolar Hemorrhage and Microscopic Polyangiitis

Diffuse alveolar hemorrhage (DAH) is well known as a serious complication of microscopic polyangiitis (MPA). We examined the effectiveness of plasma exchange (PLEX) therapy to reduce mortality in Japanese DAH patients with MPA. This retrospective, double‐center, observational cohort study included 20 DAH patients with MPA who were admitted to Juntendo University Hospital or Juntendo Koto Geriatric Medical Center between April 1998 and March 2018. The primary outcome was non–disease‐specific mortality. The 1‐year survival rate of patients with PLEX therapy (N = 4) was higher than that of patients with conventional therapy (N = 16, 75% and 13%, respectively, P = 0.037). Higher values of the 1996 Five‐Factor Score (FFS) and 2009 FFS were associated with increased mortality, with hazard ratios of 2.29 (P = 0.040) and 2.41 (P = 0.043), respectively, by Cox univariate analysis. We investigated PLEX therapy for reducing mortality in DAH patients with MPA, and the 1996 FFS and 2009 FFS were both independent prognostic factors.     

药物诱发的中性粒细胞浆抗体相关性小血管炎合并弥漫性肺泡出血5例临床分析

目的探讨药物诱发的中性粒细胞浆抗体(ANCA)相关小血管炎(AASV)合并弥漫性肺泡出血(DAH)的临床、血清学和影像学特征。方法回顾性分析北京协和医院2001年1月至2011年5月收治的5例AASV合并DAH患者的临床、肺部影像学表现、血清学指标、治疗及预后。结果 5例AASV合并DAH患者中,丙基硫氧嘧啶(PTU)引起的2例,由头孢氨苄、阿托伐他汀、卡马西平引起的各1例。临床表现发热、咳嗽、气短、咯血,肺部可闻及湿啰音。胸部CT检查示双肺片状浸润影、磨玻璃样变。血清学检查提示红细胞沉降率、C反应蛋白(CRP)均有不同程度增高。3例核周型ANCA(p-ANCA)阳性,1例胞浆型ANCA(c-ANCA)阳性,1例p-ANCA及c-ANCA均为阳性。所有患者均给予糖皮质激素治疗,其中2例单纯口服泼尼松。2例予联合环磷酰胺治疗,1例联合血浆置换3次。结论 AASV合并DAH临床诊断有一定困难,有明确服药史患者新近出现气短、咯血和新发肺部侵润影,需考虑AASV合并DAH。