抗中性粒细胞胞浆抗体相关性间质性肺炎的临床特征及预后
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摘要
目的提出抗中性粒细胞胞浆抗体(antineutrophil cytoplasmic antibody,ANCA)相关性间质性肺炎概念并分析其临床特征与预后。方法回顾性分析比较2011年1月至2016年8月本院36例诊断符合间质性肺炎(interstitial pneumonia,IP)但不符合ANCA相关性血管炎(ANCA-associated vasculitis,AAV)诊断的ANCA阳性的间质性肺炎(ANCA-IP),19例同时符合IP及AAV诊断(AAV-IP)及40例特发性间质性肺炎(idiopathic interstitial pneumonia,IIP)患者的临床资料、治疗及预后。采用Kruskal-Wallis H检验、卡方分割法、多元Logistic回归、Kaplan-meier法进行统计分析。结果 (1)ANCA-IP、AAV-IP、IIP三组间比较年龄(χ~2=0.177,P=0.915)、性别(χ~2=3.555,P=0.169)比较差异无统计学意义;呼吸困难更常见于IIP组(χ~2=17.042,P=0.001); AAV-IP组患者WBC(χ~2=11.333,P=0.003)、Cr(χ~2=17.371,P=0.001)、CRP(χ~2=8.549,P=0.014)、ESR(χ~2=13.062,P=0.001)均显著高于ANCA-IP及IIP组;ANCA-IP患者胸部HRCT更多表现为蜂窝肺(χ~2=6.671,P=0.036)。(2)ANCA-IP组内治疗方式对比,不同治疗方式对预后有显著差异(χ~2=6.440,P=0.040),与大剂量激素+CTX组相比,小剂量激素/对症治疗组患者预后更好(χ~2=6.438,P=0.011);IIP患者不同治疗方式间比较无显著差异(χ~2=0.029,P=0.865)。(3)随访过程中,1例(2.8%)ANCA-IP患者在25月后进展为AAV。(4)多元Logistic回归分析结果显示,大剂量激素+CTX的治疗方式(OR=0.029,P=0.018)是存活的相关危险因素。结论ANCA-IP患者病情可能长期保持稳定而不进展为AAV,它可能是AAV疾病的早期阶段,也可能是一个独立的疾病,应避免过度免疫治疗。
Objective To clarify the concept of anti-neutrophil cytoplasmic antibodies(ANCA) associated interstitial pneumonia(IP) and analyze its clinical characteristics and prognosis.Methods Thirty-six patients diagnosed as IP but not conformed to ANCA associated vasculitis(ANCA-IP group),19 both IP and ANCA associated vasculitis(AAV-IP group),and 40 idiopathic interstitial pneumonia(IIP group) were studied by retrospectively. The clinical features, laboratory indexes,pulmonary high resolution CT(HRCT) images,treatment and prognosis were compared among these three groups. Kruskal-Wallis H test,chi square method,multivariate Logistic regression and Kaplan-meier method were used for statistical analysis. ResultsThere were no significant differences in age and sex among these three groups. Dyspnea was the most common clinical manifestation in the IIP group. White blood cells(WBC), serum creatinine(Cr),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR) were all significantly higher in the AAV-IP group. Honeycomb sign on HRCT was found more frequently in the ANCA-IP group. The patients treated with low dosagesof glucocorticoidhad a better prognosis than those with large dosages combined with cyclophosphamide. No differences were exhibited among different treatments in the IIP group. Only one patient(2.8%) in the ANCA-IP group progressed to AAV after a follow-up of 25 months.Multivariate Logistic regression analysis showed that large doses of glucocorticoid combined with cyclophosphamide treatment was a related risk factor for survival of ANCA-IP patients.Conclusions ANCA-IP patients may be in a stable condition for a relatively long time, and hardly progress to AAV. ANCA-IP may be an early stage of AAV or an independent state of the disease, which suggest that aggressive immunosuppressive therapy might be appropriate.
Objective To clarify the concept of anti-neutrophil cytoplasmic antibodies(ANCA) associated interstitial pneumonia(IP) and analyze its clinical characteristics and prognosis.Methods Thirty-six patients diagnosed as IP but not conformed to ANCA associated vasculitis(ANCA-IP group),19 both IP and ANCA associated vasculitis(AAV-IP group),and 40 idiopathic interstitial pneumonia(IIP group) were studied by retrospectively. The clinical features, laboratory indexes,pulmonary high resolution CT(HRCT) images,treatment and prognosis were compared among these three groups. Kruskal-Wallis H test,chi square method,multivariate Logistic regression and Kaplan-meier method were used for statistical analysis. ResultsThere were no significant differences in age and sex among these three groups. Dyspnea was the most common clinical manifestation in the IIP group. White blood cells(WBC), serum creatinine(Cr),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR) were all significantly higher in the AAV-IP group. Honeycomb sign on HRCT was found more frequently in the ANCA-IP group. The patients treated with low dosagesof glucocorticoidhad a better prognosis than those with large dosages combined with cyclophosphamide. No differences were exhibited among different treatments in the IIP group. Only one patient(2.8%) in the ANCA-IP group progressed to AAV after a follow-up of 25 months.Multivariate Logistic regression analysis showed that large doses of glucocorticoid combined with cyclophosphamide treatment was a related risk factor for survival of ANCA-IP patients.Conclusions ANCA-IP patients may be in a stable condition for a relatively long time, and hardly progress to AAV. ANCA-IP may be an early stage of AAV or an independent state of the disease, which suggest that aggressive immunosuppressive therapy might be appropriate.
引文
[1] Davies DJ,Moran JE,Niall JF,et al.Segmental necrotising glomerulonephritis with antineutrophil antibody: possible arbovirus aetiology[J]. Br Med J (Clin Res Ed),1982,285:606.
[2] N?le B,Specks U,Lüdemann J,et al.Anticytoplasmic autoantibodies: their immunodiagnostic value in Wegener granulomatosis[J].Ann Intern Med, 1989,111:28-40.
[3] Nada AK,Torres VE,Ryu JH,et al.Pulmonary fibrosis as an unusual clinical manifestation of a pulmonary-renal vasculitis in elderly patients[J].Mayo Clin Proc, 1990,65:847-856.
[4] Gaudin PB,Askin FB,Falk RJ,et al.The pathologic spectrum of pulmonary lesions in patients with anti-neutrophil cytoplasmic autoantibodiesspecific for anti-proteinase 3 and anti-myeloperoxidase[J].Am J Clin Pathol,1995,104:7-16.
[5] Nozu T, Kondo M, Suzuki K,et al.A comparison of the clinical features of ANCA-positive and ANCA-negative idiopathic pulmonary fibrosis patients[J]. Respiration, 2009,77:407-415.
[6] Hozumi H, Oyama Y, Yasui H,et al. Clinical significance of myeloperoxidase-anti-neutrophil cytoplasmic antibody in idio-pathic interstitial pneumonias[J].PLoS One, 2018,13:e0199659.
[7] American Thoracic Society; European Respiratory Society.American Thoracic Society/European Respiratory Society International MultidisciplinaryConsensus Classification of the Idiopathic Interstitial Pneumonias[J].Am J Respir Crit Care Med,2002,165:277-304.
[8] Jennette JC, Falk RJ, Bacon PA,et al.2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides[J]. Arthritis Rheum, 2013,65:1-11.
[9] Bloch DA, Michel BA, Hunder GG, et al.The American College of Rheumatology 1990 criteria for the classification of vasculitis. Patients and methods[J]. Arthritis Rheum, 1990,33:1068-1073.
[10] Jennette JC, Falk RJ, Andrassy K, et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference[J]. Arthritis Rheum, 1994,37:187-192.
[11] Katsumata Y, Kawaguchi Y, Yamanaka H. Interstitial lung disease with ANCA-associated vasculitis[J]. Clin Med Insights Circ Respir Pulm Med,2015,9(Suppl 1):51-56.
[12] Comarmond C,Crestani B,Tazi A,et al.Pulmonary fibrosis in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis: a series of 49 patients and review of the literature[J].Medicine(Baltimore),2014,93:340-349.
[13] Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management[J]. Am J Respir Crit Care Med, 2011,183:788-824.
[14] Tanaka T,Otani K,Egashira R,et al.Interstitial pneumonia associated with MPO-ANCA:clinicopathological features of nine patients[J].Respir Med, 2012,106:1765-1770.
[15] Guilpain P,Chéreau C,Goulvestre C,et al.The oxidation induced by antimyeloperoxidase antibodies triggers fibrosis in microscopic polyangiitis[J].Eur Respir,2011,37:1503-1513.
[16] Fernandez Casares M, Gonzalez A, Fielli M, et al. Microscopic polyangiitis associated with pulmonary fibrosis[J]. Clin Rheumatol, 2015,34:1273-1277.
[17] Hozumi H, Enomoto N, Oyama Y, et al. Clinical implication of proteinase-3-antineutrophil cytoplasmic antibody in patients with idiopathic interstitial pneumonias[J].Lung, 2016,194:235-242.
[18] Hervier B,Pagnoux C,Agard C,et al.Pulmonary fibrosis associated with ANCA-positivevasculitides.Retrospective study of 12 cases and review of the literature[J].Ann Rheum Dis, 2009,68:404-407.
[19] Greenan K, Vassallo D, Chinnadurai R, et al. Respiratory manifestations of ANCA-associated vasculitis[J]. Clin Respir J, 2018,12:57-61.
[20] Huang H,Wang YX,Jiang CG,et al.A retrospective study of microscopicpolyangiitis patients presenting with pulmonary fibrosis in China[J]. BMC Pulm Med, 2014,14:8.
[21] Alba MA, Flores-Suárez LF, AG H, et al. Interstital lung disease in ANCA vasculitis[J]. Autoimmun Rev, 2017,16:722-729.
[22] Oiwa H, Ooi K, Oyama T, et al. Idiopathic interstitial pneu-monia as a possible cause of antineutrophil cytoplasmic antibody-associated vasculitis: A case report[J]. Arch Rheumatol, 2018, 15;33:89-92.
[23] Schirmer JH,Wright MN,Vonthein R,et al.Clinical presentation and long-term outcome of 144 patients with microscopic polyangiitis in a monocentric German cohort[J]. Rheumatology (Oxford), 2016,55:71-79.
[24] Borie R, Crestani B. Antineutrophil cytoplasmic antibody-associated lung fibrosis[J]. Semin Respir Crit Care Med, 2018,39:465-470.
[25] Foulon G, Delaval P, Valeyre D, et al.ANCA-associated lung fibrosis: analysis of 17 patients[J]. Respir Med, 2008,102:1392-1398.
[26] Kagiyama N,Takayanagi N,Kanauchi T,et al.Antineutrophil cytoplasmic antibody-positive conversion and microscopic polyangiitis development in patientswith idiopathic pulmonary fibrosis[J]. BMJ Open Respir Res, 2015,2:e000058.
[27] Kishore N, Gupta N, Dhar A, et al. Interstitial lung disease with usual interstitial pneumonia pattern preceding the presentation of ANCA-associated vasculitis by 4 years: coincidence or correlation[J]. Breathe (Sheff), 2018,14:e105-e110.
[28] Idiopathic Pulmonary Fibrosis Clinical Research Network, Raghu G, Anstrom KJ, et al. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis[J]. N Engl J Med, 2012,366:1968-1977.
[2] N?le B,Specks U,Lüdemann J,et al.Anticytoplasmic autoantibodies: their immunodiagnostic value in Wegener granulomatosis[J].Ann Intern Med, 1989,111:28-40.
[3] Nada AK,Torres VE,Ryu JH,et al.Pulmonary fibrosis as an unusual clinical manifestation of a pulmonary-renal vasculitis in elderly patients[J].Mayo Clin Proc, 1990,65:847-856.
[4] Gaudin PB,Askin FB,Falk RJ,et al.The pathologic spectrum of pulmonary lesions in patients with anti-neutrophil cytoplasmic autoantibodiesspecific for anti-proteinase 3 and anti-myeloperoxidase[J].Am J Clin Pathol,1995,104:7-16.
[5] Nozu T, Kondo M, Suzuki K,et al.A comparison of the clinical features of ANCA-positive and ANCA-negative idiopathic pulmonary fibrosis patients[J]. Respiration, 2009,77:407-415.
[6] Hozumi H, Oyama Y, Yasui H,et al. Clinical significance of myeloperoxidase-anti-neutrophil cytoplasmic antibody in idio-pathic interstitial pneumonias[J].PLoS One, 2018,13:e0199659.
[7] American Thoracic Society; European Respiratory Society.American Thoracic Society/European Respiratory Society International MultidisciplinaryConsensus Classification of the Idiopathic Interstitial Pneumonias[J].Am J Respir Crit Care Med,2002,165:277-304.
[8] Jennette JC, Falk RJ, Bacon PA,et al.2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides[J]. Arthritis Rheum, 2013,65:1-11.
[9] Bloch DA, Michel BA, Hunder GG, et al.The American College of Rheumatology 1990 criteria for the classification of vasculitis. Patients and methods[J]. Arthritis Rheum, 1990,33:1068-1073.
[10] Jennette JC, Falk RJ, Andrassy K, et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference[J]. Arthritis Rheum, 1994,37:187-192.
[11] Katsumata Y, Kawaguchi Y, Yamanaka H. Interstitial lung disease with ANCA-associated vasculitis[J]. Clin Med Insights Circ Respir Pulm Med,2015,9(Suppl 1):51-56.
[12] Comarmond C,Crestani B,Tazi A,et al.Pulmonary fibrosis in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis: a series of 49 patients and review of the literature[J].Medicine(Baltimore),2014,93:340-349.
[13] Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management[J]. Am J Respir Crit Care Med, 2011,183:788-824.
[14] Tanaka T,Otani K,Egashira R,et al.Interstitial pneumonia associated with MPO-ANCA:clinicopathological features of nine patients[J].Respir Med, 2012,106:1765-1770.
[15] Guilpain P,Chéreau C,Goulvestre C,et al.The oxidation induced by antimyeloperoxidase antibodies triggers fibrosis in microscopic polyangiitis[J].Eur Respir,2011,37:1503-1513.
[16] Fernandez Casares M, Gonzalez A, Fielli M, et al. Microscopic polyangiitis associated with pulmonary fibrosis[J]. Clin Rheumatol, 2015,34:1273-1277.
[17] Hozumi H, Enomoto N, Oyama Y, et al. Clinical implication of proteinase-3-antineutrophil cytoplasmic antibody in patients with idiopathic interstitial pneumonias[J].Lung, 2016,194:235-242.
[18] Hervier B,Pagnoux C,Agard C,et al.Pulmonary fibrosis associated with ANCA-positivevasculitides.Retrospective study of 12 cases and review of the literature[J].Ann Rheum Dis, 2009,68:404-407.
[19] Greenan K, Vassallo D, Chinnadurai R, et al. Respiratory manifestations of ANCA-associated vasculitis[J]. Clin Respir J, 2018,12:57-61.
[20] Huang H,Wang YX,Jiang CG,et al.A retrospective study of microscopicpolyangiitis patients presenting with pulmonary fibrosis in China[J]. BMC Pulm Med, 2014,14:8.
[21] Alba MA, Flores-Suárez LF, AG H, et al. Interstital lung disease in ANCA vasculitis[J]. Autoimmun Rev, 2017,16:722-729.
[22] Oiwa H, Ooi K, Oyama T, et al. Idiopathic interstitial pneu-monia as a possible cause of antineutrophil cytoplasmic antibody-associated vasculitis: A case report[J]. Arch Rheumatol, 2018, 15;33:89-92.
[23] Schirmer JH,Wright MN,Vonthein R,et al.Clinical presentation and long-term outcome of 144 patients with microscopic polyangiitis in a monocentric German cohort[J]. Rheumatology (Oxford), 2016,55:71-79.
[24] Borie R, Crestani B. Antineutrophil cytoplasmic antibody-associated lung fibrosis[J]. Semin Respir Crit Care Med, 2018,39:465-470.
[25] Foulon G, Delaval P, Valeyre D, et al.ANCA-associated lung fibrosis: analysis of 17 patients[J]. Respir Med, 2008,102:1392-1398.
[26] Kagiyama N,Takayanagi N,Kanauchi T,et al.Antineutrophil cytoplasmic antibody-positive conversion and microscopic polyangiitis development in patientswith idiopathic pulmonary fibrosis[J]. BMJ Open Respir Res, 2015,2:e000058.
[27] Kishore N, Gupta N, Dhar A, et al. Interstitial lung disease with usual interstitial pneumonia pattern preceding the presentation of ANCA-associated vasculitis by 4 years: coincidence or correlation[J]. Breathe (Sheff), 2018,14:e105-e110.
[28] Idiopathic Pulmonary Fibrosis Clinical Research Network, Raghu G, Anstrom KJ, et al. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis[J]. N Engl J Med, 2012,366:1968-1977.