【作者】 李凤娟；

【导师】 徐伟；

【作者基本信息】 吉林大学 ， 临床医学硕士（内科学）（专业学位）， 2021， 硕士

【摘要】 目的:结缔组织疾病(Connective tissue disease,CTD)包括:系统性红斑狼疮(Systemic lupus erythematosus,SLE)、类风湿性关节炎(Rheumatoid arthritis,RA)、系统性硬化症(Systemic sclerosis,SSc)、干燥综合征(Sjogren’s syndrome,SS)、肌炎/皮肌炎(Polymyositis/Dermatomyositis,PM/DM)等。虽然不同类型的结缔组织疾病均可导致间质性肺炎(Interstitial pulmonary disease,ILD),但是不同类型的结缔组织相关间质性肺疾病(Connective tissue disease-Interstitial pulmonary disease,CTD-ILD)的影像学特征、临床表现及预后不尽相同。因此结缔组织相关间质性肺疾病临床表型分析显得尤为重要。目前尚无明确的CTD-ILD诊断标准,本研究主要通过分析CTD-ILD不同表型临床表现、辅助检查以及危险因素,旨在对诊疗提供参考。方法:1.收集2009年-2020年初次诊断为结缔组织病患者的一般情况、临床表现以及实验室检查。2.对结缔组织病依据有无合并间质肺分为合并间质肺组和未合并间质肺组。3.分别比较不同结缔组织疾病合并间质肺和未合并间质肺的一般情况、临床表现以及实验室检查。4.应用Logistic二元回归分析不同结缔组织疾病发生间质性肺炎的危险因素。结果:1.干燥综合征合并间质肺组平均年龄大于未合并间质肺组((49)<0.05)。首发症状中,合并间质肺组呼吸系统症状较未合并间质肺组多见((49)<0.05)。干燥综合征合并间质肺胸部CT/HRCT以斑片影多见。实验室检查中,合并间质肺组白细胞计数、乳酸脱氢酶、甘油三酯较未合并间质肺组水平高((49)<0.05),高密度脂蛋白较未合并间质肺组水平低((49)<0.05)。合并间质肺组核糖体U1RNP抗体、抗线粒体M2抗体干燥综合征合并间质肺组阳性例数较干燥综合征未合并间质肺低((49)<0.05),JO-1抗体阳性例数较未合并间质肺组高((49)<0.05)。老年(年龄≥60岁)(OR=5.541,95%CI:1.409-21.797)、HDL降低(OR=8.192,95%CI:1.065-63.004)者为干燥综合征发生间质肺的危险因素。2.肌炎/皮肌炎患者合并间质性肺疾病组发病年龄高于未合并间质性肺疾病组发病年龄((49)<0.05)。在首发症状中,合并间质性肺组和未合并间质肺组均以皮疹多见((49)<0.05);合并间质肺组呼吸系统症状较未合并间质肺组多见((49)<0.05),肌无力18例(46.7%)、皮疹26例(66.7%)比未合并间质肺组少见((49)<0.05)。肌炎/皮肌炎合并间质肺胸部HRCT/CT以斑片影(29例40.8%)最多见。实验室检查中,合并间质肺组C-反应蛋白、谷氨酰转肽酶、血清球蛋白、Ig M较未合并间质肺组高((49)<0.05),血清白蛋白较未合并间质肺组水平低((49)<0.05)。自身免疫性抗体中,合并间质肺组和未合并间质肺组均以52KD蛋白阳性最常见((49)<0.05)。CRP(OR=1.187,95%CI:1.052-1.338)升高为肌炎/皮肌炎发生间质性肺炎的独立危险因素。3.类风湿性关节炎患者合并间质性肺疾病组发病年龄高于未合并间质性肺疾病组发病年龄((49)<0.05)。在首发症状中,合并间质性肺组和未合并间质肺组均以关节疼痛多见((49)<0.05);合并间质肺组呼吸困难、全身乏力、咳嗽、咳痰、浮肿、发热较未合并间质肺组多见((49)<0.05),晨僵比未合并间质肺组少见((49)<0.05)。胸部HRCT/CT显示类风湿性关节炎合并间质性肺肺部改变以斑片影最多见。类风湿性关节炎合并间质肺组白细胞、LDH、肌钙蛋白、PCT、λ轻链、C4、CA50、细胞角蛋白19片段、抗O、CA125、鳞状上皮SSc均较类风湿性关节炎未合并间质肺组高((49)<0.05),血清总蛋白、白蛋白、白球比、类风湿因子较类风湿性关节炎未合并间质肺组低((49)<0.05)。合并间质肺组和未合并间质肺组均以52KD蛋白阳性最常见((49)>0.05);合并间质肺组干燥综合征SSA抗体、组蛋白抗体较未合并间质肺组阳性率高((49)<0.05),史密斯抗体、抗线粒体M2抗体、核糖体P蛋白抗体、抗增殖性细胞核抗体较未合并间质肺组阳性率低((49)<0.05)。抗O(OR=1.070,95%CI:1.002-1.142)水平增高、细胞角蛋白19片段(OR=21947.218,95%CI:6.139-78461528.392)水平增高为类风湿性关节炎发生间质性肺炎的危险因素。4.系统性红斑狼疮合并间质性肺组平均年龄高于未合并间质肺组((49)>0.05)。首发症状中,合并间质肺组以关节疼痛多见(P<0.05),未合并间质肺组以皮疹多见((49)<0.05)。合并间质肺组关节疼痛、咳嗽、咳痰、呼吸困难较未合并间质肺组多见((49)<0.05),皮疹、浮肿比未合并间质肺组少见((49)<0.05)。胸部HRCT/CT显示以斑片影(52例92.9%)最多见。实验室检查,合并间质肺组血红蛋白、球蛋白、CEA、HCT、CRP、AFP、CA153、神经元特异性烯醇化酶、β2微球蛋白较未合并间质肺组高((49)<0.05),LDL、ALB、HDL、Ig A较系统性红斑狼疮未合并间质肺组低((49)<0.05)。自身免疫性抗体中,合并间质肺组JO-1抗体、抗双链DNA抗体较未合并间质肺组阳性率低((49)<0.05)。高GP、高CRP、低ALB、高CA153、高β2微球蛋白为发生间质性肺炎的危险因素。5.系统性硬化症合并间质肺组和未合并间质肺组发病年龄比较两组无统计学差异。首发症状中,合并间质肺组发热、雷诺现象、关节肿胀、疼痛较未合并间质肺组多见((49)<0.05),皮疹、皮肤硬化比合并间质肺组少见((49)<0.05)。胸部HRCT/CT显示系统性硬化症合并间质肺以斑片影、囊状影最多见。合并间质肺组淋巴细胞计数较系统性硬化症未合并间质肺组高((49)<0.05),血清总蛋白、血清白蛋白较系统性硬化症未合并间质肺组低((49)<0.05)。自身免疫性抗体中,合并间质肺组和未合并间质肺组均以硬皮病70抗体阳性最常见((49)>0.05)。结论:1.不同类型CTD患者,合并间质肺时其临床表现、实验室检查及影像学表现有差异。2.同一类型CTD患者,合并间质肺组与未合并间质肺组临床表现、实验室等辅助检查有差异。3.不同CTD患者发生ILD危险因素不同。老年(年龄≥60岁)、HDL降低是干燥综合征患者发生间质性肺炎的危险因素。高CRP水平为肌炎/皮肌炎患者发生间质性肺炎的独立危险因素。高GP、高CRP、低ALB、高CA153、高β2微球蛋白为系统性红斑狼疮患者发生间质性肺炎的危险因素。高抗O水平、高细胞角蛋白19片段水平为类风湿性关节炎患者发生间质性肺炎的危险因素。更多还原

【Abstract】 Objective:Connective tissue disease(CTD)includes: Systemic lupus erythematosus(SLE),Rheumatoid arthritis(RA),Systemic sclerosis(SSc),Sjogren ’s syndrome(SS),Polymyositis/Dermatomyositis(PM/DM),etc.Although different types of connective tissue diseases can cause Interstitial pulmonary disease(ILD),However,the imaging features,clinical manifestations and prognosis of different types of Connective tissue disease-interstitial pulmonary disease(CTD-ILD)are different.Therefore,the clinical phenotypic analysis of connective tissue associated interstitial pulmonary disease is particularly important.At present,there is no clear diagnostic criteria for CTD-ILD.This study aims to provide reference for diagnosis and treatment by analyzing different clinical manifestations of CTD-ILD phenotypes,auxiliary examinations and risk factors.Methods:1.General information,clinical manifestations and laboratory tests of patients first diagnosed with connective tissue disease from 2009 to 2020 were collected.2.According to the presence or absence of interstitial lung,the patients weredivided into two groups: group with interstitial lung and group withoutinterstitial lung.3.The general conditions,clinical manifestations and laboratory examinationsof different connective tissue diseases with interstitial lung and withoutinterstitial lung were compared.4.Logistic binary regression was used to analyze the risk factors of interstitial pneumonia in different connective tissue diseases.Results:1.The mean age of SS group with interstitial lung was higher than that of the group without interstitial lung((49)<0.05).In the first symptoms,respiratory symptoms were more common in the group with interstitial lung than in the group without interstitial lung((49)<0.05).Chest CT/HRCT of interstitial lung in Sjogren’s syndrome was mostly patchy.In laboratory tests,the levels of white blood cell count,lactate dehydrogenase and triglyceride in the patients with interstitial lung were higher than those in the patients without interstitial lung((49)<0.05),and the levels of high-density lipoprotein were lower than those in the patients without interstitial lung((49)<0.05).The number of positive cases of ribosomal U1 RNP antibody and anti-mitochondrial M2 antibody in Sjogren’s syndrome combined with interstitial lung group was lower than that in Sjogren’s syndrome combined with interstitial lung group((49)<0.05),and the number of positive cases of JO-1 antibody was higher than that in the uncombined interstitial lung group((49)<0.05).Old age(≥60 years old)(OR=5.541,95%CI: 1.409-21.797)and reduced HDL(OR=8.192,95%CI:1.065-63.004)were risk factors for the development of interstitial lung in Sjogren’s syndrome.2.The age of onset of PM/DM patients with interstitial pulmonary disease group was higher than that of the group without interstitial pulmonary disease((49)<0.05).In the first symptoms,rash was more common in both the patients with interstitial lung and those without interstitial lung((49)<0.05).Compared with the group without interstitial lung,respiratory symptoms were more common in the group with interstitial lung((49)<0.05),muscle weakness was less common in 18 cases(46.7%)and rash was less common in 26 cases(66.7%)than in the group without interstitial lung((49)<0.05).Myositis/Dermatomyositis combined with interstitial lung chest HRCT/CT was most common in patches(29 cases,40.8%).In laboratory tests,C-reactive protein,glutamyltranspeptidase,serum globulin and Ig M were higher in patients with interstitial lung than those without interstitial lung((49)<0.05),and serum albumin levels were lower in patients with interstitial lung than those without interstitial lung((49)<0.05).Among the autoimmune antibodies,52 k D protein positive was the most common in both the interstitial lung group and the uninterstitial lung group((49)<0.05).Elevated CRP(OR=1.187,95%CI: 1.052-1.338)was an independent risk factor for myositis/dermatomyositis with interstitial pneumonia.3.The age of onset of RA patients with interstitial pulmonary disease was higher than that of the group without interstitial pulmonary disease((49)<0.05).In the first symptoms,joint pain was more common in the patients with interstitial lung and those without interstitial lung((49)<0.05).Dyspnea,general fatigue,cough,sputum,edema and fever were more common in the group with interstitial lung than in the group without interstitial lung((49)<0.05),and morning stiffness was less common than in the group without interstitial lung((49)<0.05).Chest HRCT/CT demonstrates rheumatoid arthritis with interstitial pulmonary changes with patchy lesions predominating.WBC,LDH,tropoprotein,PCT,λ light chain,C4,CA50,cytokeratin19 fragment,anti-O,CA125,squamous SSC in rheumatoid arthritis with interstitial lung group were higher than those in rheumatoid arthritis without interstitial lung group((49)<0.05).Serum total protein,albumin,white bulb ratio and rheumatoid factor were lower than those in rheumatoid arthritis group without interstitial lung((49)<0.05).52 k D protein positive was the most common in patients with and without interstitial lung((49)>0.05).The positive rates of SSA antibody and hiprotein antibody in patients with Sjogren’s syndrome were higher in patients with interstitial lung than those without interstitial lung((49)<0.05),while the positive rates of Smith antibody,anti-mitochondrial M2 antibody,ribosomal P protein antibody and anti-proliferative nuclear antibody were lower in patients with interstitial lung than those without interstitial lung((49)<0.05).Increased levels of anti-O(OR=1.070,95%CI: 1.002-1.142)and cytokeratin 19 fragment(OR=21947.218,95%CI:6.139-78461528.392)were risk factors for interstitial pneumonia in rheumatoid arthritis.4.The mean age of SLE with interstitial lung was higher than that of the group without interstitial lung((49)>0.05).Among the first symptoms,joint pain was more common in the group with interstitial lung((49)<0.05),and rash was more common in the group without interstitial lung((49)<0.05).Arthritis pain,cough,expectoration and dyspnea were more common in the group with interstitial lung than in the group without interstitial lung((49)<0.05),and rash and edema were less common in the group with interstitial lung than in the group without interstitial lung((49)<0.05).Chest HRCT/CT showed patchy opacities(92.9% of 52 cases).Laboratory examination showed that the hemoglobin,albumin,CEA,HCT,CRP,AFP,CA153,neuron-specific enolase,hospitalization times and β2 microglobulin were higher in the group with interstitial lung than in the group without interstitial lung((49)<0.05).LDL,ALB,HDL and Ig A were lower than those in SLE group without interstitial lung((49)<0.05).Among autoimmune antibodies,the positive rates of JO-1 antibody and anti-double-stranded DNA antibody in the combined interstitial lung group were lower than those in the uncombined interstitial lung group((49)<0.05).High GP,high CRP,low ALB,,high CA153 and high β2 microglobulin were the risk factors of interstitial pneumonia.5.There was no significant difference in the age of onset between the patients with SSc complicated with interstitial lung and those without.Among the first symptoms,fever,Raynold’s phenomenon,joint swelling and pain were more common in the group with interstitial lung than in the group without interstitial lung((49)<0.05),while rash and sclerosis of the skin were less common in the group with interstitial lung than in the group without interstitial lung((49)<0.05).Chest HRCT/CT showed systemic sclerosis with interstitial lung with patchy and cystic shadows most frequently.The lymphocyte count in patients with interstitial lung was higher than that in patients with systemic sclerosis without interstitial lung((49)<0.05),and the serum total protein and serum albumin were lower than those in patients with systemic sclerosis without interstitial lung((49)<0.05).Among the autoimmune antibodies,scleroderma 70 antibody positive was the most common in patients with and without interstitial lung((49)>0.05).Conclusion:1.Patients with different types of CTD combined with interstitial lung have different clinical manifestations,laboratory examination and imaging manifestations.2.In patients with the same type of CTD,there were differences in clinical manifestations,laboratory examinations and other auxiliary examinations between the patients with interstitial lung and those without interstitial lung.3.Risk factors of ILD are different in patients with different CTD.Older age(≥60years old)and reduced HDL are risk factors for interstitial pneumonia in patients with Sjogren’s syndrome.High CRP level is an independent risk factor for interstitial pneumonia in patients with myositis/dermatomyositis.High GP,high CRP,low ALB,high CA153 and high β2 microglobulin are the risk factors of interstitial pneumonia in SLE patients.High levels of anti-O and cytokeratin 19 fragments are risk factors for interstitial pneumonia in patients with rheumatoid arthritis.更多还原