类风湿关节炎合并肺间质病变的临床特点

目的 分析类风湿关节炎（RA）合并肺间质纤维化（ILD）患者的临床特点,为尽早发现和诊断RA-ILD提供有价值的临床信息.方法 回顾性分析2008年1月～2009年1月于我院就诊的40例RA-ILD患者与42例未合并ILD的RA患者的临床资料,并对两组患者的临床资料加以比较.结果 RA-ILD组患者多数以咳嗽为首发症状,全部患者高分辨率CT检查均存在不同程度的ILD表现.RA-ILD组患者的病程、晨僵时间长于未合并ILD的RA组患者（P＜0.05）.RA-ILD患者组的DAS28评分、血沉、C反应蛋白、抗环瓜氨酸（CCP）抗体、Ro-52阳性率高于未合并ILD的RA组患者（P均＜0.05）.结论 RA-ILD患者多数以咳嗽为首发症状,高分辨率CT能较早的提示ILD并评价其严重程度.RA病程、活动性、炎性指标、抗CCP抗体及抗Ro-52可能是与RA-ILD密切相关的重要指标.     

Changing patterns of pulmonary abnormalities in rheumatoid arthritis

BackgroundAs a first step in identifying the developmental pathways of pulmonary abnormalities in rheumatoid arthritis (RA), we sought to determine the existing and changing patterns of pulmonary abnormalities.MethodsWe conducted a retrospective cohort study of consecutive patients with RA who underwent high-resolution computed tomography before and during biologic therapy. The presence of 20 pulmonary abnormalities and the changes in those abnormalities were recorded. Patterns of pre-existing and changing abnormalities were examined via cluster analysis, and their relationship was also assessed using the Kaplan–Meier method and log-rank test.ResultsA total of 208 subjects were included. Pulmonary abnormalities were observed in 70% of patients: 39% had interstitial lung disease, and 55% had airway disease (AD). Several different pulmonary abnormalities were commonly found to co-exist in several patterns in the same patient. In most patients with pulmonary abnormalities, AD was present alone or in combination with other abnormalities. During the observation period (mean 3.2 years), 172 pulmonary abnormalities had changed in 91 patients: 115 pulmonary abnormalities newly emerged, whereas 42 worsened and 25 demonstrated improvement. Pulmonary abnormalities changed in several patterns. Correlations were observed between pre-existing and new/worsening abnormalities at individual and regional levels, such as new ground-glass opacity (GGO) and pre-existing AD, small nodular patterns, and honeycombing. AD was a possible initial abnormality.ConclusionsPulmonary abnormalities occurred and changed in several patterns, which suggests the existence of developmental pathways of pulmonary abnormalities. AD may play an important role in the development of these abnormalities, including GGO.     

类风湿关节炎相关性间质性肺疾病的研究进展

类风湿关节炎相关性间质性肺疾病发病率高,是类风湿关节炎患者的主要死因之一.其发病机制尚不明确,病史不清,以慢性咳嗽和缓慢进展的呼吸困难为主要症状,肺功能显示限制性通气功能障碍,影像学改变以磨玻璃样阴影、网格状阴影、蜂窝肺最为常见,支气管肺泡灌洗提示存在肺泡炎,病理类型以普通型间质性肺炎最为多见,激素治疗效果差,预后不佳...     

类风湿关节炎相关间质性肺疾病的早期诊断及药物治疗进展

间质性肺疾病是类风湿关节炎患者最常见关节外表现,病死率高.类风湿关节炎相关间质性肺疾病的病因及治疗效果尚不明确.本文就其早期诊断与药物治疗作一综述,以期改善其预后.     

Pulmonary involvement in rheumatoid arthritis

The primary objective of this investigation was to assess the relationships between clinical characteristics, lung involvement, and frequency of pulmonary involvement in rheumatoid arthritis (RA). Using high-resolution computed tomography (HRCT) and pulmonary function tests (PFT), we prospectively evaluated 52 patients with RA (eight males and 44 females, mean age 53.6 years). The HRCT was abnormal in 35 patients (67.3%), the most frequent abnormalities being reticulonodular patterns, which were found in 22 patients (62.9%), ground-glass attenuation (20%), and bronchiectasis (17%). In this group of patients, PFT results were normal in 13 patients (37%). Titers of rheumatoid factor and erythrocyte sedimentation rate were significantly higher in abnormal HRCT presence. Higher Larsens score, advanced age, and severe disease were significant risk factors for lung involvement (p<0.001, p<0.01, and p<0.01, respectively) and are suggested by our data to be statistically significant predictors of lung involvement in RA.     

Interstitial lung disease in rheumatoid arthritis: Current concepts in pathogenesis,diagnosis and therapeutics

Rheumatoid arthritis (RA) is the most common chronic autoimmune inflammatory joint disease. RA-associated interstitial lung disease (RA-ILD) is a major extra-articular complication and causes symptoms that lead to a deterioration in the quality of life, high utilization of health resources, and an increased risk of earlier mortality. Early in the course of RA-ILD, symptoms are highly variable, making the diagnosis difficult. Therefore, a rational diagnostic strategy that combines an adequate clinical assessment with the appropriate use of clinical tests, including pulmonary function tests and high-resolution computed tomography, should be used. In special cases, lung biopsy or bronchioalveolar lavage should be performed to achieve an early diagnosis. Several distinct histopathological subtypes of RA-ILD are currently recognized. These subtypes also have different clinical presentations, which vary in therapeutic response and prognosis. This article reviews current evidence about the epidemiology of RA-ILD and discusses the varying prevalence rates observed in different studies. Additionally, aspects of RA-ILD pathogenesis, including the role of cytokines and other molecules such as autoantibodies, as well as the evidence linking several drugs used to treat RA with lung damage will be discussed. Some aspects of the clinical characteristics of RA-ILD are noted, and diagnostic strategies are reviewed. Finally, this article analyzes current treatments for RA-ILD, including immunosuppressive therapies and biologic agents, as well as other therapeutic modalities. The prognosis of this severe complication of RA is discussed. Additionally, this paper examines updated evidence from studies identifying an association between drugs used for the treatment of RA and the development of ILD.     

Relationship among the HLA–DRB1 shared epitope,smoking, and rheumatoid factor production in rheumatoid arthritis

Objective

Rheumatoid factor (RF) production in rheumatoid arthritis (RA) is generally associated with more severe disease. In some studies, RF production has been associated with carriage of HLA–DRB1 alleles encoding the RA‐associated shared epitope (SE). Patients who smoke are also more likely to be RF positive. In this study, we investigated whether the association between RF production and smoking was influenced by carriage of the SE.

Methods

The smoking histories of 371 RA patients attending a hospital clinic were recorded. RF levels and SE status were determined for every patient, and the associations between the SE, smoking, and RF production were examined. HLA–DRB1 typing was performed using polymerase chain reaction. Results were analyzed using chi‐square tests and logistic regression analysis.

Results

Patients who had ever smoked were significantly more likely to be RF positive than nonsmokers (odds ratio 2.2, P < 0.0001). This remained significant (P = 0.003) after correction for age, sex, and disease duration in a logistic regression model. An association was also found between RF positivity and carriage of the SE (P = 0.03, after correction for age, sex, and disease duration), but significance was reduced or lost after correction for previous or current smoking (P = 0.05 and 0.09, respectively). Examination of the major SE phenotypes in this RA population by multivariate logistic regression analysis revealed that only DRB1*0401 was associated with RF positivity, and that this was independent of the influence of smoking.

Conclusion

Our data confirm that RF production in RA patients is associated with smoking. This does not appear to depend on an HLA–DR‐restricted immune response. The association of the SE with RF positivity is primarily due to HLA–DRB1*0401. This appears to be independent of the association with smoking, although smoking further increases the likelihood of RF production in DRB1*0401 patients.

     

类风湿关节炎合并间质性肺病及血清表面活性蛋白研究进展

类风湿关节炎合并间质性肺病发病率、病死率高,早期易误诊、漏诊,尤其后期出现肺间质纤维化,临床治疗很困难.近年来,血清表面活性蛋白在间质性肺病研究较多.本文基于对类风湿关节炎合并间质性肺病的诊断和治疗进展方面的现代认识及血清表面活性蛋白在间质性肺病的研究进展进行综述,为该疾病早期诊断和治疗效果观察提供新的方法和手段.     

类风湿关节炎相关性间质性肺疾病的临床研究

目的 探讨类风湿关节炎相关性间质性肺疾病(rheumatoid arthritis-associated interstitial lung disease,RA-ILD)的临床特点和相关因素.方法 回顾性分析我院2009年住院的135例RA病例.以患者首次出现RA症状为研究起点,以肺高分辨率CT检查发现ILD为研究终点.研究因素包括:性别、年龄、病程、临床表现(包括关节炎、类风湿结节、发热、口干及眼干、雷诺现象、皮疹等)、生化指标、免疫指标、治疗措施等40个变量.经后退法建立Logestic回归分析模型,计算OR值及95%CI.结果 ①135例RA患者中48例发生ILD,占35.6%.其中40例(83.3%)诊断RA平均(85±75)个月后确诊合并ILD;其中29例(60.4%)在检出ILD时无呼吸系统症状.②单因素分析显示RA-ILD组年龄、病程、咳嗽、呼吸困难、Velcro音、类风湿因子(rheumatoid factor,RF)、C3、γ-球蛋白高于RA无ILD组(P＜0.05或P＜0.01).③经后退法建立Logestic回归分析模型,多因素分析显示咳嗽(OR=4.387,95%CI:1.143～16.831,P＜0.05)、Velcro音(OR=6.727,95%CI:2.220～20.378,P ＜0.01)、RF(OR=3.522,95%CI:1.304～9.512,P ＜0.05)是RA-ILD的危险因素.④多因素分析发现的3个危险因素中,RF预测RA-ILD的敏感性最高(79.2%),咳嗽的阳性预测值最高(73.3%).结论 大多数患者RA的诊断先于ILD.部分RA患者的肺问质病变为亚临床型.咳嗽、Velcro音及RF阳性是RA患者发生肺间质病变的相关因素,当患者出现以上症状、体征或实验室检查异常时应该高度警惕发生肺间质病变可能,及时完善相关检查,给予合理治疗,改善预后.

Abstract：

Objective To analyse the clinical feature and risk factors of rheumatoid arthritisassociated interstitial lung disease (RA-ILD). Methods The data of 135 patients with rheumatoid arthritis (RA) hospitalized in the hospital in 2009 were retrospectively analyzed. The study factors included gender, age, disease duration, clinical manifestations (including arthritis, rheumatoid nodules, fever, dry mouth and dry eyes, Raynaud's phenomenon, skin rash), biochemical and immunological indexes, and treatment measures. The date were analyzed with Logistic regression analysis. Results In 135 RA patients, 48 cases (35.6%) had interstitial lung disease (ILD), in which 40 cases (83.3%) were diagnosed combined ILD (85±75) months after the diagnosis of RA, and 29 cases (60.4%) had no respiratory symptoms in the detection of ILD. Univariate analysis showed that age, duration, incidence of cough, dyspnea and Velcro tone, positive rate of rheumatoid factor (RF), C3 and γ-globulin in RA-ILD group were higher than those in RA without ILD group ( P ＜0.05 or P ＜0.01). Multivariate analysis showed that cough (OR =4.387,95%CI :1.143-16.831, P ＜0.05), Velcro tone (OR =6.727,95% CI :2. 220-20. 378, P ＜0.01),and RF ( OR =3. 522,95% CI :1. 304-9. 512, P ＜0.05) were risk factors of RA-ILD. Multivariate analysis identified that the sensitivity of RF was highest (79.2%), and the positive predictive value of cough was highest (73.3%) in three risk factors. Conclusions RA is diagnosed before ILD in most of patients. The interstitial pulmonary damages of some RA patients are subclinical. Cough,Velcro tone and RF are interrelated factors of interstitial pulmonary damages in RA patients. When patients have these symptoms, signs or abnormal laboratory examination, interstitial lung disease should be highly alerted, the relevant checks should be consummated in time, and rational treatment should be carried out to improve prognosis.     

Nodular pulmonary amyloidosis in a patient with rheumatoid arthritis

We describe a 67-year-old white woman with a long-standing active rheumatoid arthritis who refused treatment. Chest roentgenograms performed in 2000 revealed a pulmonary nodule in the mid-left lung. Progression of the nodule was followed annually by computerized tomography (CT). In the last CT in 2002, we observed multiple nodules in both lungs in the absence of lymph gland involvement. The patient was operated by videothoracoscopy to resect one of the pulmonary nodules. Pathological examination of the excised tissue revealed amyloid A-type (AA) amyloidosis. Although pulmonary amyloidosis is rare in patients with systemic AA amyloidosis, we recommend that this possibility be considered when confronted with a patient with these characteristics.     

Interstitial lung disease in Egyptian patients with rheumatoid arthritis: Frequency,pattern and correlation with clinical manifestations and anti-citrullinated peptide antibodies level

Introduction

Interstitial lung disease (ILD) represents 13% of the overall mortality in rheumatoid arthritis (RA) patients.

High-resolution CT and pulmonary function tests in rheumatoid arthritis patients with subclinical interstitial lung disease in Kuwait

BackgroundInterstitial lung disease (ILD) is a frequent extra-articular manifestation of RA and can cause significant morbidity and mortality.Aim of the workTo characterize and define the frequency of radiological and functional abnormalities capable of identifying “subclinical” RA-ILD with particular concern to the effect of methotrexate (MTX) therapy.Patients and methodsSixty patients with RA were recruited with no respiratory manifestations. They were classified into two groups: group 1 included 35 patients receiving MTX and group 2 included 25 patients receiving only nonsteroidal anti-inflammatory drugs. Patients were also classified according to chest high resolution CT (HRCT) as RA-ILD or RA-noILD. Pulmonary function test (PFT) abnormalities were also used to further characterize occult respiratory defects.Results38.3% of RA patients had subclinical ILD (25% in group 1 and 13.3% in group 2), while 61.7% were RA-no ILD. The percentage of patients with RA-ILD was insignificantly more in group 1 than group 2 (42.9% and 32% respectively). HRCT score revealed minimal to mild involvement in both groups. Long-standing RA with mean articular duration >50 months carries a significant risk for ILD. Other variables as age, gender, smoking, disease activity or rheumatoid factor seropositivity were not significant risk factors for development of RA-ILD.ConclusionsLung involvement should always be considered in patients with RA particularly those on MTX therapy even in the absence of chest symptoms. A tight control by PFTs, chest radiography and/or HRCT is necessary. Further studies evaluating the potential effect of MTX on progressive ILD with RA are needed.     

吸烟相关性肺朗格汉斯细胞组织细胞增生症病例报告和文献复习

目的 观察吸烟相关性肺朗格汉斯细胞组织细胞增生症(pulmonary Langerhans cell histiocytosis,PLCH)病理学、免疫组织化学特征及其影像学的动态变化.并复习有关PLCH的诊治进展.方法 1例经开胸肺组织活检、免疫组织化学和高分辨率CT(HRCT)证实的吸烟相关性PLCH患者,动态观察戒烟1年后肺HRCT影像学改变.结果 患者有吸烟史(吸烟指数200),确诊后经戒烟1年后肺HRCT显示结节性和囊性病变完全消失.结论 吸烟是本例PLCH患者发病主要原因,戒烟是治疗吸烟相关性PLCH的主要方法.     

Tacrolimus-induced lung injury in a rheumatoid arthritis patient with interstitial pneumonitis

Abstract

A 74-year-old woman was experiencing rheumatoid arthritis complicated with interstitial pneumonitis (IP), and tacrolimus treatment was started. She presented with dyspnea. Chest X-ray and computed tomography (CT) showed ground-glass opacity and IP. Although tacrolimus was stopped, she died of respiratory failure. At autopsy, both the upper and lower lung fields showed usual IP and the organizing stage of diffuse alveolar damage. The former is common, but the latter is uncommon, suggesting tacrolimus may cause severe alveolar damage.     

Tacrolimus-induced lung injury in a rheumatoid arthritis patient with interstitial pneumonitis

A 74-year-old woman was experiencing rheumatoid arthritis complicated with interstitial pneumonitis (IP), and tacrolimus treatment was started. She presented with dyspnea. Chest X-ray and computed tomography (CT) showed ground-glass opacity and IP. Although tacrolimus was stopped, she died of respiratory failure. At autopsy, both the upper and lower lung fields showed usual IP and the organizing stage of diffuse alveolar damage. The former is common, but the latter is uncommon, suggesting tacrolimus may cause severe alveolar damage.     

Efficacy of intensive immunosuppression in exacerbated rheumatoid arthritis-associated interstitial lung disease

Objectives: Acute or subacute exacerbations are recognized as a severe complication of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Nevertheless, the role of intensive immunosuppression in RA-ILD remains elusive. We attempted to evaluate the clinical characteristics and efficacy of immunosuppressive treatment in exacerbated RA-ILD.

Methods: Clinical data, including respiratory function, imaging, treatment, and prognosis, were retrospectively collected for 17 patients with RA-ILD who required hospitalization at the University of Tokyo Hospital due to an acute exacerbation (12 patients) or subacute exacerbation (5 patients).

Results: Patients with RA-ILD demonstrated a significantly higher titers of anticyclic citrullinated peptide antibodies compared with RA patients in Japanese Ninja registry, suggesting the role of adaptive immunity. Immunosuppressive treatment suppressed the deterioration of pulmonary functions with improved ground grass opacity and consolidation. In particular, in patients with less fibrosis on computed tomography (CT) images showed a better response to treatment. Although five patients treated with combination therapy, including cyclophosphamide, showed a severely decreased lung volume, these intensive therapies provided a good prognosis without fatalities for the average observation period of 474 days.

Conclusions: Immunosuppressive therapy is effective for exacerbations of RA-ILD. For severe cases with low respiratory function, intensive therapy, including cyclophosphamide, has a potential to improve the prognosis.     

类风湿关节炎相关间质性肺疾病的临床研究

目的研究类风湿关节炎相关间质性肺疾病（RA-ILD）的临床特点。方法选取136例行胸部CT扫描的类风湿关节炎（RA）患者,回顾性分析其临床及辅助检查资料。结果①符合RA-ILD的患者60例（44.1%）;RA-ILD组年龄平均为（63.17±10.20）岁,RA病程〉20年、有吸烟史、药物过敏史的患者构成比[（11/18.3%）,（14/23.3%）,（11/18.3%）]均高于单纯RA组[（58.25±10.22）岁和（5/6.6%）,（7/9.2%）,（2/2.6%）]（P〈0.05）。受累和畸形关节数[（12.22±3.44）,（2.77±2.40）个]显著多于单纯RA组[（10.04±3.1）,（1.09±1.81）个]（P〈0.01）,双手腕关节X线平片分期[（2.87±0.78）期]和血清抗环瓜氨酸肽（CCP）抗体水平[（503.75±341.93）RU/ml]均高于单纯RA组[（2.53±0.65）,（373.74±405.02）RU/ml]（P〈0.05）;两组性别比、RA病情活动性及类风湿因子（RF）水平无明显差异。②RA-ILD患者主要表现为咳嗽（34/56.7%）和进行性胸闷（25/41.7%）,其中20例（33.3%）无呼吸系统表现。③网格状影（35/60,58.3%）是RA-ILD最常见的胸部CT表现,其次为磨玻璃影（27/60,45.0%）、纤维索条影（24/60,40.0%）;胸部X线平片诊断RA-ILD的误诊率和漏诊率分别为24.7%（18/73）和21.8%（12/55）。结论①RA常累及肺引起ILD;RA发生ILD与年龄、RA病程〉20年、吸烟史、药物过敏史、RA病情严重度及抗CCP抗体有关;②无呼吸系统表现的RA-ILD患者比例较高,网格状影、磨玻璃影和纤维索条影是常见的胸部CT表现。     

Anti-CCP antibodies in rheumatoid arthritis and psoriatic arthritis

Our aim is to assess the prevalence and associated clinical features of anti-CCP (cyclic citrullinated peptide) antibodies for RF (rheumatoid factor)-positive and RF-negative rheumatoid arthritis (RA) and psoriatic arthritis (PsA). In a prospective, cross-sectional, multi-centre study, we determined the titres of anti-CCP antibodies in 208 RA patients (129 RF-positive, 79 RF-negative), 56 PsA patients and 39 healthy controls (HC). Clinical parameters including disease activity (disease activity score 28-DAS28), physical disability (health assessment questionnaire-HAQ), functional capacity (functional class) and radiological erosions were investigated in patients with RA. In PsA patients, clinical and radiological features were determined. Anti-CCP2 antibodies were measured using a second-generation anti-CCP enzyme-linked immunosorbent assay (Euro-Diagnostica, Netherlands). One-hundred four of 129 RF-positive RA (81%), 16 of 79 RF-negative RA (20%), seven of 56 PsA patients (12.5%) and none of the HC had anti-CCP antibodies. RA patients with anti-CCP antibodies had significantly higher disease activity, greater loss of function and more frequent erosive disease than anti-CCP antibody-negative group. In subgroup analysis, anti-CCP antibodies in RF-negative patients were also associated with erosive disease. All PsA patients with anti-CCP antibodies had symmetric arthritis with higher number of swollen joints. The prevalence of anti-CCP antibodies in RF-positive RA patients was significantly higher than in RF-negative RA and PsA patients. Anti-CCP antibodies were also associated with erosive disease in RF-negative RA patients. Both anti-CCP and RF tests were negative in 30% of the patients. Anti-CCP positivity was a frequent finding in PsA and associated with symmetrical polyarthritis.