Lung-dominant connective tissue disease among patients with interstitial lung disease: prevalence,functional stability,and common extrathoracic features

OBJECTIVE:

To describe the characteristics of a cohort of patients with lung-dominant connective tissue disease (LD-CTD).

METHODS:

This was a retrospective study of patients with interstitial lung disease (ILD), positive antinuclear antibody (ANA) results (≥ 1/320), with or without specific autoantibodies, and at least one clinical feature suggestive of connective tissue disease (CTD).

RESULTS:

Of the 1,998 patients screened, 52 initially met the criteria for a diagnosis of LD-CTD: 37% were male; the mean age at diagnosis was 56 years; and the median follow-up period was 48 months. During follow-up, 8 patients met the criteria for a definitive diagnosis of a CTD. The remaining 44 patients comprised the LD-CTD group, in which the most prevalent extrathoracic features were arthralgia, gastroesophageal reflux disease, and Raynaud''s phenomenon. The most prevalent autoantibodies in this group were ANA (89%) and anti-SSA (anti-Ro, 27%). The mean baseline and final FVC was 69.5% and 74.0% of the predicted values, respectively (p > 0.05). Nonspecific interstitial pneumonia and usual interstitial pneumonia patterns were found in 45% and 9% of HRCT scans, respectively; 36% of the scans were unclassifiable. A similar prevalence was noted in histological samples. Diffuse esophageal dilatation was identified in 52% of HRCT scans. Nailfold capillaroscopy was performed in 22 patients; 17 showed a scleroderma pattern.

CONCLUSIONS:

In our LD-CTD group, there was predominance of females and the patients showed mild spirometric abnormalities at diagnosis, with differing underlying ILD patterns that were mostly unclassifiable on HRCT and by histology. We found functional stability on follow-up. Esophageal dilatation on HRCT and scleroderma pattern on nailfold capillaroscopy were frequent findings and might come to serve as diagnostic criteria.     

不同影像学特发性间质性肺炎患者外周血细胞因子及肺功能比较研究

目的 通过对不同影像学特发性间质性肺炎(IIP)患者及正常人外周血几种细胞因子及肺功能对比研究,探讨细胞因子在IIP进展中的作用.方法 对蜂窝肺组、磨玻璃影组IIP患者及对照组外周血白介素1(IL-1)、白介索2受体(IL-2R)、IL-5、IL-6、干扰素(IFN)、肿瘤坏死因子(TNF)水平及用力肺活量(FVC)占...     

Interpretation of autoantibody positivity in interstitial lung disease and lung-dominant connective tissue disease

The initial evaluation of patients with interstitial lung disease (ILD) primarily involves a comprehensive, active search for the cause. Autoantibody assays, which can suggest the presence of a rheumatic disease, are routinely performed at various referral centers. When interstitial lung involvement is the condition that allows the definitive diagnosis of connective tissue disease and the classical criteria are met, there is little debate. However, there is still debate regarding the significance, relevance, specificity, and pathophysiological role of autoimmunity in patients with predominant pulmonary involvement and only mild symptoms or formes frustes of connective tissue disease. The purpose of this article was to review the current knowledge of autoantibody positivity and to discuss its possible interpretations in patients with ILD and without clear etiologic associations, as well as to enhance the understanding of the natural history of an allegedly new disease and to describe the possible prognostic implications. We also discuss the proposition of a new term to be used in the classification of ILDs: lung-dominant connective tissue disease.     

Rare idiopathic interstitial pneumonias: LIP and PPFE and rare histologic patterns of interstitial pneumonias: AFOP and BPIP

In the 2013 reclassification of the idiopathic interstitial pneumonias (IIPs), two rare IIPs (idiopathic lymphoid interstitial pneumonia (LIP), idiopathic pleuroparenchymal fibroelastosis (IPPFE)) and two rare histologic patterns (acute fibrinous and organizing pneumonia (AFOP), bronchiolocentric pattern of interstitial pneumonia (BPIP)) are described. All these entities are rare with small series published to date, mostly containing primary and secondary forms of disease. LIP is histologically characterized by diffuse polyclonal lymphoid cell infiltrate surrounding the airways and expanding the interstitium. Thin‐walled cysts and diffuse ground glass are considered the typical radiologic features. The clinical course is highly variable with corticosteroid responsiveness evident in approximately half of cases. IPPFE is defined histologically by coexisting upper lobe pleural and intra‐alveolar fibrosis with elastosis. Dense subpleural irregular fibrosis and consolidation are the cardinal radiologic features. A history of recurrent lower respiratory tract infection is frequent. Responses to immunomodulation have not been reported and the rate of progression appears to be highly variable. AFOP is a rare histologic pattern lying within the spectrum of acute/subacute lung injury, characterized by organizing pneumonia and intra‐alveolar fibrin deposition without hyaline membranes. BPIP is characterized histologically by fibrosis and/or inflammation confined to the alveolar interstitium around bronchovascular bundles, overlapping with peribronchial metaplasia and fibrosis in some series. Currently, AFOP and BPIP are both best viewed as histological entities rather than true clinical disorders, in the absence of characteristic associated imaging patterns and clinical features.     

A case of polymyositis complicated with interstitial pneumonitis and pneumomediastinum

Pneumomediastinum as a complication of interstitial pneumonia with leakage of air into the mediastinum or subcutaneous tissues is a rare complication of dermatomyositis (DM). Herein we report a case of pneumomediastinum complicating polymyositis (PM), which is usually associated with DM. A 61-year-old man was hospitalized in our department because of deterioration of interstitial pneumonia. Treatment with high-dose corticosteroid and cyclosporin A steadily improved his interstitial pneumonia. Two weeks later, he developed subcutaneous emphysema and chest X-ray showed pneumomediastinum. Both subcutaneous emphysema and pneumomediastinum improved gradually without any additional treatment.     

特发性肺间质纤维化与继发于结缔组织病的肺间质病的临床比较

目的　对比老年人特发性肺间质纤维化 (IPF)与继发于结缔组织病的肺间质病 (SPF)的临床表现、治疗方法与预后的异同。　方法　统计分析 5 7例IPF患者 ,与 4 0例SPF患者的临床表现、治疗方法和预后。　结果　SPF的病程比IPF短 ,分别为 8 5个月与 2 4 0个月 ;二者的住院病死率分别为 30 0 %和 2 6 3% ,均为P <0 0 5。IPF较SPF的症状和体征多见。SPF的常见病因为干燥综合征、多发性肌炎、类风湿性关节炎和系统性硬化症。多发性肌炎较早出现SPF。影像学上 ,网格状改变IPF较SPF多 ,P <0 0 1;SPF较多出现胸膜受累 ,P <0 0 5。应用糖皮质激素不能改变预后。　结论　肺间质疾病在老年人中发病率和病死率高。SPF的症状和体征不典型 ,应引起关注。干扰素的疗效有待证实。     

Health-related quality of life in a multiracial Asian interstitial lung disease cohort

BackgroundUnderstanding health-related quality of life (HRQL) in patients with interstitial lung disease (ILD) provides insight into disease burden and treatment effects on patients’ well-being. We examined HRQL in a multiracial Asian ILD cohort using the King’s brief ILD (K-BILD) and EuroQol 5-dimension-3-level (EQ5D-3L) questionnaires and their associations with several clinical variables.MethodsThis was a single-centre cross-sectional study of ILD patients in a university-affiliated tertiary public hospital in Singapore. All patients completed two self-administered HRQL questionnaires upon study entry, and their clinical information was retrieved from electronic medical records.ResultsNinety-nine patients (56% male, 75% Chinese) were included. The median (interquartile range) age was 63 (54–72) years. The most common ILD diagnosis was connective tissue disease-related ILD (n=51, 52%), followed by idiopathic pulmonary fibrosis (n=27, 27%). The mean (standard deviation) scores for the EQ5D-3L utility value, EQ5D Visual Analogue Scale (VAS) and K-BILD total were 0.806 (0.284), 75.1 (12.8) and 63.9 (14.3), respectively. A moderate correlation was found between the EQ5D-3L and K-BILD total and domain scores. The HRQL scores also correlate moderately with the modified Medical Research Council dyspnoea scale (mMRC) scores. There was a weak-to-moderate correlation between HRQL and forced vital capacity (FVC), carbon monoxide diffusing capacity (DLCO) and Charlson comorbidity index. Multiple linear regression showed a significant association of K-BILD total [beta coefficient 0.244, 95% confidence interval (CI): 0.075–0.414; P=0.005], K-BILD ‘breathlessness and activities’ (beta coefficient 0.448, 95% CI: 0.192–0.703; P=0.001), and the ‘psychological’ domain (beta coefficient 0.256, 95% CI: 0.024–0.488; P=0.031) with DLCO %pred after adjustment for age, sex, BMI, race, smoking history, comorbidities, FVC %pred and ILD diagnosis. Non-Chinese race was a predictor of better K-BILD ‘psychological’ domain (beta coefficient 8.680, 95% CI: 0.656–16.704; P=0.034) after adjustment.ConclusionsHRQL is significantly impaired in ILD patients, and low DLCO is a strong predictor of this impairment     

Idiopathic interstitial pneumonias with connective tissue diseases features: A review

A systematic approach is recommended to search for clinical and biological features of connective tissue disease (CTD) in any patient with interstitial lung disease (ILD). In the diagnostic approach to ILD, a diagnosis of CTD should be considered particularly in women and subjects younger than 50 years, and in those with an imaging and/or pathological pattern of non‐specific interstitial pneumonia. However, the diagnosis of CTD may be difficult when ILD is the presenting or the dominant manifestation of CTD. A proportion of patients with ILD present symptoms that belong to the spectrum of CTD and/or biological autoimmune features, but do not fulfil diagnostic criteria for a given CTD. Some imaging and histopathological patterns may also suggest the presence of an underlying CTD. Although studies published to date used heterogeneous definitions and terminology for this condition, evidence is accumulating that even limited CTD features are relevant regarding symptoms, imaging features, pathological pattern and possibly evolution to overt CTD, whereas the impact on prognosis needs confirmation. Conversely, autoantibodies alone do not seem to impact the prognosis or management in patients with otherwise typical idiopathic pulmonary fibrosis and no extra‐pulmonary manifestation. A collective international multidisciplinary effort has proposed a uniform definition and criteria for ‘interstitial pneumonia with autoimmune features’, a condition characterized by limited CTD features occurring in the setting of ILD, with the aim of fostering future clinical studies. Referral of ILD patients suspect to have CTD to a rheumatologist and possibly multidisciplinary discussion may contribute to a better management.     

几种弥漫性结缔组织病肺间质病变的影像分析

目的了解与弥漫性结缔组织病相关的肺间质病变（CTD—ILD）的发生率、影像学特征及其与病种和临床指标的相关性。方法回顾分析我院几种弥漫性结缔组织病患者（共412例）资料，X线胸片检查或有肺部临床症状患者作胸部高分辨CT（HRCT）进一步检查确诊。了解ILD在不同弥漫性CTD中的发生率，对比X线与HRCT的差异，统计常用CT分类在本组疾病中的分布比例．探讨CT分类与不同病种或临床特征之间的关系。结果在412例弥漫性结缔组织病中，HRCT诊断的ILD共40例，总发生率为9．7％。其中皮肌炎／多肌炎为25％，硬皮病为23．8％，原发性干燥综合征为9．6％，系统性红斑狼疮为6．3％。胸片与CT符合率40％，胸片误诊漏诊率60％。ILDCT分类以两种病变共存最多见，其中毛玻璃样变占40．1％，实变影32．8％，网格影16．4％，蜂窝状影9．8％。呼吸道症状和补体C3，C4水平在毛玻璃样变组及实变影组；C反应蛋白（CRP）水平在蜂窝状影和实变影组较其他对照组明显高，它们之间差异有统计学意义（P〈0．05）。结论HRCT发现CTD—ILD的敏感性及准确性明显优于X线，其中以毛玻璃及实变影最多见；影像学改变与呼吸道症状及炎症指标有一定关系，尽早进行HRCT的检查有助ILD的早期诊断及预后判断。     

311例间质性肺疾病患者临床特点分析

目的分析总结311例间质性肺疾病(interstitial lung disease,ILD)患者临床资料,探讨间质性肺疾病临床特点。方法回顾性分析2012年7月至2014年6月收住新疆医科大学附属中医医院呼吸科间质性肺疾病患者311例,收集患者一般资料、临床诊断信息。结果 311例间质性肺疾病患者年龄在21岁至94岁,男女比例约为2∶1。311例间质性肺疾病病例中特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)所占比例最多,共116例(37.3%),其次为结缔组织病(connective tissue diseases,CTD),共77例(24.8%)。间质性肺病中年轻女性CTD更多见,年长吸烟男性IPF更多见。结论目前IPF仍是ILD中最主要病种,中年女性应注意CTD的发生,与职业相关的间质性肺疾病仍存在,ILD诊断是难点,简单无创的诊断方法是我们应该努力的方向。     

A case of dermatomyositis complicated with pneumomediastinum

We herein describe a 16-year-old boy with pneumomediastinum, pneumothorax, and subcutaneous emphysema as the initial symptoms of dermatomyositis (DM). His pneumomediastinum disappeared after strict bed rest and he was thereafter successfully treated with oral prednisolone and cyclosporine A. His condition was further complicated with mild interstitial lung disease, arrhythmia, and skin ulcers on his fingertips, right elbow, ear, and sacral region. Pneumomediastinum is a rare complication of DM and its pathogenesis remains unclear. We review the literature and discuss the possible mechanism of this disease.     

352例结缔组织病并间质性肺疾病临床特点分析

目的本研究通过比较分析结缔组织病并间质性肺疾病（connectivetissuediseaseandinterstitiallungdisease,CTD-ILD）患者的临床特点,旨在提高临床医师对CTD-ILD疾病的认识水平。方法收集并回顾性分析2011年1月1日至2012年12月31日于郑州大学第一附属医院初诊为CTD-ILD的患者的临床特征及影像学特点。结果CTD-ILD患者352例,男女发病比例为1：2．67,平均发病年龄（53．07±13．65）岁。CTD-ILD患者全身症状发生率高于呼吸系统症状。CTD-ILD的高分辨率CT表现多为对称性磨玻璃影、网格状、胸腔积液等改变,主要累及中肺和下肺。结论CTD-ILD多发生于育龄期女性,部分肺部病变首发于CTD症状之前,并可独立进展。高分辨率CT有助于ILD的早期诊断及治疗方案制定。     

特发性非特异性间质性肺炎与普通型间质性炎疾病特征和预后的比较分析

目的 与普通型间质性肺炎(usual interstitial pneumonia,UIP)进行比较分析,探讨特发性非特异性间质性肺炎(idiopathic nonspecific interstitial pneumonia,INSIP)的疾病特征和预后以及与UIP的鉴别诊断.方法 发对经电视胸腔镜或小切口开胸肺活检诊断的21例INSIP患者和18例UIP患者的临床-影像-病理学资料及疗效、预后进行比较分析.结果 INSIP多见于40～50女性,临床表现无特异性,主要表现为活动后气促、咳嗽、咯痰、双下肺可有或无吸气相爆裂音;高分辨率CT(HRCT)表现为双肺弥漫分布的磨玻璃样淡斑片状和不规则网织状阴影,部分可有蜂窝肺.INSIP的病理特征为病变进展相对一致,按病理表现可分为细胞型、纤维化型和混合型.与UIP相比,纤维母细胞灶、肌硬化、镜下蜂窝肺和肺泡结构改建的检出率在INSIP和UIP分别是19.05%和100%(P<0.001),19.05%和88.89%(P<0.05),23.81%和94.44%(P<0.01),33.33%和100%(P<0.01).两者对糖皮质激素的反应率分别为76.19%和38.89%(P<0.01),各型INSIP的预后均明显好于UIP.结论 经 INSIP的一般临床表现差异不明显,HRCT对疑难病例的鉴别诊断有帮助,明确诊断依赖肺活检病理诊断;纤维母细胞灶、伴胶原沉积的瘢痕化和蜂窝变组成不同时相的病变共同构成诊断UIP的形态特征,也是与INSIP的鉴别要点.     

高分辨率CT及积分在结缔组织病并发间质性肺炎及预后中的价值

目的 比较不同结缔组织病(CTD)并发间质性肺炎(ILD)的肺高分辨率CT(HRCT)影像学特征,探讨肺HRCT积分对判断患者预后的预测价值.方法 回顾性收集117例各类CTD 临床资料和影像学资料以及随访结果,对肺HRCT病变进行评分,研究肺HRCT积分与患者预后的关系.结果 117例CTD患者中有95例在肺HRCT上显示有ILD,其中,系统性红斑狼疮(SLE)34%,类风湿关节炎(RA)31%,多发性肌炎/皮肌炎(PM/DM)9%,成人斯蒂尔病(AOSD)9%,干燥综合征(SS)5%,系统性硬化症(SSc)7%,混合性结缔组织病(MCTD)5%.CTD并发ILD肺HRCT最常见的表现是小叶间隔增厚,其次为毛玻璃样变,之后依次为不规则线状影或胸膜下线、网格影、支气管血管束增厚、马赛克灌注、蜂窝肺、薄壁囊肿、结节灶、大片实变病变、肺大泡.AOSD和SSc患者纤维化积分显著高于渗出积分(P＜0.05);CTD并发ILD患者5年生存率为48.5%(95%可信区间为22.4%～67.9%),纤维化积分≥2分是预测患者预后不良的危险因素(P=0.032),其敏感性为82%,特异性为87%.结论 不同CTD并发的ILD有不同的影像学特征,肺HRCT可以较好地发现并鉴别,肺HRCT纤维化积分可以判断患者的预后.     

Clinico-radio-pathological characteristics of unclassifiable idiopathic interstitial pneumonias

Background

The purpose of this study was to clarify the clinico-radio-pathological characteristics and prognostic factors of unclassifiable-idiopathic interstitial pneumonias (U-IIPs) diagnosed by surgical lung biopsy.

结缔组织病所致间质性肺疾病的研究进展

结缔组织病（CTD）包括许多种疾病,如红斑狼疮、硬皮病、类风湿关节炎、干燥综合征、皮肌炎/多发性肌炎及血管炎等。间质性肺病多发生于CTD中,其中早期表现为肺泡炎,而晚期则表现为弥漫性肺间质纤维化,病程终末期可出现呼吸衰竭,因为其发生率和病死率较高,目前已成为研究热点。该病病因和发病机制复杂,预后及治疗方法和效果取决于组织病理类型、风湿病的基础情况及相关的肺动脉高压。本文就CTD所致间质性肺病的现代认识进行综述。