Radionuclide imaging for the assessment of esophageal motility disorders in mixed connective tissue disease patients: relation to pulmonary impairment

Esophageal functional abnormalities may lead to regurgitation, chronic esophagitis and life-threatening conditions such as aspiration pneumonia. In mixed connective tissue disease patients, previous reports showed that esophageal dysfunction varies according to the method employed for investigation. Our study was conceived to: (i) assess esophageal motility and mucosal aspects in patients with mixed connective tissue disease by endoscopy, cine-esophogram and scintigraphy focusing on the prevalence of each exam; and (ii) verify the association between pulmonary and esophageal dysfunctions. Twenty-four mixed connective tissue disease patients were enrolled for this study. Cine-esophogram and upper digestive endoscopy with mucosal biopsy were performed according to previous standardization. Radionuclide esophageal scintigraphy was performed with a semisolid meal with (99m)Tc. Eleven healthy individuals voluntarily submitted to scintigraphy as controls. Cine-esophogram showed esophageal delayed emptying in 90% of patients. At scintigraphy there was a significant delay in total esophageal transit time in the group of patients when compared to healthy controls (35.3 +/- 8.2 s. vs. 13.6 +/- 9.5 s.; P < 0.0001). The whole esophageal body showed dysmotility in 96% of patients. The cine-esophogram detected functional esophageal impairment similar to scintigraphic findings. Histopathologic examination found esophagitis in 95% of studied patients. Reduced lung volumes were associated with esophagitis and delayed esophageal clearance at scintigraphy, observed at the distal portion of the esophagus. Esophageal scintigraphy is easy to perform, with good acceptance by patients with low radiation exposition. It is a useful non-invasive test for follow-up and interventional studies concerning esophagus dysfunction.     

结缔组织生长因子在肾间质纤维化中的表达及其意义

目的 :研究结缔组织生长因子 (connectivetissuegrowthfactor,CTGF)在原发性肾小球肾炎小管间质病变中的表达及其与肾间质纤维化之间的关系。　 方法 :选择不同类型原发性肾小球肾炎患者 42例 ,根据小管间质病变分级分为四组 :0级 8例 ,1级 12例 ,2级 12例 ,3级 10例。应用免疫组织化学方法分别观察四组中CTGF、TGF β1、FN和COL Ⅲ的表达 ,并将CTGF表达水平与患者血肌酐 (SCr)和内生肌酐清除率 (Ccr)进行比较。　 结果 :肾小管上皮细胞 (从近端小管到髓质集合管 )是间质中CTGF的主要来源 ,CTGF表达量与肾小管间质病变程度成正比 (P=0 0 0 5 )。此外 ,CTGF与TGF β1、FN和COL Ⅲ的表达量成正相关 (P均 <0 0 5 ) ;与患者Ccr升高水平成正比 (P <0 0 0 5 )。　 结论 :随着慢性肾小管间质病变程度加重 ,CTGF蛋白质分子表达量显著增加 ,它可能在肾间质纤维化形成过程中起重要作用。CTGF作为TGF β1的下游因子 ,可能通过促进细胞外基质 (ECM)如FN和COL Ⅲ等合成增加 ,参与肾间质纤维化发生。     

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。     

超声在结缔组织病相关肺间质病变中的应用

肺是结缔组织病(connective tissue disease,CTD)的重要靶器官,可出现肺动脉高压(pulmonary hypertension,PAH)、肺泡出血、肺间质病变(interstitial lung disease,ILD)等多种表现,其中ILD是一类以炎症和不同程度纤维化为主要表现的弥漫性肺损伤。目前有多种方式来评估ILD的类型、范围及严重程度。     

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.     

305例结缔组织病相关间质性肺病临床特点分析

目的分析结缔组织病相关间质性肺病(Connective tissue disease associated interstitial lung disease,CTD-ILD)临床特征。方法回顾性分析305例西京医院临床免疫科CTD-ILD的临床特征及类风湿关节炎间质性肺病(Rheumatoid arthritis associated interstitial lung disease,RA-ILD)和干燥综合征间质性肺病(Sjogren's syndrome associated interstitial lung disease,p SS-ILD)患者胸部高分辨CT特点。结果 CTD患者ILD的发病率为11.78%,其中多发性肌炎相关ILD的发病率最高(53.13%),其次为抗中性粒细胞胞浆抗体相关性血管炎(40.74%)、混合结缔组织病(35.14%)和硬皮病(29.73%)。p SS-ILD和RA-ILD在CTD-ILD中所占比例最大,分别为24.92%和23.61%,两者约占所有CTD-ILD的一半。结论 CTD患者ILD的发病率高,RA-ILD和p SS-ILD是CTD-ILD的主要疾病,加强对CTD-ILD的早期筛查和早期治疗非常重要。     

Healing of severe reflux esophagitis with PPI does not improve esophageal dysmotility

Esophageal dysmotility is frequently associated with gastroesophageal reflux disease (GERD). The aim of this study was to investigate the relationship between the severity of reflux esophagitis and esophageal dysmotility and evaluate the effect of prolonged treatment with proton pump inhibitor (lansoprazole 30 mg/day) on esophageal motility in patients with severe reflux esophagitis associated with esophageal motility disorder. Twelve healthy subjects (HS) and 100 patients with reflux disease were involved in the study consisting of two parts: (i) comparison of esophageal motility in HS and patients with non-eroseive reflux disease (NERD), mild esophagitis and severe esophagitis; (ii) effect of 3-6 months lansoprazole therapy on esophageal motility in 23 patients with severe esophagitis, pathologic acid reflux and esophageal peristaltic dysfunction. Results included the following. (i) Esophageal dysmotility was noted in both patients with NERD and erosive GERD. (ii) Severe esophagitis was associated with severe esophageal dysmotility. (iii) Healing of severe esophagitis did not improve esophageal dysmotility. The resting lower esophageal sphincter pressure was 3.9 mmHg (range 1.7-20) before treatment and 4.8 mmHg (range 1.2-18.3) after esophagitis healing (P = 0.23, vs. before treatment), the amplitude of distal esophageal contraction was 28.8 mmHg (range 10.9-80.6) before treatment and 33.3 mmHg (range 10.0-72.5) after esophagitis healing (P = 0.59, vs. before treatment) and the frequency of failed peristalsis was 70% (range 0-100%) before treatment and 70% (range 0-100%) after esophagitis healing (P = 0.78, vs. before treatment). Both esophageal motility disorders and acid reflux play important roles in the mechanism of GERD, especially in severe esophagitis. Esophageal dysmotility is not secondary to acid reflux and esophagitis; it should be a primary motility disorder.     

Lung transplantation in IIP: A review

The idiopathic interstitial pneumonias (IIP) encompass a large and diverse subtype of interstitial lung disease (ILD) with idiopathic pulmonary fibrosis (IPF) and non‐specific interstitial pneumonia (NSIP) being the most common types. Although pharmacologic treatments are available for most types of IIP, many patients progress to advanced lung disease and require lung transplantation. Close monitoring with serial functional and radiographic tests for disease progression coupled with early referral for lung transplantation are of great importance in the management of patients with IIP. Both single and bilateral lung transplantation are acceptable procedures for IIP. Procedure selection is a complex decision influenced by multiple factors related to patient, donor and transplant centre. While single lung transplant may reduce waitlist time and mortality, the long‐term outcomes after bilateral lung transplantation may be slightly superior. There are numerous complications following lung transplantation including primary graft dysfunction, chronic lung allograft dysfunction (CLAD), infections, gastroesophageal reflux disease (GERD) and airway disease that limit post‐transplant longevity. The median survival after lung transplantation is 4.7 years in patients with ILD, which is less than in patients with other underlying lung diseases. Although long‐term survival is limited, this intervention still conveys a survival benefit and improved quality of life in suitable IIP patients with advanced lung disease and chronic hypoxemic respiratory failure.     

Evaluation and management of patients with symptoms after anti‐reflux surgery

Over the past two decades, there has been an increase in the number of anti‐reflux operations being performed. This is mostly due to the use of laparoscopic techniques, the increasing prevalence of gastroesophageal reflux disease (GERD) in the population, and the increasing unwillingness of patients to take acid suppressive medications for life. Laparoscopic fundoplication is now widely available in both academic and community hospitals, has a limited length of stay and postoperative recovery time, and is associated with excellent outcomes in carefully selected patients. Although the operation has low mortality and postoperative morbidity, it is associated with late postoperative complications, such as gas bloat syndrome, dysphagia, diarrhea, and recurrent GERD symptoms. This review summarizes the diagnostic evaluation and appropriate management of such postoperative complications. If a reoperation is needed, it should be performed by experienced foregut surgeons.     

Multidisciplinary team discussion: the emerging gold standard for management of cardiopulmonary complications of connective tissue disease

Cardiopulmonary complications of connective tissue diseases (CTDs), particularly pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD), are major determinants of morbidity and mortality. Multidisciplinary meetings may improve diagnostic accuracy and optimise treatment. We review the literature regarding multidisciplinary meetings in CTD-ILD and PAH and describe our tertiary centre experience of the role of the multidisciplinary meeting in managing CTD-PAH.     

TH17在结缔组织病相关性间质性肺病中的意义

目的探讨外周血Th17及IL-17在结缔组织病相关性间质性肺疾病的表达及意义。方法收集23例正常对照组及28例病理类型为非特异性间质性肺炎(NSIP)的结缔组织病相关性间质性肺疾病(CTD-ILD)患者的外周血单个核细胞及血浆,分别检测PBMC中Th17的比例及血浆中IL-17的表达情况,并收集入组患者肺功能指标TLC(pre/ref%)及DLco(pre/ref%)数据。结果与正常对照组相比,CTD-ILD患者组Th17比例明显增加,差别具有统计学意义(P0.05),CTD-ILD患者IL-17细胞因子的浓度较正常对照组的血浆浓度明显增加(P0.01)。但CTD-ILD患者外周血Th17及IL-17与患者肺功能指标TLC(pre/ref%)及DLco(pre/ref%)之间均无显著相关性。结论在CTD-ILD患者体内Th17及其细胞因子IL-17明显升高,可能参与疾病的发生。     

Open-label study of clarithromycin in patients with undifferentiated connective tissue disease

OBJECTIVE: The macrolide family of antibiotics (erythromycin, clarithromycin, and others), have both antimicrobial and immunomodulatory effects. This study explored the effect of clarithromycin on the clinical course of patients with undifferentiated connective tissue disease (UCTD) in a 12-week open-label study. METHODS: The diagnosis of UCTD was based on symptoms/signs of connective tissue disease, and the presence of 1 or more positive autoimmune disease tests, but with insufficient criteria to make a definitive diagnosis. Screening and monthly follow-up visits over 12 weeks included the following: history and physical examination; concurrent medications; the 68/66 tender/swollen joint count; visual analog scores 0 to 100 mm for patient and physician global assessment of disease activity, and patient pain; antinuclear antibody panel, rheumatoid factor, erythrocyte sedimentation rate, C-reactive protein, and blood chemistry. RESULTS: Seven patients with rheumatic disease were treated with clarithromycin; 6 of 7 had symptomatic relief. Two subjects treated empirically before the decision to perform an open-label study responded favorably. Four of 5 patients who completed the prospective open-label study had mean maximal improvements from baseline of 78, 75, and 79% in patient pain, patient global, and investigator global assessments, respectively. Pain relief occurred as early as 1 week. Drug withdrawal with rechallenge in 2 patients resulted in flare followed by recapture of symptomatic relief. CONCLUSIONS: Clarithromycin, a macrolide antibiotic, led to clinical improvement in patients with UCTD. Efficacy and safety data support further investigation of macrolide antibiotic use as a primary or adjunctive treatment in various connective tissue diseases.     

Clinical characteristics and survival in idiopathic pulmonary fibrosis and connective tissue disease-associated usual interstitial pneumonia

Background

Previous studies have reported conflicting survival rates for connective tissue disease (CTD)-associated usual interstitial pneumonia (UIP) and idiopathic pulmonary fibrosis (IPF/UIP). This study investigated the differences in the clinical characteristics and prognoses of patients diagnosed with CTD-UIP and IPF/UIP.

Methods

A retrospective review of patients with IPF (n=88) and CTD-UIP (n=67) from January 2008 to June 2013 was completed. We compared the demographics and clinical characteristics between the two groups. Survival rates were compared using a log-rank and Cox proportional hazard regression analysis.

Results

Undifferentiated-CTD (UCTD) accounted for 33% of the established CTD-UIP cases. No significant differences were identified in the demographic characteristics or physiological parameters between the UCTD and CTD patients (all P>0.05). However, the CTD-UIP patients were more likely to be young, female, and nonsmokers compared with the IPF/UIP group (all P<0.01). There was no difference in survival between the IPF/UIP and CTD-UIP patients [hazard ratio (HR), 1.74; 95% confidence interval (CI), 0.86-3.50; P=0.113]. However, the removal of the UCTD patients from the CTD group revealed that IPF/UIP was associated with a 2.47-fold increased risk of mortality compared with CTD-UIP (HR, 2.47; 95% CI, 1.01-6.09; P=0.049).

Conclusions

Our findings indicate that the survival of CTD-UIP patients was similar compared with that of IPF/UIP patients. However, it appears that UCTD influences the survival rate of CTD-UIP patients.     

Anti‐reflux surgery for patients with esophageal atresia

Gastroesophageal reflux (GER) is almost constant in esophageal atresia and tracheoesophageal fistula (EA/TEF). These patients resist medical treatment and require antireflux surgery quite often. The present review examines why this happens, the long‐term consequences of GER and the main indications and results of fundoplication in this particular group of patients. The esophagus of EA/TEF patients is malformed and has abnormal extrinsic and intrinsic innervation and, consequently, deficient sphincter function and dysmotility. These anomalies are permanent. Fifty percent of patients overall have GER, and one‐fifth have Barrett's metaplasia. Close to 100%, GER of pure and long‐gap cases require fundoplication. In the long run, these patients have 50‐fold higher risk of carcinoma than the control population. GER in EA/TEF does not respond well to dietary, antacid, or prokinetic medication. Surgery is necessary in protracted anastomotic stenoses, in pure and long‐gap cases, and when there is an associated duodenal atresia. It should be indicated as well in other symptomatic cases when conservative treatment fails. However, confection of a suitable wrap is anatomically difficult in this condition as shown by a failure rate of 30% that is also explained by the persistence for life of the conditions facilitating GER.     

The development of connective tissue diseases in patients with autoimmune hepatitis: a case series

OBJECTIVES: To study the prevalence of connective tissue diseases (CTD) in patients with autoimmune hepatitis (AIH). METHODS: We identified 11 cases of AIH over the past 7 years at our institution, through a systematic chart review of patients with this diagnosis. Their charts were reviewed for the development of systemic CTD. RESULTS: Three of the 11 patients with a definitive diagnosis of AIH developed systemic CTD. All were white: 2 women and 1 man, with an age range of 33 to 62 years, and with disease duration of 1 to 7 years. One patient developed systemic lupus erythematosus (SLE) with vasculitis and peripheral neuropathy. The second developed limited scleroderma and the third developed undifferentiated connective tissue disease (UCTD) and interstitial lung disease. There appear to be shared susceptibility alleles for AIH and CTD in addition to the shared positive autoantibodies. CONCLUSIONS: Patients with AIH may be at increased risk for developing systemic CTD. Conversely, a review of the literature reveals that patients with systemic CTD may be at increased risk of developing AIH. Patients with either AIH or CTD should be monitored for further development of concurrent autoimmune diseases.     

Classification tree criteria of pulmonary hypertension in mixed connective tissue disease

Abstract

Tree criteria for the classification of pulmonary hypertension (PH) in mixed connective tissue disease (MCTD) were developed by stratifying patients into groups according to the physician’s diagnosis, mean pulmonary artery pressure (mPA) and prognosis, respectively. A classification tree for PH diagnosed by the physician was constructed with two criteria: dilatation of the pulmonary artery segment evident on chest roentgenography (or an accentuated pulmonic sound as a surrogate) and shortness of breath on exertion, which demonstrated a sensitivity of 96% and a specificity of 99%. A classification tree for PH diagnosed by mPA was also constructed with almost similar criteria: an accentuated pulmonic sound (or dilatation of the pulmonary artery segment evident on chest roentgenography as a surrogate) and shortness of breath on exertion, which demonstrated a sensitivity of 100% and a specificity of 100%. The prognostic classification tree was constructed with four criteria: an accentuated pulmonic sound, systolic pulsation at the left sternal border, shortness of breath on exertion and retro-sternal pain on exertion, which demonstrated a sensitivity of 62% and a specificity of 98%. The classification tree criteria for the diagnosis and prognosis of PH in MCTD were found to be accurate and useful for the screening of PH.