临床病例评析——关节炎发热喘憋

目的 探索类风湿关节炎(RA)患者合并发热和肺部病变的诊断和鉴别诊断方法的要领。方法 对1例55岁,出现关节炎、发热和喘憋的男性患者进行详尽的临床诊治分析。结果 患者的关节表现符合RA,经过肺高分辨率CT进行肺部空洞的鉴别诊断,并经过试验性抗真菌治疗的验证,最后确定诊断为RA合并肺间质病变和真菌感染。结论 RA患者出现发热和肺部空洞性病变要考虑到肺真菌感染的可能性。     

Fibrinopeptide A reactive peptides and procoagulant activity in bronchoalveolar lavage: relationship to rheumatoid interstitial lung disease

Extravascular, primarily, alveolar fibrin deposition is commonly associated with the alveolitis of many interstitial lung diseases including the interstitial lung disease associated with rheumatoid arthritis (RA). We therefore hypothesized that coagulation pathways, which promote fibrin formation, would be activated in the alveolar lining fluids of patients with rheumatoid interstitial lung disease. To test this hypothesis, we studied the bronchoalveolar lavage (BAL) fluids from patients with rheumatoid interstitial lung disease (n = 7) and patients with RA unassociated with interstitial lung disease (n = 10) to characterize and quantitatively compare the BAL procoagulant material and levels of fibrinopeptide A (FPA), which is cleaved from fibrinogen by thrombin. FPA reactive peptide concentrations were significantly greater in rheumatoid interstitial lung disease than RA when normalized per ml of concentrated BAL fluid (p = 0.02), per mg BAL total protein (p = 0.01) or BAL albumin content (p = 0.03) and correlated with BAL antigenic neutrophil elastase concentrations (r = 0.87). Procoagulant activity was present in similar concentration of BAL of patients with RA and rheumatoid interstitial lung disease and was mainly attributable to tissue factor associated with factor VII (or VIIa). Our results demonstrate that tissue factor and factor VII are endogenous in the alveoli of subjects with RA and interstitial lung disease and could interact with distal coagulation substrates which may enter the alveoli in interstitial lung disease to locally promote fibrin deposition.(ABSTRACT TRUNCATED AT 250 WORDS)     

Development of sarcoidosis 6-month post discontinuation of etanercept: coincidence or real association?

There have been numerous reports of granulomatous diseases developing in patients receiving anti-tumour necrosis factor (TNF) therapy. Herein, we report a patient who developed sarcoidosis 6?months after discontinuation of etanercept. To date, all reported cases have occurred in patients undergoing ongoing treatment with TNF blockers with resolution on its discontinuation. A 47-year-old man was diagnosed with seropositive rheumatoid arthritis (RA) in 2003. He was initially treated with methotrexate and corticosteroids. In 2005, adalimumab was added due to ongoing disease activity. However, he had persistent low-grade synovitis of bilateral wrist joints and remained oral glucocorticoids dependent. In October 2008, adalimumab was switched to etanercept with marginal benefit; however, etanercept was continued until March 2009. Rituximab was discontinued due to an immediate allergic reaction. In September 2009, he developed bilateral ankle synovitis with erythema nodosum. Further investigations (chest X-ray and CT scan of thorax) revealed new development of bilateral hilar lymphadenopathy and interstitial nodular changes typical of sarcoidosis. His baseline therapy of methotrexate was continued. His recent repeat chest X-ray and CT scan of thorax (March 2010) has shown significant spontaneous resolution of his mediastinal lymphadenopathy and pulmonary nodules. Apart from the initial brief course of NSAIDs, his sarcoidosis resolved spontaneously without requiring any further therapy. For his rheumatoid arthritis, he has been recently commenced on abatacept and his baseline therapy of methotrexate has been continued. It remains speculative as to whether the concurrence of RA and sarcoidosis is purely serendipitous, or is related to an immunodysregulatory state attributable to TNF blockade.     

Lymphomatoid granulomatosis and diffuse alveolar damage associated with methotrexate therapy in a patient with rheumatoid arthritis

We report on a patient of rheumatoid arthritis (RA) who sequentially developed an axillary mass and a fatal interstitial pneumonia during a 2-year course of methotrexate (MTX) therapy. Autopsy revealed a systemic lymph node involvement and the diagnosis of Epstein–Barr virus (EBV)-related lymphoproliferative disease (LPD) with the features of lymphomatoid granulomatosis was made. The lung tissue specimens revealed a typical diffuse alveolar damage (DAD), and small nodules consisting of atypical B lymphocytes showing positive staining for EBV were sparsely recognized only in basal lungs. This is the first report of a RA patient receiving MTX therapy sequentially developing MTX-associated lymphomatoid granulomatosis and DAD.     

Diffuse interstitial lung disease in rheumatoid arthritis. Views on immunological and HLA findings

Immunological parameters including HLA typing were studied in 32 patients with rheumatoid arthritis (RA) associated diffuse interstitial lung disease (DILD) and in 32 age- and sex-matched RA control patients. The male RA patient group with DILD also included patients with other intrathoracic manifestations and had a higher prevalence of HLA-B8 and Dw3 than did healthy controls, thus agreeing with our earlier results that RA patients with this antigen combination are prone to multiple intrathoracic complications. Patients with DILD had higher titres of rheumatoid factor (RF) and lower complement (C4) levels than matched RA controls. The RF titre was in inverse correlation with C3 and C4 levels, suggesting that RF immune complexes may also promote rheumatoid lung disease via activation of the classical pathway of complement.     

Poor prognosis in patients with rheumatoid arthritis hospitalized for interstitial lung fibrosis

Fifty-seven patients with rheumatoid arthritis (RA) were treated in hospital for diffuse interstitial lung fibrosis. Although interstitial fibrosis (either on the basis of lung function tests or chest roentgenograms or both) is fairly common among patients with RA, according to this study interstitial fibrosis of sufficient extent or severity to warrant hospitalization was rare: incidence of hospitalization due to the lung disease in RA patients was one case per 3,500 patient-years. Eight patients had a largely reversible lung disease associated with drug treatment (gold, D-penicillamine or nitrofurantoin.) The remaining 49 had interstitial fibrosis of unknown cause. Causes for hospitalization were respiratory and general symptoms in 38, but infiltrations on routine chest roentgenographic examinations alone in eleven patients. Forty-five out of the 49 patients had crackles on auscultation. The most typical findings in lung function tests were restriction and a decreased diffusion capacity. These 49 patients showed a poor prognosis, with a median survival of 3.5 years and a five-year survival rate of 39 percent.     

Alveolar macrophage gold retention in rheumatoid arthritis

Alveolar macrophages obtained by bronchoalveolar lavage (BAL) were evaluated by electron dispersive microanalysis (EDX) for the presence of elemental gold. EDX revealed gold in 90% (9/10) of patients with RA who were currently receiving chrysotherapy or who had discontinued chrysotherapy less than 24 months before BAL. All patients who had discontinued chrysotherapy more than 24 months before BAL (range: 3-14 years) were EDX negative (4/4), as were patients with RA who had never received gold therapy (5/5). Seven patients with RA (7/19) had clinical evidence of interstitial lung disease and 12 patients (12/19) had no interstitial lung disease. There was no correlation between chrysotherapy and the development of interstitial lung disease. These results demonstrate that gold is retained for prolonged periods in pulmonary tissue macrophages but do not identify any relationship between gold and chronic rheumatoid lung disease.     

Intrathoracic lymphadenopathy. A rare manifestation of rheumatoid pulmonary disease

This is the first antemortem report of a patient with long-standing RA and interstitial lung disease who developed reactive mediastinal adenopathy coincident with increases in the activity of his interstitial process. Mediastinal adenopathy was discovered by means of CT of the chest as part of an evaluation of interstitial lung disease. The increasing use of better imaging techniques for this purpose will undoubtedly reveal more patients with this finding. Mediastinal lymphadenopathy complicating rheumatoid lung is clinically relevant; speculation is provided regarding the mechanism of the lymph node enlargement in this setting.     

Radiographic appearance of bronchiolitis obliterans organizing pneumonia (BOOP) developing during Bucillamine treatment for rheumatoid arthritis

Bucillamine, a disease-modifying antirheumatic drug, can have adverse effects, including lung injury. Development of interstitial pneumonia during treatment for patients with rheumatoid arthritis (RA) can pose a difficult differential diagnosis between a direct manifestation of RA and a drug effect. Our review of previous reports suggested bucillamine-induced interstitial pneumonia in the patient described here, visualized by chest radiography and computed tomography based on patchy ground-glass opacities in a peribronchial or peripheral distribution, suggesting the appearance of bronchiolitis obliterans organizing pneumonia (BOOP). As is typical for BOOP, steroid responsiveness may have contributed to recovery.     

Clinical characteristics affecting survival in patients with rheumatoid arthritis undergoing cervical spine surgery: a controlled study

A controlled study of the clinical characteristics affecting survival in patients with rheumatoid arthritis (RA) with cervical spine involvement treated surgically demonstrated a strong association between disease severity, the frequency of severe extraarticular manifestations, especially interstitial lung disease, and a decreased probability of survival. These probabilities at 1 and 5 years postoperatively were 74 and 54%, respectively. Death resulted most often from infection or comorbid conditions. All surgery patients with interstitial lung disease died within 28 months postoperatively. In patients with RA undergoing cervical spine surgery, fatality rates appear to be increased in patients with severe extraarticular manifestations, especially interstitial lung disease.     

Cranial and peripheral neuropathy in rheumatoid arthritis with special emphasis to II,V, VII,VIII and XI cranial nerves

Background: Cranial neuropathy in rheumatoid arthritis (RA) is relatively rare compared to the frequently reported peripheral neuropathy. Methods: We investigated the occurrence of subclinical cranial and peripheral nerve involvement in 55 patients with RA. Results: Patients had a mean age of 43.1 years and a mean duration of illness of 6.4 years. All patients presented with electrophysiological findings suggestive of peripheral neuropathy. In addition, 69.1% of them had entrapment neuropathies, in which carpal tunnel syndrome was the most common (54.6%). Sensorimotor neuropathy at sites other than usual entrapment sites was diagnosed in 70.9%, while bilateral distal sensory neuropathy in lower limbs was identified in 29.1%. Among cranial nerves examined, optic and vestibulocochlear neuropathies were common (29.1% of eyes and 40% of ears examined). Spinal accessory neuropathy was reported in 21.8% of records. Neither facial nor trigeminal nerves were affected. Electrophysiological characteristics of neuropathies were indicative of axon loss. Significant association was identified between neuropathy and patients’ ages (P < 0.01), duration of the illness (P < 0.001), presence of rheumatoid nodules (P < 0.001) and disease stages (P < 0.001). Conclusions: Our results indicate that cranial and non‐compressive neuropathies are not uncommon in RA. This extends the pathologic disease spectrum. We do not confirm, but suggest the contribution of chronic immune‐mediated vasculitis and/or neurotoxicity in RA neuropathies. Of clinical importance, subclinical neuropathy may never progress and/or be of clinical significance, which contradicts that of comparable diseases, such as systemic lupus erythematosus. Advances in genetics implicate a complex immune genetics which controls susceptibilities and adaptive molecular mechanisms as a culprit of phenotypical heterogenicity among related diseases.     

Utility of pulmonary ultrasound to identify interstitial lung disease in patients with rheumatoid arthritis

Clinical Rheumatology - To analyze the diagnostic utility of lung ultrasound (US) to detect interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients comparing with high-resolution...     

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.     

Neuromuscular sarcoidosis

Neuromuscular sarcoidosis is recognized with increasing frequency. Although reported to occur in only 5% of patients with sarcoidosis, major centers are reporting up to 20% neuromuscular involvement. While the majority of patients with neurologic involvement present with 7 (th) nerve palsy, the reported frequency of sarcoidosis of the brain, meninges, spinal cord, and muscles is rising. The diagnosis of neuromuscular sarcoidosis is usually accepted when a patient with previous biopsy-proven sarcoidosis presents with a compatible neurologic syndrome. In addition to cranial nerve abnormalities, these syndromes include leptomeningitis, seizures, mass lesions of brain and spinal cord, pituitary dysfunction, and neuropathies. Occasionally, the typical intrathoracic, ocular, cutaneous and lymph node presentations of sarcoidosis are not present or are unrecognized and the diagnosis is established by biopsy of neuromuscular tissue. Biopsy exhibiting granulomas is not specific and requires absence of evidence of known granulomagenic agents plus presence of multiorgan disease. An isolated granuloma in neural tissue without other organ involvement is not diagnostic of sarcoidosis. Treatment of neuromuscular sarcoidosis is usually prolonged. Facial palsy often improves spontaneously. Prednisone is still the drug of choice. Most authorities agree that 30 to 40 mg qd is sufficient with concomitant azathioprine or cyclophosphamide.     

Cardiovascular disease in rheumatoid arthritis: medications and risk factors in China

This study aims to assess the risk factors of cardiovascular disease (CVD) and to determine the association of traditional and biologic disease-modifying anti-rheumatic drugs (DMARDs) with risk for CVD in Chinese rheumatoid arthritis (RA) patients. A cross-sectional cohort of 2013 RA patients from 21 hospitals around China was established. Medical history of CVD was documented. The patients’ social background, clinical manifestations, comorbidities, and medications were also collected. Of the 2013 patients, 256 had CVD with an incidence of 12.7%. Compared with non-CVD controls, RA patients with CVD had a significantly advanced age, long-standing median disease duration, more often male and more deformity joints. Patients with CVD also had higher rates of smoking, rheumatoid nodules, interstitial lung disease, and anemia. The prevalence of comorbidities, including hypothyroidism, diabetes mellitus (DM), hypertension, and hyperlipidemia, was also significant higher in the CVD group. In contrast, patients treated with methotrexate, hydroxychloroquine (HCQ), and TNF blockers had lower incidence of CVD. The multivariate analysis showed that the use of HCQ was a protective factor of CVD, while hypertension, hyperlipidemia, and interstitial lung disease were independent risk factors of CVD. Our study shows that the independent risk factors of CVD include hypertension, hyperlipidemia, and interstitial lung disease. HCQ reduces the risk of CVD in patients with RA.     

Pulmonary complications of infliximab therapy in patients with rheumatoid arthritis

We describe 5 patients with rheumatoid arthritis (RA) who developed pulmonary complications following infliximab therapy; 4 patients had preexisting usual interstitial pneumonia. As the pathophysiology of the pulmonary insult is unknown, we advise caution in the use of anti-tumor necrosis factor-alpha therapy in patients with RA with underlying lung disease of sufficient severity to withhold methotrexate treatment.     

Cigarette smoking and pulmonary diffusion defects in rheumatoid arthritis

The pathogenesis of lung disease in rheumatoid arthritis (RA) has still to be defined. Risk factors associated with lung involvement in RA were investigated by means of pulmonary function studies in 40 RA patients without apparent lung disease. A decreased carbon monoxide (CO) diffusion capacity indicative of interstitial lung disease (ILD) was the main pulmonary function defect found in the first 20 patients. The occurrence was associated with current cigarette smoking. This association was confirmed in a case control study performed subsequently. These data suggest that ILD in RA is stimulated by smoking and provide an additional argument that modification of smoking behaviour in RA patients might lead to less severe complications. Received: 15 January 1998 / Accepted: 12 March 1998     

Thoracic surgical procedures in patients with rheumatoid arthritis

OBJECTIVE: Rheumatoid arthritis (RA) is associated with a variety of pleuropulmonary manifestations, some of which require surgical intervention. We investigated the spectrum of indications and results, as well as outcome associated with thoracic surgical procedures in rheumatoid patients. METHODS: Identification and retrospective review of medical records of 100 patients with RA at a tertiary-referral medical center undergoing thoracic surgical procedures over a 24-year period from January 1, 1976, to December 31, 1999. RESULTS: Sixty-four patients underwent surgical lung biopsy for localized lung lesions, 57 of which were nodules or masses; 24 lesions proved to be malignant. Surgical lung biopsy was undertaken in 40 patients for diffuse interstitial lung disease, 4 cases of which were found to be infectious. Five other patients underwent surgery for pleural disease, 3 of which proved to be benign pleuritis. CONCLUSION: Patients with rheumatoid disease undergo thoracic surgical procedures for a variety of indications, including benign and malignant localized lesions and pleural disease as well as diffuse parenchymal lung disease. The overall in-hospital mortality rate was low. However, the subgroup with diffuse interstitial lung disease was found to have a 20% in-hospital death rate following surgical lung biopsy.     

Adalimumab-induced interstitial pneumonia with an improvement of pre-existing rheumatoid arthritis-associated lung involvement

A 78-year-old man with an 18-year history of rheumatoid arthritis (RA) was treated with tumor necrosis factor (TNF)-α inhibitor adalimumab. Chest computed tomography showed a previously detected consolidation. The patient's arthritic symptoms substantially decreased with the initiation of adalimumab, with a simultaneous improvement of the lung lesion. However, additional interstitial pneumonia was found a month after starting adalimumab. This course suggested that adalimumab might be effective against RA-associated lung disease, but may also have caused drug-induced interstitial pneumonia. This is the first report indicating that TNF-α inhibitor shows simultaneously conflicting actions in a patient with RA-related lung disease.