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.     

Severe pulmonary hypertension in rheumatoid arthritis

We report a patient with seropositive rheumatoid arthritis who had clinical and haemodynamic findings of severe pulmonary arterial hypertension. Histopathology proved this to be plexogenic rather than thromboembolic. We report the case to highlight this rare association.     

Obstructive pulmonary disease in rheumatoid arthritis

Twenty-six of 43 patients (60.5%) with classic rheumatoid arthritis (RA) participating in a controlled, prospective study were found to have maximal midexpiratory flow rates (MMEFs) suggestive of obstructive pulmonary disease. Cigarette smokers with RA had significantly lower MMEFs than either nonsmokers with RA or smokers with degenerative joint disease. There was an increased prevalence of the Pi phenotype MS among the RA patients. Interstitial fibrosis, tobacco smoking, and protease inhibitor deficiencies were all significant factors in producing airway obstruction in patients with RA.     

Leflunomide-related lung injury in patients with rheumatoid arthritis: imaging features

Imaging findings of 26 cases of leflunomide (Arava)-related acute lung injury were analyzed. Thirteen cases had pre-existing interstitial pulmonary disease on chest X-ray or computed tomography. The main features of clinically determined leflunomide-induced acute lung injury were similar to those caused by other drugs: diffuse or widespread patchy ground-glass opacities and/or consolidation, frequently accompanied by septal thickening and intralobular reticular opacities. We categorized these findings into four patterns: diffuse alveolar damage (DAD), acute eosinophilic pneumonia, hyperreaction, and cryptogenic organizing pneumonia. The DAD group had a higher mortality rate, but statistically not a significant one. It is impossible to exclude infectious disease such as pneumocystis carinii pneumonia based on imaging findings, and detailed correlation of imaging findings with clinical and laboratory findings is essential in order to make a correct diagnosis.     

Effect of methotrexate on pulmonary involvement in patients with rheumatoid arthritis

Objective: The aim of this study is to determine the effects of methotrexate (MTX) therapy on pulmonary involvement in patients with rheumatoid arthritis (RA). Method: Fifty‐five non‐smoking RA patients were included in the study. Routine laboratory investigations, pulmonary function tests (PFT), high resolution computed tomography (HRCT) and arterial blood gas analysis were performed in all of the patients. Randomly dividing the patients into two groups, the first group were given 7.5 mg/week MTX and the second group were given 250 mg/day chloroquine phosphate. At the end of the sixth month all the tests and the analysis were repeated and evaluated by using χ² and Student's t‐test; P < 0.05 was considered statistically significant. Results: At the beginning of the study, HRCT examination revealed 92.7% pulmonary involvement in 55 RA patients. At the sixth month although the RA patients in the chloroquine group did not show any difference, RA patients in the MTX group displayed statistically significant increases in their pulmonary involvement (P < 0.05). Patients in the MTX group also displayed significant decreases at FEV₁/FVC and significant increases at FEV₁ in PFT and O₂ saturation (P < 0.05, P < 0.05 and P < 0.01, respectively). In the chloroquine group we observed significant increases in FEV₁ and vital capacity (P < 0.05). Conclusion: Although the MTX therapy increases the risk of pulmonary involvement in patients with RA, it also increases the ventilation which in turn increases the functional capacity of the patient. Considering the beneficial effect on the radiological progression of the disease, we think that MTX therapy should be taken into account as the first choice in the treatment of RA.     

Misoprostol heals gastroduodenal injury in patients with rheumatoid arthritis receiving aspirin

High-dose aspirin therapy for rheumatoid arthritis is frequently associated with severe gastrointestinal injury. To explore the possibility of reversing such damage, we conducted a double-blind, multicenter study with misoprostol, a prostaglandin E1 analog, which has demonstrated mucosal protective, gastric antisecretory, and ulcer healing properties. We also studied possible interference of misoprostol with continuing aspirin treatment in the management of patients with rheumatoid arthritis. Patients with confirmed rheumatoid arthritis and endoscopically documented gastroduodenal lesions were randomly assigned to receive 200 micrograms of misoprostol four times a day (123 patients) or placebo (116 patients). Each concurrently received 650 to 1300 mg of aspirin four times a day. After eight weeks of treatment, misoprostol was statistically superior to placebo in healing gastric mucosal injury (70% vs 25%) and duodenal mucosal injury (86% vs 53%). Patients with gastric or duodenal ulcers on admission had superior ulcer healing rates with misoprostol (67% vs 26%). There was no evidence of interference with the antirheumatic properties of aspirin. Mild to moderate adverse experiences were equally noted in misoprostol and placebo groups. Misoprostol, coadministered with aspirin, is well tolerated and highly effective in healing aspirin-associated gastroduodenal lesions in patients with rheumatoid arthritis without altering the therapeutic benefits of aspirin.     

Gold and pulmonary function in rheumatoid arthritis

The effect of gold therapy on pulmonary function in rheumatoid arthritis has been studied prospectively in a group of 14 patients and retrospectively in 96 patients. There was no evidence that gold had any adverse effect on pulmonary function.     

Obstructive pulmonary disease in rheumatoid arthritis.

Twenty-six of 43 patients (60.5%) with classic rheumatoid arthritis (RA) participating in a controlled, prospective study were found to have maximal midexpiratory flow rates (MMEFs) suggestive of obstructive pulmonary disease. Cigarette smokers with RA had significantly lower MMEFs than either nonsmokers with RA or smokers with degenerative joint disease. There was an increased prevalence of the Pi phenotype MS among the RA patients. Interstitial fibrosis, tobacco smoking, and protease inhibitor deficiencies were all significant factors in producing airway obstruction in patients with RA.     

Raised pulmonary artery pressures measured with Doppler echocardiography in rheumatoid arthritis patients

OBJECTIVE: To study the prevalence of echocardiographic abnormality and pulmonary hypertension in an unselected population of patients with rheumatoid arthritis (RA). METHOD: One hundred and forty-six RA patients, irrespective of cardiopulmonary symptoms, were assessed clinically and by echocardiography, including pulmonary artery pressure measurement, ECG, pulmonary function tests and high-resolution computed tomography scanning of the thorax. RESULTS: Two-dimensional echocardiography demonstrated significant cardiac disease in the form of reduced left ventricular ejection fraction (<64%) in 9% of patients, moderate mitral regurgitation in 4%, aortic stenosis in 4%, aortic regurgitation in 3% and Valsalva sinus rupture in 0.7%. In addition, 1% had detectable pericardial effusions. Thirty-one per cent of the RA patients had an estimated pulmonary artery systolic pressure of 30 mmHg or more, and 21% of all the RA patients had pulmonary hypertension without significant cardiac disease or lung disease evident on pulmonary function testing. CONCLUSIONS: A wide and frequent variety of echocardiographic cardiac abnormalities may be found in an unselected population of patients with RA. Using Doppler echocardiography, we have found pulmonary hypertension secondary to lung disease in 6% of the population and a larger than expected prevalence of mild primary pulmonary hypertension in patients with RA. The latter observation may be relevant to the high incidence of cardiovascular-related deaths observed in patients with RA     

Radiological and functional assessment of pulmonary involvement in the rheumatoid arthritis patients

The aim was to evaluate the findings of high resolution computed tomography (HRCT) and pulmonary function tests (PFT) in the rheumatoid arthritis (RA) patients with and without pulmonary symptoms and to determine their role in prediction of respiratory system involvement. Among 54 consecutive RA patients, 22 (41%) were symptomatic and 32 (59%) were asymptomatic after detailed respiratory examination. Abnormal findings in PFTs were present in 10 (45%) symptomatic and 15 (47%) asymptomatic patients. PFT results were similar in both groups. A total of 18 (82%) symptomatic and 16 (50%) asymptomatic patients had abnormalities in HRCT scans. About 16 (80%) of 20 patients with normal HRCT scans had no pulmonary symptoms at all and we noted a significant correlation (P < 0.05). HRCT was more useful mean than PFTs in evaluation of pulmonary involvement in the RA patients; however, no correlation was present between various respiratory symptoms and abnormal findings both in PFTs and HRCT scans.     

Nodular pulmonary opacities in patients with rheumatoid arthritis. A diagnostic dilemma

Nodular opacities are a well-known pulmonary manifestation of rheumatoid arthritis (RA), occurring most often in seropositive men who smoke and have subcutaneous nodules. In the past 15 years two cases of lung carcinoma presenting as pulmonary nodules have been reported in patients with rheumatoid disease. We present seven patients with seropositive RA and subcutaneous nodules who had new pulmonary nodule(s) noted on chest roentgenograms. All but one were current smokers. Carcinoma was found in all patients at bronchoscopy or thoracotomy. Four patients had solitary nodules (one was cavitary); the remaining three patients had multiple bilateral nodules that cavitated in one case. All patients had interstitial abnormality (peribronchial/vascular thickening) with basal predominance in three, and there was evidence of pleural thickening/fluid in three patients. These results strongly suggest that histologic proof of presumed rheumatoid pulmonary nodules be obtained.     

Broncho-alveolar lavage in pulmonary involvement in rheumatoid arthritis

This study was designed to investigate by bronchoalveolar lavage (BAL) the characteristics of lung involvement in rheumatoid arthritis (RA). Twenty six patients with RA were included; ten were active smokers. Chest X Ray, pulmonary function tests and BAL were performed in all patients. Bronchiolitis was found in 7% of cases, pleurisy in 30% of cases. 83% of patients were found to have diffuse alveolar and/or interstitial disease, 17% rheumatoid nodules. Functional evaluation showed a restrictive pattern and a significant reduction in the carbon monoxyde diffusing capacity. Smokers had elevated BAL macrophages and decreased lymphocytes compared with non-smokers: respectively 89% vs 62.9% and 7.3% vs 18.9%. Patients with bronchiolitis had lower FVC than others: 38 +/- 14% vs 61 +/- 3%, and their BAL neutrophils were increased: 71 +/- 23% vs 7.5 +/- 2%. There was an inverse correlation between neutrophil counts and FVC in non-smokers, and diffusing capacity. We conclude that BAL inflammatory cells profiles are abnormal in RA and modified by a smoking history and the existence of a bronchiolitis.     

类风湿性关节炎相关肾损害的临床病理特征

目的：了解与类风湿性关节炎相关的。肾损害临床病理特点。方法：排除药物相关，经临床及肾活检确诊的与类风湿性关节炎本身相关的肾损害患者42例，回顾分析其临床病理特征。结果：42例患者中男性10例，女性32例，年龄为（47．1&#177;12．5）岁（15～71岁）。关节炎病程为（108．7&#177;89．5）月（4～240月），肾脏病病程（12．7&#177;22．0）月（3～120月）。42例患者均存在蛋白尿，平均尿蛋白为（3．15&#177;2．40）g／24h（0．45～12．74）g／24h，其中18例（42．9％）为。肾病综合征。27例（64．3％）伴血尿，其中4例（9．5％）为肉眼血尿，21例（50％）伴高血压，14例（33．3％）血肌酐升高。病理改变以系膜增生性病变伴IgA沉积（28．6％）和不伴IgA沉积（26．2％）最常见，其次为膜性病变（23．8％），节段坏死性肾炎（16．7％），膜增生性肾炎（4．7％）。系膜增生性病变伴IgA沉积、节段坏死性肾炎者血尿、肾功能不全发生率较系膜增生性病变不伴IgA沉积和膜性病变患者高（血尿分别为83．3％，85．7％，9．1％，50％；肾功能不全发生率分别为41．7％，57．1％，27．3％，20％），而大量蛋白尿（≥3．5g／d）发生率低于后者（分别为25％，28．6％，54．5％，50％），伴新月体形成，慢性小管间质病变程度较后者明显。6例检测血清ANCA的节段坏死性肾炎的患者中3例阳性（50％）。结论：类风湿性关节炎相关肾损害可表现为系膜增生性病变（伴IgA和不伴IgA沉积），膜性病变和节段坏死性肾炎，常伴慢性小管问质病变及血管病变。系膜增生性病变伴IgA沉积和节段坏死性肾炎患者血尿、肾功能不全发生率高，而系膜增生性病变不伴IgA沉积和膜性病变患者以蛋白尿为主，血尿及。肾功能不全发生率低。节段坏死性肾炎ANCA阳性率较高。