Intensive immunosuppressive therapy for endogenous lipoid pneumonia associated with rheumatoid arthritis

Abstract

Endogenous lipoid pneumonia is an uncommon inflammatory pulmonary disease that is caused by lipids from an endogenous source, the treatment for which has not been established. We report the first case of endogenous lipoid pneumonia presenting as lung consolidation and which was associated with rheumatoid arthritis. Treatment was successful with intensive immunosuppressive therapy. When a physician finds lung consolidation in a patient with active rheumatic disease, lipoid pneumonia should be considered.     

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.     

A case of organizing pneumonia induced by tocilizumab

A 66-year-old woman rheumatoid arthritis was treated with methotrexate and tocilizumab. Chest radiography revealed bilateral consolidation of an upper lesion in the lung. Laboratory data indicated a hepatic disorder and increased eosinophils. Transbronchial lung biopsy specimens showed organizing pneumonia. Infection was unfavorable based on culture and PCR. Drug lymphocyte stimulation test showed positive results both for methotrexate and tocilizumab. We were concerned that her pneumonitis was drug-induced. And the symptoms appeared after the infusion of tocilizumab. Here, we report a case of tocilizumab-induced organizing pneumonia.     

Consolidation with a twisted appearance along the airways: A report of five cases of interstitial pneumonia

High-resolution CT showed areas of airspace consolidation with a twisted appearance of the airways, along with areas of peribronchial ground-glass attenuation and traction bronchiectasis, in five patients with interstitial pneumonia. These areas of airspace consolidation were termed “twisted consolidation” (TwC). The five patients included two patients receiving treatment for rheumatoid arthritis (RA), one patient with newly diagnosed RA, and one patient who subsequently showed RA. Three patients showed improvement after steroid administration. An association of TwC with RA is suspected, but further studies are necessary.     

A case of pulmonary nontuberculous mycobacteriosis induced by tocilizumab treatment for rheumatoid arthritis

A 65-year-old woman whose rheumatoid arthritis was treated with tocilizumab (TCZ) was found in chest radiography to have a new consolidation in the right lower lung field. Positive Mycobacterium intracellulare and Mycobacterium avium cultures in sputum and bronchial secretions yielded a diagnosis of pulmonary nontuberculous mycobacteriosis. The most common adverse TCZ effect is infection. This case highlights the fact that those treated with TCZ should be considered at elevated risk for developing nontuberculous mycobacteriosis.     

改良床旁肺部超声评估方案对重症患者肺实变和肺不张的诊断价值

  目的 探讨改良床旁肺部超声评估方案（BLUE方案）对重症患者肺实变和肺不张的诊断价值。方法 选呼吸衰竭需机械通气超过48 h的患者,同时行床旁胸部X线、CT检查及BLUE方案、改良BLUE方案检查患者肺实变、肺不张情况,并与床旁胸部X线和CT对比,同时比较改良BLUE方案与BLUE方案评价肺实变与肺不张的差异。结果 最终78例患者纳入本研究。胸部CT发现70例（89.74%）患者存在不同程度的肺实变、肺不张。床旁胸部X线诊断肺实变、肺不张的敏感性为31.29%,特异性为75.00%,诊断准确率为38.46%。改良BLUE方案发现68例患者存在肺实变、肺不张,诊断肺实变、肺不张的敏感性为95.71%,特异性为87.50%,诊断准确率为94.87%,与胸部CT比差异无统计学意义（P>0.05）。BLUE方案发现48例患者存在肺实变、肺不张,诊断敏感性为65.71%,特异性为75.00%,诊断准确率为66.67%。BLUE方案未发现的肺实变、肺不张,胸部CT证实肺实变、肺不张部位主要位于双肺下叶后基底段。结论 重症机械通气患者肺实变、肺不张发生率高,改良BLUE方案可以发现绝大部分肺实变、肺不张,具有较高的敏感性、特异性及诊断准确率,由于其具有即时、床旁、无创、可重复的优越性,将成为床旁评价重症患者肺实变、肺不张的首选的、重要的安全检查手段。     

Rheumatoid pleural effusion: lack of response to intrapleural corticosteroid

Two cases of rheumatoid arthritis with large persistent, asymptomatic pleural effusions are presented. Repeated thoracentesis and intrapleural instillation of corticosteroid proved ineffective in management. However, the persistence of the effusion did not result in any respiratory complications. In one case the effusion disappeared spontaneously long after articular disease remitted, and in neither case did the size of the effusion parallel articular disease activity. It would appear that treatment directed solely at elimination of large rheumatoid pleural effusions is both unrewarding and unnecessary, as long as the underlying lung is normal.     

Comparative study of carcinoembryonic antigen in rheumatoid synovium, tumour, and normal adult lung.

Material reacting like carcinoembryonic antigen (CEA) in the radioimmunoassay has been extracted from rheumatoid synovial membranes. This CEA activity has been compared to that found in hepatic metastases from colorectal tumours and in normal adult lung. The antigen in the rheumatoid synovium has been shown to be more sensitive to perchloric acid and to isolate with a lower weight than that derived from the tumour and lung. Immunodiffusion studies with anti-CEA indicate that the CEA-like determinants in the rheumatoid synovium have partial identity with tumour CEA and that a significant proportion of them are associated with large molecular weight material. Production of an antiserum to these CEA-like components in the rheumatoid synovium should enable further identification of their relationship to tumour CEA and might allow a better judgement of whether or not they represent the expression of neoantigens in the disease.     

MDCT Evaluation of Costal Bone Lesions: Comparison of Axial,Multiplanar, and 3D Volume-Rendered Images: A Retrospective Study

The aim of this retrospective study was to compare accuracies of axial, multiplanar, and volume-rendered 3-dimensional (3D) images in the diagnosis of costal bone lesions.Forty-one patients, aged from 10 to 72-years old, with costal bone lesions underwent multidetector CT (MDCT). Axial, multiplanar, and 3D-volume-rendered images were reviewed by 3 reviewers for the property of the lesions (fracture, tumor, and tumor-like lesions or inflammation). In case of fracture, the diagnosis was demonstrated with the location of the fracture and the amounts of the costal bone involved. In case of a tumor or tumor-like lesions, the diagnosis was demonstrated pathological property. Final diagnosis was determined by biopsy or surgery. Diagnostic accuracy and interreviewers agreement were evaluated.For the diagnosis of fractures, average accuracy was 77%, 100%, and 100% for axial, multiplanar, and 3D-volume-rendered images, respectively. For the diagnosis of tumor and tumor-like lesions, average accuracy was 90% for axial, 96% for multiplanar, and 99% for 3D-volume-rendered images. For the diagnosis of inflammation lesions, average accuracy was 100% for all the 3 image formats. Interobserver agreement independence of imaging formats was high.Multiplanar and 3D-volume-rendered images were superior to axial images in diagnosis of fracture, tumor, and tumor-like lesions; however, for the evaluation of inflammation lesions, there were no difference by 3 image formats.     

A case of poorly differentiated lung adenocarcinoma showing air-space consolidation caused by aerogenic metastasis]

A 78-year-old woman was admitted to our hospital because of dyspnea. A chest radiograph and a computed tomogram on admission showed air-space consolidation in the left upper lung field, and so pneumonia was diagnosed. Although antibiotics were administered, the air-space consolidation did not improve. A transbronchial lung biopsy was performed, yielding a pathologic diagnosis of poorly differentiated lung adenocarcinoma. Despite combination chemotherapy with docetaxel and UFT, the air-space consolidation expanded, and the patient finally died of respiratory failure 3 months after diagnosis. Autopsy revealed air-space consolidation due to poorly differentiated lung adenocarcinoma, with large atypical cells diffusely floating in the alveolar spaces. It has been recognized that bronchiolo-alveolar carcinoma and well-differentiated lung adenocarcinoma present with air-space consolidation, reflecting the cancer cells lining the alveolar walls. However, in this case, the air-space consolidation was due to cancer cells diffusely floating in the alveolar spaces in aerogenic metastasis. It was considered that this is a rare case, which presented with a very interesting development pattern.     

Immune Reconstitution Inflammatory Syndrome Associated with Pneumocystis jirovecii Pneumonia and Cytomegalovirus Colitis in a Patient with Rheumatoid Arthritis

A 68-year-old woman presenting with rheumatoid arthritis was admitted due to pancytopenia caused by methotrexate. Pneumocystis jirovecii pneumonia was diagnosed based on the abnormal shadows observed on chest computed tomography, the presence of serum β-D-glucan, and positive P. jirovecii-DNA results in a sputum analysis. Subsequently, after treatment with leucovorin and trimethoprim-sulfamethoxazole, lung consolidation was found to be aggravated, along with a rapidly increasing leukocyte count. In addition, cytomegalovirus colitis was diagnosed. Both conditions were associated with immune reconstitution inflammatory syndrome caused by recovery from leukopenia. The patient was successfully treated with intravenous methylprednisolone pulse therapy and ganciclovir.     

Apical fibrocavitary lesions of the lung in rheumatoid arthritis. Report of two cases and review of the literature

Two patients with rheumatoid arthritis and fibrocavitary lesions in the upper lobes of the lungs are described. Postmortem pathologic studies of the lungs revealed the presence of clinically unsuspected necrobiotic nodules with cavitation and excluded other possible causes such as infections and vasculitis. These findings support the view that apical fibrocavitary disease is a clinically distinct pattern of lung involvement in rheumatoid arthritis.     

Management of extra-articular disease manifestations in rheumatoid arthritis

PURPOSE OF REVIEW: To discuss the rationale for various treatment strategies in rheumatoid arthritis with extra-articular manifestations, and to review advances in understanding the impact of extra-articular rheumatoid arthritis and its management. RECENT FINDINGS: Recent epidemiologic studies of extra-articular rheumatoid arthritis manifestations have emphasized their major role as predictors of premature mortality in patients with rheumatoid arthritis, and provide a rationale for aggressive ant-rheumatic treatment of extra-articular rheumatoid arthritis. Previous uncontrolled or nonrandomized studies favor the use of cyclophosphamide in patients with systemic rheumatoid vasculitis, and methotrexate in the case of other manifestations of extra-articular rheumatoid arthritis. Recent case reports indicate that patients with rheumatoid lung disease may respond to cyclosporine or tumor necrosis factor inhibitors, and that tumor necrosis factor blocking therapy also may be successful in cases of treatment-resistant vasculitis. By contrast, it has been suggested that tumor necrosis factor inhibitors may induce some manifestations of extra-articular rheumatoid arthritis. Data indicating a high risk of serious infections and cardiovascular disease in patients with extra-articular rheumatoid arthritis underline the importance of carefully monitoring such patients. SUMMARY: Extra-articular rheumatoid arthritis is a serious condition, and rheumatoid arthritis patients with extra-articular manifestations should be aggressively treated and monitored. Advances in the understanding of the pathogenesis of rheumatoid arthritis and developments of new, more specific drugs may be of particular benefit to patients with extra-articular disease.     

Rheumatoid lung nodulosis and osteopathy associated with leflunomide therapy

Background Leflunomide (LEF) is indicated in adults for the treatment of active rheumatoid arthritis (RA). LEF inhibits dehydroorotate dehydrogenase, a key enzyme of the pyrimidine synthesis in activated lymphocytes. Among rare adverse effects, fatal interstitial lung disease has been recently reported during treatment of RA with LEF in Japan. Clinical trials outside Japan do not suggest that LEF causes an excess of pulmonary adverse effects. Development and increase of peripheral rheumatoid nodules in typical sites of RA patients following LEF therapy has been recently reported. Objectives Two cases with new and accelerated development of rheumatoid lung nodulosis during LEF therapy were described in this study. Methods LEF treatment was administered to two male patients (77 and 66 years old) with long-standing active seropositive nodular RA with failure of multiple second line drugs and without lung involvement. Clinical and laboratory assessment using the American College of Rheumatology response criteria, chest computed tomography (CT), quantification of serum rheumatoid factor (RF), and monocyte count of peripheral blood along with routine laboratory follow up were performed on both patients before and during therapy. In case 1, a bone scan was performed due to sustained limbs pain. Open lung biopsy was performed in case 1 and core lung biopsy in case 2. Results Both patients achieved full clinical remission during 2 months of LEF therapy. In case 1, the first complaints were limbs pain after 10 months of treatment associated with intensive bone uptake on a bone scan consistent with hypertrophic pulmonary osteopathy. Productive cough developed after 3 months of the therapy in case 2. Initially, these complaints were not attributed to therapy. New lung disease was present on CT with cherry-like progressive cavitary nodules, predominantly involving the basal segments of the right lung. The first lung lesions were found by CT 13 months (case 1) and 7 months (case 2) after the beginning of therapy and were erroneously related to bronchiectasia in case 2. In both cases, the lung biopsy showed necrosis surrounded by epithelioid mononuclear inflammation with giant cells, consistent with rheumatoid lung node. The time that elapsed between the beginning of the first symptoms to LEF discontinuation was very long: 13 months in case 1 and 24 months in case 2. Discontinuation of LEF therapy was followed by an arrest in growth of lung nodules, resolution of limb pain, and gradual improvement of bone scan. A significant decrease of monocyte count and RF level in peripheral blood was observed during LEF therapy in both cases. Conclusion For the first time, we described rheumatoid lung nodulosis as complication of successful LEF therapy for RA. Hypertrophic pulmonary osteopathy with severe limbs pain and dry cough were the first manifestations of the lung nodulosis. Monocytopenia during LEF therapy is proposed to be involved in pathogenesis of this rare complication of LEF therapy.     

Synovitis,acne, pustulosis,hyperostosis, osteitis syndrome with invisible organizing pneumonia: A case report

We report the case of a 59-year-old female patient, presenting with pustular rash on both hands and pain in the lumbosacral part and left lower limb. A magnetic resonance imaging examination of the left leg was undertaken and the result showed that a malignant lesion with bone destruction of the left femoral shaft could not be excluded. Subsequently, bone tumor was excluded by pathological examination. Lung computed tomography scan showed patchy consolidation and cord shadow in the middle left lung. Subsequently, lung cancer was excluded by pathological examination, and the histopathological changes of lung were consistent with those of organized pneumonia. Blood tests revealed elevated C-reactive protein and erythrocyte sedimentation rate. Antinuclear antibody, rheumatoid factor, and human leukocyte antigen-B27 were unremarkable. Whole body bone scintigraphy via technetium 99m-methyl diphosphonate showed increased radionuclide uptake in the left middle femur. Based on her clinical manifestations, imaging results and bone scintigraphy, the patient was diagnosed as having synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome. Loxoprofen and Tripterygium wilfordii Hook F led to impressive clinical and radiologic improvement.     

Drug therapy for osteoporosis associated with rheumatoid arthritis (estrogen replacement therapy)

Various types of drug therapy are available for the management of osteoporosis associated with rheumatoid arthritis. Hormone replacement therapy plays an especially important part in the management of this condition. Although hormone replacement therapy increases lumbar bone mineral density in patients who have osteoporosis and rheumatoid arthritis, similar to those with primary osteoporosis, its effect on femoral bone mineral density remains controversial. Since hormone replacement therapy is also effective for rheumatoid arthritis, it is an important treatment option in patients who also have osteoporosis. Evidence is awaited from studies with new designs, including assessment of fracture risk.     

Rheumatoid arthritis, corticosteroid therapy and hip fracture.

OBJECTIVE--To identify the risk of hip fracture in patients with rheumatoid arthritis and those taking corticosteroids. METHODS--In a population based case-control study, we compared 300 consecutive patients with hip fracture aged 50 years and over from a defined district and 600 age and sex matched community controls. RESULTS--The risk of hip fracture was increased in patients with rheumatoid arthritis (odds ratio (OR) 2.1; 95% confidence interval (CI) 1.0 to 4.7) and those receiving corticosteroids (OR 2.7; 95% CI 1.2 to 5.8). The risk attributable to rheumatoid arthritis was markedly reduced by adjusting for functional impairment, while that for steroid use remained after adjusting for body mass index, smoking, alcohol, and functional status. CONCLUSIONS--Hip fracture risk is approximately doubled amongst patients with rheumatoid arthritis and among those taking steroids. These risk increases are, to some extent, independent of each other. In rheumatoid arthritis, the risk was most closely associated with functional impairment, whereas steroid use did not appear to be confounded by this variable.     

Short Term vs Long Term Dexamethasone Treatment: Effects on Rat Diaphragm Structure and Function

The effects of dexamethasone treatment duration (2.5 vs 10 weeks) on diaphragm myosin heavy chain isoforms, fiber types, and contractile characteristics were studied in male rats. Compared with ad libitum-fed and pair-fed controls, dexamethasone significantly decreased body weight, costal diaphragm weight, and the relative expression of myosin heavy chain isoform MHC-2B. Compared with pair-fed controls, the effect on MHC-2B expression was greater after 10 weeks than after 2.5 weeks. Type I and type II costal diaphragm fiber atrophy occurred, and type II fiber atrophy was greater after 10 weeks. Costal diaphragm-specific forces were not affected significantly by dexamethasone, regardless of the treatment duration or control group comparison. Fatigue resistance indexes were increased significantly after long term treatment compared with pair-fed controls and after both short term and long term treatment compared with ad libitum-fed controls. In conclusion, the effects of dexamethasone on MHC isoform phenotype expression, fiber type costal diaphragm atrophy, and fatigue resistance were dependent on treatment duration, with greater effects after long term (10 weeks) treatment. Accepted for publication: 24 November 1997     

A case of rheumatoid arthritis involving disseminated torichosporonosis

A 75-year-old man who developed disseminated trichosporonosis had a long history of immunosuppressive therapy with weekly methotrexate and low-dose prednisolone for rheumatoid arthritis (RA). He had been administered 30 mg of prednisolone per day for organizing pneumonia, probably due to the RA, for about 3 months before admission for a lumbar compression fracture. He then developed bilateral aspiration pneumonia with pleural effusion, treated successfully with broad-spectrum antibiotics meropenem and ciprofloxacin, and fluid management. He then developed acute, progressive respiratory failure with changes in both lung lobes in chest computed tomography (CT). Meropenem, ciprofloxacin, micafungin, and pulsed steroid administration were ineffective. He died of respiratory failure, after which Trichosporon asahii was first detected in blood and urine culture. Disseminated trichosporonosis was determined based on positive blood culture, elevated serum glucuronoxylomannan antigen and beta-D glucan, and the man's lack of clinical progress. He had numerous risk factors for trichosporonosis, including neutrophilic dysfunction due to prolonged steroid therapy, administration of broad-spectrum antibiotics and micafungin, and central venous catheterization. Disseminated trichosporonosis is a chiefly hematological infection and case reports without hematological disorders are rare, so we report this instructive case.     

Clinical and radiological results of GSB III total elbow arthroplasty in patients with rheumatoid arthritis

Total elbow arthroplasty (TEA) with the GSB III prosthesis was performed in 32 patients (36 elbows) with rheumatoid arthritis between 2001 and 2009. At final follow-up, 31 patients (35 TEAs) were available for clinical and radiological evaluation. The mean follow-up period was 6.3 (2.0–10.3) years, with a minimum follow-up of 2 years. The mean Mayo elbow performance score was significantly improved from 48 points preoperatively to 83 points at final follow-up. The radiographic loosening rate was 14.3% for humeral components and 5.7% for ulnar components. There were 4 cases of intraoperative fracture and 1 case of humeral shaft fracture at 4 months after surgery. The rates for loosening and fracture were relatively low when compared with those in other studies of linked TEA. There were 2 cases of ulnar nerve palsy, but there was no deep infection or triceps disruption. The clinical results of TEA using the GSB III prosthesis in patients with rheumatoid arthritis were found to be satisfactory.