Multiple intrapulmonary rheumatoid nodules]

A 66-year-old woman who had been treated at a nearby hospital since 1977 for rheumatoid arthritis complained of cough. Chest X-ray films disclosed multiple nodular shadows with cavitation in the fields of both lungs. The patient was admitted to our hospital and a thoracoscopic lung biopsy was performed. Histologically, the nodule consisted of necrotizing granuloma, indicating a necrobiotic nodule. Rheumatoid nodule was diagnosed because the patient exhibited rheumatoid arthritis. The chest X-ray shadow disappeared without medication. Rheumatoid nodules without coniosis are uncommon, but should be considered in the differential diagnosis of lung nodular lesions in patients with rheumatoid arthritis.     

Case report and literature analysis of the clinical factors relating to the development of fibrotic changes in gold lung

A 26-year-old female with gold lung induced by Shiosol (gold thiomalate) administered for her rheumatoid arthritis is presented. Chest X-ray films after treatment with prednisolone hardly improved and showed diffuse fibrotic shadow. We reviewed previously reported cases of gold lung and tried to determine the clinical factors which might affect the development of pulmonary fibrotic changes in gold lung. The cases reported in Japan were classified into two groups according to the improvement of X-ray films after steroid therapy: group A in which the chest X-ray film returned to almost normal, group B these with diffuse fibrotic shadow. No significant difference was observed in the values of %VC and PaO2 admission between the two groups. The total dose of gold received was greater (p less than 0.05) and the duration of gold received was longer (p less than 0.01) in group B than in group A. These findings suggest that the development of pulmonary fibrosis does not depend on the severity of the injury indicated by pulmonary function, but in part on the amount of gold which has been stored in pulmonary macrophages. No statistical difference was shown in the initial dose of steroids between these groups. The duration between the onset of gold lung and the start of steroid therapy were longer in group B than than group A (p less than 0.05). Thus, early diagnosis and treatment with steroids are highly recommended in the clinical management of patients with gold lung.     

Successful treatment using cyclosporine in a patient with rhupus complicated by aplastic anemia: a case report and review of the literature

Systemic lupus erythematosus (SLE) co-morbid with rheumatoid arthritis (RA) is known as 'Rhupus syndrome' and is estimated to be present in between 0.01 and 2% of SLE and RA patients. The occurrence of aplastic anaemia in a patient with rhupus is very rare and a treatment for this condition has not been reported. A 52-year-old woman presented complaining of nausea and dizziness during the preceding month. She had been treated for rheumatoid arthritis for 16 years. At the time of presentation, she had a malar rash, multiple arthritis, pancytopenia, pleural effusion, proteinuria, and positive anti-nuclear and anti-dsDNA antibodies. A kidney biopsy revealed ISN/RPS class IV-G (A) lupus nephritis. Bone marrow aspiration and biopsy showed aplastic anaemia with no evidence of viral infection. The patient was successfully treated using cyclosporine and prednisolone and she remained symptom-free at the one-and-a-half-year follow-up. To our knowledge, this is the first report of a successful treatment using cyclosporine in a patient with rhupus complicated by aplastic anaemia.     

Wegener's granulomatosis in a woman with asymptomatic primary biliary cirrhosis

A 60-year-old woman was admitted to our hospital in June 1985, complaining of fever, cough and right lower chest pain, with a five-year history of asymptomatic primary biliary cirrhosis. Chest X-ray on admission showed an infiltrative shadow in the right lower lung field. She was first treated with various antibiotics unsuccessfully. Hemoptysis continued. Dyspnea and anemia appeared. Chest X-ray 17 days after admission showed multiple infiltrative shadows in the both lung fields. She was treated with steroid pulse therapy successfully. During prednisolone treatment decreasing nodular shadows with cavities appeared on chest X-ray. An open lung biopsy was performed in March 1986. The histologic findings showed a necrotizing vasculitis with granuloma and perivascular fibrosis. She was treated with prednisolone and prednisolone-azathioprine therapy unsuccessfully, but successfully with prednisolone-cyclophosphamide therapy. This case was a rare case of Wegener's granulomatosis with transition from fulminant type to granulomatous type. No similar case of Wegener's granulomatosis with asymptomatic primary biliary cirrhosis has been reported in the literature.     

Autoimmune cholangiopathy associated with rheumatoid arthritis

We herein describe a patient with autoimmune cholangiopathy complicated with rheumatoid arthritis. A 58-year-old female was admitted to our hospital due to complications of arthralgia in her fingers, shoulders, elbows, knees and ankles. She presented with abnormally elevated levels of transaminases, alkaline phosphatase and was also negative for hepatitis B virus, hepatitis C virus and the serum mitochondrial antibody test, but had high titers of serum antinuclear antibody, rheumatoid factor and rheumatoid arthritis hemagglutination. A liver biopsy specimen showed chronic non-suppurative destructive cholangitis. She was thus diagnosed to have autoimmune cholangiopathy and rheumatoid arthritis. She began treatment with prednisolone 40 mg per day. After 20 days of steroid therapy, her hepatic function tests improved and the arthralgia symptoms disappeared. This is, to our knowledge, the first case of autoimmune cholangiopathy associated with rheumatoid arthritis, in which both symptoms improved with steroid therapy.     

A case of rheumatoid lung disease in which lung involvement preceded arthritis]

A 75-year-old man was admitted because of dyspnea on exertion and diffuse pulmonary interstitial shadows. An open lung biopsy revealed unclassified interstitial pneumonia. The abnormal shadow subsided spontaneously. Three years later, however, rheumatoid arthritis developed with a simultaneous relapse of interstitial pneumonitis, which was alleviated by steroid therapy. We report here the rheumatoid lung disease that preceded the onset of arthritis, together with a review of the literature.     

A case of smoldering adult T-cell leukemia complicated by various pulmonary infections]

A 46-year-old man was admitted to Oita Medical College Hospital on October 16, 1987, because of cough and sputum. Chest X-ray and chest CT films showed diffuse reticulonodular shadow. The specimens obtained by transbronchial lung biopsy revealed cysts of pneumocystis carinii. Abnormal lymphocytes with lobulated nuclei were found 2-7% of peripheral leucocytes. The anti HTLV-I antibody was positive. According to these data, we diagnosed the patient as smoldering adult T cell leukemia with pneumocystis carinii pneumonia. The abnormal shadow on chest X-ray disappeared after SMX-TMP and pentamidine treatment. After about 1 year, he was again admitted for high fever. Chest X-ray showed infiltration with cavity in right upper lobe. Streptococcus pneumoniae was isolated from the sputum. The infiltration shadow on chest X-ray disappeared after antibiotics treatment. However, multiple nodular shadow appeared on the chest X-ray and ATL cell infiltration was found in the specimens of transbronchial lung biopsy. ATL cells in peripheral blood also increased and serum LDH and Calcium levels were markedly high. According to these data, we diagnosed the patient as having a ATL crisis. Although chemotherapy for ATL was started, the ATL, cell infiltration shadow on the chest X-ray enlarged, and bilateral diffuse patchy shadows was appeared on the chest X-ray. He died of respiratory failure on April 26, 1989. Cytomegalovirus pneumonia and ATL cell infiltration were revealed by necropsy.     

Cellular interstitial pneumonia and follicular bronchiolitis diagnosed by open lung biopsy in a patient with rheumatoid arthritis

A 54-year-old woman under treatment for rheumatoid arthritis was admitted because of aggravation of dyspnea on effort and restrictive pulmonary dysfunction. Although chest X-ray revealed no marked change, the symptoms progressively worsened, necessitating open lung biopsy for diagnosis and treatment. Based on the histopathological findings of the biopsied tissue, the patient was diagnosed as having active rheumatoid lung complicated with cellular interstitial pneumonia and follicular bronchiolitis. The patient responded well to adrenocorticosteroid and immunosuppressor therapy, and is now being followed up as an outpatient. Rheumatoid arthritis can be complicated by diverse lung diseases. Among them one important disease is interstitial pneumonia, which serves as a prognostic factor. When cellular interstitial pneumonia is treated with adrenocorticosteroid therapy, it responds well and its prognosis is good. Therefore, its early detection and appropriate adrenocortical therapy are essential. Patients with rheumatoid arthritis presenting with dyspnea on effort and pulmonary dysfunction should be examined for cellular interstitial pneumonia, follicular bronchiolitis and other lung diseases, even when no marked change is visible on chest X-ray films.     

A case of adult onset Still's disease complicated with cryptogenic organizing pneumonia

Only a few pathologic reports exist describing adult onset Still's disease (AOSD) with pulmonary involvement. We report this very rare case of AOSD complicated with cryptogenic organizing pneumonia (COP). A 32-year-old woman was referred with high spiking fever, salmon-pink rash in her arms and legs, and polyarthralgia. The laboratory data showed marked increases in white blood cell count, an erythrocyte sedimentation rate, and C reactive protein, ferritin, and liver dysfunction. All cultures remained negative, as were autoantibodies and rheumatoid factor. The patient was strongly suspected of AOSD according to specific diagnostic criteria. However, chest X ray disclosed an infiltrative shadow accompanied by air bronchogram in the upper lobe of the right lung and therapy with antibiotics was initiated. As the patient did not respond to antibiotics and a remittent fever of over 38°C, a flexible bronchoscopy was performed. Organizing pneumonia was diagnosed by transbronchial lung biopsy (TBLB) histology and radiologically, and the lesions were thought to be due to pulmonary involvement of AOSD. Therefore, she was diagnosed with AOSD complicated with COP. Oral treatment with prednisolone (30 mg/day) resulted in rapid disappearance of the infiltrative shadow. Symptoms and markers of inflammation also improved. Clinicians should be aware that COP can be a complication of AOSD.     

Atelectasis of the right lower lobe in association with bronchiolitis obliterans organizing pneumonia]

A 58-year-old woman with underlying rheumatoid arthritis was admitted to the hospital because of a dry cough and the presence of an abnormal shadow in the right lower lung field. Consolidation and volume loss in the right lower lobe with air bronchogram were recognized on a chest tomogram. Bronchofiberscopic examination disclosed neither stenosis nor tumors in the large bronchi. Organizing pneumonia was recognized pathologically in transbronchial lung biopsy (TBLB) specimens. The volume of the right lower lobe decreased rapidly, and new infiltration shadows appeared in the right upper and middle lobes. Another bronchofiberscope examination revealed organizing pneumonia, and macrophage infiltrations were seen in the alveoli on histopathological examination of the TBLB specimens. The diagnosis of RA-associated BOOP was made on the basis of agreement of the expansion of the shadows on chest radiographs, the RA symptoms and the RA factor. The patient was treated with prednisolone, and the clinical course was satisfactory, with no recurrence. This case was of interest because BOOP inducing lobar cicatricial atelectasis is very rare.     

A randomised trial of differentiated prednisolone treatment in active rheumatoid arthritis. Clinical benefits and skeletal side effects

OBJECTIVES: To study benefits and skeletal side effects of carefully monitored prednisolone treatment in patients with active rheumatoid arthritis. METHODS: One hundred and two patients with active rheumatoid arthritis were randomly allocated to treatment with disease modifying anti-inflammatory drug (DMARD) alone or DMARD and prednisolone in a one year follow up study. Prednisolone was given in a dose regimen adapted to the disease activity of the individual patient. The mean dose was 6 mg and the mean cumulated dose was 2160 mg. Patients were followed up with disease activity parameters, radiograph of the hands (Larsen score), and bone mineral density (BMD) of the lumbar spine, distal forearm and hand. At one year 26 patients had withdrawn from the investigation leaving 76 patients for evaluation. RESULTS: The results showed that disease activity in the prednisolone treated group was reduced within two weeks. In the DMARD alone group disease activity was gradually reduced over months. At six months there was no difference between the groups as evaluated by an improvement score using a number of ACR criteria. Prednisolone in the present set up was not able to protect significantly against radiological disease progression, although there was a trend towards less progression in Larsen score in the prednisolone group, a matter that was further underlined in an intention to treat analysis. BMD data revealed a significant reduction in spinal BMD in the prednisolone group, whereas prednisolone seemed to have a protective effect against bone loss in the hand and distal forearm. CONCLUSIONS: This study does not allow any firm conclusions for or against the treatment of rheumatoid arthritis with prednisolone. The data suggest that the beneficial effects of prednisolone are not as clear cut in established rheumatoid arthritis as in early disease. Furthermore the data indicate that treatment in the chosen relatively low dose does not provide sufficient control of disease. On the other hand the spinal bone loss observed in the prednisolone group does invite considerations about using higher doses.     

Report of anti-CCP antibody positive paraneoplastic polyarthritis and review of the literature

A 45-year-old female presented to the rheumatology clinic with complaint of pain and swelling of multiple small joints of the hands and feet. She also complained of cough and shortness of breath onset around the same time. Since her cyclic citrullinated peptide antibody (anti-CCP) and rheumatoid factor tests were positive, rheumatoid arthritis (RA) was diagnosed and she was started on prednisone with plans for additional disease modifying therapy. Chest X-ray showed a small right pleural effusion. While additional pulmonary evaluation was being planned, a few weeks later she presented with dyspnea, fever and tachycardia. Spiral CT showed pulmonary emboli and increased pleural effusion and patient was started on anticoagulation. A chest tube was placed and exudative pleural effusion was drained. Cytology sample from bronchoscopy raised concerns for adenocarcinoma. Open lung biopsy confirmed moderately differentiated adenocarcinoma. The patient died of lung cancer in the hospital 8 weeks from her diagnosis of RA. We describe a case of paraneoplastic polyarthritis with positive anti-CCP antibody test which has not been reported before. We also review the literature on paraneoplastic arthritis which has been described in association with various other malignancies besides lung cancer.     

A case of rheumatoid arthritis complicated with methotrexate-induced pneumonitis and pneumocystis pneumonia]

A 62-year-old woman with rheumatoid arthritis was given 4 mg/body methotrexate (MTX) every week and 5 mg prednisolone every day. She developed a severe cough starting in the evening after starting taking MTX and after a fever of 38 degrees and dyspnea appeared the patient was hospitalized. On admission, chest CT findings showed diffuse ground glass attenuation. Pathological findings of specimens obtained by transbronchial lung biopsy showed alveolitis with epithelioid cell granuloma. As a section of the specimen did not show cyst staining by Grocott stain, MTX-induced pneumonitis was diagnosed. The same day, methylprednisolone pulse therapy was started and trimethoprim-sulfamethoxazole (TMP-SMX) was given simultaneously, while MTX was discontinued. On hospital day 3, subsequent data showed a high serum level of beta-D glucan and a positive PCR result for Pneumocystis jiroveci in bronchoalveolar lavage fluid (BALF). Additional section of the specimen showed eosinophilic foamy areas on HE staining and cysts measuring 8 microm, consistent with the Pneumocystis jiroveci lesions by Grocott stain. We present a case of rheumatoid arthritis complicated by methotrexate-induced pneumonitis in which pneumocystis pneumonia was demonstrated by clinical and pathological findings.     

Successful use of immunosuppressive agents for the treatment of progressive rheumatoid interstitial lung disease: a case report]

Interstitial pneumonia (IP) is sometimes a fatal complication of rheumatoid arthritis (RA). We describe a patient with progressive rheumatoid interstitial pneumonia, who responded to intravenous intermittent cyclophosphamide (IV-CY) and cyclosporine (CsA). A 62-year-old man with rheumatoid arthritis was admitted to this hospital because of dyspnea. Examinations on admission revealed that he had active RA with vasculitis and IP Initially, he responded to high-dose corticosteroid therapy. A lung biopsy performed after initial corticosteroid therapy revealed diffuse interstitial pneumonia with marked infiltrations of macrophages into the air spaces. On corticosteroid therapy with prednisolone 30 mg/day, the IP became exacerbated and was refractory to the current high-dose steroid treatment. He responded to intravenous cyclophosphamide, but his IP remained unstable. After CsA treatment was started, a clinical remission was obtained. In this case, CsA was the most effective agent tried. Clinical and pathological considerations led us to speculate that activated alveolar macrophages played a crucial role in the pathogenesis of steroid-resistant IP in this patient, and that the clinical remission induced by CsA may have been due to its inhibitory effect on alveolar macrophages.     

A case of organizing pneumonia which had to be treated with steroids in the early phase of the disease against delayed resolution of severe pneumonia occurring even after antibiotic therapy]

A 58-year-old male was referred to our division because of antibiotic-resistant pneumonia. A chest X-ray film revealed severe pneumonia over the left lung field but laboratory data showed no leukocytosis. Transbronchial lung biopsy findings showed the evidence consistent with organizing pneumonia. One-month prednisolone therapy produced a disappearance of the pneumonia shadow, but a giant bulla was found at the same site. It was considered that it was necessary to treat this case with a combination of effective antibiotics and steroids in the early phase of the disease.     

A case of migratory air space infiltration after radiation therapy for breast cancer]

A 54-year-old woman underwent conserving surgery for right breast cancer, and received a cumulative dose of 50 Gy of radiation therapy to the remaining part of the right breast. About five months after the termination of irradiation, cough and low-grade fever developed. The chest radiograph showed an infiltrative shadow in the right lung field. Organizing pneumonia was identified in the transbronchial lung biopsy specimen. After prednisolone was given to the patient the clinical symptoms and infiltrates seen in the radiograph disappeared. In the course of tapering the prednisolone dose, new infiltrative shadows developed in the upper right lung and the left lung. The histologic changes were shown by transbronchial lung biopsy to be organizing pneumonia. The increased dose of prednisolone resulted in the rapid improvement of the clinical symptoms and chest radiograph abnormalities. This case suggests that breast radiation after conserving surgery for breast cancer may cause a pathologic process similar to that of bronchiolitis obliterans organizing pneumonia.     

A case of pulmonary actinomycosis marked by diagnostic difficulty]

A 59-year-old man was admitted to our hospital for evaluation of an abnormal lung shadow. Chest X-ray and computed tomographic (CT) films showed a mass shadow in the left lower lobe. The shadow decreased in size after the administration of imipenem/cirastatin and clindamycine. Although a transbronchial lung biopsy failed to confirm the diagnosis, histologic examination of percutaneous aspiration biopsy specimens revealed sulfur granules. Actinomycosis was diagnosed but we did not rule out the possibility of coexistent carcinoma. A left lower lobectomy was performed, and the patient has been well without any complaints or recurrence of actinomycosis for 6 months after surgery. We concluded that pulmonary actinomycosis should be considered another candidate for the differential diagnosis of mass shadows from lung cancer.     

A case of aprindine-induced pneumonitis

A 73-year-old man had been treated with Aprindine because of paroxysmal atrial fibrillation. On July 13, 1987, five months after the commencement of aprindine administration, he developed dyspnea and low grade fever. His chest X-ray revealed multiple infiltrative shadows in both lung fields. He was treated by various antibiotics, but the infiltrative shadows increased. BALF showed increased percentage of lymphocytes and a decrease in the OKT4/T8 ratio, and the histological findings of TBLB carried out on August 6, 1987, showed alveolitis with Masson bodies. The lymphocyte stimulation test by drugs was positive only for aprindine. After cessation of Aprindine administration, his complaints and laboratory data improved, but his abnormal shadow on chest X-ray did not diminish completely. Open lung biopsy was performed for differential diagnosis of BOOP, on Sep. 14, 1987. The histopathology of specimens of the lung was compatible with drug-induced pneumonitis. The administration of 30 mg of prednisolone was started on Oct. 14, 1987, and the dosage was decreased gradually. The abnormal shadow on chest X-ray improved. To our knowledge, there has been no reported case of Aprindine-induced pneumonitis, and this could be the first report.     

Serious liver disease induced by infliximab

Infliximab, a chimeric monoclonal antibody that binds the tumor necrosis factor α (TNFα), is used in the treatment of rheumatoid arthritis (RA) and Crohn’s disease (CD). Previous cases of significant secondary liver disease associated with infliximab treatment have been reported in patients with RA, CD, and psoriatic arthritis. Two additional patients with RA who developed a serious liver disease associated with infliximab treatment are reported here. A 39-year old RA patient was admitted with cholestatic liver disease after 8 months of treatment with infliximab. She had no history of hepatic diseases, exposure to hepatotoxic or illicit drugs, or alcohol abuse. A liver biopsy showed severe ductal proliferation with collapse and enucleation of the hepatocytes. Despite aggressive treatment with oral prednisolone, she developed hepatic failure. On the 45th day, a liver transplant was performed. The second patient, a 54-year old RA patient, was diagnosed with autoimmune hepatitis after 12 infliximab infusions. She fulfilled autoimmune hepatitis type 1 criteria. A liver biopsy disclosed an altered lobulillar structure with chronic inflammation and the formation of collagen bands. She was treated with prednisolone and azatioprine and a complete recovery was noted 1 month later. These cases should alert rheumatologists to the possibility of new adverse reactions (liver injury) associated with the use of TNFα blockers in an autoimmune setting.     

A case of pulmonary Mycobacterium gordonae infection with pleural effusion]

A 65-year-old woman, treated with prednisolone (5 mg daily) for rheumatoid arthritis, visited our hospital because of right chest pain. Chest CT showed small nodular shadows in the right lung accompanied with right pleural effusion. A pulmonary Mycobacterium gordonae infection was diagnosed, since M. gordonae was identified twice from her sputum. She was treated with rifampicin, ethambutol and streptomycin for two months, and then streptomycin was replaced with clarithromycin. Three months after the initial treatment, M. gordonae was eradicated from her sputum. Pleural puncture revealed bloody, exudative, lymphocytotic pleural effusion, but no malignant cells were identified. Although pathological diagnosis by thoracoscopic pleural biopsy could not be performed, it is likely that the pleural effusion was associated with the pulmonary M. gordonae infection in the present case.