Acute respiratory distress syndrome associated with rapid aggravation of rheumatoid arthritis.

A 76-year-old woman with seropositive rheumatoid arthritis (RA) developed acute respiratory distress syndrome (ARDS) following an appearance of severe inflammatory symptoms in multiple synovial joints. High-dose pulse therapy with methylprednisolone induced a marked improvement in pulmonary conditions. To the best of our knowledge, this is the first case in the literature to show a causal relationship between ARDS and RA. We should be alert to the possibility that ARDS can occur as an acute-type pulmonary complication of RA, particularly when patients show rapid aggravation of rheumatic activity.

A followup study of asymptomatic carriers of Pneumocystis jiroveci during immunosuppressive therapy for rheumatoid arthritis.

OBJECTIVE: To examine the preventive effects of prophylaxis against Pneumocystis jiroveci-induced pneumonia (PCP) in patients receiving immunosuppressive therapy for rheumatoid arthritis (RA) who are colonized by this organism. METHODS: We performed molecular testing by polymerase chain reaction (PCR) for P. jiroveci on induced sputum or bronchoalveolar lavage fluids of 82 patients with RA. During primary prophylaxis, asymptomatic carriers of this organism were examined by high-resolution computed tomography and PCR every 2 weeks. RA patients who had developed PCP received PCR tests every week. Once negative results were obtained, PCR testing was scheduled at Months 1, 3, and 6, followed by reexaminations every 6 months. RESULTS: We found 9 cases of asymptomatic carriage of P. jiroveci. All the carriers had received low doses of methotrexate. Upon introduction of PCP prophylaxis, 5 cases tested negative for PCR within 1 month. Three carriers developed PCP before starting prophylaxis, but these tested negative for PCR after short periods (1-2 weeks) of PCP treatment. Once P. jiroveci was eradicated, all cases maintained negative PCR results during followup without prophylactic intervention, even after resuming immunosuppressive therapy. One patient refused PCP prophylaxis, but no PCP developed. CONCLUSION: RA patients with asymptomatic carriage of P. jiroveci benefited from short-term prophylaxis against PCP. Positive PCR results appeared to be predictive of future development of PCP in RA patients. Identification of P. jiroveci carriers will encourage prompt introduction of PCP prophylaxis when rheumatologists consider immunosuppressive therapy for RA.

Comparison of pulmonary abnormalities on high-resolution computed tomography in patients with early versus longstanding rheumatoid arthritis.

OBJECTIVE: To identify the predominant radiological abnormalities in the lungs of patients with early rheumatoid arthritis (RA) and in those with longstanding RA. METHODS: We performed high-resolution computed tomography (HRCT) on a total of 126 patients with early RA (n = 65) and longstanding RA (n = 61). The most likely diagnosis for each case was made on the basis of the predominant HRCT findings and their extent in the lungs. Pulmonary function tests were done for RA patients with parenchymal abnormalities. RESULTS: The most frequent finding was bronchial dilatation (41.3%), followed by ground-glass attenuation (27.0%), parenchymal micronodules (15.1%), subpleural micronodules (15.1%), reticulation (11.9%), bronchial wall thickening (11.9%), nodules (10.3%), honeycombing (8.7%), and airspace consolidation (4%). Parenchymal micronodules and bronchial wall thickening, indicative of small airway diseases, were more prominent in the patients with longstanding RA. There were no significant differences in the frequency of interstitial abnormalities such as ground-glass attenuation, reticulation, honeycombing, or consolidation between the 2 groups. We identified 10 patients with bronchiolitis pattern, 11 with nonspecific interstitial pneumonia (NSIP) pattern, 2 with usual interstitial pneumonia (UIP) pattern, and 2 with organizing pneumonia (OP) pattern. Mean values of FEV1/FVC ratio and FEV25-75 were lower in the patients with the bronchiolitis pattern, and DLCO was decreased in the patients with the NSIP or UIP pattern. CONCLUSION: Interstitial abnormalities were frequently observed even in patients with early RA, although most of them had no respiratory symptoms. Bronchiolar abnormalities were associated with the duration of RA.

Delayed spinal infection after laminectomy in a patient with rheumatoid arthritis interruptedly exposed to anti-tumor necrosis factor alpha agents.

We report a case of spondylodiscitis caused by Staphylococcus aureus 8 months after laminectomy of the lumbar spine, occurring in a rheumatoid arthritis (RA) patient interruptedly treated with anti-tumor necrosis alpha (TNFalpha) agents. The patient had suffered from seropositive RA for 2 years. An intravenous infusion (200 mg) of infliximab, a chimeric antibody against human TNFalpha, was introduced; however, due to Pneumocystis jiroveci pneumonia, this therapy was withdrawn. Four months later, the patient underwent an L3-L4 and L4-L5 laminectomy for spinal stenosis. Two months after surgery, we started treatment with 25 mg of etanercept, a soluble humanized TNF receptor dimer, subcutaneously twice a week. At that time, wound healing was satisfactory and no evidence of infection was obtained. Eight months after surgery, septic spondylodiscitis of the lumbar spine occurred. To the best of our knowledge, this is the first case in the literature to show a delayed type of postoperative infection as a complication of non-instrumented orthopedic surgical procedures. Despite interruption of anti-TNFalpha therapy before surgery, patients may remain at risk of developing postoperative infections.

Asymptomatic carriage of Pneumocystis jiroveci in elderly patients with rheumatoid arthritis in Japan: a possible association between colonization and development of Pneumocystis jiroveci pneumonia during low-dose MTX therapy.

Low-dose methotrexate (MTX) has been used effectively for rheumatoid arthritis (RA) because of its favorable risk-benefit ratio. One of the recent concerns arising from this therapy is a possible increase in the rate of opportunistic infections, particularly Pneumocystis jiroveci pneumonia (PCP). In this study, we report two cases of PCP occurring during low-dose methotrexate therapy for RA and review 13 additional cases from the literature on Japanese patients with RA. The average age of these patients was 67.7 years, and most were over the age of 60. MTX-associated PCP appears to occur more frequently in elderly individuals in Japan. To identify individuals with a high risk of PCP, we performed a polymerase chain reaction on specimens from induced sputum or bronchoalveolar lavage fluids from 55 patients with RA. At that point in time, they showed no evidence of PCP development. We found six patients (10.9%) having asymptomatic carriage of P. jiroveci. The mean age of the P. jiroveci-positive patients was 74.7 years, which was significantly older than the P. jiroveci-negative patients (mean age 63.6 years). Of the RA patients over the age of 65, 18.8% (6 cases out of 32) were carriers of P. jiroveci. There were no significant differences in RA duration or counts of white blood cells or lymphocytes between the positive and negative groups. Notably, we encountered a case of PCP occurring in an asymptomatic carrier of P. jiroveci during low-dose MTX therapy for RA. This case appeared to be a reactivation of latent infection. By careful follow-up on the carriers of P. jiroveci, we succeeded in promptly diagnosing PCP, and we employed the appropriate therapeutic strategies for this possibly life-threatening complication.

A simultaneous onset of organizing pneumonia and rheumatoid arthritis, along with a review of the literature.

Organizing pneumonia (OP) is a specific type of interstitial pneumonia that has been noted as one of the pulmonary manifestations during the course of rheumatoid arthritis (RA). In this study, we report a case with a simultaneous development of OP and RA. The patient presented with concurrent flu-like symptoms and arthralgia of multiple joints, and antibiotic therapy was not effective. The rheumatoid factor (RF) and anti-cyclic citrullinated antibodies were both high. Multiple air-space opacities on chest radiographs and bilateral peripheral consolidations on high-resolution computed tomography films were evident. The histology of transbronchial lung biopsy samples was characterized by intra-alveolar buds of granulation tissue consisting of intermixed myofibroblasts and connective tissues. Treatment with prednisolone induced a complete recovery from OP without relapses. Our review of previous reports about RA-associated OP (RA-OP) suggested that the high titer of RF and increased disease activity of RA indicate a great risk of developing OP. This condition may represent a lung's reaction in the RA-associated inflammatory and/or immune process. We should be aware of RA-OP cases in which pulmonary manifestations precede articular symptoms. In these cases, respiratory manifestations are the main evidence of RA activity. In most cases of steroid-resistant RA-OP, the use of immunosuppressants was effective. Since OP may progress to fibrotic lung disease during the course of RA, we may consider performing a second lung biopsy for steroid-resistant patients, even if they have once been diagnosed as OP.

Early rheumatoid arthritis in a patient with Sjögren's syndrome and pulmonary nodular amyloidosis: clinical implication of early limited use of infliximab.

Infliximab, an anti-tumor necrosis factor alpha antibody, is among the most effective therapies for rheumatoid arthritis (RA). In this study, we report a patient with early RA of 6 months who has Sjögren's syndrome and pulmonary nodular lesions concomitantly. The patient did not respond to methotrexate (MTX, 6;Smg per week) for 3 months. When introduction of infliximab therapy is considered, we need to exclude the possibility of pulmonary granulomatous infection and malignancy. With the use of computed tomography-guided percutaneous needle biopsy and subsequent histological examinations, this case was rapidly and confidently diagnosed as localized pulmonary nodular amyloidosis. Immunochemical staining showed light chain type nodular amyloidosis by a deposition of immunoglobulin kappa light chains, which is a rare condition in a patient with Sjögren's syndrome. We started combination therapy of infliximab (200;Smg per infusion) and MTX (6;Smg per week). Because of severe systemic eruption, this therapy was stopped halfway through the third infusion of infliximab, and MTX monotherapy was continued. Despite the withdrawal of infliximab therapy, the C-reactive protein values were decreased to an undetectable level at week 14, and the disease activity score for 28 joints was 3.1 at week 22. Clinical remission has been maintained more than 14 months with MTX alone. Infliximab has been used only for patients with recalcitrant RA, because the cost of its lifelong use would be an economic burden in most cases. An optimal and affordable strategy for the treatment of early RA should be developed. Our findings may support the idea that the combination therapy of infliximab and MTX for early RA alters the course of the disease.

Methotrexate pneumonia lacking dyspnea and radiographic interstitial patterns during treatment for early rheumatoid arthritis: bronchoalveolar lavage and transbronchial lung biopsy in a differential diagnosis.

Methotrexate (MTX) pneumonia is an unpredictable and sometimes life-threatening adverse effect occurring in the treatment of rheumatoid arthritis (RA). We present a case of MTX pneumonia lacking severe respiratory symptoms and typical radiographic findings. A 66-year-old man with early RA presented with intermittent fever and nonproductive cough during the MTX therapy, but neither hypoxemia nor dyspnea was a complaint. His chest X-ray films revealed multiple bilateral consolidations, but interstitial infiltrates were not observed. High-resolution computed tomography showed no ground-glass opacities. In contrast, the histological findings of transbronchial lung biopsy (TBLB) samples were characterized by the interstitial infiltration of mononuclear cells and hyperplasia of type II alveolar cells, which are the main features of drug-induced interstitial inflammation. Special stains for microorganisms were negative for the TBLB samples. Although cultures of bronchoalveolar lavage (BAL) fluids were slightly positive for Haemophilus influenzae, intensive antibiotic therapy was ineffective. A discontinuation of MTX followed by steroid therapy induced the patient's dramatic recovery. A new treatment with tacrolimus was started for RA. We would like to emphasize that the histological examinations and microbiological studies using BAL and TBLB are useful for the exclusion of other causes and the diagnosis of MTX pneumonia, especially in a case without typical respiratory symptoms and radiographic patterns.

Association of galectin-9 with eosinophil apoptosis.

BACKGROUND: There is no information whether galectin-9 (a novel eosinophil chemoattractant) was associated with pathogenesis of eosinophilic disorders. METHODS: We assessed the expression of galectin-9 with imunostaining and in situ hybridization both in the lesion of angiolymphoid hyperplasia with eosinophilia, and peripheral blood eosinophils of eosinophilic patients (E-Eos) in comparison with those of normal volunteers (N-Eos). Regulation of expression of galectin-9 on eosinophils and the effect of galectin-9 on apoptosis of eosinophil were also evaluated. RESULTS: Many eosinophils infiltrating the site were positive for galectin-9. Surface and intracellular immunoreactive galectin-9 was more evident in E-Eos than N-Eos. When eosinophils were cultured with IL-5 in vitro, the surface galectin-9 expression of E-Eos was significantly downregulated, although that of N-Eos was not affected. Treatment of eosinophils with dexamethasone or anti-Fas antibody significantly upregulated the surface galectin-9 expression of E-Eos. In contrast, dexamethasone partially downregulated the surface galectin-9 of N-Eos, although anti-Fas antibody failed to affect on the surface galectin-9 expression. We also found that recombinant galectin-9 significantly suppressed apoptosis of E-Eos (p = 0.0431), whereas it apparently enhanced apoptosis of N-Eos (p = 0.0173). Furthermore, dexamethasone-induced apoptosis of N-Eos was significantly suppressed by galectin-9 (p = 0.0431), whereas galectin-9 failed to induce significant change in dexamethasone-induced apoptosis of E-Eos. In contrast, apoptosis induced by anti-Fas antibody in both N-Eos (p = 0.0431) and E-Eos (p = 0.0431) was enhanced by galectin-9. CONCLUSIONS: These findings suggested that galectin-9 was produced by eosinophils, and galectin-9 showed heterogeneous effects and kinetics to eosinophils, and this factor might be one of crucial factors in eosinophilic inflammation.

[A case of neurogenic pulmonary edema associated with epileptic seizure].

We report a case of neurogenic pulmonary edema associated with epileptic seizure. A 36-year-old woman had had several episodes of fainting and postictal respiratory failure, and since July 1998 had been admitted to a nearby hospital three times. On October 12, 1999, she was again admitted to a nearby hospital with the same symptom, and was transferred from that hospital to ours for evaluation of the recurrent respiratory disorder. Low-grade fever, mild leukocytosis, hypoxemia and bilateral diffuse opacities were observed as previously on chest radiography, and improved within several days without any specific therapy. The negative C reactive protein level, normal cardiac function and faintly bloody bronchoalveolar lavage fluid were also observed. There was no evidence of aspiration pneumonia, infectious disease, or underlying heart or lung disease. Electroencephalography showed spikes in accord with the left temporal lobe, and the cause of the patient's fainting was thought to be temporal lobe epilepsy. After all other causes had been excluded, this case was diagnosed as neurogenic pulmonary edema associated with epileptic seizure. Only about 40 cases of the postictal pulmonary edema have been reported since 1908, and the pathophysiologic mechanism of this condition is still unknown. Neurogenic pulmonary edema associated with epileptic seizure is rare, but the importance of awareness of this condition needs to be emphasized because it is suspected to be the cause of unexpected sudden death in epileptics. We should consider the disease as important in the differential diagnosis of acute respiratory failure associated with epilepsy.