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Toshihiro Nanki,
Ikumi Onoue, Kenji Nagasaka,
Aiko Takayasu,
Masashi Ebisawa,
Tadashi Hosoya,
Toshizumi Shirai,
Takahiko Sugihara,
Shinya Hirata,
Tetsuo Kubota,
Masayoshi Harigai,
Nobuyuki Miyasaka
Annals of the rheumatic diseases 01/2013; · 8.11 Impact Factor
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ABSTRACT: OBJECTIVE: To investigate the safety and efficacy of a dose-escalation regimen of trimethoprim-sulfamethoxazole (TMP/SMX) for prophylaxis against Pneumocystis jiroveci pneumonia (PCP) in rheumatic diseases. METHODS: Data from 41 patients, who received glucocorticoids with or without immunosuppressive agents and prophylactic use of TMP/SMX, were retrospectively analyzed. Thirteen patients were started on a daily dose of 10 % of single-strength (SS) TMP/SMX, which was increased gradually (dose-escalation group), while 28 patients were started on 1 SS tablet daily (routine group). RESULTS: In the dose-escalation group, the retention rate was 100 % at 6 months. In the routine group, 5 patients discontinued TMP/SMX; the retention rate was 82.1 %. Moreover, the retention rate when taking a daily dose of 50 % or more of SS TMP/SMX, or 1 SS tablet thrice-weekly, was significantly higher in the dose-escalation group (100 versus 71.4 %, P = 0.032). No PCP was observed in the dose-escalation group; however, 1 patient in the routine group, who had discontinued TMP/SMX, developed PCP. The rate of adverse effects was less, although nonsignificant, in the dose-escalation group (30.8 versus 46.4 %, P = 0.344). CONCLUSIONS: In rheumatic diseases, a dose-escalation regimen of TMP/SMX resulted in a higher retention rate and was safer than the routine regimen.
Modern Rheumatology 08/2012; · 1.58 Impact Factor
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ABSTRACT: A 73-years-old man, who was a farmer, developed fever, fatigue, and muscle weakness. His serum creatine kinase (CK) level was found to be high. Computed tomography showed the presence of bibasilar subpleural interstitial infiltrates. He was therefore clinically given a diagnosis of polymyositis. After high-dose glucocorticoid (GC) and GC-pulse therapies were started, his symptoms improved, and the CK level decreased. The patient's son was 44-years-old. He moved back into his parent's home, quit his corporate job and started working in the agricultural field. He then developed fever, myalgia, and muscle weakness. His serum CK level was high. Therefore, he also was given a diagnosis of polymyositis. After high-dose GC and immunosuppressive therapies were stared, his symptoms improved and CK level decreased. Polymyositis may be triggered by specific environmental exposures in genetically susceptible individuals. The son developed the disease immediately after he moved into his parent's home and changed his profession to farming which was same as his father's profession. Moreover, the father and his son may have had common genetic factors. We believe that some environmental factors triggered the onset of polymyositis in the father and his son.
Japanese Journal of Clinical Immunology 01/2012; 35(2):144-9.
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ABSTRACT: We describe 3 siblings who suffered from marked eosinophilia with organ involvement. One sibling, who experienced cervical lymphadenopathy and peripheral neuropathy with eosinophilia (5,834 cells/μL) following bronchial asthma, was diagnosed with Churg-Strauss syndrome (CSS) according to the criteria of the American College of Rheumatology. Another sibling, who suffered from severe asthma with persistent polyarthritis and eosinophilia (2,496 cells/μL), was also diagnosed with CSS according to the criteria of the Japanese Ministry of Health, Labour and Welfare. The remaining sibling, who had eosinophilic pleuritis with peripheral blood eosinophilia (699 cells/μL), did not fulfill the widely used criteria for CSS or hypereosinophilic syndrome (HES) ; however, he fit the newly proposed criteria for HES. Glucocorticoid treatment relieved their symptoms. Although the diagnoses and the criteria used for diagnosis differed between the siblings, all 3 patients showed common features such as eosinophilia with organ involvement that required treatment, indicating the possibility of familial eosinophilia (FE). Furthermore, the clinical features observed differed substantially from those of previously reported FE patients, therefore, these 3 siblings may be affected by a type of FE distinguishable from those previously described.
Japanese Journal of Clinical Immunology 01/2012; 35(6):533-8.
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ABSTRACT: A 34-year-old woman with discoid lupus erythematosus and lupus profundus was admitted to our hospital showing signs of a fever, malaise, and abdominal swelling. Diagnosis of cytophagic histiocytic panniculitis (CHP) was made based on lobular panniculitis with a hemophagocytosis. Treatment with high doses of prednisolone combined with cyclosporine A (CsA) was not effective enough. However, after changing CsA to tacrolimus (TAC), CHP improved. Our case demonstrates that TAC may be a novel therapy for CHP.
Modern Rheumatology 03/2011; 21(5):553-6. · 1.58 Impact Factor
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ABSTRACT: A 76-year-old woman with rheumatoid arthritis who had been taking methotrexate (MTX) for 9 months was admitted because of acute respiratory failure. A chest radiograph revealed diffuse ground-glass attenuation. MTX-induced interstitial pneumonia (IP) was strongly suspected. Her respiratory failure worsened in spite of steroid pulse therapy. Intravenous administration of ulinastatin, however, dramatically improved her clinical condition. The second ulinastatin treatment was also effective. This case suggests that peripherally administered ulinastatin may be effective for steroid-resistant MTX-induced IP.
Modern Rheumatology 02/2011; 21(1):79-84. · 1.58 Impact Factor
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ABSTRACT: A 63-year-old man was admitted to our hospital because of persistent fever, weight loss, painful foot, and purpura on his extremities. He had lower extremity peripheral neuropathy, and skin biopsy of the purpura revealed vasculitis. Serum tests for myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA), proteinase 3-ANCA, and ANCA (indirect fluorescent antibody method) were all negative. Computed tomography revealed a 6-cm large, irregularly shaped lesion in the right kidney, while the nasal sinuses and lungs were intact. Based on these findings, a diagnosis of suspected systemic vasculitis associated with renal cell carcinoma was made. Thus, right nephrectomy was performed. However, the pathological findings showed a large infarct with necrotizing vasculitis of the arcuate, interlobular, and perinephric small arteries and a crescent formation in the glomerulus. Based on these findings, he was diagnosed with microscopic polyangiitis. Due to rapidly worsening symptoms of purpura and neuropathy, treatment with a high dose of corticosteroid was initiated on postoperative day 2, which led to improvement of his symptoms. Vasculitis accompanied with a mass-like lesion is occasionally confused with malignancy. The lesion in our patient was considered to have originated by asymptomatic renal infarction. This case suggests that a renal mass-like lesion with vasculitis should be diagnosed with care.
Japanese Journal of Clinical Immunology 01/2011; 34(3):162-7.
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ABSTRACT: A 64-year-old woman with rheumatoid arthritis (RA) began to complain of recurrent non-productive cough 5 months after starting adalimumab. The chest radiograph and high-resolution computed tomographic findings revealed diffuse ground-glass attenuation. Her clinical course suggested that interstitial pneumonia (IP) may have been induced by adalimumab, and she was successfully treated with a medium dose of corticosteroid. This case indicates that adalimumab-associated IP should be considered if a RA patient develops non-productive cough following adalimumab therapy.
Modern Rheumatology 05/2010; 20(5):518-21. · 1.58 Impact Factor
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ABSTRACT: A 30-year-old pregnant woman experienced mild dyspnea in April 2009. She complained of mild myalgia and was subsequently admitted to our hospital in June 2009 because of worsening dyspnea. Physical examination revealed fine crackles in the lower lung field, but no eruptions externally. Laboratory findings revealed elevated serum levels of myogenic enzymes (aldolase, 17.6 IU/l and myoglobin, 247.2 ng/ml) and positive titers for the anti-Jo-1 antibody and hypoxia (PaO(2), 79.4 Torr). The chest radiograph revealed a ground-glass opacity. The patient was diagnosed as interstitial pneumonia (IP) associated with polymyositis (PM) at 20 weeks of gestation. On July 9, we commenced the initial treatment-steroid pulse therapy with 60 mg/day of prednisolone and 3 mg/day of tacrolimus. We also induced abortion. The treatment of corticosteroids and tacrolimus was, however, ineffective even after increasing the tacrolimus dose to 6 mg/day. On July 30, she suddenly experienced chest pain along with severe dyspnea. Computed tomography revealed the presence of pneumomediastinum and deterioration of the IP. We added cyclophosphamide pulse therapy to the existing regimen ; this improved the disease course, reduced hypoxia, and improved radiographic findings. We believe that this is a rare case of IP with PM during pregnancy.
Japanese Journal of Clinical Immunology 01/2010; 33(3):142-8.
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Modern Rheumatology 12/2008; 19(2):216-8. · 1.58 Impact Factor
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ABSTRACT: We report a case of systemic lupus erythematosus (SLE) complicated with hypertrophic pachymeningitis. A 34-year old woman who was diagnosed as SLE in 1985 was admitted to our hospital for a high grade fever and a headache. Laboratory findings showed increased titer of anti-double strand DNA antibody and decreased number of platelets. She complained a severe headache and hearing loss which were worsened by head-up position, resembling the symptoms of intracranial hypotension. MRI findings revealed thickened dura and she was diagnosed as hypertrophic pachymeningitis. Both clinical symptoms and laboratory findings were resolved after methyl-prednisolone pulse therapy followed by a high dose of prednisolone. Although hypertrophic pachymeningitis is a rare complication with SLE, it should be considered in SLE patients with severe headache.
Japanese Journal of Clinical Immunology 03/2007; 30(1):55-60.
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Tetsuo Kubota,
Tokiko Nii,
Toshihiro Nanki,
Hitoshi Kohsaka,
Masayoshi Harigai,
Yukiko Komano,
Takahiko Sugihara,
Yoshinori Nonomura,
Wataru Hirose, Kenji Nagasaka,
Tetsushi Sakurai,
Nobuyuki Miyasaka
Modern Rheumatology 02/2007; 17(6):531-3. · 1.58 Impact Factor
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ABSTRACT: It is known that the cyclin-dependent kinase inhibitor (CDKI) gene p21(Cip1) suppresses rheumatoid inflammation by down-modulating type I interleukin-1 receptor (IL-1RI) expression and inhibiting JNK activity. The purpose of this study was to determine whether CDK activity directly modulates the production of inflammatory molecules in patients with rheumatoid arthritis (RA).
Genes for the CDKIs p16(INK4a) and p18(INK4c), a constitutively active form of retinoblastoma (RB) gene product, cyclin D1, and CDK-4, were transferred into RA synovial fibroblasts (RASFs). RASFs were also treated with a synthetic CDK-4/6 inhibitor (CDK4I). Levels of matrix metalloproteinase 3 (MMP-3), monocyte chemoattractant protein 1 (MCP-1), and IL-1RI expression were determined by Northern blotting, real-time polymerase chain reaction analysis, and enzyme-linked immunosorbent assay. CDKIs were immunoprecipitated to reveal their association with JNK.
Transfer of the p16(INK4a) and p18(INK4c) genes and CDK4I suppressed the production of MMP-3 and MCP-1. Unlike p21(Cip1), neither CDKI gene inhibited IL-1RI or JNK. The expression of MMP-3 was up-regulated when CDK-4 activity was augmented. This regulation functioned at the messenger RNA (mRNA) level in MMP-3, but not in MCP-1. Transfer of active RB suppressed the production of MMP-3 and MCP-1 without changing their mRNA levels.
CDK-4/6 modulated the production of MMP-3 and MCP-1. MMP-3 production was regulated primarily at the mRNA level in an RB-independent manner, whereas MCP-1 production was controlled posttranscriptionally by RB. These results show that cell cycle proteins are associated with control of mediators of inflammation through multiple pathways.
Arthritis & Rheumatism 08/2006; 54(7):2074-83. · 7.87 Impact Factor
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ABSTRACT: Interstitial lung disease (ILD) is a common complication of polymyositis (PM) and dermatomyositis (DM), and accounts for a significant proportion of their morbidity and mortality because of the resistance to therapeutic agents including corticosteroids. Its pathogenic mechanism is not known, but several studies have provided findings implicating that T-cells, especially activated CD8+ cells, may play essential roles, and thus could be therapeutic targets in this disease. To test this hypothesis, we began clinical investigation of the efficacy of T-cell-specific immunosuppressants, cyclosporine (CsA) and FK506, in PM/DM patients with ILD. In our retrospective nationwide multi-center study compiling a total of 53 patients, a combination of CsA and corticosteroids resulted in favorable early and long-term outcome in the majority of patients except for DM patients with acute ILD. In this subset, those who received the combination as an initial therapy had better survival than those who initially received corticosteroids alone. FK506 has a similar mode of action but is up to 100-fold more potent than CsA in vitro, and has been used in more refractory ILD cases. We next reviewed 5 PM/DM patients with ILD who failed on various immunosuppressants including CsA and were subsequently treated with FK506 in our hospital, and found that 3 improved promptly, 1 gradually and steadily, and another case responded slowly after prednisolone dose was increased. None developed adverse effects. In summary, these T-cell targeted therapies have a potential to be the cornerstone of the treatment for ILD in PM/DM patients. The combination therapy with CsA and corticosteroids may be efficacious especially when used early. FK506 may be advantageous even in refractory cases to CsA. These findings indicate that further investigation is warranted. Currently, prospective investigation of FK506 is underway.
Autoimmunity 09/2005; 38(5):383-92. · 2.47 Impact Factor
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ABSTRACT: We performed a retrospective analysis to establish a statistical model for the prediction of Pneumocystis pneumonia (PCP) in patients with connective tissue diseases (CTD) undergoing medium- or high-dose corticosteroid therapy, to identify independent risk factors for PCP and to evaluate the efficacy of the prophylactic use of trimethoprim-sulfamethoxazole (TMP/SMX) against PCP. One hundred and twenty-four patients who were receiving the equivalent of or more than 30 mg/day of prednisol-one (PSL) were classified into two groups according to the presence (prophylaxis group, n = 46) or absence (nonprophylaxis group, n = 78) of prophylactic TMP/SMX. We developed a statistical model that was suitable for predicting the development of PCP using a logistic regression analysis. The initial steroid dosage, decreased peripheral blood lymphocyte counts at 2 weeks (<500/microl), and usage of immunosuppressant during 2 weeks after the institution of PSL (>or=30 mg/day) were found to independently contribute to the development of PCP. Finally, in the patient group with a defined risk for PCP, a significant prophylactic effect of TMP/SMX was demonstrated. We recommend the prophylactic use of TMP/SMX for patients with CTD undergoing medium- or high-dose corticosteroid therapy who are determined to have a high risk of developing PCP.
Modern Rheumatology 01/2005; 15(2):91-6. · 1.58 Impact Factor
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ABSTRACT: Forced expression of a cyclin-dependent kinase inhibitor gene, p21(Cip1) in the synovial tissues was effective in treating animal models of rheumatoid arthritis. Synovial hyperplasia in the treated joints was suppressed, reflecting the inhibitory effect of p21(Cip1) on cell cycle progression. Additionally, lymphocyte infiltration, expression of inflammatory cytokines, and destruction of the bone and cartilage were inhibited. To determine why the cell cycle regulator gene exerted such anti-inflammatory effects, we investigated gene expression by rheumatoid synovial fibroblasts with or without the p21(Cip1) gene transferred. We have found that p21(Cip1) gene transfer down-regulates expression of various inflammatory mediators and tissue-degrading proteinases that are critically involved in the pathology of rheumatoid arthritis. These molecules included IL-6, -8, type I IL-1R (IL-1R1), monocyte chemoattractant protein-1, macrophage inflammatory protein-3alpha, cathepsins B and K, and matrix metalloproteinases-1 and -3. Down-regulation of IL-1R1 by p21(Cip1) resulted in attenuated responsiveness to IL-1. Inhibition of the inflammatory gene expression by p21(Cip1) was seen even when IL-1 is absent. This IL-1R1-independent suppression was accompanied by reduced activity of c-Jun N-terminal kinase, which was associated with p21(Cip1), and inactivation of NF-kappaB and AP-1. These multiple regulatory effects should work in concert with the primary effect of inhibiting cell cycle in ameliorating the arthritis, and suggest a heretofore unexplored relationship between cyclin-dependent kinase inhibitor gene and inflammatory molecules.
The Journal of Immunology 11/2003; 171(9):4913-9. · 5.79 Impact Factor
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ABSTRACT: Rheumatoid arthritis (RA) is characterized by chronic inflammation of multiple joints. Large numbers of T cells, which produce type 1 cytokines, infiltrate into RA synovium. Chemokines and chemokine receptors are considered to contribute to the T cell infiltration. In this study, we examined the role of CX3CL1/fractalkine and its receptor CX3C chemokine receptor 1 (CX3CR1) in the T cell migration into RA synovium.
Using flow cytometry, immunohistochemistry, and reverse transcription-polymerase chain reaction, we analyzed CX3CR1 expression by peripheral blood and synovial T cells, and CX3CL1 expression in synovium from patients with RA. Cytokine and cytotoxic molecule expression by CX3CR1-positive T cells was analyzed by flow cytometry.
CX3CR1 expression by peripheral CD4+ and CD8+ T cells was up-regulated in RA patients. The peripheral CD4+ and CD8+ T cells expressing CX3CR1 predominantly produced interferon-gamma and tumor necrosis factor alpha, and expressed cytotoxic molecules such as granzyme A and perforin. Furthermore, CX3CR1+,CD3+ T cells infiltrated into RA synovium. CX3CL1, the unique ligand of CX3CR1, was expressed by endothelial cells and synoviocytes in RA synovium, but not in osteoarthritis synovium.
Our findings suggest that the interactions of CX3CL1 and CX3CR1 might contribute to the accumulation of CX3CR1+ T cells expressing type 1 cytokines and possessing cytotoxic granules in RA synovium.
Arthritis & Rheumatism 12/2002; 46(11):2878-83. · 7.87 Impact Factor
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ABSTRACT: Objective
Rheumatoid arthritis (RA) is characterized by chronic inflammation of multiple joints. Large numbers of T cells, which produce type 1 cytokines, infiltrate into RA synovium. Chemokines and chemokine receptors are considered to contribute to the T cell infiltration. In this study, we examined the role of CX3CL1/fractalkine and its receptor CX3C chemokine receptor 1 (CX3CR1) in the T cell migration into RA synovium.Methods
Using flow cytometry, immunohistochemistry, and reverse transcription–polymerase chain reaction, we analyzed CX3CR1 expression by peripheral blood and synovial T cells, and CX3CL1 expression in synovium from patients with RA. Cytokine and cytotoxic molecule expression by CX3CR1-positive T cells was analyzed by flow cytometry.ResultsCX3CR1 expression by peripheral CD4+ and CD8+ T cells was up-regulated in RA patients. The peripheral CD4+ and CD8+ T cells expressing CX3CR1 predominantly produced interferon-γ and tumor necrosis factor α, and expressed cytotoxic molecules such as granzyme A and perforin. Furthermore, CX3CR1+,CD3+ T cells infiltrated into RA synovium. CX3CL1, the unique ligand of CX3CR1, was expressed by endothelial cells and synoviocytes in RA synovium, but not in osteoarthritis synovium.Conclusion
Our findings suggest that the interactions of CX3CL1 and CX3CR1 might contribute to the accumulation of CX3CR1+ T cells expressing type 1 cytokines and possessing cytotoxic granules in RA synovium.
Arthritis & Rheumatism 11/2002; 46(11):2878 - 2883. · 7.87 Impact Factor
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Hideyuki Iwai,
Ryuji Koike,
Jun Ogawa,
Takahiko Sugihara,
Hiroyuki Hagiyama, Kenji Nagasaka,
Yoshinori Nonomura,
Junko Nishio,
Toshihiro Nanki,
Rieko Tsubata,
Hitoshi Kohsaka,
Tetsuo Kubota,
Nobuyuki Miyasaka
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ABSTRACT: A 36-year-old man was admitted to a hospital with complaints of fever, polyarthralgia and dyspnea. Erythema was observed on his face, extensor surface of the fingers and extremities, and a chest X-ray revealed massive bilateral pleural effusion. He had no sign of myopathy at this point. Pleural fluid was proved to be exudative and contained extremely high levels of hyaluronic acid. He was also complicated with interstitial pneumonitis and was given a pulse therapy with methyl prednisolone followed by daily administration of 55 mg prednisolone (PSL). Twenty days after the commencement of the therapy, pleural effusion decreased but muscle weakness gradually appeared, accompanied by elevation of myogenic enzymes. Myogenic changes on electromyogram, and irregularity of the muscle fibers with slight inflammatory cell infiltrates in a biopsy specimen were demonstrated. He was transferred to our hospital, and a diagnosis of dermatomyositis was made. Later, pleural effusion waxed and waned depending on the dosage of PSL, but no other causative disorder was demonstrated by extensive examinations. This case indicates that the pleuritis could be one of the vasculitic manifestations of dermatomyositis.
Japanese Journal of Clinical Immunology 07/2002; 25(3):270-6.
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Takahiko Sugihara,
Rhuji Koike,
Yurika Nosaka,
Jun Ogawa,
Hiroyuki Hagiyama, Kenji Nagasaka,
Yoshinori Nonomura,
Junko Nishio,
Toshihiro Nanki,
Hitoshi Kohsaka,
Tetsuo Kubota,
Nobuyuki Miyasaka
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ABSTRACT: We report a case of a 27-year-old Japanese female with Sjogren's syndrome (SS), who suffered from several episodes of subcutaneous and mesenteric panniculitis with a recurrence within one year. After a history of fever and skin rash, the patient underwent surgery at a local hospital with a diagnosis of acute appendicitis complicated with an ileocecal abscess. She was also diagnosed as having SS. After the operation, the fever and skin rash persisted. She was treated with prednisolone (PSL), and her symptoms resolved. A recurrent bout of abdominal pain with fever, annular erythema on the trunk and a nodular erythematous rash on the lower extremities occurred six months after the operation. A skin biopsy from the lower extremities showed findings that were compatible with panniculitis. Abdominal computer tomography (CT) showed a diffuse swelling with soft tissue density in the intestinal mesenterium and para aortic area. A retrospective examination of the operative specimen obtained from the local hospital revealed centrilobular infiltration of neutrophils in the mesenteric adipose tissue with fat necrosis, which is compatible with mesenteric panniculitis. Twenty mg/day of PSL was successful in treating the systemic panniculitis, and the abnormal diffuse soft tissue density on the abdominal CT disappeared after three weeks of PSL administration. Systemic panniculitis is a rare complication in SS, and the pathogenesis is unclear.
Japanese Journal of Clinical Immunology 07/2002; 25(3):277-84.
