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    Objectives: To assess the efficacy of mizoribine (MZR) pulse therapy for rheumatoid arthritis (RA) patients resistant to biologics.
    Subjects and methods: Eight RA cases were analysed in this study. All cases were female, and their average age was 69.0±10.8 years old. Infliximab, etanercept, adalimumab, and tocilizumab had been administered for 3, 2, 2, and 1 patient, respectively. We performed MZR pulse therapy (300 mg/week; 100 mg every 12 hours, weekly), and estimated the activity of RA before and after the therapy. We also measured the blood concentration of MZR at approximately 3 hours postdose.
    Results: After 12 weeks, tender joint count, swollen joint count, ESR, CRP, DAS28-ESR, DAS28-CRP, SDAI, CDAI, and patient VAS were significantly improved, and this improvement was sustained at 24 weeks. At 12 weeks, EULAR good response was achieved in 2 patients, moderate response was in 4, and no response was in 2. At 24 weeks, EULAR good response was achieved in 5 patients, and moderate response was in 3. Some patients received reduced dose of PSL and/or DMARDs. One patient was refractory to 300 mg/week of MZR, but improved at 450 mg/week of MZR. In patients who responded to MZR pulse therapy, the blood peak level was higher than or equal to 0.90 μg/ml.
    Conclusions: The addition of MZR pulse therapy is a useful strategy for RA patients refractory to biologics.

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    The time of an operation, infections, healing wounds and an exacerbation of arthritis have been pointed out as problems in joint surgery for RA patients being administered biological drug. (Materials and methods) Seventeen joints with total knee arthroplasty (TKA) in 15 patients with RA during a biological treatment which were followed for one year or more were examined. The average age was 59.4 years old at TKA. The clinical results of TKA, perioperative problems, and the disease activity of RA were investigated. (Results) There were no cases associated with complications and there was also no perioperative exacerbation of arthritis. The clinical results of TKA were good, and there were no cases which produced loosening and an infection 4.7 years after TKA. The value of DAS28-ESR at the time before a biologics administration improved gradually before the TKA operation and for one year after operation. Improved DAS28 also was maintained postoperatively for about five years. (Conclusion) It was possible to delay TKA in cases where biological treatments were effective, if the degeneration of the knee joint is slight or moderate. In cases where the degeneration is progressing, TKA should be actively introduced because further improvement of RA inflammation and ADL can be expected.

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    A 33-year-old woman with systemic sclerosis was admitted to our hospital because of fever, headache and confusion. Although aseptic meningitis was diagnosed and her symptoms were improved by administration of antivirals and antibiotics, fever and elevated serum creatine kinase levels associated with scleroderma persisted. After she received high-dose glucocorticoid therapy, headache and confusion also relapsed. Brain magnetic resonance imaging showed hyperintense lesions in the posterior lobes on T₂-weighted and fluid-attenuated inversion recovery images. She was diagnosed with reversible posterior leukoencephalopathy syndrome and provided with control of blood and brain pressures. Her symptoms and imaging findings resolved immediately.

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    A 43-year-old man with bronchial asthma whohad been treated with inhaled corticosteroid/long-acting β2 stimulator was admitted to our hospital because of acute onset of numbness in the extremities and exertional dyspnea. On the basis of neurological examinations, he was diagnosed as having multiple mononeuritis. Chest computed tomography demonstrated bilateral diffuse ground-glass attenuations and pleural and pericardial effusion, whereas arterial blood gas analysis revealed severe hypoxia (PaO2 46.1 Torr on room air). Blood analyses demonstrated an increase of white blood cells (43,500/ul), peripheral eosinophilia (32,625/ul), and elevated levels of lactate dehydrogenase (LDH)(514 IU/l), surfactant protein D (SP-D)(325 ng/ml), Creactive protein (CRP)(6.28 mg/dl), immunoglobulin E (IgE)(932 IU/ml) and brain natriuretic peptide (BNP)(386.1 pg/ml). Serum myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) and proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA) were negative. Although no blood was evident in sputum samples, bronchoalveolar lavage fluid appeared grossly bloody. On the basis of these findings we diagnosed this patient as having Churg-Strauss syndrome (CSS) with diffuse alveolar hemorrhage (DAH).
    The abnormal shadows on chest X-ray films and computed tomography scans, peripheral blood eosinophilia, numbness of the extremities and neurological abnormalities caused by multiple mononeuritis resolved rapidly in response to methylpredonisolone pulse therapy, intravenous cyclophosphamide and intravenous immunoglobulin. The present case of CSS associated with DAH is rare, and few similar cases have been reported in detail previously.

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[in Japanese]

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[in Japanese]

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[in Japanese]

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[in Japanese]

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[in Japanese]

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