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    Usefulness of combined therapy involving addition of salazosulfapyridine (SASP-combined therapy) was evaluated in patients with rheumatoid arthritis refractory to Methotrexate (MTX). The study involved 47 patients with RA (6 males and 41 females) with a mean age of61. 8years. Mean duration of sickness was 12 years and 11 months. Mean DAS28CRP at the start of SASP-combined therapy was 3. 10. The outcome of treatment in these cases was compared with the outcome of MTX-combined therapy for 14 SASP refractory cases (mean DAS28CRP:2.78) and 14 cases refractory to other drugs treated with MTX＋SASP simultaneously(mean DAS28CRP: 3.45). The response rate (percentage of cases showing moderate or good responses) was slightly lower in the SASP-combined therapy group (57.4%) than in the MTX-combined therapy group (78.6%) and the simultaneous MTX＋SASP therapy group (85.7%). A noteworthy finding was that remission was maintained in 30.6％ of all cases in analysis of long-term outcome of SASP-combined therapy. In analysis of changes in modified total Sharp score (mTSS) in 11 cases where the time course of the score could be followed for one year or longer, mean TSS at the time of evaluation after the start of SASP-combined therapy (4.43) was significantly lower than the mean score at the start of therapy (8.79), that is, a significant ΔTSS on the minus side was recorded in the SASP-combined therapy group during this period, suggesting usefulness of this therapy in suppressing bone/joint destruction. Taken together, these results allow us to say that combined therapy involving addition of SASP is a useful alternative when dealing with patients with rheumatoid arthritis refractory to MTX.

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    In this paper, the clinical effect of mizoribine (new prescription in2009) for rheumatoid arthritis (RA) in our hospital was investigated. Twenty-one patients (10males and11females) were studied. The average age of the patients was 70.3years (ranging from 41to83years). Seventeen patients took 150 mg/day of mizoribine (once a day), two patients took 100 mg/day (once a day) and two remaining patients took 300 mg/week (pulse treatment with methotrexate (MTX). As for the clinical evaluation of mizoribine assessed by DAS28, two patients showed good responses and eight patients had moderate responses whereas eleven patients had no response. The ratio of good and moderate responses in relation to all the patients was47.6％.In the patients over70years old, the ratio was71％. No patients suffered from side effects appeared. Mizoribine might be a good option for rheumatoid arthritis in elderly patients, because it is a well-balanced medicine in terms of safety and efficacy.

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Objective: To examine whether (1) etanercept (ETN) 25 mg once weekly is effective in maintaining a clinical response in patients with rheumatoid arthritis (RA) who have responded to 50 mg once weekly (dose reduction group), and (2) whether low dose ETN treatment (25 mg weekly or biweekly) is effective enough to improve disease activity of RA.
Methods: In the dose reduction group, 18 patients were included. The ETN dose was decreased from 50 mg once weekly to 25 mg once weekly. Parameters of RA disease activity (mean values of ESR, CRP, DAS28ESR and DAS28CRP) were assessed at the following points: before dose reduction, 3 months after dose reduction, and 6 months after dose reduction. In the low dose treatment group, 7 patients were included. ETN was initiated at a dose of 25 mg weekly or biweekly. Parameters of RA disease activity were evaluated in the same way as the dose reduction group. Remission rates were also studied in both groups.
Results: In the dose reduction group, disease activity parameters resulted in unaltered after 6 months. In the low dose treatment group, the CRP, DAS28ESR and DAS28CRP values significantly decreased (2.88±2.46 to 0.32±0.42, 4.37±1.52 to 3.16±1.38, and 3.97±1.23 to 2.32±0.82, respectively) after 6 months. Remission rates of ETN dose reduction group and low dose treatment group increased from 66.6 to 72.2%, and 14.2 to 50.0%, respectively.
Conclusion: The sustained effect in the ETN dose reduction group and obvious improvement of clinical parameters of the low dose treatment group suggest that both treatment methods can induce clinical benefits in some RA patients who can’t be prescribed the full dose of ETN.

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Purpose: As mizoribine (MZR) had been the only official immunosuppressive therapy for lupus nephritis in Japan until tacrolimus was admistered in January 2007, efficacy and safety of MZR for steroid refractory patients with systemic lupus erythematosus (SLE) was studied.
Methods: We identified the SLE patients treated with MZR. We checked retrospectively the reason for adding MZR, the steroid dose, and the levels of complement and anti-DNA antibody.
Results: We found treatment of MZR 44 patients (46 courses) among 197 patients with SLE tracked by our hospital since 1997.The reasons for adding MZR were as follows: difficulty of tapering steroid 11 cases (23.9%), elevation of anti-DNA antibody 27 cases (58.7%), hypocomplementemia 7 cases (15.2%), proteinuria 2 cases (4.3%), skin lesions 5 cases (10.9%), and post-therapy after intra venous cyclophosphamide (IVCY) treatment 8 cases (17.4%). MZR was considered to be effective in 31 cases (70.5%). Hair loss as an adverse effect of MZR was only found in one case. Although MZR treatment was not effective in aggressively relapsed cases and they were treated with more than doubling dose of steroid and/or azathioprine or IVCY, MZR was effective for the patients for whom it was difficult to spare a moderate dose of steroids.
Conclusion: MZR is mainly used for the patients with lupus nephritis, kidney transplantation, and rheumatoid arthritis in Japan. This has the characteristics of weak immunosuppressive effect but less adverse effect. In this study we confirmed the efficacy of MZR for mildly relapsed SLE and steroid sparing effect.

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    The effective period of antibiotic prophylaxis on postoperative infectious complications was evaluated in our centre on 135 patients undergoing total knee replacement. Of 135 patients, 45 received CEZ or CMZ over 48 hours(1 g at induction of anesthesia and 1 g every 12 h,d.i.v.), 90 patients did MINO for oral administration at least for 14 days after drip administering of cefem over 48 hours as shown in ahead.
    There was no significant difference in the rate of patients who developed superficial surgical site infection between these two groups (one patient in the former and two patients in the later group). CRP and WBC were evaluated in these two groups and the level of CRP was higher at 1 week after surgery in the later group. The difference in the two groups was not significant in the occurrence of proven or suspected infections involving other body systems. Preoperative HbA1c did not show correlation statistically with the occurrence of SSI nor infections involving other body systems―, even though the level of WBC at 1,2 weeks after surgery and CRP at 1 week was significantly higher in the group with more than 6.4 of HbA1c.

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    MRI examinations of the hands of three patients with rheumatoid arthritis (all women; ages: 56, 76, and 54 years) were performed using the Rheumatoid Arthritis MRI Scoring System (RAMRIS) before tocilizumab treatment and after achieving remission at 6, 10 and 16 months. Mean DAS28 and mean scores for synovitis, bone marrow edema, and bone erosion prior to tocilizumab treatment were 4.58, 6.0, 22.0, and 29.3, respectively. After tocilizumab treatment, these parameters were 2.06, 2.7, 14.0, and 24.7, respectively.
    MRI assessment revealed that tocilizumab improved, but did not completely normalize, synovitis and bone edema in all patients. In case 1, the patient showed improvements in synovitis and bone marrow edema several months later after achieving clinical remission.

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    The treatment of patients with active RA (rheumatoid arthritis) and respiratory complications, such as obsolete tuberculosis and lung fibrosis,is an important clinical issue for rheumatologists. In most cases, classic DMARDs (disease-modifying antirheumatic drugs) were used and ineffective already. Methotrexate and leflunomide are not suitable because of preexisting respiratory complications. It is risky to use TNF (tumor necrosis factor) inhibitors because they increase the risk of tuberculosis and other infectious diseases.
    Monotherapy with tocilizumab, which is an IL-6 (interleukin-6) inhibitor, was superior to monotherapy with methotrexate or TNF inhibitors. Tocilizumab was generally well tolerated in patients with active RA. The incidence of serious infections was also generally low, no greater than the incidence observed with MTX or TNF inhibitors. Tocilizumab does not increase the risk of tuberculosis. Therefore, tocilizumab was adopted to treat two high-risk patients, a 63-yearold woman with obsolete pulmonary tuberculosis and chronic bronchitis and an 82-year-old woman with lung fibrosis. DAS28ESR was 5.02 and 6.04, respectively. Tocilizumab was carefully administrated under following conditions: (ⅰ) adequate treatment and/or control of any comorbidity (e.g., infectious diseases, lifestyle diseases, etc.) before and during administration of tocilizumab, (ⅱ) appropriate infection control precautions and health care, and (ⅲ) prompt response to adverse events. After treatment with tocilizumab, RA rapidly remitted and QOL improved. Though tocilizumab therapy is not to be recommended positively for high-risk patients, tocilizumab can be a therapeutic option.

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    Diffuse alveolar hemorrhage (DAH) is a rare pulmonary complication of collagen-vascular diseases. DAH patients develop severe hypoxemia caused by wide alveolar collapse. DAH that originates in vasculitis is generally treated with the immunosuppressive agent; for instance, mPSL pulse therapy and/or cyclophosphamide. However, it takes a couple of days for the effects to appear. Mechanical ventilation is used to support these patients until the treatment takes effect. Most of the ventilation used during conventional management of these patients may be directed at recruitable and probably more healthy units, resulting in their overdistension, which is thought to be one of the causes of ventilator-associated lung injury. We make APRV (airway pressure-release ventilation) for DAH as a supportive management.
    Here, we report three cases with DAH; a 36-year-old woman with systemic lupus erythematosus, a 46-year-old woman with anti neutrophil cytoplasm autoantibodies-related vasculitis, and a 72-year-old woman with rheumatoid vasculitis and severe vasculitis. They were treated with the immunosuppressive agent and APRV. Their DAH resolved by 25～30 mmH₂O peek pressure of APRV in a short period. In our experience, APRV ameliorated pulmonary hemorrhaging. However, subcutaneous emphysema and pneumomediastinum were caused by the high Peek pressure in two cases. Therefore, these prompted us to pay attention to the setting of APRV pressure.

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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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[in Japanese]

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