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    Rheumatoid arthritis (RA) is often associated with pain affecting functionary. Diseasemodifying antirheumatic drugs (DMARDs) and anti-inflammatory treatments may influence pain only to a certain degree, and additional pain treatment may be required. Interventional pain treatment and the use of opioids in musculoskeletal disease has been established in some areas. Although there are no controlled trials available in RA, it is mostly accepted that opioids control pain from RA and they are being increasingly used. Many RA patients continue to experience pain their current treatment with nonopioid analgesics. The use of strong opioids has always been controversial, although increasingly more clinicians feel that opioids are well tolerated and effective and should be made available when nonopioids have failed to control pain. The conditions under consideration clinically fall into two mechanisms, inflammaion and other, the latter taken to include mechanical and neuropathic. A neuropathic mechanism should be considered where there are no signs of nociceptive pathology, specifically inflammation, in the region of pain complaint but where there is allodynia or hyperalgesia to mechanical stimuli. The need for improved pain control in RA is heightened by the insidious and chronic nature of this disease. It is recommended that all clinicians regularly monitor pain levels in their patients and the use strong opioids and the interventional methods as a further step in the treatment of pain from RA.

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    Although tight control is important in treatment of rheumatoid arthritis (RA), it is unclear which composite measure of RA is best to evaluate clinical disease activity of RA. The aim of this study is to compare four composite measures (DAS28-ESR, DAS28-CRP, SDAI, CDAI) in patients with RA treated with anti-TNF agents. The rates of high disease activity (HDA) were 85.4% using DAS28-ESR, 92.1% using DAS28-CRP, 73.0% using SDAI and 73.0% using CDAI at the time of starting anti-TNF therapy in all cases (n＝89). Significantly more patients were evaluated as HDA using DAS28-ESR and using DAS28-CRP than using SDAI and using CDAI. The rates of HDA were 26.9% using DAS28-ESR,35.9% using DAS28-CRP,14.1% using SDAI and 18.0% using CDAI at the time of last visit in only cases who continued anti-TNF therapy (n＝78). The rates of low disease activity (LDA) were 26.9% using DAS28-ESR, 35.9% using DAS28-CRP, 39.7% using SDAI and 39.7% using CDAI at the time of last visit in only cases who continued anti-TNF therapy (n＝78). Significant fewer patients were evaluated as HDA using SDAI than using DAS28-ESR and using DAS28-CRP. The rates of remission were 16.7% using DAS28-ESR, 21.8% using DAS28-CRP, 12.8% using SDAI and 7.7% using CDAI at the time of last visit in only cases continuing anti-TNF therapy (n＝78). There was a statistically significant difference between the rate of remission using DAS28-CRP and the rate of remission using CDAI. Although all patients were evaluated as LDA using all four measures in the EULAR good response group (n＝21), one case using SDAI and one case using CDAI were evaluated as LDA in the no-response group according to the EULAR criteria (n＝15). These results suggest that (1) DAS28-CRP was most sensitive to reflect the change of disease activity, (2) that it was very difficult to achieve remission evaluated by SDAI or CDAI, (3) that physicians must understand the character of each composite measure for RA and (4) that good response according to the EULAR criteria was a beneficial target to treat RA.

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    Oxidative stress is caused by excess reactive oxygen species (ROS) and leads to cell injury, which is involved in many diseases including connective tissue diseases (CTDs) such as systemic lupus erythematosus (SLE) or systemic sclerosis (SSc). In environments of tissue hypoxia or ischemia like lung tissue in patients with pulmonary arterial hypertension (PAH), ROS were produced and able to deteriorate PAH in several ways. To clarify the participation of oxidative stress in the pathogenesis of connective tissue diseases especially with regard to complication of PAH, plasma 8-isoprostane and serum total ROS (i.e., total free radical levels derived from reactive oxygen species) levels were measured in patients with CTDs (SLE, SSc or mixed connective tissue diseases (MCTD)) and healthy controls. Plasma 8-isoprostane levels were not related to any diseases, especially not to SSc or complication of PAH. Total ROS was associated with patient age or complication of PAH. Furthermore, in CTD patients with PAH, total ROS levels were significantly correlated with serum brain natriuretic peptide (BNP) levels or estimated systolic pulmonary arterial pressures by Doppler echocardiogram. These results not only confirmed that oxidative stress played a role in the pathogenesis of CTDs including PAH but also indicate that measurement of plasma ROS can be effectual for detection of complication of PAH in patients with CTDs.

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    We report a case of malignant rheumatoid arthritis (MRA) with distal symmetric sensorimotor neuropathy which showed a good response to tacrolimus therapy. A 72-yr-old female, with a 7 years history of RA was admitted to our hospital because of severe polyarthralgia, numbness of the foot and high fever. After admission she showed progressive symmetrical hypesthesia to anesthesia of bilateral distal lower limb and left footdrop. The diagnosis of MRA was made and we started etanercept and steroid pulse therapy but peripheral neuropathy did not recover. Five months later, tacrolimus was added, then not only polyarthritis but also distal neuropathy begun to improve and complete remission was obtained. This case suggests tacrolimus therapy should be considered for MRA refractory to steroid and anti-tumor necrosis factor treatment.

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    Here, we report a case of effective treatment of an intractable systemic lupus erythematosus (SLE) using mycofenol mofetil and tacrolimus. In this case, the SLE activity was resistant to single immunosuppressive drug therapy such as azathioprin, tacrolimus, cyclosporin A, mycofenol mofetil and prednisolone. Moreover, although she was also treated with 5courses of corticosteroid pulse therapy, double membrane filtration plasmapheresis, and plasma exchange, none of these were effective. After informed consent, treatment using a combination of mycofenol mofetil and tacrolimus together with prednisolone was started. After two months, proteinuria, edema, hypocomplementemia, and alopecia were improved. Thus, the combination therapy including mycofenol mofetil and tacrolimus should be considered as a treatment for SLE, if it is intractable to standard treatment.

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    Here we present a case of microscopic polyangiitis (MPA) who was refractory to the standard therapy by glucocorticoid and cyclophsophamide (CY) but responded quite well to infliximab.
    The 77-year-old female patient, who had been diagnosed with systemic sclerosis long before, presented with general malaise, fever, polyarthralgia, and body weight loss in 2007. The laboratory data revealed rapidly worsening renal function with proteinuria and abnormal sediments, elevated inflammatory markers represented by CRP, and positive MPO-ANCA.
    The treatment by glucocorticoid including pulsed methylprednisolone (MPSL) together with intravenous cyclophosphamide (IVCY) ameliorated these abnormal laboratory data and clinical conditions, and remission of MPA was achieved. However, in spite of sufficient glucocorticoid dosage and 18 courses of IVCY (total CY 9000mg), disease flare occurred twice during 18 months of the treatment course. Moreover, serious side effects such as multiple osteoporotic compression fractures occurred and we had to consider an alternative treatment.
    Infliximab, a monoclonal antibody ag1ainst tumor necrosis factor alpha, has been reported to be effective against refractory ANCA-associated vasculitis (AAV), while other reports dispute its efficacy. To make matters worse, it has the risk of inducing autoimmunity including vasculitis.
    After obtaining informed consent from the patient, infliximab was administered and in relatively short time remission was achieved. So far remission has been successfully maintained for 10 months without complications.
    There is even now a controversy over whether infliximab is effective against AAV or even harmful against it. More experiences should be accumulated to answer this question.

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    A 76-year-old woman had visited our hospital with diabetes mellitus and hypertension. In 2007, urinary protein, antinuclear antibody, scleroderma, and pericardial effusion appeared. In January 2008, she was diagnosed with systemic sclerosis (SSc) by skin biopsy. Afterward, pericardial effusion was increasing gradually, and she was admitted to our hospital with pleural effusion, dyspnea, and systemic edema. She received pleural puncture to remove the effusion and additional diuretic was administered. Her symptoms improved and she was discharged. In April, she was admitted again because pericardial effusion and pleural effusion were increasing. Despite the pleural puncture and the increased-dose of diuretic, her pericaldial effusion was not improved, although the pleural effusion decreased. Prednisolone was initiated at 45 mg/day (1 mg/kg), and the pericardial effusion decreased. Three months later, her renal function worsened gradually and pericardial effusion increased again. She died of renal failure and heart failure. Although pericardial effusion and pericarditis are well-known complications of SSc, the symptoms caused by the pericardial effusion are rarely shown. Pericardial effusion is a prognostic factor preceding renal failure and renal crisis, and the effect of steroid is poor. We thought, through-out our case, a considerable condition that the steroid for pericardial effusion was effective temporarily and that pericardial effusion correlated with renal failure.

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Objective: To evaluate the progression rate to rheumatoid arthritis (RA) in patients with undifferentiated arthritis (UA) with a positive anti-cyclic citrullinated peptides (CCP) antibody and a negative C-reactive protein (CRP).
Methods: We calculated the rate of progression to RA in 50 patients with UA with a positive anti-CCP antibody and a negative CRP from retrospective clinical data.
Results: Among the 50 UA patients, 22 patients (44%) progressed to RA by 1987 ACR criteria during 25.1±13.9months observation. Patients who progressed to RA had a significantly higher rheumatoid factor and a greater number of swollen joints on first visit and more were found to be CRP-positive, satisfy the criteria for early RA by JCR 1994, and satisfy the diagnostic criteria for RA by ACR/EULAR 2009than patients who had not progressed to RA.
Conclusion: Even if CRP is negative upon the first visit, the rate of development to RA in UA patients with a positive anti-CCP antibody and more swollen joints on first visit is high.

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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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