[in Japanese]

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[in Japanese]

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[in Japanese]

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    To investigate the influence of atmospheric pressure variation on autonomic nerves in patients with rheumatoid arthritis (RA), we measured catecholamines (adrenaline (AD), noradrenaline (NAD), dopamine (DP), and vanillyl mandelic acid (VMA)) in 24-hour urine(1:00 am-1:00 am).　One hundred and five urine samples were collected from 9 RA patients (2 males and 7 females, with a mean age of 67.67±9.87 years at the time of the study). When the atmospheric pressure was classified into low, intermediate, and high pressure (990-1,000, 1,001-1,010, and 1,011-1,020 hPa, respectively), there were 19 samples in low, 52 samples in intermediate, and 34 samples in high atmospheric pressure, and the urinary AD, NAD, and VMA levels were greater at a high than at a low atmospheric pressure, and significant differences were noted in the AD level between those at low and high atmospheric pressures (6.55±5.66 and 10.67±5.88 μg/l, respectively), and the NAD level between those at low and high atmospheric pressures (133.9±83.09 and 198.38±93.67 μg/l, respectively) and between those at intermediate and high atmospheric pressures (151.57±80.88 and 198.38±93.67 μg/l, respectively), suggesting that the sympathetic nerve function was enhanced at a high atmospheric pressure. Thus, parasympathetic nerve function may be dominant at a low atmospheric pressure, while sympathetic nerve function may be dominant at a high atmospheric pressure in RA patients, showing that atmospheric pressure variation affects autonomic nerves.

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    We investigated the proportion of smokers in patients with rheumatoid arthritis (RA). 115 patients with RA and 59 of patients with osteoarthritis (OA) were recruited to this study. All patients were interviewed on their smoking history. A smoker was defined as a person who smoked at least one cigarette a day and an ex-smoker as a person who had stopped smoking for at least six months at the onset of RA. Patients with RA were diagnosed according to the 1987 ACR criteria, and we examined rheumatoid factor, blood count, CRP and ESR. 15 cases (65.2%) among 23 male patients and 11 cases (17.4%) among 92 female patients with RA were smokers. The proportion of smokers was higher than that of the general population. In the patients with RA, the examination of rheumatoid factor showed a significantly higher titer in the male smokers than in the male non-smokers. Men who are current smokers have an increased risk of developing seropositive RA.

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Objective: To investigate the satisfaction with care among patients with rheumatoid arthritis (RA), and to identify factors associated with patient satisfaction.
Methods: The self-report questionnaires were distributed to 500 RA patients who had participated in the general meeting of members of Riumachi Tomonokai (the association of patients with RA) on May 2009. The questionnaire consisted of six key areas: demographic data, characteristics of physician and healthcare provider, disease features, assessments of physicians’ attitude, assessments of patients’ knowledge about RA, patient-physician relationships including patient satisfaction. Participants responded on five-point Likert type scales and were classified as high-satisfied or low-satisfied according to the scales.
Results: The response rate was 76.4%. 90% was woman and 70% was aged 60 or over. The disease duration of 58% patients was more than twenty years. Patients were, in general, satisfied with the care they received at out-patient clinics. As a result of the multiple regression analysis, five items were extracted as factors that influenced the patient satisfaction. “The physician is responding enough to my worry”, “The physician speaks face to face to me”, “The physician asks me if I have anything to worry before the examination ends”, “The patient understands physician’s explanation enough”, and “the examination time is just good length”
Conclusion: When the physician considers the patient’s anxiety, takes communications appropriately, and offers clinical information appropriately, he can satisfy the patient. It was thought that satisfying the patient improved trust in the physician, and the effect of treatment was taken consequently. Physicians should train the communication skills to improve patient satisfaction.

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Objective: To analyze the relation between changes of anti-CCP antibody levels and disease activities of RA.
Patients and Methods: Anti-CCP antibody and IgM-Rheumatoid factor (RF) were measured twice in 101 patients with definite RA (16 male, 85 female). The average age of RA onset was 48.5±13.0 years and the average disease duration of RA at the first measurement was 8.7±9.6 years. The average interval between the two measurements was 5.4±1.1 years. DAS28-3CRP in each patient was calculated at the last measurement.
Results: Levels of anti-CCP antibodies and IgM-RF had no relation with disease activities of RA. Patients with a rising level of anti-CCP antibody showed significantly high DAS28-3CRP and poor treatment response compared to those without the antibody rising. Neither DAS28-3CRP nor treatment response differed significantly in changes of IgM-RF.
Conclusion: The DAS28-3CRP of anti-CCP antibody rising level was significantly higher than that of non rising level.

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    Many patients visit primary care clinics to seek medical care for arthralgia. Among these patients are those with non-inflammatory diseases, who often get better only by taking rest and/or conservative treatment. If they have inflammatory diseases such as rheumatoid arthritis (RA), however, they should be correctly diagnosed and treated at an early stage. Anti-CCP antibody is an autoantibody specific for RA and is of great help for the diagnosis of RA in ‘arthritis’ patients. The usefulness of anti-CCP antibody in patients with ‘arthralgia’ remains to be clarified in terms of the diagnosis of ambiguous early-stage RA. We measured this antibody in 100 patients who visited our outpatient clinic for a chief complaint of joint pains, and followed them up until 1 year later to study whether this antibody would be helpful in the prediction of RA development or in the diagnosis of RA. At the initial examination, 40% of those patients were positive for the antibody. After the one-year follow-up, 30 (75%) of the 40 antibody-positive cases were classified as having RA, while only 4 (7%) of the 60 antibody-negative cases were found to have RA (p＜0.001). Specificity of the antibody testing was as high as 84.9%, indicating that the anti-CCP antibody measurement appears to be useful for prediction of RA development and helpful for RA diagnosis in patients with ‘arthralgia’.

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    The Immunosuppressive drug Bredinin^® (mizoribine) was approved in 1992 for the indication of rheumatoid arthritis (RA) in Japan. Due to its safety profile, Bredinin^® is widely used as a Disease Modifying Antirheumatic Drug in Japan. Four nationwide post-marketing surveillance studies were conducted in Japan by the drug originator Asahi Kasei Pharma to clarify the prescription patterns and safety profile of Bredinin^®.
    Adverse events were correlated by baseline weight, duration of RA, number of previous RA drugs, the American College of Rheumatology classification criteria for RA, and renal function. Stepwise multiple regression analysis was used to clarify the risk factors for adverse events.
    Of the 6,375 patients registered, data collection and analysis for 6,309 participants is reported. The mean age of the participants was 62.9±11.9 years old, and 4,905 participants (77.8%) were women. Duration of RA, number of previous RA drugs, and lowered renal function each independently contributed to the incidence of adverse events.
    The four studies in this surveillance showed that Bredinin^® was mainly used to treat moderate RA and that the daily dose was generally decreased for patients with lower renal function. The analysis suggests that dose adjustments based on monitoring of renal function by measuring Ccr and the serum concentration of Bredinin^® may be useful in improving the safety profile of Bredinin^® for the treatment of RA.

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    We analyzed a nationwide post-marketing surveillance study of mizoribine (MZR) for rheumatoid arthritis (RA) to assess the efficacy and safety of MZR in terms of renal function using chronic kidney disease (CKD) stage and to assess the effect of MZR on renal function using estimated glomerular filtration rates (eGFR).
    Of the 1,805 registered patients in the study, 417 patients treated with MZR were assessed using eGFR.
    The improvement rate in ACR20 after 6 months for all 417 cases was 29.2%, and the rate for each sub-group based on CKD stage did not significantly differ. Adverse reactions to the MZR treatment were seen in 13.7% of the 417 cases, and the incidence of adverse reactions did not significantly differ between CKD stage sub-groups.
    Deterioration of renal function was not seen in any of the CKD stage sub-groups. However, significant improvement was observed for patients in stage 3 as eGFRs at the start and at six months were 50.2±7.0mL/min/1.73m² and 60.2±17.9mL/min/1.73m², respectively.
    These results suggest that MZR can effectively be used for RA patients in CKD stage 3.

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OBJECTIVE: Tacrolimus is an immunosuppressant with a calcineurin inhibitory effect. In Japan, administration of tacrolimus for the treatment of RA was approved in 2005. Our aim is to examine the efficacy and safety of tacrolimus for RA patients who have therapeutic difficulties with uncontrollable disease activity.
METHOD: 55 patients with RA who were resistant or intolerant to other disease-modifying antirhuematic drugs (DMARDs) were enrolled. They were administrated with tacrolimus (1-3 mg/day). We evaluated the effects of tacrolimus at 6, 12, 24 and 30 months by using DAS28 (CRP) and EULAR response criteria. We also examined whether MTX had influence on the efficacy of tacrolimus or not.
RESULT: The continuation rates at 6 months was 78%. 63.6% (21cases) of the patients achieved good or moderate responses at6monthes.Response rates seemed to be higher when they were treated in combination with MTX. After 6 months of treatment, 16 out of 43 cases achieved clinical remission. We didn’t see any serious adverse events.
CONCLUSION: Tacrolimus is safely and effectively used as a combination therapy with other DMARDs and prednisolone even for RA cases with high risk background when started with low dose and at an early stage of the disease. Blood concentration measurements and adjusting doses should be required for preventing severe adverse events.

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Objective: To study the clinical and radiographic efficacy of tacrolimus for patients with rheumatoid arthritis (RA). Methods: We enrolled 24 patients with RA who showed an insufficient response to other disease-modifying antirheumatic drugs (DMARDs). Disease activity and clinical response were evaluated by disease activity score of 28 joints -4/erythrocyte sedimentation rate (DAS28-4/ESR) and European League Against Rheumatism (EULAR) improvement criteria. Joint destruction of eight patients was assessed using the modified total sharp score (mTSS) at baseline and 1 year after the start of tacrolimus therapy. Results: Thirteen patients (54.1%) were evaluated as having a moderate or good response at 1 year after tacrolimus therapy, but tacrolimus was discontinued in nine cases who showed no or inadequate response. The mean values of the estimated yearly progression rate of mTSS at baseline, was 24.3, while that value was 3.62 at 1 year after the start of tacrolimus therapy, indicating the inhibition of joint destruction. Conclusion: Our study suggests that tacrolimus therapy for patients with RA, refractory to other DMARDs, appears to be efficacious not only in controlling the clinical symptoms, but also in suppressing the progression of joint damage.

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    Objective. Etanercept therapy effectively suppresses disease activity and improves symptoms of depression in patients with rheumatoid arthritis (RA). To elucidate the medication’s mechanism, changes in tumor necrosis factor (TNF)-α, interleukin (IL)-6 and dehydroepiandrosterone -salfate (DHEA-S) were examined.
    Method. Self-rating Depression Scale (SDS), serum concentrations of TNFα, IL-6 and DHEA-S were assessed in 16 RA patients, at baseline and after 14 and 30 weeks of Etanercept treatment. Disease activity was evaluated with the disease activity score 28 (DAS28) ESR4. Quality of life was evaluated with the modified health assessment questionnaire (mHAQ).
    Results. According to the EULAR improvement criteria of RA, patients were classified into two groups; the responsive group which has moderate-high response improvement and the no responsive group which has no response improvement. Total scores on the SDS and mHAQ were improved and the serum levels of IL-6 and DHEA-S also decreased in the patients in the moderate-high improvement group. On the other hand, there was no significant change in total scores on the SDS and mHAQ in the patients in the no improvement group. After treatment, there were no significant changes in serum levels of TNFα, IL-6 or DHEA-S.
    Conclusion. Etanercept may improve depression in patients with RA by suppressing the expression of IL-6 and DHEA-S.

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    Among 215 patients who were diagnosed with rheumatoid arthritis (RA) according to the criteria established by the American College of Rheumatology (ACR) in 1987, concomitant Fibromyagia (FM), which was evaluated according to the ACR criteria published in 1990, was detected in 20 (9.3%).
    In 2 of these patients, FM symptoms initially developed, leading to RA. The mean interval until RA development was1year. In 12, the concomitant development of RA and FM was confirmed on the initial consultation. Five patients were negative for C-reactive protein (CRP), and 7 were positive for CRP. The former showed a depressive state. In 5 of the latter, a depressive state was noted. In the other 6 patients, FM symptoms appeared during the course of RA. In 3, there was a marked increase in the CRP level after the onset of FM (mean rate of increase: 1.9mg/dl). In 2, the presence of stressor was confirmed. In the remaining patients, no etiological factor could be specified.
    Thus, the pathogenesis of FM in the presence of RA may involve a depressive state, mental/physical stress, and inflammatory stress, including a increase in the CRP level, in addition to its predisposition.

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    Quantitative evaluation of brainstem on magnetic resonance imaging (MRI) was conducted in patients with neuro-Behçet’s disease (NB) in order to delineate the differences in the pathogenesis of acute NB and chronic progressive NB. Areas of the mesencephalic tegmentum and pons were measured on sagittal sections of T1-weightened images of MRI using Advantage Workstation ver 3.0 software in 9 patients with acute NB, 14 patients with chronic progressive NB, and 46 age-and sex-matched control patients with non-Behçet’s neurological complications. Areas of the mesencephalic tegmentum (acute NB: 135.11±24.29 mm²［mean±SD］, chronic progressive NB: 98. 64±24.40mm², control: 143.64±21.70 mm²) as well as those of the pons (acute NB: 490.11±97.00 mm², chronic progressive NB: 395.71±88.90 mm², control: 526.97±50.74 mm²) were decreased significantly in chronic progressive NB compared with acute NB and control, whereas there were no significant differences between acute NB and control. In chronic progressive NB, the reduction of the brainstem areas tended to be correlated with the duration of the disease, although it did not reached the statistical significance. These results confirm that brainstem atrophy is more prominent in chronic progressive NB than in acute NB. Moreover, the data suggest that quantitative analysis of brainstem areas might be useful for early diagnosis as well as for evaluation of the disease activity in chronic progressive NB.

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    Tumor necrosis factor (TNF) inhibitors were shown to be more effective than single methotrexate (MTX) as a treatment for patients with newly-diagnosed rheumatoid arthritis (RA). Infliximab, one of the TNF inhibitors of chimeric monoclonal antibody against TNFα, has been demonstrated to decrease disease activity which leads to a complete remission, and the protection of joint destruction in early RA patients with MTX medication. Furthermore, several reports indicate that some of these patients maintain a complete remission (CR) after the injection of infliximab is stopped if MTX medication is continued.
    This paper presents a case in which a 69-year-old female patient with RA continues CR for more than 18 months after stopping infliximab injections even though the MTX medication is continued. The patient has a 17-year history of RA, and advanced joint destruction, in stage IV. This case, therefore, suggests the possibility that infliximab may be stopped even in an advanced condition of RA if the CR is continued. This case also suggests that an indication of infliximab for patients with RA may be expanded for elderly patients and more advanced disease conditions.

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    A 22-year-old woman with systemic lupus erythematosus (SLE) newly developed hematuria and proteinuria in August 2007, and was admitted to our hospital in February 2008. On admission, chest radiographic examinations and pulmonary function tests revealed that she also had interstitial pneumonia (IP). Findings of renal biopsy were consistent with ISN/RPS IV-G(A) nephritis. IP responded well to prednisolone 45 mg/day, although the proteinuria persisted with such treatment. To ameliorate renal function, tacrolimus was initiated at 3 mg/day. Six days later, generalized convulsion followed by coma developed. She was radiographically diagnosed with reversible posterior leukoencephalopathy syndrome (RPLS) on the basis of signal intensity in T2 FLAIR of brain MRI. She showed the elevations of IL-6, IL-8 and IgG index on the cerebrospinal fluid evaluations suggesting central nervous system (CNS) lupus. Tacrolimus was withheld, and methylprednisolone pulse therapy (1000 mg for 3 days) with anti-epileptics was initiated. On the next day, her level of consciousness became clear. After this episode, she uneventfully showed improvements in CNS vulnerability and renal dysfunction. Renal damage might elevate blood concentration of tacrolimus to induce RPLS together with malfunction of blood-brain barrier seen in CNS lupus. At present time, we concluded the RPLS of this case is a complication of SLE, however, the drug-induced RPLS is not completely neglectable. We should be very careful about tacrolimus administration for patients presumed to have renal dysfunction to prevent further adverse effects.

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    The case involved a 21-year-old woman with the chief complaint of arthritis in the left foot at the time of onset (10 years of age). Treatment was initiated with aspirin and weekly low-dose MTX. Rheumatoid factor (RF), which had been shown to be positive, rapidly became negative and the symptoms also subsided. Dry synovitis subsequently developed, which is a characteristic of extended oligoarthritis; arthritis was manifested in various areas and RF was also gradually elevated. Despite the use of various immune suppressors given in combination, improvement could not be maintained. Ten years after onset, the level of matrix metalloproteinase-3 was higher than 800 ng/ml; the level of anti-cyclic citrullinated peptide antibody was also as high as 83.3/Uml; additionally, severe destruction of the joint was predicted in the future, and thus administration of infliximab was initiated. Prior to infliximab administration, the DAS28-ESR was 6.0; however, it became 2.7 after 2 weeks and was markedly improved and maintainedafterwards. With regard to the HLA-DNA types of this case, HLA-DRB1*0405, a DR4 type prevalent among Japanese, HLA-DPB1*0201 prevalent in oligoarthritis, and HLA-A*02 prevalent in extended oligoarthritis, were detected. In juvenile idiopathic arthritis, RF-positive cases are excluded from the extended oligoarthritis category, and thus the classification of the disease type of RF-positive cases similar to our case became a task for the future. For cases of childhood showing resistance to various treatments during the course of the disease, it is important to determine the prognosis by HLA-DNA typing at the early stage, as well as to consider an use of biological agents.

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    TINU syndrome (tubulointerstitial nephritis and uveitis syndrome) is known as interstitial nephritis associated with uveitis, the cause of which is not clear so far. As most of the reports related with this disease were published by pediatricians and ophthalmologists, adult cases are not so common. We report on a case of a woman in her 40s suffering from TINU syndrome with fever, general fatigue and headache. We confirmed the diagnosis by a clinical course and the result of a renal biopsy. Blurry vision was apparent before the intake of loxoprofen sodium (a non-steroidal anti-inflammatory drug), the fact of which indicates that the beginning of the disease was before the intake of loxoprofen sodium. Although this syndrome is rare, patients with this syndrome may visit a clinic, hospital of rheumatologist, because a fever of unknown origin, joint pain and myalgia and so on can be the main symptoms of this syndrome. In this sense,rheumatologists should be aware of this disease.

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