Whether or not arthroplasty improves the sequelae of infliximab therapy in patients with rheumatoid arthritis (RA) was studied in 59 patients with RA. The patients who received arthroplasy during treatment with infliximab (n＝7) were compared with those who did not receive arthroplasy in view of parameters of disease activity. Clinical parameters such as the duration of morning stiffness, grip strength, C-reactive protein value and blood sedimentation rate all continuously improved during 1.5 years of infliximab therapy in the patients who did not receive arthroplasty. However, these parameters that improved once all deteriorated 1.5 years after the start of infliximab therapy in the patients who received arthroplasty. An exception was the number of tender joints, and this parameter was particularly improved after 1.5 years of infliximab therapy in the patients who received arthroplasty. No infectious episodes related to arthroplasty were seen. The results showed that the patients with RA who required arthroplastywere less responsive to infliximab therapy probably because of having a relatively higher level of disease activity other than C-reactive protein values. The results also indicate that arthroplasty performed during infliximab therapy is safe and improves the joint pain of patients with RA.

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    We started therapy with infliximab (IFX) at our hospital in 36 rheumatoid arthritis (RA) patients with an inadequate response to low dose methotrexate (MTX). In 21 patients, the therapy duration has currently reached 22 weeks or longer, the longest being 134 weeks. During the therapy, RA activity was evaluated using markers such as CRP, MMP-3, RF and ESR. After the start of IFX, all the markers showed a decrease, which persisted for 134 weeks, and the therapy was continued in approximately 80% of the patients. Four patients dropped out; the reasons were spondylodesis for atlantoaxial subluxation in one patient and switching to etanercept (ETN) due to attenuation of IFX effects in two patients. The fourth patient was considered as a complete responder with a marked improvement in CRP after the start of IFX. The patient achieved a remission-like status approximately 1 year after the start of the therapy, which has still been maintained despite the subsequent discontinuation. On the other hand, three patients required an increase in steroid doses during the IFX therapy, and four patients were treated at decreased doses. Although some clinicians have pointed out attenuation of IFX effects after 22 weeks, the above findings revealed its infrequency. This clinical evaluation demonstrated that IFX may be sustainably effective and relatively safe, having long-lasting, excellent effects in RA patients (especially early RA), which existing DMARDs do not have. As a new treatment for RA, IFX is considered an indispensable drug as a new treatment for RA. However, adequate monitoring of adverse reactions is necessary.

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    Etanercept is an effective drug used for refractory rheumatoid arthritis (RA) patients. Etanercept was usually injected subcutaneously twice a week 25-mg fixed doses to the RA patients. We had a case who died2weeks after initial administration of etanercept because of the sudden decreases of the numbers of white blood cells and platelets, although her clinical symptoms and disease activity score were highly improved. Her body weight was 35 kg. We have now used a 25-mg weekly injection of etanercept for the patients whose weights were below 50 kg.
    In this report we investigated the efficacy and safety of etanercept therapy with RA patients and assessed the effectiveness between administering the drug once a week and twice a week.
    Fifteen patients with RA were divided into two groups; ten patients were received at a 25 mg of etanercept subcutaneously in once a week and5received the drug twice a week. According to the disease activity score 28 (DAS28) and patient satisfaction, a good response to the clinical manifestations in RA patients were seen in the both groups.
    In the view of efficacy, safety and drug cost, therefore, etanercept is recommended for use in 25-mg doses once a week by subcutaneous administration in RA patients whose weight is low (below 50 kg).

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Background: The reliability of the drug induced lymphocyte stimulation test (DLST) for Methotrexate (MTX) has not been established. We investigated the specificity of the DLST for MTX in patients with rheumatoid arthritis (RA).
Methods: The DLST for MTX was performed in 10 RA patients who had never been treated with MTX［MTX(－) group］and in 16 RA patients who were being treated with MTX but who had not suffered any adverse effects［MTX(＋) group］.
Results: Among all 26 patients, the false-positive rate of the DLST was high at 57.7% (15/26) and the stimulation index (SI) (median± standard deviation) was 2.0±6.4. Among the 10 patients who had never been treated with MTX, the false-positive rate was 70.0% (7/10) and the S.I. was 3.1±6.0. Among the 16 patients who were undergoing treatment with MTX but who had not suffered any adverse effects, the false-positive rate was 50.0% (8/16) and the SI was1.9±6.9. There was no significant difference in the SI between the MTX(＋) and MTX(－) groups. Extremely high SI values were observed in one patient in the MTX(＋) group (29.3) and in one patient in the MTX(－) group (21.1).
Conclusions: A positive result on the DLST for MTX in RA patients is largely non-specific, and is unreliable for identifying whether MTX is the agent responsible for any unwanted events.(First published in Allergy ＆ Clinical Immunology International, 17: 156-161, 2005)

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    The ultimate goals in managing Rheumatoid Arthritis (RA) are to prevent or control joint damage, prevent loss of function, and decrease pain. Methotrexate (MTX) is one of the DMARDs which has been widely used for RA. For RA treatment, the MTX tablets are generally ingested in equal numbers on 2-4 consecutive occasions at 12-hour intervals, always beginning on the same day of the week. However we did not find any reports about the effects of MTX associated with the medication method. In this time, we tried to give MTX (median dose 5.8 mg per week) without folic acid for more than 6 months to the patients on only 2 occasions separated by 12 hours in a week in order to evaluate the effects, safety and compliance. We measured DAS28-CRP and researched the side effects of MTX. The results showed that 59 of all 67 patients had continued taking the medicine. Meanwhile, we changed from MTX to Infliximab for 3 patients, and had used Etanercept with MTX for 6 patients because of insufficient effects. But we obtained a good efficacy rate (91.9%) based on the value of DAS28-CRP and only slight side effects (5.8%) which only consisted of a fever and gastrointestinal injury. These disappeared swiftly after stopping the medication. Therefore this medication method seems to be acceptable.

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Objective: To study the short-term efficacy and safety for infliximab in patients with refractory juvenile idiopathic arthritis (JIA).
Methods: Nine patients with JIA were enrolled. Four patients were with systemic onset polyarticular course JIA (sJIA) and 5 patients were with rheumatoid factor positive polyarticular JIA (pJIA). The patients had failed to respond to methotrexate or any other disease modifying anti-rheumatic drugs. Infliximab was given intravenously at weeks 0, 2, 6, and at 4 to 8 week intervals thereafter. Improvement of the patients was assessed at 0, 2, 6, 12, and 24 weeks according to Disease Activity Score (DAS) 28 and JIA core set.
Results: According to DAS28, the sJIA group improved immediately at 2 weeks and 3 patients (75%) obtained more than a moderate response at 24 weeks but one patient worsened from the baseline at 24 weeks. The pJIA group did not achieve a good response until 12 weeks but all 4 patients obtained more than moderate responses except one drop-out case because of human anti-chimeric antibody. JIA core set 70% was achieved at 24 weeks by 2/4 (50%) patients with sJIA and by 4/4 (100%) patients with pJIA without one drop-out case.
Conclusion: In our study, infliximab provided a significant rapid reduction in disease activity in the short term, but response to infliximab differed between sJIA and pJIA patients. More study is needed to elucidate the long term safety and efficacy of infliximab in the treatment of refractory sJIA and pJIA.

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    PAH and digital ulcers are the refractive pathological conditions of collagen diseases. In this study, we treated four cases as the subjects for studying therapeutic effects of ERA (bosentan).
［Subjects］ Case one was a 65 years old, female MCTD＋RA patient. Case two was 70 years old female(dcSSc), case three was 68 years old female(lcSSc), case four was 63 years old female(dcSSc).
［Results］ Case one patient showed marked improvement of symptoms caused by PAH after day four of ERA administration，thereafter PAP gradually decreased from 70 mmHg to 27 mmHg...Case two showed improvement in six-minute walk test from 115 m to 140 m and, coldness of fingers improved after one week of administration. Her night-time cough markedly decreased and she could get a sound sleep after three years absence.
    From day 10 of administration, case three began to show improvement in digital ulcer, which was refractory. But liver damage appeared four weeks later and gradually aggravated, therefore, eighteen weeks after we resigned the treatment.
    Case four terminated administrations due to vertigo occurred on day five of administration. But, the digital ulcer deteriorated, therefore, we started the treatment again five months later. Thereafter, the digital ulcer became in healing condition.
［Conclusion］ The effects of ERA were identified at NYHA III stage of PAH therapies, and its effectiveness is promising as new therapeutics for digital ulcers due to peripheral circulation failure.

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    Deep vein thrombosis (DVT) is a serious complication after lower extremity surgery. We investigated the effectiveness and safety of anticoagulation therapy with medicine during post surgical period.
    The number of samples was 54. We divided patients into two groups; 25 patients with anticoagulation therapy and 29 without it. Before operation, we examined lower extremities with ultrasonography to confirm that they don’t have DVT. The former group was given Heparin for two days and Warfarin for one month as anticoagulation therapy. After 1 week, we also examined the lower extremities by ultrasonography. We checked the degree of bleeding, the reduction of hemoglobin, and the incidence of DVT.
    The mean amount of post-operative bleeding was 420 ml in the former group and 457 ml in the latter group (p＞0.05). The reduction of hemoglobin indicated 1.42 g/dl and 1.29 g/dl respectively (p＞0.05). DVT was found in three out of 25 in the former group and four out of 29 in latter group (p＞0.05).
    It could be concluded that it was safe though it had no tangible evidence for its effectiveness. Hence, further examination would be needed with higher dose of anticoagulation.

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    Multicentric reticulohistiocytosis is characterized by the presence of papulonodular cutaneous eruption and arthropathy. If the onset of arthropathy precedes the eruption of skin lesion in a case, we may diagnose him with rheumatoid arthritis (RA) by mistake. We report a case of multicentric reticulohistiocytosis in an adult woman who had been diagnosed with RA first recognized in a skin lesion biopsy.
    A 59-year-old woman with arthralgia in the bilateral knee and ankle following papulonodula in her face and fingers had been diagnosed with rheumatoid arthritis. However, she visited us because her arthritis had been getting worse. We made her consult a dermatologist about papulonodula and it was diagnosed as a skin lesion of multicentric reticulohistiocytosis by a biopsy. Radiography showed no findings. In a blood test, CRP was 2.89 mg/dl, rheumatoid factor was 78 IU/ml, erythrocyte sedimentation rate (ESR) was 61 mm/hr, antinuclear antibody test was positive, and value of anti SS-A autoantibody is high. We started treating her with prednisolone and auranofin, and her skin lesion and arthritis were improving. While malignancies of various types may develop in up to 18% of such cases, she has not had any malignant complications. Also, she has not had any autoimmune diseases. Without malignant complications, skin lesions may regress spontaneously after 5-10 years or more, but there may be residual joint impairment and we must follow up this case carefully.

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