LTB4 and its receptors play a critical role in the recruitment of leukocytes to the inflammatory sites in patients with rheumatoid arthritis (RA). Inhibition of inflammatory cells infiltration to rheumatoid synovitis represents a potential target for treatment of RA. There are no useful target drugs to LTB4 and its receptors until now. These results support is not a mojor contribut to the inflammatory process in RA. Moreover other lipoxygenase system (15LOX and 12LOX) produce antiinflammtory mediator Lipoxin A4(LXA4). via transcellular synthesis. This LXA4 and its receptor ALX also expressed synovial tissues of patients with RA.Both of proinflammtory lipid mediator LTB4 and antiinflammtory mediatorLXA4 produced in synovial joints with rheumatoid arthritis. Recent report showed that LTB4 producing enzyme leukotoriene A4 hydrolase (LTA4H) contribute to the defense of mycobacterium infection. These data suggested that lipoxygenase system regulate the pathophysiology and self-defense in patients with RA.

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    Treatment for rheumatoid arthritis (RA) has dramatically developed by the usage of biologics. Better clinical efficacy can be achieved by setting a clear treatment goal with the usage of methotrexate as an anchor drug in combination with biologics. However, biologics requires parenteral administration and long-lasting treatment is necessary in most patients. Therefore an orally available anti-rheumatic drug with similar efficacy with biologics has been desired.　Tofacitinib is an oral medicine as effect as biologics and was approved in Japan at March2013. Unsurprisingly, adverse events with a different profile from biologics have been observed in the clinical trials. Most of all,2～4fold increase compared to pre-existing biologics was observed in herpes zoster. Surprisingly, it was increased in Asian population especially in Japan and Korea. Incidence of malignancy was similar to biologics, however rare malignancy such as sarcoma has been observed. It is conceivable that suppressed lymphocytes such as CD4＋,CD8＋ and natural killer cells are involved in these events. Evaluation of patients in our department revealed that low CD8＋T cell count prior to treatment with tofacitinib was a risk factor for infectious adverse events. This indicates the possibility of patient selection suitable for treatment with tofacitinib. Therefore, the results from the post-marketing study will be important and we should keep an eye on it.

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Objective: This study aimed to assess the incidence of infusion reactions and impact on efficacy in patients with rheumatoid arthritis (RA) receiving1-hour infliximab(IFX)infusions.
Subjects and Methods: IFX was administered by1-hour infusion to22patients with RA who provided informed consent and had not experienced an infusion-related reaction during or following any5or more2-hour IFX infusions. The incidence of infusion reaction and impact on DAS28-ESR and HAQ was assessed in these patients.
Results: The incidence of infusion reactions was0% (0/22patients) in the1-hour infusion group. There was no evidence of worsening in DAS28-ESR and HAQ scores over time in patients with 1-hour infusion following the first3shortened-duration infusions.
Conclusion: By careful observation during and following the first5or more2-hour IFX infusions, it was feasible to safely administer the same dose of IFX by1-hour infusion thereafter. There was no appreciable influence of shortened-duration on efficacy of IFX.

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OBJECTIVE: Biologics have been shown to improve the outcomes in patients with rheumatoid arthritis (RA). Those drugs are so expensive that, under an insurance system of Japan, the understanding and acceptance of cost effectiveness of those drugs by Japanese patients with RA remains unknown. This paper aimed to clear the cost effectiveness evaluation to the biologics by the patients who are taking those drugs. METHODS: We assess the cost-effectiveness of biologics using an unsigned questionnaire for 445 RA patients taking biologics periodically in ambulatory care. RESULT: Almost all patients estimated that general effects of biologics were good. The monthly increase in expense caused by biologics was 30-60 thousand yen. More than half of RA patients perceived that the cost is expensive in relation to the effectiveness of those drugs. Although the patients whose income actually increased were only 10%, the patients with increased income had increase of600thousand yen or more in annual income. Irrespective of the existence of increases of income, more than2/3of the patients could have more than two hours of working time per day after the start of the biologics treatment. CONCLUSION: Rheumatologists need to understand such cost and burden on RA patients, and should introduce biologics for suitable patients.

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Objective: The Revised Fibromyalgia Impact Questionnaire (FIQR) is a self-administered questionnaire for the comprehensive evaluation of patients with fibromyalgia. The questionnaire was developed to address the limitations of the Fibromyalgia Impact Questionnaire. In order to use the FIQR with Japanese patients, we developed a Japanese version of the FIQR (JFIQR).
Methods: After obtaining permission for development, the FIQR was translated and linguistically validated, according to the general cross-cultural adaptation process: 1) forward-translation, 2) back-translation, and 3) cognitive debriefing.
Results: The original FIQR was independently translated into Japanese by two native-Japanese translators, and then a single forward-translation was produced after reconciling differences between the two translations. Next, back-translation was performed by a native-English translator. Finally, cognitive debriefing interviews were conducted in 6 Japanese fibromyalgia patients (5 females and1male, average age 51.7 years old), to assess respondents’ comprehension of the questions and response scales. Overall, the patients had no difficulties with the wording and correctly interpreted each question.
Conclusion: Through the translation and adaptation process, a JFIQR was finally developed.

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    Fibromyalgia (FM) is a common chronic pain disorder characterized by widespread pain. Japanese FM patients are estimated to number more than 2 million based on nationwide monitoring. We usually evaluate the pain by the Visual Analog Scale (VAS) and the Numeric Rating Scale (NRS). But these methods are subjective methods by patients. If we can quantify of pain, it will be one of the cognitive therapy of pain. Therefore quantification of pain is needed for evaluation and treatment of FM patients. A system for quantification of pain (Pain Vision^®) has been developed in Japan. Using Pain Vision^®, we can objectively evaluate the patient’s pain.
    We measured the pain in 83 FM patients who met the ACR criteria in 1990 and compared the value between the recent NRS values and Pain Score among these patients. As a result, the average pain threshold of male FM patients is 9.35±2.64 with a pain degree of 649.91±312.94, and the average pain threshold of female FM patients is 7.93±2.30 with a pain degree 688.08±526.65. The average pain degree of FM patients was much higher than seen in rheumatoid arthritis (RA) patients. Also female FM patients have a lower pain threshold and might be related with hyperesthesia. On the other hand, a pain threshold with RA patients is not low.
    There was no difference in RA and FM for the average of the NRS. However, FM patients who have high NRS scores have a high pain degree.
    The measurement by Pain Vision is very helpful for us to objectively know the threshold and the pain degree.
    In conclusion, the pain degree by Pain Vision® was able to quantify and evaluate the pain in patients with FM.

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    A 69-year-old woman was admitted into our hospital for dyspnea on exertion. She had been treated with methotrexate since the age of 61.Due to inadequate response to methotrexate, she was treated by addition of infliximab or tocilizumab, however, those were stopped due to lack of efficacy and adverse event, respectively. Therefore, the administration of abatacept was started, while methotrexate was continued. Nine months later, she had dyspnea on exertion and a CT scan revealed ground glass shadow in the bilateral lung field, predominantly in the upper lobe. Exclusion of pulmonary infection, such as bacterial, pneumocystis, cytomegalovirus pneumonia, and other pulmonary diseases, diagnosis of interstitial pneumonia was carried out. After high dose of prednisolone was started, she rapidly improved. However, new ground glass shadows in the bilateral upper lung field and the middle lobe were seen on a chest CT scan, one month later. At that time, detection of cytomegalovirus antigenemia and inclusion body of giant cell from bronchoalveolar lavage fluid revealed complication of cytomegalovirus pneumonia. Administration of Gancyclovir resulted in complete recovery. Abatacept is supposed to have less severe adverse reactions based on its post-marketing surveillance in Japan as compared with those of infliximab, etanercept, tocilizumab, or adalimumab, although the patient demographics and the time of each surveillance period ware different. Furthermore, there are only few reports regarding interstitial pneumonia or cytomegalovirus pneumonia after the administration of abatacept. Therefore, this case report suggests that possibility of these complications should be kept in mind when we use abatacept.

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    We report a case of Behçet disease in which neuropsychiatric symptoms developed with the administration of infliximab (IFX) for an ocular lesion. A 27-year-old man had refractory iridocyclitis, retinouveitis, and recurrent aphthous stomatitis at the age of 25.He was diagnosed with Behçet disease. Because his ocular lesion was resistant to conventional immunosuppressive agents such as corticosteroids, cholchicine or cyclosporine, IFX (5mg/kg/6～8weeks) was administered. IFX was effective for his ocular lesion. Fifteen months after starting the IFX treatment, he was admitted to our hospital with complaints of pyrexia, headache, and slurredspeech. Although brain MRI revealed no abnormal lesions, the CSF IL-6 level was markedly elevated (172pg/ml: reference value＜6.0pg/ml). Based on these, we diagnosed him with neuro-Behçet’s disease (NBD). We treated him with steroid pulse therapy followed by a 40mg daily administration of prednisolone. After these treatments, his symptoms improved and the IL-6 level decreased. There are no reports of NBD developed during IFX therapy, though there are some reports in which anti-TNF-α therapy seems to be effective for patients with refractory NBD. This case suggests that infliximab may not be able to fully prevent the development of NBD.

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    The idiopathic inflammatory myopathies are systemic autoimmune diseases characterized by chronic inflammation, leading to progressive weakness of the proximal muscles. Myositis-specific or associated autoantibodies are often found in the serum of polymyositis (PM) and dermatomyositis patients. Anti-SRP (signal recognition particle) antibody is thought to be associated with severe forms of the disease, particularly those with heart and lung involvement and resistant to adrenocorticosteroids. We present a66-year-old female polymyositis patient with serious muscle weakness and high CPK level (21550IU/L). Despite initial therapy with high-dose methylprednisolone (1g/day x3days,i.v.) followed by prednisolone (1mg/kg/day,p.o.) plus cyclosporine A (150mg/day), muscle weakness was not improved and CPK levels were not reduced to less than3000IU/L. After treatment with intravenous immunoglobulin (IVIG), muscle strength was gradually improved and CPK levels were reduced to less than700IU/L. To our knowledge, there were few reports that PM positive for serum anti-SRP antibody treated with IVIG. IVIG might be a therapeutic agent of choice for steroid-resistant cases of serum anti-SRP antibody-positive PM.

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