Much of Japanese rheumatologists has only notice of a disease name as fibromyalgia (FM), moreover they have a negative concept for FM and attitude of refusing the management of FM patients. From 2003, Japanese Ministry of Health, Labor and Welfare (MHLW) organized the study group for research on FM, thereafter, the study group is showing epidemiological, various clinical and basic medical findings of FM in Japan.
    In this review the following findings obtained from the study group of MHLW would be described; clinical epidemiological findings of FM in Japan, pathophysiological studies containing by brain imaging study of PET-CT using ¹⁸FDG or specific ligand (¹¹C-PK11195) of activating microglia (neuroinflammation), autoantibody (anti-VGKC antibody) analysis, socio-psychological basis of juvenile FM and developing clinical guideline for FM management in Japan. It would be clarified that development of curative management based on the pathogenesis of FM, as well as good recovering of ADL/QOL For the eradication of FM, further strategic studies for FM should be done by the Japanese study group.

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    Rheumatoid arthritis (RA), the hallmark of which is the presence of an intense inflammation of the synovium, is a systemic autoimmune inflammatory disease that causes secondarily not only generalized osteoporosis but also paraarticular osteoporosis. Impaired activity of daily livings (ADL), and increased cytokines with osteoclast stimulatory activity within involved joint sites are responsible for the development of generalized osteoporosis but also paraarticular osteoporosis, respectively. The incidence of hip fracture is increased approximately two-fold in RA patients. The risk of vertebral fracture is likely to be increased particularly in those with glucocorticoid administration.
    It is increasingly recognized that the increased calcium/phosphate release form the bone resulting from bone resorption might contribute to the development of atherosclerosis. We previous showed in a series of the reports that advanced atherosclerotic changes were observed in RA patients with higher bone resorption. Since evidence has been accumulated to indicate that the administration of anti-bone resorbing agents, such as bisphosphonate, might prevent against the development of atherosclerotic change and the occurrence of acute myocardial infarction.
    These data clearly indicate the importance of treatment of abnormal bone metabolism in RA patients not only to prevent fracture but also to attenuate RA-induced aggravation of atherosclerotic changes.

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Purpose: The aim of this study was to evaluate the efficacy and safety of golimumab (GLM) by examining outcomes for rheumatoid arthritis at multiple facilities.
Subjects and methods: Participants comprised 162 patients with rheumatoid arthritis given GLM at 5 different facilities in Fukuoka from September 2011 to October 2014. Medical records were retrospectively examined and the Disease Activity Score 28 using C-reactive protein values and the Simplified Disease Activity Index were used for efficacy evaluations. Participants were divided into the bio-naïve and switch groups, the 50-mg and 100-mg groups, and the MTX combination and non-combination groups.
Results: The remission rate was significantly higher in the bio-naïve group than in the switch group (p<0.005). Over the long-term, therapeutic effects were significantly greater in the MTX combination group than in the non-combination group (p<0.05). When dosages of GLM were compared, the 50-mg group was found to have improved significantly compared with the 100-mg group (p<0.05). No serious adverse events occurred during the study period.
Conclusions: GLM is just as effective and safe as other biological drugs and is also effective in patients who did not respond to other drugs and patients who could not use concomitant MTX.

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Objective: Interstitial lung disease (ILD) is an extra-articular involvement of rheumatoid arthritis (RA) and has a poor prognosis. It is difficult for rheumatologists to choose disease modified anti-rheumatic-drugs (DMARDs) to RA-ILD patients because DMARDs generally have adverse events such as drug-induced interstitial pneumonia. In the present study, we examined use examples of biological DMARDs (Bio) for RA with ILD.
Methods: There were 23 RA-ILD patients of 259 RA patients between April 2013 and March 2014 in our hospital. Of them there were 8 Bio cases (infliximab (IFX): 1 cases, tocilizumab (TCZ): 2 cases, abatacept (ABT): 3 cases, golimumab (GLM): 2 cases).
Results: The mean age was 61.3±5.0 years. There were 6 females. We chose Bio to RA-ILD patients with earlier stage and progressing class of Steinbrocker classification. There were 4 Bio-naïve cases and 4 Bio-switch cases. There were 4 cases with concomitant methotrexate therapy. All cases continued Bio more than 52 weeks without ILD deterioration. The PSL dose of all cases did not increase in 52 weeks.
Conclusions: The use of Bio for RA-ILD patients increases the risk of ILD deterioration. However, we decide to use Bio carefully to control RA disease activity. In the present study, we showed the possibility of using Bio to RA-ILD patients.

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    A 66-year-old man has been suffering from bilateral leg edema for five years. He noticed muscle weakness of his legs 4 years ago, and then went to a hospital where elevation of serum creatine kinase levels was found, although the diagnosis was not yet determined. Since one year ago, he has felt pain and thickening of the skin of his abdomen and back, while progressive bilateral leg edema and muscle weakness caused gait disturbance. Therefore, he admitted to our hospital. He was diagnosed with systemic sclerosis from the histological findings of his abdominal skin biopsy specimen and positive test for serum anti-centromere antibody. We regarded his bilateral leg edema and muscle weakness as the skin and muscle lesions from systemic sclerosis after exclusion of the other causes and started to treat him using glucocorticosteroid. His symptoms dramatically improved in a few weeks. The absence of sclerodactyly in this patient might cause the difficulties or delay in the diagnosis of Systemic sclerosis.

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    Systemic sclerosis (SSc) remains one of intractable connective tissue diseases, because of inability of fibrotic tissue with modification of the architecture to respond to medical treatment. To overcome this limitation, novel treatment concept has been proposed: intervention in the early disease phase when the pathological lesions are still reversible. Implementation of this strategy requires accurate early diagnosis and prediction of future outcomes, including progression of organ involvement. In this regard, new classification criteria for SSc enable us to recognize SSc patients earlier than before, even those without skin sclerosis. In addition, disease subgrouping is feasible using classification of the patients into diffuse and limited cutaneous SSc, in combination with SSc-related antinuclear antibodies. Outcomes of SSc patients may be drastically improved by early diagnosis and intervention in near future.

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    Central nervous system involvement in Behçet’s disease, usually called neuro- Behçet’s disease (NB), is classified in acute type and chronic progressive type. Acute NB is characterized by acute meningoencephalitis with or without focal lesions, presenting high intensity areas in T2-weightened images on magnetic resonance imaging (MRI) scans. Cyclosporin (CyA)-related acute neurological manifestations are almost identical with CyA-unrelated acute NB in terms of clinical manifestations, laboratory data and responses to steroids, except for the paucity of relapse on discontinuation of CyA. Chronic progressive NB is characterized by slowly progressive dementia, ataxia and dysarthria with persistent elevation of cerebrospinal fluid (CSF) IL-6 and progressive brainstem atrophy on MRI. Diagnostic criteria have been proposed depending on the results of retrospective multicenter cohort studies, using CSF cell counts for acute NB and CSF IL-6 with brain stem atrophy on MRI for chronic progressive NB, respectively. Acute attacks of acute NB well respond to moderate to high doses of corticosteroids, whereas colchicine is effective to prevent relapses of acute NB especially in patients who developed acute NB in the absence of CyA. Chronic progressive NB is resistant to conventional treatment with steroid, cyclophosphamide, or azathioprine, but responds to low dose methotrexate. Thus, methotrexate has been shown to reduce the rate of mortality and severe disability significantly in a retrospective cohort study. Infliximab has been also found to be effective in patients with chronic progressive NB in case of inadequate responses to methotrexate.

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    Treatment changed dramatically in the field of rheumatology with the advent of methotrexate and biologics such as anti-TNF or anti-IL-6. Early treatment, window of opportunity, tight control and treat to target are emphasized triumphantly. Who are expected to implement newer treatment to the RA patients? RA specialists are, of course. Specialists/rheumatologists are responsible for evaluation of the patients’-status, initiation of the treatment and preparation for the adverse events which could happen anytime. However, the number of the specialists is very limited, especially in the rural areas. To implement newer treatment even in those areas with scarce rheumatologists, we need a team comprising rheumatologists and general practioners or home doctors (HHC: hospital and health-care clinic co-operation).
    The roles of the rheumatologists and general practioners are distinct. The rheumatologists’ is mentioned above. Generalists are expected to practice near the patients’ home along with a close-relationship between patients and doctors as family practitioners. Care is the main theme of the generalists. By co-operating with generalists, rheumatologists can reduce the number of everyday patients, which will allow them longer time for the treatment. Each patient has two doctors in charge: rheumatologist and general practioner. This type of co-operation is ideal not only in rheumatology but also in any field of medicine. However, this is not prevailing in Japan thanks to huge endeavor imposed on big hospitals. It may not be so easy to pave the way to set the stage for HHC.

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    Salazosulfapyridine (SASP) and bucillamine (BUC) are low molecular weight chemical compounds approved for the treatment of rheumatoid arthritis (RA) for decades. Dose escalation should be applied for both drugs to minimize the treatment-emergent adverse events such as rash and gastrointestinal discomfort for SASP, and rash and proteinuria for BUC. SASP can be started before methotrexate (MTX) in non-severe patients with early RA, although the addition of SASP to MTX may not be successful. On the other hand, the efficacy of the combination therapy of BUC and MTX has been suggested in both remission induction before the introduction of biological agents and remission maintenance after discontinuation of biological agents.

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    Abatacept is a non-TNF biologic DMARD controlling T-cell costimulation in the antigen presentation of immunoreaction. Abatacept has an influence on the cell expressing CD80/CD86. Recently, it is suggested that abatacept is involved in the decrease of an antigen presenting cell and the differentiation of osteoclast. Its efficacy and safety are shown to be equal to adalimumab in a direct competitive trial and are recommended as a first-line drug of biologic DMARDs in a variety of guidelines. However, the maintenance of the remission after the abatacept cancellation is difficult like other biologic DMARDs. Some studies showed a suppressive effect of the ACPA production about etiology of the rheumatoid arthritis, but the clear conclusion is not provided, so the further examinations are remained in the future.

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