Sjögren’s syndrome (SS) is a chronic inflammatory autoimmune disease primarily characterized by lymphocyte-mediated destruction of the exocrine glands, resulting in dry eye and dry mouth. The inflammatory process can affect any extraglandular organ. Therefore, in addition to the common dryness signs and symptoms, systemic manifestations may occur during the evolution of the disease. SS is associated with other autoimmune rheumatic diseases, such rheumatoid arthritis and systemic lupus erythematosus. When extraglandular manifestations developed, the distinction between SS-induced and other connective tissue disease-induced may be difficult in some patients. Thus, SS has various clinical conditions. The therapeutic management for patients with SS is based on the management of both sicca and systemic manifestations. The management of extraglandular manifestations must be tailored to the organs involved.
　Recently, new wave in management of SS has emerged. First, SS has been targeted for medical expenses subsidy as specified incurable disease from January 2015 in Japan, if patients satisfy the diagnostic and disease severity criteria. Then, new ACR-EULAR classification criteria were published in 2016. Finally, in 2017, the evidence-based practice guideline for SS was published by the research team of Ministry of Health, Labour and Welfare. Adequate understanding of diagnostic criteria, disease activity assessment indexes, characterization of glandular and extraglandular manifestations and therapeutic effects of medications including biologics, is necessary for accurately grasping clinical conditions and therapeutic planning. In addition, there are also necessary to perform research appropriately.

　The essence of the osteoporosis treatment is to control bone metabolic turnover. Since the approval of alendronate in 1993, various osteoporosis medicines including denosumab and teriparatide have been developed, and we have become able to control bone metabolic turnover to some extent. Furthermore, abaloparatide which is a facilitator of bone formation was approved by the Food and Drug Administration of the United States in 2017, and romosozumab which is a facilitator of bone formation without accelerating bone turnover is simply waiting for approval. The arrival of a new osteoporosis medicine which is more effective than what have been using has been much a waited to accomplish the “goal-directed treatment” of osteoporosis. Osteoporosis treatment will advance further with the arrival of such drugs with higher bone anabolic potential. I will explain osteoporosis medicines released 2013 and after, including these 2 drugs.

Objectives：Introduction of biological disease-modifying antirheumatic drugs (bDMARDs) in early rheumatoid arthritis (RA) patients is well documented, however, there are few reports of biologic use in established elderly RA patients over 75 years of age. We herein evaluated the use of etanercept (ETN), which has a short half-life and considered to be safe, for elderly RA patients.
Patients and Methods：Out of 336 patients treated with ETN at Niigata Rheumatic Center from May 2008 to March 2014, the clinical course and data of the patients who started ETN at 75 years of age or older were analyzed. The efficacy and safety of ETN was evaluated at 24 months.
Results：Forty-eight patients (18 males, 30 females) with a median age of 79.0 ± 2.9 years were analyzed. Clinical parameters such as articular findings, serum marker level, and the disease activity score improved significantly and the average dose of prednisolone (PSL) after using ETN were also decreased significantly compared with before using it. Adverse events occurred in 11 patients. Seven patients stopped ETN and 4 of these patients developed an infection. One patient (85 years of age) died due to tuberculosis and another (80 years of age) died due to pneumocystis pneumonia.
Conclusions：We may have to pay attention to the adverse event especially in the serious infection for elderly RA patients, but ETN is thought to be an effective treatment for elderly RA patients over 75 years of age.

Purposes : Subcutaneous injection of adalimumab (ADAsc(0.8)) was known to be painful, but an improved device (ADAsc(0.4)) was approved in November 2016. Here we compared the efficacy and pain level of injection among ADAsc(0.4), ADAsc(0.8), and other subcutaneous injection of biological disease-modifying anti-rheumatic drugs (sc-bDMARDs).
Methods : Patients with rheumatoid arthritis (RA), who were treated by sc-bDMARDs in our hospital, and agreed to take part in this survey, were enrolled （ADAsc group, n=72; other sc-bDMARDs group, n=351).
Results : The disease activity of RA did not change after switching from ADAsc(0.8) to ADAsc(0.4). Injection pain evaluated using the Short-Form McGill Pain Questionnaire version 2 (SF-MPQ-2) improved from 4.50 (1.00-19.0) to 1.00 (0.00-5.00), p<0.001. Furthermore, 55.4% and 78.6% of the patients expressed a marked preference for the ADAsc(0.4) in terms of needle-related pain, and the pain associated with infusion, respectively. Multivariate analysis indicated that more severe injection pain (SF-MPQ-2 score >2) was associated with use of the ADAsc(0.8), abatacept, etanercept, and certrilumab pegol, in comparison to the ADAsc(0.4).
Conclusion : The ADAsc(0.4) has achieved a lower level of injection-related pain, and become more usable.

Background: With treat-to-target (T2T), the physician always has to evaluate disease activity and joint damage of rheumatoid arthritis (RA) patients exactly to maintain the activities of daily living of the patient for the long term. However, the amount of work required by physicians to complete T2T can be onerous, so the cooperation of medical staff is necessary to practice T2T.
Purpose: To clarify the role and effectiveness of medical clerks (MCs) in a rheu-matic disease clinic. Patients and methods: In our rheumatic disease clinic, MCs have supported rheumatologists since April 2011. We individually investigated 50 RA patients in May 2010 (before MC support: “preceding period”), April 2011 (1 year after the start of MC support: “early period”), April 2013 (3 years after the start of MC support: “middle period”) and April 2015 (5 years after the start of MC support: “late period”). We assessed the prevalence of T2T practice, disease activity, and drug use. When all components of the Simplified Disease Activity Index (SDAI) of patients had been listed in the medical record and radiography of hand and foot joints had been un-dertaken more than once a year, the medical examination was defined as “T2T practice”. Disease activity was assessed using the SDAI and Clinical Disease Ac-tivity Index (CDAI).
Results: Prevalence of T2T practice was 50%, 86%, 94% and 100% at preceding, early, middle and late periods, respectively. Prevalence of T2T practice increased after the start of MC support. Accordingly, disease activities improved gradually. SDAI remission was 30.8% in the preceding period, 28.5% in the early period, 30% in the middle period and 58% in the late period, respectively. CDAI remission improved towards the late phase, similar to that seen with the SDAI. The mean dose of methotrexate (MTX) increased gradually towards the late phase, but the prevalence of MTX use did not show a remarkable change. Prevalence of use of biological disease-modifying anti-rheumatic drugs did not increase during the study period. The mean dose and prevalence of use of corticosteroids decreased gradually to-wards the late phase.
Conclusion: MC support in rheumatic disease clinics aids T2T practice for rheu-matologists. The disease activities of RA patients can be improved by MC support.

　We describe two females (64 and 70 years old) and one male (63 years old) with elderly onset large vessel vasculitis (LVV). All cases presented with prolonged fever and aggressive inflammatory reaction (CRP 8-10 mg/dl) without vascular insufficiency and the diagnosis was made during the early phase based upon FDG uptake within wall of large vessel detected by PET/CT. Several HLA types associated with Takayasu arteritis (TAK) or giant cell arteritis (GCA) were not found in all cases. All cases responded well to steroid therapy (prednisolone 0.6-1.0 mg/kg/day) for the induction of remission and two of the three cases needed other immunosuppressants, such as azathioprine or methotrexate, for maintenance therapy. Because of the lack of characteristic findings in GCA including myalgia by polymyalgia rheumatica, we simply diagnosed these patients as LVV rather than large vessel GCA (LV-GCA). Although elderly onset LVV tends to be diagnosed as LV-GCA, diagnosis of TAK is not necessarily incorrect. Since the classification of LVV is still less mature, further elaboration is needed. The detection of LVV by conventional imaging techniques is difficult in elderly cases, however PET/CT, which is not covered by health insurance at this time, is very beneficial for early diagnosis. It is urgent to create a better environment for precise diagnosis and treatment of elderly onset LVV.

　Antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is known as a systemic vasculitis with unknown etiology whereas ANCA, a hallmark of AAV, is considered to promote pathologic process of these disorders. AAV are classified as microscopic polyangiitis (MPA), granulomatous polyangiitis (GPA), eosinophilic granulomatous polyangiitis (EGPA) and renal limited vasculitis (RLV). There have been some differences of clinical characteristic of AAV between Japan and foreign countries since Japanese patients with AAV contain the higher incidence of MPA, myeloperoxidase (MPO)-ANCA, elderly onset of age and interstitial lung disease (ILD). Regrading to therapy of AAV, rituximab (RTX), a chimeric anti-CD20 monoclonal antibody, targeted to clearance of B cells, have been reported to be effective in AAV patients that are mostly evidenced in foreign countries with GPA patients, launched in USA at 2011 toward GPA and MPA. These clinical applications are also launched in Japan at 2013. As compared with foreign countries, evidences of clinical investigation of RTX in AAV patients is still limited in Japan. We are going to discuss the established evidences of RTX toward treatment of AAV and positioning of RTX among Japanese guideline toward clinical application of AAV 2017.

　Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized mainly by chromic joint inflammation. Many biological therapies for RA have become available during the past decade including TNF blockers, abatacept, or tocilizumab, making clinical remission an achievable goal. However, responsiveness to biological agents is variable among individuals, and there are poor responders to certain biological agents. Given the destructive nature of RA, the risk of adverse events, and the considerable costs of biologic therapy, there is a need to identify predictors of response to biologics. Abatacept (ABT) is a soluble human recombinant protein in which the extracellular domain of human cytotoxic T lymphocyte-associated molecule 4 is bound to the Fc portion of human IgG1. The safety and efficacy of ABT in patients with RA have been demonstrated in many worldwide studies for those who are methotrexate (MTX)-naïve, MTX-inadequate responders or anti TNF-α-inadequate responders.
　Consequently, the strategies for treatment of elderly patients with RA tend to focus more on safety when compared with younger patients. The aim of our present study was to identify the predictive factors associated with sustained clinical remission for biologic-naïve patients with RA and to compare them between elderly (≧65 yrs) and younger patients (≦65 yrs). We discuss the positioning of RA treatment of ABT compared with the other biologics such as anti-TNF-α inhibitor and tocilizumab.

　Nontuberculous mycobacterium collectively refers to a large number of species of mycobacteria other than Mycobacterium tuberculosis. Nearly 90% of nontuberculous mycobacteria (NTM) diseases are infections by Mycobacteria avium complex (MAC). Among NTM diseases (NTMD), Mycobacterium abscessus infection is resistant to various therapies. The main infectious site of NTMD is the lungs. There are two major types of pulmonary lesion caused by NTMD: one is milder form nodular-bronchiectatic type, and the other is severe form fibro-cavity type. For the diagnosis of NTMD, chest CT findings compatible with NTMD and detection of mycobacteria with sputum twice or more are nessesary. There are two times as many NTMD infections in RA patients than in the general population, and ten times as many NTMD infections in RA patients receiving TNF-alpha blocker than in the general population. In RA patients with NTMD, b-DMARDs are contraindicated, so we cannnot prescribe those agents to such patients. In 2014, the Japanese Respiratiry Society created a guideline for b-DMARDs therapy for RA patients with NTMD. This guideline allows use of b-DMARDs therapy for such patients only in the case of MAC infection and the milder nodular-bronchiectatic type. Therefore, although b-DMARDs can be can introduced in to anti-RA therapy for RA patients with NTMD, b-DMARD therapy should be applied to RA patients with NTMD very carefully.