Objective: To establish a treatment strategy for women of child-bearing age（WoCBA）with rheumatoid arthritis（RA）.

Methods: We performed a review of recommendations, guidelines, original articles, and case reports.

Result: Methotrexate should be discontinued when RA patients plan to become pregnant. Sarazosulfapyridine, azathioprine（AZA）, cyclosporine（CyA）, or tacrolimus（TAC）can be used. AZA, CyA and TAC were previously contraindicated for pregnant women in Japan, however, in July 2018 this policy changed and the drugs are no longer considered to be contraindicated. Etanercept（ETN）and certolizumab-pegol（CZP）are biologic agents that are recommended for patients with high disease activity. It was reported that CZP hardly passes through placenta and shows almost no secretion in milk; however, there is little evidence in Japan because CZP only became available in 2012 while ETN became available in 2005.

Conclusion: We must establish the treatment strategy of WoCBA in patients with RA including the usage of CZP in Japan.

Object: To clarify the actual condition of long-term care requirements in elderly patients with rheumatoid arthritis（RA）and to examine the factors contributing to the need for care.

Method: We surveyed long-term care certification status of 712 elderly RA patients （age > 65 years）who were outpatients at our hospital and are in the Japanese long-term care insurance system. The patients were classified as（A）certified as requiring long-term care 1–5,（B）requiring support afforded by long-term care certification, and（C）not certified. These groups were examined by comparing data on parameters such as the duration of disease and Disease Activity Score（DAS）28, Japanese Health Assessment Questionnaire（JHAQ）, and treatment details.

Results: The numbers of patients in groups A, B, and C were 103, 80, and 525, respectively, and ４ patients were excluded as their certification status was unknown. Accreditation rate of group A and B, 26.3%, was higher than the general elderly population. JHAQ was the most contributing variable that predicted the need for long-term care（OR: 5.00, 95% Confidence Interval: 3.24 - 7.97）during multivariate logistic analysis using age, gender, medication, and composite measures as independent variables. ROC curve analysis of JHAQ as an independent variable for long-term care certification yielded a cutoff value of 0.75, AUC of 0.88, sensitivity of 84.2%, and specificity of 79.6%.

Conclusion: Patients with RA tended to have a greater need for long-term care than the general population. JHAQ makes the greatest contribution to assess the need for caregiving, and the degree of care needed can be estimated from its score. Therefore, measures for reduction of JHAQ scores of RA patients to less than 0.75 and prevention of complications can reduce the need for long-term care of patients.

We investigated tapering or stopping of concomitant methotrexate（MTX）and inhibitory effect by tocilizumab（TCZ）treatment on large joint destruction in rheumatoid arthritis（RA）patients in this retrospective study. Thirty one cases（23 female and 8 male）who continued TCZ over 2 years were utilized in this study. Baseline characteristics, time course of disease activity and usage of concomitant drugs such as MTX were investigated. Delta-modified Sharp score（ΔmTSS）per year was used to evaluate small joint destruction. ARASHI score was used to evaluate large joints destruction. Shoulders, elbows, hips, knees and ankles were evaluated using ARASHI score. Baseline characteristics of 31 cases were as follows. Average age: 56 years old. Average RA duration: 6.6 years. Average CDAI was 23.3 at baseline, 6.8 at one year and 5.0 at two years. Rate of concomitant MTX was 74.2% at baseline, 45.2% at one year and 29.0% at 2 years. Average ΔmTSS was 8.1 at baseline, 2.7 from baseline to one year and 1.1 from one year to two years. Evaluation using ARASHI change score from baseline to two years was as follows［worsened, not changed, improved（%）］. Shoulders（51 joints）［9.8, 86.3, 3.9］. Elbows（56 joints）［12.5, 73.2, 14.3］. Hips（53 joints）［0, 94.3, 5.7］. Knees（52 joints）［9.6, 65.4, 25.0］. Ankles（53 joints）［3.8, 91.6, 5.7］. Joint surgery was not performed in evaluated joints during study periods. MTX was tapered or stopped during TCZ treatment. Over 90% of large joints were not destroyed during two-year period of TCZ treatment.

  Objectives: We report the comparison of the efficacy of switching bisphosphonates（BPs）to either denosumab（DMB）or daily teriparatide（dTPTD）at 24 months in treating osteoporosis in patients with rheumatoid arthritis（RAOP）.

  Methods: Fifty-four RAOP females treated by switching BPs to DMB（DMB group; n=18）or dTPTD（dTPTD group; n=36）were used for this retrospective study. We compared baseline data, percent change of（%-）bone mineral density（BMD）in lumbar spine（LS-）and total hip（TH-）, absolute values of N-terminal propeptide of type 1 collagen（P1NP）and tartrate-resistant acid phosphatase（TRACP）-5b, %P1NP and %TRACP-5b every 6 months.

  Results: Types of prior BP treatment were significantly different between two groups. Baseline P1NP were significantly greater in the dTPTD group than in the DMB group. In the DMB group and the dTPTD group at 24 months, %LS-BMD were 6.4% and 11.0%（p=0.069）, %TH-BMD were 3.9% and 3.9%（n. s.）, the absolute values of P1NP and TRACP-5b were 28.5μg/L and 76.3μg/L（p<0.001）and 338.5mU/dL and 563.9mU/dL（p<0.001）, and %P1NP and %TRACP-5b were 36.4% and 144.6%（p<0.05）and 13.4% and 61.8%（p<0.05）, respectively. There were 3 fragility fractures in the DMB group and 2 fragility fractures in the dTPTD group（p=0.3193）. Hypercalcemia was obtained more frequently in the dTPTD group than in the DMB group（12 cases vs. 1 case, p=0.040）.

  Conclusions: Both switching BPs to DMB and dTPTD were effective to increase LS- and TH-BMD in RA-OP. LS-BMD tended to increase greatly with dTPTD than with DMB, while TH-BMD similarly increased both with DMB and dTPTD.

  Objective: The purpose of this study was to examine short-term efficacy of sarilumab therapy in patients with rheumatoid arthritis（RA）.

  Subjects and methods: Five patients with RA who underwent sarilumab treatment were assessed. 200 mg of sarilumab was administered SC by subcutaneous injection every 2 weeks for 12 weeks to patients with RA. Disease activity of RA was examined by DAS28-ESR and ultrasonography.

  Results: All patients were women（mean age 64.0 ± 17.8, mean disease duration 16.5 ± 14.0 years）. DAS28-ESR was significantly improved（4.58 ± 0.65 at baseline to 2.90 ± 0.76 at 12 weeks p= 0.03）. Total power Doppler score was also significantly improved（10.6 ± 2.2 at baseline to 2.0 ± 1.9 at 12 weeks p= 0.0067）.

  Conclusions: These findings suggested that sarilumab may lead to rapid improvement assessed by DAS28-ESR and ultrasound in patients with rheumatoid arthritis.

  Remitting Seronegative Symmetrical Synovitis with Pitting Edema（RS3PE）described for the first time in 1985 by McCarty et al. is characterized by an uncommon elderly-onset, bilateral, symmetric, tenosynovitis and pitting edema of extensor tendons at the wrist and at the feet.

  The levels of vascular endothelial growth factor（VEGF）, a cytokine able to increase vascular permeability and dilation, are significantly higher in RS3PE patients than in controls. The increased VEGF level is attributed to the increased vascular flow in the impaired joints.

  Although the C-reactive protein level and erythrocyte sedimentation rate were increased in this disease, it is seronegative for rheumatoid factor and antibodies against citrullinated peptides. Serum matrix metalloproteinase 3 concentration is elevated, especially in the patients with malignancies. Hand and foot magnetic resonance imaging and ultrasonography showed that extensor tenosynovitis was the responsible lesion for the edema in the subcutaneous and peritendinous soft tissue of the dorsum in both conditions equally. The remitting course and the absence of radiographic joint destruction differentiate RS3PE syndrome from rheumatoid arthritis.

  We have recently observed 9 cases of paraneoplastic RS3PE. The malignancies were solid, and the stomach, colon, breast, prostate and lung were involved. The most frequent histological type was adenocarcinoma.

  Its clinical symptoms and signs dramatically respond to 10-15mg/day prednisolone and remit within 1-2 weeks.

  Polymyalgia rheumatica（PMR）is an inflammatory disorder causing pain in the shoulder, the pelvic girdles, and the neck, which usually affects individuals older than 50 years old, more women than men, and more Caucasians than other ethnic groups. Increases in acute phase reactants are typical but non-specific. The disease might present as an isolated condition or in association with giant cell arteritis（GCA）, although the exact cause of these illnesses is still unknown, occurring in the same time or at different times. Several diseases, including inflammatory rheumatic and autoimmune diseases, infections, and malignancies can mimic PMR. Imaging techniques such as echograms and FGD-PET/CT scans have identified the presence of bursitis. Daily prednisolone leads to rapid amelioration of symptoms in most patients, however, relapses are common with tapering. Therefore, studies aimed to establish the optimum initial dose, speed of steroid tapering, and optimum length of treatment should be done. Methotrexate might be used in relapsing patients. The effectiveness of biologics, such as anti-interleukin 6 agent, is revealed in patients with GCA, but requires further investigation in patients with PMR who are refractory to steroids. PMR is observed as one of adverse events with immune checkpoint inhibitor treatments. In addition to epidemiological explorations worldwide, a new core set of biomarkers for clinical trials in PMR and GCA will emphasize the need for formal validation to measure disease activity, physical function, steroid-associated adverse events, and the risk of developments of CGA in patients with the condition.

  IgG4-related disease（IgG4-RD）is a newly recognized systemic fibroinflammatory condition characterized by tumor-like swelling of involved organs, elevated levels of serum IgG4, diffuse infiltration of IgG4-positive plasma cells, and fibrosis in lesions. The most frequently involved organs are salivary and lacrimal glands（so-called Mikulicz’s disease）, and pancreas（autoimmune pancreatitis type 1）. In addition, bile ducts, kidney, retroperitoneum, aorta and lung are often affected in a synchronous or metachronous clinical course. It is necessary to suspect IgG4-RD in case of mass-forming lesions of unidentified origin in those organs. First-line treatment for IgG4-RD is glucocorticoids（GC）based on the prompt, positive response to GC. However, osteonecrosis of femoral head has occasionally occurred after starting GC treatment in IgG4-RD patients like other rheumatic diseases. Because long-term administration of GC has been inevitable due to high rate of relapse in the clinical course, it is necessary to pay attention to adverse effects of GC such as osteoporosis and opportunistic infections. Although the etiology of IgG4-RD has been not been elucidated, several molecules and immune cells involved in the pathological condition of IgG4-RD are being identified and introduction of therapies targeting these molecules and cells is expected. In fact, favorable treatment outcomes with monoclonal antibodies targeting CD20 and CD19 present on B cells have been reported.

  Autoinflammatory disease is defined by recurrent episodes of generalized inflammation and fever in the absence of infections or autoimmune causes. Autoinflammatory disease is an innate immune-mediated inflammatory disorder in contrast to an autoimmune disease, which is defined as a disease caused by the abnormalities in adoptive immunity; however, autoimmune disease and autoinflammatory disease have a number of similar clinical characteristics. FMF is the most common monogenic autoinflammatory disease, and is characterized by recurrent attacks of fever and polyserositis. It is associated with mutations in the MEFV gene encoding pyrin, which result in inflammasome activation and the uncontrolled production of IL-1β. A nationwide survey conducted in Japan indicated that Japanese FMF patients are clinically or genetically distinct from Mediterranean FMF patients, suggesting a genotype–phenotype correlation. In Japanese patients with FMF, MEFV mutations in exon 10 are associated with the more typical FMF phenotype. Conversely, Japanese FMF patients with mutations in exons 2 or 3 of the MEFV gene present with an atypical FMF phenotype. Colchicine is the mainstay of FMF treatment, and its regular use prevents febrile attacks and decreases the long-term risk of AA amyloidosis. However, a minority of FMF patients are colchicine-resistant, and anti-IL-1 treatment has proven beneficial in suppressing inflammation in these patients. Although Japanese FMF patients may develop less severe disease compared with Mediterranean FMF patients, they should nevertheless be treated early to prevent recurrent attacks and the subsequent development of AA amyloidosis.

  Castleman disease（CD）is a very rare non-neoplastic lymphoproliferative disease with a characteristic pathological feature in lymph nodes, which was originally reported by Dr. Benjamin Castleman in 1956. The clinical course varies from a mild form to a very severe form with high mortality, suggesting a heterogenous pathogenesis of CD.

  CD is pathologically classified as hyaline vascular（HV）, plasma cell（PC）, and mixed type, while this disease is also clinically classified as unicentric（UCD）and multicentric（MCD）. The majority of patients with UCD exhibits HV type and can be cured by complete surgical resection of pathologic lymph nodes. On the other hand, the majority of patients with MCD exhibit PC type and complications in various organs along with constitutional symptoms, and thus often refractory to standard treatment. MCD with unknown etiology is designated as idiopathic MCD（iMCD）, and recently became specified as an incurable disease in Japan.

  This review describes the etiology and pathogenesis of CD, and focuses particularly on recent updates of the diagnosis and assessment of disease activity of iMCD. Steroids and cytotoxic agents had long been used for treatment of iMCD, however its prognosis was often aggravated by various complications such as infections and malignancies. Discovery of a pivotal role of IL-6 in the pathogenesis of iMCD has now made IL-6 blockade as the first-line treatment. Some patients with iMCD, however, are refractory to standard therapies including IL-6 blockade.

  A recent notable collaboration between CD experts nationally and internationally has helped further clarify the pathogenesis of this intractable disease, thus paving a new avenue for a novel therapeutic strategy in the future.