Synovitis of rheumatoid arthritis（RA）starts as the infiltration of CD3 T-cells around the capillaries in sublining connective tissues. An RA-specific histopathologic finding may be the polymorphous proliferation of fibroblasts in sublining layer, probably due to proinflammatory cytokines such as IL-1 and TNFa. The amount of infiltrating inflammatory cells in synovitis lesions does not correlate to the bone destruction of affected joints. Pannus destroys the bone, and the infiltration of lymphocytes and plasma cells in proliferating synovial tissue does not reflect the extent of pannus formation. Treatment of RA with biologic agents causes the thinning of synovial layer, the decrease of inflammatory cell infiltration, and the fibrosis of synovial tissue. The remarkable effects of biologic agents on RA synovitis lesion indicate the importance of targeted cytokines in the pathogenesis of RA synovitis. Therefore, it is important to take notice of the histopathologic findings reflecting the biologic effects of these cytokines.

Objective: To investigate the current situation of regional rheumatology care/regional medical collaboration and clarify the modifiable factors regulating patient referral（direction/quantity）.

Methods: We conducted a questionnaire survey with our collaborative meeting members. Questionnaire items with regard to the year 2017 were as follows: total number of patients, number of newly referred/reversely referred patients along with the reason, specific treatment for newly diagnosed/continuously visiting patients, and treatment policy of each facility in three situations（onset, deterioration, and stable phase）where patients may move.

Results: Among a total of 22 institutions/23 departments, 13/14（1 hospital and 12 clinics; 9 internal departments and 5 orthopedic departments; 4 specialist centers and 10 non-specialist centers）answered the questionnaire. The total number of patients in 2017 was 1028. There were 832 continuously visiting patients from the previous year, 130 newly referred patients, 145 newly diagnosed patients, and 129 reversely referred patients. With regard to newly diagnosed patients, 77% of patients were treated at specialized facilities; of these patients, 63% received methotrexate（MTX）/biological products. Even in non-specialized facilities, 50% of patients received MTX. Specialists responded to the three situations by themselves; however, the medical policy of non-specialists was associated with the degree of treatment experience. The number of newly referred patients was strongly correlated with that of reversely referred patients.

Conclusions: Close medical collaboration with a small number of trustworthy non-specialists, who aim to treat more than 20 patients, should be more efficient, particularly in areas with few specialists/specialty facilities.

Objective: To assess elderly patients with rheumatoid arthritis（RA）.

Methods: Data from 852（695 women）patients with RA managed at our hospital and who were registered on the National Database of Rheumatic Diseases in Japan were secondary used for this study.

Results: Renal function was impaired in the elderly patients on being administered MTX less frequently and at a lower dose. The steroid dose was low（average < 5 mg/day）regardless of age. However, the frequency of steroid use was high in patients ≥ 75 years old. Although the frequency of treatment with biologics did not differ between the young and elderly patients, agents other than the biologics that targeted the tumor necrosis factor were used more in the older patients. Among elderly patients aged ≥ 75 years, the duration of the disease was longer and the physical function poorer in patients who developed RA at ≤ 60 years of age than those who developed RA at > 60.

Conclusion: Impaired renal function was associated with less frequent use of MTX and the physical function deteriorated in elderly patients with a longer duration of RA.

  Polypharmacy（PP）is associated with an increased risk of adverse drug reactions. In Rheumatoid arthritis（RA）patients, the combination with symptomatic treatment drugs in addition to anti-rheumatic drugs is the factor of PP. We investigated PP using a guideline, and the relationship between PP and the kind of drugs in RA.

  Outpatients at our hospital were retrospectively analyzed using information in electronic medical records. The study included 77 patients with RA aged > 75 years who were being treated with methotrexate（MTX）.

  We found that the number of drugs was < 5 in 48 patients, 6-9 in 13 patients, and ≥ 10 in 16 patients. The percentages of the drugs requiring careful prescription were 52%, 84% and 100% in each group. The prescription rates of drug are prednisolone（PSL）36%, non-steroidal anti-inflammatory drugs 53%, folic acid 73%, disease modifying anti-rheumatic drugs 9%, and biologics 13%. PP was correlated with the use of supportive care drugs for the prevention of side effects from MTX and PSL. Our data suggest that PP is common in RA patients, and that it is necessary.

  We pharmacists should monitor the proper use of therapeutic agents based on the guideline. Moreover, early diagnosis and early treatment of RA is necessary for avoidance of the duration of long-term PSL use，and pharmaceutical intervention is also important for that.

  Tocilizumab（TCZ）is reported to be effective for the treatment of adult Still’s disease（ASD）; However, some reports warn that TCZ can cause macrophage activation syndrome（MAS）in ASD. Consequently, further investigation of TCZ therapy for patients with ASD is required. The current retrospective study evaluated the use of high-dose steroid and TCZ in seven cases of ASD between 2016 and 2017. We specifically focused on clinical change over the first three months of TCZ treatment. The median age was 44 years（inter quartile range 41-59）. Of the total participants, three were males. Additionally, out of the total, five cases were newly diagnosed, and two were recurrent. In all the cases, the steroid dose was rapidly tapered and 8 mg/kg of TCZ was administered intravenously every 1–6 weeks to ensure remission. TCZ was discontinued after the third administration in one case due to intra-abdominal infection. Transient thrombocytopenia, frequently accompanied by elevated serum ferritin levels was observed in six cases after the first or second TCZ administration. However, this side effect improved with no further serious adverse events such as MAS. Therefore, TCZ was not stopped and the steroid dose was not increased.

  These results demonstrated that TCZ treatment is very effective for tapering the steroid dose in refractory or severe ASD. Although thrombocytopenia and elevated serum ferritin levels frequently occur after introducing TCZ, these symptoms improved and did not require withdrawal from TCZ.

  A 30-year-old man was admitted to our hospital because of spike fever and rash. He had been suffering from facial rash, discoid lupus on his anterior chest wall and polyarthralgia which was exacerbated every summer since 5 years ago. Two years later, he was diagnosed as having acute myocarditis of unknown cause, and thereafter fever sometimes occurred which went down with non-steroidal anti-inflammatory drugs. Because these symptoms became resistant to the previous treatment 3 weeks earlier, he was admitted to our hospital. On admission, there were pancytopenia and elevated level of serum ferritin, and bone marrow findings showed he had hemophagocytic syndrome（HPS）without any evidence of infectious diseases or hematologic malignancy. His symptoms strongly suggested that he had systemic lupus erythematosus（SLE）although his serum anti-nuclear antibody was negative, so lupus-band test of the skin was performed, revealing he had SLE complicated by HPS. This case suggests that histological examination such as lupus band test of the skin should be planned when clinical symptoms suggest occurrence of SLE despite negative serological data.

Aim: To examine the clinical outcome of certolizumab pegol（CZP）in patients with rheumatoid arthritis（RA）.

Methods: Eighteen patients with RA（16 women and 2 men; mean age, 58.5±12.1 years; age range, 25-75 years; average disease duration, 6.3 years）who were given CZP were registered; of these 18 patients, 7 were biological agent–naïve. Twenty-one biological agents were previously used（etanercept, 8; adalimumab, 4; tocilizumab, 4; abatacept, 2; infliximab, 2; golimumab, 1）. Methotrexate was used in 14 cases（average dose, 7.1 mg/week; range, 4-10 mg/week）. Prednisolone was used in 5 cases（average dose, 4.5 mg/day; range, 2.5-5 mg/day）. The Disease Activity Score 28（DAS28）, European League Against Rheumatism response, retention rate, and adverse events were examined.

Results: The DAS28 score significantly decreased from 4.34（at first CZP administration）to 3.73（at 1.5 months after CZP administration）（p=0.0008）, to 3.10（at 3 months）（p=0.0037）, to 2.53（at 6 months）（p = 0.0006）, and 2.67（at 12 months）（p = 0.0019）. Moderate response was acquired in most cases（13/18, 72.2%）. The continuation rate was 67% at 24 weeks and 61% at 1 year. Administration was suspended for being ineffective in 5 cases（all of which were primary failures）and due to adverse events in 2 cases（1 for pain during injections and 1 because of worsening bronchial asthma, which was an underlying disease）.

Conclusions: Despite the high rate of refractory RA cases in this study, DAS28 showed low disease activity 6 months after CZP treatment, suggesting that CZP is effective for patients with refractory RA.

  Microscopic polyangiitis（MPA）is the most prevalent anti-neutrophil cytoplasmic antibody（ANCA）-associated vasculitis（AAV）in Japan. Approximately 7% of cases of MPA are associated with primary cancers. The ratio of solid cancers in AAV-associated malignant tumors is extremely high（92%）, whereas that in malignant tumors associated with whole vasculitis syndrome remains 17%. We herein report a case of MPA with ANCA against myeloperoxidase（MPO-ANCA）that was associated with advanced colorectal cancer and lung squamous cell carcinoma. This is the first report of an MPA case simultaneously associated with different histological types of multiple solid cancers. Because of the deterioration of MPA, we started to treat the patient with 60 mg/day prednisolone and scheduled excision of the cancers after the treatment. However, the patient died due to invasive pulmonary aspergillosis during tapering of prednisolone. The solid cancers may have been associated with the onset and deterioration of MPA. Analysis of previous case reports suggested that treatment for the cancers improves the outcome of AAV（p < 0.05）, which should be carefully re-evaluated with increased number of cases. Systematic screening for solid cancers at the diagnosis of MPA is recommended due to the possibility of multiple cancer association.

Objective:

Patients with elderly rheumatoid arthritis（RA）have physical and social problems.

Team medical care is considered important for their resolution, but there is no established method. In order to understand the patientʼs physical function, mental state, and consciousness, and to facilitate team medical care, in addition to the original questionnaire, a comprehensive geriatric assessment7（CGA7）was conducted to diagnose nursing.

Methods:

Nine patients who were hospitalized for the first time in our hospital（73–84 years old, average age 82.2 years old）were evaluated.

At the time of hospitalization, the evaluation was carried out by CGA7 while using our original RA questionnaire（Table 2）by the nurse. According to the evaluation, patients are classified into three groups: Group I, which has no problems with physical and cognitive function（GⅠ）, GroupⅡ, which has no cognitive problems but has decreased physical function（GⅡ）, and Group Ⅲ, which has problems with cognitive decline, decreased self-management ability, and decreased physical function（GⅢ）. Team medical care was performed in accordance with the classification.

Results:

We provided general patient guidance to GⅠ（2 patients）, GⅡ（5 patients）was provided with rehabilitation guidance and lifestyle improvement guidance for fall prevention in order to restore physical function, and GⅢ（2 patients）underwent reviews of oral medications by doctors, was provided oral management guidance including family members by pharmacists, and also provided nutrition guidance by nutritionists.

Conclusion:

For hospitalized elderly RA patients, nursing diagnosis using RA questionnaire and CGA7, to perform team medical care and post-hospitalization guidance in the hospital according to individual cases may be useful for the evaluation of appropriate patients and smooth appropriate execution of team medical care.

  Bone is a crucial element of the skeletal-locomotor system, but also functions as an immunological organ that harbors hematopoietic stem cells and immune progenitor cells. In addition, the skeletal and immune systems share variety of molecules, including cytokines and receptors. The term “osteoimmunology” was coined to describe the research on the shared molecules and interactions between the skeletal and immune systems, and has been developed mainly based on the studies on the pathogenesis of rheumatoid arthritis. The TNF family cytokine RANKL is one of the most typical “osteoimmune” factors. RANKL plays crucial roles in not only osteoclast differentiation, but also the immune organs including lymph nodes and thymus. Furthermore, excess RANKL signal causes abnormal osteoclast activation, resulting in a variety of skeletal diseases in patients with rheumatoid arthritis, osteoporosis and bone metastasis. A fully human anti-RANKL neutralizing antibody is now used in the treatment of bone loss disorders. RANKL is synthesized as a membrane-bound molecule, which is cleaved into soluble form by proteases. The functional difference between soluble and membrane-bound forms of RANKL has been poorly understood in vivo so far. Recently, we have elucidated the physiological and pathological significances of soluble RANKL by generating mice that selectively lack soluble RANKL. Here, I review the osteoimmunological function of RANKL and the distinct role of soluble RANKL in bone metastasis by introducing our recent research.