Sae Ochi

Pathological role of osteoclast costimulation in arthritis-induced bone loss

Abnormal T cell immune responses induce aberrant expression of inflammatory cytokines such as TNF-α, leading to osteoclastmediated bone erosion and osteoporosis in autoimmune arthritis. However, the mechanism underlying enhanced osteoclastogenesis in arthritis is not completely understood. Here we show that TNF-α contributes to inflammatory bone loss by enhancing the osteoclastogenic potential of osteoclast precursor cells through inducing paired Ig-like receptor-A (PIR-A), a costimulatory receptor for receptor activator of NF-κB (RANK). In fact, bone erosion and osteoporosis, but not inflammation, caused by aberrant TNF-α expression were ameliorated in mice deficient in Fc receptor common γ subunit or β2-microglobulin, in which the expression of PIR-As and PIR-A ligands is impaired, respectively. These results establish the pathological role of costimulatory receptors for RANK in bone loss in arthritis and may provide a molecular basis for the future therapy of inflammatory diseases.

Leflunomide-induced polymyositis in a patient with rheumatoid arthritis

Although rheumatoid arthritis (RA) and myositis are major autoimmune diseases, co-occurrence of the two is rare. We treated a patient who developed polymyositis (PM) following the treatment of RA with leflunomide. Prednisolone (PSL) in combination with methotrexate (MTX) was effective in managing the PM, but the RA relapsed during the treatment. Based on the clinical course, we suspect that the PM was induced by the leflunomide treatment and suggest that clinicians should consider the possibility of this rare adverse event in cases of cholestyramine-resistant elevation of transaminases.

全身性エリテマトーデスに肥厚性硬膜炎を合併し，低髄圧症候群様の頭痛・難聴を呈した1例

We report a case of systemic lupus erythematosus (SLE) complicated with hypertrophic pachymeningitis. A 34-year old woman who was diagnosed as SLE in 1985 was admitted to our hospital for a high grade fever and a headache. Laboratory findings showed increased titer of anti-double strand DNA antibody and decreased number of platelets. She complained a severe headache and hearing loss which were worsened by head-up position, resembling the symptoms of intracranial hypotension. MRI findings revealed thickened dura and she was diagnosed as hypertrophic pachymeningitis. Both clinical symptoms and laboratory findings were resolved after methyl-prednisolone pulse therapy followed by a high dose of prednisolone. Although hypertrophic pachymeningitis is a rare complication with SLE, it should be considered in SLE patients with severe headache.

Assessment of Risks of Pulmonary Infection During 12 Months Following Immunosuppressive Treatment for Active Connective Tissue Diseases: A Large-scale Prospective Cohort Study

Objective. Pulmonary infections (PI) are leading causes of death in patients with connective tissue diseases (CTD). The PREVENT study (Pulmonary infections in patients REceiving immunosuppressiVE treatmeNT for CTD) assessed risk of PI in patients with active CTD in the contemporary era of advanced immunosuppressive therapy. Methods. In patients who started corticosteroids (n = 763), conventional immunosuppressants or biologics for active CTD were enrolled. Clinical and laboratory data, usage of drugs, and occurrence of PI were collected for 12 months. Baseline risk factors were investigated using Cox regression analysis. A nested case-control (NCC) study was performed with 1:2 matched case-control pairs to assess the risk for each drug category. Results. During the observation period, 32 patients died (4.2%) and 66 patients were lost to followup (8.6%). Patients with PI (n = 61, 8%) had a significantly worse accumulated survival rate than patients without (p < 0.01). Cox hazard regression analysis using baseline data showed that these factors were significantly associated with PI: age ≥ 65 years (HR 3.87, 95% CI 2.22–6.74), ≥ 20 pack-years of smoking (2.63, 1.37–5.04), higher serum creatinine level (1.21, 1.05–1.41 per 1.0 mg/dl increase), and maximum prednisolone (PSL) dose during the first 2 weeks of treatment (2.81, 1.35–5.86 per 1.0 mg/kg/day increase). Logistic regression analysis by an NCC study revealed that maximum PSL dose within 14 days before PI (OR 4.82, 95% CI 1.36–17.01 per 1.0 mg/dl increase; 2.57, 1.28–5.16 if ≥ 0.5 mg/kg/day) was significantly associated with the events, while other immunosuppressants were not. Conclusion. Physicians should be aware of the higher risks for corticosteroids of PI than other immunosuppressants and assess these risk factors before immunosuppressive treatment, to prevent PI.

The Great East Japan Earthquake: Analyses of Disaster Impacts on Health Care Clinics

OBJECTIVE Local health facilities play a critical role in mitigating the deterioration of health after catastrophic disasters. However, limited information is available on clinic damage. Therefore, the National Institute of Public Health conducted surveillance on clinic damage after the 2011 Great East Japan Earthquake (GEJE) to identify risk factors. METHODS A cross-sectional study using a paper-based questionnaire was conducted that targeted 728 clinics located in coastal areas in the 3 prefectures most affected by the GEJE. RESULTS The risk of building damage was inversely correlated with distance from the coast, whereas the risk of ceasing operations was significantly correlated with building damage and some specialties of clinics, namely, internal medicine and pediatrics.DiscussionIn mountainous countries like Japan, clinics often need to be built in coastal areas, where the majority of residents live. This surveillance revealed that clinics built in readily accessible locations and that provide care with high needs are more likely to get damaged by tsunamis. As clinics are often the frontline health facilities in disaster settings, local disaster plans need to include plans to reinforce disaster preparedness among clinics. For effective planning and resource allocation, nationwide hazard vulnerability analysis using a global standard will be helpful. (Disaster Med Public Health Preparedness. 2018; 12: 291-295).

Hypertrophic pachymeningitis in a patient with antiphospholipid syndrome and chronic hepatitis C virus infection

Abstract Herein, we discuss a case of a 51-year-old female who was presented with a severe headache and high-grade fever. Deep venous thrombosis of the left leg and erythema nodosum had been pointed out two months previously. On admission, laboratory tests showed hepatitis C virus (HCV) infection, prolonged coagulation time and positive anticardiolipin antibody. Lung perfusion scintigraphy revealed multiple peripheral perfusion defects. The serological features and thrombosis strongly suggested the existence of antiphospholipid antibody syndrome (APS). From the findings of the magnetic resonance imaging (MRI) and computed tomography (CT) scan, pachymeningitis was diagnosed. An oral corticosteroid (prednisolone 60 mg/day) was effective for treating the patient’s headache and fever, as well as the thickening of the dura mater. Based on her clinical history, her pachymeningitis was suspected to be associated with APS. Persistent HCV infection might have triggered these autoimmune conditions. We recommend to include autoimmune conditions as differential diagnosis for HCV patients who present atypical or nonspecific cranial symptoms.

Pseudo-SLE by human immunodeficiency virus infection

A 61-year-old woman was admitted for long-lasting fever and recurrent opportunistic infections during the treatment of SLE. She had been diagnosed as SLE and type-IV nephritis based on a renal biopsy and serological findings. A colonoscopy and liver biopsy revealed disseminated Mycobacterium avium complex infection. Human immunodeficiency virus (HIV) infection status was then examined and found to be positive. From the clinical course, the first symptoms were inferred to have been those of HIV infection.