釜田 康行

OBJECTIVES: Dermatomyositis (DM) patients with anti-melanoma differentiation-associated protein 5 (MDA5) antibodies are known for poor prognosis. This study was designed to identify humoral factors that are readily detectable in the disease and may reflect its activity and pathophysiology. METHODS: We first quantified the serum level expression of 28 cytokines in the serum of patients with collagen vascular diseases using bead-based multiplex immunoassays. We completed these evaluations at hospital admission and followed up with three DM patients with anti-MDA5 antibodies during hospitalisation. We also performed an immunohistochemical analysis of skin samples obtained from two patients. RESULTS: The serum level of interferon gamma-induced protein 10 (IP-10) was significantly higher in DM patients with anti-MDA5 antibodies than in those without the antibody, decreasing drastically upon treatment. Interestingly, this time course paralleled not that of interferon (IFN)-γ, which was originally reported to be the inducer of IP-10, but that of IFN-α2. Immunohistochemical analysis revealed that most of the IP-10-positive cells were macrophages. Furthermore, monocytes stimulated with type I IFN in vitro produced IP-10 in a dose-dependent manner. CONCLUSIONS: IP-10 is a potentially useful disease activity marker of DM with anti-MDA5 antibodies, correlating more with IFN-α2 then IFN-γ. IP-10 released from macrophages might prompt the infiltration of macrophages themselves. Thus, the type I IFN/IP-10 axis may play a pivotal role in the pathogenesis of this intractable disease.

A 53-year-old woman with a 6-year history of rheumatoid arthritis (RA) presented with pharyngeal pain, fever, and altered mental status. The patient had been treated with methotrexate (MTX) 12 mg/week, baricitinib 4 mg/day, and tacrolimus 2 mg/day. Magnetic resonance imaging of the brain revealed diffuse high-intensity lesions in the cerebral white matter, basal ganglia, brainstem, and right cerebellar hemisphere. She was diagnosed with Epstein-Barr virus (EBV) encephalitis due to elevated levels of EBV-DNA in the cerebrospinal fluid and serum. Although MTX-associated lymphoproliferative disorders are well-known complications in patients with RA, EBV encephalitis requires careful attention for such patients undergoing treatment with multiple potent immunosuppressants.

A 68-year-old woman presenting with rheumatoid arthritis was admitted due to pancytopenia caused by methotrexate. Pneumocystis jirovecii pneumonia was diagnosed based on the abnormal shadows observed on chest computed tomography, the presence of serum β-D-glucan, and positive P. jirovecii-DNA results in a sputum analysis. Subsequently, after treatment with leucovorin and trimethoprim-sulfamethoxazole, lung consolidation was found to be aggravated, along with a rapidly increasing leukocyte count. In addition, cytomegalovirus colitis was diagnosed. Both conditions were associated with immune reconstitution inflammatory syndrome caused by recovery from leukopenia. The patient was successfully treated with intravenous methylprednisolone pulse therapy and ganciclovir.

A 72-year-old woman was admitted to our hospital with bilateral pleural effusions. She had a 31-year history of systemic lupus erythematosus and had been treated with prednisolone and azathioprine. Pleural fluid culture revealed Salmonella enterica subsp. arizonae infection. This pathogen rarely infects humans but is commonly found in the gut flora of reptiles, especially snakes. Our patient had not come in contact with reptiles. Despite antibiotic therapies and negative pleural cultures, the pleural effusion persisted. Colon cancer was detected concomitantly, and she finally died. The autopsy revealed that the pleuritis was due to underlying diffuse large B cell lymphoma.

UNLABELLED: For the first time ever, the details of osteoporotic treatment were unveiled through the big data published by the government of Japan. The number of patients being treated is low and treatment start is late, especially in men. Our data are useful for education to not only patients but also doctors. PURPOSE: To analyze the current status and trend of osteoporosis treatment in Japan by analyzing the data on main drugs for osteoporosis disclosed in the National Database open data. METHODS: We used the National Database open data released by the Ministry of Health, Labour and Welfare in September 2018. Data on bisphosphonates, denosumab, and teriparatide were extracted to calculate the number of patients treated with these drugs based on the number of prescriptions filed. Using these prescription numbers, the proportion of patients treated with bisphosphonates, denosumab, or teriparatide among osteoporosis patients was calculated. Further, the data on the incidence of hip fractures were employed to validate the appropriateness of the timing of treatment initiation to osteoporosis patients in Japan. RESULTS: The number of patients in men administered bisphosphonates, denosumab, or teriparatide was about one tenth of that in women. The proportion of osteoporosis patients in men treated with bisphosphonates, denosumab, or teriparatide was highest in age group over 80 years at 19.4%. The proportion of osteoporosis patients in women treated with bisphosphonates, denosumab, or teriparatide was highest in age group 70-79 years at 23.7%. The incidence of hip fractures increases sharply over 80 years of age in both genders. CONCLUSION: Our findings suggested that osteoporosis treatment should be initiated in younger age, especially in men, in order to avoid osteoporotic fractures in Japan.

<p>  16歳男性．入院約1か月前に咽頭痛が出現し自然軽快したが，約2週前に両下腿の紫斑，両大腿・下腿の筋痛が出現した．他院でアレルギーを疑われ抗ヒスタミン薬を処方されたが改善なく，足関節痛も出現した．約1週前に再度他院を受診し，腹痛が出現し尿潜血も認めたことからIgA血管炎が疑われ，当科へ紹介され入院した．入院時は腹部全体に自発痛・圧痛を認め経口摂取困難で，両下肢全体に点状の紫斑が散在し，両手関節炎を認めた．絶食補液で経過をみたところ，関節炎は自然に軽快したが，紫斑，腹痛は残存した．下腿皮膚生検でIgA沈着を伴う白血球破砕性血管炎を認め，上下部消化管内視鏡検査では胃，十二指腸，回腸に発赤・びらんが散在したことからIgA血管炎と診断した．尿蛋白・潜血も認めたが軽度であり，紫斑，腹痛が遷延したことから，入院7日目にコルヒチン1 mg/日で治療を開始した．その後数日で紫斑は消失し，入院13日目に経口で摂食が可能となり，消化器症状の再燃もなく入院25日目に退院した．IgA血管炎では遷延する症状に対して副腎皮質ステロイドが使用されるが，症例によってはコルヒチンも有用な場合がある．</p>

肺高血圧症は，稀な疾患ではあるが進行性かつ難治性で治療に難渋する．膠原病でもしばしば肺高血圧症の合併を認めるが，その予後は極めて不良である．しかし，近年プロスタサイクリンであるエポプロステノールをはじめ，エンドセリン受容体拮抗薬であるボセンタンや，ホスホジエステラーゼ-5阻害薬であるシルデナフィルなど，強力な血管拡張作用を有する薬剤が本邦でも使用できるようになった．これらの薬剤は運動耐容能をはじめ，循環動態，ADLの改善，さらには肺高血圧症の予後の改善が大いに期待できる薬剤である．本稿では肺高血圧症の治療薬のうち，最近本邦で認可されたエンドセリン受容体拮抗薬とホスホジエステラーゼ-5阻害薬について解説する．<br>

2005年1月から6月までにアレルギーリウマチ科に入院した100症例を対象とし,入院時と入院1週間後に血中Dダイマー値を測定した。Dダイマーレベルが高値またはその変化が大きかった症例と,下肢深部静脈血栓症(DVT)を疑わせる症状を有する症例について下肢静脈超音波検査を行い,DVTの有無を検査した。その結果,100例中5例にDVTを認めた。うち3例は入院前からDVTを発症しており,2例は入院中に新たにDVTを発症した。DVTがみつかった5症例は全例臨床症状を伴っていたが,臨床症状を伴っていてもDダイマーレベルが上昇していない症例は,下肢静脈超音波検査にてDVTは見られなかった。Dダイマーレベルの変化と臨床症状が見られた症例に対して下肢静脈超音波検査を行うことにより,効率的にDVTを診断できるものと考えられた。