インフリキシマブ投与中にリステリア髄膜脳炎を発症した成人スチル病の1例 A case in which the subject was affected by Listeia meningoencephalitis during administration of infliximab for steroid-dependent adult onset Still's disease

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  症例は,22歳女性.2005年6月頃に高熱,関節痛および四肢に皮疹が出現し,近医皮膚科を受診した.その際の血液検査で肝機能障害を指摘され,翌日同院内科に入院となった.CRPは著明に高値を呈したが,感染徴候はなく,骨髄像も正常であった.持続する39℃以上の発熱,皮疹,白血球増加,咽頭痛,脾腫,肝機能障害,血液検査で自己抗体陰性,高フェリチン血症を認めたことから,成人スチル病と診断された.プレドニゾロン30 mg/日より治療が開始されたが,無効であり,ステロイドパルス療法を実施,加療継続のため7月中旬に当科転院となった.ステロイドとシクロスポリンの併用により,活動性のコントロールを試みたが,高フェリチン血症の増悪,肝障害の出現を認め,2回目のステロイドパルス療法を実施した.一時的に症状は改善を認めるものの,ステロイド減量困難であることから,シクロスポリンをメトトレキサートに変更し,インフリキシマブの投与を開始した.経過中,ST合剤の処方を開始したが,薬剤性肝障害も疑われたため,中止した.8月下旬に2回目のインフリキシマブ投与を実施し,速やかに臨床症状および検査値異常の改善を認めた.しかし9月上旬に突然,高熱と頭痛が出現したため,髄液検査,血液・髄液培養および頭部MRI撮影を実施した結果,リステリア髄膜脳炎と診断した.経過中,複視および意識障害が出現し,画像上,脳膿瘍の形成を認めたが,長期間にわたるアンピシリンとゲンタマイシンの併用療法により治癒することができた.成人スチル病に対しては,インフリキシマブ投与は中止し,二重膜濾過血漿交換を併用することで,ステロイド剤の減量をはかることが可能であった.その後,症状の再燃,血液検査値異常の出現は認めず,2005年12月に当科退院となった.リウマチ性疾患の治療は,生物学的製剤の出現により,従来の治療では抵抗性を示していた病態における治療成績の劇的な改善が得られている.しかし一方,日和見感染症の発症も大きな問題であり,十分な予防と対策が必要になる.今回,私たちはステロイド依存性の成人スチル病に対してインフリキシマブを投与中,リステリア髄膜脳炎を発症した一例を経験した.リステリア症も,結核と同様に,今後注意すべき合併症の一つとして考えられるため,考察を加え報告する.<br>

  The subject was a 22-year-old woman who developed high fever and arthralgias and eruptions in the extremities around June 2005. She sought medical advice at a nearby dermatology clinic, where hepatic dysfunction was noted on blood testing. The patient was thus hospitalized the next day. Although CRP levels were significantly high, no sign of infection was observed and bone marrow cell differentiation was normal. Adult onset Still's disease was diagnosed based on the observation of persistent high fever >39°C, eruptions, increased leukocytes, pharyngeal pain, splenomegaly, hepatic dysfunction, negative autoantibody results from blood testing, and high serum ferritin levels. Administration of prednisolone 30 mg/day was initiated, but proved ineffective. Steroid pulse therapy was conducted, and the subject was transferred to our medical facility for continued treatment. Attempts were made to control the disease using combined steroid and cyclosporine administration ; but exacerbation of high serum ferritin levels and hepatic dysfunctions were observed, so a second course of steroid pulse therapy was conducted. Symptoms improved temporarily, but steroid levels were difficult to reduce. Cyclosporine was therefore replaced by methotrexate, and administration of infliximab was initiated. In the course of treatment, administration of a sulfamethoxazole/trimethoprim combination was initiated, but was discontinued due to suspicion of drug-induced hepatic injury. A second administration of infliximab was conducted in late August, and rapid improvements in clinical symptoms and abnormal test values was observed. However, high fever and headache developed suddenly in early September. Based on the results of spinal fluid testing, blood and spinal fluid cultures and MRI of the head, Listeria meningoencephalitis was diagnosed. Diplopia and impaired consciousness occurred during the disease course, and formation of a brain abscess was observed on imaging. However, symptoms were controlled by long-term combination administration of ampicillin and gentamicin. Administration of infliximab was discontinued for treatment of adult onset Still's disease, and steroid levels were reduced following double-membrane filtration plasma exchange. On follow-up, no relapse of symptoms or abnormalities in blood test values were observed, so the subject was discharged from our medical facility in December 2005. In treatment for rheumatic diseases, a dramatic improvement in treatment results for pathologies displaying tolerance against conventional treatments has been acquired with the development of biological drugs. However, opportunistic infections represent a serious problem, and appropriate preventative measures are required. The present report describes a case in which the subject was affected by Listeria meningoencephalitis during administration of infliximab for steroid-dependent adult Still's disease. Since listeriosis is one of the complications, along with tuberculosis, that warrants precautionary measures, this case is reported and discussed.<br>

収録刊行物

  • 日本臨床免疫学会会誌 = Japanese journal of clinical immunology  

    日本臨床免疫学会会誌 = Japanese journal of clinical immunology 29(3), 160-168, 2006-06-30 

    The Japan Society for Clinical Immunology

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各種コード

  • NII論文ID(NAID)
    10018057787
  • NII書誌ID(NCID)
    AN00357971
  • 本文言語コード
    JPN
  • 資料種別
    NOT
  • ISSN
    09114300
  • データ提供元
    CJP書誌  J-STAGE 
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