頸部リンパ節および耳下腺病変にミノサイクリンが著効したサルコイドーシスの1例

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1 症例報告 ミノサイクリンが著効したサルコイドーシスの1例 頸部リンパ節および耳下腺病変にミノサイクリンが著効した サルコイドーシスの1例 増永愛子 1) 石川理惠 1) 森本耕三 1) 神宮浩之 1) 安藤常浩 1) 生島壮一郎 1) 武村民子 2) 折津 愈 1) 江石義信 3) 要旨 症例; 74歳 女性 右頸部腫瘤を主訴に前医受診 頸部リンパ節摘出術を行い組織診でサルコイドーシスが疑われ 当院紹介 右膝の皮膚生検 気管支肺胞洗浄の結果 サルコイドーシスと診断した 経過観察していたが右頸部リ ンパ節が再度腫大し 右耳下腺腫大も出現した 治療適応と考えたが糖尿病の合併があったためステロイド剤の使 用は見合わせ ミノサイクリンを開始した 直後からリンパ節 耳下腺の著明な縮小が得られた 診断時の組織標 本で に対する単クローン抗体 PAB抗体 陽性の顆粒を認めたため ミノサイクリン投与 後に患者の承諾を得て再度頸部リンパ節生検を行った 組織の中心部は壊死を伴った硝子化が大部分を占めその中 はPAB抗体は陰性であったが 硝子化の周囲の巨細胞内にはPAB抗体陽性像が見られた サルコイドーシスにおける の関与およびミノサイクリンによる治療について報告する 日サ会誌 2008; 28: キーワード サルコイドーシス アクネ菌 ミノサイクリン 抗菌薬 リンパ節 A Case of Sarcoidosis with Marked Improvement of Cervical Lymph Node and Parotid Gland Involvement by Minocycline Hydrochloride Aiko Masunaga1), Rie Ishikawa1), Kozo Morimoto1), Hiroyuki Kamiya1), Tsunehiro Ando1), Soichiro Ikushima1), Tamiko Takemura2), Masaru Oritsu1), Yoshinobu Eishi3) ABSTRACT A 74 year old woman visited a hospital complaining of right cervical lymphadenopathy. The cervical lymph node was removed and histology revealed non-caseating epithelioid cell granuloma, suspicious of sarcoidosis. She was referred to our hospital for further examination. We diagnosed her as having sarcoidosis, based on biopsy of the right knee skin and findings of bronchoalveolar lavage fluid. Later, right cervical lymph node and parotid gland became enlarged. As she did not agree to take corticosteroids because she had diabetes mellitus, we chose Minocycline hydrochloride. Minocycline treatment induced the size reduction of cervical lymph node and parotid gland. A second biopsy of cervical lymph node was carried out with informed consent. Histopathology of lymph node revealed massive hyalinization with remnant of regressive granuloma and giant cells. Immunohistochemical study of monoclonal antibody against lipoteichoic acid (PAB) revealed positive granules in the granuloma before Minocycline treatment, whereas PAB positive granules were found in giant cells around hyalinization and PAB had no reaction in the hyalinization after therapy. This case demonstrates that Minocycline induced reduction of granuloma but PAB positive granules remain, suggesting that Minocycline acts as an immunomodulator in addition to suppressing intracellular bacteria. [JJSOG 2008; 28: 93-97] Keywords: Sarcoidosis, 1 日本赤十字社医療センター呼吸器内科 2 同病理部 3 東京医科歯科大学大学院人体病理学分野 著者連絡先 増永愛子 東京都渋谷区広尾 日本赤十字社医療センター呼吸器内科 TEL FAX aiko.masunaga@ab.auone-net.jp, Minocycline hydrochloride, Antibiotics, Lymph node 1) Department of Respiratory Medicine, Japanese Red Cross Medical Center 2) Department of Pathology, Japanese Red Cross Medical Center 3) Department of Human Pathology, Graduate School, Tokyo Medical and Dental University 93

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3 症例報告 ミノサイクリンが著効したサルコイドーシスの1例 Figure 1. Cervical MRI before therapy, showing swelling of right cervical lymph nodes and parotid glands. Figure 3. a Figure 2. Five months after initiation of minocycline hydrochloride therapy, right cervical lymph nodes and parotid glands became smaller markedly. The clinical course. b Figure 4. a) Histopathological feature of cervical lymph node biopsy before therapy. Non-caseating epithelioid cell granulomas with giant cells were observed. (HE, 10) b) Immunohistochemical analysis on cervical lymph node biopsy stained with PAB antibody. PAB antibody positive granules were detected in non-caseating epithelioid cell granulomas. ( 100) 95

4 日サ会誌 2008, 28 (1) a b c d Figure 5. Histopathological findings of cervical lymph node biopsy after minocycline treatment. Hyaline degeneration was observed throughout the lymph node (a, HE, 4), with regressive granuloma round the hyalinization. Hyalinized and regressive granulomas were observed. (b, HE, 10) One giant cell and macropharges aggregated. (c, HE, 20) Possitive reaction to PAB was observed in the giant cells. (d, 100) 考察 サルコイドーシスの原因は未だ不明であるが 疾患 感受性のある宿主が環境中の何らかの起因体に暴露さ れて誘導されるTh1タイプの過敏性免疫反応に起因す るらしいと言われている 1) またサルコイドーシスと の関係については以前より報告されているが 日本人サルコイドーシス患者のリンパ節中の の定量系PCRの解析が報告されて以来 2) 病 1) 因説がさらに注目されている また肉芽腫反応は細 胞内停滞性抗原に対する宿主の防御反応であると考え られるが のDNAがサルコイドーシスの肉芽 腫内に集積して存在することが報告されており 3) こ のことも がサルコイドーシスの肉芽腫の形成 に関与していることを示唆している 同様にPAB抗体の検討においても サルコイドーシ スの肉芽腫内の巨細胞や類上皮細胞内に抗体陽性顆粒 96 が充満しているとの報告が多くされている 4,5) その一 方で成熟 陳旧化した肉芽腫内では抗体陽性像は量 強度ともに減弱している 4) 本症例でも PAB抗体は治療前後の組織標本におい て陽性であったが 治療前は肉芽腫内で広範に強く陽 性所見を示したのに対して 治療後は組織の大部分は 硝子化に陥り 同部位はPAB抗体は陰性で 周辺の巨 細胞で陽性所見を示すのみであった PAB抗体では生 菌と死菌あるいはdormant phaseにある菌との区別が 出来ないことから 本症例の治療後のPAB抗体陽性所 見からは のviablityの推定は出来ない ちな みに本症例の治療後の摘出リンパ節の組織培養では は陰性であった しかし これらの結果は肉芽 腫からの完全な抗原除去を目指す場合には より長期 で強力な抗菌療法が必要であることを示唆している可 能性はある

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36 仮面尿崩症を呈した神経サルコイドーシスの1例 症例報告 不明熱にて発症し 仮面尿崩症を呈した神経サルコイドーシスの1例 笹森 寛 泉山典子 齋藤若奈 宍倉 裕 菊地 正 三木 2 3 4 5 6 鈴木靖士 齋藤泰紀 手塚文明 武村民子 江石義信 祐 菊池喜博 要旨 症例は20歳男性 2007年3月末より38 台の発熱出現し近医受診 CTにて縦隔リンパ節腫脹および両側肺野 に10 mm内外の空洞性病変を複数認めた

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