呼吸器および消化管粘膜を侵す腫瘍性天疱瘡

Paraneoplastic Pemphigus Involving the Respiratory and Gastrointestinal Mucosae.

• Kentaro Odani
• Akane Itoh
• Soshi Yanagita
• Yasuhito Kaneko
• Mitsuhiro Tachibana
• Takashi Hashimoto
• Yutaka Tsutsumi

抄録

腫瘍性天疱瘡（PNP）は、口腔粘膜と気管支粘膜を侵す自己免疫性粘膜皮膚疾患で、血液悪性腫瘍のまれな合併症である。血清学的には、様々なデスモゾーム関連タンパク質に対する血清自己抗体が注目されています。PNPはしばしば閉塞性気管支炎や日和見感染により致死的になる．70歳の日本人男性が乾性咳嗽，口内炎，咽頭痛を訴えた．口唇と口腔粘膜の侵食がひどく，胸部と腹部に皮膚浸出を認めた．生検の特徴はPNPと一致し，IgGとIgMの沈着が角化細胞の血漿膜上に認められた．血清学的検査では、desmoglein-3、desmocollins-2および-3、水疱性天疱瘡抗原-1、envoplakinおよびperiplakinに対する自己抗体を示した。全身検査の結果，マントル細胞リンパ腫，ステージ4Bと診断された．化学療法後、部分寛解に達した。PNPにはメチルプレドニゾロンと免疫グロブリンの静脈内投与を行い、口腔内病変は一時的にしか反応しなかった。発症から2ヵ月後に呼吸不全で死亡した。剖検の結果，低悪性度リンパ腫と全身性日和見感染症が残存し，侵食した気管支・気管支粘膜にコロニー化し，広範な血管浸潤を認めた．サイトメガロウイルス（CMV）に感染し、間質性肺炎を引き起こした。口咽頭、呼吸器、食道、消化管粘膜はCMVにびまん性に感染した。末梢肺では閉塞性気管支炎が認められた．気管支および消化管粘膜ではPNP関連のアカントリシス様病変が顕微鏡的に確認された．粘膜柱状細胞ではIgGの沈着とCaspase-3の切断による免疫反応性アポトーシス細胞死が認められた。粘膜浸潤の病因について考察した。

Paraneoplastic pemphigus (PNP), an autoimmune mucocutaneous disorder involving the oral and bronchial mucosae, is a rare complication of hematologic malignancy. Serologically, serum autoantibodies against varied desmosome-related proteins are of notice. PNP is often lethal due to bronchiolitis obliterans and opportunistic infection. A 70-year-old Japanese male complained of dry cough, stomatitis, and sore throat. The lips and oral mucosa were severely eroded, and skin eruptions were seen on the chest and abdomen. The biopsy features were consistent with PNP, and the deposition of IgG and IgM was shown on the plasma membrane of the involved keratinocytes. Serological studies demonstrated autoantibodies to desmoglein-3, desmocollins-2 and -3, bullous pemphigoid antigen-1, envoplakin and periplakin. Systemic evaluation disclosed mantle cell lymphoma, stage 4B. After chemotherapy, partial remission was reached. PNP was treated with methylprednisolone and intravenous immunoglobulins, and the oral lesion only temporarily responded. He died of respiratory failure two months after onset. Autopsy revealed residual indolent lymphoma and systemic opportunistic infections. colonized the eroded bronchial/bronchiolar mucosa, associated with extensive vascular invasion. Coinfection of cytomegalovirus (CMV) and caused interstitial pneumonia. The oropharyngeal, respiratory, esophageal, and gastrointestinal mucosae were diffusely infected by CMV. Bronchiolitis obliterans was observed in the peripheral lung. PNP-related acantholysis-like lesions were microscopically identified in the bronchial and gastrointestinal mucosa. IgG deposition and cleaved caspase-3-immunoreactive apoptotic cell death were proven in the involved mucosal columnar cells. Pathogenesis of the mucosal involvement is discussed.

Copyright © 2020 Kentaro Odani et al.