薬剤関連消化管疾患の病理組織学的特徴

Histopathological Features of Drug-related Digestive Diseases

要旨●薬剤の直接的あるいは間接的作用により生じるさまざまな消化管疾患が存在するが，NSAIDs（胃腸潰瘍，collagenous colitis），PPI（胃ポリープ，collagenous colitis），抗癌薬（胃腸炎），抗菌薬（出血性腸炎，偽膜性腸炎），ポリスチレンスルホン酸ナトリウム（消化管穿孔），免疫抑制薬（感染症），漢方薬（特発性腸間膜静脈硬化症），下剤（大腸メラノーシス），高リン血症治療薬（炭酸ランタン沈着症），直接トロンビン阻害薬（食道潰瘍）が代表的な薬剤関連消化管疾患である．最近，免疫関連有害事象としての消化管傷害とPPI関連ポリープが新たに注目されており，その病理組織学的特徴も知られるようになってきた．薬剤関連消化管疾患の特に重要な病理組織学的所見として，①陰窩増殖帯上皮細胞のアポトーシス小体の出現，②粘膜内の好酸球浸潤，③上皮内Tリンパ球浸潤の増加が報告されており，これらは特異的ではないが薬剤性を含む特殊な疾患の可能性を示唆する所見である．病理診断の際にはこれらの所見に加えそれぞれの疾患に特徴的な病理組織学的所見の有無に常に注意を払う必要があり，それにより生検組織のみでも薬剤性の可能性を疑うことが可能である．

　There are many drug-related digestive diseases such as those caused by NSAIDs（nonsteroidal anti-inflammatory drugs）. These diseases include gastrointestinal ulcers, collagenous colitis, proton pump inhibitor-associated gastric polyps, and anti-cancer drug-related gastroenteritis. In addition, NSAIDs include certain antibiotics that can cause hemorrhagic colitis and pseudomembranous colitis. Further, kayexalate can lead to perforation, immunosuppressive drugs can cause infection, herbal medicine can lead to mesenteric phlebosclerosis, laxatives are associated with melanosis coli, hyperphosphatemia drugs may cause lanthanum carbonate-related lesions, and direct thrombin inhibitors can cause esophageal ulcers. Recently, research has focused on digestive diseases of immune-related adverse events and proton pump inhibitor-related gastric polyps and their histopathological features have been elucidated.

　Particularly important histopathological findings of drug-related gastrointestinal diseases include the appearance of apoptotic bodies in the epithelium, eosinophil infiltration in the mucosa, and increased intraepithelial infiltration of T lymphocytes. These findings are not specific but are indicative of some particular diseases, including drug-related diseases. At the time of pathological diagnosis, it is important to pay attention to the presence or absence of characteristic histopathological findings of associated diseases in addition to these findings to assess possible drug properties even with a biopsy tissue specimen alone.