非ステロイド系抗炎症剤（NSAID）起因性腸病変の臨床病理学的特徴と病態

Clinicopathological Characteristics and Pathological Mechanism of Non-steroidal Anti-inflammatory Drug (NSAID)-induced Intestinal Lesions

要旨　非ステロイド系抗炎症剤(non-steroidal anti-inflammatory drug；NSAID)起因性消化管病変の病理組織学的特徴を明らかにするため，NSAID起因性小腸・大腸炎(潰瘍)の32症例からの生検材料53個および，小腸膜様狭窄症3例と小腸穿孔性潰瘍2例の外科的切除材料の組織学的特徴を解析した．生検群は，①アポトーシス性細胞傷害型，②非特異性腸炎型，③好酸球性腸炎型，④虚血性腸炎型，⑤出血性腸炎型，⑥膠原線維性大腸炎型の6型に分類された．生検群を臨床像から腸炎型(8症例，生検21個)と潰瘍型(24症例，生検37個)に分けると，アポトーシス性細胞傷害型は腸炎型(5.9％)より潰瘍型(41.7％)で有意に多く，穿孔性潰瘍と膜様狭窄症でもアポトーシス性細胞傷害型と同様の組織像であり，NSAID起因性潰瘍の発生にアポトーシスが重要な役割を果たしていることが示唆された．また，NSAIDの作用機序である薬剤による直接細胞傷害(アポトーシス性細胞傷害)とCOX抑制(prostaglandin系)を介した細胞傷害，血管透過性亢進による循環不全(虚血)，アレルギー(好酸球増加)などの程度と組み合わせの差により，NSAID起因性消化管病変は多様な臨床像・組織像を呈すると考えられた．

　In order to elucidate the clinicopathological features of non-steroidal anti-inflammatory drug (NSAID)-induced intestinal lesions, 32 cases (53 lesions of biopsy specimens)from NSAID-induced enteritis (including ulcers), 3 cases of small intestinal diaphragm disease and 2 cases of perforated small intestinal ulcers were histologically reviewed.

　Lesions of biopsy specimens were classified into 6 types: (1) apoptotic cytotoxicity-type, (2) non-specific enteritis-type, (3) eosinophilic enteritis-type, (4) hemorrhagic enteritis-type, (5) ischemic enteritis-type, (6) collagenous colitis-type. When clinically divided into enteritis-type and ulcer-type, apoptotic cytotoxicity-type was more frequently recognized in ulcer-type (41.7％) than in enteritis-type (5.9％). In addition, all the perforated ulcers and diaphragm disease were also classified into apoptotic cytotoxicity-type. These redults suggest that apoptosis plays an important role in ulcer formation.

　NSAID-induced enteritis reveals variable clinical and histological features, which are considered to depend on the degree and combination of apoptotic cytotoxicity, inhibiting cyclo-oxygenase(inhibiting prostaglandin system), increased vascular permeability(ischemia)and allergy (eosinophilic infiltration).