手術例からみた難治性潰瘍性大腸炎におけるサイトメガロウイルス感染

Cytomegalovirus Infection in Patients with Refractory Ulcerative Colitis: Histological and Clinical Correlation in Surgical Resection Cases

要旨　サイトメガロウイルス（CMV）感染は潰瘍性大腸炎（UC）の難治化要因として注目されているが，その病理組織学的特徴については不明な点が多い．今回，難治性UC切除連続例35例を対象として，CMV感染の病理組織学的特徴を明らかにするとともに，組織学的CMV感染と生検診断および血中抗原による臨床診断法との関連性について，臨床病理学的ならびに免疫組織化学的立場より比較検討し，以下の結果を得た．①CMV感染陽性率は切除標本上で51.4％（18/35）であり，そのCMV陽性細胞の存在部位は主として潰瘍部の肉芽組織の血管内皮細胞であった．②CMV陽性率は血中抗原で44.0（11/25），生検組織で15.4％（4/26）であった．そして，血中抗原陽性11例のうち10例（90.9％）と生検陽性4例のうち4例（100％）では切除標本上にもCMV陽性細胞を認めた．なお後者の陽性例はすべて肉芽組織が採取されており，免疫組織化学染色（IHC）法により明確に診断された．③CMV感染陽性者の臨床的特徴は陰性者と比較し有意に高齢であった（p＝0.0025）．④血中抗原の陽性細胞数と切除標本における組織学的感染細胞数とは相関しなかった．以上の結果から，難治性UCにおいてはCMV感染を常に念頭に置く必要があり，そのCMV感染診断の向上には，潰瘍底の肉芽組織から生検材料を採取すること，およびHE染色による組織診断法に加え免疫組織化学染色法と血中抗原測定法を併用することが重要であると結論した．

　Cytomegalovirus (CMV) infection has been known as a refractory factor of ulcerative colitis (UC). However, the characteristic pathologic features have not been made clear. The aim of the present study is to investigate characteristic pathologic findings of CMV in refractory UC, and to elucidate the relationship between its clinical and pathological findings. Patients ; Among 35 consecutive UC patients who had undergone colectomy, 25 patients were examined by antigenemia assay prior to the operation and 26 patients were examined by endoscopic biopsy prior to the operation. Methods ; Comparison of clinical background of patient's age, sex, disease duration, total dose of corticosteroid, and disease type were made between CMV infected and non-infected patients. Hematoxylin and eosin (HE), and immunohistochemical staining were performed in all cases. Furthermore, in five cases in situ, hybridization was made to detect CMV DNA. Positive rate of CMV infection was 51.4％ (18/35) histologically (in step-wise specimens) in the surgical specimens. The rate was 44％ (11/25) determined by antigenemia assay, and 15.4％ (4/26) determined by biopsy specimens. Percentage of positive staining in surgical specimens was 90.9％ among the antigenemia positive cases. Histologically, CMV positive cells were located in the endothelial cells of the granulation tissue of the ulcer base. Relationship between number of positive cells found in the antigenemia assay and the number of positive cells found by immunohistochemical examination of resected specimens is not significant. Conclusion ; CMV infection was seen in about half of the surgical specimens of refractory UC, and there was a good correlation between the histological positive rate of CMV infection and that of antigenemia assay. In refractory UC patients, concomitant CMV infection should be considered and should be tested by antigenemia assay and by immunohistochemical staining method in order to obtain a definite clinical and histological diagnosis. These tests will result in earlier treatment by antiviral agents.