Cytomegalovirus in Ulcerative Colitis Bryan Warren

Case History: This 32 year old man had ulcerative colitis for 4 years. Recently he developed very severe diarrhea. Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer This case has crypt architectural distortion, mucin depletion and diffuse chronic and acute inflammation commensurate with ulcerative colitis. Numerous cytomegalovirus inclusions are seen. Cytomegalovirus infection may be considered as primary or reactivation infection or super infection. Cytomegalovirus is usually not eliminated after a primary infection but may persist as a low-grade infection albeit in a dormant state. Later reactivation and transmission are therefore possible. The virus may become apparent when the body's immune system is compromised in anyway, such as in a transplant, HIV or blood transfusion. Cytomegalovirus may be transmitted sexually or via infected organs or needle stick injury or by means of blood. Colonic infection with cytomegalovirus are most commonly seen to complicate pre existing ulcerated or inflammatory disorders and they are a common complication of ulcerative colitis but may also be seen in almost any ulcer or in association with large bowel adenocarcinoma. Cytomegalovirus infections in general seem to home in on areas of pre existing inflammation which explains their favouritism for colonising the colon of patients with ulcerative colitis. The symptoms in ulcerative colitis will not usually change except will become more severe when there is superimposed cytomegalovirus infection. Cytomegalovirus colitis may be associated with cytomegalovirus elsewhere in the gut. If the virus colonises the myenteric plexus, it may cause pseudo obstruction of the bowel. The macroscopic features of cytomegalovirus infection in ulcerative colitis do not differ significantly from those of severe ulcerative colitis. If cytomegalovirus is found in isolation or sometimes in ulcers in pouches after ileo-anal reservoir surgery there may be discreet ulcers with slightly overhanging edges, which may sometimes mimic Crohn's disease particularly in the pouch and this is a well known catch in pouch pathology. Therefore any such ulcers seen in the pouch should not be assumed to be Crohn's disease but should be biopsied carefully with a thought to look for cytomegalovirus inclusions. In non UC patients one may see dark violaceous lesions bearing some resemblance to Kaposi's sarcoma they may be discreet or diffuse inflammation or pseudomembranous colitis or perforations. In the most severe form of cytomegalovirus colitis there are multiple ulcers and perforations and it may occasionally be mistaken macroscopically for ischaemic colitis. When it is severe our inclusions are present at many sites in many different tissues in the mucosa and in the bowel wall not just in the vascular endothelial cells. The inclusions are more numerous in areas of ulceration particularly in the vascular endothelial cells, the granulation tissue, the pseudopolyps and even in the intervening mucosa. More subtle infections may require enhanced awareness and deeper levels. Immunohistochemistry for cytomegalovirus is an important technique however my own view is that several patients with ulcerative colitis may have occasional cytomegalovirus inclusions but are symptomatically reasonably well. I am not sure that these are very relevant, except as a pointer to possible more severe infection in the future. When cytomegalovirus is significant in ulcerative colitis and indeed likely to provoke toxic megacolon, the inclusion bodies are much more numerous as illustrated in the case shown. The case shown was one of toxic megacolon developing in ulcerative colitis after more and more immunosuppressive therapy and failure to respond to such therapy. It is reasonable to consider doing a further biopsy to look for cytomegalovirus inclusions or other infected agents for patients with ulcerative colitis failing to respond to increasing amounts of immuno suppressive therapy. The important message for this case is that when the patient fails to respond to increasingly more immunosuppressive and potentially more toxic therapy a superimposed infection with cytomegalovirus or sometimes with other organisms will have to be considered and a simple rectal biopsy as in this case may reveal the diagnosis. This will allow therapy to be tailored to take account of the superimposed cytomegalovirus infection. References Hashiro GM, Horikami S, Loh PC: Cytomegalovirus isolations from cell cultures of human adenocarcinoma of the colon. Intervirology 1979; 12:84. Goodman ZA, Boitnott JK, Yardley JH: Perforation of the colon associated with cytomegalovirus infection. Dig Dis Sci 1979; 24:376 Foucar E, Mukai K, Foucar K, et al: Colon ulceration in lethal cytomegalovirus infection. Am J Clin Pathol 1981; 76:788. Sonsino E, Mouy R, Foucaud P, et al: Intestinal pseudoobstruction related to cytomegalovirus infection of myenteric plexus. N Engl J Med 1984; 311:196. Rasing LA, DeWeger RA, Verdonck LF et al. The value of Immunohistochemistry and in situ hybridization in detecting cytomegalovirus in bone marrow transplant recipient. APMIS 1990; 98:479