key: cord-0006902-c5cyzddd authors: Alam, Imran; Shanoon, Divina; Alhamdani, Ali; Boyd, A.; Griffiths, A.P.; Baxter, J.N. title: Severe Proctitis, Perforation, and Fatal Rectal Bleeding Secondary to Cytomegalovirus in an Immunocompetent Patient: Report of a Case date: 2007-01-01 journal: Surg Today DOI: 10.1007/s00595-006-3335-1 sha: ce6a41cfc745ec42906b0a5d6fbb50be04358800 doc_id: 6902 cord_uid: c5cyzddd Cytomegalovirus (CMV) infection is associated with significant morbidity and mortality in immunocompromised patients. In immunocompetent individuals, the infection is usually subclinical but it can sometimes be life threatening. We describe a case of fatal CMV proctitis in a 71-year-old man following an Ivor–Lewis esophagectomy. After surgery he developed renal failure, methicillin-resistant Staphylococcus aureus pneumonia, and acute respiratory distress syndrome. He recovered but developed melena and massive fresh rectal bleeding. Sigmoidoscopy revealed severe proctitis and a biopsy was consistent with ischemia. Despite undergoing a proctectomy he continued to bleed and died despite every effort. The final histological examination of the rectum revealed a CMV infection. nary team and a decision was made to proceed with an Ivor-Lewis esophagectomy. Other co-morbidities included diabetes mellitus and 2nd-degree heart block. Following surgery, he developed renal failure, methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, and acute respiratory distress syndrome (ARDS). A computed tomography (CT) scan of the abdomen and pelvis was normal. He recovered but thereafter developed melena. The gastroscopy findings were normal. He continued to have intermittent heavy melena and fresh rectal bleeding. The hemoglobin level dropped to 5.0 g/l and he received 15 units of blood. An emergency EUA (examination under anesthesia) and flexible sigmoidoscopy revealed a lot of blood, severe inflammation, and multiple ulcers in the rectum and sigmoid colon, but no active bleeding. Multiple biopsies were taken and the rectum was packed over two big drains to keep the bowel decompressed. He was initially treated by steroids and broad-spectrum antibiotics. A repeat CT scan revealed severe proctitis. After 48 h the packs were removed and repeat EUA did not show any evidence of any further bleeding. A rectal biopsy histology revealed nonspecific inflammation and ulceration, which was probably ischemic. He continue to deteriorate, developing sepsis and multiorgan failure but without any further bleeding until 10 days when an episode of profuse rectal bleeding caused his hemoglobin to dropped to 5.1 g/dl. An emergency proctectomy and colostomy were performed. Postoperatively, he developed secondary hemorrhaging and thus underwent a re-exploration. There was no active bleeding but generalized oozing in the peritoneum cavity that could not be controlled despite using all possible means. At that stage it was decided to pack the wound for 24-48 h, correct the coagulation abnormalities, sepsis, and re-explore under a more controlled situation. However, he continued to bleed into the abdominal drains, despite all attempts to correct the Introduction Cytomegalovirus (CMV) infection in immunocompromised patients is often a major cause of morbidity and mortality. We herein describe a case of fatal CMV proctitis with no prior evidence of immunodeficiency or inflammatory bowel disease. A 71-year-old man was diagnosed as having esophageal adenocarcinoma. He was evaluated by a multidiscipli-coagulation abnormalities, and the outcome was fatal. A histological examination of the rectum demonstrated severe inflammation, multiple ulcers, one perforation ( Fig. 1) , and evidence of CMV infection with abundant characteristic nuclear inclusion bodies on hematoxylineosin staining (Fig. 2) and immunohistochemistry (Fig. 3 ). These were found almost exclusively in the bases of the ulcers, and they were associated with endothelial swelling, perivascular inflammation, and vascular occlusion with microthrombi. Cytomegalovirus is a DNA virus (herpes virus group). After an initial infection, the genome of the virus per-sists in the host and may spontaneously reactivate later. Approximately 50%-80% of the general population becomes seropositive by the age of 35 years. 1 Clinically significant infections are usually found when immunological mechanisms have been altered or suppressed by neoplasia, chronic infections, immunosuppressive therapy, or autoimmune deficiency syndrome (AIDS). 2 A CMV infection is increasingly common because of rising number of patients with immunodeficiency conditions such as AIDS and organ transplantation. Lesions attributable to focal or widespread CMV infection can involve many organs, including the retina, liver, lung, and the gastrointestinal tract. 3 In immunocompetent individuals it is rare but it can affect patients with diabetes 4 and severe trauma. 5 Gastrointestinal CMV disease is not infrequently encountered in seemingly immunocompetent patients without a human immunodeficiency virus (HIV) infection. It can affect any part of the gastrointestinal tract, with esophagus and colon being the most common sites. 6 The clinical manifestations include malaise, anorexia, fever, nausea, diarrhea, abdominal pain, ileus, gastrointestinal bleeding, and perforation. 7 The mortality is high and the prognosis is particularly poor in elderly individuals (over 65 years). Cytomegalovirus also tends to be complicated with pre-existing inflammatory bowel diseases, particularly steroid-resistant cases. In one study, Yashihisa et al. 8 found CMV to be present in 21% of surgical specimens of ulcerative colitis, and all cases were steroid resistant. Rectal ulcerations leading to life-threatening hemorrhaging and perforation can be due to a benign process (idiopathic, inflammatory bowel disease, infective, drug induced, traumatic) and malignancy ( Table 1 ). The dif- ferential diagnosis of CMV proctitis includes acute hemorrhagic rectal ulcer syndrome, solitary rectal ulcer, stercoral ulcers, infective proctitis secondary to amoebiasis, tuberculosis and syphilis, ischemic proctitis, radiation-and drug-induced proctitis, and trauma. Acute hemorrhagic rectal ulcer syndrome is almost nonexistent in the Western world, while few cases have been reported in Japan. 9 It affects the elderly population and is characterized by a sudden onset of massive, painless hemorrhaging from rectal ulcers and serious medical illness for which other causes are excluded. 9 Rectal ulcers are usually above the dentate line, and can be solitary or multiple without significant inflammation or ecchymosis. 10 It may be difficult to differentiate this disease from infective rectal ulcers. However, a negative culture of stool and biopsy specimen and absence of intranuclear inclusion bodies (typical of CMV infection) in biopsy tissue specimens can help in making an accurate diagnosis. 2, 10 Solitary rectal ulcer syndrome (mucosal prolapse syndrome) is a clinical condition associated with functional anorectal evacuatory disorders. 11 The diagnosis is based on the patient history, the endoscopic appearance, and a histological examination of the biopsy specimen. The macroscopic appearance ranges from hyperemia to ulceration or even a polypoid lesion, and the lesions are not necessarily solitary. The microscopic features include mucosal thickening, fibrosis, and extension of smooth muscle fibers upward between the crypts, and full thickness rectal histology reveals architectural derangements. 12 Stercoral ulceration is the loss of bowel integrity from the pressure effects of inspissated feces. 13 Such lesions usually occur in constipated, bedridden patients and present as an isolated lesion in the rectosigmoid area, and a solid fecal mass is usually adherent to the margin of the ulcer. 10 Perforation and hemorrhaging are the principal complications resulting in a high mortality if not diagnosed early. 13, 14 The diagnosis of perforated stercoral ulceration should be considered in any patient with a long-standing history of constipation who presents with acute abdominal pain and clinical findings consistent with a perforation of a hollow viscus. Macroscopically the lesions are round or oval and the microscopic characteristics are represented by superficial ischemic necrosis of the rectal wall. 15 The rectal wall is usually inflamed and edematous, and characterized by multiple, shallow, serpigenous ulcerations in amoebic proctitis. The diagnosis is confirmed by a history, stool culture, biopsy (detection of trophozoites), and serology. 7 Rectal tuberculosis is rare in the absence of other lesions in the chest and small and large intestine. 16 Radiation-and drug-induced proctitis can readily be excluded based on the patient's history. 10 Ischemic proctitis is often associated with clearly identifiable precipitating factors (aortoiliac procedure, shock, and sepsis) and lesions are characterized by edema and erythema either with or without ulceration. It can be ruled out by a negative stool culture, endoscopic findings, and the absence of inclusion bodies in the biopsy specimen. 10 Cytomegalovirus colitis is usually associated with mucosal lesions that are probably due to vascular endothelial infection, thus leading to endothelial cell swelling, capillary occlusion, thrombosis, ischemia, and ulceration, and presenting clinically as hemorrhagic enteritis, colitis, or occasionally it causing full thickness damage and a perforation of the colon. 17 Perivascular inflammation or vasculitis may also develop. The role of CMV as a primary colonic pathogen is disputed and it is uncertain whether the virus can initiate infection or simply prevent the healing of ulcers. 18 Endoscopy with a biopsy is the investigation of choice. The ulcers are usually numerous, round, or serpiginous, often reaching the muscular layer, and occasionally perforating. The best approach is to confirm the presence of CMV by histological examinations and thus rule out any other pathogens using microbiological techniques. The CMV inclusion bodies are typically round, eosinophilic, intranuclear, or intracytoplasmic, and they are seen in endothelial and mucosal cells or fibroblasts surrounding the ulcer. 2 Diagnostic success is influenced by the number of biopsies and the expertise of the pathologist. Immunohistochemical techniques, such as immunoperoxidase staining and in situ DNA hybridization, increase the sensitivity of the histological diagnosis, 3 particularly when the organisms are present in low concentrations. The application of polymerase chain reaction (PCR), serology, and culture of mucosal biopsy, blood, urine, stool, and throat are not helpful in diagnosis of CMV infection. 3 However, advances have been made in searching for markers of CMV disease in HIV-infected hosts. Prospective studies in AIDS patients have proven CMV PCR to be a sensitive surrogate marker for active disease, but these techniques have not been studied in non-HIV cases. 3 The radiological investigations (barium enema and CT scan) are usually nonspecific. A high index of suspicion can lead to early diagnosis and treatment. Antiviral therapy (gancyclovir 10-15 ml/kg daily) for 2-3 weeks can reduce mortality, morbidity, and the need to perform surgical intervention. Our patient was more vulnerable because of his age, the presence of diabetes, and postoperative complications. The autopsy histological findings revealed the presence of a CMV infection. If the histology of the initial biopsy had confirmed the diagnosis, then the outcome might have been different. Cytomegalovirus infection leading to proctitis, massive rectal bleeding, and perforation is a rare event but it carries a high mortality if not properly treated. 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