Life-Threatening Gastrointestinal Bleeding in an Immunocompromised Patient

Question: A 79-year-old man presented to the hospital after several weeks of easy bruising and a syncopal episode. On admission he was noted to have a retroperitoneal hematoma requiring several transfusions. During initial evaluation his coagulation tests were noted to be abnormal, leading to the diagnosis of an acquired factor VIII inhibitor (FVIII; activity <1% and FVIII inhibitor level 408BU). He was treated with 4 doses of rituximab and high-dose steroids for several weeks with improvement in his FVIII activity level. He was admitted to our hospital several weeks later with a melena and fatigue. During this admission, he was noted to have new-onset pancytopenia (white blood cell count, 0.6K/μL; hemoglobin, 6.6 M/μL; platelets, 87K/μL). A broad workup for pancytopenia was initiated with normal vitamin B12, folate, and copper, and nondetectable hepatitis B and C virus, HIV, and Epstein–Barr virus. Cytomegalovirus (CMV) viral load was 213,508 IU/mL, for which he was started on IV ganciclovir. Melena persisted and was associated with hemodynamic instability requiring transfer to the intensive care unit. Esophagogastroduodenoscopy and colonoscopy were performed. Esophagogastroduodenoscopy demonstrated 3 small nonbleeding duodenal ulcers with no high-risk stigmata. Colonoscopy demonstrated a 5- to 6-cm fungating, ulcerated, nonobstructing mass in the ascending colon with active bleeding (Figure A), which was firm on biopsy concerning for a malignancy. Colonic mass histology demonstrated ulcer with many CMV viral inclusions but no definitive evidence of malignancy. The patient continued to have ongoing bleeding with accompanying hemodynamic instability despite correction of underlying coagulopathy and initiation of antiviral therapy. Given ongoing colonic bleeding, lack of therapeutic endoscopic options, and concern for possible underlying malignancy, the decision was made to proceeded with surgical resection of the colonic mass (Figure B). What is most likely etiology of this colonic lesion? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. The patient underwent an open hemicolectomy. The surgical specimen was negative for malignancy; however, it was consistent with a CMV-induced pseudotumor with extensive deep ulceration (Figure C) and CMV-infected cells in submucosal capillary endothelium (Figure D) involving the terminal ileum and cecum. Unfortunately, the patient eventually succumbed to his illness with the cause of death noted to be from extensive hemorrhage in his gastrointestinal tract and retroperitoneum on autopsy. Although uncommon, CMV colitis can present with a large mass-like lesion in the colon. Reports of CMV-induced pseudotumor have be limited to cases reports, and predominantly occur in patients with AIDS or post-transplant patients on immunosuppressive therapy.1Rajan D. Jacob R. Rashid S. et al.Cytomegalovirus infection presenting as a colonic mass in a patient with acquired immunodeficiency syndrome.Int Med Case Rep J. 2011; 4: 55-58Crossref PubMed Scopus (6) Google Scholar The exact mechanism of pseudotumor formation is poorly understood; however, it is postulated that CMV invasion of vascular endothelial cells leads to vascular endothelial thickening with stromal and epithelial cell hypertrophy.2Francis N.D. Boylston A.W. Roberts A.H. et al.Cytomegalovirus infection in gastrointestinal tracts of patients infected with HIV-1 or AIDS.J Clin Pathol. 1989; 42: 1055-1064Crossref PubMed Scopus (103) Google Scholar CMV can affect the entire gastrointestinal tract from the esophagus to the rectum, although it seems to have an affinity for the right colon and the ileocecal valve, as was seen in our case. CMV-induced pseudotumors often respond to IV antiviral therapy and may even resolve completely.2Francis N.D. Boylston A.W. Roberts A.H. et al.Cytomegalovirus infection in gastrointestinal tracts of patients infected with HIV-1 or AIDS.J Clin Pathol. 1989; 42: 1055-1064Crossref PubMed Scopus (103) Google Scholar Surgery should be reserved for patients who fail to respond to medical therapy or those with colonic obstruction or refractory bleeding, which unfortunately was the case for our patient. Acquired FVIII inhibitors are rare (1.3 cases per million people per year) and are associated with underlying illness in ≥50% of cases, namely connective tissues disorders, and less commonly solid and lymphoproliferative malignancies, which was a major factor in our decision to proceed with surgery. Patients often present with catastrophic bleeding episodes with a mortality as high as 8%–22% owing to a combination factors including delays in diagnosis and treatment, higher incidence in the elderly, and due to the severity of bleeding.3Ma A.D. Carrizosa D. Acquired factor VIII inhibitors: pathophysiology and treatment.Hematology Am Soc Hematol Educ Program. 2006; : 432-437Crossref PubMed Scopus (123) Google Scholar