Acute Diarrhea in an Immunocompromised 55-Year-Old Man

Abstract

Question: A 55-year-old man presented with a 2-week history of acute-onset diarrhea characterized by the passage of multiple, explosive, watery, nonbloody bowel movements per day after attending the state fair. The patient’s past medical history was significant for Waldenstrom macroglobulinemia status post autologous stem cell transplantation and splenectomy 3 and 7 years ago, respectively. Owing to autoimmune hemolytic anemia, repeat autologous stem cell transplantation and initiation of chronic immunosuppression therapy was started 3 months before presentation. Current medications included cyclosporine and prednisone 50 mg orally once daily along with prophylactic acyclovir, fluconazole, and trimethoprim-sulfamethoxazole. Physical examination was notable for Cushingoid features and dry mucous membranes; abdominal examination and vital signs were unremarkable. Stool studies for bacterial enteric pathogens, Clostridium difficile toxin polymerase chain reaction (PCR), ova and parasites, Cryptosporidium/Cyclospora antigens (Ag), Giardia Ag, and Rotavirus Ag. Blood testing for cytomegalovirus (CMV) PCR and human immunodeficiency virus were negative. A 48-hour stool collection revealed a total stool weight of 2317 g and 39 g of fat/24 hours (normal, 2-7 g/24 hours). Computed tomographic enterography demonstrated a normal-appearing small bowel, evidence of prior splenectomy, and bilateral lower lobe pulmonary nodules measuring up to 1 cm in diameter. Upper endoscopy revealed several nodular antral erosions (Figure A), but was otherwise unremarkable. Biopsies from the gastric erosions and duodenum demonstrated enlarged nuclei with “smudgy” chromatin and intranuclear inclusions on hematoxylin and eosin staining (Figure B, arrows). CMV immunostaining was negative. Colonoscopy showed normal-appearing colonic and ileal mucosa and corresponding random biopsies including Congo red, CMV, and herpes simplex virus immunostains were normal. What is the most likely diagnosis based on the clinical presentation, endoscopic description, and histologic findings? Look on page 624 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Given the acute onset of diarrhea in the setting of immunosuppression and recent attendance at the state fair, an infectious etiology was highly suspected, which prompted adenovirus-specific in situ hybridization on duodenal biopsies that returned positive (Figure C). Follow-up PCR testing of stool and plasma for adenovirus were also indicative of adenovirus infection. Owing to the pulmonary nodules incidentally noted on computed tomographic enterography, bronchoscopy with bronchoalveloar lavage and transbronchial biopsy was pursued which confirmed pulmonary involvement by disseminated adenovirus infection via positive PCR. The patient was started on intravenous cidofovir1Saquib R. Melton L.B. Chandrakantan A. et al.Disseminated adenovirus infection in renal transplant recipients: the role of cidofovir and intravenous immunoglobulin.Transpl Infect Dis. 2010; 12: 77-83Crossref PubMed Scopus (40) Google Scholar with discontinuation of cyclosporine and prednisone tapering. After 2 months of therapy, the patient experienced complete symptomatic resolution. The patient was monitored with periodic quantitative real-time adenovirus DNA PCR. Follow-up CT scanning of the chest demonstrated an interval decrease in pulmonary nodule size, indicative of resolving infection. To date, the patient has been resumed on low-dose prednisone therapy without clinical evidence of recurrence. This case highlights disseminated adenovirus as an unusual cause of steatorrhea, even in the absence of macroscopic mucosal injury, which likely can be explained by disruption of intestinal epithelial lipid transport. Impaired cellular immunity, in particular compromised T-cell function or number is a well-recognized risk factor for disseminated adenovirus infection.2Echavarría M. Adenoviruses in Immunocompromised Hosts.Clin Microbiol Rev. 2008; 21: 704-715Crossref PubMed Scopus (336) Google Scholar Gastrointestinal manifestations of adenovirus include gastroenteritis, hemorrhagic colitis, and hepatitis,2Echavarría M. Adenoviruses in Immunocompromised Hosts.Clin Microbiol Rev. 2008; 21: 704-715Crossref PubMed Scopus (336) Google Scholar with diarrhea being the most common presenting symptom. Because adenovirus is not a routine component to panel-based stool pathogen testing, awareness of this condition as a cause of diarrhea in the setting of immunosuppression is crucial to facilitate directed therapy while minimizing unnecessary diagnostic evaluation.