March24, 2023

Abstract Volume: 3 Issue: 1 ISSN:

Cytomegalovirus Infection as a Cause of Pseudomembranous Colitis

Dr. Qasim Abbas*, Dr. Jawahir lal1


1. Department of Internal Medicine, GI-unit, Sultan Qaboos University Hospital, Muscat, Oman.

Corresponding Author: Dr. Qasim Abbas, Department of Internal Medicine, GI-unit, Sultan Qaboos University Hospital, Muscat, Oman.


Copy Right: © 2021 Dr. Qasim Abbas. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Received Date: June 23, 2021

Published date: July 01, 2021

Cytomegalovirus Infection as a Cause of Pseudomembranous Colitis

Background

Cytomegalovirus colitis is most commonly diagnosed in immunocompromised patients, though it has been recognized in immunocompetent hosts as a cause for acute diarrheal illness. (1) CMV gastrointestinal disease rarely occurs in immunocompetent patients and could resolve completely without the use of antiviral drugs. (2) CMV colitis is increasingly recognized in apparently immunocompetent patients in some immunomodulating conditions, such as elderly, pregnancy, chronic renal failure, coronary artery disease, ischemic heart disease, congestive heart failure, diabetes mellitus, steroid use, blood transfusion, and prolonged stay in the intensive care units (ICUs). (3-5) In addition to manifesting with a solitary ulcer, multiple ulcers, diffuse colitis, and polypoid lesions, occasionally CMV colitis may present with pseudomembranes, leading to misdiagnosis as CDI-associated pseudomembranous colitis. (6,7) In a review of 31 patients with CMV colitis by Wilcox et al. pseudomembrane formation was the clinical presentation in 2% of the patients. (8) This scenario should be considered particularly when C. difficile toxin assays or cultures are negative. (9,10)

We report a case of Cytomegalovirus (CMV) infection in an immunocompetent patient presenting as pseudomembranous colitis. Due to rarity in healthy patients, CMV colitis is often initially overlooked but should be considered especially in elderly patients with refractory diarrhea.

 

Case Summary

An 80-year-old man with a case of Alzheimer's disease on mirtazapine was admitted with abdominal pain and distention, the abdomen was distended, tense and tender. He was given a diagnosis of acute large bowel pseudo-obstruction (Ogilvie syndrome) based on abdominal x-ray and CT-scan findings (figure 1, 2). He was treated conservatively with correction of his electrolytes and rectal tube insertion. 

The abdominal pain and distension were improved but he started to develop diarrhea, stool studies were consistently negative for ova, parasites, and C. difficile. The patient underwent a flexible sigmoidoscopy that revealed pseudomembranous colitis (figure 3) biopsies revealed necrotic tissue mixed with blood, fibrin and inflammatory cells containing many macrophages and no evidence of specific organisms using special stains (figure 4). 

The patient was treated with antibiotics including intravenous metronidazole and oral vancomycin. 

There was no improvement in his symptoms after 1 week of treatment and he started to develop bloody diarrhea, repeat sigmoidoscopy showed partial resolution of pseudomembranes with the presence of multiple variable size ulcers seen in the rectum and sigmoid colon and repeated biopsies revealed cytomegalovirus induced inflammatory reaction with ulceration and granulation tissue formation (figure 5). Serum CMV DNA 4599 IU/mL.

The patient was immediately started on intravenous ganciclovir and his diarrhea resolved. Although CMV is a rare colonic pathogen in the immunocompetent patient, it should be considered in the differential diagnosis of pseudomembranous colitis in such patients.


Discussion

Pseudomembranous colitis has been characteristically associated with C. difficile infection. (11-13)

Thus, it has been the standard medical practice to treat patients in whom pseudomembranes are seen on endoscopy for C. difficile colitis.

However, pseudomembranous colitis has been associated with other etiologies, including shigellosis, (14-16) Escherichia coli, (17-19) fungal infections, (20) and ischemia. (21,22) Cytomegalovirus colitis has also been associated with pseudomembrane formation. (8,23–28)

CMV colonization is common in the general population. It is prevalent in 40–100% of adults by the age of 30 years and approximately 70% of the population over the age of 60 years. (29,30)

The mechanism of injury and pseudomembrane formation in CMV colitis might be similar to that of ischemic colitis. The inflammatory changes in CMV are usually neutrophilic and usually affect endothelial cells. The endothelial cells usually contain owl-eyed nuclear or granular cytoplasmic inclusions. Because of this vascular involvement, it has been postulated that ischemia may play a contributory role in the pathogenesis of CMV and that this, in turn, may contribute to ulcer and pseudomembrane formation as seen in ischemic colitis.

With a non-specific presentation, the clinician must have a high index of suspicion to diagnose CMV colitis, particularly in the immunocompetent host. The estimated rate for colectomy in patients with CMV colitis is 20–30% and is higher for patients with a delayed diagnosis and treatment. (31) Therefore, we emphasize that CMV colitis is another important diagnostic consideration that should be considered, especially in the immunocompetent population who present with diarrhea and pseudo membranes.


Figure 1: Plain abdominal x-ray showing dilated large bowel loops without mechanical obstruction.

Figure 2: Abdominal CT-scan showing dilated large bowel loops without mechanical obstruction

Figure 3: Flexible sigmoidoscopy showing pseudomembranous colitis

Figure 4. H & E stain showing necrotic tissue mixed with blood, fibrin and inflammatory cells containing many macrophages

Figure 5. Histology showing IHC for CMV Antibody with positive nuclear staining

 

References

1.Galiatsatos P, Shrier I, Lamoureux E, et al. “Meta-analysis of outcome of cytomegalovirus colitis in immunocompetent hosts”. Dig Dis Sci 2005; 50:609–16

2.Harano Y, Kotajima L, Arioka H. “Case of cytomegalovirus colitis in an immunocompetent patient: a rare cause of abdominal pain and diarrhea in the elderly”. Int J Gen Med 2015; 8:97-100.

3.Chen YM, Hung YP, Huang CF, Lee NY, Chen CY, Sung JM, et al. “Cytomegalovirus disease in non-immunocompromised, human immunodeficiency virus-negative adults with chronic kidney disease”. J Microbiol Immunol Infect 2014; 47:345-9.

4.Farah Musa AR, Fulop T, Kokko K, Kanyicska B, Lewin JR. Csongra´di E´. “Cytomegalovirus colitis in a critically ill, dialysis dependent, acute kidney injury patient without immunosuppressive therapy”. Clin Nephrol 2015; 84:44-9.

5.Chan KS, Yang CC, Chen CM, Yang HH, Lee CC, Chuang YC, et al. “Cytomegalovirus colitis in intensive care unit patients: difficulties in clinical diagnosis”. J Crit Care 2014; 29. 474-1-6.

6.Seo TH, Kim JH, Ko SY, Hong SN, Lee SY, Sung IK, et al. “Cytomegalovirus colitis in immunocompetent patients: a clinical and endoscopic study”. Hepatogastroenterology 2012; 59:2137-41.

7.Battaglino MP, Rockey DC. “Cytomegalovirus colitis presenting with the endoscopic appearance of pseudomembranous colitis”. Gastrointest Endosc 1999; 50:697-700.

8.Wilcox CM, Chalasani N, Lazenby A, et al. “Cytomegalovirus colitis in acquired immunodeficiency syndrome: a clinical and endoscopic study”. Gastrointest Endosc 1998; 48:32–43.

9.Heininger A, Vogel U, Aepinus C, Hamprecht K. “Disseminated fatal human cytomegalovirus disease after severe trauma”. Crit Care Med 2000; 28:563-6.

10.Momin N, Telisinghe PU, Chong VH. “Cytomegalovirus colitis in immunocompetent patients”. Singapore Med J 2011; 52-170-2.

11.Tedesco FJ, Barton RW, Alpers DH. “Clindamycin-associated colitis: a prospective study”. Ann Intern Med 1974; 81:429–33.

12.Green RH. “The association of viral activation with penicillin toxicity in guinea pigs and hamsters”. Yale J Biol Med 1974; 47:166–81.

13.Hafiz S. “Clostridium difficile and its toxins [dissertation]”. Leeds, UK: University of Leeds; 1974.

14.Kelber M, Ament ME. Shigella dysenteriae I. “A forgotten cause of pseudomembranous colitis”. J Pediatr 1976; 89:595–6.

15.Butlert T, Dunn D, Dahms B, et al. “Causes of death and the histopathologic findings in fatal shigellosis”. Pediatr Infect Dis J 1989; 8:767–2.

16.Sachdev HP, Chadha V, Malhotra V, et al. “Rectal histopathology in endemic shigella and Salmonella diarrhea”. J Pediatr Gastroenterol Nutr 1993; 16:33–8.

17.Hunt CM, Harvey JA, Youngs ER, et al. “Clinical and pathologic variability of infection by enterohemorrhagic (Vero cytotoxin producing) Escherichia coli”. J Clin Pathol 1989; 42:847–52.

18.Kelly J, Oryshak A, Wenetsek M, et al. “The colonic pathology of Escherichia coli 0157:H7 infection”. Am J Surg Pathol 1990; 14:87–92.

19.Marshall WF, McLimans CA, Yu PKW, et al. “Results of a 6-month survey of stool cultures for Escherichia coli 0157:H7”. Mayo Clin Proc 1990; 65:787–92.

20.Prescott RJ, Harris M, Banerjee SS. “Fungal infections of the small and large intestine”. J Clin Pathol 1992; 45:806–1.

21.Lee EL, Smith HJ, Miller GL, et al. “Ischemic pseudomembranous colitis with perforation due to polyarteritis nodosa”. Am J Gastroenterol 1984; 79:35–8.

22.Baruchel S, Deilfer JC, Siaglet D, et al. “Pseudomembranous colitis in sickle cell disease responding to exchange transfusion”. J Pediatr 1992; 121:915–7.

23.Beaugrand M, Paynard T, Callard P, et al. “Recherche d’une infection à cytomegalovirus au cours des colites pseudo-membraneuses: 6 observations”. Nouv Presse Med 1981; 10:1199–1203.

24.Gertler SL, Pressman J, Price P, et al. “Gastrointestinal cytomegalovirus infection in a homosexual man with severe acquired immunodeficiency syndrome”. Gastroenterology 1983; 85:1403–6.

25.Frager DH, Frager JD, Wolf EL, et al. “Cytomegalovirus colitis in the acquired immune deficiency syndrome: radiologic spectrum”. Gastrointest Radiol 1986; 11:241–6.

26.Rene E, Marche C, Chevalier T, et al. “Cytomegalovirus colitis in patients with acquired immunodeficiency syndrome”. Dig Dis Sci 1988; 33:741–50.

27.Franco J, Massey BT, Komorowski R. “Cytomegalovirus infection causing pseudo-membranous colitis”. Am J Gastroenterol 1994; 89:2246–8.

28.Beaugeria L, Ngo Y, Goujard F, et al. “Etiology and management of toxic megacolon in patients with human immunodeficiency virus infection”. Gastroenterology 1994; 107:858 63.

29.Dowd JB, Aiello AE, Chyu L, et al. “Cytomegalovirus antibodies in dried blood spots: a minimally invasive method for assessing stress, immune function, and aging”. Immun Ageing 2011; 8:3.

30.Ng FH, Chau TN, Cheung TC, et al. “Cytomegalovirus colitis in individuals without apparent cause of immunodeficiency”. Dig Dis Sci 1999; 44:945–52.

31.Panaccione R. “Cytomegalovirus (CMV) colitis: a great mimicker of treatment refractory inflammatory bowel disease (IBD)”. GastroSource. http://www. gastrosource.com

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5