Miscellaneous Enteric Viruses

Abstract

Acute viral gastroenteritis is second only to the common cold as a cause of illness in the United States. It often occurs in outbreaks, sometimes associated with food or water, and is a major recurrent problem in public health. Although most infections are self-limited, viral gastroenteritis can cause severe dehydration (particularly rotavirus), as well as chronic diarrhea in children with immunodeficiency syndromes such as severe combined immunodeficiency. Enteric viral infections are also a significant cause of diarrhea in patients with AIDS. Similar to adenovirus, rotavirus and enterovirus are associated with intussusception in children.

Acute viral gastroenteritis is second only to the common cold as a cause of illness in the United States. It often occurs in outbreaks, sometimes associated with food or water, and is a major recurrent problem in public health. Although most infections are self-limited, viral gastroenteritis can cause severe dehydration (particularly rotavirus), as well as chronic diarrhea in children with immunodeficiency syndromes such as severe combined immunodeficiency. Enteric viral infections are also a significant cause of diarrhea in patients with AIDS. Similar to adenovirus, rotavirus and enterovirus are associated with intussusception in children.

Many enteric viruses do not cause disease in humans; others seldom if ever cross the stage of the surgical pathologist, as they are detected in stool samples rather than biopsy specimens. Common enteric viruses known to cause diarrhea in humans include, but are not limited to, adenovirus, rotavirus, coronavirus, astrovirus, Norwalk virus and other enteric caliciviruses, and echovirus and other enteroviruses (see Table 23.1). Interestingly, enteric involvement has been documented in the coronavirus-associated severe acute respiratory syndrome (SARS), and diarrhea was a common presenting symptom in that outbreak.

Table 23.1 Comparison of selected enteric viruses causing diarrheal illness in humans

Pathologic findings. Many surgical pathologists are unfamiliar with the non-specific biopsy findings of viral enteritis, as we so rarely encounter these specimens. Pathologic studies are limited, and may not reflect the spectrum of changes in mild illness since most biopsy specimens are obtained from relatively sick patients.

Small bowel biopsy findings include villous fusion, broadening, and blunting (Figs. 23.1, 23.2, and 23.3); crypt hypertrophy (Fig. 23.4); and an increased mononuclear cell infiltrate within the lamina propria with variably present neutrophils (Fig. 23.5). There may be an increase in intraepithelial lymphocytes as well (Fig. 23.6). Reactive and degenerative epithelial changes are usually present, particularly at the surface, including epithelial cell disarray and loss of nuclear polarity (Figs. 23.7 and 23.8). Increased apoptosis may be seen in surface and glandular epithelium. In the limited number of human studies available, the severity of the histologic lesion does not appear to correlate with clinical severity of illness. Most human studies of the histopathology associated with enteric viral infection are limited to the duodenum. The rare reports that have evaluated the large bowel report histologic findings ranging from normal to focal cryptitis with increased apoptosis. With the exception of adenovirus infection in immunocompromised patients (see Chapter 22), inclusions are not seen on light microscopy.

Fig. 23.1

A low-power view of severe viral enteritis shows villous blunting, broadening, and fusion in the small bowel mucosa

Fig. 23.2

Villous blunting, broadening, and fusion, along with an increased mononuclear cell infiltrate in the lamina propria and sloughing of surface epithelium

Fig. 23.3

Villous fusion in a case of viral enteritis

Fig. 23.4

Marked villous blunting and broadening, along with crypt hypertrophy and surface degenerative changes

Fig. 23.5

Viral enteritis often shows an increase in mononuclear cells in the lamina propria, along with scattered granulocytes

Fig. 23.6

Increased intraepithelial lymphocytes may be seen in surface and glandular epithelium

Fig. 23.7

Surface degenerative changes including pyknotic nuclei and loss of nuclear polarity

Fig. 23.8

Surface degenerative changes including epithelial cell disarray, loss of nuclear polarity, and sloughing of epithelial cells

Differential diagnosis. The differential diagnosis includes celiac disease, NSAID injury, and peptic ulcer disease. The histologic changes in viral enteritis rapidly return to normal as the patient’s symptoms abate, and serologic assays for celiac disease should be negative. Peptic ulcer disease usually features more neutrophils and active inflammation than viral enteritis, and lacks villous fusion and significant apoptosis. A history of NSAID usage (rare in pediatric patients) can help distinguish viral enteritis from NSAID injury, and again villous fusion is unusual in an adverse drug reaction. Viral culture and electron microscopic examination of tissue or feces may be valuable ancillary diagnostic tests.

Selected References

• 1. Agus SG, Dolin R, Wyatt RG, et al. Acute infectious nonbacterial gastroenteritis: intestinal histopathology. Ann Intern Med 79:18–25, 1973.

• 2. Barnes GL, Townley RRW. Duodenal mucosal damage in 31 infants with gastroenteritis. Arch Dis Child 48:343, 1973.

• 3. Blacklow NR, Greenberg HB. Viral gastroenteritis. N Engl J Med 325:252–64, 1991.

• 4. Davidson GP, Barnes GL. Structural and functional abnormalities of the small intestine in infants and young children with rotavirus enteritis. Acta Paediatr Scand 68:181–6, 1979.

• 5. Estes MK, Hardy ME. Norwalk virus and other enteric caliciviruses. In: Blaser MJ, Smith PD, Ravdin JI, et al. (eds): Infections of the Gastrointestinal Tract. New York: Raven Press, 1995, pp. 1009–34.

• 6. Goldstein NS. Non-gluten sensitivity-related small bowel villous flattening with increased intraepithelial lymphocytes: not all that flattens is celiac disease. Am J Clin Pathol 121:546–50, 2004.

• 7. Guarner J, de Leon-Bojorge B, Lopez-Corella E, et al. Intestinal intussusception associated with adenovirus in Mexican children. Am J Clin Pathol 120:845–50, 2003.

• 8. Lack EE, Gang DL. In: Conner DH, Chandler FW: Pathology of Infectious Diseases. Stamford, CT: Appleton and Lange, 1997, pp. 101–106.

• 9. Leung WK, To KF, Chan PK, et al. Enteric involvement of severe acute respiratory syndrome-associated coronavirus infection. Gastroenterol 125:1011–7, 2003

• 10. Madely CR. The emerging role of adenoviruses as inducers of gastroenteritis. Pediatr Infect Dis 5:S63–74, 1986.

• 11. Matsui SM. Astroviruses. In: Blaser MJ, Smith PD, Ravdin JI, et al. Infections of the Gastrointestinal Tract. New York: Raven Press, 1995, pp. 1035–45.

• 12. Morotti RA, Kaufman SS, Fishbein TM, et al. Calicivirus infection in pediatric small intestine transplant recipients: pathological considerations. Hum Pathol 35:1236–40, 2004.

• 13. Rodriguez WJ, Kim HW, Brandt CD, et al. Fecal adenoviruses from a longitudinal study of families in metropolitan Washington, D.C.: laboratory, clinical, and epidemiologic observations. J Pediatr 107:514–20, 1985.

• 14. Saif LJ, Greenberg HG. Rotaviral gastroenteritis. In: Conner DH, Chandler FW. (eds): Pathology of Infectious Diseases. Stamford, CT: Appleton and Lange, 1997, pp. 297–302.

• 15. Schreiber DS, Blacklow NR, Trier JS. The mucosal lesion of the proximal small intestine in acute infectious nonbacterial gastroenteritis. N Engl J Med 288:1318–23, 1973.

• 16. Schreiber DS, Blacklow NR, Trier JS. The small intestinal lesion induced by Hawaii agent acute infectious nonbacterial gastroenteritis. J Infect Dis 129:705–8, 1974.

• 17. Thomas PD, Pollok RCG, Gazzard BG. Enteric viral infections as a cause of diarrhoea in the acquired immunodeficiency syndrome. HIV Med 1:19–24, 1999.

• 18. Vernacchio L, Vezina RM, Michell AA, et al. Diarrhea in American infants and young children in the community setting: incidence, clinical presentation and microbiology. Ped Infect Dis J 25:2–7, 2006.

• 19. Walter JE, Mitchell DK. Astrovirus infection in children. Cur Opin Infect Dis 16:247–53, 2003.

• 20. Washington K. Immunodeficiency disorders of the GI tract. In: Odze RD, Goldblum JR, Crawford JM. (eds): Surgical Pathology of the GI Tract, Liver, Biliary Tract, and Pancreas. Philadelphia, PA: Elsevier, 2004, pp. 57–71.

• 21. Winn WC. Adenoviruses. In: Conner DH, Chandler FW. (eds): Pathology of Infectious Diseases. Stamford, CT: Appleton and Lange, 1997, pp. 63–67.