Postnatal Cytomegalovirus Infection as a Potential Trigger for Very Early Onset Crohn's Disease in an Immunocompetent Infant
American Journal of Gastroenterology
Intestinal complications of congenital and postnatal cytomegalovirus (CMV) infections include bloody diarrhea, necrotizing enterocolitis, and perforation. CMV infection triggering inflammatory bowel disease (IBD) is rarely recognized, with most cases reported in adults ( >60% ulcerative colitis). Proposed mechanisms include alteration of intestinal immunity with viral proteins upregulating inflammation. IBD in infancy is rare and often associated with monogenic pathogenic mutations. We describe a girl with colitis onset at 2 weeks of age in whom postnatal CMV infection appears to have been the event triggering the recognition of Crohn’s disease (CD).
A 15-day-old term breast-fed girl with nonsyndromic anomalies and negative urine CMV PCR on day 2 of life presented with frequent bloody/mucousy stools. Milk-protein allergy was suspected. With amino acid-based formula, she had fewer bowel movements, but mucous/blood persisted. Sigmoidoscopy at 4 months revealed moderately congested mucosa with erosions throughout the sigmoid colon and rectum (Figure 1A); methylprednisolone was started. Biopsies showed chronic moderate to severe colitis with negative CMV by immunostaining; urine CMV PCR was positive. CMV IgG and IgM were markedly elevated. Endoscopy 3 days later showed chronic inactive duodenitis, mild chronic gastritis, chronic inactive ileitis, and chronic colitis with rare CMV-positive cells in the descending colon and rectum. She was treated with valganciclovir (VAL) for CMV colitis and azathioprine (AZA) + prednisolone for possible CD, with partial response. Immune deficiency work up was negative (Table 1). On day 229 of life, colonoscopy revealed some disease improvement; CMV-positive cells were more abundant (Figure 1B/1C). She was switched to IV ganciclovir for 6 weeks followed by oral VAL; AZA was discontinued and steroids weaned. Symptoms persisted and she was treated with bowel rest and parenteral nutrition. Biopsies on day 266 of life showed CD pathology with absence of CMV. At 9 months, she started infliximab (INF) and demonstrated clinical improvement. VAL was stopped after her third INF dose. Table 1 details event chronology.
This case illustrates how postnatal CMV infection in a seemingly immunocompetent infant without CD-associated gene mutations can lead to earlier IBD onset. Treatment of CMV colitis is needed in conjunction with immunosuppressive therapy for CD. The frequency of CMV infection as a trigger for infantile CD needs further study.
Cascardo C, Kazyak K, Bohr M, Amin M, Gebara S, Freij BJ. Postnatal cytomegalovirus infection as a potential trigger for very ealy onset Crohn's disease in an immunocompetent infant. Am J Gastroenterol. 2022 Oct;117(10 Suppl):e2125-e2126. doi:10.14309/01.ajg.0000870060.81770.40.
American College of Gastroenterology Annual Scientific Meeting, October 21-26, 2022, Charlotte, NC.