Hidden Herpesvirus Reactivation Linked to Severe Childhood Colitis Flare-Ups

A quiet passenger virus that lurks in most of the world’s population may be helping to drive some of the most severe flare-ups of ulcerative colitis in children, according to a retrospective study from Gazi University in Ankara, Türkiye, published in BMC Infectious Diseases. The research, led by pediatric infectious diseases specialist Tugba Bedir Demirdag and colleagues, set out to answer a deceptively simple question: when a child with ulcerative colitis suddenly worsens, how often is cytomegalovirus reactivation hiding in the inflamed colon, and does its presence actually change the course of the disease?

Ulcerative colitis is a chronic inflammatory bowel disease in which the immune system attacks the lining of the colon and rectum, producing ulcers, bleeding, diarrhea and abdominal pain. In children the disease can be particularly aggressive, and flares are typically treated with corticosteroids, potent anti-inflammatory drugs that suppress the immune response. That treatment, however, creates a biological paradox. The very immunosuppression that calms the inflamed gut can also lift the brakes on cytomegalovirus, a beta-herpesvirus that establishes lifelong latency after primary infection and is notorious for reactivating in immunocompromised hosts. Once reactivated in the colonic mucosa, the virus can amplify tissue injury, worsening the very inflammation it thrives within.

Clinicians have long debated how to interpret cytomegalovirus found in colonic biopsies. Adult studies suggest viral reactivation complicates a meaningful fraction of steroid-refractory colitis cases, but pediatric data have remained sparse and inconsistent. The contribution of colonic cytomegalovirus reactivation to ulcerative colitis exacerbations in children, the authors note, is still incompletely understood. Their study was designed to determine how common the virus is in pediatric flares and to evaluate whether its detection carries real clinical weight, in terms of disease severity, steroid response and the ultimate need for surgery.

To do so, the team turned to their institutional records, identifying pediatric patients with ulcerative colitis exacerbations who underwent colonoscopy between 2004 and 2021. Colonoscopy in this setting serves a dual purpose: it allows direct visualization of the inflamed bowel and provides biopsy tissue that can be interrogated in several complementary ways. The researchers assessed cytomegalovirus reactivation using three distinct methods: polymerase chain reaction testing on colon tissue, polymerase chain reaction testing on blood, and conventional histopathological examination of biopsy specimens, in which pathologists look under the microscope for the characteristic enlarged cells, so-called owl’s-eye inclusion bodies, that signal viral replication.

The technical distinction between these methods proved to be the heart of the study’s findings. Polymerase chain reaction, or PCR, amplifies viral DNA sequences millions of times over, making it exquisitely sensitive even when only trace amounts of viral genetic material are present. Histopathology, by contrast, detects only the visible cytopathic effects of active viral replication, and blood PCR captures systemic viremia rather than local infection confined to the gut wall. A virus can smolder in the colonic mucosa without ever spilling into the bloodstream, and it can leave faint DNA traces without producing the dramatic cellular changes pathologists recognize.

The results bore this out strikingly. Among 78 colonoscopic procedures performed in 68 pediatric patients with ulcerative colitis, tissue PCR was positive in 11 specimens, or 14 percent of the total. Yet blood PCR and histopathological evidence of reactivation were each detected in only two cases, roughly 3 percent. In other words, the most sensitive method, direct testing of colon tissue, flagged cytomegalovirus several times more often than either systemic blood testing or microscopic examination. Had the investigators relied on blood PCR or histology alone, the majority of tissue-positive cases would have gone entirely unnoticed.

More importantly, tissue positivity was not merely a laboratory curiosity. More than half of the patients with tissue PCR positivity, 55 percent, exhibited corticosteroid resistance, meaning their disease failed to respond to standard steroid therapy, a statistically significant association with a p-value of 0.008. Tissue PCR positivity was also significantly associated with severe disease activity, with a p-value of 0.03. Together, these findings suggest that when cytomegalovirus DNA is present in the colonic tissue of a child in flare, the flare tends to be more severe and less likely to yield to first-line immunosuppression, consistent with the idea that viral reactivation compounds inflammation and undermines steroid efficacy.

The surgical outcome told a different story. The researchers found no statistically significant associations between tissue PCR positivity, cytomegalovirus viremia, or histopathological detection and colectomy, the removal of the colon that represents a last-resort outcome in refractory disease, with p-values of 0.54, 0.17 and 0.23 respectively. Despite being linked to severity and steroid resistance, viral presence in the tissue did not ultimately predict which children lost their colon. This disconnect is clinically meaningful: it implies that detecting cytomegalovirus should raise concern and prompt closer monitoring, but it does not by itself condemn a child to the most drastic surgical outcome.

The study’s authors conclude that tissue PCR results should therefore be interpreted alongside clinical and histopathological findings rather than in isolation. A positive tissue PCR in a severely ill, steroid-resistant child may warrant consideration of antiviral therapy or treatment escalation, whereas an isolated positive result in a child responding well to treatment may carry less urgency. The low concordance between tissue PCR, blood PCR and histology in this cohort underscores that no single test captures the full picture, and that integrating virological, microscopic and clinical data remains essential for sound decision-making in pediatric inflammatory bowel disease.

For a field in which pediatric evidence often lags behind adult practice, the study offers a valuable long-term perspective, drawing on colonoscopies performed across nearly two decades. It also received no specific external funding and was approved by the Gazi University Faculty of Medicine ethics committee. While retrospective single-center designs have inherent limitations, the consistent signal linking tissue-level viral detection to severe, steroid-resistant disease strengthens the case for routinely considering cytomegalovirus testing of colonic tissue in children experiencing ulcerative colitis exacerbations. As clinicians refine their approach to these vulnerable young patients, the message from Ankara is clear: the quiet passenger in the gut deserves a closer look.

Subject of Research: Cytomegalovirus reactivation in pediatric ulcerative colitis exacerbations and its association with disease severity and outcomes

Article Title: Cytomegalovirus and ulcerative colitis in pediatrics: association with severity and the outcome

Article References: Cytomegalovirus and ulcerative colitis in pediatrics: association with severity and the outcome. (n.d.). https://doi.org/10.1186/s12879-026-14557-z

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14557-z

Keywords: cytomegalovirus, ulcerative colitis, pediatrics, inflammatory bowel disease, colitis, CMV reactivation, PCR, colonoscopy, corticosteroid resistance, histopathology, BMC Infectious Diseases, viral infection