Background <p>Cytomegalovirus (CMV) is a ubiquitous herpesvirus and an important, often underappreciated, viral pathogen of the gastrointestinal tract.Although CMV infection is typically asymptomatic in immunocompetent individuals, gastric involvement, a rare manifestation of gut CMV disease, poses a significant diagnostic challenge due to non-specific clinical and endoscopic features. The mechanisms by which CMV disrupts the gastric mucosal barrier, induces local inflammatory responses, and causes systemic protein loss remain incompletely characterised in immunocompetent hosts.To our knowledge, this is one of the youngest reported female cases of CMV gastritis with protein-losing gastropathy in an immunocompetent adult. This report aims to illuminate the pathophysiological mechanisms underlying severe CMV gastroduodenitis and the critical role of histopathological confirmation in establishing the diagnosis.</p> Case presentation <p>A 23-year-old previously healthy woman presented with progressive epigastric pain, vomiting, non-bloody diarrhoea, and severe bilateral lower-limb oedema following a self-limited flu-like illness.Physical examination revealed diffuse abdominal tenderness and marked peripheral oedema.Laboratory investigations showed elevated inflammatory markers, anaemia, and profound hypoalbuminaemia (serum albumin 20.4&#xa0;g/L). CMV serology demonstrated markedly elevated IgM and IgG titres. Imaging studies demonstrated splenomegaly with small infarcts. Upper gastrointestinal endoscopy revealed severe gastric mucosal erythema with sloughing and exudation, as well as duodenal inflammation. Histopathological examination of gastric and duodenal biopsies demonstrated viral cytopathic changes consistent with CMV infection, including characteristic intranuclear owl-eye inclusions, confirming the diagnosis. The patient was treated with oral valganciclovir 900&#xa0;mg twice daily for three weeks alongside supportive therapy, resulting in rapid clinical improvement, resolution of oedema, and significant normalisation of laboratory parameters. At one-month follow-up, she was asymptomatic with complete recovery.</p> Conclusions <p>This case illuminates the pathophysiological mechanisms by which CMV, a virus with well-characterised tropism for gastrointestinal epithelium that can disrupt the gastric mucosal barrier sufficiently to cause profound systemic protein loss. The low serum immunoglobulin G observed on admission most likely reflected secondary enteric immunoglobulin loss rather than pre-existing immunodeficiency, a distinction with important diagnostic implications. The case underscores that histopathological confirmation is the cornerstone of diagnosis, as serological and endoscopic findings alone are insufficient to distinguish active CMV tissue invasion from more common gastrointestinal conditions.The dramatic biochemical and clinical response observed following antiviral therapy provides an instructive in vivo correlate of the virus’s direct pathological role in mucosal injury.</p>