A case series study of fever-diarrhea-hematochezia triad as the first presentation in plasma EBV DNA-positive diseases.

Aims: To characterize the clinical spectrum and outcomes of fever-diarrhea-hematochezia triad as the first presentation in plasma EBV DNA-positive diseases (EBV-FDH). Methods: This retrospective case series study was conducted at Qilu Hospital of Shandong University. We identified patients aged ≥14 years presenting with the triad of fever (>38 °C), diarrhea (≥3 loose stools/day), and hematochezia, accompanied by plasma EBV DNA positivity (≥500 copies/mL). All cases underwent a standardized diagnostic protocol including comprehensive laboratory tests, imaging, endoscopic and histopathological evaluation. Final diagnoses were established through multidisciplinary consensus. Results: The cohort (mean age 46.5 years; 71.4% male) frequently had immune abnormalities (50%). Lymphadenopathy (78.6%) and weight loss (50%) were common. Laboratory examinations revealed universal hypocholesterolemia, with reduced ApoB and elevated Lp(a)​ further characterizing the lipid-metabolic disturbance. Endoscopy revealed widespread ulcers. Diagnoses included CAEBV, ENKTL, IBD, etc. Misdiagnosis occurred in 57.1% of cases. Treatments varied (corticosteroids, chemotherapy, surgery). Treatment strategies were heterogeneous. Despite high overall mortality (64.3%), five patients achieved long-term survival, including one who received intensive therapies such as hematopoietic stem cell transplantation and combination chemotherapy, suggesting a potential benefit of aggressive intervention in selected cases. Conclusions: EBV-FDH is a severe syndrome with high mortality, often misdiagnosed initially. A high clinical suspicion and multimodal evaluation are crucial. Aggressive treatment, including surgery and HSCT, can enable survival in select patients.