OBJECTIVES: Cyclic vomiting syndrome (CVS) remains a diagnostic challenge due to its nonspecific presentation despite consensus-based diagnostic criteria. There is a need for improved, evidence-based diagnostic criteria. We hypothesized that symptoms differ quantitatively between children with CVS versus other vomiting conditions and that current diagnostic criteria are not sufficiently sensitive for diagnosing CVS. METHODS: Observational, prospective study of children ages 3-18 years with unexplained vomiting episodes evaluated in the outpatient gastroenterology clinic, emergency department, and inpatient units at Children's Wisconsin. Parents completed symptom surveys at 0, 3, and 6 months. Diagnostic workup and treatment response were monitored by chart review. A final diagnosis (CVS vs. non-CVS) was assigned for group comparisons and receiver operating characteristics (ROC) analysis of diagnostic cutoffs. RESULTS: Of 108 subjects enrolled, 46 CVS and 54 non-CVS patients were analyzed. The groups reported overall different episode frequencies with more CVS versus non-CVS (81% vs. 55%) having ≥4 episodes/preceding 12 months (p = 0.013). CVS patients also had longer vomiting episodes (p = 0.03). To distinguish CVS from non-CVS, ROC analyses demonstrated the highest sensitivity for a frequency of 4-10 episodes/12 months (p = 0.002) and a duration threshold of >
2 h (p <
0.002). CVS patients reported specific episode characteristics: photophobia (p = 0.003), diaphoresis (p = 0.002), multiple emeses/hour (p = 0.002), stereotypical episodes (p = 0.008), and continued retching after gastric emptying (p = 0.008). Less than half of CVS patients met Rome IV and North American Society for Pediatric Gastroenterology, Hepatology & Nutrition diagnostic criteria. CONCLUSIONS: Children with CVS display a distinctive vomiting pattern and clinical features compared to other vomiting conditions. Our findings will help improve current diagnostic criteria.