Etiologies of Cyclic Vomiting Syndrome in Children: A Systematic Review of 1,373 Patients

Purpose: Cyclic vomiting syndrome (CVS), is a diagnosis of exclusion within the disorders of the gut-brain interaction, consisting of recurrent vomiting episodes unexplained by another medical condition or its triggers. When a patient presents with a recurrent vomiting episode, a broad differential is considered. The aim of this systematic review is to provide a hierarchal differential diagnostic approach to children with known or possible recurrent vomiting. Methods: This study followed the Preferred Reporting Items in Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, EMBASE and Scopus databases were searched using the following criteria: (1) Subjects aged 18 or under with vomiting spells classified as cyclic vomiting syndrome according to Rome IV criteria or equivalents for older publications and; (2) experimental, observational, or cross-sectional studies of 10 or more patients. A comprehensive literature search was performed with specific search criteria that included the diagnosis of cyclic vomiting syndrome. The results were analyzed using a Bayesian methodology to determine the rate estimates and 95% credible intervals for each disease. Results: Seventeen studies (1,375 patients and 1,415 events) were recovered. 80.4% of the differential included: psychological stress (26.2%; 95% credible intervals [CredI], 24-28.5), infection (22%; 95% CredI, 19.9-24.2), motion sickness (19.3%; 95% CredI, 17.3-21.4) and migraine (12.9%; 95% CredI, 11.2-14.7). Surgical causes (4.8%; 95% CredI, 3.6-6.2) and mitochondrial diseases (0.4%; 95% CredI, 0.1-0.8) were uncommon. Conclusion: Many triggers and diagnoses are associated with recurrent vomiting and CVS: psychological stress, infection, motion sickness, and migraine accounted for most cases. Serious surgical or metabolic diseases were less common.