S0459 Irritable Bowel Syndrome Is Associated With the Primary and Secondary Mast Cell Disorders

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INTRODUCTION: There is increasing evidence that some patients with irritable bowel syndrome (IBS) have increased number of mast cells (MCs) or increased MC degranulation. Yet, association of IBS with primary (mast cell malignancy (MCM), mastocytosis (MA), mast cell activation syndrome (MCAS)) and secondary (chronic spontaneous urticaria (CSU)) MC disorders (MCDs) has not been studied. We investigated this using two large databases. METHODS: The Explorys database (Cleveland, OH) is an aggregate of de-identified electronic health record (EHR) data from 26 US healthcare systems. Systemized Nomenclature of Medicine (SNOMED) classification was used to identify adult patients diagnosed with both IBS and each of MCM, MA (SNOMED code “urticaria pigmentosa”), and CSU (SNOMED code “urtiaria” with exclusion of “acute urticaria” and “urticaria pigmentosa”), from 1994-2020. As there is no SNOMED code for MCAS, we identified patients with IBS and MCAS using Epic's Slicer Dicer, a self-service tool for obtaining de-identified customized EHR data, from two local academic centers. We excluded patients with inflammatory bowel disease, celiac disease, thyroid disease, autoimmune disorders and vasculitis. We collected demographics, procedural history, medication exposures, relevant comorbidities and clinical features. In each cohort, whether IBS preceded MCD or vice versa was searched using the temporal attributes feature on Explorys. RESULTS: Of >53 million included patients from Explorys, 617,140 had IBS, of which nearly 4% (N = 23,200) had a MCD. We created three overlap cohorts: IBS + CSU (N = 23,050), IBS + MA (N = 100), IBS + MCM (N = 80). Of 8 million adults in slicer dicer 67,924 had IBS and we created the fourth overlap cohort, IBS + MCAS (N = 92). IBS was strongly associated with all four MCDs (Table 1). In all four overlap cohorts, IBS and MCD were equally likely to precede the other, approximately 50% had IBS-D and 30% IBS-C. Nearly half experienced nausea, but typical symptoms of MCDs (flushing, hypotension) were poorly reported. There was strong female predominance, most carried private insurance, and while few were underweight many were obese (Table 2). Comorbidities, procedures and medication exposures common to IBS or MCDs were found more frequently than IBS alone (Table 3). CONCLUSION: MCDs are at least 4 times more likely to be present in patients with IBS. This data supports the role of MC hyperactivity in the pathogenesis of some IBS patients. Further investigation of this mechanism is warranted.Table 1Table 2Table 3