INTRODUCTION: Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) is an immune-mediated disease characterized by abrupt onset neurobehavioral changes. Inflammatory bowel disease (IBD) includes ulcerative colitis (UC) and Crohn's disease (CD), chronic conditions characterized by gastrointestinal inflammation. We describe eight individuals with both PANS and IBD. METHODS: All individuals with both IBD and PANS were identified from Stanford Immune Behavioral Health Clinic, Cedars-Sinai Medical Center Pediatric Inflammatory Bowel Disease Program, and Dartmouth Neuroimmune Psychiatric Disorders (NIPD) Clinic. Data was collected by chart review. RESULTS: Eight cases of PANS with IBD were identified. Five were male. Mean age of onset was 9.3 years for PANS and 15.6 years for IBD. PANS preceded development of IBD in 7 of 8 cases by a mean of 8.4 years. Seven patients (88%) had a first-degree relative with an immune-mediated disease, including 5 with psoriasis or psoriatic arthritis. Five patients themselves had arthralgias or arthritis (63%). All of the 5 cases where PANS preceded IBD treatment sufficiently for analysis were free of major behavioral relapses after IBD was managed. CONCLUSION: The triad of PANS, joint complaints, and family history of autoimmunity, including psoriasis, may represent a subset of PANS at heightened risk for IBD and additional immune-mediated disorders. For children with this triad, clinicians should have a low threshold to evaluate for gastrointestinal inflammation with biomarkers like hemoglobin, CRP, fecal calprotectin and diagnostic endoscopy when indicated. PANS symptoms may improve with effective treatment of IBD. The high prevalence of joint complaints in our cohort and psoriasis in first-degree family members suggests this subset of PANS may share immune mechanisms with psoriasis and arthritis. Treatment strategies used in IBD and arthritis should be studied for potential application in PANS.