A 13-year-old female with Aicardi syndrome and treatment-resistant epilepsy presented to the emergency department with several weeks of nonbloody diarrhea, abdominal distention, and vomiting. Review of systems was otherwise unremarkable, and she had no sick contacts, recent medication, or diet changes, travel history, or pathogen exposure. Physical exam was notable for hyperactive bowel sounds and intermittent discomfort with palpation in the right upper quadrant and epigastrium. On past medical history, she had global developmental delay, feeding difficulties requiring gastrostomy tube feeds, and treatment-refractory epilepsy for which she had a vagal nerve stimulator and was treated with cannabidiol, clobazam, felbamate, and levetiracetam. Cannabidiol therapy was initiated in 2016 using a product called Haleigh’s Hope (CBD oil; Haleigh’s Hope, Commerce City, CO) but was transitioned to the FDA-approved form of cannabidiol in 2018 with a recent dose escalation 3 months prior.

Initial evaluation in the emergency department revealed an unremarkable, Comprehensive Metabolic Panel (CMP), COVID-19 Polymerase Chain Reaction (PCR), Clostridium difficile PCR, ova and parasite test, multiplex PCR assay for gastrointestinal pathogens, and celiac panel. Absolute eosinophil count was 650 k/µL, C-reactive protein was 2.1 mg/dL, and stool was hemoccult positive with calprotectin of 2530 µg/g. She was hospitalized for intravenous hydration and consultation with pediatric gastroenterology. Despite a negative infectious evaluation, she was discharged on a 10-day course of metronidazole as preemptive coverage for inflammatory diarrhea until further outpatient workup.

At follow-up 10 days after hospitalization, she continued to have persistent diarrhea with intermittent hematochezia, feeding intolerance, abdominal pain, and weight loss. She underwent cross-sectional computer tomography (CT) imaging and upper endoscopy and colonoscopy with biopsy. The abdominal CT was normal with no bowel wall thickening. Upper endoscopy was unremarkable, but colonoscopy revealed small superficial ulcers and erythematous plaques in her rectum and sigmoid colon. Biopsies revealed >40 eosinophils per high-powered field in her distal, mid, and proximal esophagus; colonic biopsies were normal with no evidence of inflammation or viral effect, suggesting that her hematochezia was likely secondary to perianal irritation.

Although eosinophilic esophagitis (EoE) was not thought to be the cause of her persistent diarrhea, because of the abnormal histopathology, she was treated with a proton pump inhibitor, which was eventually advanced to a 5-food elimination diet. However, she continued to have profuse diarrhea.

After 6 months of ongoing gastrointestinal symptoms with no distinct etiology, pediatric neurology recommended a gradual decrease of the cannabidiol from 20 mg/kg/day (450 mg BID) to 15 mg/kg/day (350 mg BID). Over the next 2 weeks, the diarrhea and abdominal pain resolved, and the patient quickly regained the 8 kg she had lost. Fecal calprotectin declined to 197 µg/g, and repeat upper endoscopy, colonoscopy and video capsule endoscopy demonstrated complete resolution of her esophageal eosinophilia. Her peripheral eosinophilia decreased to 110 k/µL. She remains on cannabidiol 10 mg/kg/day and has not had any further gastrointestinal issues.