Diagnostic Approach to Eosinophilic Gastrointestinal Disease and Bile Acid Diarrhea

Primary Diagnostic Considerations

The presence of mucus in stool, intermittent rash, bloating, and gas are consistent with food protein sensitivity or eosinophilic gastroenteritis, which can present with these exact symptoms, according to the American Gastroenterological Association 1.
Normal calprotectin (<50 mg/kg) and normal S100A12 effectively exclude active inflammatory bowel disease (IBD), as both markers have >90% sensitivity for IBD, as recommended by the American Gastroenterological Association 2, 3.
Elevated fecal lactoferrin with normal calprotectin is unusual but can occur when there is mucosal inflammation without significant neutrophil infiltration, as seen in eosinophilic disorders, according to the American Gastroenterological Association 2, 3.

Nocturnal diarrhea is an alarm feature that suggests organic disease and can occur with bile acid malabsorption, particularly when symptoms worsen over time, as noted by the European Society of Gastrointestinal Endoscopy 4.
Bile acid diarrhea typically presents with watery diarrhea that worsens after meals and can be associated with bloating and gas, according to the American Gastroenterological Association 1, 4.
The American Gastroenterological Association suggests testing for bile acid diarrhea using SeHCAT scanning or serum 7α-hydroxy-4-cholesten-3-one 2, 3.

IgA tissue transglutaminase (tTG) with total IgA must be checked to exclude celiac disease, which can present with chronic diarrhea, bloating, and malabsorption, as recommended by the American Gastroenterological Association 2, 3, 6.
Giardia antigen testing or PCR is strongly recommended due to high prevalence and excellent test performance in chronic diarrhea, according to the Centers for Disease Control and Prevention 2, 3, 6.
Colonoscopy with biopsies from right and left colon is mandatory to exclude microscopic colitis, which has entirely normal-appearing mucosa on endoscopy but shows characteristic histologic changes, as recommended by the American Society for Gastrointestinal Endoscopy 4, 5.

Complete blood count, comprehensive metabolic panel, liver function tests, iron studies, vitamin B12, folate, and thyroid function tests to assess for anemia, malabsorption, and metabolic abnormalities, as recommended by the American College of Gastroenterology 6, 5.
IgA-tTG with total IgA to screen for celiac disease, according to the American Gastroenterological Association 2, 3, 6.
Giardia antigen or PCR testing, as recommended by the Centers for Disease Control and Prevention 2, 3, 6.
Colonoscopy with biopsies from right and left colon (not rectum) even if mucosa appears normal, to exclude microscopic colitis and assess for eosinophilic infiltration, as recommended by the American Society for Gastrointestinal Endoscopy 4, 5.