Table 1.

Differential diagnosis of nonresponsive celiac disease

Etiology	Diagnostic approach	Comments
Gluten contamination*	Dietary review, celiac serology, intestinal biopsy	Most frequent cause of nonresponsive celiac disease
Small intestine bacterial overgrowth*	Breath tests, culture of intestinal fluid, empiric trial with antibiotics	Frequent
Exocrine pancreatic insufficiency	Fecal elastase or other indirect pancreatic function tests, empiric trial with pancreatic enzymes	Low fecal elastase observed in up to 30% treated celiacs with diarrhea
Microscopic colitis	Colonic biopsies	Frequent, suspect if recurrent watery diarrhea
Refractory celiac disease*	Detection of abnormal (clonal) intraepithelial lymphocytes, extensive endoscopic and imaging evaluation	Rare, diagnosis of exclusion that may be supported by positive findings
Functional bowel disorders	Clinical criteria	Common, diagnosis should be strongly suspected in patients with normal histology and prominent symptoms
Protein-losing enteropathy	Fecal α-1 antitrypsin	Rare, suspect if severe hypoalbuminemia or lymphopenia
Lactose and fructose intolerance	Breath tests, food exclusion trial	Prevalence in nonresponsive CD unknown
Giardiasis*	Microscopic analysis of stool or intestinal fluid, Giardia antigen in stool	Frequent cause of chronic symptoms and malabsorption. Prevalence of giardiasis in nonresponsive CD unknown
Malignancies	Bowel & body imaging, deep- enteroscopy with biopsies	Rare but important especially in old adults

^*Disorders associated with abnormal duodenal biopsy on follow-up