An approach to the investigation of nonresponsive celiac disease and refractory celiac disease

NRCD: nonresponsive celiac disease; RCD: refractory celiac disease; DGP: deamidated gliadin peptide; EMA: endomysium antibodies; HLA: human leukocyte antigen; GFD: gluten-free diet; IELs: intraepithelial lymphocytes; TTGA: tissue transglutaminase antibody.
* NRCD may be defined as persistent symptoms, signs, or laboratory abnormalities typical of celiac disease despite 6 to 12 months of dietary gluten avoidance.
¶ Positive celiac serologies despite 12 months of treatment with a gluten-free diet suggest that there may be ongoing gluten ingestion.
Δ Causes of nonceliac, small intestinal villous atrophy that may be misdiagnosed as celiac disease include autoimmune enteropathy, tropical sprue, small intestinal bacterial overgrowth, hypogammaglobulinemia and combined variable immunodeficiency, collagenous sprue, eosinophilic enteritis, Crohn disease, and peptic duodenitis.
◊ Conditions that present clinically in a similar fashion to celiac disease but where villous atrophy is not evident include irritable bowel syndrome, food intolerances, small intestinal bacterial overgrowth, eosinophilic enteritis, Crohn disease, and microscopic colitis.
§ RCD may be defined as persistent or recurrent malabsorptive symptoms and signs with small intestinal villous atrophy despite a strict GFD for more than 12 months and in the absence of other disorders, including overt lymphoma.
¥ Abnormal intestinal lymphocytes may be identified by immunohistochemistry of IELs or by flow cytometry showing an increased number of CD3-positive cells lacking CD8, or by the identification of clonal T-cell receptor gene rearrangement by molecular analysis.