American Journal of Gastroenterology



ACG Clinical Guidelines: Diagnosis and Management of Celiac Disease

Alberto Rubio-Tapia, Ivor D Hill, Ciarán P Kelly, Audrey H Calderwood and Joseph A Murray


Figure 4.

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An approach to the investigation of non-responsive celiac disease (NRCD) and refractory celiac disease (RCD) (adapted from references Rubio-Tapia (6) and Abdallah (261). (1) NRCD may be defined as persistent symptoms, signs, or laboratory abnormalities typical of celiac disease (CD) despite 6–12 months of dietary gluten avoidance. (2) Causes of non-celiac, small-intestinal villous atrophy that may be misdiagnosed as CD include autoimmune enteropathy, tropical sprue, small-intestinal bacterial overgrowth, hypogammaglobulinemia and combined variable immunodeficiency, collagenous sprue, eosinophilic enteritis, Crohn's disease, and peptic duodenitis. (3) Conditions that present clinically in a similar fashion to CD but where villous atrophy is not evident include irritable bowel syndrome, food intolerances, small-intestinal bacterial overgrowth, eosinophilic enteritis, Crohn's disease, and microscopic colitis. (4) Positive celiac serologies despite 12 months of treatment with a gluten-free diet (GFD) suggest that there may be ongoing gluten ingestion. (5) 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. (6) 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. DGP, deamidated gliadin peptide; EMA, endomysium antibodies; HLA, human leukocyte antigen; IELs, intraepithelial lymphocytes; TTGA, tissue transglutaminase antibody.