Clinical and Histologic Mimickers of Celiac Disease

Amrit K Kamboj, Amy S Oxentenko, Amrit K Kamboj, Amy S Oxentenko

Abstract

Celiac disease is an autoimmune disorder of the small bowel, classically associated with diarrhea, abdominal pain, and malabsorption. The diagnosis of celiac disease is made when there are compatible clinical features, supportive serologic markers, representative histology from the small bowel, and response to a gluten-free diet. Histologic findings associated with celiac disease include intraepithelial lymphocytosis, crypt hyperplasia, villous atrophy, and a chronic inflammatory cell infiltrate in the lamina propria. It is important to recognize and diagnose celiac disease, as strict adherence to a gluten-free diet can lead to resolution of clinical and histologic manifestations of the disease. However, many other entities can present with clinical and/or histologic features of celiac disease. In this review article, we highlight key clinical and histologic mimickers of celiac disease. The evaluation of a patient with serologically negative enteropathy necessitates a carefully elicited history and detailed review by a pathologist. Medications can mimic celiac disease and should be considered in all patients with a serologically negative enteropathy. Many mimickers of celiac disease have clues to the underlying diagnosis, and many have a targeted therapy. It is necessary to provide patients with a correct diagnosis rather than subject them to a lifetime of an unnecessary gluten-free diet.

Conflict of interest statement

Guarantor of the article: Amy S. Oxentenko, MD.

Specific author contributions: Amrit K. Kamboj: Drafting the manuscript and approved the final draft; Amy S. Oxentenko: Drafting and editing the manuscript and approved the final draft.

Financial support: None.

Potential competing interests: None.

Figures

Figure 1
Figure 1
(a and b) Histologic features associated with celiac disease. Histologic features associated with: (a) an early phase of celiac disease, characterized by a tip-predominant intraepithelial lymphocytosis alone (see arrow); and (b) a later phase of celiac disease, characterized by intraepithelial lymphocytosis, crypt hyperplasia, villous atrophy (partial in this case with a villous:crypt ratio of 1:2), and a chronic inflammatory cell infiltrate in the lamina propria. (a at 200 ×, b 100 × ; Haemotoxylin and Eosin stain).
Figure 2
Figure 2
(a and b) Histologic features associated with early mimickers of celiac disease. Histologic features associated with early mimickers of celiac disease (in this case, NSAID use). Early histologic mimickers demonstrate increased intraepithelial lymphocytes, often in a non-tip-predominant pattern (see arrow), no villous atrophy, and crypts that are either normal or have minimal hyperplasia (a at 100 ×, b at 200 × ; Haemotoxylin and Eosin stain).
Figure 3
Figure 3
(a and b) Histologic features associated with late mimickers of celiac disease. Histologic features associated with late mimickers of celiac disease (in this case, drug-induced from olmesartan). Late histologic mimickers are characterized by increased intraepithelial lymphocytosis, partial or total villous atrophy, crypt hyperplasia, and chronic inflammation in the lamina propria. This figure also demonstrates a prominent collagen band that can be seen in cases of drug-induced enteropathy (a at 100 ×, b at 200 × ; Haemotoxylin and Eosin stain).
Figure 4
Figure 4
Proposed algorithm for work-up of seronegative enteropathies.
Figure 5
Figure 5
Proposed algorithm for management of seronegative enteropathies after other etiologies have been excluded.

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Source: PubMed

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