Gluten-Induced Extra-Intestinal Manifestations in Potential Celiac Disease-Celiac Trait

Abstract

Celiac disease patients may suffer from a number of extra-intestinal diseases related to long-term gluten ingestion. The diagnosis of celiac disease is based on the presence of a manifest small intestinal mucosal lesion. Individuals with a normal biopsy but an increased risk of developing celiac disease are referred to as potential celiac disease patients. However, these patients are not treated. This review highlights that patients with normal biopsies may suffer from the same extra-intestinal gluten-induced complications before the disease manifests at the intestinal level. We discuss diagnostic markers revealing true potential celiac disease. The evidence-based medical literature shows that these potential patients, who are "excluded" for celiac disease would in fact benefit from gluten-free diets. The question is why wait for an end-stage disease to occur when it can be prevented? We utilize research on dermatitis herpetiformis, which is a model disease in which a gluten-induced entity erupts in the skin irrespective of the state of the small intestinal mucosal morphology. Furthermore, gluten ataxia can be categorized as its own entity. The other extra-intestinal manifestations occurring in celiac disease are also found at the latent disease stage. Consequently, patients with celiac traits should be identified and treated.

Keywords: celiac trait; early developing celiac disease; extra-intestinal manifestations; genetic gluten intolerance; gluten; latent celiac disease; mild enteropathy; natural history; potential celiac disease.

Figure 1

Natural history of developing celiac disease (CD) at the small intestinal mucosal level. Each line represents one individual. We are born with a normal mucosal morphology, a villus height (VH), and a crypt depth (CrD) ratio of approximately three and villi three times taller than crypts are deep. Upon gluten ingestion, mucosal injury proceeds rapidly or gradually at different ages, in childhood or only at an older age. Before developing a manifest mucosal lesion (diseased mucosa on biopsy, VH:CrD <2) every CD patient belongs to the category latent “true potential” CD (normal on biopsy, VH:CrD >2).

Figure 2

Small intestinal mucosal immunoglobulin (Ig) A deposits are shown in a villus tip from a dermatitis herpetiformis patient with normal mucosal morphology. IgA is stained with green (A), transglutaminase 2 (TG2) with red (B), and subepithelial colocalisation of IgA and TG2 can be seen in yellow (C).

Figure 3

Celiac trait. Gluten-induced extra-intestinal manifestations exist in both patients with normal (latent celiac disease, CD) and diseased small intestinal mucosa (overt CD). Drawing adapted from the “cooking pot” of splashing extra-intestinal manifestations, which is first presented at the International Celiac Disease Symposium in Dublin 1992, and from drawings in references No. 34, 53, and 54.