Celiac Disease Revisited

Abstract

Celiac disease (CD) is a systemic disease triggered by gluten ingestion in genetically predisposed individuals. It manifests primarily as an autoimmune enteropathy associated with specific circulating autoantibodies and a human leukocyte antigen haplotype (HLA-DQ2 or HLA-DQ8). It afflicts roughly 1% of the population, though the majority of patients remain undiagnosed. Diarrhea and malabsorption are classic manifestations of CD; however, both children and adults can be paucisymptomatic and present extraintestinal manifestations such as anemia, osteoporosis, and abnormal liver tests. CD screening is not recommended for the general population, and it should be focused on high-risk groups. CD diagnosis is challenging and relies on serological tests, duodenal histology, and genetic testing. Particularly difficult presentations to manage are seronegative patients, seropositive patients without villus atrophy, and patients who have started a gluten-free diet before the diagnostic workup. The only proven treatment is a lifelong gluten-free diet. We present an in-depth review on the physiopathology and management of CD, with a particular emphasis on diagnostic challenges.

Keywords: Celiac disease; Diagnostic challenges; Duodenal histology; Human leukocyte antigen; Serological tests.

Fig. 1

Pathogenesis of CD. Gluten peptides reach the lamina propria through a leaky gut, with increased intestinal permeability, which may be due to drug-induced inflammation or dysbiota-induced disassembly of enterocyte tight junctions. Gluten peptides are then deamidated by tTG, which allows them to be presented to CD4-T cells by APC that exhibit MHC class II molecules encoded by the haplotypes HLA-DQ2 or HLA-DQ8. This will trigger T-helper 1 and T-helper 2 immune responses that result in mucosal cytotoxicity and inflammation, as well as autoimmune extraintestinal phenomena.

Fig. 2

CD diagnosis flowchart.