Diagnostic Dilemmas in Celiac Disease

Michael X Ma; Mina John; Geoffrey M Forbes


Expert Rev Gastroenterol Hepatol. 2013;7(7):643-655. 

In This Article

Abstract and Introduction


Celiac disease (CD) is an immune-mediated systemic condition triggered by dietary gluten occurring in genetically susceptible individuals. Our understanding of its numerous and varied clinical presentations has evolved over time, which has contributed to the incidence of CD increasing. In most cases, the diagnosis is readily established and patients promptly improve after commencing a gluten-free diet (GFD). However, in some, the diagnosis is not straightforward and presents a challenge to clinicians. Potential dilemmas include those with positive serology but normal histology, negative serology but abnormal duodenal mucosal histology, failure to respond to a GFD or response to a GFD without evidence of CD. In recent years, development of new assays and modifications to existing diagnostic algorithms for CD has also challenged the traditional role of small-bowel histology as critical in CD diagnosis.


Celiac disease (CD) is a chronic immune-mediated disorder characterized by gastrointestinal pathology with associated systemic manifestations. In genetically susceptible individuals, exposure to dietary gluten typically results in small-bowel mucosal inflammation, villous atrophy and crypt hyperplasia. The presenting clinical features of CD are varied, which contribute to underrecognition of this condition. Untreated CD can cause significant and varied medical complications, with associated negative impacts on psychosocial well-being and quality of life. Timely treatment of CD through early and accurate diagnosis, therefore, has significant clinical and economic benefits to individuals and the broader community. This article will review current diagnostic algorithms for CD and discuss diagnostic challenges in patients with possible CD, and those in whom the diagnosis has previously been established. We review recent controversies with respect to nonceliac gluten sensitivity and diagnosis based on combination serology alone; we also suggest that projected developments in CD diagnostics may occur over the next 5 years.