1. Celiac Disease Diagnosis
2. Gluten-Free Diet
3. Intestinal Biopsy
4. Marsh Classification
5. Celiac Disease Pathology

Over the past decades, the medical community has made significant strides in understanding celiac disease (CD), an autoimmune condition triggered by the ingestion of gluten, a protein found in wheat, barley, and rye. The proactive identification and management of this condition are crucial since undiagnosed and untreated CD can lead to severe health complications, including nutritional deficiencies, osteoporosis, neurological disorders, and even increased risk of certain types of cancer.

The landmark article titled “Diagnosing celiac disease: A critical overview” published in “The Turkish Journal of Gastroenterology” by Ensari A and Marsh MN, DOI: 10.5152/tjg.2018.18635, addresses the evolution of diagnostic practices for CD with a particular focus on histopathological findings and clinical decision-making.

Traditionally, the diagnosis of CD rested on the observation of a malabsorptive state or severe mucosal lesions in the small intestine. However, with the introduction of the Marsh classification system, which detailed the immunopathological spectrum of gluten-induced mucosal changes, the criteria for diagnosis have considerably expanded. This classification eloquently describes the innate and adaptive immune responses to gluten that result in the varying degrees of intestinal damage seen in CD.

The current gold standard for diagnosing CD involves performing intestinal biopsies and interpreting the findings using the Marsh classification, from Marsh I that indicates increased intraepithelial lymphocytes, to Marsh III that is characterized by different degrees of villous atrophy. Nevertheless, the article by Ensari and Marsh sheds light on the controversies surrounding the necessity and practicality of the subclassifications of the Marsh system, such as Marsh 3a, 3b, and 3c. The authors argue that the subclassifications increase pathologists’ workload without adding significant clinical value since gastroenterologists do not rely on these minutiae for treatment decisions.

As CD can present with a wide spectrum of histological features, there is a desire for improved and more insightful approaches to evaluate mucosal pathology. The standard histopathology, while indeed useful, may not capture the full range of cellular changes, particularly considering the variability among individuals with gluten sensitivity. This has fostered the development of molecular-based techniques and stem cell research that might offer a finer resolution of the condition’s impact on the intestinal mucosa.

Recent advancements suggest that molecular-based assays and immunohistochemistry might provide the heightened sensitivity needed to capture subtle but clinically relevant changes within the small intestine. For instance, validating assays for detecting gluten-induced epithelial changes could pave the way for less invasive and potentially more precise diagnostic options.

The discussion in the reviewed article heralds a potential paradigm shift where diagnosing CD may eventually rely less on histopathology and instead combine various diagnostic measures such as serological tests, genetic predisposition, and advanced molecular techniques. This integrated approach could allow for earlier disease detection, particularly in individuals who may exhibit “potential” CD, where traditional biopsy methods fall short.

The transformative ideas presented in the article prompt a re-examination of current diagnostic practices and call for a more dynamic, layered diagnostic approach. It is a cogent reminder for continued collaboration between gastroenterologists, pathologists, and researchers to refine diagnostic criteria for CD and to develop more precise, practical, and patient-friendly tools.


1. Ensari A, Marsh MN. Diagnosing celiac disease: A critical overview. Turk J Gastroenterol. 2019;30(5):389-397. DOI: 10.5152/tjg.2018.18635
2. Ludvigsson JF, Montgomery SM, Ekbom A. Small-intestinal histopathology and mortality risk in celiac disease. JAMA. 2009;302(11):1171-1178. DOI: 10.1001/jama.2009.1320
3. Zanini B, Caselani F, Magni A, et al. Celiac disease with mild enteropathy is not mild disease. Clin Gastroenterol Hepatol. 2013;11(3):253-258. DOI: 10.1016/j.cgh.2012.09.027
4. Marsh MN, Johnson MW, Rostami K. Mucosal histopathology in celiac disease: A rebuttal of Oberhuber’s sub-division of Marsh III. Gastroenterol Hepatol Bed Bench. 2015;8(2):99-109. PMID: 25926934
5. Leffler DA, Schuppan D, Pallav K, et al. Kinetics of the histological, serological and symptomatic responses to gluten challenge in adults with celiac disease. Gut. 2013;62(7):996-1004. DOI: 10.1136/gutjnl-2012-302196

In conclusion, as celiac disease diagnosis evolves, attention turns to refining the criteria and developing techniques that can diagnose the condition with greater accuracy and sensitivity. The article by Ensari and Marsh echoes the need for innovative thinking in the field of celiac disease diagnostics and the adoption of personalized approaches that align with advancements in medical technology.