Measuring Change In Small Intestinal Histology In Patients With Celiac Disease

Abstract

Small intestinal histologic abnormalities in celiac disease include atrophy of the intestinal villi, hypertrophy of the crypts and lymphocytic infiltration of intraepithelial spaces and lamina propria. These findings are central to diagnosis and their severity and change over time are valuable to monitor disease course and response to therapy. Subjective methods to grade celiac disease histological severity include the Marsh-Oberhuber and Corazza-Villanacci systems. Quantitative histology uses villus height (Vh), crypt depth (Cd), and intra-epithelial lymphocyte count (per 100 enterocytes) to provide objective measures of histologic changes including Vh:Cd ratio. Here we examine the available literature regarding these methodologies and support the use of quantitative histology as the preferred method for accurately and reproducibly demonstrating change of relevant histologic end points over time. We also propose a Quantitative-Mucosal Algorithmic Rules for Scoring Histology (Q-MARSH) system to partially align quantitative histology results with the traditional Marsh, Marsh-Oberhuber, and Corazza-Villanacci systems. Q-MARSH can provide a standardized, objective, and quantitative histology scoring system for use as a clinical or research application.

Baseline quantitative histology in therapeutics trials reveals villus atrophy in most patients with coeliac disease who appear well controlled on gluten‐free diet

“…Severity of mucosal injury was similar across the three countries where patients were recruited, Australia, New Zealand and the United States. Persistent villus atrophy revealed by quantitative histology in our cohort of ‘well controlled’ patients is, in fact, higher than the 38% recently reported for 1345 patients with self‐reported moderate or severe coeliac disease‐associated symptoms . Even though it is well known that persistent duodenal villus atrophy is not efficiently detected by transglutaminase serology in patients on gluten‐free diet, our findings suggest that standard processing and subjective evaluation of duodenal biopsies also fails to detect villus atrophy in many patients with treated coeliac disease.…”

“…This study had four principal findings. We confirm that quantitative histology demonstrates persistent duodenal mucosal injury in the majority of patients with coeliac disease on gluten‐free diet, and extend this observation to patients who are seronegative and would be considered ‘well controlled’. Second, villus height to crypt depth ratio, and intraepithelial lymphocytosis both increase progressively from the proximal to distal duodenum.…”

“…The height of the villus‐crypt axis (ie the sum of villus height and crypt depth) has been depicted as a constant, which implies that there is a reciprocal relationship between villus height and crypt depth . Figure shows the relationships between paired measurements of duodenal villus height and adjacent crypt depth, and their ratio or sum for the pooled set of 169 biopsy assessments from 93 patients.…”

“…Quantitative histology provides accurate assessment of duodenal mucosal injury in coeliac disease by using highly reproducible measurements of villous height, crypt depth and intraepithelial lymphocyte density in well‐oriented distal duodenal biopsies . With implementation of rigorous standard operating procedures, quantitative duodenal histology outperforms conventional qualitative histology using grouped classifications such as Marsh score, and is emerging as a preferred measure of efficacy in therapeutics trials for coeliac disease .…”

Biomarkers of Inflammation and Intestinal Mucosa Pathology in Celiac Disease

“…2). The lamina propria normally contains a mixture of plasma cells, lymphocytes, and occasional eosinophils and macrophages 65 , but in CD there is a massive influx of inflammatory cells consisting largely of plasma cells and lymphocytes 69 .…”