How patchy is villous atrophy?

A recent prospective study assessed the degree, frequency, distribution and variability of villous atrophy in duodenal samples of children with coeliac disease. The aim of this study was to help clarify if it is possible for people to have patchy villous atrophy and whether normal or mostly normal biopsies could be found in people with coeliac disease.

How was this study carried out?

In this study 686 children with positive serum anti tissue transglutaminase (tTGTissue Transglutaminase - an antibody that is measured in the blood as part of the diagnosis process for coeliac disease. Depending on the laboratory performing the test, one or more antibodies may be measured (see Endomysial antibody)) immunoglobulin (Ig) A antibodies, or raised serum IgG anti-gliadin antibodies in cases of IgA deficiency, were recruited from a regional referral centre at a children’s hospital in Italy.  The children had all been referred for upper gastrointestinal endoscopy with biopsy for suspected coeliac disease during the period July 2005 to October 2009.

In each child four or five endoscopic biopsies were taken from the duodeno-jejunal flexure/ distal duodenum, intermediate duodenum, proximal duodenum, and duodenal bulb. The duodenal lesions were classified according to Marsh classification:

• Normal mucosa is Marsh 0
• Intraepithelial lymphocytosis (increase in number of intraepithelial lymphocytes to > 25 for every 100 epithelial cells) is Marsh 1
• Intraepithelial lymphocytosis and crypt hyperplasia is Marsh 2
• Intraepithelial lymphocytosis, crypt hyperplasia and villous atrophy is Marsh 3 
  • Mild villous atrophy is Marsh 3a
  • Moderate villous atrophy is March 3b
  • Severe/total villous trophy is Marsh 3c

What are the findings of the study?

A degree of villous atrophy was found in 659 of the 686 children in at least one biopsy site and 235 children had the same degree of villous atrophy throughout the duodenum. Total villous atrophy (Marsh 3c) was the most common level of damage and was found in 545 children. However 59.9% of those children also had biopsy samples with a lesser degree of damage.

In this study 430 children had different degrees of atrophy at different biopsy sites. However the difference between damage seen across the biopsy sites was not greater than one degree of the Marsh classification for each child. In 116 of the children different levels of damage were found in the same biopsy and some areas of the biopsy sample appeared normal. However, the areas that appeared normal showed abnormal intraepithelial lymphocyte (IEL) count after further investigation by CD3 immunostaining.

The frequency of total villous atrophy increased significantly from the duodenal bulb to distal duodenum/ proximal jejunum.

Conclusion and recommendations from this study

In conclusion this study shows there can be variability of the histological lesions among different duodenal sites and there can also be differences within the same biopsy, with no biopsy being completely normal.

This study found that even a single biopsy taken from anywhere along the duodenum would be sufficient to confirm diagnosis of coeliac disease in most cases. However as biopsy handling and the pathologists experience may vary, whenever coeliac disease is suspected multiple biopsies from different duodenal sites should still be recommended to minimise misdiagnosis. Application of CD3 immunostaining to all duodenal biopsies helps to identify Marsh classification 1. Awareness of the variability of biopsy samples may help in making a correct diagnosis.

Reference

Ravelli A, Villanacci V et al(2010) How patchy is patchy villous atrophy?: Distribution pattern of histological lesions in the duodenum of children with coeliac disease. American Journal Gastroenterology advance online publication. 1-7.