Confocal endomicroscopy in the evaluation of celiac disease

We read with interest “Diagnostic value of confocal endomicroscopy in celiac disease” by Günther et al. [1]. Using confocal endomicroscopy (CEM) in celiac disease, they successfully quantified intraepithelial lymphocytes and villous atrophy but not crypt hyperplasia. These results differed from those of our prospective study where crypt hypertrophy was a highly sensitive and specific marker of celiac disease [2]. There were several reasons for this.

Günther’s CEM procedures interrogated three sites in the descending duodenum. Another three descending duodenal locations were scanned with the addition of topical acriflavine in those with celiac disease. Our study protocol evaluated five sites: (i) duodenal cap, (ii) D2 proximal to the ampulla, (iii) D2 at the level of the ampulla, (iv) distal duodenum, and (v) proximal jejunum. We found that the duodenal bulb was the best site for finding both villous atrophy and crypt hypertrophy. This site is most affected by a gluten load and there is emerging evidence that this site should be biopsied to improve the sensitivity of diagnosing celiac disease [3]. Numerically, the duodenal cap was the site with the highest confocal celiac score, which graded in a linear scale the proportion of images with definite changes of celiac disease on CEM. Therefore it was possible that the investigators missed the changes of crypt hypertrophy by not imaging this site.

In terms of the endoscopic technique, CEM has a limited depth of imaging of 250 micrometers. Maximal depth of imaging can be obtained by gentle pressure against the duodenal tissue to “stretch” the superficial mucosa. This can be best achieved in a straight long scope position in the duodenal cap ([Fig. 1]). Reliance on suctioning the descending duodenum to achieve en face confocal imaging may not achieve the equivalent maximal depth of imaging. In addition, in the study of Günther et al., crypt hypertrophy was defined as recognition of at least two crypts in the duodenal mucosa. In our definition, only one crypt was sufficient, and that maintained a high sensitivity (92.3 %) and specificity (88.2 %) for diagnosing celiac disease, according to the receiver operating characteristic [2]. The gold standards used in our study were “histological features of celiac disease” as well as “diagnosed celiac disease”, because “crypt hypertrophy” seen in a horizontal plane cannot be directly compared with vertical sections on histopathology.

Fig. 1 Crypt hypertrophy on confocal endomicroscopy in the duodenal bulb (500 µm × 500 µm).

In terms of patient recruitment, we included patients who were newly diagnosed with celiac disease who were most likely to harbor disease with a higher Marsh grading of severity. Subtotal and total villous atrophy allows the crypts to be seen easily on deeper imaging and this was captured by our definition of crypt hypertrophy. Therefore “confocal endomicroscopic features of crypt hypertrophy” actually incorporates a combination of true crypt hypertrophy with villous atrophy that allowed deeper imaging into the mucosa. Hence “crypt hypertrophy” on CEM was a highly sensitive and specific marker of celiac disease.

Competing interests: None

References

• 1 Günther U, Daum S, Heller F. et al . Diagnostic value of confocal endomicroscopy in celiac disease.  Endoscopy. 2010;  42 197-202
• 2 Leong R W, Nguyen N Q, Meredith C G. et al . In vivo confocal endomicroscopy in the diagnosis and evaluation of celiac disease.  Gastroenterology. 2008;  135 1870-1876
• 3 Hopper A D, Cross S S, Sanders D S. Patchy villous atrophy in adult patients with suspected gluten-sensitive enteropathy: is a multiple duodenal biopsy strategy appropriate?.  Endoscopy. 2008;  40 219-224