33.1 Introduction

Small bowel disorders causing malabsorption represent a clinical challenge. Celiac disease (CD) is the most common small bowel disorder causing malabsorption. Standard endoscopy is the method of choice to take samples of the duodenum for histologic analysis in the diagnosis of small bowel disorders. Standard endoscopy without routine biopsy has a limited capability to detect subtle alterations of the small bowel mucosa because of the low-magnification view, patchy nature of intestinal lesions, and dependency of macroscopic features on degree/severity of mucosal lesion. Currently, routine intestinal biopsies are recommended for evaluation of small bowel disorders and malabsorption including CD. Over the past decade, technology development has greatly improved our capability to examine the small bowel broadening the diagnostic role of endoscopy.

The aim of this chapter is to review the new endoscopic tools available in the diagnosis of small bowel disorders with emphasis on celiac disease (as a prototype) including water-immersion technique, capsule endoscopy (CE), enteroscopy, narrow-band imaging, confocal laser endomicroscopy, and chromoendoscopy.

33.2 Standard Endoscopy

Villous atrophy is the usual hallmark histologic abnormality for most small bowel mucosal disorders causing malabsorption (▶Table 33.1). Characteristic endoscopic findings of villous atrophy include reduced duodenal folds, scalloping of folds, fissures, mosaic pattern, and nodularity (▶Fig. 33.1). ¹ , ² Sensitivity for diagnosis of CD is low (50–94%), but when the endoscopic signs are present, these have a high specificity (95–100%) for villous atrophy and hence CD. ³ Low sensitivity for CD diagnosis may be explained because endoscopic markers are absent with lesser degrees of intestinal damage. ⁴ Thus, a normal macroscopic appearance of the small bowel mucosa does not necessarily imply normality. Low sensitivity implicates that duodenal biopsies should always be taken when the diagnosis of a malabsorption disorder is suspected. These endoscopic features have been reported in other small bowel disorders other than CD but their sensitivity and/or specificity have not been estimated. Detection of visible villous atrophy does not determine the etiology.

Several endoscopic technologies and techniques have been developed to improve the visualization of the intestinal mucosa compared to standard endoscopy (▶Table 33.2). ³ , ⁵ , ⁶ , ⁷ , ⁸ , ⁹ , ¹⁰ , ¹¹ , ¹² , ¹³ , ¹⁴

33.2.1 Water-Immersion Technique

Water-immersion technique is based on magnification of intestinal villi when the duodenum is filled with water. This is an easy and safe procedure that adds very little time to a standard upper endoscopy. ⁵ , ¹⁵ The simple technique consists of removal of air from the duodenum lumen by suction followed by rapid instillation of 90 to150 cc of water. This procedure has been useful to increase diagnostic yield during initial investigation of CD by standard upper endoscopy, targeting duodenal biopsy sites, and CD follow-up ⁵ (▶Fig. 33.2).

33.3 Chromoendoscopy and Magnification Endoscopy

Dye-staining chromoendoscopy with indigo carmine or methylene blue enhances the visualization of the mucosal surface. However, dye-staining chromoendoscopy alone was not useful to increase the detection of CD. ¹⁶ Enhanced magnification endoscopy (e.g., acetic acid + magnification) has superior accuracy compared to standard endoscopy for CD diagnosis. ⁶

33.4 Narrow-Band Imaging

Narrow-band imaging uses a narrowing of the bandwidths of the blue and green filters enhancing visualization with a deeper superficial penetration than white light. Narrow-band imaging can help detect villous atrophy (sensitivity > 93%) and grade (sensitivity 83%). ¹²

33.5 Confocal Laser Endomicroscopy

This novel technology allows in vivo imaging of the mucosa at 1000× magnification. It has been explored in CD with good correlation between endoscopic findings and histology. A small study in children showed good interobserver agreement among endoscopists (Kappa 0.76). ¹³ Confocal laser microscopy offers the promise of diagnosis of CD during ongoing endoscopy or at the very least a more precise targeting of the abnormal small bowel mucosa.

33.6 Optical Coherence Tomography

Optical coherence tomography relies on the in vivo evaluation of duodenal mucosa using light waves echo. Among 18 patients with positive serologies for CD and 22 dyspeptic patients, there was excellent concordance between optical coherence tomography and histology for villi morphology in both CD and controls. ¹⁷ In a larger study from the same group that included 134 children (67 with positive serologies for CD), sensitivity and specificity were 82 and 100%, respectively. ¹⁴

33.7 Device-Assisted Enteroscopy

Device-assisted enteroscopy is an invasive endoscopic method with the potential for examination of the whole intestine, which has the advantage of direct biopsy sampling and therapeutic intervention. ¹⁸ , ¹⁹ Mastering device-assisted enteroscopy requires considerable training and experience. Highly experience endoscopists can examine the entire intestine in about 50 to 86% of cases. ¹⁹ Device-assisted enteroscopy can be used to target areas beyond the reach of other endoscopic methods (▶Fig. 33.3). ²⁰ , ²¹ The indications for device-assisted enteroscopy in small bowel disorders are not standardized. However, it may be helpful to exclude/confirm complications of CD such as malignancies or ulcerative jejunitis in patients with refractory celiac disease. ²² , ²³ , ²⁴

33.7.1 Capsule Endoscopy

CE has potential for evaluation of the whole small bowel. ²⁵ Integrated optical magnification allows for excellent evaluation of the villous pattern. CE has good sensitivity and specificity (> 85%) for detection of villous atrophy as compared to histology (▶Fig. 33.4) ¹¹ , ²⁶ CE could be useful for evaluation of refractory CD or when a severe complication is suspected such as lymphoma or cancer. ²⁷ , ²⁸ CE may replace diagnostic biopsy when upper endoscopy is either declined or contraindicated. ²⁹

33.8 Selected Small Bowel Diseases

33.8.1 Celiac Disease

CD is an immune-mediated disorder of the small bowel induced by the ingestion of a group of proteins collectively called gluten (the storage protein component of wheat, barley, and rye) in genetically susceptible individuals. ³⁰ The small intestinal damage is characterized by villous atrophy, crypt hyperplasia, and chronic inflammation, which usually reverts to normal after gluten exclusion. The endoscopic appearance is similar to other small bowel disorders causing malabsorption associated with villous atrophy.

CD affects almost 1% of the North American general population with increasing incidence over time. ³¹

The clinical presentation varies from a malabsorption syndrome with diarrhea and involuntary loss of weight to “silent” without significant symptoms even though villous atrophy is found in the intestine in both scenarios. ³² The diagnosis of CD is supported by the presence of disease-specific autoantibodies (tissue transglutaminase antibodies [tTGA] or/and endomysial antibodies [EMA]), confirmed by an abnormal intestinal biopsy and the clinical response to gluten exclusion. ³³ Lifelong medically supervised gluten-free diet is very effective to control symptoms and prevent complications.

Diagnostic Approaches

CD is characterized by the development of diverse antibodies that are made against the components of the environmental factor (gliadin) (antigliadin antibodies) or connective tissue (tTGA and EMA) Diagnostic performance of serology is affected by reduced gluten ingestion. It is recommended that serology testing is done when the patient is on a regular gluten-containing diet. Total immunoglobulin A (IgA) testing is usually performed to exclude IgA deficiency that make IgA-based serology useless from a diagnostic perspective (▶Table 33.3).

Table 33.3 Serologic test and their diagnostic accuracy in celiac disease

Test	Sensitivity	Specificity
Antigliadin	< 80%	~ 80%
DGP antibodies α	84%	> 90%
EMA a	90–97%	99–100%
tTGA b	95–98%	90–98%
DGP, deamidated gliadin peptide antibodies; EMA, endomysial antibodies; tTGA, tissue transglutaminase antibodies.
aSensitivity and specificity varies between studies, and according to the immunoglobulin isotype of the antibody or antigenic substrate used.
bSensitivity of the IgG isotype is very low (~ 40%) in the absence of selective IgA deficiency.

Antigliadin Antibodies

The low sensitivity/specificity of antibodies against unaltered gliadin along with the existence of alternative serologic tests with better diagnostic performance has rendered the standard antigliadin antibodies obsolete and therefore are not recommended. ³³ However, a new generation of antigliadin antibody assays has been developed to detect antibodies to synthetic deamidated gliadin peptides with a high sensitivity and specificity (similar to tTGA). ³⁴

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