1 literature review peter r. mcnally, do, facp, facg university of colorado school of medicine,...

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Literature ReviewLiterature Review

Peter R. McNally, DO, FACP, FACGPeter R. McNally, DO, FACP, FACG

University of Colorado School of Medicine, University of Colorado School of Medicine,

Center for Human SimulationCenter for Human Simulation

Aurora, Colorado 80045Aurora, Colorado 80045

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Video Capsule Enteroscopy in the Diagnosis Video Capsule Enteroscopy in the Diagnosis of Celiac Disease: A multicenter Study. of Celiac Disease: A multicenter Study. Am Am J Gastroenterol. 2007;102;1624-163.J Gastroenterol. 2007;102;1624-163.

Rondonotti E, Spada C, Cave D, Pennazio Rondonotti E, Spada C, Cave D, Pennazio M, Riccioni M, De Vitis I, Schneider D, M, Riccioni M, De Vitis I, Schneider D,

Sprujevnik T, Villa F, Langeleir J, Arrigoni Sprujevnik T, Villa F, Langeleir J, Arrigoni A, Costamagna G, de Franchis R. A, Costamagna G, de Franchis R.

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IntroductionIntroduction

• Celiac Disease (CD) is one of the most common Celiac Disease (CD) is one of the most common genetic disorders seen in North America. genetic disorders seen in North America. Estimates of prevalence range from 1 in 100-Estimates of prevalence range from 1 in 100-120 persons.120 persons.11

• The clinical manifestations of CD are many, The clinical manifestations of CD are many, when CD is full blow is it manifest by diarrhea when CD is full blow is it manifest by diarrhea weight loss, anemia, & malabsorption.weight loss, anemia, & malabsorption.22

Rondonotti E, et al. Am J Gastro. 2007;1902:1642-31.Rondonotti E, et al. Am J Gastro. 2007;1902:1642-31.

1. Statement NIH Consensus Development Conference on Celiac 1. Statement NIH Consensus Development Conference on Celiac Disease Disease http://www.consensus.nih.gov/cons/118/118cdc_intro.htm2. AGA Institute medical position statement on the diagnosis and 2. AGA Institute medical position statement on the diagnosis and management of celiac disease. Gastroenterology. 2006;131;1977-1980.management of celiac disease. Gastroenterology. 2006;131;1977-1980.

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• Serologic tests have become the preferred method of Serologic tests have become the preferred method of screening patients for CD and include: AGA, AmEA, & screening patients for CD and include: AGA, AmEA, & TTG.TTG.33

• ““Gold Standard” for the diagnosis of Celiac Disease is Gold Standard” for the diagnosis of Celiac Disease is identification of Marsh Criteria by small bowel biopsy.identification of Marsh Criteria by small bowel biopsy.22

• Video Capsule Endoscopy (VCE) is a new technology Video Capsule Endoscopy (VCE) is a new technology opening a window for “non-invasive” examination of opening a window for “non-invasive” examination of the small intestine. Common VCE findings of Celiac the small intestine. Common VCE findings of Celiac Disease include: scalloping, nodular mucosa, reduced Disease include: scalloping, nodular mucosa, reduced mucosal folds, &/or erosions.mucosal folds, &/or erosions.55


3. Rostom A, et al. Gastroenterol. 2005;128:S38-S463. Rostom A, et al. Gastroenterol. 2005;128:S38-S465. Korman LY, et al. Endoscopy 2005;37:951-9.5. Korman LY, et al. Endoscopy 2005;37:951-9.

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AimAim

Test the performance of VCE in patients with Test the performance of VCE in patients with both signs/symptoms of and (+) CD serology both signs/symptoms of and (+) CD serology compared to conventional endoscopy and compared to conventional endoscopy and duodenal biopsy.duodenal biopsy.

Determine the longitudinal extent of mucosal Determine the longitudinal extent of mucosal involvement of CD beyond the duodenum and involvement of CD beyond the duodenum and its correlation with clinical & serologic its correlation with clinical & serologic markers.markers.


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Study Design:Design: Prospective multi-center enrollment Study Design:Design: Prospective multi-center enrollment of 43 consecutive subjects with clinical signs and of 43 consecutive subjects with clinical signs and symptoms and at least one positive serologic test (+) for symptoms and at least one positive serologic test (+) for CD.CD.Center Enrollment: 10 Milan, 10 Truin, 15 Rome, 8 BostonCenter Enrollment: 10 Milan, 10 Truin, 15 Rome, 8 Boston

Signs & SymptomsSigns & Symptoms– Chronic diarrheaChronic diarrhea– Weight LossWeight Loss– Dermatitis HerpetiformisDermatitis Herpetiformis– History of Multiple History of Multiple

spontaneous abortionsspontaneous abortions– Iron DeficiencyIron Deficiency– OsteoporosisOsteoporosis– Autoimmune Thyroid Autoimmune Thyroid

DiseaseDisease– Diabetes Mellitus Type I Diabetes Mellitus Type I

Serologic TestsSerologic Tests– IgA-AGAIgA-AGA 67% (+)67% (+)– IgG-AGA IgG-AGA 67% (+)67% (+)– IgA-AmEAIgA-AmEA 67% (+)67% (+)– IgA-TTGIgA-TTG 77% (+)77% (+)

AGA: Antigliadin Antibody AGA: Antigliadin Antibody

AmEA: Endomysial Antibody AmEA: Endomysial Antibody

TTG: TissueTransglutaminaseTTG: TissueTransglutaminase


Inclusion Criteria: >1 Sign and Symptom (+) >1 serologic Test

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Study Design:Design: Prospective multi-center enrollment Study Design:Design: Prospective multi-center enrollment of 43 consecutive subjects with clinical signs and of 43 consecutive subjects with clinical signs and symptoms for and at least one positive serologic test (+) for symptoms for and at least one positive serologic test (+) for CD. CD. Center Enrollment: 10 Milan, 10 Truin, 15 Rome, 8 BostonCenter Enrollment: 10 Milan, 10 Truin, 15 Rome, 8 Boston


Exclusion Criteria: Exclusion Criteria: – History Small Bowel ObstructionHistory Small Bowel Obstruction– History DysphagiaHistory Dysphagia– Cardiac PacemakerCardiac Pacemaker– Electrical ImplantsElectrical Implants– Prior gastric/small bowel surgeryPrior gastric/small bowel surgery– IgA deficiencyIgA deficiency– Chronic NSAID use or occasional use Chronic NSAID use or occasional use

previous monthprevious month

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Study Design: Diagnostic ProceduresStudy Design: Diagnostic Procedures

• VCE (Given Imaging, Yoqneam, Isreal).VCE (Given Imaging, Yoqneam, Isreal).– Pill cam swallowed after 12 hr overnight fastPill cam swallowed after 12 hr overnight fast– Image analysis using Given Imaging softwareImage analysis using Given Imaging software– Small bowel transit time divided in thirdsSmall bowel transit time divided in thirds

• Prox 1/3Prox 1/3rdrd

• Mid 1/3Mid 1/3rdrd

• Distal 1/3Distal 1/3rdrd

• EGD’s > 4 biopsies of 2EGD’s > 4 biopsies of 2ndnd portion duodenum: portion duodenum: Marsh Criteria on histologic examinationMarsh Criteria on histologic examination


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Study Design: Diagnostic CriteriaStudy Design: Diagnostic CriteriaBiopsy: Marsh Histologic Criteria for CDBiopsy: Marsh Histologic Criteria for CD

– Type 0 : normal histologyType 0 : normal histology– Type I : Type I : Intraepithelial lymphocytes (IEL) Intraepithelial lymphocytes (IEL)– Type II : crypt hyperplasia + normal villiType II : crypt hyperplasia + normal villi– Type III : villous atrophyType III : villous atrophy

Video Capsule Endoscopy Criteria for CDVideo Capsule Endoscopy Criteria for CD– ScallopingScalloping– Nodular mucosaNodular mucosa– Reduced mucosal foldsReduced mucosal folds– ErosionsErosions


1010

VCE showing scalloping VCE showing scalloping and nodular mucosaand nodular mucosa


1111

VCE showing ulceration VCE showing ulceration (a)(a) and and decreased mucosal folds decreased mucosal folds (b)(b)


a b

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DemographicsDemographicsGender (M/F) & mean ageGender (M/F) & mean age 19/24 & 35 yrs19/24 & 35 yrs

DiarrheaDiarrhea 49%49%

Wt lossWt loss 14%14%

Abd painAbd pain 65%65%

Dermatitis HerpetiformisDermatitis Herpetiformis 7%7%

Iron DeficiencyIron Deficiency 32%32%

Duodenal HistologyDuodenal Histology

Marsh 0Marsh 0 11/43 (26%)11/43 (26%)

Marsh IMarsh I 1/43 (2.3%)1/43 (2.3%)

Marsh IIMarsh II 3/43 (7%)3/43 (7%)

Marsh IIIMarsh III 28/43 (65%)28/43 (65%)


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Results: VCE Changes observedResults: VCE Changes observed


VCE Mucosal Changes N (%)

Scalloping 25 (89%)

Nodularity – mosaic pattern 12 (43%)

Reduction of mucosal folds 10 (35%)

Erosions – ulcers 2 (7%)

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Histologic Grading vs. VCE findingsHistologic Grading vs. VCE findings


VCEVCE Marsh 0Marsh 0 II IIII IIIIII TotalTotal

NormalNormal 1010 11 00 33 1414

AbnormalAbnormal 11 00 33 2525 2929

TotalTotal 1111 11 33 2828 4343

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Serology & VCE vs. HistologySerology & VCE vs. Histology


Marsh 0Marsh 0 Marsh IMarsh I Marsh IIMarsh II Marsh IIIMarsh III

IgA AmEAIgA AmEA 1/10 1/10 (10%)(10%)

1/11/1

(100%)(100%)

2/32/3

(66%)(66%)

22/2522/25

(88%)(88%)

IgA TTGIgA TTG 1/91/9

(11%)(11%)

1/11/1

(100%)(100%)

3/33/3

(100)(100)

25/2625/26

(96%)(96%)

VCE Abn: VCE Abn: prox 1/3prox 1/3rdrd

1/111/11

(9%)(9%)

0/10/1

(0%)(0%)

3/33/3

(100%)(100%)

25/2825/28

(89%)(89%)

VCE Abn: VCE Abn: middle 1/3middle 1/3rdrd

0/100/10

(0%)(0%)

0/10/1

(0%)(0%)

2/22/2

(100%)(100%)

16/2716/27

(59%)(59%)

VCE Abn: VCE Abn: distal 1/3distal 1/3rdrd

0/100/10

(0%)(0%)

0/10/1

(0%)(0%)

0/30/3

(0%)(0%)

3/273/27

(11%)(11%)

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Result SummaryResult Summary1.1. One of 43 pts with dermatitis herpetiformis & (+) One of 43 pts with dermatitis herpetiformis & (+)

AmEM was Marsh 0 on biopsy, but positive for AmEM was Marsh 0 on biopsy, but positive for patchy mucosal changes on VCE.patchy mucosal changes on VCE.

2.2. Four pts with (+) CD serology and Marsh Criteria Four pts with (+) CD serology and Marsh Criteria [(Gr I (1) & Gr III (3)] were negative on VCE (12.5%).[(Gr I (1) & Gr III (3)] were negative on VCE (12.5%).

3.3. No patients had distal CD changes without No patients had distal CD changes without coincident proximal VCE mucosal changes.coincident proximal VCE mucosal changes.

4.4. VCE mucosal changes in distal 1/3VCE mucosal changes in distal 1/3rdrd were only were only seen with advanced Marsh III changes.seen with advanced Marsh III changes.


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ConclusionConclusion1.1. This study showed that the miss rate for VCE to This study showed that the miss rate for VCE to

detect CD among symptomatic, serology and detect CD among symptomatic, serology and biopsy proven subjects is 4/32 (12%).biopsy proven subjects is 4/32 (12%).

2.2. VCE identified CD mucosal changes in one subject VCE identified CD mucosal changes in one subject with Dermatitis Herpetiformis and (+) EMA with with Dermatitis Herpetiformis and (+) EMA with biopsy negative CD. Suggesting endoscopic biopsy negative CD. Suggesting endoscopic sampling error in 1/43 (2%).sampling error in 1/43 (2%).

3.3. Mucosal changes of CD seen with VCE, always Mucosal changes of CD seen with VCE, always start proximally and tend to predict more advanced start proximally and tend to predict more advanced Marsh Criteria II & III when the 2Marsh Criteria II & III when the 2ndnd and 3 and 3rdrd portions portions of the small bowel exhibit VCE mucosal changes.of the small bowel exhibit VCE mucosal changes.


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Reviewer CommentsReviewer Comments

1.1. Endoscopy and mucosal biopsy remains the gold Endoscopy and mucosal biopsy remains the gold standard for the diagnosis of CD. However, when standard for the diagnosis of CD. However, when biopsies are (-) and clinical suspicion is still high, i.e., biopsies are (-) and clinical suspicion is still high, i.e., (+) EMA & TTG, then VCE may be helpful in identifying (+) EMA & TTG, then VCE may be helpful in identifying subtle, patchy mucosal abnormalities that may support subtle, patchy mucosal abnormalities that may support directed mucosal biopsies.directed mucosal biopsies.

2.2. Although VCE changes are common among CD pts Although VCE changes are common among CD pts (87.5%), the finding in this study that 4 of 32 (12%) CD (87.5%), the finding in this study that 4 of 32 (12%) CD pts with (+) serologies and Marsh histology have pts with (+) serologies and Marsh histology have ‘normal’ VCE should emphasize the need for CAUTION ‘normal’ VCE should emphasize the need for CAUTION as the negative predictive value is 71.4%.as the negative predictive value is 71.4%.

1 literature review peter r. mcnally, do, facp, facg university of colorado school of medicine,...

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