Celiac Disease and Gluten Sensitivity - PowerPoint Presentation

Slide1

Celiac Disease and Gluten Sensitivity

A Case-based Approach to Gastroenterology

Kimberly Carter, MS, PA-C

Division of Gastroenterology

University of Pennsylvania

Kimberly.Carter2

@uphs.upenn.edu

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My bloating got better when I started a GFD…

Does that mean I have celiac disease?

Slide3

Why Differentiate?

PatientImprove well-beingDecrease

intestinal symptoms

Reduce systemic complications

Practitioner

Risk Stratify

Screen family members

Healthcare Economics

Avoid unnecessary invasive and costly testing

Slide4

Objective

Compare Celiac Disease (CD) vs. Gluten Sensitivity (GS) as it relates to serological/HLA testing and diagnostic work-upNOTE: No diagnostic criteria for non-celiac gluten sensitivity

Review diagnostic algorithm of CD

Identify limitations of serologic testing

Understand the utility of HLA testing

Define gluten sensitivity (GS)

Discuss management of CD and GS

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Case Study # 1

23-year-old female with Type I DM presents with a 1 year history of abdominal cramping accompanied by bloating, gas, and alternating constipation and diarrhea in the setting of a 10 lbs. weight loss.

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Labs

Immunoglobulin A 243 (50-500 mg/dL)

Tissue Transglutaminase IgA

58 (H)

<=19 unit(s)

TSH 2.90 (

0.27-4.20

uIU

/

mL

)

Hemoglobin

9.5 (L) (12.0-16.0 g/dL)

Hematocrit

30 (L) (36-46 %)

MCV

71 (L) (80-100 fL)

Ferritin

5 (L) (13-150 ng/mL)

Iron

16 (L) (28-170

ug

/

dL

)

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Scalloped mucosa

Duodenal mucosa with expansion of the lamina propria, increased intraepithelial lymphocytes and villous blunting

Slide8

Case Review

Young female with an elevated tTG IgA in the setting of luminal symptoms, weight loss, anemia, and diabetes with duodenal biopsies consistent with villous atrophy confirming celiac disease.

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Celiac Disease

Chronic autoimmune disease of the small intestine triggered by the ingestion of gluten Causes intestinal inflammation

Impairs absorption of nutrients

Contributes to systemic complications

Milito

T, Muri M, Oakes J, et al. Celiac disease: Early diagnosis leads to the best possible outcome.

Journal of the American Academy of Physician Assistants

. 2012;25(11):43-47.

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Celiac Disease

Celiac Disease Foundation

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Establishing a diagnosis

Clinical suspicion SerologyBiopsyTherapy Response

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Who should be tested

High risk groups1st

degree relative

Type I Diabetes and Thyroid Disease

Down syndrome, Turner syndrome

Gastrointestinal symptoms

Misdiagnosed IBS/lactose intolerance

Asymptomatic/

Extraintestinal

manifestations

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Extraintestinal manifestations

Osteopenia, osteoporosisReproductive disordersNeuropsychiatric symptomsDermatitis

herpetiformis

Nutrient Deficiencies

Elevated LFTs

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Serologic testing

Appropriate initial diagnostic work-up and assess therapy responseSerology obtained on gluten containing diet

Immunoglobulin A (IgA) anti-tissue transglutaminase (tTG)

IgA endomysial antibody

IgG or IgA deamidated gliadin peptides (DGPs)

Quantitative IgA

5% IgA deficiency

.

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Serologic diagnostic accuracy

Fasano A,

Catassi

C. Celiac Disease.

The New England Journal of Medicine

. 2012;367:2419-2426.

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Endoscopic evaluation

Gross Findings

Scalloping

Fold flattening

Fissuring

Nodular mucosa

Histologic features

Intraepithelial lymphocytes

Crypt hyperplasia

Villous blunting/

atrophy (Marsh III Criteria)

NOTE: Absence of visual endoscopic findings does not exclude the disease

Setty

M, Hormaza L, Guandalini S. Celiac Disease Risk Assessment, Diagnosis, and Monitoring.

Molecular Diagnosis & Therapy

. 2008;12(5):289-298.

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Management of Celiac Disease

C

Consultation with a skilled

dietitian

E

Education about

the disease

L

Lifelong adherence to a gluten-free

diet

I

Identification

and treatment of nutritional deficiencies

A

Access to an advocacy group

C

Continuous long-term follow-up by a multidisciplinary

team

Milito T, Muri M, Oakes J, et al. Celiac disease: Early diagnosis leads to the best possible outcome.

Journal of the American Academy of Physician Assistants

.

2012;25(

11):43-47.

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Gluten-free diet

Eliminates wheat, rye, and barleyRice, corn, millet, potato, buckwheat, and soybeans are safeCommon gluten free foods

fresh fish, meats, milk, cheese, fruits,

vegetables

Gluten-free substitutes are often expensive and may be difficult to access

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Management of Celiac Disease

Annual LabsCBC, CMP, anti-

gliadin

,

tTG

Screen for and replete micronutrient

deficiencies

(iron studies, B1, B6,

folate

, B

12, Zinc)

Fertility counseling

Screen for osteopenia/osteoporosis with DEXA at diagnosis

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Therapy Response

Clinical remission: ImmediateSerologic response: Weeks-monthsMucosal healing: 6-24 monthsPoor response to GFD

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Clinical Challenges: Diagnostic Dilemmas

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Case Study # 2

26-year-old female with no significant PMH presents with 3 year history of abdominal discomfort accompanied by bloating, gas, and constipation. Symptom improvement on GFD. ROS: headaches, fatigue and 15 lbs weight loss in the past 6 months.

Serology

Anti

-

endomysial

<1:10

tTG

IgA < 5

Gliadin

IgG

37 (H)

Gliadin

IgA <20

IgE

14.3

Allergens: below detectable limits wheat

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Diagnostic Dilemma

Suggestive clinical features but negative serologic tests

Gluten free diet

Selective IgA deficiency

Wheat allergy or gluten sensitivity

Seronegative celiac disease

Kelly, CP. Diagnosis of celiac disease. In: UpToDate, Lamont, JT (Ed), UpToDate, Waltham, MA. (Accessed on April 30, 2014).

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Diagnostic Dilemma

Positive serologic tests but negative small bowel biopsiesFalse positive serology

1

st

generation

gliadin

Kelly

, CP. Diagnosis of celiac disease. In:

UpToDate

, Lamont, JT (Ed),

UpToDate

, Waltham, MA. (Accessed on April 30, 2014).

Slide25

Diagnostic Dilemma

Non-celiac enteropathy

Kelly

, CP. Diagnosis of celiac disease. In:

UpToDate

, Lamont, JT (Ed),

UpToDate

, Waltham, MA. (Accessed on April 30, 2014).

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Slide27

Diagnostic Challenge

Wide range of clinical manifestationsEquivocal serology< Marsh III Criteria

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Utility of HLA genotyping

Asymptomatic individuals with a FH or autoimmune diseaseBorderline serology/biopsies

Discordance between symptoms, serology and biopsies

Rostom

A,

Murry

J,

Kagnoff

M. Medical Position Statement on Celiac Disease.

Gastroenterology

. 2006;131(6):1977-1980.

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Utility of HLA genotyping

HLA-DQ2 and HLA-DQ8HLA-DQ2: 90-95% of celiacHLA-DQ8: 5% of celiacHigh negative predicative

value

Note: 30-40% of the general population has either HLA DQ2 or DQ8

Rostom A, Murry

J, Kagnoff M. Medical Position Statement on Celiac Disease.

Gastroenterology

. 2006;131(6):1977-1980.

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Case Review

Young female with negative celiac specific serology on gluten containing diet with response to a GFD.

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Case Study # 2

HLA Typing DQ 2 Positive DQ 8 Negative

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Normal duodenum: No evidence of fold flattening, scalloping, or fissuring.

Small bowel mucosa with no specific pathologic change

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Noglutensolution.com

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Diagnostic model

Kabbani

T,

Vanga

R,

Leffler

D, et al. Celiac Disease or Non-Celiac Gluten Sensitivity? An Approach to Clinical Differential Diagnosis.

American Journal of Gastroenterology

. 2014;109:741-746.

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Gluten sensitivity

Diagnosis based on exclusion criteria while on gluten containing dietNegative celiac specific serology

No histologic features of villous atrophy

Variable HLA status

Variable presence of first generation anti-gliadin antibodies

Wheat allergy excluded

Catassi

C, Bai J, Bonaz B, et al. Non-Celiac Gluten Sensitivity: The New Frontier of Gluten Related Disorders.

Nutrients.

2013;5(10):3839-3853.

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Case Review

Negative celiac specific serology on gluten dietNo villous atrophyVariable HLA statusPositive

Gliadin

Wheat allergy excluded

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Differentiating…

Celiac vs. Wheat Allergy vs. Gluten sensitivity

Aziz I, Hadjivassiliou M, Sanders D. Does gluten sensitivity in the absence of coeliac disease exist?

BMJ

. 2012;345:7907.

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In Summary

Important to differentiate between CD and GSRecognize the limitations of serologic testingUtilize HLA testing when appropriate: high negative predictive value

Develop a care management plan