A Casebased Approach to Gastroenterology Kimberly Carter MS PAC Division of Gastroenterology University of Pennsylvania KimberlyCarter2 uphsupennedu My bloating got better when I started a GFD ID: 932479
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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
My bloating got better when I started a GFD…
Does that mean I have celiac disease?
Slide3Why Differentiate?
PatientImprove well-beingDecrease
intestinal symptoms
Reduce systemic complications
Practitioner
Risk Stratify
Screen family members
Healthcare Economics
Avoid unnecessary invasive and costly testing
Slide4Objective
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
Slide5Case 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.
Slide6Labs
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
)
Slide7Scalloped mucosa
Duodenal mucosa with expansion of the lamina propria, increased intraepithelial lymphocytes and villous blunting
Slide8Case 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.
Slide9Celiac 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.
Slide10Celiac Disease
Celiac Disease Foundation
Slide11Establishing a diagnosis
Clinical suspicion SerologyBiopsyTherapy Response
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
Extraintestinal manifestations
Osteopenia, osteoporosisReproductive disordersNeuropsychiatric symptomsDermatitis
herpetiformis
Nutrient Deficiencies
Elevated LFTs
Slide14Serologic 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
.
Serologic diagnostic accuracy
Fasano A,
Catassi
C. Celiac Disease.
The New England Journal of Medicine
. 2012;367:2419-2426.
Slide16Endoscopic 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.
Slide17Management 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.
Slide18Gluten-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
Slide19Management 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
Slide20Therapy Response
Clinical remission: ImmediateSerologic response: Weeks-monthsMucosal healing: 6-24 monthsPoor response to GFD
Slide21Clinical Challenges: Diagnostic Dilemmas
Slide22Case 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
Slide23Diagnostic 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).
Slide24Diagnostic 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).
Slide25Diagnostic Dilemma
Non-celiac enteropathy
Kelly
, CP. Diagnosis of celiac disease. In:
UpToDate
, Lamont, JT (Ed),
UpToDate
, Waltham, MA. (Accessed on April 30, 2014).
Slide26Slide27Diagnostic Challenge
Wide range of clinical manifestationsEquivocal serology< Marsh III Criteria
Slide28Utility 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.
Slide29Utility 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.
Slide30Case Review
Young female with negative celiac specific serology on gluten containing diet with response to a GFD.
Slide31Case Study # 2
HLA Typing DQ 2 Positive DQ 8 Negative
Slide32Normal duodenum: No evidence of fold flattening, scalloping, or fissuring.
Small bowel mucosa with no specific pathologic change
Slide33Noglutensolution.com
Slide34Diagnostic 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.
Slide35Gluten 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.
Slide36Case Review
Negative celiac specific serology on gluten dietNo villous atrophyVariable HLA statusPositive
Gliadin
Wheat allergy excluded
Slide37Differentiating…
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.
Slide38In 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