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?
Why Differentiate?
• Patient
• Improve well-being
• Decrease intestinal symptoms
• Reduce systemic complications
• Practitioner
• Risk Stratify
• Screen family members
• Healthcare Economics
• Avoid unnecessary invasive and costly testing
Objective
• Compare Celiac Disease (CD) vs. Gluten
Sensitivity (GS) as it relates to serological/HLA
testing and diagnostic work-up
• NOTE: No diagnostic criteria for non-celiac
gluten sensitivity
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•
•
•
•
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
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.
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)
Scalloped mucosa
Duodenal mucosa with expansion of the lamina propria, increased intraepithelial
lymphocytes and villous blunting
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.
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.
Celiac Disease
Celiac Disease Foundation
Establishing a diagnosis
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Clinical suspicion
Serology
Biopsy
Therapy Response
Who should be tested
• High risk groups
• 1st degree relative
• Type I Diabetes and Thyroid Disease
• Down syndrome, Turner syndrome
• Gastrointestinal symptoms
• Misdiagnosed IBS/lactose intolerance
• Asymptomatic/Extraintestinal
manifestations
Extraintestinal manifestations
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•
•
•
•
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Osteopenia, osteoporosis
Reproductive disorders
Neuropsychiatric symptoms
Dermatitis herpetiformis
Nutrient Deficiencies
Elevated LFTs
Serologic testing
• Appropriate initial diagnostic work-up and
assess therapy response
• Serology 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.
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.
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.
Gluten-free diet
• Eliminates wheat, rye, and barley
• Rice, corn, millet, potato, buckwheat, and
soybeans are safe
• Common gluten free foods
• fresh fish, meats, milk, cheese, fruits, vegetables
• Gluten-free substitutes are often expensive
and may be difficult to access
Management of Celiac Disease
• Annual Labs
• CBC, 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
Therapy Response
• Clinical remission: Immediate
• Serologic response: Weeks-months
• Mucosal healing: 6-24 months
• Poor response to GFD
Clinical Challenges: Diagnostic Dilemmas
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
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).
Diagnostic Dilemma
• Positive serologic tests but negative small
bowel biopsies
• False positive serology
• 1st generation gliadin
Kelly, CP. Diagnosis of celiac disease. In: UpToDate, Lamont, JT (Ed), UpToDate, Waltham, MA.
(Accessed on April 30, 2014).
Diagnostic Dilemma
• Non-celiac enteropathy
Kelly, CP. Diagnosis of celiac disease. In: UpToDate, Lamont, JT (Ed), UpToDate, Waltham, MA.
(Accessed on April 30, 2014).
Serologic
Performance
Characteristics
Clinical
Suspicion
Duodenal
Biopsy
Diagnostic Challenge
• Wide range of clinical manifestations
• Equivocal serology
• < Marsh III Criteria
Utility of HLA genotyping
• Asymptomatic individuals with a FH or
autoimmune disease
• Borderline 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.
Utility of HLA genotyping
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HLA-DQ2 and HLA-DQ8
HLA-DQ2: 90-95% of celiac
HLA-DQ8: 5% of celiac
High 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.
Case Review
Young female with negative celiac specific
serology on gluten containing diet with
response to a GFD.
Case Study # 2
• HLA Typing
DQ 2 Positive
DQ 8 Negative
Normal duodenum: No evidence of fold flattening, scalloping, or
fissuring.
Small bowel mucosa with no specific pathologic change
Noglutensolution.com
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.
Gluten sensitivity
• Diagnosis based on exclusion criteria while on
gluten containing diet
• Negative celiac specific serology
• No histologic features of villous atrophy
• Variable HLA status
• Variable presence of first generation antigliadin 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.
Case Review
• Negative celiac specific serology on gluten
diet
• No villous atrophy
• Variable HLA status
• Positive Gliadin
• Wheat allergy excluded
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.
In Summary
• Important to differentiate between CD and
GS
• Recognize the limitations of serologic
testing
• Utilize HLA testing when appropriate: high
negative predictive value
• Develop a care management plan