Celiac Disease: Securing a Diagnosis in thea Diagnosis in...

Audrey H. Calderwood, MD, MS, FACG

Celiac Disease:Securing a Diagnosis in theSecuring a Diagnosis in the

Setting of a Gluten-free Diet

Audrey H. Calderwood, MD, MS, FACGAssistant Professor of Medicine

Boston University School of Medicine

Objectives

• Background• Background

• Rationale

• Recommendations

• Key points• Key points

ACG 2015 Boston Regional Postgraduate Course Copyright 2015 American College of Gastroenterology

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Background

• Celiac disease important implications for ti t d f il bpatients and family members

• Increasing awareness of gluten among lay people

• Non-celiac gluten sensitivity– 18 million Americans


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The Challenge

• How do you make a diagnosis of celiac disease• How do you make a diagnosis of celiac disease in setting of GFD?

• Barriers – Patient reluctance to resume diet– Low priorityLow priority– Step wise

Rubio-Tapia et al. Am J Gastroenterol 2013;108:656-76


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Recommendation #1:CD should be differentiated from NCGS

• Risk for nutritional deficiency• Complications• Risk to family members• Duration and intensity of dietary adherence

Conditional recommendation/ Moderate evidence

Rationale

Celiac disease Non-celiac gluten sensitivity

N t t iPathogenesis Automimmune

Not automimmuneNot allergic

?

Gluten exposure <20 ppm LiberalTitrate to symptoms

Implications Testing of Nonefor family first degree relatives None

Complications LymphomaNutritional deficiencies None

Long-term surveillance Yes No


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Prevalence CD among pts on GFD

Kabbani et al. Am J Gastroenterol 2014: 109;741-746.

Recommendation #2:Do not rely on serologies

• Standard diagnostic tests should not be relied• Standard diagnostic tests should not be relied on to exclude CD if on GFD– TTG IGA– IGA– DGP IgA, IgG (young children)

Strong recommendation / High evidence


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Timing matters

• GFD < 1 month– Check serology and histology

• BUT, if negative can’t exclude CD

80% f CD ti t GFD ill h ti• 80% of CD patients on GFD will have negative serologies at 6-8 months

Recommendation #3:Search for old celiac serology results

(before GFD)• Positive IgA tTG or • Negative IgA tTG or

IgA/IgG DGP (>2x ULN)at any time

• Plus a clinical response to GFD

• Positive likelihood ratio

IgA/IgG DGP on a regular diet

• Plus a clinical response to GFD

• Positive likelihood ratioPositive likelihood ratio for celiac disease:

130 [95% CI 18.5 - 918.3]

Positive likelihood ratio for NCGS:

9.6 [95% CI 5.5 - 16.9]

Kabbani TA et al. Am J Gastroenterol 2014. May;109(5):741-6. Slide concept courtesy of Dr. Ciaran Kelly


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Factors in the differential diagnosis of celiac disease vs. NCGS

Seek out “old” serology results (prior to GFD)

C li NCGSCeliac (n=101)

NCGS(n=125) P value

Age of onset (y) 42.2 38.0 0.03

Female gender 76.2% 78.4% 0.8

Typical CD symptoms (Diarrhea, weight loss) 67.3% 24.8% <0.0001

Family history of celiac 28.7% 12.8% 0.004

Other autoimmune disease 28.7% 12% 0.002

Any nutrient deficiency * 57.4% 18.4% <0.0001

* Iron deficiency anemia, severe vitamin D deficiency, vitamin B12 or Zinc deficiency

Kabbani TA et al. Am J Gastroenterol 2014. May;109(5):741-6. Slide courtesy of Dr. Ciaran Kelly

Role of HLA genotyping

• HLA DQ-2 and DQ-8 not influenced by diet

• 25-30% of Caucasians

• Critical to check before gluten challenge

• Patient benefits– Time– Inconvenience– Discomfort


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Recommendation #4

• Check HLADQ-2 and HLADQ-8 to exclude CDCheck HLADQ 2 and HLADQ 8 to exclude CD

prior to formal gluten challenge

• NPV > 99%

• PPV 12%• PPV 12%


Hadithi M et al. Ann Intern Med 2007; 147:294-302.

Recommendation #5

• Formal gluten challenge should be considered

to diagnose or exclude CD in those on GFD



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Historical Gluten Challenge

• 10 gram gluten x 6-8 weeks

Exposure to gluten after GFD• 20 adults with biopsy-proven CD• 14 day gluten challenge (3 or 7.5 grams/day)y g g ( g / y)• Visits

– Day 3: labs, biopsies– Day 7: labs– Day 14: labs, biopsies– Day 28: labs y

• > 75% met diagnostic criteria after 2 weeks • No differences between 3 and 7.5 grams diet

– High doses of gluten exposure are not routinely needed

Green PH and Cellier C. NEJM 2007;357:1731-43; Leffler D et al. Gut 2012


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Serologic markers over 28 day period after gluten challenge


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Gluten Challenge

• 3 gram x 6-8 weeks

• If symptoms:– 3 gram x 2 weeks3 gram x 2 weeks

• If intolerable stop

Algorithm


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Recommendation #6

P ti t ith d t t hi h i i f• Patients with moderate to high suspicion of

CD who opt to continue GFD without formal

gluten challenge should be managed like

those with CD

Conditional recommendation / Low evidence

Case presentation

• 38 year-old woman with long standing bl ti di h d f tibloating, diarrhea and fatigue

– Does not have old serologies– HLA DQ-2 and HLA DQ-8 positive– Formal gluten challenge x 8 weeks

+ TTG IGA– + TTG IGA– EGD with duodenal biopsies

Yes, you have celiac disease


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Take home points

• Important to distinguish NCGS from CDp g

• Look for old serology results prior to GFD

• Use HLA-typing

• Perform a formal gluten challenge

• For those unwilling to undergo gluten challenge, consider managing as CD


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Celiac Disease: Securing a Diagnosis in thea Diagnosis in...

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