celiac disease - internal medicine | acp · review on the diagnosis and management of celiac...
TRANSCRIPT
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Celiac Disease
Donald Schoch, M.D.
Ohio ACP Meeting
October 17, 2014
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Conflicts of Interest
• None to disclose
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• Format
• Present a case
• Do a pretest about the evaluation
• Review case
• Discuss the questions & answers
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The patient is a 40 year old female being seen
because of crampy abdominal discomfort and
diarrhea. The discomfort is generalized and mild.
There are no obvious precipitating or relieving
factors. The diarrhea consists of one to two slightly
loose stools a day. She only rarely has formed
bowel movements.
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She denies rectal bleeding, nocturnal diarrhea, or
malodorous stools. She has had both symptoms for
several years, but they have become somewhat
more pronounced recently. Her GI history and ROS
are otherwise unremarkable.
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PMH – Neg.
SH, FH, & ROS – Neg.
PE – Normal
Labs
Recent labs done in the ER were all normal,
including: CBC, CMP, TSH, & ESR
KUB – nonspecific bowel gas pattern
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Question #1
She tells you that she has been hearing a lot about gluten
sensitivity and wants to know if she has celiac disease.
What is the best first test or set of tests?
1. Anti-gliadin antibody
2. Tissue transglutaminase (tTG) Ab - IgA class
3. Tissue transglutaminase (tTG) Ab - IgA class & Total IgA
level
4. Empiric trial of a gluten free diet
5. EGD with small bowel biopsy
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She asks you if Celiac disease is very common in
the United States.
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Question #2
The prevalence of celiac disease in the United States is
currently thought to be approximately:
1. 10%
2. 1%
3. 0.1%
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You order a tissue transglutaminase (tTG), and it
comes back positive.
She has a follow-up appointment two weeks later.
Her history and exam are unchanged.
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Question #3
What do you do next?
1. Recommend a gluten-free diet
2. Recommend EGD with small bowel biopsies
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She doesn't want an EGD and requests a referral to
a nutritionist for dietary counseling regarding a
gluten-free diet.
She comes back in two months and has been
following the diet very carefully. However, she
wasn't able to keep the appointment with the
nutritionist.
Her symptoms are only slightly better.
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She now tells you that she and her husband are
having marital problems. This has been extremely
upsetting. In the past she has had a change in
bowel habits and similar abdominal discomfort
when under stress. Several years ago she was told
that she might have irritable bowel syndrome.
She asks you if her lack of response to the diet
means that she has irritable bowel syndrome (IBS)
and not celiac disease.
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Question 4
She might have celiac disease but is not following a strict
gluten-free diet.
• True
• False
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Question #5
The initial tTG could have been a false positive, and she
might not have celiac disease.
• True
• False
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You have a medical student observing you. She has
just finished reviewing clinical epidemiology and asks
you to explain what the positive predictive value
(PPV) of a tTG is.
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Question #6
Assuming the prevalence of celiac disease is 15%, and the
sensitivity and specificity of the tTG are both 98%, the PPV
will be:
1. 95%
2. 90%
3. 50%
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When you tell the patient that it is hard to know at
this point whether or not she has celiac disease,
she says she is willing to undergo an EGD if that will
help. However, she wants to keep her invasive
testing to a minimum and is even willing to go back
on a gluten-containing diet if that will help make the
diagnosis.
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In order to follow her wishes and keep the testing to
a minimum as well as maximizing the chance of
having a conclusive test, you suggest that she
resume a gluten-containing diet and then have an
EGD. She agrees.
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Question 7
How long should she be on a gluten-containing diet before
having an EGD?
1. She hasn't been on the gluten-free diet long enough to
affect the biopsies. You can do the EGD and SB biopsies
now.
2. Wait four weeks. That is probably enough for most
patients.
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Question 8
• Some patients can take years before having a relapse
after resuming a gluten-containing diet.
• True
• False
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You eventually make the diagnosis of celiac disease
by small bowel biopsy on a gluten-containing diet.
On a follow up appointment, she says that she has
been reading on the Internet that her children and
other first degree relatives may be at increased risk
for celiac disease. She requests that you call their
pediatrician to discuss this issue.
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Question 9
Her children have an increased risk of developing celiac
disease.
• True
• False
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Question 10
Her children's pediatrician reports that your patient is
insisting her children be tested. He tells you that they are
asymptomatic. He wants to know the best first test to
order.
You suggest:
1. Tissue transglutaminase (tTG) IgA
2. EGD with small bowel biopsy
3. HLA Testing to determine if they have DQ2 or DQ8
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Resources
• AGA Institute Medical Position Statement on the Diagnosis and
Management of Celiac Disease
– GASTROENTEROLOGY 2006;131:1977–1980
• American Gastroenterological Association (AGA) Institute Technical
Review on the Diagnosis and Management of Celiac Disease
– GASTROENTEROLOGY 2006;131:1981–2002
• National Institutes of Health Consensus Development Conference
Statement on Celiac Disease, June 28–30, 2004
– GASTROENTEROLOGY 2005;128:S1–S9
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Definition
• Celiac disease is a life-long inflammatory condition of the
gastrointestinal tract that affects the small intestine in genetically
susceptible individuals.
• Small bowel mucosal inflammation and villous atrophy which
occur with exposure to the wheat protein gluten
• Older and less preferred terms
• Nontropical sprue
• Celiac sprue
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Etiology
• An inappropriate T-cell–mediated immune response to ingested
gluten that causes inflammatory injury to the small intestine in
genetically predisposed persons.
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Serological Testing
• These tests have increased our understanding of the prevalence of
celiac disease.
• Test while on a diet containing gluten, ideally a significant amount of
gluten.
• False negatives can result from testing patients who have already
started a gluten-free diet.
• Antibodies remain elevated for 1 to 12 months.
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IgA Antihuman Tissue Transglutaminase AB
(tTG)
– Tissue transglutaminase is an intracellular enzyme.
– Released by inflammation
– Test Characteristics
• Sensitivity of 90% to 96%
• Specificity is greater than 95%
– Not positive in patients with IgA deficiency
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IgA Endomysial Antibody
Immunofluorescence (EMA)
• EMA and tTG appear to have equivalent diagnostic accuracy.
• tTG is the specific protein that is identified by the IgA-EMA.
• Technical issues with the test mean IgA tTG AB is used instead.
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Antigliadin Antibody (AGA)
• No longer routinely recommended because of lower sensitivity and
specificity
• Frequent false positives
• An older test
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Patients with negative serologic testing and
suggestive symptoms
• Possibilities
• IgA deficiency
• False negative test
• Low-gluten diet at the time of testing
• Not celiac disease
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Prevalence of IgA Deficiency
• 1:500 to 1:700 individuals in the population
• Occurs in 2% to 5% of patients with Celiac disease
• Testing strategy for IgA deficient patients
– IgG-tTG or IgG-EMA tests are available
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Question #1
She tells you that she has been hearing a lot about gluten sensitivity
and wants to know if she has celiac disease. What is the best first test
or tests?
1. Anti-gliadin antibody
2. Tissue transglutaminase (tTG) Ab - IgA class
3. Tissue transglutaminase (tTG) Ab - IgA class & Total IgA level
4. Empiric trial of a gluten free diet
5. EGD with small bowel biopsy
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Prevalence of Celiac Disease
• More common than previously recognized
• Range of 0.5% to 1% in the United States
• Includes symptomatic and asymptomatic individuals
• Limited studies about prevalence in non-Caucasians
• Appears to be more common in Northern Europe population
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Question #2
The prevalence of celiac disease in the United States is currently
thought to be approximately:
1. 10%
2. 1%
3. 0.1%
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Question #6
Assuming the prevalence of celiac disease is 15%, and the sensitivity
and specificity of the tTG are both 98%, the PPV will be:
1. 95%
2. 90%
3. 50%
Note: The question weights the prevalence and test characteristics in
favor of a high PPV.
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How is the diagnosis made?
• No one test can conclusively make or exclude the diagnosis.
• There is a spectrum of celiac disease.
• There is a range of laboratory and pathology findings.
• Ideally, all testing should be done while the patients is on a
gluten-containing diet.
• Serologic testing is the first step.
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Small bowel biopsies
• Indicated in patients with positive celiac antibody testing
– Except with biopsy-proven dematitis herpetiformis
• Done by EGD
• Endoscopic appearance by itself is not enough to rule out the
diagnosis.
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Making the Diagnosis
• Presumptive diagnosis
• Positive serologic tests and biopsy
• Definitive diagnosis
• Symptoms resolve on a gluten-free diet
• Repeat small bowel biopsy to document normalization on a
gluten-free diet is no longer recommended to establish the
diagnosis.
• When diagnosis is uncertain
• Consider obtaining HLA haplotypes
• Over 97% of patients with celiac disease have the DQ2 and/or
DQ8 marker
• High negative predictive value
• If the patient is negative for DQ2 and DQ8, it is very unlikely
that they have celiac disease.
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Question #4
She might have celiac disease but is not following a strict gluten-free
diet.
• True
• False
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Question #5
The initial tTG could have been a false positive, and she might not have
celiac disease.
• True
• False
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Question #3
What do you do next?
1. Recommend a gluten-free diet
2. Recommend EGD with small bowel biopsies
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Question 7
How long should she be on a gluten-containing diet before having an
EGD?
1. She hasn't been on the gluten-free diet long enough to effect the
biopsies. You can do the EGD and SB biopsies now.
2. Wait four weeks. That is probably enough for most patients.
Case slide 6c
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Question 8
• Some patients can take years before having a relapse after
resuming a gluten-containing diet.
• True
• False
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Screening
• First-degree relatives of patients with celiac disease are at higher
risk for biopsy-confirmed celiac disease than those in the general
population.
– Prevalence of 10%.
• There are no current recommendations to screen the general
population for celiac disease.
• First-degree relatives should be screened only if they have
suggestive symptoms.
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Question 9
Her children have an increased risk of developing celiac disease.
• True
• False
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Question 10
Her children's pediatrician reports that your patient is insisting that her
children be tested. He tells you that they are asymptomatic. He wants
to know the best first test to order.
You suggest:
1. Tissue transglutaminase (tTG) IgA
2. EGD with small bowel biopsy
3. HLA Testing to determine if they have DQ2 or DQ8
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Question #3
What do you do next?
1. Recommend a gluten-free diet
2. Recommend EGD with small bowel biopsies
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Treatment
• Six key elements to management
• Consultation with a skilled dietitian
• Education about the disease
• Lifelong adherence to a gluten-free diet
• Identification and treatment of nutritional deficiencies
• Access to an advocacy group
• Continuous long-term follow-up by a multidisciplinary team
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Treatment (cont.)
• Needs to be life long
• Gluten-free diet
• Wheat, rye, and barley
• Oats
• Data about tolerance is unclear
• Most commercially available oat products are contaminated
with wheat gluten.
• Recommendation is to avoid oats
• Beer
• Gluten-free beer is available
• Made with rice, sorghum, buckwheat and corn
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Screening
• Specific diseases (a partial list)
• Type 1 diabetes mellitus
• Especially individuals with gastrointestinal (GI) symptoms
• Benefits of screening individuals without GI symptoms is
unclear
• Autoimmune thyroid and hepatobiliary disorders
• Primary biliary cirrhosis
• Down and Turner syndromes