Formal
Guidelines
Symptom
checklists
Blood
tests
Biopsy
Genetic Tests and Family Risk
Inconsistent
Test Results
Non-Celiac Gluten Sensitivity
Stool Testing
Formal
Guidelines
Could
Gluten Be Causing Your Health Problems?
A screening handout based on the current medical guidelines
Celiac
Disease Testing Algorithms, Mayo Clinic
Celiac
Disease Diagnosis: simple rules are better than complicated
algorithms
Proposes that CD can be diagnosed if 4 out of 5 criteria are
satisfied
Guideline
for the Diagnosis and Treatment of Celiac Disease in Children:
Recommendations of the North American Society for Pediatric
Gastroenterology, Hepatology and Nutrition
Summary
of Guidelines
Complete
Guidelines
AGA
Institute Medical Position Statement on the Diagnosis and
Management of Celiac Disease
AGA
Institute Technical Review on the Diagnosis and Management
of Celiac Disease (provides supporting information for
the medical position statement above)
World
Gastroenterology Organisation (WGO) Practice Guidelines
NICE
(British) guidelines
National
Guideline Clearinghouse Guideline Synthesis
A comparison of guidelines from AGA, WGO, and NICE
Detection
of Celiac Disease in Primary Care: A Multicenter Case-Finding
Study in North America
Blood
Tests
Celiac
Disease Testing Algorithms from Mayo Clinic.
Celiac
Disease Comprehensive Cascade
Celiac
Disease Serology Cascade
Celiac
Disease Comprehensive Cascade for Patients
(already) on a Gluten-Free Diet
A
good
summary of the blood tests, from the NIH Celiac awareness
campaign
The
University of Chicago Celiac Disease Center has a free
screening every October, using the tTG-IgA blood test.
An
over-the-counter screening
test for Celiac Disease (tTG-IgA) is available in Canada
and many other countries. Efforts are underway to get this
test approved in the U.S. While it is not available for retail
sale here yet, it is okay to order a kit for personal use
from the Canadian distributor. You can order it by phone by
calling (416) 704-0573. Here
is an article from Canadian Family Physician: "Home
Blood Testing for Celiac Disease"
If
all else fails and you cannot be tested through your doctor,
it's possible to order
your own tests
Arup
Laboratories has introduced a combination tTG-DGP test (consisting
of tissue transglutaminase and deamidated gliadin peptide)
called the Celiac
Disease Dual Antigen Screen. The
deamidated gliadin peptide antibody included in this test
is replacing
the older antigliadin antibody test.
For more information about the deamidated gliadin peptide
antibody, see these articles: 1
and 2.
Prometheus Labs has a good reputation for celiac testing.
If you would like to be sure that your testing is done through
them, you can call and they will send you a free transportation
kit. You will still need a doctor's order, but using this
kit the sample will be sent directly to Prometheus. To receive
a kit, call 1-888-423-5227, and press option 1. For descriptions
of their Celiac tests, go to this
link and click yes.
The
original antigliadin antibody blood tests (AGA-IgA and AGA-IgG)
are not a good test for diagnosing CD (1).
They may be an indicator of other types of gluten sensitivity
or wheat allergy. They are helpful for monitoring diet compliance.
A
growing body of evidence shows that if tTG test results are
high enough, a small-bowel biopsy may not be necessary:
Strongly
Positive tissue transglutaminase antibodies are associated
with Marsh 3 histopathology in adult and pediatric celiac
disease
Coeliac
Disease: a biopsy is not always necessary for diagnosis
Can
Tissue Transglutaminase Antibody Titers Replace Small-Bowel
Biopsy to Diagnose Celiac Disease in Select Pediatric Populations?
A
discussion
of the above article
Biopsy
How
many biopsy samples?
Dr.
Rex at IU Medical Center takes 6 to 8 samples.
Genetic
Tests
About
genetic testing
from University of Chicago Celiac Disease Program
Prometheus
is now offering a gene test that uses a saliva sample. You
can order a kit from them online at MyCeliacID
Kimball
Genetics offers a gene
test by cheek swab (no blood test needed, which would
be particularly nice for children)
In
this
study, relatives of Celiac patients who had the DQ2 gene
were frequently found on biopsy to have latent or fully-developed
CD even though their celiac blood tests were negative.
This
is video
of Dr. Michelle Pietzak discussing her study determining the
percentage of people who have CD in specific HLA types.
Inconsistent
Test Results
Negative
tTG blood test and positive biopsy:
Celiac Disease can be missed by blood tests (1).
There is some recent research that shows that tTG may be produced
in the small intestine even though it does not show up on
the blood tests (see 3
4).
Surprisingly, negative blood tests are more likely to occur
in elderly people with severe damage (reference needed). Table
1 in this article
lists possible causes of villous atrophy that are not related
to gluten. Some additional causes are listed in the first
table in this article.
Positive
tTG blood test and negative biopsy:
Celiac
Disease can be missed by the biopsy
(2).
But one thing to consider is whether the biopsy
is really negative. Increased intraepithelial lymphocytes
with a positive blood test is likely to be Celiac Disease,
although some studies adhere to stricter criteria. Biopsy
slides can be reviewed by a second pathologist, and you or
your doctor can contact a Celiac
Center to arrange this.
This is a study of the response of people
with a positive tTG and negative biopsy to the gluten-free
diet:
Abstract
from 2007 Digestive Disease Week
Usefulness
of gluten-free diet in gluten-genetically predisposed subjects
positive to intestinal-mucosa anti-transglutaminase antibodies.
T. Not1; F. Ziberna1; S. Vatta1; S. Martelossi1; R. Marzari2;
F. Florian2; V. Villanacci3; D. Sblattero4; A. Ventura1
1. Pediatric Department University of Trieste, Children Hospital
IRCCS Burlo Garofolo, Trieste, Italy.
2. Department of Biology, University of Trieste, Trieste,
Italy.
3. II Pathology Department, Brescia City Hospital, Brescia,
Italy.
4. Department of Medical Sciences, University of Eastern Piemont
, Novara, Italy.
Celiac disease (CD) auto-antibodies against tissue transglutaminase
(anti-tTG) are produced in the intestinal mucosa even when
not measurable in serum. Aim: To investigate by means the
phage display libraries technique, whether the intestinal
mucosa production of IgA anti-tTG could be important in the
diagnostic work-up of early-stage CD, when mucosal histology
is not yet diagnostic among subjects with high risk of CD
such as first degree relatives of CD patients (FDR) or subjects
with autoimmune disease (SAD) tested negative for serum anti-tTG
but positive for CD related HLA DQ2 or DQ8. Methods: We propose
to FDR with or without symptoms and to SAD a prospective study
to uncover early-stage of gluten intolerance by measuring
the mucosal VH5 restricted gene family anti-tTG clones in
two biopsies: before and after one year of gluten free-diet
(GFD). We report clinical, histological and biomolecular features
before and after GFD. The present study was approved by the
independent ethical committee of our hospital. Results: From
March 2005 we enrolled 38 subjects (25F,median age 25y): 34
FDR and 4 SAD. 14 FDR were with autoimmune disease, 3 FDR
with anaemia, 1 with unexplained hypertransaminasaemia, 1
with diarrhoea, 1 with severe constipation and 16 FDR were
asymptomatic. 4 SAD were 1 with alopecia, 1 type1-diabetes
and anemia, 1 with thyroiditis, 1 with thyroiditis and chronic
urticaria . 29/38 subjects were positive for CD related HLA
(26 DQ2,3 DQ8) and 27 agreed to the study. Intestinal biopsy
showed normal mucosa in 22 and type 2 lesion in 5. Anti-tTG
mucosal clones were present in 22/27 biopsies. 23/27 agreed
to the GFD (4 asymptomatic and 19 symptomatic subjects). During
GFD (median 10 m. range 4-12 m.) symptoms and signs that could
have been related to gluten had disappeared in 12/19 (63%)
symptomatic subjects. Haemato-chemical parameters returned
to normal ranges in 4 subjects with iron deficiency anemia
and in one with hypertransaminasemia. Overall, 2 subjects
with severe constipation, 1 with dermatitis herpetiformis
1 with chronic urticaria and 1 with diarrhoea completely improved.
One FDR with autoimmune hepatitis reduced for the first time
the need for immunosuppressive therapy and one with autoimmune
pancytopenia dramatically improved. Conclusion: In the contest
of genetic predisposition to gluten intolerance intestinal
anti-tTG antibodies may represent the earliest marker of gluten
dependent immune response. The GFD strongly improved symptoms
and autoimmune disease supporting that gluten is harmful in
these subjects. We are working on the second biopsies to measure
the mucosal anti-tTG antibodies after one year of GFD.
Non-Celiac
Gluten Sensitivity:
Negative blood test and negative biopsy - but feeling better
on the GF diet
The chance of true Celiac Disease being missed by
both the blood test and the biopsy would be small, and negative
tests should prompt a search for other reasons for symptoms.
It
can be very frustrating for people who feel that they react
to gluten but have negative tests. However, the idea of "gluten
sensitivity" without Celiac Disease is gaining some recognition.
See this article
by a celiac specialist and pamphlet
from Gluten Intolerance Group. Gluten sensitivity is mentioned
several times in this lecture.
Also, this is an article
about a possible mechanism for gluten to cause intestinal
symptoms without villous atrophy. In support of the idea of
non-celiac gluten sensitivity, there
is some evidence that gluten damages cells in everyone
(5,6
7),
and increases intestinal permeability in everyone
(8).
Increased intestinal permeabililty may even cause autoimmune
diseases (9).
So, perhaps gluten is not really good for anybody (At the
very least, wheat toast and crackers may not be the best thing
to eat when recovering from a stomach virus-ed.).
It
is worthwhile to have all of the standard testing for Celiac
Disease, partly because positive tests help people stick to
the diet. However, gluten challenge may not be a good
idea for people who have had severe symptoms, such as
neurological problems. Further damage could be irreversible.
But
when all the testing is done, if you have negative tests but
find that you feel better on the gluten-free diet, there is
room for common sense. The gluten-free diet is healthy, and
if you feel better on it, listen to your body.
Stool
testing:
The
only study I am aware of has found that stool testing is not
useful for the diagnosis of celiac disease:
http://www.bmj.com/cgi/rapidpdf/bmj.38688.654028.AEv1
Gluten
challenge:
From
clinicaltrials.gov
many
individuals who present for evaluation of possible celiac
disease but who are already on a gluten free diet cannot be
tested accurately as there is currently no way of differentiating
between healthy individuals and individuals with well treated
celiac disease. The standard practice in such cases is to
perform a 'Gluten Challenge' whereby the patient eats
the equivalent of 2 slices of bread per day for six to eight
weeks before returning for evaluation with serologic
testing and endoscopy with duodenal biopsy. The use of the
gluten challenge in clinical practice is limited by patient
symptoms and resistance to such a long test period, after
which it may take a number of weeks for the intestine to heal
and the symptoms to resolve. Autoantibodies to tissue transglutaminase
or antibodies to deamidated gliadin, while being excellent
tools to predict celiac disease in patients who have been
on a long-term gluten containing diet, display low sensitivities
to detect short-term and/or recent gluten exposure.
Papers
presented at the NIH Consensus Development Conference on Celiac
Disease
Clinical
presentation of Celiac Disease in the adult population
Narrative
Review: Celiac Disease: Understanding a Complex Autoimmune
Disorder
Guidelines from the NIH Consensus Conference
Diagnosis
of Celiac Disease
Recommendations from Columbia University. This includes a
list of associated
conditions and indications for screening for celiac disease
FAQ
for Physicians
from Warren Research Center for Celiac Disease
Detecting
Celiac Disease in Adult Patients
An overview from the Journal of the American Academy of Physician
Assistants
What if you suspect you have Celiac Disease?
from the National Foundation for Celiac Awareness
Serologic
and Genetic Testing
a discussion of the blood tests for CD/Celiac Disease Center
at Columbia University
Biopsy
Diagnosis of Celiac Disease
from the Celiac Disease Center at Columbia University
Current
Approaches to Diagnosis and Treatment of Celiac Disease
Endoscopy
in Celiac Disease
with endoscopy photos/Celiac Disease Center at Columbia
University
Review
of Evidence, Agency for Healthcare Research and Quality
The
section on diagnosis from the NIH Consensus Conference is
copied in below. For the complete Consensus Statement, click
here.
The
single most important step in diagnosing celiac disease is
to first consider the disorder by recognizing its myriad clinical
features. There is no one test that can definitively diagnose
or exclude celiac disease in every individual. Just as there
is a clinical spectrum of celiac disease, there is also a
continuum of laboratory and histopathologic results. The combination
of clinical and laboratory features may result in a diagnosis
of celiac disease.
All
diagnostic tests need to be performed while the patient is
on a gluten-containing diet. The first step in pursuing a
diagnosis of celiac disease is a serologic test. Based on
very high sensitivities and specificities, the best available
tests are the IgA antihuman tissue transglutaminase (TTG)
and IgA endomysial antibody immunofluorescence (EMA) tests
that appear to have equivalent diagnostic accuracy (TTG is
the specific protein that is identified by the IgA-EMA). Antigliadin
antibody (AGA) tests are no longer routinely recommended because
of their lower sensitivity and specificity. Serologic testing
for celiac disease in children less than 5 years of age may
be less reliable and requires further study.
Biopsies
of the proximal small bowel are indicated in individuals with
a positive celiac disease antibody test, except those with
biopsy-proven dermatitis herpetiformis. Endoscopic evaluation
without biopsies is inadequate to confirm or exclude a diagnosis
since endoscopic findings are not sufficiently sensitive for
celiac disease. Multiple biopsies should be obtained because
the histologic changes may be focal. Biopsies should be obtained
from the second portion of the duodenum or beyond. The pathology
report should specify the degree of crypt hyperplasia and
villous atrophy as well as assess the number of intraepithelial
lymphocytes. Some degree of villous atrophy is considered
necessary to confirm a diagnosis of celiac disease. The finding
of intraepithelial lymphocytes with crypt hyperplasia without
villous blunting is less definitive. Standardization of the
pathology reports in celiac disease is desirable, using published
criteria such as modified Marsh criteria (1999). Communication
between the pathologist and the individual’s physician
is encouraged to help correlate the biopsy findings with laboratory
results and clinical features. Second opinions on biopsy interpretation
may be sought when biopsy results are discordant with serologic
markers or clinical findings.
With
concordant positive serology and biopsy results, a presumptive
diagnosis of celiac disease can be made. Definitive diagnosis
is confirmed when symptoms resolve subsequently with a gluten-free
diet. A demonstration of normalized histology following a
gluten-free diet is no longer required for a definitive diagnosis
of celiac disease.
In
an individual with suggestive symptoms and a negative serology
test, three scenarios are possible. First, the individual
may have selective IgA deficiency. If an IgA deficiency is
identified, an IgG-TTG or IgG-EMA test should be performed.
Second, the serologic test may be a “false negative,”
and if this is suspected the test could be repeated, an alternative
serologic test could be conducted, and/or a small intestinal
biopsy could be performed. Third, the patient may not have
celiac disease.
When
the diagnosis of celiac disease is uncertain because of indeterminate
results, testing for certain genetic markers (HLA haplotypes)
can stratify individuals to high or low risk for celiac disease.
Greater than 97 percent of celiac disease individuals have
the DQ2 and/or DQ8 marker, compared to about 40 percent of
the general population. Therefore, an individual negative
for DQ2 or DQ8 is extremely unlikely to have celiac disease
(high negative predictive value).
Patient
preferences should be elicited in developing recommendations
in the setting of a positive celiac disease serology and normal
biopsy results. A single best approach cannot be prescribed.
Choices include additional small bowel biopsies, periodic
monitoring with celiac disease serology tests, or a trial
of gluten-free diet.
