Formal
Guidelines
Blood tests
Biopsy
Genetic Tests
Gluten Challenge
Inconsistent
Test Results
Non-Celiac Gluten Sensitivity
Formal
Guidelines
Update
on Celiac Disease: New Standards and New Tests
New June, 2008 from
Mayo Clinic; includes the new deamidated gliadin peptide test
Guideline
for the Diagnosis and Treatment of Celiac Disease in Children:
Recommendations of the North American Society for Pediatric
Gastroenterology, Hepatology and Nutrition
Complete
Guidelines
Summary
of Guidelines
AGA
Institute Technical Review on the Diagnosis and Management
of Celiac Disease
AGA Institute Medical Position Statement on the Diagnosis
and Management of Celiac Disease
Blood
Tests
Update
on Celiac Disease: New Standards and New Tests
New June, 2008 from
Mayo Clinic. Includes the new deamidated gliadin peptide test.
This information should supersede any older recommendations.
Consider having testing done through Mayo Clinic if possible.
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 this article.
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.
If
you are having difficulty being tested (ie, your doctor refuses
or cost is a major issue), an over-the-counter tTG-IgA test
is now available in Canada (and many other countries), and
can be ordered
online.
The
original antigliadin antibody blood tests (AGA-IgA and AGA-IgG)
appear to be useless for diagnosing CD (1).
They may be helpful for monitoring diet compliance, but there
too are being replaced by the new deamidated gliadin peptide
antibody.
Can
Tissue Transglutaminase Antibody Titers Replace Small-Bowel
Biopsy to Diagnose Celiac Disease in Select Pediatric Populations?
The author proposes that if the tTG level is high enough,
a biopsy may not be necessary. Another study is in progress.
For a further discussion, click
here. Here's a new
article on the subject.
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
Kimball
Genetics offers a gene
test by cheek swab (which would be particularly nice for
children)
Gluten
Challenge
There
is lots of conflicting advice on what constitutes a gluten
challenge:
How
long do I need to be eating gluten before I am tested for
Celiac Disease?
From the University of Chicago Celiac Disease Program website
Gluten
Challenge see article by Dr. Guandalini
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.
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 quite 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 pamphlet
from Gluten Intolerance Group, and also gluten sensitivity
is mentioned several times in this lecture
by Celiac specialists. 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, 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, including neurological damage
which 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.
Went
on the diet before the blood tests/biopsy. (coming
soon)
Stool
testing (coming
soon)
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.
