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Testing for CD
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Many different tests have been used or proposed for CD screening:
* Routine blood count, serum chemistry, etc. These are general
health-screening tests. They are only useful if they come back
abnormal, and for many celiacs these tests come back normal.
* Absorption tests. There is a xylose test in which the patient
drinks a "foreign" sugar solution and then the level of this
sugar in the blood or urine is monitored. If it is properly
absorbed then the level should rise at a certain known rate. You
need to have a normal intestine in order for it to be absorbed
properly, so it is not a bad test. It is not painful and picks
up many celiacs but not all.
* Antibody blood tests. These are fairly specific to CD. One
disadvantage is that these tests don't pick up other causes of
malabsorption, which may be why they have not been as popular in
the USA as they have been in other countries.
* The small intestine biopsy remains the "gold standard" for
diagnosing CD. At the Finland symposium there was a whole
session devoted to debating how many biopsies are needed to
diagnose CD. There are still experts who believe that three
biopsies are needed, while many others think that one is enough.
However, none of the 392 celiac experts at the symposium thought
CD could be diagnosed without a biopsy. (Dr. Murray thinks that
in the next 4-5 years blood tests may become reliable enough to
diagnose CD in some circumstances without a biopsy.)
* Small bowel x-rays. This is where you swallow a white chalky
liquid. This test is pretty much useless for diagnosing CD.
(30-40 years ago the barium solution used behaved differently so
that it wasn't a bad test for CD, but with modern barium it is
not useful.)
* An empirical trial of the GF diet. Why not just go on the GF
diet and see if you get better? Well, suppose you try a GF diet
for six months and you feel better. But you decide the diet is a
real hassle, so you want to be sure you really have CD. You then
visit Dr. Murray to get a definite diagnosis. What you are
faced with is a gluten challenge, which is not fun for anybody.
Otherwise, there is no way to know if you are a celiac or not.
If you have a biopsy after six months on a GF diet, the
pathologist is probably not going to be able to tell you anything
definitive. So the moral of the story is: Get a biopsy and a
confirmed diagnosis before going on a GF diet. There are very
few exceptions to this rule. On rare occasions where the patient
is not physically well enough to undergo a biopsy, or the health
care company completely refused to pay for it and the patient
can't afford to pay for it themselves, Dr. Murray has diagnosed
CD on the basis of a positive antibody test followed by a good
cli nical response to the GF diet. But this is absolutely the
last alternative to pursue.
In the past, three biopsies were required to diagnose CD. The
European Society for Pediatric Gastroenterology and Nutrition (ESPGAN)
developed criteria in 1969-1970 for defining CD. They said you needed
three biopsies: The initial biopsy to show the damaged villi, a
second biopsy after being on a GF diet showing that the villi have
healed, and a third biopsy showing damaged villi after a gluten
challenge.
In 1990 ESPGAN revised their criteria. They now say that in most
cases only one biopsy is needed. If there is a clinical response to a
GF diet (meaning the symptoms go away), so that there is some
definable improvement, then no additional biopsies and no gluten
challenge are necessary to make the diagnosis. Now there occasionally
may still be a second biopsy to show healing, but it is not
specifically to confirm diagnosis. The second biopsy is usually for a
different reason, such as looking for a complication or making sure
that healing has occurred (and sometimes it doesn't occur despite the
best efforts of doctor and patient). The gluten challenge is now
reserved for less than 10% of the cases that Dr. Murray sees; usually
those that have minimal damage and in whom it is not easy to determine
if the GF diet has really helped.
Older patients may respond to the GF diet but not completely heal.
Why not? Well, they may be healing fully further down the small
intestine but not in the area near the stomach, which has been exposed
to the most gluten for the longest time. However, it is only in the
area near the stomach that you can effectively take small intestine
biopsies. So a biopsy might not show the true extent to which healing
has occurred.
What about all the atypical cases; people who present, but don't yet
have symptoms? Where do they fit in the ESPGAN criteria? And do
milder degrees of damage cause problems? The other thing is the
response to a gluten challenge. Some people don't get sick at all;
they don't get any symptoms. They may have damage in their gut but no
symptoms, sometimes even after six months. There was one patient that
went 14 years on a gluten challenge before they developed intestinal
damage. This tells us that if a celiac eats gluten there won't
necessarily be any reaction, so you can't use how you react to judge
whether or not an item is GF. On the other hand, Dr. Murray said
that some people will get intestinal changes within two hours of
ingesting gluten; this has been shown by taking a biopsy of a
fast-reacting celiac before and two hours after some gluten was
ingested.
If a celiac is having a gluten challenge Dr. Murray looks for
symptoms to begin occurring again, or if not then he follows the
antibody tests until they become positive. After the return of
symptoms, or a positive antibody test, or after about six months, then
Dr. Murray generally performs a biopsy.
There are two basic serological (blood) antibody tests: antigliadin
(antibodies directed against a component of gluten) and connective
tissue (antibodies directed against our own tissues). The
antiendomysial test is an example of the second type of antibody test.
It is very operator-dependent (unfortunately).
A study reported in Gut in 1992 suggests that the celiac antibody
blood tests are 100% sensitive and 99% specific to CD. Some HMOs have
pointed to these studies as proof that a biopsy is unnecessary. But
there are some problems with that study. It was based on a serum bank
saved from previously-diagnosed celiacs. These were celiacs who were
originally found because of screening with these blood tests. So
negative results would automatically not be found in the serum bank.
In September the University of Iowa tested seven reference labs in the
USA. They took 20 serum samples from untreated celiacs, split them
seven ways, and sent them to seven different labs across the country
for analysis. All of the untreated celiacs were diagnosed by biopsy
and had not previously had the antibody tests. They also sent 20
serum samples from people who were biopsy-proven to NOT have CD. Dr.
Murray just got the data back in the last week. Each lab tested the
samples blindly, using their own methods. The results:
* The endomysial antibodies at all the labs were 100% specific. In
other words, none of the 20 non-celiacs tested positive.
* The sensitivity of the endomysial antibodies, meaning how often
is the test positive for celiacs, varied a lot: from 55% to 90%.
So with this test alone, you would not find all the celiacs. In
other words, every lab had some false negatives on this test.
* The sensitivity of the IgA and IgG antigliadin tests was quite
variable. If you combined this test with the endomysial antibody
test, the sensitivity is about 95-100%. In other words, if both
of these tests came back negative from the same lab, the chances
of having CD are less than one in twenty. So these tests are not
bad. They aren't quite as good as some European studies have
suggested, but they are not bad. (This is reassuring.)
However, there is one caveat with these test results: the 20 celiac
samples were "classic" celiac cases. These were not patients with
mild damage. So patients with mild damage might not have abnormal
antibody levels. [Yet these are the very patients that are hard to
diagnose, and for which better tests are needed!--editor]
Some of the potentials for these antibody tests include:
* Screening whole populations, or higher-risk populations such as
diabetics.
* Monitoring the response to a GF diet. These tests should become
negative after a celiac has been on a GF diet for awhile.
There are problems with the blood tests. For example, there is no
standardization between the various labs. None of the labs do these
tests the same way, and none of them report the results the same way.
A "high" positive from one lab is not necessarily going to be a "high"
positive from another. That means you may not be able to compare
results from one year to the next if the samples are sent to different
labs. (This often happens as HMO's change contracts.)
Who should be screened? Dr. Murray usually screens people with Type
I diabetes, unexplained iron-deficiency anemia (Dr. Murray does not
accept heavy menstrual flow in women as an explanation), unexplained
bone disease, functional diarrhea, irritable bowel syndrome, history
of "transient" gluten-sensitivity ("Well, I had it as a child and
outgrew it..."--you DON'T outgrow CD), or lactose intolerance (if
Caucasian).
How should close relatives of a known celiac be screened? Obviously,
a biopsy would be ideal as it would determine for sure whether or not
villi damage is present. But a more reasonable first step is to use
the celiac antibody blood tests to screen close relatives. Tissue
typing could also be done to determine whether or not a relative is at
risk for developing CD, but there is not enough information on the
American population. The type of tissue you see in celiacs also
occurs in about 20% of Caucasians.
You also have to follow up intermittently, since a relative might not
develop CD until after the first screening. For example, suppose you
are a celiac and you have a child. Dr. Murray recommends keeping the
child GF the first year, then putting them on a gluten-containing
diet. At the age of two, or at the appearance of any symptoms, they
would then be screened for CD using the antibody tests. Then check
them again at age 9 or 10, before they go into that pubertal growth
spurt.
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