Celiac disease, also known as gluten sensitive enteropathy is very
common but frequently missed. It is an autoimmune disease of intestinal
damage due to gluten in people who are genetically predisposed. Classic
Celiac disease is diagnosed by abnormal blood tests and an abnormal
appearing intestine on biopsy and symptoms that resolve with a gluten free diet.
Several
blood tests exist for Celiac disease. They have varying degrees of
accuracy. Some are more sensitive, meaning they will be positive in
milder forms of the disease but are not specific, meaning a positive
test may not indicate Celiac disease. Others are felt to be very
specific, meaning that when they are positive, it is almost certain you
have the disease.
The most specific tests are tests for Celiac disease endomysial antibodies (EMA) and
tissue transglutaminase antibody (tTG) tests. These two tests are
IgA based tests and can be negative if you are deficient in the
immunoglobin IgA, which occurs in 10-20% of people with Celiac. When
either EMA or tTG are positive Celiac disease is very likely and
usually the intestine biopsy is positive. Recent studies indicate that
the tTG may only be positive in 40% of true Celiacs when mild degrees of
intestine damage are present on biopsy. Seronegative Celiac, meaning
the blood tests are negative but the biopsy is positive, may occur in up
to 20% of Celiacs.
Antibodies for gliadin (AGA), the toxic
fraction of gluten are considered very sensitive but not specific for
Celiac disease. Newer assays for AGA antibodies for gluten that has
undergone a chemical change
called deamidation appear to be more specific for Celiac disease (Gliadin II,
Inova) than the older gliadin tests. They also may be as or more accurate than EMA and tTG
antibody tests but are not yet widely available.
The most
distressing problem for people with lesser forms of gluten intolerance
who have blood tests and/or biopsies that are normal or borderline yet
respond to a gluten free diet is either not being taken seriously or
knowing for sure if they are sensitive to gluten. For these individuals
stool
antibody testing for antigliadin and tTG have been helpful. Such
stool testing has been performed in research labs and published in a few
studies but are only recently available through the commercial lab,
Enterolab. Founded by a former Baylor research gastroenterologist, Dr
Ken Fine, the tests are available to people online without a doctors
order but are not generally covered by insurance. Dr. Fine, who patented
the test, has yet to publish the results of his findings in a peer
reviewed journal so his tests are not widely accepted. However, his
unpublished data and the clinical experience of some of us who have used
his test have
indicated the tests are very sensitive for signs of gluten
sensitivity. He reports that they are 100% sensitive for Celiac disease
and highly sensitive
for gluten sensitivity of lesser degrees. In the presence of symptoms, that reverse on a gluten-free diet,
abnormal stool antibody levels can be found in most people before blood tests or biopsies become
abnormal.
Small intestine biopsies during upper gastrointestinal endoscopy
are considered the "gold standard" for the diagnosis of Celiac disease.
However, recent studies have demonstrated that some people with gluten sensitivity, especially relatives of Celiacs
with little or no symptoms, have changes from gluten injury to the
intestine that can not be seen with normal microscope examination. They
can only be seen with special stains not routinely done or with a
research electron microscope. The special stains are known as
immunohistochemistry stains. They stain specialized white
blood cells called lymphocytes in the intestinal lining tips or
villi. When these lymphocytes are increased it is known as
intraepithelial lymphocytosis or increased IELs and it is the earliest
sign
of gluten induced injury or irritation. Electron microscopy also
reveals very early ultrastructural changes in some individuals when
blood tests and standard biopsy examination are normal. When people who
have these changes are
offered the option of a gluten-free diet they usually responded
favorably. In contrast, those who continue to eat gluten often later
developed classic Celiac disease.
What these studies suggest is that a "normal small intestine biopsy" may exclude
Celiac disease as defined by strict criteria but it is not a gold
standard for detecting gluten sensitivity. This fact is appreciated by
many individuals who have respond to a gluten-free diet they start
based on their symptoms, family history, suggestive blood test or stool antibody
test(s).
Another source of confusion is in the genetics of Celiac and gluten sensitivity.
Testing for specific blood type patterns on white blood cells known as HLA
DQ2 and DQ8 is increasingly being employed to determine if a person carries either of the two gene
pattern present in 95-98% of Celiacs and predisposing them to the
development of Celiac disease. Some use the absence of these two
patterns
as a way of excluding the possibility of Celiac disease and the need for testing or
gluten-free diet. However, there are rare reports of documented Celiac disease in people who are DQ2 and
DQ8 negative. Moreover, recent studies indicate other DQ
patterns may be associated with gluten sensitivity though unlikely to
predispose to classic Celiac disease.
Testing for all the DQ patterns is advocated by Dr. Fine, based on his
experience with stool antibody test results. He reports that other DQ types are
associated with elevated levels of gliadin and tTG in the stool and symptoms that respond to a gluten-free diet.
According to his unpublished data, all the DQ types except DQ4 are associated with
a risk of intolerance to gluten. Therefore, testing for all the DQ types allows a person to
determine if they carry one of the two high risk gene types for Celiac disease or
any of the other "minor DQ" genes Fine has found associated with gluten sensitivity.
Enterolab's stool testing for gliadin antibodies and tissue
transglutaminase antibodies, though not widely accepted, have gained favor in the lay
public's opinion as an option for determining sensitivity to gluten
either despite negative blood tests and/or biopsies or in place of the
more invasive tests. Most doctors still recommend the accepted blood
tests and small
bowel biopsy for confirmation of Celiac. Though the reports in the lay community
are overwhelmingly positive they have not been subjected to peer review in
the medical community pending Dr. Fine publishing his data or other researchers reproducing his results.
However, doctors open to
the broader problem of gluten
sensitivity are reporting these tests helpful in many patients suspected of gluten
intolerance. Especially when someone has symptoms consistent with
gluten sensitivity but has negative or inconclusive blood tests and/or
biopsies these tests may be very helpful though some are not certain
how to interpret the tests. The national Celiac organizations are uncertain about how to
comment on their application without published research though a recent article
in the British Medical Journal did show stool tests highly specific for Celiac. Dr.
Fine has publicly commented that his unpublished data demonstrates those with
abnormal stool tests indicating gluten sensitivity
overwhelmingly respond favorably to a gluten free diet with improvement of
symptoms and general quality of life.
Another problem is that
there are not universally agreed upon definitions for gluten sensitivity
or intolerance. This becomes especially difficult for those who do not
meet strict criteria for Celiac disease yet may have abnormal tests
and/or symptoms that respond to a gluten-free diet. Those individuals
become confused when they try to find information but do not have a
formal diagnosis of Celiac disease. Consensus in the medical community
on definitions and more research in this area is greatly needed.
The few doctors who appreciate the spectrum of gluten
intolerance or sensitivity are outnumbered by the medical majority that continue to
insist on strict criteria for diagnosis for Celiac disease before recommending a
gluten-free diet. Doctors either unfamiliar with the limitations of
the tests as documented by Celiac research or who insist on the
strict criteria for Celiac being the only indication for recommending a gluten free
diet unfortunately may confuse or frustrate gluten sensitive
individuals. Some of these people then seek answers on the internet or
from alternative practitioners. Many have their diagnosis missed,
challenged, dismissed, or are misinformed. As a result they fail to
benefit from the health
