<<Disclaimer: Verify this information before applying it to your situation.>>
Celiac Disease: An Under-Recognized Disorder
----------------------2----------------------
by Thomas Alexander, MD
summarized by Tom and Carolyn Sullivan
The speaker for our Feb. 8 general meeting was our physician advisor,
Thomas J. Alexander, M.D. He presented an overview of the current
thinking on clinical presentation of celiac disease and then handled
questions and answers. A summary is provided here for those who were
unable to attend.
Definition
----------
Celiac disease (CD) is a life-long autoimmune disorder of the
intestinal tract which can have its onset anytime during childhood or
adulthood. It varies in severity, with classic symptoms of
malabsorption noted in some patients while others remain completely
asymptomatic.
Prevalence
----------
It is more common in the European population with more recent studies
suggesting an incidence as high as 1:250. There is a 2:1 female
preponderance. It is felt that the disease is grossly
under-diagnosed, perhaps in large part due to the relatively recent
understanding of the disease and the wide spectrum of symptoms which
are increasingly recognized. In one study, the number of patients
diagnosed over three successive five-year periods increased seven-fold
when the disease was considered in less severe or atypical cases.
Pathogenesis
------------
In a genetically predisposed individual, the intestinal immune system
is abnormally activated by gliadin, a specific portion of the
predominant wheat protein molecule, gluten. As a result, an
inflammatory reaction takes place resulting in the destruction of the
villi, with the first portion of the small intestine generally the
most severely damaged. This damage then limits the small intestine's
ability to absorb nutrients.
95% of patients with CD have the HLA-DQA1 0501 and HLA-DQB1 0201 genes
encoded for the HLA-DQ protein. The remaining 5% have the DR4 and DQ8
genes. But there is more than just genetics involved, as only 30% of
siblings with the identical haplotype will also have CD. Even in
identical twins, when one has CD only about 75% of the time will the
other twin also have CD. Clearly something else is involved in
"triggering" the onset of CD in individuals that are genetically
predisposed to it.
Diagnosis
---------
There are three important syndromes which occur in CD with the degree
of severity varying greatly.
1. Malabsorption with diarrhea, foul-smelling gas, and weight loss.
2. Iron deficiency without blood loss. These patients frequently
present with chronic or even life-long anemia with
hemoccult-negative stools, without any significant symptoms of
malabsorption such as diarrhea or weight loss.
3. A common presentation noted in children is that of unexplained
diarrhea and/or growth retardation often associated with
irritability. The onset may occur in infancy when gluten is
introduced into the diet, or at a later age.
Other non-classic presentations may include osteoporosis,
oligoarthritis, hypertransaminasemia, atypical Sturge-Weber syndrome
(epilepsy with cerebral calcifications), and dental enamel defects
(horizontal grooves).
Laboratory Studies
------------------
Laboratory studies which would suggest malabsorption and CD would
include iron deficiency anemia, hypocarotenemia, hypoalbuminemia,
elevated prothrombin time, and decreased D-Xylose absorption.
Serologic studies which would suggest CD include the anti-gliadin,
anti-endomysial and anti-reticulin antibodies (typically ordered as a
celiac panel) which are about 85-90% accurate. These tests are used
for screening purposes; they cannot be used to make a firm diagnosis.
More recently, autoantibodies to tissue transglutaminase have been
shown to be 95% accurate in predicting CD. Small bowel x-rays are
abnormal in less than 50% of celiac patients.
In time, the tissue transglutaminase autoantibody tests may prove to
be accurate enough to be the single screening blood test for CD. The
only way to definitively diagnose CD is through a small intestinal
biopsy followed by clinical response to a gluten-free (GF) diet.
Pathologic features of the disease may include shortened or absent
villi with crypt hyperplasia. However, these findings may also be
present in a variety of other conditions. Features which are more
specific for CD include increased numbers of lymphocytes (type of
immune cells) mixed in with and below the cells of the villi
(enterocytes).
Complications
-------------
These include the complications of malabsorption such as weight loss,
vitamin and mineral deficiencies, coagulopathy, osteopenia, bone
fractures, lymphocytic gastritis, and lymphocytic colitis. Intestinal
strictures and ulcerations may occur. Other complications include
refractory and collagenous sprue as well as malignancy. There is a
3-4 fold increased incidence of all malignancies, half of which occur
in the intestinal tract. The risk of malignancy returns to that of
the general population after 5 years on the GF diet.
Untreated CD may also negatively affect pregnancy outcome with
relative incidences of spontaneous abortion and low birth weight being
nearly 9 and 6 times higher respectively. These improve markedly in
treated celiac patients.
Other major complications include osteoporosis, short stature, delayed
puberty, infertility, and lactose intolerance. CD may be present in
up to 20% of patients with unexplained neurologic dysfunction.
Associated Disorders
--------------------
CD occurs with greater incidence in patients with other autoimmune
disorders. It is present in about 90% of those individuals with
dermatitis herpetiformis (DH). It has also been seen with increased
frequency in insulin dependent (Type 1) diabetes, autoimmune thyroid
disease, and liver disease.
Latent Celiac Disease
---------------------
This is an ill-defined syndrome where there are positive serologies
with otherwise normal biopsies. These patients have increased gamma
delta T cell receptor lymphocytes. 25% develop histologic features of
CD at 5 years.
Treatment
---------
Life long adherence to a strict GF diet is mandatory. This includes
avoidance of all products made from grains in the wheat family such as
wheat, rye, barley, triticale, and spelt. Pure oats have been shown
to be safe for periods up to 1 year. However, commercially available
oat products are typically grown in fields or milled in plants where
there is wheat contamination.
All food products must be constantly and carefully examined for the
presence of any "hidden glutens" which are often used as food
additives or in processing.
Adherence to the diet can be confusing and overwhelming, particularly
in the newly diagnosed patient. Patient support groups at the
national and particularly the local level have been invaluable in
helping these patients adjust to their restrictions.
Most patients achieve symptomatic improvement within 2-3 weeks of
beginning the diet. Histologic improvement occurs 4-6 months later.
If there is no improvement, it is usually because of noncompliance to
the diet although other causes include refractory sprue, collagenous
sprue, and small bowel lymphoma.
There is often a "honeymoon" period during the teen years when celiac
patients who ingest gluten may be relatively symptom-free. However,
the disease does NOT disappear and their symptoms typically recur in
their twenties.
Post-Diagnosis Management
-------------------------
While most patients will improve with careful attention to the diet,
it is still advisable to obtain an annual CBC, biochemical panel, iron
levels, B12, folic acid, and vitamin D-250H.
A one-year post-treatment biopsy is important in establishing a new
baseline as all patients do not heal completely in spite of strict
adherence to the diet.
Bone densitometry at the time of diagnosis and periodically thereafter
is important particularly in female patients.
Celiac antibodies may be helpful in monitoring some patients,
particularly those in whom noncompliance with the diet is suspected.
|
