Celiac
Disease (Celiac Sprue, Sprue Or Gluten Enteropathy)Introduction:
Celiac disease is an inborn hypersensitivity to gluten, to be
more precise, a hypersensitivity to the sub-fraction of gluten, called "gliadin". Recently a new test has been developed, which is
very specific and sensitive, called endomysial antibody (EMA) titre.
With this test it has been established that many more people than were previously
thought of have celiac sprue. For instance, in Ref. 9 the authors found
by studying a sample population in New Zealand that 1.2% of the population were
positive for celiac disease, which was 3-fold more common than previously thought.
A recent review cited that one in 133 people in North America are affected with
celiac disease (Ref. 34). The pathophysiology of celiac disease (CD) is
such that the antibodies against gliadin (from wheat , rye, barley or other food
products) form immune complexes when they get into contact
with gliadin in the small intestine. These IgA deposits can be visualized
in small bowel biopsy samples or skin biopsy samples by immunofluorescence. This
leads to chronic inflammation, scarring and atrophy
(three different degrees of it shown). The end result is malabsorption.
This means that the small intestine can no longer absorb the normal amount of
nutrients as one would expect to normally occur. This malabsorption syndrome is
what causes all of the symptoms of this gluten intolerance. According to Ref.34,
90% to 95% of CD patients carry a genetic marker HLA-DQ2, which can be tested
for in the lab. The remainder of CD patients are HLA-DQ8 positive. However, 10%
to 30% of the general population without symptoms of CD have a positive HLA-DQ2
test. This subpopulation is likely at risk of developing CD down the road and
needs to be screened more often with blood tests to see whether the titers are
changing. If there is any doubt a small bowel endoscopy with biopsy needs to be
performed and the samples are examined for IgA deposits by immunofluorescence. Using
these screening tools it has become apparent that most cases of CD present with
non-gastrointestinal symptoms, such as itchy skin (dermatitis herpetiformis),
osteoporosis or osteopenia, delayed puberty, short stature, iron deficiency, hepatitis
or joint pains. If the physician thinks about the possibility of CD, the appropriate
tests will be found to be positive for CD. Signs and symptoms: Often
and perhaps even most of the time celiac disease has no symptoms, at least not
initially.
The more severe cases would have some fatty stools and bowel movements that are
more frequent. In the past it was thought that this was solely a disease of toddlers
who would present with a failure to grow, have abdominal cramps and diarrhea.
Now we know that the gastrointestinal symptom presentation is only the tip of
the iceberg of CD symptoms. 90% of CD patients have no gastrointestinal symptoms.
The older child and adults may present with symptoms of dermatitis herpetiformis,
dental enamel defects, osteoporosis in males with bone and muscle aches. Iron
deficiency is very common as is an elevation of transaminases from a non-specific
reactive hepatitis or an autoimmune hepatitis. All of these symptoms can disappear
when a strict gluten free diet is followed. In those children or adults
who have gastrointestinal symptoms there may be some abdominal cramps after certain
foods. If these patients had celiac disease as children already, then body growth
may have been inhibited and for that reason these patients often are of a short
stature. Other symptoms can be an itchy skin condition with skin lesions distributed
in a symmetric fashion over the knees, elbows, buttocks and the back. This is
due to dermatitis herpetiformis. It is now known that this skin disease is merely
another presentation of celiac disease and the EMA titre is often positive in
these patients as well. Other consequences of the malabsorption, such as iron
deficiency, can lead to anemia (microcytic anemia, often more in children). B12
and folic acid deficiency leads to another form of anemia, which will look different
under the microscope (megaloblastic anemia, often in adult celiac disease). The
lack of vitamin D can lead to bone deformities and rickets. There might be bone
pain as well. The more atrophy in the small intestine there is, the less absorption
of sugars such as xylose will take place and this leads to an osmotically driven
diarrhea. Along with the diarrhea there is a loss of valuable minerals and protein.
The end result is a slow form of starvation. In women there is a problem with
fertility and lack of menstrual periods. Late onset of puberty can be another
sign of CD. Some children present with joint aches and pains, which can
develop into chronic arthritis. As arthritis is typically more a disease of older
people, symptoms of chronic arthritis in children should make the physician very
suspicious of CD. Diagnosis: Because the symptoms
can be so subtle, it was difficult in the past to make the diagnosis. Now there
is the more specific endomysial antibody titre test as mentioned above, which
will clearly show whether or not the patient has celiac disease. Another test
measures antibodies against tissue transglutaminase (TTG IgA). This latter test
is highly sensitive and specific for CD. However, the physician needs to think
about ordering this test. There are some other tests that might be useful:
if there is a combination of low calcium, potassium and sodium, coupled with a
low albumin count and a high alkaline phosphatase, this should be a trigger to
the physician to order the EMA titre or TTG IgA test. To determine the degree
of malabsorption the 5 gram D-xylose test can be ordered, which will determine
what percentage of this sugar is absorbed. The most direct test is an endoscopic
procedure where the gastroenterologist uses endoscopy to visualize the first part
of the small bowel(called jejunum) and takes several mini biopsies. These will
confirm the presence of celiac disease and also the severity and the amount of
atrophy. This has some prognostic implications, as not every case will respond
to a simple gluten free diet. The gold standard to make the definitive diagnosis
of CD is still a small bowel biopsy with immunofluorescence analysis to show IgA
deposits. Treatment: Before treatment is instituted,
the diagnosis must have been established beyond a shadow of a doubt (see above).
The main part of the therapy is to strictly avoid gluten in the diet. This is
a major step in anybody's life and unfortunately, there is no exception and no
holiday from this for the rest of the life of the person with celiac disease.
On the other hand, once the patient is used to a strict gluten free diet, being
symptom free is so rewarding that most patients have no problem staying on this
diet lifelong. Dr. Sigman stated in Ref. 34 "It is extremely important that
physicians take the time to explain the importance of remaining on the gluten-free
diet for life". Daily multivitamins are also recommended as gluten-free
pastas and flours lack B vitamins, folic acid and iron. Ref. 34 recommends that
a yearly visit to the treating physician should include ordering tests such as
TTG IgA , iron tests, complete blood count, albumin, vitamin B12 and folic acid,
thyroid function tests and other micronutrient levels depending on the clinical
situation. The gluten-free diet has been shown to reduce the risk of micronutrient
deficiencies. It will possibly also diminish the risk of developing other immune
disorders and intestinal lymphoma.
Celiac
disease and gluten free diet: I would like to explain why
it is so important to take this dietary step seriously: Let me explain
this by way of an analogy to an asthmatic patient who has been diagnosed with
an allergy to cat and dog hair. The allergist says that unfortunately there is
no allergy shot that can be given, but the patient must avoid indoor exposure
to cats and dogs. If the patient abides by this recommendation, he/she will be
fine with the asthma. However, if the asthmatic has a cat that he/she really loves
and does not get rid of, there will likely be a serious asthma attack down the
road. Alternatively, there could be a slow process of closing down the
airways from the immune complex (cat dander firmly attached to the circulating
antibody in the asthmatic's system), which would then lead to lung fibrosis, a
dangerous irreversible lung condition similar to end stage emphysema. The
same phenomenon of circulating antibodies that have to be taken seriously, is
happening in celiac disease, except that the target organ here is not the lung,
but the lining of the small intestine (jejunum). With the asthmatic the transport
of air across the lung is at stake. With the celiac disease the transport of all
of the nutrients into our system is at stake. Because the gluten
free diet is so crucial, a referral to a knowledgeable
dietitian is important. Supplements likely will also be needed for a period of
time. In more serious cases supplementation may have to be given on an ongoing
basis. Your doctor will advise you regarding your particular case. From
time to time the EMA titre or tissue transglutaminase (TTG IgA) should be repeated
. The authors of Ref. 10 have shown that the EMA titre can be successfully used
to monitor gluten diet compliance. The titre disappears in a compliant patient,
but reoccurs in non compliant patients. A similar observation, although more crude,
is the xylose absorption test, which will be normal with a compliant patient,
but return to abnormal values with non-compliance. The gluten-free diet
will prevent long-term complications from uncontrolled intestinal inflammation.
| Practical
point and prevention | Hummel
et al. (Ref. 11) found an interesting connection between diabetes and celiac disease.
This group followed children of patients with type I diabetes (insulin dependent)
and checked them for EMA titers. To their surprise they found that there is a
significantly higher percentage of children with celiac disease when compared
to the normal population. Also, there was a significant number of these children,
who were not yet symptomatic, but showed established celiac disease on endoscopic
biopsy. It appears that with more experience targeted screening might be possible
for high risk groups of celiac disease using the endomysial antibody (EMA) titre
or blood tests for tissue transglutaminase (TTG IgA). |
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