Celiac’s
disease has life-long and serious
consequences, necessitating a careful and
thorough diagnostic evaluation. It is
estimated a substantial proportion of
celiac’s disease may remain undiagnosed. The
following steps are currently recommended by
experts. Besides symptomatic individuals,
other high risk populations should be
screened as well. These include symptomatic
relatives of individuals with known celiac’s
disease, individuals with iron deficiency
anemia, premature or severe osteoporosis,
type 1 diabetes mellitus, certain types of
skin, liver, nervous system or thyroid
disease, as well as specific genetic
disorders (e.g. Down’s and Turner’s
syndromes). A careful history, including
food reactions and family history, is always
required.
The tests discussed below should initially
be performed before exclusion of gluten from
the diet.
Blood tests
Screening for celiac’s disease is best
performed in blood samples using IgA
anti-transglutaminase antibodies. This test is
accurate in about 90% of cases, but there are
differences between the different test assays
available. The tests are much less exact in
milder than in more severe forms of the
disease. IgA anti-endomysial antibody testing
is an alternative, but considerably more
costly and difficult to perform. Total IgA
levels should be measured, if they are
suspected to be low. Anti-gliadin antibody
tests should no longer be used, except the
newest generation of deamidated gliadin
peptide (α-DGP) antibody tests. Finger tip
prick blood tests are being marketed, but
their usefulness remains to be ascertained.
In case of a positive blood antibody test,
a conclusive diagnosis should be made from
duodenal biopsies. The antibodies can also be
used to monitor long term dietary compliance,
as they correlate with the degree of
intestinal inflammation due to the disease
process.
In case of negative antibody tests and
normal total IgA levels, small intestinal
biopsy is the conclusive diagnostic step for
exclusion of celiac’s disease.
Genetic
The genetic markers HLA-DQ2 and HLA-DQ8 are
very strongly associated with celiac’s
disease, as about 95% of patients have DQ2 and
about 5% have DQ8. However, close to 40% of
western populations without celiac’s disease
also have these markers. Therefore, as
virtually all celiac’s disease patients have
these markers, absence of the markers
virtually excludes the diagnosis, but a
positive test is not conclusive for celiac’s
disease. Consequently, a positive test must
be confirmed by small intestinal biopsies.
Biopsy
Conclusive proof or exclusion of celiac’s
disease is always by duodenal biopsy.
Pathologists look for characteristic changes
in the tissue samples, such as a decrease in
the height of the hair-like folds (villi) and
the troughs (crypts) of the duodenal lining
and an increase in specific inflammatory cells
in a part of this lining. These changes may be
very subtle and difficult to recognize as well
as unevenly distributed in the small
intestine, which is why multiple (at least
four, better six) biopsies deep down in the
duodenum are recommended. If these first
biopsies are inconclusive, a second set of
biopsies taken after exposure to high
concentrations of gluten for several weeks may
be required. Occasional follow-up endoscopies
with biopsies are recommended, especially in
the case of inadequate symptom relief despite
dietary adaptation. The large majority of
non-response is due to dietary mistakes,
although a small percentage of patients do not
respond despite meticulous exclusion of
gluten. In the latter case, further diagnostic
evaluation by a specialist is warranted.
Further diagnostic considerations
A significant reduction of symptoms on a
strict gluten-free diet is an important aspect
of the diagnostic evaluation. If there is
inadequate symptomatic relief, the diagnostic
work-up needs to continue. This will include
further biopsies, stool tests for parasites,
blood tests for infectious diseases including HIV and
allergies, breath tests for
food intolerances and, possibly,
colonoscopy. Capsule endoscopy, where a
miniature capsule-sized video camera is
swallowed, can reveal celiac’s disease and
exclude other disease. A conclusive diagnosis
of celiac’s disease is, however, not possible
due to the inability to take tissue samples.
Patients with celiac’s disease often have
accompanying diseases or deficiencies, (e.g.
vitamins and minerals). Specialist follow-up
is absolutely necessary (see
Celiac’s disease).
The microscopic changes seen in celiac’s
disease may occasionally resemble those seen
in other diseases, such as infections. If
there is any uncertainty, such diseases should
be excluded using further tests.