the criteria, arriving to the most recent European

role of intestinal biopsies for the celiac disease (CD) diagnosis has changed
over time, switching from three biopsies needed in the late 1960s (the first on
a gluten containing diet presenting typical histological damage, the second on
a gluten free diet showing the healing of the mucosa and the third
demonstrating the recurrence of the histological changes after the gluten
reintroduction) to the 1990 guidelines requiring only the first intestinal
biopsy, but associated with clinical and laboratoristic criteria, arriving to the
most recent European pediatric guidelines, that encompass the biopsies sparing
in well selected cases (1). However, the benefit of sampling duodenal mucosa in
non-suspected CD patient performing an upper gastro-intestinal endoscopy is
still debated.

et al. (2) recently published their study performed on a hospital based
endoscopy settings. Among more than 8,000 patients who underwent an upper
gastrointestinal endoscopy due to abdominal pain/dyspepsia, gastroesophageal
reflux, anemia/iron deficiency, diarrhea and weight loss, only the 57%
underwent the duodenal biopsies and the CD diagnosis was made in 0.49% of
cases. The factors associated with intestinal biopsy performance were younger age,
female’s sex and symptoms such as weight loss, diarrhea and anemia. It is
remarkable that all already diagnosed CD patients or suspected CD patients were
not included in the study, so that in this cases the duodenal biopsies
avoidance would have resulted in a missed diagnosis.

recent paper published by Stoven et al. (3) investigated the diagnostic yield
from sampling the duodenal bulb in addition to distal duodenum in adults in
which an upper gastrointestinal endoscopy was performed without a specific
suspicion of CD. In this study, duodenal bulb biopsies did not increased
significantly the rate of CD diagnosis (only 0.1% in their cohort) and the
authors concluded that routinely mucosal sampling should not be encompassed in
low-risk pretest patients. However, it is well known that first degree
relatives of CD patients have a ten time higher risk of CD when compared to
general population (4) and subjects suffering from iron deficiency anemia (5)
and/or gastrointestinal symptoms (such as diarrhea, nausea, chronic dyspepsia
or bloating) (6) are at higher risk of CD, when compared to general population.

 When considering patients with known CD,
Stoven et al reported two cases (7%) with histological lesions localized only
in the duodenal bulb and this strengthen the importance of performing biopsies
in this site also at the follow-up of CD. In a previous paper we reported our
experience of a child on a gluten challenge in which the bulb was the only
duodenal area involved (7) and a woman with autoimmune thyroiditis with
histological changes consisting with CD localized only in the duodenal bulb (8).

a not-so-distant past, the only target considered suitable for CD biopsies was
the distal duodenum, insofar as the bulb has Brunner’s glands and more lymphoid
tissue together with the appearance of shorter, broader or blunted villi, that
may led to difficulties in histological interpretation. Nowadays, an expert
pathologist can easily identify histological changes consistent with CD also in
the duodenal bulb, and besides, the presence of Brunner’s gland make the bulb
easily distinguishable from the distal duodenum, so that all specimens
collected during upper endoscopy could be fixed in the same formalin bottle,
without increasing processing charges.

 Analyzing the diagnostic value of bulb
biopsies, several studies supported its crucial role for CD, since the rate of
histological changes localized only in the duodenal bulb ranges from 1.8% to 7%
at diagnosis (8-12).

point widely discussed in literature is the benefit of biopsies orientation.
Sometimes it is considered a mission impossible, since it is time consuming and
requires expert assistants (13). However in our experience (8) biopsy
orientation on filter paper resulted in 90% of well oriented specimen that is
important to establish a correct evaluation of the villous /crypt ratio, a
crucial point of the CD histological features and avoid the occurrence of
inconclusive biopsies.

authors tried to increase the diagnosis yield of intestinal biopsies through
the use of additional tools. Koskinen et al. (14) demonstrated that
anti-transglutaminase2 IgA deposits can be found in all celiac disease patients
at diagnosis, even in absence of serum CD specific autoantibodies, and can last
for long period even after dietary treatment. This technique could be used in
specialized centers as additional diagnostic tool in case of doubts, however it
requires a frozen specimen and a skilled pathologist.

The detection of autoantibodies
(both anti-endomysium IgA and anti-transglutaminase antibodies) from organ
culture has been proposed as complementary diagnostic tool at diagnosis (15),
but it has been demonstrated also useful to avoid gluten challenge in selected
cases (16). The technique requires two mucosal samples that are cultured in a
specific medium for 48 hours, one in the presence and one in the absence of
peptictryptic digest of gliadin, and the autoantibodies are identified from the
supernatant (by indirect immunofluorescence for anti-endomysium and
enzyme-linked immunosorbent assay for anti-transglutaminase). In selected cases
in which the intestinal biopsies are not conclusive for CD diagnosis or in
serum negative histological changes of difficult interpretation, the organ
culture system seems to be a promising tool (15), even if some doubts aroused
about their specificity (17).

In conclusion intestinal
biopsies for CD diagnosis seems to be a controversial topic that requires
further investigations. In our opinion routinely biopsies should not be
recommended in individuals with low pre-test risk of CD. However, a correct
definition of these patients is crucial, since CD presentation is not limited
to malabsorptive symptoms anymore and a delayed or a missed diagnosis could
lead to not negligible complications, such as osteoporosis (18) infertility (19)
and intestinal lymphoma (20).

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