therole of intestinal biopsies for the celiac disease (CD) diagnosis has changedover time, switching from three biopsies needed in the late 1960s (the first ona gluten containing diet presenting typical histological damage, the second ona gluten free diet showing the healing of the mucosa and the thirddemonstrating the recurrence of the histological changes after the glutenreintroduction) to the 1990 guidelines requiring only the first intestinalbiopsy, but associated with clinical and laboratoristic criteria, arriving to themost recent European pediatric guidelines, that encompass the biopsies sparingin well selected cases (1). However, the benefit of sampling duodenal mucosa innon-suspected CD patient performing an upper gastro-intestinal endoscopy isstill debated.Pitmanet al. (2) recently published their study performed on a hospital basedendoscopy settings.
Among more than 8,000 patients who underwent an uppergastrointestinal endoscopy due to abdominal pain/dyspepsia, gastroesophagealreflux, anemia/iron deficiency, diarrhea and weight loss, only the 57%underwent the duodenal biopsies and the CD diagnosis was made in 0.49% ofcases. The factors associated with intestinal biopsy performance were younger age,female’s sex and symptoms such as weight loss, diarrhea and anemia. It isremarkable that all already diagnosed CD patients or suspected CD patients werenot included in the study, so that in this cases the duodenal biopsiesavoidance would have resulted in a missed diagnosis.
Arecent paper published by Stoven et al. (3) investigated the diagnostic yieldfrom sampling the duodenal bulb in addition to distal duodenum in adults inwhich an upper gastrointestinal endoscopy was performed without a specificsuspicion of CD. In this study, duodenal bulb biopsies did not increasedsignificantly the rate of CD diagnosis (only 0.1% in their cohort) and theauthors concluded that routinely mucosal sampling should not be encompassed inlow-risk pretest patients. However, it is well known that first degreerelatives of CD patients have a ten time higher risk of CD when compared togeneral population (4) and subjects suffering from iron deficiency anemia (5)and/or gastrointestinal symptoms (such as diarrhea, nausea, chronic dyspepsiaor 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 onlyin the duodenal bulb and this strengthen the importance of performing biopsiesin this site also at the follow-up of CD. In a previous paper we reported ourexperience of a child on a gluten challenge in which the bulb was the onlyduodenal area involved (7) and a woman with autoimmune thyroiditis withhistological changes consisting with CD localized only in the duodenal bulb (8).
Ina not-so-distant past, the only target considered suitable for CD biopsies wasthe distal duodenum, insofar as the bulb has Brunner’s glands and more lymphoidtissue together with the appearance of shorter, broader or blunted villi, thatmay led to difficulties in histological interpretation. Nowadays, an expertpathologist can easily identify histological changes consistent with CD also inthe duodenal bulb, and besides, the presence of Brunner’s gland make the bulbeasily distinguishable from the distal duodenum, so that all specimenscollected during upper endoscopy could be fixed in the same formalin bottle,without increasing processing charges. Analyzing the diagnostic value of bulbbiopsies, several studies supported its crucial role for CD, since the rate ofhistological changes localized only in the duodenal bulb ranges from 1.8% to 7%at diagnosis (8-12).Anotherpoint widely discussed in literature is the benefit of biopsies orientation.Sometimes it is considered a mission impossible, since it is time consuming andrequires expert assistants (13). However in our experience (8) biopsyorientation on filter paper resulted in 90% of well oriented specimen that isimportant to establish a correct evaluation of the villous /crypt ratio, acrucial point of the CD histological features and avoid the occurrence ofinconclusive biopsies.Someauthors tried to increase the diagnosis yield of intestinal biopsies throughthe use of additional tools.
Koskinen et al. (14) demonstrated thatanti-transglutaminase2 IgA deposits can be found in all celiac disease patientsat diagnosis, even in absence of serum CD specific autoantibodies, and can lastfor long period even after dietary treatment. This technique could be used inspecialized centers as additional diagnostic tool in case of doubts, however itrequires a frozen specimen and a skilled pathologist. The detection of autoantibodies(both anti-endomysium IgA and anti-transglutaminase antibodies) from organculture has been proposed as complementary diagnostic tool at diagnosis (15),but it has been demonstrated also useful to avoid gluten challenge in selectedcases (16). The technique requires two mucosal samples that are cultured in aspecific medium for 48 hours, one in the presence and one in the absence ofpeptictryptic digest of gliadin, and the autoantibodies are identified from thesupernatant (by indirect immunofluorescence for anti-endomysium andenzyme-linked immunosorbent assay for anti-transglutaminase).
In selected casesin which the intestinal biopsies are not conclusive for CD diagnosis or inserum negative histological changes of difficult interpretation, the organculture system seems to be a promising tool (15), even if some doubts arousedabout their specificity (17).In conclusion intestinalbiopsies for CD diagnosis seems to be a controversial topic that requiresfurther investigations. In our opinion routinely biopsies should not berecommended in individuals with low pre-test risk of CD. However, a correctdefinition of these patients is crucial, since CD presentation is not limitedto malabsorptive symptoms anymore and a delayed or a missed diagnosis couldlead to not negligible complications, such as osteoporosis (18) infertility (19)and intestinal lymphoma (20).