Although EMA are a well known hallmark of coeliac disease and the prevalence is more than 90% in classical forms of coeliac disease, our study and other recent studies clearly showed that the prevalence of EMA (as well as AGA) is lower than expected in clinical practice,2C4 probably due to the high prevalence of slight histological lesions in these patients (Marsh I-IIIa lesions according to the Marsh classification5). clinical practice. Although EMA are a well known hallmark of coeliac disease and the prevalence is more than 90% in classical forms of coeliac disease, our study and other recent studies clearly showed that the prevalence of EMA (as well as AGA) is lower than expected in clinical practice,2C4 probably due to the high prevalence of slight histological lesions in these patients (Marsh I-IIIa lesions according to the Marsh classification5). In contrast, the sorbitol H2-breath test (H2-BT) seems to be more effective than EMA in diagnosing this form of coeliac disease, probably because of a better correlation with slight histological lesions.6 In the light of these experiences, sorbitol H2-BT may be a good alternative to small bowel biopsy in identifying coeliac disease in patients with IDA but unfortunately this is not always true. In fact, in clinical practice, it is easy to observe patients with IDA EMA? and a negative sorbitol H2-BT test who show slight histological lesions (Marsh I-II type lesions) with disappearance of IDA and improvement in histology after a gluten free diet (GFD). In these cases the use of noninvasive methods (such as EMA) may be a serious mistake as we may run the risk of not identifying hidden coeliac disease. These experiences are very important and should be considered in the cost/benefit ratio of diagnosing coeliac disease. Other important points are the patchiness of the disease, difficulties for pathologists in obtaining biopsies orientated sufficiently, and the cost of small bowel biopsy. Pearce are not in favour of biopsy. Firstly, BRD4770 many patients suspected of having coeliac disease have upper gastrointestinal endoscopy as an initial investigation which provides an opportunity to perform a biopsy on the second part of the duodenum. Although routine biopsies in all patients undergoing endoscopy would have significant resource implications, endoscopic abnormalities of the second portion of the duodenum associated with coeliac disease have been described,7 and these may be used to select patients for biopsy, even if recent studies have re-evaluated the accuracy of endoscopic markers of the disease.8 Secondly, multiple biopsy samples obtained from the second portion of the duodenum overcome the problem of the patchiness of the histological lesions (and we routinely take at least six endoscopic biopsies from the descending duodenum). Also, the pathologist’s expertise in the Marsh classification of histological lesions in coeliac disease may certainly overcome the problem of incorrectly orientated biopsies. Thirdly, I disagree about the excessive expensive of histological evaluation. In Italy the cost of histological evaluations from a single seat (in this case descending duodenum) is about $12.40: I do not believe that this is an excessive additional cost to a routine upper gastrointestinal endoscopy. In light of these consideration, the final question is: should we always perform small bowel biopsies in patients with IDA or other pathologies hiding a subclinical/silent form of coeliac disease? BRD4770 I believe that small bowel biopsy remains the gold standard in diagnosing subclinical forms of coeliac disease (such as IDA), even if the sorbitol H2-BT test is promising as a noninvasive method9: the sorbitol H2-BT test seems to be more promising in the follow up of the disease after a GFD (unpublished data). It remains to be determined whether serological testing for antibodies Gata3 to antitissue transglutaminase improves the diagnosis in cases of mild mucosal lesions. I think that patients at high risk for coeliac disease (such as those with unexplained IDA) should always undergo duodenal biopsy. The costs could be quite high due to the high number of endoscopies that need to be BRD4770 performed but is cost/effectiveness if we consider the significant proportion of patients with coeliac disease who may be missed if screened by serology alone..