Statistics from Altmetric.com
Editor,—We noted in the guidelines for the management of iron deficiency anaemia (Gut2000;46(suppl IV):iv1–iv5) that it is recommended that small bowel biopsies should be taken in all patients presenting with iron deficiency anaemia. This has been the subject of much discussion between the pathology department and ours recently.
Antiendomysial antibodies (EMAs) give at best close to 100% sensitivity and specificity1 2 although other studies suggest around 95% sensitivity with much lower values for specificity depending on the exact criteria for gluten sensitive enteropathy adopted.3 4 This has been discussed at both the recent British Society of Gastroenterology (BSG) meeting (Ciclitira PJ. State of the Art Lecture: Coeliac Disease—pathogenesis and prevention. BSG Annual Meeting, March 2000) and the American Gastroenterology Association (AGA) meeting (Schuppan D.Sprue: new insights into pathogenesis and management. AGA Postgraduate Course, May 2000).
A possible reason for these differences in sensitivity and specificity in the literature is that standards vary between different pathology departments in the techniques of anti-EMA assessment.5Most hospital biochemistry departments perform the tests using monkey oesophagus tissue bought from commercial suppliers; on the market at present there are 19 different suppliers of monkey oesophagus and 23 different suppliers of the enzyme immunoassay (EIA) (United Kingdom External Quality Assessment Services for Autoimmune Serology (NEQAS)). These tissue samples will be of varying quality, and the EIAs will vary in their accuracy. To compound the problems the immunofluorescent technique is essentially subjective, and results will vary between different observers. Our laboratory automatically measures total IgA levels, patients deficient in IgA will have negative IgA EMA, and laboratories need to have the resources to measure IgG EMA in these patients.
Our biochemistry laboratory is evaluating antitissue transglutaminase antibody (AtTGA) assays to replace the monkey oesophagus immunofluorescence system, which should be more automated and therefore more cost effective. Initial sensitivity and specificity for AtTGA assays are promising.6
There is some evidence that endoscopic markers are useful in detecting villous abnormality in coeliac disease7 and we await the development of high resolution endoscopy.8 It seems that although duodenal biopsy is traditionally regarded as the gold standard, there is still the possibility that false negatives in patients with patchy villous changes will occur with these screening methods. A recent abstract from the AGA from Columbia University, New York, found that fewer than half of duodenal biopsy samples in their study were orientated sufficiently to allow evaluation of villous atrophy, and 39% of patients had patchy disease.9
The implications in terms of resources for the histology departments in handling multiple duodenal biopsies in all patients with iron deficiency anaemia are considerable and this is currently the subject of an internal audit at our hospital. Although for the reasons stated anti-EMA has varying sensitivity and specificity, there is potential for considerable improvement in this area, with close to 100% values for both being possible, particularly with newer assays that will be automated and more efficient. Paradoxically, when these tests become more widely available there may be many more referrals to gastroenterology departments due to positive serological tests and this may in fact increase further the number of duodenal biopsy specimens reaching histopathology departments even if duodenal biopsy were a second line test. We wonder if the guidelines for duodenal biopsy and anti-EMA in iron deficiency anaemia should be the subject of further discussion.
Callum B Pearce is financially supported by Fresenius Ltd.
Editor,—Pearce et alraise the possibility of using the endomysial antibody (EMA) test instead of histology of small bowel biopsies as a test for coeliac disease in the investigation of iron deficiency anaemia (IDA). They wish to consider this because of the considerable resource implications for histology departments.
The EMA test is excellent but its value is dependent on the prevalence of coeliac disease in the population being tested (the pre-test probability). Based on all peer reviewed published studies from 1985 to 1999, we have calculated specificity to be 98.4 % (95% confidence interval (CI) 98.0–98.8) and sensitivity to be 93.8% (95% CI 92.7–94.9).1-1 These give a likelihood ratio for a positive test of 59 and for a negative test of 0.06. We have found that the prevalence of coeliac disease in IDA is 4%. Thus using the Fagan nomogram, if the EMA test is positive, the post-test probability of coeliac disease is 75%—that is, one in four patients with IDA who have a positive EMA test will have normal histology on small bowel biopsy. If the EMA test is negative, the post-test probability is 0.2%, which effectively excludes coeliac disease.
We therefore agree that the EMA test could be used instead of small bowel biopsy to exclude coeliac disease in patients with IDA. However, as most of the cost of obtaining a histological diagnosis may be in the endoscopic examination (during which small bowel biopsies are taken by most gastroenterologists since we validated the technique in 19811-2) and as most patients will be having an endoscopy anyway, it seemed reasonable to us to apply the definitive test (that is, histology) in all those undergoing endoscopy. For those not undergoing endoscopy, such as menstruating women under 45 years, we recommend the EMA test in our guidelines.
We agree that patchiness of mucosal abnormality, which we formally documented in 1976,1-3 needs to be taken into consideration and we routinely take at least four endoscopic biopsies. We realise that this may increase the cost of histology. If after a proper cost benefit study histology is found to be excessively expensive, consideration could be given to immediate stereomicroscopic assessment of biopsies which was popular in the 1960s and early 1970s,1-4 1-5 and which we still apply when time allows. This is a very simple technique which allows visualisation at a glance of the whole surface of biopsies as well as helping to unfold and correctly orientate the specimens before fixation if histology is still deemed necessary. However, both this and high resolution endoscopy need experience for correct interpretation and would also need good quality photography for a permanent record if fixed biopsies were not stored.
In conclusion, we agree that the EMA test is a reasonable alternative to exclude coeliac disease in IDA but until we have a proper cost benefit study indicating otherwise, we recommend histology of endoscopic small bowel biopsies when endoscopy is already being undertaken.