Coeliac disease

C oeliac disease (CD) is a gluten dependent enteropathy with a very high prevalence and an increased mortality rate. Our knowledge regarding the clinical and pathogenetic aspects of CD has increased considerably over the past few years, but its diagnosis today—like several decades ago—is still based on the biopsy confirmed presence of duodenal–jejunal mucosal lesions that improve after a gluten free diet. Although the greatest diagnostic challenge in CD concerns the identification of patients to be subjected to intestinal biopsy, rather than the choice of histopathological criteria, it is believed that the currently used criteria are often the source of disagreement between pathologists and clinicians and, at times, of misdiagnosis for the patients. Based on the dynamic development pattern of coeliac lesions and on the frequent finding of cases of CD with mild lesions, Marsh proposed a four stage grading, namely: (1) type 1 infiltrative lesions, characterised by normal mucosal architecture with an increased number of intraepithelial lymphocytes (IELs); (2) type 2 hyperplastic lesions, characterised by an increase in crypt depth without villous flattening; (3) type 3 destructive lesions, characterised by villous atrophy and crypt hypertrophy; and (4) type 4 hypoplastic lesions, characterised by villous atrophy with normal crypt height and IEL count. Oberhuber and colleagues subsequently proposed a new standardised report scheme, based on the Marsh classification, in which stage 3 was split further into 3a, 3b, and 3c, characterised by mild villous flattening, marked villous flattening, and completely flat mucosa, respectively. At present, the Marsh classification of intestinal coeliac lesions, as modified by Oberhuber et al, is used by most pathologists to evaluate the intestinal lesions of patients with CD, both for diagnosis and to assess the regression of the lesions after a gluten free diet. There is no doubt about the efficacy of the Marsh–Oberhuber grading system. It is more than conceivable that, considering the broad spectrum of lesions possibly present in CD and reflecting their pattern of progression, it is valid under optimal clinical conditions. Nevertheless, we are concerned about the preservation of this validity in day to day clinical practice and with respect to the individual patient; that is, we are worried about its effectiveness and efficiency under these circumstances. An analysis based on many years of clinical experience reveals a series of theoretical and above all practical problems. As far as the first are concerned, it is known that the greater the number of diagnostic categories of a method the lower the interobserver and intraobserver agreement, with a consequent reduction in its diagnostic reproducibility. This reduction, in turn, reflects indirectly, but to a considerable extent, on the accuracy of any diagnostic method. Although it is true that a highly reproducible method or criterion is not necessarily accurate, it is also true that a non-reproducible method or criterion cannot be accurate. Therefore, a simpler grading system would be expected to minimise any disagreement between pathologists and to facilitate the comparison between serial biopsy specimens in the follow up of treated patients.