Letter: histological assessment of disease activity in ulcerative colitis--the problem of score evaluation and validation.

Abstract

We read with interest the excellent review of Marchal Bressenot et al.1 on the histological assessment of disease activity in ulcerative colitis (UC), and would like to express our appreciation for the accurate analysis of the data, focused on four scoring systems.2-5 However, some concepts still remain unexplained. Should histological remission in UC (and also in CD, Crohn's disease) be considered a clinical target, and do we need a standardised histological scoring system for IBD which must be validated, reliable and reproducible? A key point is represented by the absence of a validated histopathological evaluation of the colonic mucosa and the subsequent inappropriate use of terms such as ‘resolving IBD’ or ‘quiescent IBD’ as indicative of so called ‘mucosal healing’.4, 6-8 In fact, pharmacological treatments for UC or CD can cause the disappearance of neutrophils (both in the crypts and the lamina propria). In contrast, the disappearance of basal plasma cells and/or reduction of lamina propria plasma cells, as well as eosinophils (usually strictly associated with the latter), are usually difficult to obtain. Some clarifications are necessary. Firstly, the presence or absence of neutrophils in the crypts (with the consequent development of crypts abscesses) and in the lamina propria are a marker of disease activity. Moreover, the presence of basal plasma cells with morphological features suggestive for IBD has a high predictive value for the first diagnosis of IBD and is considered an important marker, especially in the differential diagnosis with other colitides. This feature, in addition to the presence of eosinophils intermingled with basal plasma cells in the same anatomical position has a high predictive value for the first diagnosis of IBD and is present in all phases of the disease, either in the active and in the quiescent phases as a marker of an ‘IBD’.8, 9 Thus, requirement of absence of basal plasma cells in ‘mucosal healing’ seems to be contradictory, because their presence in this phase of the disease is a sign of pre-existent IBD.8, 9 Similarly, the eosinophils are present in all phases of the disease. For this reason, only the presence or absence of neutrophils should be considered the hallmark differentiating the active from the quiescent (resolving) phase of the disease, as expression of the efficacy of the therapy (histological mucosal healing). Therefore, it is necessary to avoid any form of morphological score, extremely complicated and subjective, to reach the highest inter-observer agreement among different pathologists. The need for a correct methodological approach in the evaluation of colonic biopsies, in addition to the availability of exhaustive clinical and endoscopic data is needed in the daily routine. In this context, the adequate and correctly oriented number of biopsies is of paramount importance (as highlighted in the ECCO statements 4A and 4B).8 We hope that in the near future the histological ‘mucosal healing’ will be considered as a target for therapy in IBD and as an important endpoint of remission that must be achieved together with clinical, laboratory and endoscopic data. Declaration of personal and funding: None.