Journal of Crohn's and Colitis, 2015, 428 doi:10.1093/ecco-jcc/jjv043 Advanced Access publication March 4, 2015 Letter to the Editor

Letter to the Editor Histological Remission in Inflammatory Bowel Disease: Where Are We, and Where Are We Going? Vincenzo Villanacci,a Gabrio Bassotti,b Cord Langnerc Institute of Pathology, Spedali Civili, Brescia Italy bGastroenterology Section, Department of Medicine, University of Perugia School of Medicine, Perugia, Italy cInstitute of Pathology, Medical University of Graz, Graz, Austria


Corresponding author: Gabrio Bassotti, MD PhD, Department of Medicine, University of Perugia, Ospedale Santa Maria della MIsericordia, Piazzale Menghini 1, 06156 San Sisto, Perugia, Italy. Tel:+39-075-5784423; fax: +39-075-584-7570; Email: [email protected]

We read with great interest the excellent review of Bryant et al.1 on histological remission in inflammatory bowel disease [IBD]. However, some concepts remain still unexplained. In fact, as reported in our2 and in other authors’ experience,3 one of the main problems is represented by the absence of a validated, correct histopathological evaluation of the colonic mucosa indicative of the so called ‘mucosal healing’. In particular, in their ‘appraisal’ paragraph, the authors highlight that ‘the histological treatment target for UC [ulcerative colitis] or CD [Crohn’s disease] is to: a] induce absence of neutrophils [both in the crypts and the lamina propria]; b] induce the absence of basal plasma cells and ideally reduce lamina propria plasma cells to normal; c] reduce lamina propria eosinophils to normal’. In our opinion the above sentences need some clarification: a] the first point is absolutely shareable and we agree that the presence of neutrophils in the crypts and in the lamina propria are actual markers of disease activity, such as in the stomach; b] as indicated in the ECCO ESP Statement 10,4 the presence of basal plasma cells in the histological evaluation of colonic mucosa has a high predictive value for the first diagnosis of IBD [EL 3]. We recently5 demonstrated that this feature, in addition to the presence of eosinophils intermingled with basal plasma cells in the same anatomical position, has an high predictive value for the first diagnosis of IBD and is present in all phases of the disease, either in the active or in the quiescent phases, as a marker of an ‘inflammatory bowel disease’. Thus, we feel that the hypothesised requirement of absence of basal plasma cells in the so-called ‘mucosal healing’ of IBD is contradictory, because the presence of basal plasma cells in this phase of the disease is also a sign of the pre-existent IBD.

Finally, we want to highlight at a glance some concepts on this topic that can aid the pathologist in routine practice: a] the presence or absence of neutrophils should be considered the hallmark for the differentiation between the active and the quiescent [resolving] phase of the disease, as expression of the efficacy of the therapy [mucosal healing]; b] to reach an higher inter-observer agreement among different pathologists, it is necessary to avoid any form of morphological score in the evaluation of colonic mucosa because, as widely demonstrated in the review also, these are extremely complicated and subjective. In conclusion, we hope that in the near future 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.

References 1. Bryant RV, Winer S, Spl T, Riddell RH. Systematic review: Histological remission in inflammatory bowel disease. Is ‘complete’ remission the new treatment paradigm? An IOIBD initiative. J Crohns Colitis 2014;8:1582–97. 2. Villanacci V, Antonelli E, Geboes K, et al. Histological healing in inflammatory bowel disease: a still unfulfilled promise. World J Gastroenterol 2013;19:968–78. 3. Mosli MH, Feagan BG, Zou G, et  al. Reproducibility of histological assessments of disease activity in UC. Gut 2015;64:458. 4. Magro F, Langner C, Driessen A, et al. European consensus on the histopathology of inflammatory bowel disease. J Crohn’s Colitis 2013;7:827–51. 5. Villanacci V, Antonelli E, Reboldi G, Salemme M, Casella G, Bassotti G. Endoscopic biopsy samples of naïve “colitides” patients: Role of basal plasmacytosis. J Crohns Colitis 2014;8:1438–43.

Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: [email protected]


Histological remission in inflammatory bowel disease: where are we, and where are we going?

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