Background/Aims: Diarrhea developing in patients under immunosuppression has a variety of underlying causes. A broad spectrum of histological findings can be found in intestinal biopsies taken for the diagnostic workup of diarrhea including a pathologically increased proportion of epithelial cell apoptosis in the colon, for which the descriptive term ‘apoptotic colonopathy' was coined. In recent years, the immunosuppressive drug mycophenolate (mycophenolic acid, MPA) has been identified as a prototypical cause of apoptotic colonopathy, but other conditions may show similar or overlapping histological pictures. Methods: Cases of likely or possible MPA colonopathy (n = 18) were retrospectively identified from the archive files. Clinical information on patient history, clinical presentation and endoscopic findings were recorded. All cases were routinely processed, i.e. stained by hematoxylin and eosin (HE) stain, optionally supplemented by special histochemical and immune stains. Results and Conclusion: Histopathological hallmarks of MPA treatment-related changes in the colon mucosa are reviewed with respect to the major histopathological differential diagnoses including normal and near-normal findings, infectious diseases, graft-versus-host disease and inflammatory bowel diseases. Furthermore, the challenge of multiple concomitant pathologies while on MPA treatment, in particular infectious diseases, is discussed, and some open questions concerning the effects of MPA on colon pathology are pointed out.

1.
Lee FD: Importance of apoptosis in the histopathology of drug related lesions in the large intestine. J Clin Pathol 1993;46:118-122.
2.
Driman DK, Preiksaitis HG: Colorectal inflammation and increased cell proliferation associated with oral sodium phosphate bowel preparation solution. Hum Pathol 1998;29:972-978.
3.
Nguyen T, Park JY, Scudiere JR, Montgomery E: Mycophenolic acid (Cellcept® and Myofortic®) induced injury of the upper GI tract. Am J Surg Pathol 2009;33:1355-1363.
4.
Papadimitriou JC, Cangro CB, Lustberg A, Khaled A, Nogueira J, Wiland A, Ramos E, Klassen DK, Drachenberg CB: Histologic features of mycophenolate mofetil-related colitis: a graft-versus-host disease-like pattern. Int J Surg Pathol 2003;11:295-302.
5.
Parfitt JR, Driman DK: Pathological effects of drugs on the gastrointestinal tract: a review. Hum Pathol 2007;38:527-536.
6.
Selbst MK, Ahrens WA, Robert ME, Friedman A, Proctor DD, Jain D: Spectrum of histologic changes in colonic biopsies in patients treated with mycophenolate mofetil. Mod Pathol 2009;22:737-743.
7.
Allison AC, Eugui EM: Mechanisms of action of mycophenolate mofetil in preventing acute and chronic allograft rejection. Transplantation 2005;80:S181-S190.
8.
Behrend M, Braun F: Enteric-coated mycophenolate sodium: tolerability profile compared with mycophenolate mofetil. Drugs 2005;65:1037-1050.
9.
Behrend M: Adverse gastrointestinal effects of mycophenolate mofetil: aetiology, incidence and management. Drug Saf 2001;24:645-663.
10.
Parfitt JR, Jayakumar S, Driman DK: Mycophenolate mofetil-related gastrointestinal mucosal injury: variable injury patterns, including graft-versus-host disease-like changes. Am J Surg Pathol 2008;32:1367-1372.
11.
Lee S, de Boer WB, Subramaniam K, Kumarasinghe MP: Pointers and pitfalls of mycophenolate-associated colitis. J Clin Pathol 2012, E-pub ahead of print.
12.
Dalle IJ, Maes BD, Geboes KP, Lemahieu W, Geboes K: Crohn's-like changes in the colon due to mycophenolate? Colorectal Dis 2005;7:27-34.
13.
Shulman HM, Kleiner D, Lee SJ, Morton T, Pavletic SZ, Farmer E, Moresi JM, Greenson J, Janin A, Martin PJ, McDonald G, Flowers ME, Turner M, Atkinson J, Lefkowitch J, Washington MK, Prieto VG, Kim SK, Argenyi Z, Diwan AH, Rashid A, Hiatt K, Couriel D, Schultz K, Hymes S, Vogelsang GB: Histopathologic diagnosis of chronic graft-versus-host disease: National Institutes of Health Consensus Development Project on criteria for clinical trials in chronic graft-versus-host disease: II. Pathology Working Group report. Biol Blood Marrow Transplant 2006;12:31-47.
14.
Daniels JA, Lederman HM, Maitra A, Montgomery EA: Gastrointestinal tract pathology in patients with common variable immunodeficiency (CVID): a clinicopathologic study and review. Am J Surg Pathol 2007;31:1800-1812.
15.
Akram S, Murray JA, Pardi DS, Alexander GL, Schaffner JA, Russo PA, Abraham SC: Adult autoimmune enteropathy: Mayo Clinic Rochester experience. Clin Gastroenterol Hepatol 2007;5:1282-1290.
16.
Byers RJ, Marsh P, Parkinson D, Haboubi NY: Melanosis coli is associated with an increase in colonic epithelial apoptosis and not with laxative use. Histopathology 1997;30:160-164.
17.
Weber A, Boger R, Vick B, Urbanik T, Haybaeck J, Zoller S, Teufel A, Krammer PH, Opferman JT, Galle PR, Schuchmann M, Heikenwalder M, Schulze-Bergkamen H: Hepatocyte-specific deletion of the antiapoptotic protein myeloid cell leukemia-1 triggers proliferation and hepatocarcinogenesis in mice. Hepatology 2010;51:1226-1236.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.