Histologic Features of Tacrolimus-induced Colonic Injury.
Adolescent
Adult
Aged
Biopsy
Calcineurin Inhibitors
/ adverse effects
Child
Child, Preschool
Chronic Disease
Colitis
/ chemically induced
Colon
/ drug effects
Colonoscopy
Female
Humans
Immunosuppressive Agents
/ adverse effects
Male
Middle Aged
Prognosis
Retrospective Studies
Tacrolimus
/ adverse effects
Young Adult
Journal
The American journal of surgical pathology
ISSN: 1532-0979
Titre abrégé: Am J Surg Pathol
Pays: United States
ID NLM: 7707904
Informations de publication
Date de publication:
01 01 2022
01 01 2022
Historique:
pubmed:
18
6
2021
medline:
15
2
2022
entrez:
17
6
2021
Statut:
ppublish
Résumé
Tacrolimus is a common immunosuppressant used in solid organ transplant recipients. Although most patients develop diarrheal symptoms, data regarding patterns of injury in patients taking tacrolimus are limited. We performed this study to characterize tacrolimus-related features of colonic injury. We retrospectively identified colonic samples from 20 patients receiving tacrolimus monotherapy. Records were reviewed for symptoms, endoscopic findings, other medications, and infections. None of the patients had gastrointestinal infections or used other drugs known to cause colonic injury; none had received mycophenolate within 6 months of presentation. Cases were evaluated for the nature and distribution of inflammation and crypt abnormalities, including distortion, destruction, and apoptosis. Eighteen (90%) patients were solid organ transplant recipients. Seventeen (85%) had gastrointestinal symptoms, particularly diarrhea (75%). More than 50% had endoscopic colitis and 15% had ulcers and/or erosions. Most (90%) cases showed regenerative epithelial changes; apoptotic crypt cells were present in 55% and numerous in 10% of cases. Neutrophilic cryptitis was present in 60% of cases; 35% showed crypt destruction. Plasma cell-rich lamina propria inflammation and crypt distortion were observed in 40% and 25% of cases, respectively. There was no correlation between therapy duration and features of chronic injury. We conclude that tacrolimus can cause symptomatic colitis. Histologic abnormalities are often mild, featuring regenerative crypts and scattered apoptotic debris. However, 40% of symptomatic patients have chronic colitis, most likely reflecting drug-induced immune dysregulation. Pathologists should be aware of these associations because colitis often resolves with decreasing drug dosage rather than treatment directed toward inflammatory bowel disease.
Identifiants
pubmed: 34138798
doi: 10.1097/PAS.0000000000001761
pii: 00000478-202201000-00020
doi:
Substances chimiques
Calcineurin Inhibitors
0
Immunosuppressive Agents
0
Tacrolimus
WM0HAQ4WNM
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
118-123Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.
Références
Ponticelli C, Passerini P. Gastrointestinal complications in renal transplant recipients. Transplant Int. 2005;18:643–650.
Altiparmak MR, Trablus S, Pamuk ON, et al. Diarrhoea following renal transplantation. Clin Transplant. 2002;16:212–216.
Sarkio S, Halme L, Kyllönen L, et al. Severe gastrointestinal complications after 1,515 adult kidney transplantations. Transpl Int. 2004;17:505–510.
Troppmann C, Papalois BE, Chiou A, et al. Incidence, complications, treatment, and outcome of ulcers of the upper gastrointestinal tract after renal transplantation during the cyclosporine era. J Am Coll Surg. 1995;180:433–443.
Keown P, Hayry P, Morris P, et al. A blinded, randomized clinical trial of mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation. Transplantation. 1996;61:1029–1037.
Shields P, Neuberger JM Ginns LC, Cosimi AB, Morris PJ, Malden MA. Gastroenterologic considerations of organ transplantation. Transplantation. Oxford: Blackwell Science; 1999:628–650.
Pirsch JD, Miller J, Deierhoi MH, et al. A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. Transplantation. 1997;63:977–983.
Fisher A, Schwartz M, Mor E, et al. Gastrointestinal toxicity associated with FK 506 in liver transplant recipients. in. Transplant Proc. 1994;26:3106–3107.
Star KV, Ho VT, Wang HH, et al. Histologic features in colon biopsies can discriminate mycophenolate from GVHD-induced colitis. Am J Surg Pathol. 2013;37:1319–1328.
Selbst MK, Ahrens WA, Robert ME, et al. Spectrum of histologic changes in colonic biopsies in patients treated with mycophenolate mofetil. Mod Pathol. 2009;22:737–743.
US Multicenter FK506 Liver Study Group. A Comparison of tacrolimus (FK 506) and cyclosporine for immunosuppression in liver transplantation. N Engl J Med. 1994;331:1110–1153.
Lazenby A, Yardley F, Giardillo FM, et al. Lymphocytic (“microscopic”) colitis: a comparative histopathologic study with particular reference to collagenous colitis. Hum Pathol. 1989;20:18–28.
Coyne JD, Campbell F. Microscopic features associated with mycophenolate mofetil in gastric and colonic biopsies. Histopathology. 2012;61:993–997.
Pittman ME, Jessurun J, Yantiss RK. Differentiating posttransplant inflammatory bowel disease and other colitides in renal transplant patients. Am J Surg Pathol. 2017;41:1666–1674.
Kino T, Hatanaka H, Hashimoto M, et al. FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics. J Antibiot (Tokyo). 1987;40:1249–1255.
Thomson AW, Bonham CA, Zeevi A. Mode of action of tacrolimus (fk506): Molecular and cellular mechanisms. Ther Drug Monit. 1995;17:584–591.
Gabe SM, Bjarnason I, Tolou-Ghamari Z, et al. The effect of tacrolimus (FK506) on intestinal barrier function and cellular energy production in humans. Gastroenterology. 1998;115:67–74.
Mayer AD, Dmitrewski J, Squifflet JP, et al. Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European tacrolimus multicenter renal study group. Transplantation. 1997;64:436–443.
Sher LS, Makowka L. A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression in liver transplantation. The U.S. Multicenter FK506 Liver Study Group. N Engl J Med 1994;331:1110-1115. Hepatology. 1995;22:996–997.
European FK506 Multicentre Liver Study Group. Randomised trial comparing tacrolimus (FK506) and cyclosporin in prevention of liver allograft rejection. Lancet. 1994;344:423–428.
Sigal NH, Lin CS, Siekierka JJ. Inhibition of human T-cell activation by FK 506, rapamycin, and cyclosporine A. Transpl Proc. 1991;23(suppl 2):1–5.
Jiang H, Suguo H, Takahara S, et al. Combined immunosuppressive effect of FK 506 and other immunosuppressive agents on PHA- and CD3-stimulated human lymphocyte proliferation in vitro. Transpl Proc. 1991;23:2933–2936.
Charlton M, Levitsky J, Aqel B, et al. International liver transplantation society consensus statement on immunosuppression in liver transplant recipients. Transplantation. 2018;102:727–743.
Kurnatowska I, Banasiak M, Daniel P, et al. Two cases of severe de novo colitis in kidney transplant recipients after conversion to prolonged-release tacrolimus. Transpl Int. 2010;23:553–558.
Saeed SA, Integlia MJ, Pleskow RG, et al. Tacrolimus-associated eosinophilic gastroenterocolitis in pediatric liver transplant recipients: role of potential food allergies in pathogenesis. Pediatr Transplant. 2006;10:730–735.
Gioco R, Puzzo L, Pantane M, et al. Post-transplant colitis after kidney transplantation: clinical, endoscopic and histological features. Aging. 2020;12:24702–24709.
Kochhar G, Singh T, Lopez R, et al. Impact of de novo and preexisting inflammatory bowel disease on the outcome of orthotopic liver transplantation. Inflamm Bowel Dis. 2016;22:1670–1678.
Schorle H, Holtschke T, Hünig T, et al. Development and function of T cells in mice rendered interleukin-2 deficient by gene targeting. Nature. 1991;352:621–624.
Haagsma EB, Van Den Berg AP, Kleibeuker JH, et al. Inflammatory bowel disease after liver transplantation: the effect of different immunosuppressive regimens. Aliment Pharmacol Ther. 2003;18:33–44.
Verdonk RC, Dijkstra G, Haagsma EB, et al. Inflammatory bowel disease after liver transplantation: risk factors for recurrence and de novo disease. Am J Transplant. 2006;6:1422–1429.
Nannegari V, Roque S, Rubin DT, et al. A review of inflammatory bowel disease in the setting of liver transplantation. Gastroenterol Hepatol. 2014;10:626–630.