Histological spectrum of mycophenolate mofetil‐related colitis: association with apoptosis

Liapis, George; Boletis, John; Skalioti, Chrysanthi; Bamias, G; Tsimaratou, Katerina; Patsouris, Efstratios; Delladetsima, Ioanna

doi:10.1111/his.12222

Cited by 83 publications

(72 citation statements)

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“…The remaining diagnostic divergences were mostly due to unresolved differential diagnoses, especially viral infection (such as CMV and adenovirus) and therapy-related toxicity, which may produce histological features similar to those of GvHD [11,18]. This underscores the need for microbiological and immunohistological studies.…”

Section: Discussionmentioning

confidence: 99%

“…Discrepancies may be marginal when pathologists from single or cooperating institutions have an opportunity to adjust each other's diagnostic criteria [5,20], but when there is no such exchange of experience, they could more profoundly affect inter-institutional reproducibility [19,24]. Additionally, other diagnostic considerations include infection [2,3] and toxic side effects of applied therapies [11,18], which are both frequent in patients after HCT and could mimic GvHD histologically as well as clinically.…”

Section: Introductionmentioning

confidence: 99%

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Consensus diagnostic histopathological criteria for acute gastrointestinal graft versus host disease improve interobserver reproducibility

et al. 2015

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Graft versus host disease (GvHD) is a clinically important complication after allogeneic hematopoietic stem cell transplantation (HSCT). Its diagnosis relies on clinical and histopathological findings. In order to evaluate and improve inter-institutional diagnostic agreement on histological diagnosis and grading of acute gastrointestinal GvHD, we conducted a round robin test, which included 33 biopsies from 23 patients after HSCT. Five pathologists from different institutions independently evaluated the original sections from the biopsies submitted for diagnosis. Based on their results, consensus qualitative criteria for the assessment of typical histological features of GvHD (e.g., apoptosis, crypt destruction, mucosa denudation) were proposed, including detailed descriptions as well as histological images. In a second round robin test with involvement of the same pathologists, the reproducibility of both diagnosis and grading had improved. Remaining differences were mostly related to differential diagnostic considerations, including viral infection or toxic side effects of medication, which should be resolved by integrating histopathological findings with proper clinical information.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Consensus diagnostic histopathological criteria for acute gastrointestinal graft versus host disease improve interobserver reproducibility

et al. 2015

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“…Apoptosis-based approaches, for example, are confounded by a number of commonly used drugs may be associated with variable intensities of apoptosis [2]. Among these drugs are proton pump inhibitors (PPIs) [43], mycophenolate mofetil [44–47], non-steroidal anti-inflammatory drugs (NSAIDs) [48], and sodium phosphate bowel preparation [27]. Some infections may be associated with apoptosis, notably cytomegalovirus (CMV) [2,49,50].…”

Section: Discussionmentioning

confidence: 99%

Graft-versus-Host Disease of the Gut: A Histologic Activity Grading System and Validation

Myerson

Steinbach

Gooley

et al. 2017

Biology of Blood and Marrow Transplantation

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The pathologic interpretation of gut biopsies in hematopoietic cell transplant recipients to assess graft-versus-disease (GVHD) is well accepted and supplements clinical and endoscopic findings. However, the histologic activity grading of GVHD is controversial, with attempts to predict prognosis or response to treatment largely unsuccessful. GVHD is being diagnosed earlier in its course, raising the possibility that the pathologic grading system can be profitably modified. We have developed a histologic activity grading system designed to replace the commonly used modified-Lerner grading systems. Our system stratifies the low-level Lerner grade I category into 4 activity grade categories, based on the average frequency of apoptotic cells. The results are expressed as ordinal categories, GVHD of minimal, mild, moderate, severe histologic activity, or severe histologic activity with destruction (activity grades 1–5). In a retrospective study, 87 consecutive cases with 201 post-transplant specimens (median 48 days, range 18–1479 days) of stomach, duodenum, and colorectum, which had been activity graded at the time of the original diagnosis, were studied. Most of the biopsies diagnosed as GVHD were low grade—minimal (11%) or mild (71%) histologic activity. We hypothesized that the higher activity grades should be associated with more therapeutic intervention. The odds of increased therapy in the combined all-site specimens were increased as the activity grade increased [odds ratio (OR) = 2.9 (1.9–4.5), p=<.0001]. Thus, our grading system was validated. To investigate whether the activity grade was associated with therapy within the formerly undivided Lerner grade I category, the analysis was restricted to these 174 all-site specimens. The validation result was similar [OR = 3.1 (1.3–7.2), p=.009]. This result interestingly suggests that there is useful information hidden in the Lerner grade I category which could potentially guide immediately actionable treatment decisions. This histologic activity grade system has been in use at our institution for over 2 years, with good acceptance.

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“…10 However, the most common adverse effect of mycophenolate seen among transplant recipients is watery afebrile diarrhea, with an incidence rate of 36% in these patients. 11 Acute rejection risk and de novo donorspecific antibody formation may increase if the dose of the immunosuppressive agent is reduced in an inappropriate way.…”

Section: Discussionmentioning

confidence: 99%

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Ensaroğlu

Harmancı²,

Öcal³

et al. 2015

Exp Clin Transplant

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Objectives: We aimed to investigate the colonoscopy findings in patients after kidney transplant. Materials and Methods: We retrospectively analyzed kidney transplant patients who had colonoscopy examinations for various indications between 2011 and 2015. Results: Eighty-one patients (25 women and 56 men) with a mean age of 39 years (range, 18-64 y) were identified. Mean follow-up after transplant was 9 years (range, 1-29 y). The most common indications for colonoscopy were diarrhea (41%), anemia (29%), gastrointestinal bleeding (12%), abdominal pain (12%), and unexplained weight loss (6%). Either colitis or ileitis or both were diagnosed in 20 patients (25%), whereas polyps were found in 9 patients (11%). One patient presented with hematochezia, which was diagnosed as cytomegalovirus colitis. The remaining cases of colitis or ileitis were diagnosed as nonspecific inflammation. Indications for colonoscopy were not correlated with age, duration after transplant, or use of immunosuppressive drugs. A subgroup analysis for mycophenolate-induced colitis found that 88% of patients used mycophenolate, but presence of colitis or ileitis had no statistical correlation with its use. In patients with poor gastrointestinal symptoms, the only significant predictor of presence of colitis or ileitis was a high C-reactive protein value (> 5 mg/dL; P = .02). Conclusions:Incidence of colitis and/or ileitis is a relatively common finding in patients after kidney transplant. Opportunistic infections, mycophenolate use, and mild degree of indeterminate colitis or ileitis disease may be the underlying condition. Cytomegalovirus infection should be screened in all recipients because it may cause serious complications or death in chronically immunocompromised patients.

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Histological spectrum of mycophenolate mofetil‐related colitis: association with apoptosis

Abstract: The diagnostic hallmark of MMF-related colitis is an IBD-like histological pattern in association with increased epithelial apoptosis, while apoptotic cell death seems to be a potential pathogenetic factor of mucosa injury.

Cited by 83 publications

References 44 publications

Consensus diagnostic histopathological criteria for acute gastrointestinal graft versus host disease improve interobserver reproducibility

Consensus diagnostic histopathological criteria for acute gastrointestinal graft versus host disease improve interobserver reproducibility

Graft-versus-Host Disease of the Gut: A Histologic Activity Grading System and Validation

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