Graft-versus-host disease-like features in mycophenolate mofetil-related colitis

Papadimitriou, J; Beskow, Christian O.; Cangro, Charles B.; Wiland, Anne; Klassen, David K.; Weir, Matthew R.; Bartlett, Stephen T.

doi:10.1016/s0041-1345(01)01951-0

Cited by 49 publications

(36 citation statements)

References 6 publications

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“…Specifically, histologic features of mycophenolate mofetil-related colitis, including the presence of focal colonic ulceration, marked apoptosis, and mixed inflammation, were not observed in the 9 cases in our study in which symptoms improved following therapy. 15,16 The histologic grading of GI GVHD was initially described by Lerner et al, 4 and GVHD1 refers to the presence of ''isolated apoptotic cells without crypt loss.'' 4 The minimum diagnostic criteria for GVHD varies by institution, and some diagnose GVHD in the presence of a single apoptotic body/ biopsy piece, 2 a rather low threshold given the observance of apoptosis in normal bowel biopsies.…”

Section: Threshold Of Gvhd1mentioning

confidence: 99%

Clinicopathologic Threshold of Acute Colorectal Graft-versus-Host Disease

Gomez

Arai²,

Higgins³

et al. 2016

Archives of Pathology &Amp; Laboratory Medicine

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Colon biopsies are often used to determine the presence and severity of acute gastrointestinal graft-versus-host disease following bone marrow transplant.Context.— To establish a threshold consensus within our institution on the number of crypt apoptotic bodies (CAB) indicative of grade 1 acute colorectal graft-versus-host disease, we retrospectively reviewed colon biopsies from posttransplant patients and incorporated clinical and endoscopic findings to validate recently proposed minimum criteria for grade 1 graft-versus-host disease as 7 or more CAB per 10 contiguous crypts.Objective.— Eighty-one biopsies performed for suspected graft-versus-host disease from 74 individual patients were initially stratified based on their prior (prestudy) diagnoses: no significant abnormality, grade 1 graft-versus-host disease, and descriptive diagnoses mentioning increased apoptosis. A chart review was performed to assess the clinical and endoscopic impression at the time of biopsy and to determine the subsequent management and outcome.Design.— Twenty-six biopsies with an average of 3 CAB were considered true-negative cases, and 32 biopsies with an average of 9.75 CAB were considered true-positive cases (t = 3.95999, P < .001). True-negative cases had an average density of 1.36 CAB per crypt, and true-positive cases had an average density of 2.97 CAB per crypt (t = 3.950178, P < .001).Results.— A threshold of 7 or more CAB per 10 contiguous crypts promotes appropriate treatment of grade 1 acute graft-versus-host disease after other diagnostic entities are excluded. Although this threshold is 100% specific to grade 1 acute colorectal graft-versus-host disease after other histologic mimics are excluded, this threshold has a low sensitivity (59.4%) as patients with less than 7 CAB per 10 contiguous crypts constitute a heterogeneous group.Conclusions.—

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Section: Threshold Of Gvhd1mentioning

confidence: 99%

Clinicopathologic Threshold of Acute Colorectal Graft-versus-Host Disease

Gomez

Arai²,

Higgins³

et al. 2016

Archives of Pathology &Amp; Laboratory Medicine

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“…Gland dilatation may be seen in acute GVHD but is not specific, particularly in gastric body mucosa in patients who are taking proton pump inhibitors [33]. In more severe cases, granular cytoplasmic debris is present in the gland lumen and ; severe injury at day 20 likely represents GVHD, as effects due to chemotherapy and radiation are typically improving by this time point Cytomegalovirus [37] Increased epithelial cell apoptosis; nuclear inclusions may be sparse May occur concomitantly with GI GVHD Cryptosporidium [38] Increased epithelial cell apoptosis Rarely encountered in biopsies in HSCT population Mycophenolate mofetil [36] Colitis with increased crypt cell apoptosis, focal ulcers, mixed lamina propria inflammatory infiltrate Apoptotic bodies in sites other than colon are suggestive of GVHD Proton pump inhibitors [33] Increased epithelial cell apoptosis in gastric antral mucosa, without inflammation…”

Section: Morphologic Featuresmentioning

confidence: 99%

“…False-positive interpretations may be due to effects of chemotherapeutic conditioning regimens, concomitant infection, and certain drugs such as proton pump inhibitors [33] and mycophenolate mofetil (MMF) [36]. Biopsy specimens taken in the first 20 days after marrow ablation show diffuse apoptosis, rendering the diagnosis of acute GVHD difficult [26].…”

Section: Morphologic Featuresmentioning

confidence: 99%

“…Because the characteristic nuclear inclusions of CMV may be difficult to identify with certainty in some cases, our practice is to obtain immunohistochemical studies for CMV on biopsy specimens with ulcers and granulation tissue, as well as any case with a clinical suspicion of CMV infection. MMF has been reported to cause an active colitis with focal ulcers, marked crypt cell apoptosis, and a mixed lamina propria inflammatory infiltrate [36]. Normal biopsy specimens from sites distant from these lesions should raise the question of MMFassociated colitis rather than GVHD [24].…”

Section: Morphologic Featuresmentioning

confidence: 99%

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Pathology of graft-versus-host disease in the gastrointestinal tract

Washington¹,

Jagasia²

2009

Human Pathology

230

181

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“…Colonic biopsies of patients with mofetil-induced colitis show apoptosis of intestinal gland epithelial cells (12). Intestinal villi atrophy has been reported to be a cause of mofetil-induced diarrhea (13).…”

mentioning

confidence: 99%

Mycophenolate Mofetil and Bronchiectasis in Kidney Transplant Patients: A Possible Relationship

et al. 2006

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Bronchiectasis is a rare acquired condition, generally resulting from long-term chronic pulmonary inflammation. Mycophenolate mofetil (in short, mofetil) is a commonly used immunosuppressant in kidney transplantation. In the literature, there is no report of a relationship between mofetil use and development of bronchiectasis. Five kidney transplant patients developed complaints of cough, dyspnea, and abundant sputum production without apparent cause. Pulmonary complaints started at a range of 0-20 months after the start of mofetil treatment. Lesions were classified as bronchiectasis(-like), based on clinical presentation, chest x-ray, and computed tomography scan. Withdrawal of mofetil greatly relieved pulmonary complaints. Since the first kidney transplantation in our center in 1968, we have had no diagnosis of bronchiectasis in over 1,500 patients without mofetil treatment. These cases suggest an association between mofetil and development of bronchiectasis. Converting mofetil to another immunosuppressive drug should be considered when unexplained pulmonary complaints develop in patients receiving mofetil.

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Graft-versus-host disease-like features in mycophenolate mofetil-related colitis

Cited by 49 publications

References 6 publications

Clinicopathologic Threshold of Acute Colorectal Graft-versus-Host Disease

Clinicopathologic Threshold of Acute Colorectal Graft-versus-Host Disease

Pathology of graft-versus-host disease in the gastrointestinal tract

Mycophenolate Mofetil and Bronchiectasis in Kidney Transplant Patients: A Possible Relationship

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