Use of the National Institutes of Health Consensus Guidelines Improves the Diagnostic Sensitivity of Gastrointestinal Graft-Versus-Host Disease

Cardona, Diana M.; Detweiler, Claire J.; Shealy, Michael J.; Sung, Anthony D.; Wild, Daniel; Poleski, Martin; Balmadrid, Bryan; Howell, David N.; Sullivan, Keith M.

doi:10.5858/arpa.2017-0054-oa

Cited by 6 publications

(6 citation statements)

References 42 publications

(27 reference statements)

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“…12,17,18 Furthermore, we used the GI-GVHD histological In a previous adult patient study, with a design similar to our study, 64% of the endoscopies with histopathology-based non-GI-GVHD diagnosis in CSHA were reclassified as GI-GVHD in a re-evaluation. 37 The corresponding result in our study was 48%.…”

supporting

confidence: 65%

Diagnostic disagreement between clinical standard histopathological‐ and retrospective assessment of histopathology‐based gastrointestinal graft‐versus‐host disease in children

Mårtensson

Szakos

Mellgren

et al. 2020

Pediatric Transplantation

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supporting

confidence: 65%

Diagnostic disagreement between clinical standard histopathological‐ and retrospective assessment of histopathology‐based gastrointestinal graft‐versus‐host disease in children

Mårtensson

Szakos

Mellgren

et al. 2020

Pediatric Transplantation

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“…The normal number of crypt apoptotic bodies in small intestinal mucosa is controversial, though for the purposes of graft-versus-host-disease diagnosis, the National Institutes of Health consensus statements suggests 1 per biopsy fragment [14]. This value is highly sensitive, though not specific for graft-versus-host disease [15, 16].…”

Section: Introductionmentioning

confidence: 99%

“…Despite this confusion about the threshold, excessive crypt apoptosis is abnormal and is associated with certain disease states, such as graft-versus-host disease, acute cellular rejection in small bowel allografts, and medication injury, such as in patients with toxicity due to mycophenolate mofetil [16, 17]. Apoptosis in intestinal crypts has been demonstrated in biopsies of active celiac disease by a variety of methods, including nick-end labelling assays [15, 17] and immunohistochemistry for epithelial apoptosis markers [18–20]. Studies have shown an increase in the degradation end products of apoptosis (i.e.…”

Section: Introductionmentioning

confidence: 99%

An association between crypt apoptotic bodies and mucosal flattening in celiac disease patients exposed to dietary gluten

et al. 2019

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Background Celiac disease (CD) is characterized histologically by inflammation and villous atrophy. Villous atrophy is thought to result from a disruption of epithelial cellular proliferation and death. Epithelial cells in intestinal mucosa normally proliferate in the crypts and migrate towards the lumen, eventually dying. Apoptotic bodies in crypts are usually abnormal and are associated with certain disease states. The presence of crypt apoptosis in celiac disease has not been thoroughly examined by routine histologic assessment of crypt apoptotic body count (ABC). Methods We quantified the ABC in duodenal biopsies from celiac patients before and after initiation of a gluten-free diet (GFD). We examined twenty-three duodenal biopsies from adult patients with celiac disease at diagnosis and following GFD and determined the maximum ABC in 10 consecutive crypts. Fourteen biopsies from heartburn patients served as controls. Results Mean duration between paired biopsies was 2.9 (0.5–8.5) years. Mean maximum ABC in active celiac disease was 5.44 per crypt and decreased to 2.60 with GFD ( p = <.0001). The mean maximum ABC in controls was 1.79, lower than both active celiac disease and GFD ( p = <.0001 and p = .019 respectively). Flat lesions with total villous atrophy (mean: 6.44) showed a higher ABC compared to non-flat lesions (mean: 4.87); p = .04. Conclusions Crypt ABC is markedly elevated in active celiac disease and decreases significantly with GFD, however it does not achieve normalcy. Total villous atrophy is associated with a higher ABC than all other lesions. Crypt apoptosis is likely a significant contributor to villous atrophy in celiac disease and can be appreciated by routine histologic examination.

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“…H&E slides were examined for apoptoses in the surface epithelium and deep crypts/glands. Deep crypt/gland apoptosis was considered increased when there was ≥2 intraepithelial apoptoses per tissue fragment based on the National Institutes of Health consortium guidelines for the histologic diagnosis of GI graft‐versus‐host disease 2,3 . In PrEP patients, the highest apoptotic body count in the surface epithelium and in the deep crypts/glands per tissue fragment was recorded for each biopsy site.…”

Section: Methodsmentioning

confidence: 99%

Markedly increased duodenal villous surface apoptosis in patients taking pre‐exposure prophylaxis (PrEP) against human immunodeficiency virus

Hutchings,

Larson,

Guindi

et al. 2024

Histopathology

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AimsPre‐exposure prophylaxis (PrEP) consists of combination antiretroviral therapy and is increasingly utilized to prevent human immunodeficiency virus (HIV) in high‐risk populations. Two index cases noted during routine care showed markedly increased duodenal villous surface apoptosis in patients on PrEP. We sought to examine the prevalence of this finding and identify any clinicopathologic correlations.MethodsGastrointestinal biopsy specimens from 23 male patients aged 18–40 years taking PrEP and 23 control patients were reviewed. Patients with HIV, inflammatory gastrointestinal diseases, and celiac disease were excluded. Apoptoses were counted on surface epithelium and deep crypts. The highest apoptotic body count per tissue fragment was recorded. Clusters were defined as groups of ≥5 apoptoses. Apoptotic counts between patients taking PrEP and controls were compared using t‐tests.ResultsIn PrEP patients, the median age was 35 years (range 25–40) and 83% (19/23) were white. The control patients were demographically similar (median age: 32 years [range 23–40]; 70% [16/23] white). Duodenal apoptosis in villous surface epithelium was increased in PrEP patients, with 14/23 (60.9%) patients having ≥10 surface apoptoses compared to 2/23 (8.7%) controls (P = 2.1 × 10−3) and 14/23 (61%) having clusters compared to 3/23 (13%) controls (P = 2.0 × 10−3). There was no significant association between increased surface apoptosis or clusters and clinical symptoms or duration of PrEP use.ConclusionMarkedly increased villous surface apoptosis, particularly in clusters, is often seen in the duodenum of patients taking PrEP. Although the mechanism and significance are unknown, knowledge of this peculiar finding may prevent unnecessary additional testing.

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Use of the National Institutes of Health Consensus Guidelines Improves the Diagnostic Sensitivity of Gastrointestinal Graft-Versus-Host Disease

Cited by 6 publications

References 42 publications

Diagnostic disagreement between clinical standard histopathological‐ and retrospective assessment of histopathology‐based gastrointestinal graft‐versus‐host disease in children

Diagnostic disagreement between clinical standard histopathological‐ and retrospective assessment of histopathology‐based gastrointestinal graft‐versus‐host disease in children

An association between crypt apoptotic bodies and mucosal flattening in celiac disease patients exposed to dietary gluten

Markedly increased duodenal villous surface apoptosis in patients taking pre‐exposure prophylaxis (PrEP) against human immunodeficiency virus

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