Clinical Signs, Histology, and CD3‐Positive Cells before and after Treatment of Dogs with Chronic Enteropathies

Chronic inflammatory enteropathies (CIE) in dogs are a group of disorders that are characterized by chronic persistent or recurrent signs of gastrointestinal disease and histologic evidence of mucosal inflammation. These CIEs are classified as either food‐responsive, antibiotic‐responsive, or immunosuppressant‐responsive enteropathy. Patients not clinically responding to immunomodulatory treatment are grouped as nonresponsive enteropathy and dogs with intestinal protein loss as protein‐losing enteropathy. Disease‐independent clinical scoring systems were established in dogs for assessment of clinical disease severity and patient monitoring during treatment. Histopathologic and routine clinicopathologic findings are usually not able to distinguish the subgroups of CIE. Treatment trials are often lengthy and further diagnostic tests are usually at least minimally invasive. Biomarkers that can aid in defining the presence of disease, site of origin, severity of the disease process, response to treatment, or a combination of these would be clinically useful in dogs with CIE. This article summarizes the following biomarkers that have been evaluated in dogs with CIE during the last decade, and critically evaluates their potential clinical utility in dogs with CIE: functional biomarkers (cobalamin, methylmalonic acid, folate, α1‐proteinase inhibitor, immunoglobulin A), biochemical biomarkers (C‐reactive protein, perinuclear anti‐neutrophilic cytoplasmic antibodies, 3‐bromotyrosine, N‐methylhistamine, calprotectin, S100A12, soluble receptor of advanced glycation end products, cytokines and chemokines, alkaline phosphatase), microbiomic biomarkers (microbiome changes, dysbiosis index), metabolomic biomarkers (serum metabolome), genetic biomarkers (genomic markers, gene expression changes), and cellular biomarkers (regulatory T cells). In addition, important performance criteria of diagnostic tests are briefly reviewed.

Section: Discussionmentioning

confidence: 99%

Clinical utility of currently available biomarkers in inflammatory enteropathies of dogs

Heilmann

Steiner

2018

“…In 4 studies of approximately 166 affected dogs (2 studies overlap, making exact enumeration impossible) no significant associations were detected between histopathologic findings and clinical signs, serum biomarkers, response to treatment, or outcome. [1][2][3][4] Another study of 16 spontaneously ill dogs and 9 disease-free controls also failed to detect any significant association. 5 One study of 58 spontaneously ill dogs and 9 disease-free controls reported a significant association between mucosal histopathology and clinical severity as measured by a canine inflammatory bowel disease activity index 6 while another study with 21 spontaneously ill dogs and no controls failed to find such a relationship.…”

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confidence: 93%

Effect of Tissue Processing on Assessment of Endoscopic Intestinal Biopsies in Dogs and Cats

Willard

Moore

Denton

et al. 2010

Background: Prior studies failed to detect significant association between hypoalbuminemia and small intestinal lesions. Hypothesis: Use of pictorial templates will enhance consistency of interpathologist interpretation and identification of intestinal lesions associated with hypoalbuminemia.Animals: Tissues from 62 dogs and 25 cats examined as clinical cases at 7 referral veterinary practices in 4 countries. Methods: Retrospective, observational study. Histopathology slides from sequential cases undergoing endoscopic biopsy were examined by 4 pathologists by pictorial templates. Changes for 9 microscopic features were recorded as normal, mild, moderate or severe, and 2-and 4-point scales were tested for consistency of interpretation. Logistic regression models determined odds ratios (OR) of histologic lesions being associated with hypoalbuminemia while k statistics determined agreement between pathologists on histologic lesions.Results: There was poor agreement (k 5 À0.013 to 0.3) between pathologists, and institution of origin of slides had effect (k 5 1.0 for 3 of 4 lesions on slides from Institution 5) on agreement between pathologists on selected histologic features. Using 2 point as opposed to 4-point grading scale increased agreement between pathologists (maximum k 5 0.69 using 4-point scale versus maximum k 5 1.0 using 2-point scale). Significant association (P 5 .019-.04; 95% OR 5 3.14-10.84) between lacteal dilation and hypoalbuminemia was found by 3 pathologists.Conclusions and Clinical Importance: Substantial inconsistency between pathologists remains despite use of pictorial template because of differences in slide processing. Distinguishing between mild and moderate lesions might be important source of the disagreement among pathologists.

“…Previous longitudinal studies in dogs with inflammatory bowel disease have shown persistent inflammation of the intestines, despite clinical improvement after treatment. 19 In people, Crohn's disease and ulcerative colitis, the 2 major clinical forms of IBD, are associated with a hypercoagulable state 18 and systemic thromboembolism is reported as an important cause of morbidity and mortality in this patient population. [14][15][16][17] Alternative markers of hypercoagulability such as TAT or thrombin generation curves were not assessed in our study but might have been of value in corroborating the TEG findings.…”

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confidence: 99%

Hypercoagulability in Dogs with Protein‐Losing Enteropathy

Goodwin

Goggs

Chan

et al. 2011

Self Cite

106

Background: Dogs with protein-losing enteropathy (PLE) have previously been reported to present with thromboembolism; however, the prevalence and pathogenesis of hypercoagulability in dogs with PLE have not been investigated so far.Hypothesis: Dogs with PLE are hypercoagulable compared with healthy control dogs. Animals: Fifteen dogs with PLE. Thirty healthy dogs served as controls (HC). Methods: A prospective study was performed including 15 dogs with PLE. All dogs were scored using the canine chronic enteropathy activity index (CCECAI). Thromboelastography (TEG) and other measures of coagulation were evaluated. Recalcified, unactivated TEG was performed and reaction time (R), kinetic time (K), alpha angle (a), and maximum amplitude (M A ) values were recorded. Nine dogs were reassessed after initiation of immunosuppressive treatment.Results: All dogs with PLE in the study were hypercoagulable with decreased R ( [33.5-49]) (all P o .001). Median antithrombin (AT) concentration was borderline low in PLE dogs; however, mean serum albumin concentration was severely decreased (mean 1.67 g/dL AE 5.1, reference range 2.8-3.5 g/dL). Despite a significant improvement in serum albumin and CCECAI, all 9 dogs with PLE were hypercoagulable at re-examination.Conclusions and Clinical Importance: The hypercoagulable state in dogs with PLE cannot be solely attributed to loss of AT. Despite good clinical response to treatment, dogs remained hypercoagulable and could therefore be predisposed to thromboembolic complications.