Chronic Enteropathy Clinical Activity Index Research Articles

Platelet indices as biomarkers for characterization and determination of severity in canine chronic enteropathy

Human studies have shown an association between certain platelet indices and active inflammatory bowel disease when compared to healthy controls. The objectives of this retrospective study were to determine if any platelet indices differ between dogs with chronic enteropathies and healthy age- and sex-matched control dogs and are predictive of the severity of chronic enteropathy based on canine chronic enteropathy clinical activity index (CCECAI) scores. Medical records for 22 chronic enteropathy-positive dogs and 22 healthy control dogs were reviewed for historical and physical examination findings, platelet indices, and histologic diagnoses of chronic enteropathy. Platelet indices were compared between the groups, and an association between platelet indices and CCECAI scores in dogs with chronic enteropathy was investigated.Chronic diarrhea and weight loss were common clinical signs associated with chronic enteropathy. Lymphoplasmacytic enteritis was the most common histologic diagnosis. Only one platelet index, platelet component distribution width (P = 0.045), was found to be significantly different between the groups. For predicting severity of disease, determined by CCECAI score, statistically significant differences in indices associated with higher scores were platelet count (P = 0.024) and platelet dry mass distribution width (P = 0.036). Only platelet component distribution width showed potential in characterizing dogs with chronic enteropathy compared to normal dogs. Elevated platelet count and decreased platelet dry mass distribution width had a significant effect on total CCECAI scores. These findings suggest further investigation into the utility of platelet indices as predictors of disease presence and severity in dogs with chronic enteropathy is warranted.

Correlating Gastrointestinal Histopathologic Changes to Clinical Disease Activity in Dogs With Idiopathic Inflammatory Bowel Disease.

Prior studies have failed to detect a convincing association between histologic lesions of inflammation and clinical activity in dogs with inflammatory bowel disease (IBD). We hypothesized that use of a simplified histopathologic scoring system would improve the consistency of interpretation among pathologists when describing histologic lesions of gastrointestinal inflammation. Our aim was to evaluate the correlation of histopathologic changes to clinical activity in dogs with IBD using this new system. Forty-two dogs with IBD and 19 healthy control dogs were enrolled in this retrospective study. Endoscopic biopsies from the stomach, duodenum, ileum, and colon were independently scored by 8 pathologists. Clinical disease activity was scored using the Canine Inflammatory Bowel Disease Activity Index (CIBDAI) or the Canine Chronic Enteropathy Clinical Activity Index (CCECAI), depending on the individual study center. Summative histopathological scores and clinical activity were calculated for each tissue (stomach, duodenum, ileum, and colon) and each tissue histologic score (inflammatory/morphologic feature). The correlation between CCECAI/CIBDAI and summative histopathologic score was significant ( P < .05) for duodenum ( r = 0.42) and colon ( r = 0.33). In evaluating the relationship between histopathologic scores and clinical activity, significant ( P < .05) correlations were observed for crypt dilation ( r = 0.42), lamina propria (LP) lymphocytes ( r = 0.40), LP neutrophils ( r = 0.45), mucosal fibrosis ( r = 0.47), lacteal dilation ( r = 0.39), and villus stunting ( r = 0.43). Compared to earlier grading schemes, the simplified scoring system shows improved utility in correlating histopathologic features (both summative histology scores and select histologic scores) to IBD clinical activity.

Association of fecal calprotectin concentrations with disease severity, response to treatment, and other biomarkers in dogs with chronic inflammatory enteropathies.

BackgroundCalprotectin is a marker of inflammation, but its clinical utility in dogs with chronic inflammatory enteropathies (CIE) is unknown.ObjectiveEvaluation of fecal calprotectin in dogs with biopsy‐confirmed CIE.Animals127 dogs.MethodsProspective case‐control study. Dogs were assigned a canine chronic enteropathy clinical activity index (CCECAI) score, and histologic lesions severity was assessed. Fecal calprotectin, fecal S100A12, and serum C‐reactive protein (CRP) were measured. Food‐ or antibiotic‐responsive cases (FRE/ARE, n = 13) were distinguished from steroid‐/immunosuppressant‐responsive or ‐refractory cases (SRE/IRE, n = 20). Clinical response to treatment in SRE/IRE dogs was classified as complete remission (CR), partial response (PR), or no response (NR).ResultsFecal calprotectin correlated with CCECAI (ρ = 0.27, P = .0065) and fecal S100A12 (ρ = 0.90, P < .0001), some inflammatory criteria, and cumulative inflammation scores, but not serum CRP (ρ = 0.16, P = .12). Dogs with SRE/IRE had higher fecal calprotectin concentrations (median: 2.0 μg/g) than FRE/ARE dogs (median: 1.4 μg/g), and within the SRE/IRE group, dogs with PR/NR had higher fecal calprotectin (median: 37.0 μg/g) than dogs with CR (median: 1.6 μg/g). However, both differences did not reach statistical significance (both P = .10). A fecal calprotectin ≥15.2 μg/g separated both groups with 80% sensitivity (95% confidence interval [95%CI]: 28%‐100%) and 75% specificity (95%CI: 43%‐95%).Conclusions and Clinical ImportanceFecal calprotectin could be a useful surrogate marker of disease severity in dogs with CIE, but larger longitudinal studies are needed to evaluate its utility in predicting the response to treatment.

Effect of Saccharomyces boulardii in dogs with chronic enteropathies: double-blinded, placebo-controlled study

Saccharomyces boulardii is used to treat acute and chronic enteropathies in humans, but to date, no studies have evaluated the use of this yeast in dogs. The current study, a...

Evaluation of Serum 3-Bromotyrosine Concentrations in Dogs with Steroid-Responsive Diarrhea and Food-Responsive Diarrhea.

BackgroundThe clinical usefulness of serum 3‐BrY concentrations for subclassifying dogs with food‐responsive diarrhea (FRD) and steroid‐responsive diarrhea (SRD) has not been studied.Hypothesis/ObjectivesTo compare serum 3‐BrY concentrations in dogs with FRD, dogs with SRD, and healthy control dogs.Animals38 dogs with FRD, 14 dogs with SRD, and 46 healthy dogs.MethodsProspective study. Measurement of 3‐BrY concentration in serum samples was performed by gas chromatography/mass spectrometry.ResultsThere was no association of peripheral eosinophilia in dogs with FRD, SRD, and healthy control dogs (P = 0.069). There was no significant correlation between peripheral eosinophil counts and serum 3‐BrY concentrations (ρ = −0.15, P = 0.13). Serum 3‐BrY concentrations in dogs with SRD (median [range] = 3.27, 0.9–26.23 μmol/L) were significantly higher than in dogs with FRD (median [range] = 0.99, 0.62–8.82 μmol/L; P = 0.007) or in healthy dogs (median [range] = 0.62, 0.62–1.79 μmol/L; P < 0.001). Also, serum 3‐BrY concentrations in dogs with FRD were significantly higher than in healthy dogs (P = 0.025). There was no significant correlation between the canine chronic enteropathy clinical activity index and serum 3‐BrY concentrations (ρ = 0.17, P = 0.23).Conclusions and Clinical ImportanceMeasurement of serum 3‐BrY concentrations, but not the peripheral eosinophil count, is helpful for detecting dogs with SRD and FRD.

Clinicopathologic and prognostic factors in short- and long-term surviving dogs with protein-losing enteropathy.

The aim of the present study was to investigate the differences in the characteristics of short- and long-term surviving dogs with protein-losing enteropathy (PLE) and to identify factors that predict its outcome. We retrospectively reviewed the medical records of 59 client- owned dogs with PLE diagnosed at three different hospitals between January 2009 and November 2013. The dogs were classified as either short-term (= 6 months; STs) or long-term (> 6 months; LTs) survivors. Clinical and clinicopathological variables were investigated between the groups and receiver operating characteristic (ROC) curve analysis was performed. Nineteen dogs were classified as STs and 40 as LTs. Body weight and blood urea nitrogen concentrations were significantly higher in the STs at diagnosis (P < 0.05). At 1 month after initiation of immunosuppressive therapy (data- driven cut-off, T1), chronic canine enteropathy clinical activity index (CCECAI) scores were higher (P < 0.01) and albumin, serum total protein and total cholesterol concentrations were lower (P < 0.01) in the STs. ROC curve analysis showed that CCECAI > 5 evaluated at T1 was the best predictor of poor outcome. Although the severity of clinical signs and the majority of clinicopathological findings at diagnosis did not influence the outcome, survival time was shorter in the dogs with high CCECAI scores at T1 and which did not respond to therapy.

Dietary management of presumptive protein-losing enteropathy in Yorkshire terriers.

To describe the clinical outcome of dietary management of Yorkshire terriers with protein-losing enteropathy without immunosuppressive/anti-inflammatory medications. Records were searched for Yorkshire terriers with hypoalbuminaemia and a clinical diagnosis of protein-losing enteropathy that were managed with diet and without immunosuppressive/anti-inflammatory medications. Serum albumin changes were compared using a one-way repeated measures ANOVA. Canine chronic enteropathy clinical activity index scores were compared using a Wilcoxon signed-rank test. Eleven cases were identified. Clinical signs were variable including: diarrhoea, respiratory signs, vomiting, lethargy and weight loss. Diets fed included home cooked (n=5); Royal Canin Gastrointestinal Low Fat (n=4); Hill's Prescription Diet i/d Low Fat (n=1); or Purina HA Hypoallergenic (n=1). Clinical signs resolved completely in eight dogs, partially resolved in two dogs and failed to respond in one dog. In dogs that responded, albumin significantly improved from baseline (mean 14·9 g/L, sd ±3·7), at 2 to 4 weeks (mean 24·2 g/L, sd ±5·5, P=0·01), and at 3 to 4 months (mean 27·0 g/dL, sd ±5·9, P=0·01). These results indicate that dietary management of protein-losing enteropathy is a potential management strategy in Yorkshire terriers. Randomised clinical trials in Yorkshire terriers with protein-losing enteropathy are necessary to compare success rate, survival and quality of life with dietary management versus combined dietary and immunosuppressive/anti-inflammatory therapy.

Does canine inflammatory bowel disease influence gut microbial profile and host metabolism?

BackgroundInflammatory bowel disease (IBD) refers to a diverse group of chronic gastrointestinal diseases, and gut microbial dysbiosis has been proposed as a modulating factor in its pathogenesis. Several studies have investigated the gut microbial ecology of dogs with IBD but it is yet unclear if this microbial profile can alter the nutrient metabolism of the host. The aim of the present study was to characterize the faecal bacterial profile and functionality as well as to determine host metabolic changes in IBD dogs.Twenty-three dogs diagnosed with IBD and ten healthy control dogs were included. Dogs with IBD were given a clinical score using the canine chronic enteropathy clinical activity index (CCECAI). Faecal short-chain fatty acids (SCFA) and ammonia concentrations were measured and quantitative PCR was performed. The concentration of plasma amino acids, acylcarnitines, serum folate, cobalamin, and indoxyl sulfate was determined.ResultsNo significant differences in the abundance of a selection of bacterial groups and fermentation metabolites were observed between the IBD and control groups. However, significant negative correlations were found between CCECAI and the faecal proportion of Lactobacillus as well as between CCECAI and total SCFA concentration. Serum folate and plasma citrulline were decreased and plasma valine was increased in IBD compared to control dogs. Increased plasma free carnitine and total acylcarnitines were observed in IBD compared with control dogs, whereas short-chain acylcarnitines (butyrylcarnitine + isobutyrylcarnitine and, methylmalonylcarnitine) to free carnitine ratios decreased. Dogs with IBD had a higher 3-hydroxyisovalerylcarnitine + isovalerylcarnitine to leucine ratio compared to control dogs.ConclusionsCanine IBD induced a wide range of changes in metabolic profile, especially for the plasma concentrations of short-chain acylcarnitines and amino acids, which could have evolved from tissue damage and alteration in host metabolism. In addition, dogs with more severe IBD were characterised by a decrease in faecal proportion of Lactobacillus.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-016-0736-2) contains supplementary material, which is available to authorized users.

Safety and efficacy of allogeneic adipose tissue-derived mesenchymal stem cells for treatment of dogs with inflammatory bowel disease: Clinical and laboratory outcomes

Mesenchymal stem cells (MSCs) have shown immunomodulatory and anti-inflammatory effects in experimental colitis, and promising clinical results have been obtained in humans with Crohn's disease and ulcerative colitis. The aim of this study was to determine the safety and feasibility of adipose tissue-derived MSC (ASC) therapy in dogs with inflammatory bowel disease (IBD). Eleven dogs with confirmed IBD received one ASC intravascular (IV) infusion (2 × 106 cells/kg bodyweight). The outcome measures were clinical response based on percentage reduction of the validated Clinical Inflammatory Bowel Disease Activity Index (CIBDAI) and Canine Chronic Enteropathy Clinical Activity Index (CCECAI), as well as normalisation of C-reactive protein (CRP), albumin, folate and cobalamin serum concentrations at day 42 post-treatment. The Wilcoxon test was used to compare variables before and after treatment.No acute reaction to ASC infusion and no side effects were reported during follow-up in any dog. Six weeks post-treatment, the CIBDAI and CCECAI decreased significantly and albumin, cobalamin and folate concentrations increased substantially. Differences in CRP concentrations pre- and post-treatment were not significant (P = 0.050). Clinical remission (defined by a reduction of initial CIBDAI and CCECAI >75%) occurred in 9/11 dogs at day 42. The two remaining dogs showed a partial response with reduction percentages of 69.2% and 71.4%. In conclusion, a single IV infusion of allogeneic ASCs was well tolerated and appeared to produce clinical benefits in dogs with severe IBD.

Urinary and faecal N-methylhistamine concentrations do not serve as markers for mast cell activation or clinical disease activity in dogs with chronic enteropathies.

BackgroundThis study sought to correlate faecal and urinary N-methylhistamine (NMH) concentrations with resting versus degranulated duodenal mast cell numbers in dogs with chronic enteropathies (CE), and investigate correlations between intestinal mast cell activation and clinical severity of disease as assessed by canine chronic enteropathy clinical activity index (CCECAI), and between urinary and faecal NMH concentrations, mast cell numbers, and histopathological scores. Twenty-eight dogs with CE were included. Duodenal biopsies were stained with haematoxylin and eosin (H&E), toluidine blue, and by immunohistochemical labelling for tryptase. Duodenal biopsies were assigned a histopathological severity score, and duodenal mast cell numbers were counted in five high-power fields after metachromatic and immunohistochemical staining. Faecal and urinary NMH concentrations were measured by gas chromatography–mass spectrometry.ResultsThere was no correlation between the CCECAI and faecal or urinary NMH concentrations, mast cell numbers, or histopathological score – or between faecal or urinary NMH concentration and mast cell numbers. Post hoc analysis revealed a statistically significant difference in toluidine blue positive mast cells between two treatment groups (exclusion diet with/without metronidazole versus immunosuppression (IS)), with higher numbers among dogs not requiring IS.ConclusionFaecal and urinary NMH concentrations and duodenal mast cell numbers were not useful indicators of severity of disease as assessed by the CCECAI or histological evaluation. The number of duodenal mast cells was higher in dogs that did not need IS, i.e. in dogs responding to an exclusion diet (with/without metronidazole), than in dogs requiring IS. Further studies comparing the role of mast cells in dogs with different forms of CE are needed.

Association between fecal S100A12 concentration and histologic, endoscopic, and clinical disease severity in dogs with idiopathic inflammatory bowel disease

Idiopathic inflammatory bowel disease (IBD) in dogs can be challenging to diagnose and fecal markers of disease that correlate with its severity could potentially be clinically useful. Surrogate inflammatory markers, such as the concentration of fecal S100A12, are used to detect active IBD in humans. The aim of this study was to determine the relationship between fecal canine S100A12 concentrations and clinical, endoscopic, and histologic disease severity.Twenty-six dogs with IBD and 90 healthy control dogs were enrolled. Spot fecal samples were collected and fecal canine S100A12 concentrations measured by an in-house ELISA. The correlation of fecal canine S100A12 concentrations with clinical disease activity (using the canine chronic enteropathy clinical activity index scoring system) and with endoscopic and histologic disease severity (using semi-quantitative grading systems) was assessed in dogs with IBD.Concentrations of fecal canine S100A12 were significantly higher in dogs with IBD (median [interquartile range]: 223 [21–3477]ng/g) than in healthy controls (median [interquartile range]: 9 [5–31]ng/g; P<0.0001). Fecal canine S100A12 concentrations correlated with the CCECAI score (ρ=0.4778; P=0.0408) and the severity of endoscopic lesions in the duodenum (ρ=0.4703; P=0.0354) and colon (ρ=0.9747; P=0.0144), but not with the severity of histopathologic changes except for inflammatory lesions in the colon (ρ=0.8669; P=0.0230). A concentration of 273ng fecal canine S100A12/g feces or greater distinguished (a) dogs with moderate to severe endoscopic disease in any GI section from dogs with at most mild endoscopic disease, and (b) dogs with very severe clinical disease (i.e., a CCECAI score of ≥12) from dogs with a CCECAI score of <12, with a sensitivity of 71% and 90%, respectively, and a specificity of 89% and 75%, respectively.This study showed that fecal canine S100A12 concentrations are increased in dogs with IBD. Further, this study showed that fecal canine S100A12 is associated with the clinical disease activity, the severity of endoscopic lesions, and the severity of colonic inflammation in dogs with IBD. Fecal S100A12 concentrations are potentially useful as a biomarker of inflammation in dogs with IBD.

Fecal calprotectin concentrations in adult dogs with chronic diarrhea

To evaluate fecal calprotectin concentrations in healthy dogs and dogs with chronic diarrhea, to identify cutoff values for fecal calprotectin concentrations for use in differentiating dogs with chronic diarrhea and a canine chronic enteropathy clinical activity index (CCECAI) < 12 from dogs with chronic diarrhea and a CCECAI ≥ 12, and to evaluate the association between histologic evidence of intestinal mucosal changes and fecal calprotectin concentrations in dogs with chronic diarrhea. Fecal samples from 96 adult dogs (27 dogs with chronic diarrhea and 69 healthy control dogs). Severity of clinical signs was evaluated on the basis of the CCECAI scoring system. Endoscopy was performed in all dogs with chronic diarrhea, and mucosal biopsy specimens were evaluated histologically. Fecal calprotectin concentration was quantified via radioimmunoassay. Fecal calprotectin concentrations were significantly higher in dogs with chronic diarrhea than in healthy control dogs. Fecal calprotectin concentrations were also significantly higher in dogs with a CCECAI ≥ 12, compared with concentrations for dogs with a CCECAI between 4 and 11. Fecal calprotectin concentrations were significantly higher in dogs with chronic diarrhea associated with histologic lesions, compared with concentrations in control dogs, and were significantly correlated with the severity of histologic intestinal lesions. Among dogs with chronic diarrhea, the best cutoff fecal calprotectin concentration for predicting a CCECAI ≥ 12 was 48.9 μg/g (sensitivity, 53.3%; specificity, 91.7%). Fecal calprotectin may be a useful biomarker in dogs with chronic diarrhea, especially dogs with histologic lesions.

Serum cobalamin and methylmalonic acid concentrations in dogs with chronic gastrointestinal disease

To determine the prevalence of hypocobalaminemia or methylmalonic acidemia (or both) in dogs with chronic gastrointestinal disease. Serum samples from 56 dogs with chronic gastrointestinal disease and 43 control dogs. Serum cobalamin and methylmalonic acid (MMA) concentrations were measured in all samples and compared between groups. A correlation between serum cobalamin and MMA concentrations and the canine chronic enteropathy clinical activity index was evaluated via the Spearman rank correlation. 20 of 56 (36%) dogs with gastrointestinal disease had hypocobalaminemia. Serum cobalamin concentrations were significantly lower in dogs with gastrointestinal disease than in control dogs. Five of 56 (9%) dogs with chronic gastrointestinal disease and 5 of 20 (25%) hypocobalaminemic dogs had increased MMA concentrations. There was a significant negative correlation (Spearman r = -0.450) between serum cobalamin and MMA concentrations in dogs with gastrointestinal disease. No correlation was found between the canine chronic enteropathy clinical activity index and serum cobalamin or MMA concentrations. These data indicated the prevalence of hypocobalaminemia in dogs with chronic gastrointestinal disease was 20 of 56 (36%). Five of 20 (25%) hypocobalaminemic dogs had increased serum MMA concentrations, which indicated that although hypocobalaminemia was common in these dogs, it did not always appear to be associated with a deficiency of cobalamin on a cellular level. Hypocobalaminemia is a risk factor for negative outcome in dogs with chronic gastrointestinal disease and should be considered in every patient with corresponding clinical signs.

CD11c + Cells are Significantly Decreased in the Duodenum, Ileum and Colon of Dogs with Inflammatory Bowel Disease

CD11c serves as a marker for human and murine dendritic cells (DCs) and cells expressing this marker have been shown to have similar morphological and functional characteristics in the canine immune system. The aim of this study was to quantify CD11c(+) cells in the duodenum, ileum and colon of healthy dogs and dogs with inflammatory bowel disease (IBD). Endoscopic biopsies from the duodenum (n=12 cases), ileum (n=8 cases) and colon (n=12 cases) were obtained from dogs diagnosed with IBD. Intestinal tissue from 10 healthy beagle dogs was used as control. Immunofluorescence microscopy was carried out using an anti-canine CD11c monoclonal antibody. Labelled cells were recorded as cells per 120,000 μm(2). The canine chronic enteropathy clinical activity index (CCECAI) was calculated for all dogs with IBD. In addition, sections from all dogs with IBD were evaluated according to the guidelines of the World Small Animal Veterinary Association Gastrointestinal Standardization Group. The number of CD11c(+) cells in the duodenum, ileum and colon of dogs with IBD was significantly reduced compared with controls (P<0.01, P<0.01 and P<0.05, respectively). There was a significant negative correlation between the number of CD11c(+) cells in the colon of dogs with IBD and the CCECAI (P=0.044, r(2)=-0.558). Chronic inflammation in canine IBD appears to involve an imbalance in the intestinal DC population. Future studies will determine whether reduced expression of CD11c could be a useful marker for the diagnosis and monitoring of canine IBD.