A Clinical Index for Disease Activity in Cats with Chronic Enteropathy

Background: There is a need for a clinically useful, quantitative index for measurement of disease activity in cats with chronic enteropathy (CE). Objective: To develop a numerical activity index that is of practical value to clinicians treating CE in cats. Animals: Eighty‐two cats with CE. Methods: Retrospective case review of 59 cats diagnosed with inflammatory bowel disease (IBD). Prospective validation study of 23 cats having either IBD or food‐responsive enteropathy (FRE). Multivariate regression analysis was used to identify which combination of clinical and laboratory variables were best associated with intestinal inflammation of IBD. This combination of variables was expressed in a score that was used as an activity index for the prospective assessment of disease activity and of the effect of treatment in cats with IBD or FRE. Results: The combination of gastrointestinal signs, endoscopic abnormalities, serum total protein, serum alanine transaminase/alkaline phosphatase activity, and serum phosphorous concentration had the best correlation with histopathologic inflammation and comprise the feline chronic enteropathy activity index (FCEAI). Positive treatment responses in cats with CE were accompanied by significant (P < .05) reductions in FCEAI scores after treatment. Conclusions and Clinical Importance: The FCEAI is a simple numerical measure of inflammatory activity in cats with CE. The scoring index can be reliably used in the initial assessment of disease severity for both IBD and FRE and as a measure of clinical response to treatment for these disorders.     

Lawsonia intracellularis infection in horses: 2005-2007

Background: Lawsonia intracellularis is an emerging equine pathogen that is a cause of equine proliferative enteropathy (EPE).
Objective: To describe the signalment, month of presentation, common clinical signs, clinicopathologic values, diagnostic tests used, antimicrobial use, and survival status in horses affected with EPE; to evaluate how affected horses sold at public auction as yearlings; and to determine results of fecal polymerase chain reaction (PCR) and serum immunoperoxidase monolayer assay (IPMA) results in age matched, clinically normal herdmates.
Animals: The study group was 57 horses treated for disease associated with L. intracellularis infection between August 2005 and January 2007.
Methods: Retrospective study examined horses exhibiting evidence of infection with L. intracellularis and testing positive for fecal PCR or serum IPMA.
Results: Horses ranged in age from 2 to 8 months with a median age of 6 months, and all were examined between August and January. Ventral edema was present in 81% of horses and hypoalbuminemia occurred in all horses. Only 50% of horses tested positive on both PCR and IPMA. Ninety-three percent of horses survived, and survival was unrelated to antimicrobial administered. Affected horses sold as yearlings an average of 68% less than other yearlings by the same sire. Age matched, clinically normal herdmates also tested positive for L. intracellularis on fecal PCR (6%) and IPMA (33%).
Conclusion: L. intracellularis infection should be considered in young horses with ventral edema and hypoalbuminemia that are examined between August and January. Both fecal PCR and serum IPMA are needed to help determine disease status. Treated animals usually survive, although they do not sell for as high a price at public auction as other yearlings by the same sire. Age matched, clinically normal herdmates also test positive for L. intracellularis on fecal PCR and serum IPMA.     

Blood neutrophil-to-lymphocyte ratio (NLR) as a diagnostic marker in dogs with chronic enteropathy

Few routinely available biomarkers are clinically useful in assessing dogs with chronic enteropathy (CE) and aid in CE subclassification. The diagnostic potential of the blood neutrophil-to-lymphocyte ratio (NLR) has not been evaluated in canine CE. We evaluated the NLR in 93 dogs with CE (no steroid treatment for ≥2 wk prior) and tested for an association with clinical, clinicopathologic, and histologic characteristics and also with CE subclassification. NLR was significantly higher in CE dogs with severe clinical disease than dogs with mild clinical disease (p = 0.047). Hypoalbuminemia (p < 0.001), but not hypocobalaminemia, was associated with higher NLRs. NLR was correlated with fecal alpha₁-proteinase inhibitor concentrations (ρ = 0.47) and the serum-to-fecal alpha₁-proteinase inhibitor ratio (ρ = –0.48; both p < 0.001) but not with serum or fecal inflammatory markers nor with the overall histologic score (all p > 0.05). Dogs with steroid- or other immunosuppressant-responsive (IRE) or nonresponsive enteropathy (NRE) had significantly higher NLRs (median: 7.3) than dogs with food-responsive enteropathy (FRE; median: 3.0; p = 0.003), and a NLR ≥5.5 best distinguished both groups of dogs. No difference in NLR was detected between dogs with IRE and dogs diagnosed with NRE. These findings suggest that leukogram changes (i.e., NLR) could be clinically useful in canine CE, and that neutrophils might play a role in the systemic inflammatory response associated with canine CE. The NLR can be easily assessed on routine hematology and can potentially aid in the subclassification of dogs with CE based on the response to treatment.     

Epizootic rabbit enteropathy: comparison of PCR-based RAPD fingerprints from virulent and non-virulent samples

Epizootic rabbit enteropathy is a gastrointestinal disorder of unknown aetiology of farmed rabbits characterised by inanition and mortality. Genomic analyses of virulent and non-virulent samples of inocula were performed using random amplification of polymorphic DNA (RAPD). Differences in bacterial DNA composition were found between inocula, but specific sequences were not linked with field cases of epizootic rabbit enteropathy.     

Ultrasonographic intestinal muscularis thickening in dogs with histologically confirmed inflammatory bowel disease: 13 cases (2010–2021)

Ultrasonographic intestinal muscularis thickening has not been described as an imaging feature of canine inflammatory bowel disease. In this retrospective case series, patients were identified by searching sonographic reports for “muscularis” and/or “muscular layer.” Patients were included if small intestinal muscularis thickening was reported, and sonographic images and histopathological samples of the small intestine were available for review. Cases with small intestines nodules, masses, or complete loss of wall layering were excluded. Sonographic images were retrospectively evaluated for jejunal muscularis layer thickness, and ratios of intestinal layer measurements were performed. Histological samples were retrospectively reviewed. Thirteen dogs met inclusion criteria: all dogs had sonographic intestinal muscularis thickening relative to the submucosa (>1.0, range of 1.3–2.5), and most dogs had muscular layer thickness above normal published ranges (11/13; all 13/13 above the weight-specific mean). More than half of the patients had overall normal wall thickness (11/13) and several had normal mucosal echogenicity (6/13). Therefore, in some dogs, the only sonographic abnormality in the small intestine was muscularis thickening. No dogs had lymphadenomegaly. Endoscopic partial-thickness (n = 11, duodenum and/or ileum) or surgical full-thickness (n = 2) samples confirmed inflammatory bowel disease. Direct comparison between jejunum sonographic characteristics and histology features was limited due to both partial thickness biopsies and lack of direct comparison between anatomical locations of ultrasonographic assessment and biopsy site. However, no cases that met the inclusion criteria had normal small intestinal histology. Comparable to cats, dogs with ultrasonographic intestinal muscularis thickening may have inflammatory bowel disease, and further workup for enteropathy is indicated.     

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

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 κ statistics determined agreement between pathologists on histologic lesions.
Results: There was poor agreement (κ=−0.013 to 0.3) between pathologists, and institution of origin of slides had effect (κ= 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 κ= 0.69 using 4-point scale versus maximum κ= 1.0 using 2-point scale). Significant association ( P = .019– .04; 95% OR = 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.     

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

Background

This 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.

Results

There 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.

Conclusion

Faecal 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.     

Expression of genes encoding inflammasome sensor subunits in the duodenal and colonic mucosae of dogs with chronic enteropathy

Inflammasomes play a pivotal role in gastrointestinal homeostasis and inflammation. However, it remains elusive whether the nucleotide-binding oligomerization domain-like receptor (NLR) family inflammasomes, such as NLR family pyrin domain-containing (NLRP) 3, NLRP6, and NLRP12, are involved in the pathogenesis of canine chronic enteropathy (CE), which includes antibiotic-responsive enteropathy (ARE), food-responsive enteropathy (FRE), immunosuppressant-responsive enteropathy (IRE), and non-responsive enteropathy (NRE). Thus, we measured mRNA expression of NLRP3, NLRP6, and NLRP12 in the intestinal mucosa of 35 dogs with CE (ARE, four dogs; FRE, 11 dogs; IRE and NRE, 20 dogs) and seven healthy dogs. As per real-time PCR analysis, significant increases in mRNA expression of NLRP3 and NLRP12 were noted in the colonic but not in the duodenal mucosa of dogs with FRE compared to healthy dogs. These findings suggested that the NLRP3 and NLRP12 inflammasomes might contribute to the development of colitis in dogs with FRE.     

Outbreak of Lawsonia intracellularis on a Standardbred breeding farm in North Carolina

Lawsonia intracellularis is a cause of protein‐losing enteropathy in weanling foals commonly causing signs including diarrhoea, oedema and unthrifty appearance. It has previously been reported as sporadic cases throughout the USA, Canada and Europe. Only recently have outbreaks on a single farm location been reported. The cases reported here are an example of multiple foals on a single farm testing serologically positive for L. intracellularis. These foals ranged in severity from asymptomatic to severely hypoproteinaemic and septic; however, none of the foals ever displayed diarrhoea, which is the most common presenting sign of this disease process.     

Changes in the coagulation parameters in dogs with protein-losing enteropathy between before and after treatment

Protein-losing enteropathy (PLE) is known to induce hypercoagulability and resultant thromboembolism in dogs. We hypothesized that hypercoagulability would improve if remission was obtained in dogs with PLE after treatment. This study aimed to evaluate the changes in the coagulation parameters after treatment in dogs diagnosed with PLE. As coagulation parameters, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, thrombin-antithrombin complex (TAT), D-dimer, and antithrombin (AT) were measured. In addition to these parameters, rotational thromboelastometry (ROTEM), which evaluates the comprehensive coagulation and fibrinolysis reactions of whole blood, was conducted and the data of clotting time (CT), clot formation time (CFT), α angle (α), maximum clot firmness (MCF) and lysis index at 60 min (LI60) were obtained. Eleven of the 14 dogs diagnosed with PLE were classified as responders to the treatment based on the changes in their plasma albumin (ALB) concentration after treatment. Significant increase in CFT and decrease of α and MCF indicating the resolution of hypercoagulability were found after treatment in responder dogs; however, there was no significant change in the coagulation and fibrinolysis parameters other than those measured by ROTEM. This study demonstrated that the hypercoagulability detected by ROTEM was significantly improved after treatment in dogs with PLE.