Colitis In Dogs Research Articles

A case of canine intestinal malakoplakia

Malakoplakia is a rare chronic granulomatous disease usually affecting the urinary bladder and other locations. In humans, the gastrointestinal tract is the second most common location but there are no reports of intestinal malakoplakia in animals. A 10-month-old female French Bulldog was presented with chronic haemorrhagic diarrhoea and anorexia with normochromic-normocytic anaemia and hypoalbuminaemia. Grossly, there was mucosal thickening and ulceration of the caecum, colon and rectum. Microscopically, transmural sheets of foamy macrophages were seen in these tissues. Macrophages were periodic acid–Schiff, vimentin and ionized calcium-binding adaptor molecule 1 positive and contained von Kossa- and Prussian blue-positive Michaelis–Gutmann bodies. Giemsa staining revealed rod-shaped bacterial colonies and fluorescence in-situ hybridization demonstrated Escherichia coli within macrophages. This is the first reported case of intestinal malakoplakia in domestic animals. Pathological features of intestinal malakoplakia share many similarities with ulcerative histiocytic colitis in dogs but it is unclear if they are different forms of the same pathological process or distinct entities.

Colonoscopic Examination, Histopathological findings and medical management of Lymphocytic-Plasmacytic colitis in a Dog

Colitis is defined as the inflammation of colon and is the most common cause of significant bowel diarrhea. Any colon damage may results in inflammation of colon and disturbances in both absorption and motility. In this case, a male German Shepherd was presented with the history of bloody diarrhea for the past one week, tenesmus and frequent voiding of small volume of faeces. Hemato-biochemical analysis revealed slight lymphocytopenia, hypoproteinemia and hypoalbuminemia. On physical examination, animal showed pain on palpation of abdomen and digital rectal examination with hematochezia. Colonoscopy was performed. Histopathological assessment of intestinal biopsy remains the gold standard for diagnosis of intestinal inflammation. The usefulness of endoscopic examination for the diagnosis and treatment of colitis in dogs was determined in this study.

Randomized controlled trial demonstrates nutritional management is superior to metronidazole for treatment of acute colitis in dogs.

To describe the outcome of dietary management of canine noninfectious acute colitis with or without concurrent oral administration of metronidazole using a randomized controlled clinical trial. 59 client-owned dogs with noninfectious acute colitis. Dogs with acute noninfectious colitis were enrolled in a 30-day diet trial after exclusion of parasitic infectious etiologies (fecal centrifugation floatation, Giardia/Cryptosporidium antigen testing) and systemic disease (CBC, biochemistry, urinalysis). Dogs were randomized into 3 placebo-controlled groups: group 1, easily digestible diet + placebo tablet; group 2, easily digestible diet + metronidazole tablet; and group 3, psyllium-enhanced easily digestible diet + placebo tablet. Dogs were evaluated serially using fecal scoring for time to remission, average fecal score, relapse after remission, and dysbiosis index. Median remission time was significantly different among the 3 groups (P < .01) with median times of 5 days (range, 4 to 10) for group 1, 8.5 days (range, 7 to 12) for group 2, and 5 days (range, 3 to 6) for group 3. Metronidazole addition affected the fecal dysbiosis index negatively at days 7 to 10. No adverse effects or complications were noted throughout the study. For canine noninfectious acute colitis, dietary management with an easily digestible diet with or without psyllium enhancement proved a superior management strategy compared to metronidazole. The omission of metronidazole reduced the adverse impact significantly on intestinal microbiota. Longitudinal clinical trials are necessary to compare the long-term response, stability, and complications associated with dietary management alone versus combined dietary and antimicrobial therapy for canine acute colitis.

Detection of invasive Escherichia coli in dogs with granulomatous colitis using immunohistochemistry.

Granulomatous colitis in dogs can be associated with infection of the colonic mucosa by invasive strains of Escherichia coli. To date, fluorescence in situ hybridization (FISH) is the gold-standard method to assess intramucosal and intracellular bacterial invasion. However, FISH requires expensive fluorescence microscopy equipment and is therefore not widely available. We investigated the use of immunohistochemistry (IHC) as an alternative method to detect invasive E. coli in dogs with granulomatous colitis. Archived paraffin-embedded blocks were selected from 26 dogs with colitis, in which FISH had been performed by an outside laboratory. Using a polyclonal antibody, IHC for E. coli was performed on sections cut from the same blocks, and the presence of invasive E. coli was recorded. All 11 specimens in which FISH had detected E. coli were also positive on IHC, with strong immunolabeling in the cytoplasm of macrophages and extracellularly in the lamina propria; all 15 specimens that were negative for invasive bacteria on FISH were also negative on IHC. We found that IHC is a sensitive technique for the detection of invasive E. coli in dogs with granulomatous colitis.

Expression of genes encoding interleukin 15 and its receptor subunits in the duodenal and colonic mucosae of dogs with chronic enteropathy

A pro-inflammatory role of interleukin (IL)-15 and IL-15 receptor (R) in chronic intestinal inflammation, such as inflammatory bowel disease, has been reported in humans. However, the contribution of IL-15 signaling in the pathogenesis of canine chronic enteropathy (CE) remains unclear. Therefore, as a first step in elucidating the importance of IL-15 signaling in canine CE, we measured the mRNA expression of IL-15 and IL-15R subunits, including IL-15Rα, IL-15Rβ, and IL-15Rγ, in the duodenal and colonic mucosae of healthy dogs and those with CE, including food-responsive enteropathy (FRE), antibiotic-responsive enteropathy (ARE), and immunosuppressant-responsive enteropathy (IRE). Real-time PCR analysis revealed significantly lower IL-15Rα mRNA expression levels in the duodenal mucosa of dogs with IRE compared to healthy dogs. In contrast, the mRNA expression levels of IL-15, IL-15Rβ, and IL-15Rγ in the duodenal mucosa and IL-15, IL-15Rα, IL-15Rβ, and IL-15Rγ in the colonic mucosa did not differ among healthy dogs and those with FRE, ARE, or IRE. These findings suggest that decreased mRNA expression of IL-15Rα might be involved in the pathogenesis of duodenitis in dogs with IRE. Moreover, even in canine CE, IL-15 signaling appears to play different roles in duodenitis and colitis in dogs with FRE, ARE, and IRE. However, there were no correlations between the gene expression levels of IL-15Rα and clinical severity or histopathological scores in the duodenum of dogs with IRE. Further studies are necessary to investigate the IL-15Rα protein localization and to determine how impaired IL-15Rα expression contributes to the development of duodenitis in dogs with IRE.

Anti-inflammatory effects of the Aralia elata and Cirsium japonicum in Raw264.7 cells and in vivo colitis model in mice and dogs

Ulcerative colitis (UC) is a severe inflammatory disease that has spread throughout the world. Cirsium japonicum (CJ) and Aralia elata (AE) are natural herbs with potent antioxidative antidiabetics and anti-inflammatory effects. In this investigation, we studied the defensive role of the combination of CJ and AE against LPS-induced inflammation in RAW 264.7 cells, dextran sulfate sodium (DSS)-induced colitis in mice, and acetic acid-induced colitis in dogs. MTT assay was performed to identify the toxic effect of CJ and AE extracts. NO, and MDA level was also measured by NO and MDA assay. To measure the pro-inflammatory protein expression, a western blot was performed. To induce colitis, 3% DSS was used for mice and 6% acetic acid was used for dogs. Histopathology and colonoscopy were executed to detect the effect of extracts. CJ and AE pretreatment reduced the level of NO, MDA, and the expression of pro-inflammatory proteins cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in RAW 264.7. Compared to the separate doses of CJ and AE, the combined dose of CJ and AE significantly reduced clinical symptoms induced by DSS in mice and acetic acid in dogs including weight loss, bloody stool, shortening of the colon, and the severity of colitis and degree of histological damage in the colon. Therefore, these results indicated that a combined dose of CJ and AE has a protective effect against LPS-induced RAW 264.7 cells, DSS-mediated colonic inflammation in mice, and acetic acid-induced colitis in dogs.

Diagnostics of colitis in dogs using additional methods of research

Digestive system pathologies make up a significant part of cases of internal non-communicable diseases in dogs, and colitis is not the least of them. The disease occurs in dogs of all breeds and ages. Colitis is accompanied by a decrease or complete lack of appetite, diarrhea, dehydration, fever, and flatulence and soreness in the intestines. The aim of this study was to show the relevance of using different instrumental and laboratory methods for diagnosing colitis in dogs. The study was carried out on dogs of various breeds and ages, which were subjected to general methods of examination, radiological and endoscopic, followed by examination of biopsies obtained using targeted biopsy. X-ray diagnostics of the intestines in dogs with colitis revealed deformation of the folds of the intestinal mucosa, as well as disturbances in peristalsis. Colonoscopy revealed changes in the mucous membrane of the colon: hyperemia, edema, reduction or complete absence of folding, changes in the vascular pattern, mucus, petechiae, superficial ulcers. The histology of biopsy specimens of the colon mucous membrane of dogs with colitis made it possible to determine the severity of inflammatory processes in the colon and to confirm the pathology found during endoscopic examination for an accurate diagnosis. In the course of the work, it was shown that the most informative method for diagnosing colitis is endoscopic examination with targeted biopsy and subsequent histological examination of the samples obtained.

Clinical characteristics and long-term outcome of E. coli-associated granulomatous ileocolitis in dogs: five cases (2010-2014).

To describe the clinical characteristics and long-term outcome of Escherichia coli-associated granulomatous ileocolitis in dogs. Retrospective review of medical records from dogs with periodic acid-Schiff positive (PAS+) granulomatous ileocolitis and mucosally invasive E. coli in the ileum and colon. Initial bacterial colonisation was evaluated using fluorescence in situ hybridization (FISH) in all dogs and corroborated with colonic and/or ileal culture, when performed. Four boxer dogs and 1 French Bulldog with PAS+ granulomatous ileocolitis (GIC) were evaluated. All dogs had chronic diarrhoea refractory to empirical therapy. Ileocolonoscopy revealed mucosal haemorrhage and ulceration in the ileum (3/4) and colon (5/5). E. coli were visualised as clusters within the ileal and colonic mucosa. Complete (CR, 4/5) or partial (PR, 1/5) clinical response to fluoroquinolones was noted in all dogs within 30 days. CR was sustained in three of four dogs (median disease-free interval 40 months, range 16 to 60). Two dogs relapsed while receiving fluoroquinolones. Repeat biopsy isolated multidrug-resistant, mucosally invasive E. coli in the ileum (1/2) and colon (2/2). Targeted antimicrobial therapy was associated with long-term PR (78 months) in both dogs. Concurrent E. coli-associated granulomatous inflammation in the ileum and colon did not impart a poor clinical outcome or lack of response to the conventional standard of care for granulomatous colitis in dogs that were aggressively diagnosed and treated. Clinical outcome was influenced by antimicrobial resistance, with response dependent upon antimicrobial therapy informed by susceptibility testing.

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.

Escherichia coli-associated granulomatous colitis in dogs treated according to antimicrobial susceptibility profiling.

BackgroundEradication of intramucosal Escherichia coli correlates with remission of periodic acid‐Schiff‐positive E coli‐associated granulomatous colitis (GC). Treatment failures attributed to multidrug resistant (MDR) bacteria necessitate alternative approaches.Hypothesis/objectivesDetermine clinical outcome of E coli‐associated GC in dogs treated based on antimicrobial susceptibility profiling and characterize E coli phylogeny and resistance mechanisms.AnimalsTwenty Boxers and 4 French Bulldogs with E coli‐associated GC.MethodsCulture, antimicrobial susceptibility profiling, and molecular characterization of E coli were performed and response to treatment was evaluated.ResultsInitial biopsy sample culture yielded fluoroquinolone‐sensitive (FQ‐S) E coli from 9/24 dogs and fluoroquinolone‐resistant (FQ‐R) E coli from 15/24. All but 1 FQ‐R E coli were MDR with susceptibility to macrophage‐penetrating antimicrobials restricted to carbapenems in 13/15 dogs. Of 22/24 treated based on susceptibility profiling, 8/9 FQ‐S dogs had complete initial clinical response (CR) during fluoroquinolone (FQ) treatment, whereas 9/13 FQ‐R dogs had complete or partial response (PR) during meropenem or doxycycline treatment. In 5/9 FQ‐S and 12/13 FQ‐R dogs with follow‐up ≥3 months, CR was sustained in 5/5 FQ‐S (median, 25 months; range, 4‐46) whereas 6/12 FQ‐R had long‐term CR (median, 59 months; range 15‐102), 4/12 PR (median, 19 months; range, 5‐65), and 2/12 had no response (NR). Four dogs with long‐term follow‐up died within 4 years of diagnosis, including 2 euthanized for refractory colitis. Escherichia coli were genetically diverse. Fluoroquinolone resistance was associated with mutations in gyrA and parC, with plasmid‐mediated resistance less common.Conclusions and Clinical ImportanceAntimicrobial treatment guided by susceptibility profiling was associated with positive long‐term outcomes in >80% of cases. Fluoroquinolone‐resistance was widespread and not clonal. Further study is required to optimize treatment for dogs with MDR E coli‐associated GC.

Monocyte chemotactic protein-1 in a randomized placebo controlled study of canine plasmacytic-lymphocytic colitis.

The purpose of this study was to determine serum and colonic monocyte chemotactic protein-1 (MCP-1) concentration in dogs with plasmacytic-lymphocytic (PL) colitis, as well as to demonstrate if the concentration of MCP-1 may be an accurate diagnostic and prognostic marker for PL colitis in dogs receiving three different therapeutic protocols. Serum and colonic MCP-1 concentration were measured in 18 dogs with PL colitis and in 6 controls. Dogs with PL colitis were randomly divided in 3 groups and for a period of 30 days received the following: Group 1, sulfasalazine, prednisone and placebo; Group 2, placebo and &amp;#x03C93/&amp;#x03C96 fatty acids, and Group 3, sul-fasalazine, prednisone and &amp;#x03C93/&amp;#x03C96 fatty acids. Colonic and serum MCP-1 concentration were de-termined at the beginning and at the end of this period. Serum MCP-1 concentrations at the be-ginning were not significantly increased in dogs with PL colitis compared to the controls. On the contrary, colonic tissue MCP-1 concentrations at the beginning were significantly increased in the same dogs compared to the controls. Moreover, the colonic tissue MCP-1 concentration in the dogs of group 3 was significantly decreased (P&amp;#x003C0.001) at the end of the experiment. The same observations were obtained from dogs of groups 1 and 2, in which the colonic MCP-1 concentra-tion also significantly decreased (P&amp;#x003C0.01). These data demonstrate that in canine PL colitis, colo-nic MCP-1 concentration is increased in comparison to those of controls and suggest that the colonic MCP-1 concentration may aid in the diagnosis of canine PL colitis.

Association between anal furunculosis and colitis in the dog: preliminary observations.

Treatment of anal furunculosis in dogs is often unsatisfactory and may be associated with significant recurrence and complications. This may be compounded by the simultaneous presence of colitis in affected animals. Clinical signs associated with colitis and anal furunculosis may be similar, including faecal tenesmus, dyschezia and haematochezia. To examine the incidence of concurrent anal furunculosis and colitis, colonic biopsies were collected from 18 dogs referred for treatment of anal furunculosis. Nine dogs (50 per cent) had a histopathological diagnosis of colitis. Clinical signs more indicative of colitis than anal furunculosis (increased frequency of defecation, mucus in faeces and diarrhoea) were not observed more frequently in dogs with confirmed colitis compared with those with furunculosis alone. Therefore, while an association between colitis and anal furunculosis may exist, clinical signs alone cannot be used as an indicator of the presence of colitis in cases of anal furunculosis. The authors recommend that colonic biopsies should be undertaken in all dogs presented with anal furunculosis. Whether specific treatment of colitis in dogs with histopathological evidence of colitis improves the outcome of treatment for anal furunculosis awaits further study.

A role for intestinal mycoplasmas in the aetiology of Crohn's disease?

Crohn's disease (CD) is an inflammatory disorder of the gastrointestinal tract. The cause is unknown but clinical studies indicate that luminal factors and bacteria in the gut are involved in disease aetiology, although the infective organisms that have been implicated in CD, such as atypical mycobacteria and helicobacters, do not explain the various lesions that occur throughout the digestive tract. However, there is some evidence to suggest that mycoplasmas may be associated with CD. For example, mycoplasmas have been linked to colitis in dogs, while intracellular structures similar in morphology to these organisms have been observed in epithelial cells by electron microscopy of CD tissue. Lipids such as cholesterol are required for the growth of some mycoplasmas and dietary studies where the fat content in enteral formula diets was reduced have been demonstrated to have significant therapeutic value in patients with CD. Further support for mycoplasmal involvement in CD derives from improvements in inflammatory indices following the use of antibiotics known to be effective against mycoplasma infections, such as clarithromycin, rifabutin and clofazimine.

Diet and Large Intestinal Disease in Dogs and Cats

Large intestinal disease, and more especially colitis, is a commonly seen problem in small animal practice. Although colitis is most frequently diagnosed in dogs, it is becoming increasing common in cats. The etiology of colitis is not known, but there is general agreement that an immune-mediated response to luminal antigen is involved. In particular, parasites, bacteria and dietary factors may be involved. In ∼10% of dogs presented with typical signs of colitis, no pathologic lesion will be found on investigation. These dogs have a functional diarrhea associated with some stress factor and are thought to have irritable bowel syndrome (IBS). This condition is most frequently observed in working dogs, although highly nervous and excitable dogs may also exhibit similar clinical signs. Until the underlying etiology of colitis is determined, treatment regimens will remain symptomatic. Recent studies have placed considerable importance on the value of diet in the prevention, immediate and long-term therapy of colitis in dogs and cats. In particular the value of “novel” protein diets, fermentable fiber and polyunsaturated fatty acids is receiving the most attention. It is now possible to maintain patients in long-term remission and to modify the severity and chronicity of colitis by using diet alone. This paper will review the subject of dietary management of colitis and IBS and present results from the author’s clinical research program.

A Grading System for Lymphocytic Plasmacytic Colitis in Dogs

Colonic mucosal samples were obtained every 4 weeks for 13 months from 6 clinically normal dogs and from 47 dogs with a clinical diagnosis of chronic inflammatory bowel disease. All samples were graded on a scale of 0-5, based upon the quantity of lymphocytes and plasma cells in the lamina propria, epithelial changes, and the presence of ulcers and erosions. A grade of less than or equal to 2.0 was considered normal and was assigned to 77 of 78 samples from clinically normal dogs and 28 of 48 samples from dogs with diarrhea. A transient increase in cellularity was noted in 1 sample from 1 control dog. Nineteen dogs with clinical disease had obvious histologic abnormalities. The grading scheme described provides the pathologist with an objective criterion for the microscopic evaluation of colonic mucosal samples obtained by endoscopic techniques and offers clinicians a method of assessing the dog's progress and response to therapy.

Salmon diet in relation to amebic colitis in the dog.

SummaryIn three experiments the character of the feces and the condition of the colon and cecum were observed in 34 young adult dogs that had been placed on either a normal or salmon diet and, after 2 weeks, either inoculated orally with cysts of Entamoeba histolytica or not inoculated.During the 34 to 96 days of observation, most of the dogs lost weight, those on the salmon diet to a greater extent than the others. No signs of vitamin deficiencies were observed. Twelve dogs on normal diet passed normal stools and displayed no intestinal lesions not attributable to worms; one of nine inoculated with E. histolytica acquired infection.After 5 to 29 days, among 22 dogs on salmon diet, 12 regularly passed blood and mucus in fluid, often dysenteric, stools. Five of these dogs had been inoculated with E. histolytica, seven had not. In two of the salmon-fed dogs the stools were consistently normal and the intestinal mucosa also appeared to be normal; in the others, the mucosa was in some degree hemorrhagic and friable, with masses of sloughed epithelial cells in the covering mucus. E. histolytica infection was demonstrated in 5 of 9 inoculated dogs, but pathological changes seen in the colon and cecum were essentially the same irrespective of amebic infection. Bloody stools and bowel lesions in some cases apparently were in part due to hookworms, and amebae might have contributed to some of the changes seen; in most instances, however, the salmon diet appeared to have provided the chief causative factor. Thus, the results from earlier studies of amebic colitis in salmon-fed dogs may require reinterpretation.

Studies on Several Cholinergic Drugs as Possible Etiologic Agents in Ulcerative Colitis

Summary In an attempt to produce ulcerative colitis in dogs in order to devise more suitable surgical methods of treatment, several cholinergic drugs were employed. In one set of animals Mecholyl was giveE intramuscularly with the production of edema, submucosal hemorrhages and superficial erosions. In a second group of animals observations were made directly on the mucosa by means of a prepared blind loop colostomy and lysozyme crystals were instilled directly into the loop after Mecholyl was given by injection. Acetylcholine was instilled directly into the prepared blind loop colostomies and Prostigmine given intravenously to a number of dogs, and direct observations made on the mucosa by means of an infant proctoscope.

Action of chloramphenicol (chloromycetin) and other drugs against Endamoeba histolytica in vitro and in experimental animals.

Summary Chloramphenicol was effective against amebae in vitro. Higher concentrations were required in the presence of coagulated whole egg than in egg yolk infusion. It exerted only transient suppressive action against amebic colitis in dogs but was effective against cecal infections in rats. Although penicillin G was not amebacidal in vitro, when given orally it exerted some therapeutic effect in dogs and was highly effective in rats. Limited observations pointed to a similar discrepancy between in vitro action and therapeutic action in rats by streptomycin. Bacitracin, subtilin and methylated subtilin did not exert encouraging antiamebic action in vitro, and bacitracin did not eradicate infections in dogs. In vitro and experimental chemotherapeutic data are presented for carbarsone, acetarsone, diiodo-oxyquinoline, chiniofon, Vioform and emetine hydrochloride. Phthalyl sulfacetimide was ineffective in rats and dogs.

Production of Ulcerative Colitis in Dogs by the Prolonged Administration of Mecholyl

Production of Ulcerative Colitis in Dogs by the Prolonged Administration of Mecholyl

REPRODUCTION OF ULCERATIVE COLITIS IN DOGS

The attempt to reproduce ulcerative colitis in dogs was prompted by the work of Reichert and Mathes, 1 who experimentally produced lymphedema of the intestinal tract. Similarity was noted between experimental lymphedema and clinical regional enteritis or terminal ileitis. The extension of ulcerative colitis into the small intestine as ileitis has been recognized in certain cases. This experimental work followed a procedure for producing obstruction of the mesenteric lymphatics by the injection of a sclerosing solution which has been described elsewhere. 1 An attempt was made to inject the solution into the lymphatics draining the terminal portion of the ileum and the colon in order to produce the disease process primarily in the colon rather than in the ileum. Preliminary injections of several types of bacteria were made in an effort to determine which is most pathogenic for the colon and produces the most marked disease process in that organ.