Histiocytic Ulcerative Colitis Research Articles

In situ hybridization to detect Escherichia coli in canine granulomatous colitis.

Canine granulomatous colitis (histiocytic ulcerative colitis) is an uncommon disease, predominantly of young French Bulldogs and Boxer dogs, that manifests from a dysregulated immune response, primarily to adherent-invasive Escherichia coli (AIEC). In conjunction with histopathology and periodic acid-Schiff staining, the diagnosis of granulomatous colitis currently relies on fluorescence in situ hybridization (ISH) or immunohistochemistry to identify and localize AIEC organisms within macrophages in the mucosa and/or submucosa. We investigated the utility of ISH for E. coli using formalin-fixed, paraffin-embedded specimens collected from 29 cases of suspected granulomatous colitis. Most confirmed cases of granulomatous colitis were in French Bulldogs (12 of 20; 60%) and Boxers (3 of 20; 15%), and the mean age was 25 ± 6 mo with no sex predilection. E. coli ISH signal localized bacterial genetic material within the mucosa in 20 of 29 (69%) cases, supporting the diagnosis. ISH signal was limited to the lumen in 8 of 29 (28%) cases, which did not support the identification of these organisms as AIEC. The remaining case had no hybridization signal, and the diagnosis of granulomatous colitis was not supported. Our results revealed that ISH is a quick and specific detection method that can effectively confirm the diagnosis of canine granulomatous colitis.

Malakoplakia in the Urinary Bladder of 4 Puppies.

Malakoplakia in humans most often affects the urinary bladder and is characterized by inflammation with von Hansemann-type macrophages, with or without Michaelis-Gutmann bodies, and is frequently associated with Escherichia coli infection. We describe the microscopic features of malakoplakia in the urinary bladder of 4 puppies. In all cases, the lamina propria of the urinary bladder was markedly expanded by sheets of large, round to polygonal macrophages with intracytoplasmic, periodic acid-Schiff-positive granules and granular inclusions, and rare Prussian blue-positive inclusions. Macrophages were positive for CD18 and Iba1. In 2 cases, Michaelis-Gutmann bodies were detected with hematoxylin and eosin stain and were best demonstrated with von Kossa stain. E. coli infection was confirmed in 2 cases with bacterial culture or polymerase chain reaction (PCR) and sequencing of the bacterial 16S ribosomal RNA gene. Transmission electron microscopy of one case demonstrated macrophages with abundant lysosomes, phagolysosomes, and rod-shaped bacteria. Microscopic features were similar to human cases of malakoplakia. In dogs, the light microscopic characteristics of malakoplakia closely resemble granular cell tumors and histiocytic ulcerative colitis.

Histiocytic Ulcerative Colitis in an American Staffordshire Terrier

A 9-year-old female American Staffordshire terrier was presented to a veterinary hospital with diarrhoea, severe prostration, hypothermia, dehydration and anaemia. The dog died 6 days after the first consultation. At necropsy examination the serosa of the large intestine showed a granular appearance and the mucosa was thickened, ulcerated and red, with prominent folding. Histological examination revealed marked inflammatory infiltration of macrophages into the mucosa and submucosa of the large intestine. These cells stained positively by the periodic acid-Schiff reaction. Immunohistochemistry showed marked presence of intracytoplasmic Escherichia coli in the macrophages. Bacteriological examination of intestinal sections yielded E. coli growthand the isolate displayed atypical characteristics when compared with strains associated with previously published cases of histiocytic ulcerative colitis (HUC). The molecular characterization showed that the isolate harboured none of the genes associated with enterotoxigenic E. coli strains and harboured only a limited number of genes associated with extra-intestinal pathotypes. Adherent and invasive E. coli are unlikely to have been involved in the pathogenesis of HUC in the present case. HUC is a rare disease with a predisposition for boxer dogs; however, sporadic occurrence in other breeds may occur. This is the first reported case of HUC in an American Staffordshire terrier.

Heterogeneity of macrophages in canine histiocytic ulcerative colitis.

Histiocytic ulcerative colitis (HUC) is a chronic enteropathy which most notably occurs in Boxer dogs and French bulldogs. The inflamed mucosa is hallmarked by large, foamy, periodic acid-Schiff (PAS)-positive macrophages infiltrating the colonic mucosa. As little is known about their origin and phenotype, an immunohistochemical study was performed using different macrophage markers. Generally, canine colonic macrophages showed high expression of ionised calcium-binding adaptor molecule 1 and MHC class II. In canine HUC, macrophages revealed up-regulation of lysozyme and L1 Ag but decreased CD163 expression compared with controls, suggesting them to be pro-inflammatory cells, whereas the healthy colonic mucosa was characterised by an anti-inflammatory macrophage phenotype. In addition, PAS reaction was used to discriminate macrophage subpopulations. PAS- macrophages displayed higher expression of L1 Ag and CD64, whereas PAS+ cells, which were only present in HUC patients, were characterised by increased expression of lysozyme, inducible nitric oxide synthase and CD204. This indicates PAS+ cells to be mature macrophages contributing to the inflammatory process, which are most likely maintained by differentiation of immature PAS- macrophages continuously recruited from blood monocytes. In summary, macrophage heterogeneity in canine HUC probably illustrates their different maturation states and functions compared with the healthy animals.

Histiocytic typhlocolitis in two colony Beagle dogs

Two young female Beagle dogs in a laboratory colony with clinical signs of loose stools and fecal blood were confirmed to have histiocytic ulcerative colitis by histologic evaluation. This syndrome is well recognized in other dog breeds such as Boxers and related French Bulldogs, Mastiffs, Alaskan malamutes and Doberman Pinschers. Formalin-fixed paraffin sections of large intestine from one dog demonstrated the presence of Escherichia coli strain LF82 by immunohistochemistry and 16S ribosomal RNA gene sequencing. E coli strain LF82 has been implicated in the pathogenesis of Crohn's disease and similar bacteria have been cultured from cases of histiocytic ulcerative colitis in Boxer dogs. Spontaneous histiocytic ulcerative colitis must be differentiated from test article-related findings in nonclinical toxicity studies in Beagle dogs.

Proper use of Quinolones for canine colitis ambulatory treatment: literature review and REQUEST guidelines

The literature analysed by REQUEST (REassesing QUinolone European STandard) using inclusion and exclusion criteria allows to make the conclusion that the proper use of fluoroquinolones (FQ) in canine colitis requires rigorously performed qualification to specific antimicrobial treatment. An infectious agent responsive to FQ therapy plays an integral role in the clinical manifestation of canine colitis, especially histiocytic ulcerative colitis (HUC) in young Boxer dogs. This supports the use of FQ in these cases. The Request guidelines for proper use of FQ in canine colitis is established, according to the available literature data.

Transient ileocolic intussusception in a dog with histiocytic ulcerative tiflocolitis: a case report

  In human medicine, the association between intussusceptions and inflammatory bowel disease is well known, even if referred to only in case reports or a small series of patients. The exact cause of intussusceptions, in general, is unknown; however, any lesion in the bowel wall or irritant in the lumen that alters the normal peristaltic pattern may initiate invagination. In Crohn’s disease the lead point may be dysrhytmic contractions secondary to the on-going inflammatory process of a thickened, inflamed segment of bowel wall. In veterinary medicine, the information available related to the association of intussusceptions and inflammatory bowel disease is limited. The present study is the first reported case of a dog in which ileocolic intussusception and histiocytic ulcerative colitis appear to be associated. Moreover, this is also the first description of the involvement of the caecum in canine histiocytic ulcerative colitis. Herein, we document a condition previously reported in humans with inflammatory bowel disease, and we believe that this work contributes to identifying the similarities between human and canine inflammatory bowel disease.    

Remission of Histiocytic Ulcerative Colitis in Boxer Dogs Correlates with Eradication of Invasive Intramucosal Escherichia coli

Historically, histiocytic ulcerative (HUC) (or granulomatous) colitis of Boxer dogs was considered an idiopathic immune-mediated disease with a poor prognosis. Recent reports of dramatic responses to enrofloxacin and the discovery of invasive Escherichia coli within the colonic mucosa of affected Boxer dogs support an infectious etiology. Invasive E. coli is associated with colonic inflammation in Boxer dogs with HUC, and eradication of intramucosal E. coli correlates with clinical and histologic remission. Seven Boxer dogs with HUC. Prospective case series. Colonic biopsies were obtained at initial evaluation in 7 dogs, and in 5 dogs after treatment with enrofloxacin. Biopsies were evaluated by standardized histopathology, and fluorescence in situ hybridization (FISH) with probes to eubacteria and E. coli. Intramucosal E. coli was present in colonic biopsies of 7/7 Boxers with HUC. Clinical response was noted in all dogs within 2 weeks of enrofloxacin (7 + or - 3.06 mg/kg q24 h, for 9.5 + or - 3.98 weeks) and was sustained in 6 dogs (median disease-free interval to date of 47 months, range 17-62). FISH was negative for E. coli in 4/5 dogs after enrofloxacin. E. coli resistant to enrofloxacin were present in the FISH-positive dog that relapsed. The correlation between clinical remission and the eradication of mucosally invasive E. coli during treatment with enrofloxacin supports the causal involvement of E. coli in the development of HUC in susceptible Boxer dogs. A poor response to enrofloxacin treatment might be due to colonization with enrofloxacin-resistant E. coli.

Antibiotic‐Responsive Histiocytic Ulcerative Colitis in 9 Dogs

Canine histiocytic ulcerative colitis (HUC) is characterized by colonic inflammation with predominantly periodic acid‐Schiff (PAS)‐positive macrophages. The inflammation results in colonic thickening, ulcerations, and distortion of normal glandular architecture. Resultant clinical signs consist of chronic large bowel diarrhea, tenesmus, and marked weight loss, and the disease frequently results in euthanasia. Conventional therapy consists of some combination of prednisone, azathioprine, sulfasalazine, and metronidazole. Nine dogs (8 Boxers and 1 English Bulldog) with histologic confirmation of HUC were treated with antibiotic therapy (either with enrofloxacin alone or in combination with metronidazole and amoxicillin). Clinical signs, physical examination findings, laboratory abnormalities, and the histologic severity of the disease were evaluated. Four of the 9 dogs had been treated previously with conventional therapy and had failed to respond favorably; then, these dogs were placed on antibiotic therapy (enrofloxacin, n = 1; enrofloxacin, metronidazole, and amoxicillin, n = 3) and had resolution of clinical signs within 3–12 days. Five dogs were treated solely with antibiotic therapy (enrofloxacin, n = 1; enrofloxacin and metronidazole, n = 1; enrofloxacin, metronidazole, and amoxicillin, n = 3), and clinical signs resolved in 2–7 days. Repeated biopsy specimens were obtained from 5 dogs after treatment, and all showed marked histologic improvement. The increase in body weight after treatment was statistically significant (P= .01). Three dogs currently are not on any treatment and have had resolution of clinical signs for up to 14 months. These observations suggest that an infectious agent responsive to antibiotics plays an integral role in the clinical manifestation of canine HUC, and they support the use of antibiotics in its treatment.

An Immunohistochemical Study of Histiocytic Ulcerative Colitis in Boxer Dogs

Histiocytic ulcerative colitis (HUC) is an inflammatory bowel disease (IBD) that occurs predominantly in dogs of the boxer breed. The lesions are characterized by mucosal ulceration and mixed inflammatory cell infiltrate that includes the presence of periodic acid-Schiff (PAS)-positive macrophages. However, the phenotype of the inflammatory cells has not been characterized further. In the present study, immunohistochemistry and computer-aided morphometric analysis were used to define populations of leucocyte subsets in the colon of 14 boxer dogs with HUC. Biopsies from six of these dogs included both lesional and non-lesional regions. Colonic tissue from 11 dogs of various breeds without evidence of gastrointestinal disease served as controls. In HUC lesions there were significantly more IgG+, IgG3+, IgG4+plasma cells, CD3+T cells, MHC class II+cells, L1+cells and PAS+cells in the lamina propria than in both control colon and non-lesional colonic regions of affected dogs. In the epithelial compartment, goblet cells were significantly decreased in HUC lesions compared to both control and non-lesional HUC colon, and intensity of enterocyte MHC class II expression was significantly increased. These observations are similar to those documented in human IBD, especially ulcerative colitis, and suggest an important role for the mucosal immune system in the pathogenesis of canine HUC.

Canine histiocytic ulcerative colitis.

To assess prevalence, breed predilection, response to therapy and prognosis of canine histiocytic ulcerative colitis (CHUC). A retrospective study of cases of CHUC seen at Sydney University Veterinary Teaching Hospital (SUVTH) over a 20-year period (1975-1994). Case records of all dogs in which colitis was suspected were reviewed. Dogs were diagnosed with CHUC based on colonorectal biopsy and histopathological examination. CHUC was diagnosed in 8 of 57 dogs presented for colitis. All affected dogs were Boxers and six were female. Dogs with milder clinical signs showed moderately good response to therapy. Four dogs were still alive 1 to 7 years after diagnosis. Three dogs were euthanased, one for reasons other than CHUC, and one was lost to follow-up. Young boxer dogs with relatively mild signs of CHUC may respond moderately well to medical and dietary therapy with fair prognosis. Euthanasia early in the course of the disease may be unwarranted. Prevalence may be increasing within the SUVTH referral population.

Histiocytic ulcerative colitis in boxer dogs in the UK

ABSTRACTHistiocytic ulcerative colitis is an uncommon cause of canine large bowel diarrhoea that is generally refractory to standard treatment for idiopathic colitis. It is characterised pathologically by mucosal ulceration with a mixed inflammatory cell infiltrate, in which periodic acid‐Schiff positive histiocytes are a dominant feature. The disease is well recognised in young boxer dogs in the USA, Australasia and mainland Europe. This paper reports the occurrence of seven cases of histiocytic ulcerative colitis seen recently in the UK, along with the clinical signs, histopathology, treatment and post mortem findings.

Canine histiocytic ulcerative colitis. An ultrastructural study of the early mucosal lesion.

Canine histiocytic ulcerative colitis (CHUC) is a chronic debilitating disease of boxer dogs. Study of this disorder may provide information essential to the understanding of pathogenic mechanisms that result in progressive large bowel ulceration. In this study, large intestinal mucosal biopsy specimens from seven affected boxers and four normal dogs were examined by light and electron microscopy. The earliest morphologic change discernible was focal, acute inflammation and epithelial cell degeneration at the luminal surface of the large bowel. These latter changes were nonspecific in nature. The basement membrane of affected epithelium consistently was effaced and intercellular spaces were dilated. Neutrophils were found between intact, degenerating epithelial cells and within the subjacent lamina propria. Convincing evidence for an infectious cause of CHUC was not found. Observed microorganisms probably were secondary invaders since they were present only in lesions exhibiting actual epithelial disruption. The PAS-positive macrophages, which are pathognomonic for the disease, were engorged with numerous digestive vacuoles that mainly contained phospholipid membranes. A developmental sequence was observed which suggested that these PAS-positive cells arose from the actively phagocytic, normal-appearing macrophages found in the surface-oriented mucosal lesions.

Vascular alterations in canine histiocytic ulcerative colitis.

The large intestines of eight boxer dogs with canine histiocytic ulcerative colitis (CHUC) and 10 normal dogs were studied by in vivo angiography and postmortem microangiography. The vascular abnormalities were correlated with the gross and histologic pathology found at necropsy. The angiographic abnormalities were variable, non-specific and were gross indicators of disease. Intestinal segments with mild, focal inflammatory lesions appeared normal, while diseased segments with more extensive inflammatory change exhibited variable vascular dilatation and hypervascularity. Microangiograms of bowel specimens with an early mucosal lesion were normal. With increased disease severity, there was microvascular dilatation with attenuation of mucosal arterioles. Areas with focal or confluent ulcerations demonstrated complete disruption of the mucosal microvascular bed and replacement with the chaotic tangle of ectatic vessels, characteristic of granulation tissue. Anatomic arteriovenous shunts were not observed.

Roentgenographic appearance of canine histiocytic ulcerative colitis.

ROENTGENOGRAPHIC APPEARANCE OF CANINE HISTIOCYTIC ULCERATIVE COLITISTHOMAS L. LAWSON, M.D., JUAN A. GOMEZ, D.V.M., EDWARD T. STEWART, M.D., OSCAR N. RAMBO, M.D. and ALEXANDER R. MARGULIS, M.D.Audio Available | Share