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Standards of Care April 2008 (Vol 10, No 3)

Ulcerative Colitis in Boxers

by Kenneth Simpson, BVM&S, PhD, DACVIM-SAIM, DECVIM-CA

    Introduction

    VECCS Logo

    Histiocytic ulcerative colitis (HUC), also known as granulomatous colitis, is a severe disease that typically affects young boxer dogs. HUC is characterized by frequent bloody, mucoid stools; thickening and ulceration of the colon; anemia; hypoalbuminemia; and weight loss. The dominant histologic features are loss of colonic epithelium and goblet cells and an accumulation of large numbers of periodic acid-Schiff-positive (PAS-positive) macro­phages. Immuno­pathologic studies show an increase in im­munoglobulin G3 (IgG3) and IgG4 plasma cells, CD3 T cells, L1, and major histocompatibility complex class II-positive cells similar to those seen in humans with ulcerative colitis.

    The predilection for boxers to develop this condition, with only sporadic cases of this type of colitis reported in other dog breeds, and the absence of a causal infectious agent have led to HUC being considered a breed-specific, immune-mediated inflammatory bowel disease of unknown etiology.

    A favorable outcome has been described in dogs receiving antibiotics such as chloramphenicol, and several reports describe clinical responses to antibiotic regimens containing fluoroquinolones. Recent studies have demonstrated that the colonic mucosa of dogs with HUC is infiltrated with Escherichia coli and that antibiotic-induced clinical remission correlates with the eradication of invasive E. coli. The E. coli strains isolated from affected dogs are consistent with a new pathogroup, termed adherent and invasive E. coli, that is associated with Crohn's disease in humans. Thus, HUC in boxers is not an idiopathic immune-mediated disease but rather a potentially curable enteropathy associated with E. coli.

    Diagnostic Criteria

    Historical Information

    Gender Predisposition

    • None.

    Age Predisposition

    • Dogs younger than 4 years of age.
    • Some dogs as young as 3 months of age.

    Breed Predisposition

    • Almost exclusively boxers.
    • Others breeds, such as Mastiffs, Alaskan malamutes, Doberman pinschers, and French bulldogs, are very sporadically affected.

    Owner Observations

    • Mucoid, bloody stools.
    • Tenesmus.
    • Failure to gain weight; weight loss.
    • Loss of appetite.

    Physical Examination Findings

    • Poor body condition.
    • Pale mucous membranes may be present.
    • Blood and mucus on rectal examination may be present.

    Laboratory Findings

    • Anemia: Variable.
    • Hypoalbuminemia: Variable.

    Other Diagnostic Findings

    • Ultrasonography may show a thickened colonic wall and enlarged colonic or mesenteric lymph nodes.
    • Endoscopy: Thickened, irregular mucosa; ulcers.
      — Histologically, endoscopic biopsies are characterized by the loss of colonic glands and marked infiltration by lymphocytes, plasma cells, and PAS-positive macrophages.
      — Lesions may be patchy in distribution, so at least seven biopsies should be taken in multiple sites throughout the colon.
      — Specialized examination with fluorescence in situ hybridization (FISH) reveals multifocal clusters of intramucosal E. coli that are characteristic of HUC.
      — Performing (aerobic) microbial culture and antibiotic sensitivity testing of E. coli cultured from freshly procured colonic biopsies taken into sterile transport medium is prudent because antibiotic resistance may impact treatment (see Resource List).

    Summary of Diagnostic Criteria

    • HUC is typically present in boxers.
    • Chronic large bowel diarrhea associated with weight loss or failure to thrive.
    • Colonic biopsies show loss of glands and infiltration with PAS-positive macrophages.
    • Demonstration of intramucosal clusters of E. coli by FISH.

    Diagnostic Differentials

    The diagnostic differentials should include other causes of large bowel diarrhea.

    • Parasites (e.g., Trichuris vulpis) are ruled out with fecal analysis and an anthel­minthic treatment trial of fenbendazole (50 mg/kg PO q24h for 3-5d).
    • Bacteria (e.g., Campylobacter spp) are ruled out with fecal culture.
    • Fungi (e.g., Histoplasma spp) are ruled out with rectal cytology or histopathology.
    • Algae (e.g., Prototheca spp) are ruled out with rectal cytology or histopathology. (Boxers appear to be predisposed to protothecosis.)
    • Nonhistiocytic inflammatory bowel disease (lymphoplasmacytic colitis, eosinophilic colitis) is ruled out with histopathology.
    • Neoplasia (e.g., lymphoma) is ruled out with histo­pathology.
    About VECCS

    Treatment Recommendations

    Initial Treatment

    Caution: Fluoroquinolones may cause cartilage damage in young, growing dogs. However, this risk may be medically justified because failure to effectively manage HUC is associated with an extremely poor prognosis.

    • Antimicrobial therapy:
      —Enrofloxacin: 5 mg/kg PO qd for 30 days (Figure 1).
      — Combinations of enrofloxacin and metronidazole (15 mg/k PO bid for 4-6 wk) and enrofloxacin, metronidazole, and amoxicillin (20 mg/kg PO bid for 4-6 wk) have been effective, but enrofloxacin is considered the active component.

    Alternative/Optional Treatments/Therapy

    • Culture and sensitivity of E. coli isolated from colonic biopsies should be used to guide antibiotic therapy in patients that do not respond to fluoroquinolones.
    • Other antibiotics that may be effective include:
      — Chloramphenicol: 50 mg/kg PO tid.
      — Clarithromycin: 7.5 mg/kg PO bid.
    • Immunosuppressive therapy should not be considered until it has been confirmed that invasive bacteria have been eradicated from the mucosa and antibiotic treatment has failed.
    • Posttreatment biopsies can be evaluated by FISH to confirm clearance of intramucosal bacteria.

    Supportive Treatment

    • A balanced diet should be provided. Soluble fiber (psyllium 1 tsp/5-10 kg added to food), tylosin (10-15 mg/kg PO bid), or sulfasalazine (20 mg/kg PO bid) may be given.

    Patient Monitoring

    • A good clinical response is marked by resolution of diarrhea and improvement in body condition.
    • Persistence of diarrhea and failure to improve body condition indicate the need to reevaluate the patient.

    Home Management

    • Affected animals should not be bred.

    Milestones/Recovery Time Frames

    • Treatment with enrofloxacin (alone or in combination with metronidazole ± amoxicillin) is generally reported to induce resolution of clinical signs within 2 weeks.
    • Approximately one-third of dogs have remained free of clinical signs during a 5- to 14-month follow-up after discontinuation of treatment. In the remaining dogs, clinical remission has been maintained by continuing enrofloxacin at dosages ranging from 68 mg PO q24h to 68 mg PO q72h for 2 to 21 months.
    • In some dogs that relapse, remission can be achieved with retreatment with enrofloxacin; however, relapse and failure to respond to enrofloxacin may be associated with antibiotic resistance.

    Treatment Contraindications

    • Immunosuppressive medications (e.g., prednisolone, prednisone, azathioprine) are contraindicated in the treatment of HUC associated with invasive E. coli.

    Prognosis

    Favorable Criteria

    • Response of clinical signs to treatment with antibiotics usually within 2 to 3 weeks.

    Unfavorable Criteria

    • Failure to respond to antibiotics.

    Barnich N, Darfeuille-Michaud A: Adherent-invasive Escherichia coli and Crohn's disease. Curr Opin Gastroenterol 23(1):16-20, 2007.

    Baumgart M, Dogan B, Rishniw M, et al: Culture independent analysis of ileal mucosa reveals a selective increase in invasive Escherichia coli of novel phylogeny relative to depletion of Clostridiales in Crohn's disease involving the ileum. ISME J 1(5):403-418, 2007.

    Davies DR, O'Hara AJ, Irwin PJ, Guilford WG: Successful management of histiocytic ulcerative colitis with enrofloxacin in two boxer dogs. Aust Vet J 82:58-61, 2004.

    German AJ, Hall EJ, Kelly DF, et al: An immunohistochemical study of histiocytic ulcerative colitis in boxer dogs. J Comp Pathol 122:163-175, 2000.

    Hostutler RA, Luria BJ, Johnson SE, et al: Antibiotic-responsive histiocytic ulcerative colitis in 9 dogs. J Vet Intern Med 18:499-504, 2004.

    Simpson KW, Dogan B, Rishniw M, et al: Adherent and invasive Escherichia coli is associated with granulomatous colitis in boxer dogs. Infect Immun 74:4778-4792, 2006.

    Stenner VJ, MacKay B, King T, et al: Protothecosis in 17 Australian dogs and a review of the canine literature. Med Mycol 45:249-266, 2007.

    Van Kruiningen HJ, Civco IC, Cartun RW: The comparative importance of E. coli antigen in granulomatous colitis of boxer dogs. APMIS 113:420-425, 2005.

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    These Care Guides are written to help your clients understand common conditions. They are formatted to print and give to your clients for their information.

    didyouknow

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