[Frontiers in Bioscience E4, 1404-1419, January 1, 2012]

Inflammatory bowel disease in veterinary medicine

Albert E. Jergens1, Kenneth W. Simpson2

1Department of Veterinary Clinical Sciences, Iowa State University, Ames, Iowa 50010 and 2Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853

TABLES

Table 1. Causes for chronic intestinal inflammation in dogs and cats

Causes for Chronic Intestinal Inflammation

Chronic infection

  • Giardia spp
  • Tritrichomonas foetus
  • Cryptosporidium spp
  • Histoplasma spp
  • Toxoplasma spp
  • Mycobacteria spp
  • Protothecosis
  • Pythiosis
  • Pathogenic bacteria (Campylobacter jejuni,
  • Salmonella spp, adherent/invasive E. coli
  • Antibiotic-responsive enteropathy

    Food allergy

    Other primary gastrointestinal diseases

    • Intestinal lymphangiectasia
  • Lymphoma
  • Adenocarcinoma
  • Other neoplasms
  • Idiopathic causes

    • Lymphocytic-plasmacytic enteritis/colitis
  • Eosinophilic gastroenterocolitis
  • Non-AIEC granulomatous enteritis
  • Important IBD mimics include antibiotic-responsive enteropathy and adverse food reactions which include food allergy and food intolerance. AIEC = adherent/invasive E. coli.

    Table 2. A summary of immunopathologic findings seen with canine and feline IBD

    Parameter

    Immunologic Abnormality

    Clinical Study

    A. Canine IBD Immunopathologic Summary

    Parameter

    Immunologic Abnormality

    Clinical Study

    Mucosal B lymphocytes

    ¯ or ­ IgG cells in small intestine

    3, 44

    Mucosal B lymphocytes

    ­ IgA, IgG cells in colon

    55

    Mucosal B lymphocytes

    ­ plasma cells in colon

    48

    Mucosal T lymphocytes

    ¯ CD3+ cells in small intestine

    3

    Mucosal T lymphocytes

    ­ CD3+, CD4+, TCRa b + cells in small intestine

    1

    Mucosal T lymphocytes

    ­ CD3+, CD8+ cells in colon

    55

    Mucosal T lymphocytes

    ¯ TCRγδ+ IEL via flow cytometry

    7

    Mucosal mast cells

    ¯ or ­ mass cells in small intestine

    1

    Mucosal macrophages

    ­ in colon of HUC

    9

    Nitrate in lavage

    ­ in colonic luminal nitrite and IgG

    45

    Mucosal iNOS

    ­ iNOS in small intestine and colon

    7

    Mucosal MHC

    ­ Class II+ cells in colon (HUC)

    9

    Mucosal cytokines

    Balanced Th1:Th2 mRNA expression in small intestine or colon

    46, 47, 49

    Mucosal cytokines

    Predominant Th1 mRNA expression in colon

    51

    Mucosal TLR

    ­ TLR2, 4, 9 in small intestine and colon

    38

    Mucosal NFκB

    ­ macrophage expression

    42

    Mucosal apoptosis

    ¯ lymphocyte caspase 3

    43

    B. Feline IBD Immunopathologic Summary

    Commensal bacteria response

    ­ Serum IgG responses

    7

    Mucosal MHC

    ­ class II+ expression in epithelia + macrophages

    53

    Mucosal cytokines via qRT-PCR

    Balanced Th1:Th2 mRNA expression in small intestine

    54

    Mucosal cytokines via qRT-PCR versus histology

    Balanced Th1:Th2 mRNA expression in small intestine

    52

    (A) Alterations in mucosal immune cells and mucosal markers are evident in canine IBD. (B) Cats with IBD show up-regulated mucosal MHC II expression while both dogs and cats have mixed Th1/Th2 cytokine activation relative to healthy animals. IEL = intra-epithelial lymphocytes; HUC = histiocytic ulcerative colitis; iNOS = inducible nitric oxide synthase; TLR = toll-like receptor.

    Table 3. Diagnostic tests for intestinal inflammation

    Test

    Rule out

    Elimination diet

    Adverse food reaction

    Fecal examination

    Nematodes/protozoa

    Fecal culture

    Bacterial enteropathogens

    Serum biochemistry

    Metabolic and systemic disease

    Specialized serology

    Specific tests to include:

    TLI

    Exocrine pancreatic insufficiency

    PLI

    Active pancreatic inflammation

    Total T4

    Feline hyperthyroidism

    Cobalamin

    Hypocobalaminemia

    Cortisol

    Hypoadrenocorticism

    Imaging

    Masses, GI obstruction

    Endoscopic biopsy

    IBD, neoplasia, fungal

    Celiotomy/biopsy

    IBD, neoplasia, fungal

    Laparoscopy/biopsy

    IBD, neoplasia, fungal

    IBD is a diagnosis of exclusion and requires elimination of IBD mimics through sequential diagnostic evaluation. TLI = trypsin-like immunoreactivity; PLI = pancreatic lipase immunoreactivity.

    Table 4. The canine IBD activity index (CIBDAI)

    Attitude/activity

    Assessment:

    0

    Normal

    1

    Slightly decreased

    2

    Moderately decreased

    3

    Severely decreased

    Appetite

    Assessment:

    0

    Normal

    1

    Slightly decreased

    2

    Moderately decreased

    3

    Severely decreased

    Vomiting

    Assessment:

    0

    None

    1

    Mild (one time/week)

    2

    Moderate (two to three times/week)

    3

    Severe (more than three time times/week)

    Stool consistency

    Assessment:

    0

    Normal

    1

    Slightly soft feces or fecal blood, mucus or both

    2

    Very soft feces

    3

    Watery diarrhea

    Stool frequency

    Assessment:

    0

    Normal

    1

    Slightly increased (two to three times/day)

    2

    Moderately increased (four to five times/day)

    3

    Severely increased (more than five times/day)

    Weight loss

    Assessment:

    0

    None

    1

    Mild (< 5% loss)

    2

    Moderate (5-10% loss)

    3

    Severe (> 10% loss)

    Cumulative score

    Disease

    0-3

    Clinically insignificant disease

    4-5

    Mild IBD

    6-8

    Moderate IBD

    ≥9

    Severe IBD

    This numerical scoring system defines clinical disease activity on the basis of six salient gastrointestinal signs. The composite CIBDAI score defines clinically insignificant disease or the presence of mild, moderate, or severe IBD.

    Table 5. The feline chronic enteropathy activity index (FCEAI)

    Variable

    Assessment

    GIT signs

    No or yes

    Attitude/activity

     

    Appetite

    Scored

    Vomiting

    0-3*

    Diarrhea

    Weight loss

     

    Endoscopic lesions

    0=no; 1=yes

    Total protein

    0=normal; 1=increased

    ALT/ALP

    0=normal; 1=increased

    hosphorous

    0=normal; 1=decreased

    Similar to the CIBDAI, this clinical scoring system incorporates multiple variables including gastrointestinal signs, endoscopic lesions, and select biochemical analytes. Clinical trials indicate that the FCEAI is useful for defining disease activity in cats having either IBD or food- responsive enteropathy. * Range of gastrointestinal signs from not present (0) to severe (3).

    Table 6. Nutritional therapy for canine and feline IBD

    Clinical Study

    Species (No.)

    Diet

    Primary/Adjunct role

    Response

    66

    Cat (28)

    Controlled

    Adjunct

    50% respond

    6

    Cat (60)

    Controlled

    Adjunct

    80% respond

    96

    Dog (6)

    Elimination

    Primary

    70% respond

    71

    Dog (58)

    Elimination

    Adjunct

    80% respond

    8

    Dog (65)

    Elimination

    Primary

    50% respond

    4

    Dog (70)

    Elimination

    Adjunct

    60% respond

    94

    Dog (54)

    Elimination

    Adjunct

    80% respond

    75

    Cat (17)

    Elimination

    Adjunct

    100% respond

    Dietary therapy for chronic IBD is an important intervention and may be used as either a primary or adjunct treatment along with the administration of pharmacologic agents.

    Table 7. Drug therapy for canine and feline IBD

    IBD Study

    Trial Design

    Drug Therapy

    Outcome

    A. Canine

         

    2

    RS

    Pred, MTZ, 5-ASA

    > 80% response

    71

    PT

    Pred, MTZ, 5-ASA

    > 80% response

    5

    RS

    Pred, MTZ, 5-ASA, tylosin

    Confounding variables; ¯ albumin = negative outcome

    59

    PT

    Tylosin

    ¯ ¯ diarrhea in all dogs

    95

    PT

    Pred, MTZ, 5-ASA,

    AZA

    ¯ ¯ diarrhea with immunosuppressive drugs

    98

    PT

    Pred

    > 75% response

    99

    PT

    Cyclosporine

    > 80% response in steroid refractory IBD

    8

    PT

    Pred

    > 50% response

    81

    PT

    Pred + MTZ

    > 75% response

    4

    PT

    Pred, cyclosporine

    > 60% response

    56

    PT

    Pred

    ¯ albumin = negative outcome

    22

    PT

    Enrofloxacin

    > 85% response in HUC

    94

    RCT

    Pred vs Pred+MTZ

    > 80% response in both groups

    B. Feline

         

    2

    RS

    Pred, MTZ

    > 80% response

    65

    RS

    Pred

    > 50% response

    66

    RS

    Pred, tylosin, 5-ASA

    70% response

    75

    PT

    Pred

    100% response

    Cumulative data shown is derived from different study designs including retrospective studies (RS), case-controlled prospective trials (PT), and randomized-controlled trials (RCT). Outcome measures include attenuation of gastrointestinal signs +/- biomarker analysis. PRED = prednisone or prednisolone; MTZ = Metronidazole; 5-ASA = sulfasalazine; AZA = azathioprine.

    Table 8. Comparative features of IBD in humans and dogs

    Feature

    Human IBD

    Canine IBD

    Genetic basis

    Yes

    Likely

    Etiology

    Unknown but likely multifactorial

    Unknown but likely multifactorial

    Commensal bacteria role

    Yes

    Yes

    Hematochezia

    Yes

    Yes

    Diarrhea

    Yes

    Yes

    Definitive diagnosis

    GI biopsy

    GI biopsy

    Disease activity assessment

    Clinical indices; biomarkers (ASCA, pANCA, CRP, calprotectin)

    Clinical indices; biomarkers (pANCA, CRP, calprotectin?)

    Response to anti-inflammatory drugs

    Yes

    Yes

    Response to antibiotics

    Yes

    Yes

    Spontaneous "flares" in GIT signs

    Yes

    Yes

    Idiopathic canine IBD shows numerous similarities to human IBD, including host defects in innate immunity contributing to disease susceptibility, prominent role for the commensal microbiota, biopsy confirmation for definitive diagnosis, use of clinical indices and biomarkers for disease assessment, and similar treatment interventions. These characteristics and others make the dog a useful animal model to study human IBD. GIT = Gastrointestinal tract