Chronic diarrhoea in small mammals

• Chronic diarrhoea - Major differentials for Chronic enteritis

  Food responsive enteropathy (FRE)

  Dysbiosis

  Antibiotic responsive enteropathy (ARE)

  Steroid responsive enteropathy - SRE (IBD)

  Non-responsive enteropathy (NRE)

  PLE - e.g. lymphangiectasia

  EPI

  Neoplasia
• What factors influence the development of chronic enteritis?

  Comorbidities

  Diet

  Genetics

  Environment

  Gut flora (microbiome)

  Environment
• Adverse reactions to food

  Adverse food reactions refer to any clinically abnormal response attributed to ingestion of a food or food additive. Adverse food reactions are categorised as either food allergy or food intolerances.
• What do food allergy reactions refer too?

  Refer to an immunologically mediated adverse reaction to food unrelated to any physiological effect of the food or food additive. Relapse when specific antigens from previous diet are reintroduced (distinguishes it from intolerance).
• What do food intolerance reactions refer too?

  Any abnormal physiological response to a food that is not believed to be immunologic in nature and may include food poisoning, food idiosyncrasy, pharmacological reaction, toxicological reaction or metabolic reaction.
• Food responsive enteropathy - aetiology

  Adverse reaction to food category.

  Chronic enteropathy - previously was referred to as subcategory of inflammatory bowel disease.

  Usually chronic small bowel diarrhoea:

  • Can see large intestinal signs which may be due to unconjugated bile acids and other SI products.

  Vomiting can be seen

  Maybe skin signs in some cases.
• Food responsive enteropathy - diet responsive conditions

  Vomiting

  Diarrhoea

  Pruritus.
• Food responsive enteropathy - food trial

  Needs to be accepted by patient and owner.

  Offending antigen excluded

  For GI disease should be no longer than 3 weeks.

  • Signs of improvement not very quickly with skin.
  • In cats with ARF most resolved within 7 days

  Reintroduction of diet should lead to relapse.

  Home cooked or commercial meal:

  • Novel intact or hydrolysed proteins (care with osmalarity)
  • Single or limited source
  • High digestibility
  • Reduced fat
  • Avoid high protein
  • Moderate amount of fermentable fibre
• Food responsive enteropathy - Diagnosis and specific approaches

  Diagnosis is by response to food trial.

  Food specific serum-immunoglobulin:

  • Commercially available
  • GI disease of various causes can increase serum IgG.

  Endoscopic food-sensitivity testing

  • Direct application of antigen to mucosa
  • Can also inject into the mucosa
  • Though more sensitive
  • Identifies IgE mediated hypersensitivity
  • Biopsies taken from reacting sites.
  • Greater sensitivity of ileocolic valve infection than gastroscopic testing.
  • Difficult to justify in place of oral challenge testing.
• Chronic diarrhoea - dysbiosis

  This is now caused the major cause/ complication of chronic enteritis.

  The current research in this area is gathering momentum and data.

  Quantitative microbiology - gut content

  • Normal bacterial counts in cats is very wide.

  Dysbiosis/ bacterial overgrowth is common in many conditions.

  • Decreased gastric acid production.
  • Increased small intestinal substrates.
  • Partial obstructions
• Dysbiosis - consequence of secondary bacterial overgrowth.

  Utilise nutrients/ interfere with absorption

  Damage epithelium and microvillar enzyme dysfunction.

  Increase mucosal permeability/ fluid loss.

  Deconjugate bile acids

  Hydroxylate fatty acids.

  Stimulate colonocyte secretion.
• Dysbiosis - clinical signs

  Chronic diarrhoea - small bowel.

  Weight loss/ failure to thrive.

  Vomiting/ borborygmus/ appetite changes
• Dysbiosis - diagnosis


  History to determine, underlying cause.

  • MDB, UA, faecal, imaging and endoscopy.
  • For idiopathic ARD screening tests negative.

  Faecal microbiome analysis.

  Serum folate/ B12 - poorly sensitive or specific

  Breath hydrogen testing

  • Complex to perform (fasting or with test meal)
  • Research tool at present.

  Circulating unconjugated bile acids

  • Deconjugated by GI bacteria and reabsorbed
  • No longer recommended.
• How to approach dysbiosis?

  Understand the individual case, how this may have developed.

  Dietary manipulation:

  • Highly digestible diet.
  • Low fat - secondary overgrowth leads to hydroxylation of fats and diarrhoea.

  Prebiotics - alter colonic flora in cats but no current evidence that alter small intestinal numbers in dogs.

  Probiotics - increasing evidence for this impacting the microbiome in a positive way.
• Steroid responsive enteropathy - overview

  Persistent/ recurrent GI signs with histopathological evidence for inflammation:

  • Mucosal infiltration with inflammatory cells.
  • Variable severity/length of SI affected.

  Characterised by cellular infiltrate:

  • Eosinophillic
  • Lymphocytic-plasmacytic
  • Granulomatous
  • Neutrophillic
  • Regional.
• SRE/IBD - pathogenesis

  Mucosa controls exposure of luminal antigens to GALT

  • GALT must be immunocompetent but also tolerant of non-pathogenic resident flora and food.
  • Loss of tolerance is critical to development of disease
  • Via breakdown of mucosal barrier
  • Dysregulation of immune response.
• SRE/IBD - clinical signs

  Middle aged animals only:

  • Uncommon in dogs <12 months
  • Cats of any age are reported but mostly middle aged.
  • Suspected to be largely the result of small intestinal IBD though no epidemiological data for this.

  Chronic diarrhoea is common - SI in character but if prolonged or involving colon can be mixed.

  Vomiting more common in cats

  Weight loss with more severe mucosal disruption
• SRE/IBD - diagnosis

  History and clinical signs:

  • Typical breeds, non-specific signs.

  Physical examination

  • Thin, thick gut loops, abdominal lymph node palpable.
  • Ascites/oedema

  R/O other differentials

  • MDB should include specPLI and TLI, folate, cobalamin, UPC, full faecal analysis.

  Diagnostic imaging

  • Radiographs and ultrasounds
• SRE/IBD - histopathology


  Previously very subjective

  • Problems with endoscopic vs full thickness biopsies.
  • Widely variable reports on same biopsy sections.
  • Difficult to determine IBD from lymphoma.

  Increased inflammatory cells in lamina propia - mild/moderate/ severe.

  Often multiple cell lines, diagnosis based on predominant cell type:

  • Lymphoplasmacytic IBD (LPE).
  • Eosinophillic IBD
  • Neutrophilic component could suggest superimposed infection.
  • Regional granulomatous form rare.
• SRE/IBD - eosinophillic enteritis

  Second most common form (after LPE).

  Can present with more severe signs:

  • GI haemorrhage
  • Bowel perforation
  • Focal mass lesions

  This form can be more difficult to control.
• SRE/IBD - eosinophillic enteritis diagnosis

  Endoparasitism

  Hypersensitivty disorders

  Mast cell tumours/ paraneoplastic disease

  Hypoadrenocorticism

  Hypereosinophillic syndrome - poor prognosis

  • Rottweilers
  • cats
• Feline triaditis complex - overview

  CE/IBD

  Pancreatitis

  Cholangiohepatitis

  • No gender, age or breed disposition
  • Middle to old-aged cats (some young).
  • SI or LI signs
  • Lethargy, anorexia or ravenous appetite.
  • Jaundice/ palpable hepatomegaly

  Severity is not linked to the severity of the infiltrate or the site involved.
• Feline triaditis complex - diagnosis

  Exclude other causes of diarrhoea/ weight loss.

  Biopsy - NB multiple sites.

  Baseline tests:

  • Complete blood count:
  • Inflammatory/eosinophilia, anaemia.
  • Serum biochemistry panel:
  • Liver disease, pancreatic serology.
  • Cobalamin
  • Urinalysis
  • Serum T4 concentration
  • FeLV/FIV test
• Feline triaditis complex - Imaging

  Radiography:

  • Rule out other conditions/ confirm liver enlargement.

  Ultrasound:

  • GI tract anatomy
  • Liver/pancreas involvement
  • Involvement of biliary system - ascending cholangitis/ cholangiohepatitis.
• Feline triaditis complex - treatment

  Depends on the severity of clinical signs:

  • Most patients have chromic dosease and are managed on out-patent basis.
  • Valuable to have owners keep a diary once start treatment.

  It is important to have a standard approach to management to rule out FRE and dysbiosis.

  • Dietary manipulation
  • Significant proportion of CE cases will have food responsive disease.
• Feline triaditis complex - treatment with anti parasitic agents

  Fenbendazole 50mg/kg PO for 3-5 days:

  • Care if suspect Giardia/ tritrichomonas as these are not treated effectively.
  • Remember these can recrudescence in case of CE
• Feline triaditis complex - treatment with vitamins

  Cobalamin malabsorption frequent in CE/IBD

  Negative prognostic indicator

  Often associated with severity of disease

  Reduced efficacy of therapy, leads to poor thrift and poor appetite.

  • Parenteral supplementation or oral supplementation
  • Injections weekly for 4 weeks then monthly OR oral daily.
  • Serology to assess response 1-4 weeks after last injection.

  Rarely need to supplement folate

  • Unclear benefit.
• Feline triaditis complex - treatment with reduction of intestinal inflammation

  Mainstay of treatment in non-FRE/ARE disease

  Prednisolone 1-2mg/kg PO SID

  • Used at this dose for 2-4 weeks before tapering
  • Care with large dogs as tolerance of prednisolone is poor and suffer muscle weakness and behavioural changes.

  Budesonide - locally acting high potency steroid

  • No benefit shown above prednisolone.

  Cats may need higher doses - up to 2mg/kg PO BID

  Adjunctive therapies:

  • Azathioprine - delayed onset
  • Cyclosporine - longer onset than prednisolone (only one licensed)
• Feline triaditis complex - treatment with alteration of microbiome

  Probiotics

  Faecal microbiota transplantation in humans

  • Increasing use in CE as an adjunct ant in poorly responsive cases

  Antibiotics:

  • Oxytetracycline, Tylosin, Metronidazole
  • Immunomodulatory properties in addition
  • Also reported for tylosin and OTC
  • Causes microbiome disruption - dysbiosis and this does not routinely resolve after cessation
• Protein losing enteropathy

  This is a form of chronic enteropathy characterised by the loss of protein through the GIT

  • Both albumin and globulins are low
  • PLN where only albumin is low.

  Carries with it a more severe disease course and worse prognosis than standard CE

  Major differentials for PLE:

  • Severe inflammatory disease (IBD), lymphangeictasia (can be seen in addition to IBD or as primary entity), neoplasia (typically lymphoma).
• Lymphangiectasia - overview

  Extensive lymphatic dilation - Lymphangiectasia

  • Balloon dilated lymphatics with LP oedema and loss of lymph into the gut lumen.

  Can be secondary to inflammation or neoplasia or primary:

  • Generalised condition of lymphatics
  • Breed association
  • Lipogranulomatous changes (microscopic granulomas).
  • Can also see secondary to blocked C. chyle thoracic duct
  • Right heart failure
  • Liver tumour.
• Lymphangiectasia - diagnostic approach

  PLE

  • Low albumin and globulin

  Low cholesterol

  Lymphopenia

  Low Ca/Mg (exacerbates the effect of hypocalcaemia)

  Ultrasound - mucosal striation

  Endoscopy - white spots on villus tips, white nodules or plaques, white fluid.

  Biopsy - endoscopy preferable but problems with depth of samples.
• Lymphangiectasia - treatment

  Treat any primary cause:

  • Neoplasia, IBD, anatomic disease

  Primary Lymphangiectasia:

  • Ultra-low fat diet
  • Fluid therapy particularly if ascitic as dehydrated
  • Albumin/Colloid for hypoproteinaemia
  • Diuretic for effusions - caution as this can worsen hypovolaemia
  • Fluid withdrawal - not indicated unless causing morbidity
  • Immune suppress if inflammatory component or if lipogranulomas are present.
• Types of intestinal tumours

  Lymphoma (LPE as precursor, FeLV negative).

  Adenocarcinoma/ adenomatous polyps

  Leiomyoma/ leiomyosarcoma

  Mast cell tumour

  Fibrosarcoma

  Haemangiosarcoma
• Presentation of intestinal tumours

  Diffuse

  • Chronic small bowel diarrhoea and weight loss
  • Melaena/ PLE
  • Vomiting

  Focal - obstruction/ motility change/ haemorrhage

  Palpable on physical

  Secondary hypoproteinamia, anaemia

  Ultrasound - focal mass/ loss of wall architecture or layering.

  Biopsy - endoscopic vs laparotomy

  • Assess spread - staging.
• Management of intestinal tumours

  Lymphoma:

  • CHOP based protocols
  • COP chemotherapy
  • Prednisolone and chlorambucil
  • Lomustine
  • Prednisolone alone
  • Caution with perforation of bowel when starting any chemotherapy

  Others

  • Surgical resection and adjunctive chemotherapy.