Diagnosis of Chronic Enteropathies

What are chronic enteropathies?

A syndrome characterized by clinical signs of GI dysfunction persisting for > 3 weeks with no identifiable underlying cause

Pathogenesis of chronic enteropathies

Complex

- pathogenic alterations in mucosal inflammatory responses and barrier dysfunction

- microbiota dysbiosis

- genetics

- diet

- environment

What clinical signs can help us distinguish between chronic enteropathies and other GI disease/GI manifestations of systemic disease?

None

What are the 3 ways we can classify chronic enteropathies?

Based on clinical severity - complicated or uncomplicated

Based on anatomical location - small or large bowel

Based on response to therapy - diet, steroid, or abx responsive

Cardinal clinical signs of uncomplicated CE

Mild signs

- chronic diarrhea most common

- vomiting

- weight loss

- anorexia

Characteristics of uncomplicated CE

- no evidence of systemic complications

- no major abnormalities in PE, cbc/chem

- patient is stable

Treatment style of uncomplicated CE

Therapeutic trials can begin with minimal diagnostics

Cardinal clinical signs of complicated CE

More prominent and/or progressive

- vomiting

- weight loss

- anorexia

Characteristics of complicated CE

Systemic complications present

- cachexia

- fever

- leukocytosis

- anemia

- hypoproteinemia

Treatment style of complicated CE

- require a more comprehensive diagnostic evaluation, including imaging and biopsies

- more aggressive therapy

- earlier therapeutic escalation

What type of response to therapy is most common in CE patients?

Diet responsive - if you can, fix the diet first

In most cases, what is the cause of chronic enteropathies?

Idiopathic

What is idiopathic chronic enteropathy?

When chronic GI signs present in absence of an underlying systemic, infectious, or neoplastic cause

What is chronic inflammatory enteropathy?

Mucosal inflammation demonstrated by histopath

Lymphoplasmacytic enteritis most common

Diagnostic criteria for CIE

Biopsies and histopath REQUIRED to diagnose

- chronic signs of intestinal dysfunction

- histopathologic inflammatory infiltrates

- exclusion of other potential underlying causes of intestinal dysfunction

Histopathologic features of CIE

- increased numbers of inflammatory cells in the mucosa

- villous blunting

- fibrosis

- crypt degeneration/abscesses

- lymphatic dilation

Diagnostic strategy for uncomplicated CE

1. History - confirm and characterize clinical signs

2. Clin path - rule out extra intestinal disorders, neoplasia, infection, and screen for nutrient deficiencies

3. Perform a therapeutic diet trial

4. Imaging - assess intestinal structure

5. Pathology - get biopsies and characterize mucosal lesions

Cardinal clinical signs of SI dysfunction

- diarrhea

- vomiting

- weight loss

- anorexia or polyphagia

Potential clinical signs of SI dysfunction

- melena and/or hematochezia

- changes in defecatory habit (tenesmus, dyschezia)

- abdominal pain/discomfort

- increased borborygmi or flatus

Clinical signs of CE have a duration of how long?

> 3 weeks

Melena indicates...

Upper GI hemorrhage

Hematochezia indicates...

Colonic or rectal hemorrhage (depending on how bright the color is)

Stool volume in small bowel vs large bowel diarrhea

Small bowel - large volume

Large bowel - small volume

Mucus in small bowel vs large bowel diarrhea

Small bowel - rare

Large bowel - common

Blood in small bowel vs large bowel diarrhea

Small bowel - melena

Large bowel - frank blood

Undigested food in small bowel vs large bowel diarrhea

Small bowel - sometimes

Large bowel - absent

Tenesmus in small bowel vs large bowel diarrhea

Small bowel - rare

Large bowel - common

Frequency of small bowel vs large bowel diarrhea

Small bowel - normal or mild increase

Large bowel - > 3x per day

Urgency of small bowel vs large bowel diarrhea

Small bowel - rare

Large bowel - common

Vomiting in small bowel vs large bowel disease

Small bowel - common

Large bowel - rare

Weight loss in small bowel vs large bowel disease

Small bowel - common

Large bowel - rare

Minimum clinicopathologic database in patients with suspected CE? Which is most important?

- cbc/chem (most important)

- UA

- resting serum cortisol (dogs)

- total T4 (cats)

- serum TLI

Why is a chem so important in CE diagnosis?

- rule out renal and hepatobiliary disorders

- screen for endocrinopathies (DM, hypoadrenocorticism)

- detect hypoproteinemia (PLE)

How can we rule out pancreatitis when working up CE?

Measure serum pancreatic lipase

If PL increased, pancreatitis may or may not be contributing to clinical signs

If PL normal, pancreatitis excluded

Bacterial and viral infections cause what type of GI disease?

Typically acute and self limiting

What are serum cobalamin and folate important tests for?

GI absorptive function and to assess metabolic interactions with intestinal microbes

What does increased cobalamin indicate?

- no known clinical relevance

- likely due to high dietary intake or supplementation

What does decreased cobalamin indicate?

- mucosal lesion in ileum causing malabsorption

- SI bacterial overgrowth or dysbiosis

What does increased folate indicate?

SI bacteria overgrowth or dysbiosis

What does decreased folate indicate?

Mucosal lesion in the proximal SI causing malabsorption

When are intestinal biopsies recommended?

- no response to dietary trial therapy

- identification of intestinal wall layering abnormalities

- identification of masses/tumors associated with the GI tract or enlargement of draining lymph nodes

Methods of collecting GI biopsies

Endoscopy - partial thickness

Surgical - full thickness

When are surgical biopsies preferred?

- full thickness biopsies are required

- lesion is localized to the jejunum (cats)

- samples from other organs are desired (liver, LNs, pancreas)

Patient selection of surgical biopsies

- must be stable for anesthesia

- ideal to perform before immunosuppressive therapy is initiated, effects on diagnostic results and wound healing

Pros of endoscopic biopsies

- minimally invasive, outpatient procedure

- low cost

- direct visualization of the luminal mucosa

- treatment can start immediately after

Cons of endoscopic biopsies

- cannot access entire gut or other organs

- small biopsies

- partial thickness, only samples superficial mucosa

Pros of surgical biopsies

- access entire GI tract

- full thickness, deeper layers of submucosa

- access to LNs, pancreas, liver

Cons of surgical biopsies

- invasive

- higher morbidity

- high cost

- immunosuppressive and chemotherapy tx postponed for wound healing

When should a fecal dysbiosis index be performed?

In patients that do not respond to initial attempt at treatment

How are cats different from dogs in their chronic enteropathy?

Less likely to have diet responsive enteropathy

More likely to have mucosal inflammatory or neoplastic diseases

Need to be more aggressive diagnostically

What 2 chronic enteropathies are common in cats?

Chronic inflammatory enteropathy (CIE)

Low grade intestinal T cell lymphoma (LGITL)

Differentiating CIE from LGITL

Immunohistochemistry (CD3) and clonality testing (PARR)

Feline chronic enteropathy is common in what signalment?

Geriatric cats

Most common clinical sign of FCE

Weight loss

FCE is commonly associated with...

Comorbidities - cholangitis, pancreatitis

Examples of complicated enteropathies

- severe or refractory CIE

- histoplasmosis, pythium

- PLE

- E. coli associated granulomatous colitis

What is critical to rule out in complicated enteropathies?

Infectious disease and neoplasia

Potential complications of PLE

- body cavity effusions that can impair ventilation and cardiac function

- hypocalcemia (tremors, twitching, muscle spasms, stiffness, seizures)

- hypotension from volume depletion and decreased oncotic pressure

- hyper coagulability and pulmonary thromboembolic disease

Predisposed breeds to PLE

- yorkies

- soft coated wheaton terriers

- norwegian lundehund

Clinical signs of PLE

- chronic weight loss (most common)

- vomiting

- diarrhea

- reduced appetite

- cavitary effusions

Common lab abnormalities in PLE

- hypoalbuminemia/panhypoproteinemia

- hypocalcemia

- hypocholesterolemia

Breed disposition to E. coli associated granulomatous colitis

- boxers

- frenchies

- mastiffs

Diagnosis of E. coli associated granulomatous colitis

Requires histopathologic diagnosis and bacterial culture of colonic tissue

Will only respond to targeted antimicrobial therapy

Clinical presentation of E. coli associated granulomatous colitis

- complicated, large bowel enteropathy

- diarrhea

- hematochezia

- tenesmus

- weight loss

- +/- hypoproteinemia

- +/- anemia