Definition

An inflammatory disease of the stomach and intestine, characterized by an infiltration of eosinophils, usually into the lamina propria, but occasionally involving the submucosa and muscularis.

Pathophysiology

• Antigens bind to IgE on the surface of mast cells, resulting in mast cell degranulation.
• Some of the products released are potent eosinophil chemotactants.
• Eosinophils contain granules with substances that directly damage the surrounding tissues.
• Eosinophils also can activate mast cells directly, setting up a vicious cycle of degranulation and tissue destruction.

Systems Affected

• Gastrointestinal-generally stomach and small intestine; large intestine may be affected.
• In the cat, hypereosinophilic syndrome can involve the GI tract, liver, spleen, kidney, adrenal glands, and heart. There are also rare reports in the dog, particularly in rottweilers.

Genetics

N/A

Incidence/Prevalence

• Eosinophilic gastroenteritis is reportedly more common in dogs than in cats.
• Less common than lymphocytic-plasmacytic gastroenteritis.
• A mixed cellular infiltrate of eosinophils, lymphocytes, and plasma cells may be present occasionally.

Signalment

Signs

Causes

• Idiopathic eosinophilic gastroenteritis
• Parasitic
• Immune-mediated-food allergy; adverse drug reaction; associated with other forms of inflammatory bowel disease
• Systemic mastocytosis
• Hypereosinophilic syndrome
• Eosinophilic leukemia
• Eosinophilic granuloma

Risk Factors

N/A

Differential Diagnosis

• All of the causes listed above are included in the differential diagnosis of eosinophilic infiltrates in the stomach and small intestine.
• Idiopathic eosinophilic gastroenteritis is a diagnosis of exclusion.
• Multiple fecal flotations and direct smears are imperative to rule in or rule out intestinal parasitism. Routine deworming with a broad-spectrum product is commonly indicated, even when all fecal examinations are negative.
• Intestinal biopsy differentiates the other causes of inflammatory bowel disease from eosinophilic gastroenteritis.
• Dietary trial should rule-in or rule-out food allergy or hypersensitivity.

CBC/Biochemistry/Urinalysis

• Hemogram may reveal a peripheral eosinophilia-more common in cats than dogs, especially common and pronounced in hypereosinophilic syndrome.
• Panhypoproteinemia or hypoalbuminemia may be present if a protein-losing enteropathy is also present.
• Liver enzyme elevations and/or azotemia may be seen with hypereosinophilic syndrome.
• Urinalysis is usually normal.

Other Laboratory Tests

• Buffy-coat smear to help rule out systemic mastocytosis, when suspected.
• Serum cobalamin levels may be low suggesting ileal disease, folate levels may be increased suggesting small intestinal bacterial overgrowth.

Imaging

• Plain abdominal radiographs provide little information but are useful to rule out other diseases that may present with similar clinical signs.
• Barium contrast radiography may demonstrate thick intestinal walls and mucosal irregularities but does not provide any information about etiology or the nature of the thickening.
• Ultrasonography-used to measure stomach and intestinal wall thickness and to rule out other diseases; used to examine the liver, spleen, and mesenteric lymph nodes in animals with hypereosinophilic syndrome. When seen, aspirates of these organs are often indicated.

Diagnostic Procedures

• Definitive diagnosis often requires histopathology of biopsy samples obtained via endoscopy or laparotomy.
• Bone marrow aspirates are recommended if systemic mastocytosis or significant peripheral eosinophilia is apparent.
• Exploratory laparotomy may be indicated if distal small intestine is involved, or abdominal organomegaly is present.

Pathologic Findings

• Thickened rugal folds, erosions, ulcers, and increased mucosal friability may be present in the stomach, although grossly it can appear normal.
• Ulcerations and erosions may be seen in the intestine.
• Eosinophilic infiltrates can be patchy in the intestine; multiple biopsies may be necessary to obtain a diagnosis.
• Histopathology reveals a diffuse infiltrate of eosinophils into the lamina propria; the submucosa and muscularis can also be involved (more common in cats).

Appropriate Health Care

• Most treated on an outpatient basis.
• Patients with systemic mastocytosis, protein-losing enteropathies, or other concurrent illnesses may require hospitalization until they are stabilized.

Nursing Care

• If the patient is dehydrated or must be NPO because of vomiting, any balanced crystalloid solution such as lactated Ringer's solution is adequate; otherwise, select fluids on the basis of secondary diseases.
• If severe hypoalbuminemia from protein-losing enteropathy, consider colloids such as hetastarch. Small dogs under 15 pounds (7 kg) may benefit from a plasma transfusion resulting in transient increase in albumin. This may result in improved stability during anesthesia, allowing for further diagnostics and biopsies.

Activity

No need to restrict unless severely debilitated.

Diet

• Dietary manipulation is usually a critical component of therapy and may take several forms.
• Highly digestible diets with limited macronutrient sources (elimination or hydrolyzed diets)-extremely useful for eliciting remission; can be used as maintenance diets once the patient is stabilized. Most cases are managed successfully long term in this way.
• Dogs-examples include: Hill's Prescription Diet d/d and Hill's z/d; Purina HA; Royal Canin Hypoallergenic diets; Iams Response Formula FP or KO; balanced homemade diets.
• Cats-examples include: Hill's Prescription Diet z/d and d/d; Purina HA; Royal Canin Hypoallergenic diets; Iams Response LB.
• Monomeric diets (e.g., elemental diet)-have non-allergenic components; can be used in patients that are not vomiting but have moderate-to-severe GI inflammation; useful if a food allergy is suspected. However, treatment with monomeric diets is rarely necessary.
• In patients with severe intestinal involvement and significant protein-losing enteropathy, total parenteral nutrition may be indicated until remission is obtained. TPN is rarely necessary.
• Once the patient is stabilized, an elimination diet trial may be instituted if food allergy or intolerance is the suspected cause to determine the offending nutrient. This is generally not done.

Client Education

Explain the waxing and waning nature of the disease, the necessity for lifelong vigilance regarding inciting factors, and the potential for long-term therapy.

Surgical Considerations

N/A

Drug(s) Of Choice

• Glucocorticoids: prednisone 2–4 mg/kg PO q24h (rarely requires high end of dose to start). Never exceed a total dose of 50 mg/day in a dog, no matter how heavy.
• Gradually taper corticosteroids approximately 25% every 2–3 weeks until at 25% of original dose, then extend to 4- to 8-week intervals before discontinuing; relapses are more common in patients that are taken off corticosteroids too quickly.
• Occasionally other immunosuppressive drugs can be used to allow a reduction in corticosteroid dose and avoid some of the adverse effects of steroid therapy. These medications are also added in refractory cases.
• When in need of rapid immunosuppression, add chlorambucil (0.1–0.2 mg/kg q24h for 7 days then q48h). Often used in place of azathioprine but can be used in addition. A recent study suggests that this addition may be superior to adding azathioprine. Avoid the simultaneous implementation of 3 different immunosuppressive drugs at the same time.
• Immunosuppressive drugs such as azathioprine (2.2 mg/kg PO q24h, tapering to q48h after 2–3 weeks) if an immune-mediated mechanism is suspected and response to dietary management and glucocorticoid administration is inadequate. Expect response to occur in 2–3 weeks.
• Budesonide, an orally administered glucocorticoid with a high first-pass effect, has been used successfully to treat cats and dogs with inflammatory bowel disease; it appears to have more of a topical effect on the intestinal tract. Reports have shown that some absorption and secondary effects on the adrenal pituitary axis occur. Current dose recommendations are 2–3 mg/m² q24h with a gradual taper over the course of 8–10 weeks (not based on scientific research) and often requires compounding for smaller dogs. The dose for cats and dogs weighing <10 kg is 1 mg q24h with a gradual taper over the course of 8–10 weeks.

Contraindications

If secondary problems are present, avoid medications that might be contraindicated for those conditions.

Precautions

• Prednisone and budesonide (less commonly) can cause GI ulceration. Once evidence has been seen, the addition of gastric protectants is indicated. Use of gastric protectants has not been shown to prevent damage but is effective as a treatment.
• Azathioprine and chlorambucil can rarely cause bone marrow suppression in dogs; avoid the use of azathioprine in cats due to its myelosuppressive effects. All patients receiving azathioprine or chlorambucil should have a complete blood count 10–14 days after the start of treatment, with rechecks monthly and then bimonthly thereafter for the entire treatment period; bone marrow suppression can be seen at any time during treatment but is usually cumulative. It is generally reversible with drug discontinuation if caught early. A chemistry panel should also be regularly evaluated.
• Pancreatitis, hepatic damage, and anorexia are other potential side effects of these drugs.

Possible Interactions

N/A

Alternative Drug(s)

N/A

Patient Monitoring

• Initially frequent for severely affected patients; monitoring peripheral eosinophil counts may be helpful; the corticosteroid dosage is usually adjusted during these visits.
• Patients with less severe disease may be checked 2–5 weeks after the initial evaluation; monthly to bimonthly thereafter until corticosteroid therapy is completed.
• Patients receiving azathioprine-monitor as mentioned above.
• Patients usually do not require long-term follow-up unless the problem recurs.

Prevention/Avoidance

If a food intolerance or allergy is suspected or documented, avoid that particular nutrient and adhere strictly to dietary restrictions.

Possible Complications

• Weight loss, debilitation in refractory cases.
• Adverse effects of corticosteroid therapy.
• Bone marrow suppression, pancreatitis, hepatitis, or anorexia caused by azathioprine and/or chlorambucil.

Expected Course and Prognosis

• The vast majority of dogs with eosinophilic gastroenteritis respond to a combination of dietary manipulation and steroid therapy.
• Cats often have a more severe form of the disease, with a poorer prognosis than dogs.
• Cats often require higher doses of corticosteroids for longer periods of time to elicit remission.

Zoonotic Potential

A consideration only when eosinophilic infiltrates are secondary to parasites (e.g., Ancylostoma, Giardia, and ascarids).

Pregnancy/Fertility/Breeding

• Prednisone has been used safely in pregnant women; corticosteroids have been associated with increased incidence of congenital defects, abortion, and fetal death.
• Azathioprine has been used safely in pregnant women and may be a good substitute for corticosteroids in pregnant animals.

See Also

• Gastroenteritis, Lymphocytic-Plasmacytic
• Inflammatory Bowel Disease
• Mast Cell Tumors

Client Education Handout Available Online