Eosinophilic Enteritis

Eosinophilic enteritis is a chronic inflammatory bowel disease (IBD) of the small intestine characterized by diffuse or segmental infiltration of the lamina propria and sometimes the submucosa and muscularis with eosinophils. It is part of a spectrum of eosinophilic gastrointestinal diseases (EGIDs) that can affect the stomach, intestines, or both. The condition leads to malabsorption, protein-losing enteropathy, and chronic diarrhea. It is distinct from eosinophilic gastroenteritis with peripheral eosinophilia, which may be more severe. The disease is often idiopathic but can be triggered by dietary antigens, parasites, or a dysregulated immune response. It is a common cause of chronic vomiting and diarrhea in dogs and cats, and can be classified as lymphocytic-plasmacytic enteritis with eosinophilic predominance or pure eosinophilic enteritis.

The exact etiology is often unknown (idiopathic). However, potential causes include: dietary hypersensitivity (e.g., to specific proteins, carbohydrates, or additives), adverse reaction to food, parasitic infections (e.g., Trichuris vulpis, Toxocara canis, Ancylostoma caninum, Giardia, Tritrichomonas foetus in cats, Physaloptera spp.), bacterial dysbiosis, and immune-mediated mechanisms. In some cases, eosinophilic enteritis may be a component of hypereosinophilic syndrome (HES), a systemic disorder with marked eosinophilia in blood and tissues. Genetic predisposition may play a role in certain breeds. Environmental factors such as stress or concurrent infections may trigger or exacerbate the condition.

Eosinophilic enteritis is most commonly diagnosed in middle-aged dogs and cats, with a median age of 6-8 years. There is no clear sex predilection. Certain breeds are overrepresented: in dogs, German Shepherds, Boxers, and French Bulldogs may be predisposed; in cats, Siamese and related breeds may have a higher incidence. The condition is seen worldwide but may be more prevalent in regions with high parasite burdens. It accounts for a significant proportion of chronic enteropathy cases in small animal practice, with some studies reporting up to 30% of IBD cases having eosinophilic infiltration. The incidence is increasing, possibly due to improved diagnostics and awareness.

The pathophysiology involves a complex interplay of genetic susceptibility, mucosal barrier dysfunction, and aberrant immune responses. Antigenic stimulation (dietary, parasitic, or microbial) triggers a Th2-type immune response, leading to the release of cytokines such as IL-4, IL-5, and IL-13. IL-5 promotes eosinophil differentiation, activation, and survival. Activated eosinophils release cytotoxic granules containing major basic protein, eosinophil cationic protein, and eosinophil peroxidase, which damage the intestinal epithelium. This leads to increased mucosal permeability, malabsorption, and protein loss. Eosinophils also release pro-inflammatory mediators, including leukotrienes and platelet-activating factor, which amplify inflammation. Chronic inflammation can result in villous atrophy, crypt hyperplasia, and fibrosis. In severe cases, eosinophilic infiltration may extend transmurally, leading to complications such as strictures or perforation.

Predisposing factors include: genetic susceptibility (breed-specific), dietary factors (novel proteins, high-fat diets, food additives), parasitic infections (especially in young animals), concurrent immune-mediated diseases (e.g., hypoadrenocorticism, inflammatory bowel disease), stress, and environmental factors. Immunosuppressive therapy (e.g., corticosteroids) may paradoxically predispose to eosinophilic infiltration in some cases. Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) can disrupt mucosal integrity, increasing antigen exposure. Age-related changes in gut immunity may also contribute.

Clinical signs are often chronic and intermittent. Common signs include: chronic diarrhea (small bowel diarrhea, often with mucus or fresh blood), vomiting, weight loss, decreased appetite, and lethargy. In severe cases, signs of protein-losing enteropathy (PLE) may be present, such as peripheral edema, ascites, and pleural effusion. Physical examination may reveal poor body condition, dehydration, thickened bowel loops on abdominal palpation, and sometimes abdominal pain. In cats, signs may be more subtle, with weight loss and vomiting being prominent. Peripheral eosinophilia is present in about 20-50% of cases but is not always seen. In hypereosinophilic syndrome, there may be systemic signs such as fever, lymphadenopathy, and organomegaly.

Differential diagnoses include: (1) Lymphocytic-plasmacytic enteritis (LPE) - the most common form of IBD; differentiation requires histopathology. (2) Food-responsive enteropathy (FRE) - often indistinguishable clinically; response to dietary trial helps. (3) Parasitic enteritis (e.g., whipworms, hookworms, Giardia) - ruled out by fecal exams and response to anthelmintics. (4) Antibiotic-responsive enteropathy (ARE) - due to dysbiosis; ruled out by response to antibiotics. (5) Intestinal lymphoma - especially in cats; requires histopathology and immunophenotyping. (6) Protein-losing enteropathy (PLE) due to other causes (e.g., lymphangiectasia, histoplasmosis). (7) Eosinophilic granuloma complex (in cats) - may involve skin and oral cavity. (8) Hypereosinophilic syndrome (HES) - systemic eosinophilic infiltration. (9) Inflammatory bowel disease with mixed infiltrates. (10) Intestinal neoplasia (e.g., mast cell tumor, adenocarcinoma).

The diagnostic approach is stepwise: (1) Complete history and physical examination. (2) Minimum database: CBC, serum biochemistry, urinalysis, and fecal examination (direct smear, flotation, and antigen testing for Giardia). (3) Serum cobalamin and folate levels to assess small intestinal function. (4) Abdominal ultrasound to evaluate intestinal wall thickness, layering, and mesenteric lymph nodes. (5) If no contraindications, perform upper GI endoscopy with multiple biopsies from duodenum and stomach. (6) Histopathology is the gold standard for diagnosis. (7) In cases where endoscopy is not feasible or lesions are segmental, full-thickness surgical biopsies may be indicated. (8) Additional tests: serum trypsin-like immunoreactivity (TLI) to rule out exocrine pancreatic insufficiency, ACTH stimulation test to rule out hypoadrenocorticism, and food elimination trial. (9) In cats, feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) testing may be considered.

Hematology: Peripheral eosinophilia may be present (often >1,500/µL), but can be absent. In chronic cases, mild non-regenerative anemia may be seen. Serum biochemistry: Hypoproteinemia (especially hypoalbuminemia) due to protein-losing enteropathy; globulins may be normal or elevated. Liver enzymes may be mildly elevated due to inflammatory response. Electrolyte imbalances (e.g., hypokalemia) may occur with chronic diarrhea. Urinalysis: Usually unremarkable; proteinuria may be present if glomerular disease coexists. Blood gas analysis: May show metabolic acidosis due to diarrhea. Specific biomarkers: Cobalamin (vitamin B12) may be decreased due to ileal disease; folate may be decreased in proximal small intestinal disease. Serum cPLI (canine pancreatic lipase immunoreactivity) or fPLI (feline) may be normal or mildly elevated. C-reactive protein (CRP) may be elevated in some cases. Serology/PCR: Fecal PCR panels for parasites (e.g., Giardia, Tritrichomonas) may be positive. In cats, FeLV/FIV testing may be positive.

Radiography: Abdominal radiographs may show gas-filled loops of small intestine, but are often unremarkable. Ultrasonography: Findings include thickening of the muscularis and submucosa, loss of normal layering, and increased echogenicity of the mucosa. Mesenteric lymph nodes may be enlarged. Doppler ultrasound may show increased blood flow. Computed Tomography (CT): May be used to evaluate for masses or strictures, but is not routinely needed. Magnetic Resonance Imaging (MRI): Not commonly used for intestinal disease. Endoscopy: Direct visualization of the duodenal mucosa may show erythema, granularity, erosions, or increased friability. Fluoroscopy: May be used to assess motility, but is not diagnostic. Echocardiography: Not indicated unless cardiac disease is suspected.

Fine Needle Aspirates (FNA): Ultrasound-guided FNA of thickened intestinal wall or enlarged lymph nodes may reveal eosinophilic inflammation, but is not definitive. Fluid analysis: If ascites or pleural effusion is present, fluid is typically a modified transudate with low cellularity. Histopathology: The hallmark is infiltration of the lamina propria with eosinophils, often with variable numbers of lymphocytes, plasma cells, and macrophages. Villous blunting, crypt hyperplasia, and epithelial erosion may be present. Special stains (e.g., Giemsa, Luna) can highlight eosinophils. In severe cases, eosinophilic infiltration may extend into the submucosa and muscularis. The presence of eosinophilic crypt abscesses or granulomas may be seen. Histopathology is essential to rule out lymphoma, which can have similar clinical signs.

Treatment is multimodal and aims to reduce inflammation, manage clinical signs, and address underlying triggers. (1) Dietary management: A highly digestible, novel protein or hydrolyzed protein diet is recommended. An elimination diet trial for 2-4 weeks is often used. (2) Anthelmintics: Even if fecal exams are negative, a broad-spectrum dewormer (e.g., fenbendazole 50 mg/kg PO q24h for 3-5 days) is often administered. (3) Antibiotics: If dysbiosis is suspected, metronidazole (10-15 mg/kg PO q12h) or tylosin (10-20 mg/kg PO q12h) may be used for 2-4 weeks. (4) Corticosteroids: Prednisolone (dogs: 1-2 mg/kg PO q12h; cats: 2-4 mg/kg PO q24h) is the mainstay. After 2-4 weeks, the dose is tapered gradually over several months. For refractory cases, budesonide (2 mg/dog PO q24h, 1 mg/cat PO q24h) may be used. (5) Immunosuppressive agents: If corticosteroids are ineffective or to reduce their side effects, cyclosporine (5 mg/kg PO q24h) or azathioprine (2 mg/kg PO q24h in dogs; 0.3-0.5 mg/kg PO q48h in cats) may be added. (6) Supportive care: Fluid therapy, antiemetics (e.g., maropitant 1 mg/kg SC q24h), and gastroprotectants (e.g., omeprazole 1 mg/kg PO q12h) may be needed. (7) In severe cases with PLE, plasma transfusions may be required. (8) Surgery: Indicated for strictures, perforation, or if full-thickness biopsies are needed.

The prognosis is generally good with appropriate treatment, but depends on the severity and underlying cause. Many dogs and cats respond to dietary modification and immunosuppressive therapy. The median survival time for dogs with eosinophilic enteritis is reported to be >3 years. Poor prognostic indicators include severe hypoalbuminemia (<2.0 g/dL), presence of ascites, lack of response to therapy within 2 weeks, and development of complications such as thromboembolism. In cats, the prognosis is more guarded, especially if hypereosinophilic syndrome is present. Recurrence is common if therapy is discontinued prematurely.

Recheck examinations should be performed at 2, 4, 8, and 12 weeks after initiation of therapy, then every 3-6 months. At each visit, body weight, body condition score, and clinical signs should be assessed. Serial serum albumin, cobalamin, and folate levels should be monitored. If the patient is on corticosteroids, blood pressure and urine protein-to-creatinine ratio should be checked periodically. Repeat abdominal ultrasound may be performed to assess intestinal wall thickness. The corticosteroid dose should be tapered slowly (e.g., 25% reduction every 2-4 weeks) to the lowest effective dose. If the patient is on azathioprine, CBC and biochemistry should be monitored every 2-4 weeks initially, then every 3 months. Long-term management may require lifelong dietary therapy and low-dose immunosuppression.

Pearls: (1) Always perform a thorough fecal examination and empirical deworming before starting immunosuppressive therapy. (2) A food elimination trial is essential; many cases are food-responsive. (3) Histopathology is crucial; do not rely on clinical signs alone. (4) In cats, always rule out lymphoma, as it can mimic eosinophilic enteritis. (5) Monitor serum cobalamin and folate; supplementation may be needed. Pitfalls: (1) Using corticosteroids without ruling out infectious causes can worsen disease. (2) Tapering steroids too quickly can lead to relapse. (3) Overlooking concurrent diseases such as hypoadrenocorticism or exocrine pancreatic insufficiency. (4) Assuming that peripheral eosinophilia is always present; it is absent in many cases. (5) Failing to consider surgical biopsies when endoscopy is non-diagnostic.

Based on Plumb's Veterinary Drug Handbook: (1) Prednisolone: Dogs: 1-2 mg/kg PO q12h for 2-4 weeks, then taper by 25% every 2-4 weeks. Cats: 2-4 mg/kg PO q24h, taper similarly. (2) Budesonide: Dogs: 2 mg/dog PO q24h; Cats: 1 mg/cat PO q24h. (3) Cyclosporine: Dogs: 5 mg/kg PO q24h; Cats: 5 mg/kg PO q24h. Monitor blood levels if possible. (4) Azathioprine: Dogs: 2 mg/kg PO q24h; Cats: 0.3-0.5 mg/kg PO q48h. (5) Metronidazole: 10-15 mg/kg PO q12h for 2-4 weeks. (6) Tylosin: 10-20 mg/kg PO q12h. (7) Fenbendazole: 50 mg/kg PO q24h for 3-5 days. (8) Maropitant: 1 mg/kg SC q24h for vomiting. (9) Omeprazole: 1 mg/kg PO q12h. (10) Cobalamin: 250-500 µg SC weekly for 4-6 weeks, then monthly. Adjust dosages for renal or hepatic impairment; avoid NSAIDs and other ulcerogenic drugs.

Key studies include: (1) A study by Allenspach et al. (2007) found that dogs with IBD, including eosinophilic enteritis, had a good response to combination therapy with prednisolone and metronidazole. (2) A consensus statement by the ACVIM (2010) on canine chronic enteropathies recommends a stepwise approach including dietary trial, antibiotics, and immunosuppressants. (3) A study by Jergens et al. (2010) evaluated histopathologic scoring systems for IBD and found that eosinophilic infiltration is a common finding. (4) A study by Craven et al. (2004) reported that cats with eosinophilic enteritis had a good response to prednisolone, but some required additional immunosuppression. (5) A meta-analysis by Washabau et al. (2010) on feline IBD highlighted the importance of excluding lymphoma. (6) Recent studies have investigated the role of fecal microbiota and probiotics in IBD, but evidence is limited. Overall, the evidence supports the use of dietary modification and corticosteroids as first-line therapy, with immunosuppressive agents reserved for refractory cases.