Eosinophilic Gastritis

Eosinophilic gastritis is a chronic inflammatory condition of the gastric mucosa characterized by infiltration of eosinophils into the gastric wall, often extending into the submucosa and muscularis. It is part of a spectrum of eosinophilic gastrointestinal diseases (EGIDs) that can affect the stomach alone or in combination with the intestines (eosinophilic gastroenteritis). The disease is typically idiopathic but may be associated with dietary hypersensitivity, adverse reactions to food, or parasitic infections. Clinically, it manifests with chronic vomiting, anorexia, and weight loss. Diagnosis requires histopathological confirmation via endoscopic biopsy. Treatment focuses on dietary modification, glucocorticoids, and supportive care. Prognosis is generally good with appropriate therapy, though relapses are common.

The exact etiology of eosinophilic gastritis is often unknown (idiopathic). However, several potential triggers have been identified: 1) Dietary hypersensitivity: Adverse food reactions, particularly to specific proteins (e.g., beef, dairy, chicken, wheat) can stimulate a type I hypersensitivity reaction with eosinophilic infiltration. 2) Parasitic infections: Gastrointestinal parasites such as Physaloptera spp., Ollulanus tricuspis, and Gnathostoma spinigerum can induce eosinophilic inflammation. 3) Immune-mediated mechanisms: Dysregulation of T-helper 2 (Th2) cell responses leading to overproduction of interleukin-5 (IL-5), IL-13, and eotaxin, which promote eosinophil recruitment and survival. 4) Genetic predisposition: Certain breeds (e.g., German Shepherds, Rottweilers) may have a genetic susceptibility. 5) Concurrent inflammatory bowel disease (IBD): Eosinophilic gastritis may be a component of a broader eosinophilic enteritis or mixed inflammatory bowel disease. 6) Mast cell tumors or systemic mastocytosis: Rarely, neoplastic mast cells can release chemotactic factors for eosinophils. 7) Drug reactions: Some drugs (e.g., antibiotics, NSAIDs) have been implicated in rare cases. The molecular triggers involve activation of eosinophils, release of cytotoxic granules (major basic protein, eosinophil cationic protein), and subsequent tissue damage.

Eosinophilic gastritis is an uncommon condition in dogs and cats. It can occur at any age but is more frequently diagnosed in young to middle-aged animals (mean age 4-6 years). There is no strong sex predilection. Certain breeds appear overrepresented: in dogs, German Shepherds, Rottweilers, and Boxers; in cats, Siamese and domestic shorthairs may be predisposed. The incidence is not well-defined, but it accounts for a small percentage of chronic gastritis cases. Geographic variation may reflect parasite prevalence, but the disease is reported worldwide. No seasonal pattern is recognized.

The pathophysiology involves a complex interplay of genetic, environmental, and immunological factors. In susceptible individuals, an initial trigger (e.g., dietary antigen, parasite) leads to activation of Th2 lymphocytes, which secrete cytokines such as IL-4, IL-5, and IL-13. IL-5 promotes eosinophil production and release from the bone marrow, while IL-13 and eotaxin (CCL11) facilitate eosinophil migration to the gastric mucosa. Eosinophils accumulate in the lamina propria and submucosa, where they degranulate, releasing cytotoxic proteins (major basic protein, eosinophil-derived neurotoxin, eosinophil cationic protein) and lipid mediators (leukotrienes, platelet-activating factor). These substances cause tissue damage, increased vascular permeability, and smooth muscle contraction, leading to mucosal edema, ulceration, and fibrosis. Chronic inflammation can result in gastric wall thickening, impaired motility, and maldigestion. In severe cases, eosinophilic infiltration may extend transmurally, causing eosinophilic gastroenteritis with systemic signs. The disease may also be associated with concurrent inflammatory bowel disease, suggesting a shared mucosal immune dysregulation.

Predisposing factors include: 1) Genetic susceptibility: Certain breeds have a higher incidence, suggesting a heritable component. 2) Age: Young to middle-aged animals are more commonly affected. 3) Dietary factors: Exposure to specific dietary proteins, especially those commonly implicated in food allergies (beef, dairy, chicken, wheat, soy). 4) Parasitic exposure: In regions where parasites like Physaloptera are endemic, infection may trigger eosinophilic gastritis. 5) Concurrent atopic dermatitis or other allergic conditions: Animals with a history of allergies may be at higher risk. 6) Immunosuppression: Animals on immunosuppressive drugs or with immunodeficiencies may have altered immune regulation. 7) Stress: Environmental stress may exacerbate clinical signs, though not a direct cause.

Clinical signs are often chronic and intermittent. The most common sign is chronic vomiting, which may occur hours after eating and can be bile-stained or contain food. Other signs include anorexia, weight loss, lethargy, and abdominal discomfort. In some cases, diarrhea may be present if the intestines are also affected. Physical examination may reveal a thin body condition, mild dehydration, and possibly a palpable thickened stomach or abdominal pain. In severe cases, hematemesis or melena may occur due to gastric ulceration. Systemic signs such as fever are uncommon but possible. The severity of signs can vary from mild to severe, and some animals may have a waxing and waning course.

Differential diagnoses for chronic vomiting and gastric inflammation include: 1) Chronic gastritis (lymphocytic-plasmacytic, granulomatous): Differentiated by histopathology showing predominant cell type. 2) Inflammatory bowel disease (IBD) with gastric involvement: Often mixed inflammatory infiltrate; eosinophilic gastritis may be a subset. 3) Gastric neoplasia (lymphoma, adenocarcinoma): Distinguished by histopathology, cytology, and imaging (thickened wall, mass effect). 4) Parasitic gastritis (Physaloptera, Ollulanus): Fecal examination or visualization on endoscopy; response to anthelmintics. 5) Gastric ulceration (NSAID-induced, stress): History of drug administration, endoscopic findings. 6) Foreign body: Imaging or endoscopy reveals obstruction. 7) Motility disorders (gastric stasis): May be primary or secondary; diagnosed via contrast radiography or scintigraphy. 8) Metabolic diseases (renal failure, hepatic disease, hypoadrenocorticism): Laboratory testing rules out. 9) Dietary indiscretion or toxicity: Acute onset, history. 10) Hypertrophic gastropathy (Ménétrier's disease-like): Rare, characterized by giant rugal folds.

The diagnostic approach should be systematic: 1) History and physical examination: Identify chronic vomiting, weight loss, and possible dietary triggers. 2) Minimum database: Complete blood count (CBC), serum biochemistry profile, urinalysis, and fecal examination (including Baermann technique for parasites). 3) Baseline imaging: Abdominal radiographs to rule out obstruction or foreign body; abdominal ultrasound to assess gastric wall thickness and lymph nodes. 4) Serum markers: Consider cobalamin and folate levels if concurrent intestinal disease is suspected. 5) Endoscopy: Visualize gastric mucosa, obtain multiple biopsy samples (at least 8-10 from stomach and duodenum). 6) Histopathology: Confirm eosinophilic infiltration (e.g., >10 eosinophils per high-power field in the gastric mucosa). 7) Response to dietary trial: If food allergy is suspected, an elimination diet trial (e.g., novel protein or hydrolyzed protein) for 8-12 weeks may be diagnostic. 8) Additional tests: If parasitic disease is suspected, gastric lavage or endoscopy may reveal parasites; serology for specific parasites (e.g., Gnathostoma) if travel history. 9) In refractory cases, consider advanced imaging (CT) or exploratory laparotomy with full-thickness biopsies.

Hematology: Peripheral eosinophilia is present in approximately 50% of cases, but its absence does not rule out the disease. CBC may also show mild anemia if chronic disease or blood loss. Serum biochemistry: Often unremarkable; may show mild hypoalbuminemia if protein-losing enteropathy is concurrent. Liver enzymes may be mildly elevated due to inflammation. Electrolyte disturbances (hypokalemia, hypochloremia) may occur with chronic vomiting. Urinalysis: Usually normal; assess hydration status. Blood gas analysis: May reveal metabolic alkalosis with hypochloremia and hypokalemia due to vomiting. Specific biomarkers: Fecal alpha-1-proteinase inhibitor can be elevated in protein-losing enteropathy. Cobalamin and folate levels may be low if small intestinal disease is present. Serology/PCR: For infectious agents (e.g., Physaloptera) if suspected. In some cases, serum IgE levels may be elevated, but this is not specific.

Radiography: Abdominal radiographs are often unremarkable but may show a thickened gastric wall or signs of gastric outflow obstruction. Contrast studies (barium) may reveal irregular mucosal pattern or delayed gastric emptying. Ultrasonography: Gastric wall thickening (especially the muscularis layer) may be observed; the wall may appear hypoechoic or have loss of normal layering. Doppler ultrasound can assess blood flow. Computed Tomography (CT): Provides detailed assessment of gastric wall thickness and lymphadenopathy; may be useful for staging if neoplasia is suspected. Magnetic Resonance Imaging (MRI): Rarely used for gastric disease but can evaluate soft tissue detail. Endoscopy: Essential for diagnosis; allows direct visualization of the gastric mucosa (erythema, erosions, nodules, thickened folds) and collection of biopsy samples. Fluoroscopy: Can assess gastric motility and emptying.

Cytology: Fine-needle aspiration of a thickened gastric wall may yield eosinophils, but this is rarely diagnostic. Endoscopic brush cytology may show eosinophils but is not definitive. Histopathology: The gold standard. Biopsy samples should be taken from multiple sites, including the gastric body and antrum. Histological features include: 1) Eosinophilic infiltration of the lamina propria and submucosa, often with >10 eosinophils per high-power field. 2) Eosinophilic cryptitis or abscesses. 3) Mucosal edema, fibrosis, and epithelial erosion or ulceration. 4) Concurrent lymphocytic-plasmacytic inflammation may be present. Special stains (e.g., Giemsa) may help identify parasites. In severe cases, transmural infiltration may be seen on full-thickness biopsies.

Treatment is multimodal and aims to reduce inflammation, manage clinical signs, and address underlying triggers. 1) Dietary management: For suspected food allergy, an elimination diet with a novel protein (e.g., rabbit, kangaroo) or hydrolyzed protein diet is recommended for at least 8-12 weeks. If clinical signs resolve, a challenge with the previous diet can confirm the diagnosis. 2) Glucocorticoids: Prednisolone is the mainstay of therapy. For dogs: 1-2 mg/kg PO q12h initially, then taper over 3-4 weeks to the lowest effective dose (e.g., 0.5 mg/kg q48h). For cats: 1-2 mg/kg PO q12h, then taper. If refractory, alternative immunosuppressants such as cyclosporine (5 mg/kg PO q24h) or azathioprine (dogs: 2 mg/kg PO q24h; cats: 0.3 mg/kg PO q48h) may be used. 3) Antiemetics: Maropitant (1 mg/kg SC q24h or 2 mg/kg PO q24h) or ondansetron (0.1-0.2 mg/kg IV q8-12h) to control vomiting. 4) Gastroprotectants: If ulceration is present, use omeprazole (0.5-1 mg/kg PO q12h) or famotidine (0.5 mg/kg PO q12h). 5) Anthelmintics: If parasitic disease is suspected or confirmed, fenbendazole (50 mg/kg PO q24h for 3-5 days) or pyrantel pamoate (5 mg/kg PO, repeated in 3 weeks) may be used. 6) Supportive care: Fluid therapy for dehydration, nutritional support (e.g., feeding tubes if anorexic), and correction of electrolyte imbalances. 7) In severe refractory cases, consider surgical resection if a focal lesion is present, but this is rare.

The prognosis for eosinophilic gastritis is generally good with appropriate treatment. Most animals respond to dietary modification and glucocorticoids within 1-2 weeks. However, relapses are common, especially if the underlying trigger is not identified. Long-term management may be required. Negative prognostic indicators include: severe weight loss, hypoalbuminemia, concurrent inflammatory bowel disease, and lack of response to initial therapy. In cases with transmural involvement or severe fibrosis, prognosis may be guarded. Mortality is low unless complications such as gastric perforation or severe protein-losing enteropathy occur.

Follow-up should be scheduled at 2-4 weeks after initiation of therapy to assess response. Recheck examinations should include body weight, clinical sign assessment, and possibly repeat blood work (CBC, biochemistry) to monitor for drug side effects. If clinical signs resolve, the glucocorticoid dose should be tapered gradually over several weeks. Repeat endoscopy with biopsy may be considered after 4-8 weeks to document histological improvement, but this is not always necessary. Long-term monitoring includes regular veterinary visits every 3-6 months, with adjustments to diet and medication as needed. Owners should be educated on the importance of strict dietary compliance and early recognition of relapse signs.

Pearls: 1) Always obtain multiple gastric biopsies during endoscopy, as lesions may be patchy. 2) Peripheral eosinophilia is not always present; do not rule out eosinophilic gastritis based on normal CBC. 3) A dietary trial with a novel protein or hydrolyzed diet is both diagnostic and therapeutic; consider it before starting immunosuppressive therapy. 4) In cats, consider concurrent eosinophilic enteritis; evaluate duodenal biopsies as well. 5) If vomiting is severe, use maropitant for symptomatic relief while awaiting diagnostic results. Pitfalls: 1) Failing to perform fecal examinations for parasites, leading to unnecessary immunosuppression. 2) Using glucocorticoids without a dietary trial, which may mask signs and complicate diagnosis. 3) Tapering steroids too quickly, leading to relapse. 4) Overlooking concurrent diseases such as hypoadrenocorticism, which can cause similar signs. 5) Assuming that eosinophilic gastritis is always food-related; some cases are truly idiopathic and require long-term immunosuppression.

Based on Plumb's Veterinary Drug Handbook, the following protocols are recommended: 1) Prednisolone: Dogs: 1-2 mg/kg PO q12h for 7-14 days, then taper by 25% every 2 weeks to the lowest effective dose (e.g., 0.5 mg/kg q48h). Cats: 1-2 mg/kg PO q12h, then taper similarly. If no response in 2 weeks, consider alternative. 2) Cyclosporine (Atopica): Dogs: 5 mg/kg PO q24h; Cats: 5 mg/kg PO q24h. Monitor blood levels if possible. 3) Azathioprine (Imuran): Dogs: 2 mg/kg PO q24h for 7-10 days, then q48h; Cats: 0.3 mg/kg PO q48h (use with caution due to potential bone marrow suppression). 4) Maropitant (Cerenia): Dogs: 1 mg/kg SC q24h or 2 mg/kg PO q24h; Cats: 1 mg/kg SC q24h or 2 mg/kg PO q24h. 5) Ondansetron: Dogs and cats: 0.1-0.2 mg/kg IV q8-12h. 6) Omeprazole: Dogs: 0.5-1 mg/kg PO q12h; Cats: 0.5-1 mg/kg PO q12h. 7) Famotidine: Dogs: 0.5 mg/kg PO q12h; Cats: 0.5 mg/kg PO q12h. 8) Fenbendazole: Dogs and cats: 50 mg/kg PO q24h for 3-5 days. 9) Metronidazole (if concurrent IBD): Dogs: 10-15 mg/kg PO q12h; Cats: 10-15 mg/kg PO q12h. Adjust doses for renal or hepatic impairment. Monitor for side effects such as polyuria, polydipsia, and panting with glucocorticoids.

Evidence-based literature on eosinophilic gastritis is limited, but several studies and consensus statements provide guidance. The ACVIM consensus statement on chronic inflammatory disorders of the gastrointestinal tract in dogs and cats (2010) highlights the importance of histopathology for diagnosis and recommends dietary trials before immunosuppressive therapy. A study by Jergens et al. (2010) evaluated the clinical and histologic response to treatment in dogs with eosinophilic gastroenteritis, showing that a combination of dietary modification and prednisolone resulted in clinical remission in most cases. Another study by Kleinschmidt et al. (2006) described the endoscopic and histologic features of eosinophilic gastritis in dogs, emphasizing the need for multiple biopsies. In cats, a retrospective study by Tucker et al. (2014) found that eosinophilic gastritis was often associated with concurrent inflammatory bowel disease and responded well to corticosteroids. There are no large randomized controlled trials, but expert consensus supports the use of novel protein diets and glucocorticoids as first-line therapy. Future research should focus on identifying specific dietary triggers and biomarkers to guide therapy.