Equine Gastric Ulcer Syndrome (EGUS)

Equine Gastric Ulcer Syndrome (EGUS) is a multifactorial disease complex characterized by ulceration and erosion of the squamous and/or glandular mucosa of the equine stomach. It is broadly classified into two distinct syndromes: Equine Squamous Gastric Disease (ESGD) and Equine Glandular Gastric Disease (EGGD). ESGD primarily affects the non-glandular squamous mucosa, which is histologically similar to the esophagus and lacks protective mucus and bicarbonate secretion, making it highly susceptible to acid injury. EGGD involves the glandular mucosa (fundic and pyloric regions), which normally has robust protective mechanisms, and its pathophysiology is less understood, often involving disruption of mucosal blood flow, altered mucus production, and inflammatory responses. EGUS is highly prevalent in performance horses, particularly Thoroughbred and Standardbred racehorses, as well as in show and pleasure horses, with reported prevalence rates exceeding 90% in some athletic populations. The syndrome is a significant cause of poor performance, behavioral changes, recurrent colic, and decreased feed intake, impacting the equine industry economically and welfare-wise. The condition is diagnosed definitively via gastroscopy, and management involves dietary modifications, environmental changes, and pharmacological acid suppression, primarily with proton pump inhibitors such as omeprazole.

The etiology of EGUS is multifactorial, involving an imbalance between aggressive factors (hydrochloric acid, pepsin, bile acids) and protective mucosal mechanisms. In ESGD, the primary cause is prolonged exposure of the squamous mucosa to gastric acid, which is exacerbated by high-concentrate diets that produce volatile fatty acids (VFAs), particularly propionic and butyric acids, which can directly damage the squamous epithelium. Intense exercise increases intra-abdominal pressure, compressing the stomach and forcing acidic contents into the squamous region, especially in horses exercised on an empty stomach. Intermittent feeding and prolonged periods of fasting allow gastric acid to accumulate, increasing exposure time. In EGGD, the etiology is more complex and may involve bacterial infection (e.g., Helicobacter spp.), non-steroidal anti-inflammatory drug (NSAID) administration, stress, and disruption of mucosal blood flow. NSAIDs inhibit cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis, which is critical for mucosal protection. Stress, including transportation, training, and social changes, activates the hypothalamic-pituitary-adrenal axis, increasing cortisol and gastric acid secretion. Additionally, high-grain diets alter the gastric microbiome, promoting the growth of acid-producing bacteria and reducing protective commensals. Parasitic infections, such as Gasterophilus spp. (bot fly larvae), can cause mechanical irritation and ulceration. Other factors include genetic predisposition, age, and concurrent diseases such as equine metabolic syndrome.

EGUS is one of the most common diseases of the equine stomach, with a worldwide distribution. Prevalence varies by discipline and management. In Thoroughbred racehorses in active training, prevalence of ESGD is reported to be 80-100%, while EGGD is found in 50-60% of these horses. Standardbred racehorses show similar high prevalence. In endurance horses, prevalence is around 70-90%. Show horses (e.g., dressage, jumping) have a prevalence of 40-60%. Pleasure horses and pasture-kept horses have lower prevalence, around 10-30%. Age is a risk factor, with foals and weanlings being susceptible, especially during stressful periods such as weaning and transport. Sex does not appear to be a significant risk factor. Breed predilection is not clearly established, but performance breeds are overrepresented due to management and exercise. Seasonality may influence prevalence, with higher rates during training seasons and competition. Housing (stall confinement vs. pasture) and diet (high concentrate, low forage) are major risk factors. Morbidity is high, but mortality is low unless complications such as gastric perforation occur. The condition significantly impacts athletic performance, leading to economic losses due to reduced training days and veterinary costs.

The pathophysiology of EGUS involves a complex interplay of aggressive and protective factors. In ESGD, the squamous mucosa is exposed to hydrochloric acid, pepsin, and bile acids. During exercise, increased intra-abdominal pressure causes the stomach to compress, pushing acidic contents into the squamous region, especially when the horse exercises on an empty stomach. High-concentrate diets lead to fermentation in the stomach, producing VFAs that diffuse into squamous epithelial cells, causing intracellular acidification and cellular damage. The squamous mucosa lacks a mucus layer and bicarbonate secretion, making it vulnerable to acid injury. Prolonged acid exposure leads to epithelial cell death, erosion, and ulceration. In EGGD, the glandular mucosa has protective mechanisms, but these can be overwhelmed. NSAIDs inhibit COX-1 and COX-2, reducing prostaglandin E2 synthesis, which is essential for mucus and bicarbonate secretion, mucosal blood flow, and epithelial proliferation. This leads to increased mucosal permeability and inflammation. Stress-induced cortisol release increases gastric acid secretion and reduces mucosal blood flow. Bacterial infections, such as Helicobacter pylori-like organisms, may colonize the glandular mucosa, causing chronic inflammation. Bile acid reflux from the duodenum can also damage the glandular mucosa. In both types, ulceration can lead to hemorrhage, pain, and in severe cases, perforation and peritonitis. The healing process involves granulation tissue formation and re-epithelialization, which can be impaired by continued acid exposure.

Predisposing factors for EGUS are numerous and can be categorized as intrinsic and extrinsic. Intrinsic factors include age (foals and young horses are more susceptible), breed (Thoroughbreds and Standardbreds are at higher risk due to management), and individual temperament (horses with anxious or nervous dispositions are more prone). Concurrent diseases such as equine metabolic syndrome (EMS) and pituitary pars intermedia dysfunction (PPID) may increase risk due to altered metabolism and stress. Extrinsic factors are primarily management-related: high-concentrate, low-forage diets; intermittent feeding with prolonged fasting; intense exercise, especially on an empty stomach; stall confinement; transportation; social stress; and administration of NSAIDs. Sudden changes in diet or routine can precipitate ulcer formation. In foals, factors such as weaning, transport, and illness are significant. In performance horses, the combination of high-grain diets and intense training is a major risk. Additionally, the use of certain medications, such as corticosteroids, may increase risk. Environmental factors like heat and humidity may contribute to stress. Overall, the most significant predisposing factor is the management system that deviates from the horse's natural grazing behavior, leading to prolonged periods of gastric acidity.

Clinical signs of EGUS vary depending on the severity and location of ulcers. Common signs include poor appetite, weight loss, decreased performance, behavioral changes (e.g., aggression, reluctance to work), and recurrent mild colic. Horses may show signs of abdominal discomfort such as pawing, flank watching, and lying down more frequently. In severe cases, acute colic may occur due to gastric perforation or pyloric obstruction. Foals may exhibit bruxism (teeth grinding), excessive salivation, and diarrhea. On physical examination, horses may have a normal temperature, but heart rate may be elevated in painful cases. Abdominal auscultation may reveal decreased borborygmi. In cases of perforation, signs of septic shock and peritonitis may be present. Gastroscopy is the definitive diagnostic tool, and findings are graded using the EGUS grading system: Grade 0 (normal), Grade 1 (mild hyperkeratosis or reddening), Grade 2 (small single or multiple ulcers), Grade 3 (large or deep ulcers), Grade 4 (extensive ulcers with hemorrhage or deep lesions). Clinical signs do not always correlate with ulcer severity, and some horses with severe ulcers may be asymptomatic. Therefore, a high index of suspicion is necessary in at-risk populations.

Differential diagnoses for EGUS include other causes of colic, poor performance, and inappetence. Key differentials include: 1) Gastric impaction, which presents with colic and nasogastric reflux, but is distinguished by gastroscopy showing impacted feed material. 2) Gastric neoplasia (e.g., squamous cell carcinoma), which may cause weight loss and colic, but is rare and diagnosed via biopsy. 3) Inflammatory bowel disease (IBD), which can cause weight loss and diarrhea, but is differentiated by intestinal biopsy and response to dietary changes. 4) Parasitic gastritis (e.g., Gasterophilus spp.), which may cause similar signs but is diagnosed by identifying larvae on gastroscopy. 5) NSAID-induced right dorsal colitis, which presents with diarrhea and colic, but is differentiated by history of NSAID use and ultrasonographic findings of thickened right dorsal colon. 6) Equine motor neuron disease (EMND), which causes weight loss and muscle tremors, but is differentiated by muscle biopsy and vitamin E levels. 7) Dental disease, which can cause poor appetite and weight loss, but is diagnosed by oral examination. 8) Chronic liver disease, which may cause inappetence and weight loss, but is differentiated by liver enzyme elevations and ultrasound. 9) Gastroduodenal ulceration in foals, which can present with similar signs but is more common in young animals. 10) Peritonitis, which can cause colic and fever, but is differentiated by peritoneal fluid analysis. Definitive diagnosis of EGUS requires gastroscopy, which allows direct visualization of ulcers.

The diagnostic algorithm for EGUS begins with a thorough history and physical examination, focusing on management practices, exercise regimen, and clinical signs. If EGUS is suspected, the next step is gastroscopy, which is the gold standard. Gastroscopy should be performed after a 12-hour fast to ensure the stomach is empty. The horse is sedated, and a 3-meter endoscope is passed via the nose into the stomach. The stomach is insufflated with air to visualize the squamous and glandular mucosa. The esophagus, stomach, and proximal duodenum are examined. Ulcers are graded using the EGUS grading system. If gastroscopy is not available, a therapeutic trial with omeprazole may be attempted, but this is not definitive. Other diagnostic tests include fecal occult blood testing, which is not sensitive or specific. Abdominal ultrasound may be useful to rule out other causes of colic. In cases of suspected perforation, abdominocentesis may be performed to assess for peritonitis. Laboratory tests, including CBC and serum biochemistry, may reveal anemia or hypoproteinemia in chronic cases. In foals, gastroscopy is also the preferred method. The diagnostic algorithm should also include assessment for concurrent diseases such as PPID or EMS, which may contribute to ulcer formation. If EGGD is suspected, gastric biopsy may be taken during gastroscopy for histopathology and culture. Overall, gastroscopy is essential for definitive diagnosis and grading of EGUS.

Laboratory findings in EGUS are often nonspecific but may support the diagnosis and rule out other conditions. Complete blood count (CBC) may show mild anemia due to chronic blood loss, but this is uncommon. Serum biochemistry may reveal hypoproteinemia or hypoalbuminemia in severe cases due to protein loss through ulcerated mucosa. In cases of perforation, peritoneal fluid analysis would show elevated white blood cell count (>10,000 cells/µL), total protein (>2.5 g/dL), and lactate (>2 mmol/L), indicating septic peritonitis. Fecal occult blood testing may be positive but is not sensitive. In foals, gastroscopy is preferred over laboratory tests. For EGGD, gastric biopsy may show inflammatory changes, and culture may identify Helicobacter-like organisms. In horses with concurrent disease, such as PPID, ACTH levels may be elevated. In cases of NSAID toxicity, renal parameters may be elevated. Overall, laboratory findings are not diagnostic for EGUS but are useful for monitoring complications and ruling out other diseases.

Imaging modalities for EGUS primarily include gastroscopy, which is the gold standard. Gastroscopy allows direct visualization of the gastric mucosa and grading of ulcers. It is performed with a flexible endoscope, typically 3 meters in length, under sedation. The stomach is insufflated with air to distend the walls and allow thorough examination. The squamous mucosa is examined first, followed by the glandular region and the pylorus. The duodenum may also be examined. Findings are graded using the EGUS grading system. Abdominal ultrasound may be used to rule out other causes of colic, such as intestinal obstruction or peritonitis, but it is not useful for diagnosing gastric ulcers. Radiography is not useful for gastric ulcers in adult horses due to the size of the stomach and the lack of contrast. In foals, contrast radiography may be used to detect gastric ulcers, but gastroscopy is preferred. CT and MRI are not used for EGUS diagnosis. Scintigraphy is not indicated. Therefore, gastroscopy is the primary imaging modality for EGUS.

Cytology and histopathology are not routinely used for EGUS diagnosis, but gastric biopsies may be taken during gastroscopy to differentiate EGGD from other conditions. Biopsies are obtained using endoscopic biopsy forceps and submitted for histopathology. Histological findings in ESGD include hyperkeratosis, erosion, and ulceration of the squamous epithelium, with infiltration of neutrophils and mononuclear cells. In EGGD, histopathology may show chronic inflammation, glandular atrophy, fibrosis, and infiltration of lymphocytes and plasma cells. Special stains may be used to identify Helicobacter-like organisms. Cytology of gastric fluid may be performed but is not diagnostic. In cases of perforation, peritoneal fluid cytology would show degenerative neutrophils and bacteria. Overall, histopathology is useful for confirming EGGD and ruling out neoplasia.

Treatment of EGUS aims to reduce gastric acidity, promote mucosal healing, and manage underlying risk factors. The primary pharmacological agent is omeprazole, a proton pump inhibitor, administered at a dose of 4 mg/kg PO once daily for 28 days. For severe cases, a higher dose of 4 mg/kg PO q12h may be used initially. Omeprazole paste is commonly used. Sucralfate, a mucosal protectant, may be administered at a dose of 20-40 mg/kg PO q6-8h, especially for EGGD. Antacids such as magnesium hydroxide or aluminum hydroxide may be used for rapid but short-lived acid neutralization. H2 receptor antagonists, such as ranitidine (6.6 mg/kg PO q8h) or cimetidine (20 mg/kg PO q6h), are less effective than omeprazole but may be used as alternatives. In cases of NSAID-induced ulcers, NSAIDs should be discontinued. Supportive care includes dietary modifications: provide free-choice forage, reduce concentrate intake, and feed small, frequent meals. Environmental changes to reduce stress, such as increased turnout and social interaction, are important. In severe cases with colic, analgesics such as flunixin meglumine (1.1 mg/kg IV) may be used, but caution is advised due to potential NSAID-induced ulceration. In cases of perforation, emergency surgery is required. For foals, treatment is similar, with omeprazole at 4 mg/kg PO once daily. Follow-up gastroscopy is recommended after 28 days to assess healing.

The prognosis for EGUS is generally good with appropriate treatment and management changes. Most squamous ulcers heal within 28 days of omeprazole therapy, with healing rates of 70-90%. Glandular ulcers may take longer to heal and have a higher recurrence rate. The prognosis is worse if the underlying risk factors are not addressed. Complications such as gastric perforation carry a grave prognosis, with high mortality. In performance horses, return to athletic function is usually possible after healing, but recurrence is common if management is not modified. Negative prognostic indicators include severe ulceration (Grade 4), concurrent disease, and failure to respond to treatment. Overall, with early diagnosis and comprehensive management, the prognosis is favorable.

Follow-up for EGUS includes repeat gastroscopy 28 days after initiation of treatment to assess healing. If ulcers have healed, maintenance therapy with omeprazole at a lower dose (1-2 mg/kg PO once daily) may be continued during periods of stress or training. If ulcers are not healed, treatment should be extended for another 28 days. Regular monitoring of clinical signs and body condition is important. Management changes should be maintained, including dietary adjustments and stress reduction. In performance horses, a gradual return to training is recommended. For horses on long-term NSAID therapy, gastroprotective agents should be considered. Annual gastroscopy may be recommended for high-risk horses. Overall, follow-up is essential to prevent recurrence.

Clinical pearls: 1) Always consider EGUS in any performance horse with poor appetite, poor performance, or mild colic. 2) Gastroscopy is the only reliable diagnostic tool; do not rely on clinical signs alone. 3) Omeprazole is the most effective treatment; ensure proper dosing and duration. 4) Address management factors, especially diet and exercise, to prevent recurrence. 5) In foals, EGUS can be life-threatening; treat aggressively. Pitfalls: 1) Using NSAIDs to treat colic in a horse with EGUS can worsen ulcers; use alternative analgesics if possible. 2) Underdosing omeprazole or stopping treatment too early leads to incomplete healing. 3) Ignoring the need for dietary changes results in recurrence. 4) Failing to consider EGGD, which may require additional therapy such as sucralfate. 5) Not performing follow-up gastroscopy to confirm healing.

Current drug protocols for EGUS are based on ACVIM consensus guidelines and Plumb's Veterinary Drug Handbook. Omeprazole: 4 mg/kg PO once daily for 28 days; for severe cases, 4 mg/kg PO q12h for 14 days, then once daily. Sucralfate: 20-40 mg/kg PO q6-8h for 14-28 days, especially for EGGD. Ranitidine: 6.6 mg/kg PO q8h or 1.5 mg/kg IV q8h. Cimetidine: 20 mg/kg PO q6h or 5 mg/kg IV q6h. Antacids: magnesium hydroxide/aluminum hydroxide 30-60 mL PO q4-6h as needed. For pain management, flunixin meglumine (1.1 mg/kg IV or PO q12-24h) should be used cautiously and only short-term; alternative analgesics such as butorphanol (0.02-0.05 mg/kg IV) may be used. In cases of perforation, broad-spectrum antibiotics such as penicillin G (22,000 IU/kg IV q6h) and gentamicin (6.6 mg/kg IV q24h) are indicated. Fluid therapy with polyionic isotonic crystalloids (e.g., lactated Ringer's solution) at a rate of 2-4 mL/kg/h is used for dehydration. For foals, omeprazole at 4 mg/kg PO once daily is recommended. Always follow current veterinary guidelines and adjust dosages based on individual patient status.

Evidence-based literature supports the high prevalence of EGUS in performance horses and the efficacy of omeprazole. A landmark study by Murray et al. (1996) demonstrated that omeprazole paste healed gastric ulcers in Thoroughbred racehorses. Subsequent studies have confirmed the superiority of omeprazole over H2 antagonists. The ACVIM consensus statement (2015) provides guidelines for diagnosis and treatment. Research on EGGD is less extensive, but studies suggest that sucralfate may be beneficial. Management strategies, such as increasing forage intake and reducing concentrate, have been shown to reduce ulcer severity. A meta-analysis by Lester et al. (2019) found that omeprazole is effective in healing squamous ulcers but less so for glandular ulcers. Overall, the evidence supports a multimodal approach to EGUS management.