The term ‘equine gastric ulcer syndrome’ has been in use since the turn of the century, but since then it has become clear that this syndrome actually consists of two quite different disease entities: equine squamous gastric disease and equine glandular gastric disease. Although they can occur simultaneously, these two entities have different risk factors, pathogenesis and treatment (Sykes et al, 2015). This article discusses the prevalence, pathogenesis, symptoms and management of equine gastric ulcer syndrome in adult horses and foals.
Prevalence
Many studies have reported on the prevalence of squamous and glandular gastric disease in adult horses (van den Boom, 2022). Both disease entities are common, and the prevalence depends on the populations studied and largely reflects the way horses are kept and used, with dietary, exercise and husbandry factors being most important.
The lowest prevalence of squamous gastric disease (11%) was reported in horses in a university riding programme, with most ulcers in 3-year-olds. This low prevalence was thought to be related to the fact that these horses did not travel, and their diet and environment remained more or less constant in 3-year-olds (Chameroy et al, 2006). When Prinsloo et al (2019) investigated the prevalence of squamous gastric disease in horses in a university teaching herd, they found that 56% of those horses had squamous gastric disease. These horses also did not travel and were provided with the same diet year round, and the difference in the prevalence of squamous gastric disease may be related to the use for teaching, rather than riding.
In high-level endurance horses, the prevalence of squamous gastric disease increased from 48% during the interseason to 93% during the race season (Tamzali et al, 2011), and in a group of 201 Warmblood horses not in training and considered to be healthy, 58% had squamous gastric disease grade ≥2; older horses were more likely to have both squamous and glandular disease (Luthersson et al, 2009).
Racehorses, especially Thoroughbreds, have consistently been reported to have the highest rates of squamous gastric disease, increasing to 90–100% when actively racing (Bell et al, 2007). These data and the fact that feral horses are much less likely to have squamous ulcers, with a prevalence of 22% (Ward et al, 2015), indicate that human use and management of horses makes them extremely prone to the development of squamous gastric ulcers, especially when used for competition and racing.
When endoscopes became available to examine the stomachs of horses, most findings were related to squamous ulceration. This can mostly be explained by the fact that shorter endoscopes were used than today, and the pyloric region could often not be visualised. Because of this, it was thought that squamous gastric disease was more common than glandular gastric disease. Longer endoscopes and the realisation that squamous and glandular gastric disease are two quite different manifestations of gastric ulceration in horses have led to an increased interest in, and understanding of, glandular gastric disease. It has become clear that glandular disease is at least as common as squamous disease, with a prevalence of 35–72% in various equine populations (van den Boom, 2022). There are some indications that Warmblood horses may be at increased risk of developing glandular gastric disease (Mönki et al, 2016), which is often present together with squamous gastric disease (Luthersson et al, 2009). Feral horses can also experience glandular gastric disease, albeit less often. An abattoir study found glandular disease in 30% of feral horses (Ward et al, 2015).
Equine gastric ulcer syndrome does not just affect adult horses; it is also an important cause of morbidity in foals, although fewer studies have been performed and mainly involved foals around the time of weaning. The reported prevalence of gastric ulcers in foals ranges from 22–57%, but may increase to as high as 97% shortly after weaning (Hewetson et al, 2018). Although it is most commonly recognised in older weanling foals (Dahlkamp et al, 2012), desquamation of the gastric mucosa has been reported in neonatal foals as young as 24 hours, although this is most likely a developmental change (Murray, 1989). Ulcers can be present in the squamous, glandular and duodenal epithelium, but they are most commonly localised in the stratified squamous epithelium adjacent to the margo plicatus (Murray, 1989). Glandular and duodenal lesions are less common, but when present, are more likely to be associated with clinical signs, although many foals with gastric ulcers show no clinical signs at all (Murray, 1989; Andrews and Nadeau, 1999). Gastroduodenal ulcer disease in foals can cause gastric outflow obstruction and secondary ulceration of the squamous epithelium and oesophagus, as a result of acid reflux (Andrews and Nadeau, 1999).
Aetiology and pathophysiology
Squamous ulceration is caused by exposure of the gastric mucosa to gastric acid and high-concentrate diets are a risk factor for squamous gastric disease, as starch leads to increased production of volatile fatty acids (Vatistas et al, 1999). The low pH caused by volatile fatty acids, together with gastric acid, causes decreased tissue resistance and barrier function of the mucosa (Widenhouse et al, 2002). In contrast, the feeding of roughage is protective as it can provide a physical barrier to protect the mucosa from acid splash. Consumption of roughage is also associated with the production of large volumes of alkaline saliva, which buffers the acids in the stomach. Horses that do not eat enough roughage are more likely to develop gastric ulcer syndrome (Galinelli et al, 2021).
Stress is often considered to be a risk factor for gastric ulceration and nervous horses are thought to be at increased risk. This notion seems to be supported by the findings of a study in show horses, which found that horses demonstrating nervous behaviour were indeed more likely to have squamous gastric disease (McClure et al, 1999). The fact that cribbing and other stereotypies, which are considered to be coping mechanisms, are associated with squamous gastric disease, also suggests a link with stress (Sykes et al, 2019). Indirect evidence for the role of stress in squamous gastric disease was provided by the finding that hair cortisol concentrations were inversely related to the severity of squamous disease (Prinsloo et al, 2019). More recent work has shown that severe squamous gastric disease can heal when horses are provided with a predictable daily routine, ad libitum roughage and removed from a herd, possibly as a result of stress reduction (Kranenburg et al, 2023). It is unknown how the composition of a group of horses influences the risk of developing gastric ulceration, but this may be related to the hierarchy within the group or to the stability of the group. Other risk factors that have been identified for squamous gastric disease include individual trainer, metropolitan yard location, lack of contact with other horses, solid partitions, playing talk radio, being owned for a shorter period, an increased time in work, travelling and current training or recent racing (Vokes et al, 2023). Standardbred trotters may have a higher risk of squamous gastric disease than Standardbred pacers, but it is not known if this is related to their different gaits, or a result of variations in how these horses are managed (Dionne et al, 2003).
Equine glandular gastric disease, which is characterised by inflammation rather than ulceration (Martineau et al, 2009), is thought to be related to a compromise of mucosal defence mechanisms (Sykes et al, 2015) and may also be linked to inflammatory bowel disease, as is the case in humans with Crohn's disease (Horjus Talabur Horje et al, 2016). One study found a correlation between histopathological evidence of gastric glandular inflammation and duodenal inflammation, with lymphoplasmacytic inflammation being most common, but eosinophilic and neutrophilic infiltration were also reported (Banse et al, 2019). Glandular gastric inflammation was not correlated with inflammation of the more distal segments of the gastrointestinal tract (Banse et al, 2019).
Inappropriate doses of non-steroidal anti-inflammatory drugs can induce glandular gastric disease in horses, but normal use of these drugs does not appear to cause glandular disease in practice (Fennell and Franklin, 2009). The preventative use of omeprazole in horses receiving non-steroidal anti-inflammatory drugs is not considered necessary, and may even be contra-indicated, given an increased incidence of intestinal complications in horses receiving both omeprazole and phenylbutazone (Ricord et al, 2021).
Stress plays a role in the development of glandular gastric disease (Sauer et al, 2018; Sykes et al, 2019) and trainer, number of caretakers and time spent with humans were shown to increase the prevalence. The reason for this is unclear, but dealing with certain, or many different people may be stressful for some horses (Mönki et al, 2016).
When horses are exercised the pressure in the abdomen and stomach increase, especially at faster gaits. This increased pressure reduces the lumen of the stomach at trot and gallop (Lorenzo-Figueras and Meritt, 2002), and gastric acid is pushed up against the squamous mucosa, increasing the risk of squamous gastric disease. The importance of exercise is highlighted by the fact that the prevalence of squamous disease increases during the race season and is very high in racing horses, although stress associated with exercise and competition may also play a role. Exercising on 5 or more days per week also considerably increased the risk of horses developing glandular gastric disease (Sykes et al, 2019), although exercise frequency is certainly not the only factor.
Although Helicobacter pylori does not appear to play a role in the development of glandular gastric disease, the local microbiota does seem to be important, although it is currently unknown what constitutes a ‘healthy’ microbiome (Husted et al, 2010; Perkins et al, 2012; Dong et al, 2016). Further work is necessary to elucidate the relationship between microbiota and glandular gastric disease.
Most of the risk factors associated with diet and exercise do not apply to foals, and in these young animals, stress is thought to be an important contributor to gastric ulcer development, especially as these tend to occur around weaning, which is known to be stressful (Dahlkamp et al, 2012). The incidence was higher in foals with a previous disorder, and especially in foals with previous or concurrent diarrhoea (Murray et al, 1990).
Clinical signs
The signs associated with gastric ulcer syndrome include poor appetite, weight loss, poor body condition, colic, discomfort when tightening the girth strap, decreased performance, altered behaviour, coat changes, teeth grinding and auto-mutilation (Sykes et al, 2015; Camacho-Luna et al, 2018). However, it is known that some horses with gastric disease show no signs at all, and some horses that do show signs do not improve when their gastric ulcers heal (Gough et al, 2022). This suggests that gastric ulcers were not responsible for causing those signs. Also, signs can be subtle and go unnoticed by owners, although the prevalence and severity of gastric ulcer syndrome were higher in horses with mild compatible signs than in horses without symptoms (Murray et al, 1989). Therefore, determining the clinical relevance of gastroscopically identified lesions can be challenging, as the severity of the lesions does not correlate with the clinical signs (Murray et al, 1989).
Equine gastric ulcer syndrome in foals can manifest as four clinical syndromes: subclinical or silent, clinical, perforating and gastric outflow obstruction secondary to pyloric stricture (Hewetson et al, 2018). The ‘silent’ ulcers are usually located in the squamous mucosa, along the margo plicatus, while clinical ulcers can be present in the squamous, glandular and/or duodenal mucosa (Murray, 1989). The clinical signs of gastric ulcer syndrome in foals include ill thrift, lethargy, inappetence, interrupted nursing, ptyalism, bruxism, frothing or drooling of milk, diarrhoea and colic (Andrews and Nadeau, 1999). Foals with gastric outflow obstruction may have secondary ulceration of the squamous mucosa of the stomach as a result of exposure to refluxed acid (Murray, 1989; Andrews and Nadeau, 1999).
As in adult horses, clinical signs cannot be used to confirm a diagnosis of gastric ulcer syndrome, but they may be used to identify animals that should undergo gastroscopic examination. In general, foals with gastric ulcer syndrome and showing clinical signs have severe lesions, but it is important to remember that even typical signs of gastric ulcer syndrome are not diagnostic and foals may be suffering from other gastrointestinal diseases (Murray, 1989). Gastric ulcers that perforate lead to severe peritonitis and are always fatal. The healing of (severe) squamous ulcers in foals may be associated with fibrosis and gastric stenosis, leading to clinical signs when the foal starts to drink less milk and eat more forage (Witt et al, 2021).
Diagnosis
When a horse shows signs that can be associated with gastric ulcer syndrome, gastroscopy should be performed to confirm, or rule out, the presence of ulcers. Horses are fasted for 12–15 hours and water withheld for several hours before gastroscopy to ensure the stomach is sufficiently empty to allow visualisation of the entire mucosa. Horses are sedated and a twitch is applied for extra restraint. Using an endoscope at least 3 m long, both the squamous and glandular portions of the stomach can be visualised. The endoscope can be passed through a short (40 cm long) endotracheal tube inserted through the ventral nasal passage into the oesophagus, to prevent a loop of the endoscope entering the oral cavity and being damaged between the horse's teeth. This has happened to the author when such a tube was not used. When squamous gastric disease is present, lesion severity can be graded and the grading system described by the Equine Gastric Ulcer Council in 1999 (Sykes et al, 2015) is most commonly used. Inter- and intra-observer reliability were substantial for grading of the squamous mucosa. However, there is a poor correlation between squamous gastric disease grade and the severity of signs, when present, and determining clinical relevance remains difficult (Murray et al, 1989). A positive response to therapy suggests that any ulcers present were clinically significant. Figure 1 shows various grades of squamous ulceration.
Grading of glandular gastric disease lesions is more problematic, with poorer inter- and intra-observer reliability and current recommendations are to use descriptive terminology for glandular disease (Sykes et al, 2015). As glandular lesions can vary considerably in appearance, being flat or raised and associated with hyperaemia and/or fibrinosuppurative exudate, and the significance of different forms being unknown, it is recommended to describe lesions by anatomical location, distribution, severity and appearance (Sykes et al, 2015). Rather than assigning a grade to glandular lesions, the authors suggest limiting the reporting of (overall) severity to absent, mild, moderate or severe. Images obtained before and after treatment can be compared to determine the effect of treatment. The use of histopathology to assess the glandular mucosa, using biopsies obtained using a transendoscopic, double-bite technique (Crumpton et al, 2015), is becoming increasingly described and may be of added benefit (Vokes et al, 2023). Figure 2 shows several examples of glandular gastric disease.
Because gastroscopy is invasive and requires fasting and expensive equipment, other diagnostic methods have been investigated. Sucrose permeability testing and the faecal occult blood test have both been shown to be inadequate for diagnosing gastric ulcer syndrome (Hewetson et al, 2017). More recently, a number of serum and salivary biomarkers have been found to be increased in horses with gastric ulcers and may prove useful as an initial screening tool to identify horses that should undergo gastroscopy (Shawaf et al, 2020).
Treatment
In general, gastric ulcers are not considered to heal spontaneously, and most horses with gastroscopically confirmed ulcers are treated. However, little is known about the natural development of gastric ulcers over time, and healing without medical treatment has been reported when management changes are implemented (Kranenburg et al, 2023). Both squamous and glandular gastric disease are the result of damage caused by gastric acid, because of increased exposure and the breakdown of local defence mechanisms, respectively. Therefore, the mainstay of treatment consists of the administration of the proton pump inhibitor omeprazole, which blocks the final step of hydrochloric acid production in parietal cells. To provide an effect, omeprazole needs to be absorbed in the small intestine and transported to the parietal cells. To avoid inactivation by gastric acid as it passes through the stomach, omeprazole needs to be protected and is most commonly administered as a buffered paste or an enteric coated formulation. A dose of 1 mg/kg of the enteric-coated formulation was equally effective for the treatment of squamous gastric disease as 4 mg/kg of a buffered omeprazole paste (Birkmann et al, 2014).
Omeprazole can effectively increase gastric pH when given once a day and, somewhat counter-intuitively, is best given when the stomach is empty (Daurio et al, 1999), before the first morning feed. Issues associated with variable bioavailability can be circumvented by using a long-acting intramuscular preparation (Sykes et al, 2017a; Gough et al, 2020), or (rarely) intravenous omeprazole. Because of local legislation, the authors can only use the long-acting formulation in horses that have not responded to treatment with oral omeprazole and have seen lower healing rates than reported by Gough et al (2020, unpublished data).
When horses with squamous gastric disease are treated for 4 weeks with oral omeprazole, 77–100% of ulcers heal, depending on the population studied. However, 3 weeks may be equally effective (Murray et al, 1997). Once weekly injections of long-acting, intramuscular omeprazole were more effective for squamous gastric disease than daily oral omeprazole, and when administered every 5 days even higher healing rates (97 and 93% for squamous and glandular disease respectively) were obtained. (Gough et al, 2020; Sundra et al, 2024). Not much is known about possible adverse effects of omeprazole in horses. A short period of rebound hypergastrinemia occurs following cessation of omeprazole treatment, although this probably does not require tapering of the dose before stopping when used for less than 8 weeks (Clark et al, 2023). Minor changes to gastric mucosal microbiota, of unknown significance, have also been reported (Cerri et al, 2020).
When glandular gastric disease is diagnosed, sucralfate (12 mg/kg twice daily orally, given 30–60 minutes after omeprazole) is often added to the treatment, which seems to improve healing (Kranenburg et al, 2020). It is usually advised to treat horses with glandular gastric disease for 8 weeks. Other therapeutic options for glandular gastric disease include the intra-muscular, long-acting omeprazole, which has been reported to have superior results to treatment with omeprazole and sucralfate (Rendle et al, 2018).
Alternatively, misoprostol, a prostaglandin analogue, can be used, which has also been reported to be superior to (oral) omeprazole in one study and with a relatively small number of horses (Varley et al, 2019). Care should be taken when using misoprostol, as it can cause fetal loss in pregnant women and should not be given concurrently with omeprazole. Esomeprazole, another proton pump inhibitor, may also be tried as a second-line treatment for glandular disease, as there is some evidence to indicate it is effective in cases of glandular disease refractive to omeprazole treatment (Rendle, 2017).
Following (successful) treatment, recurrence rates of gastric ulcers in horses are high, presumably because many of the inciting causes are still present. The importance of addressing these risk factors was demonstrated by the finding that most squamous ulcers healed 4 weeks after the introduction of management changes (Kranenburg et al, 2023) and by the fact that squamous disease recurred less often when the starch intake of horses was reduced (Luthersson et al, 2019). Providing sufficient roughage and ensuring that the horse consumes this is also important, especially for prevention of squamous gastric disease, and the frequency and timing of exercise also play a role. Exercising the horse when its stomach contains (at least a small amount) of roughage will limit ‘acid splash’, an important factor in the development of squamous gastric diease. As the number of days of exercise per week is a risk factor for glandular gastric disease (Pedersen et al, 2018; Sykes et al, 2019), ensuring two or three rest days per week seems logical. Omeprazole, at 1–2 mg/kg once daily orally, can prevent ulcer formation in horses at risk (Mason et al, 2019). However, long-term low-dose omeprazole treatment is unlikely to be effective in preventing gastric ulcer syndrome (Sykes et al, 2017b), and discontinuation is likely to lead to rebound hypergastrinaemia (Clark et al, 2023). Instead, the short-term, ‘pulsed’ use of omeprazole during times of stress has been shown to reduce the prevalence of gastric ulcer syndrome (Gehlen et al, 2021).
Conclusions
The prevalence of gastric ulcers in horses is high and this is related, at least in part, to husbandry practices. Horses with ulcers can show non-specific clinical signs, including a variable appetite, mild or recurrent colic and resentment to tightening of the girth strap, but they can also be asymptomatic. Currently, the only way to confirm the presence of gastric ulcers is by gastroscopy, but determining the clinical relevance of ulcers present remains difficult. Although treatment with omeprazole is often successful, risk factors for the development of gastric ulcers should be eliminated as far as possible, to help promote healing and reduce the likelihood of recurrence.
KEY POINTS
- Equine gastric ulcer syndrome is common in adult horses and also occurs in foals.
- Distinction must be made between equine squamous gastric disease and equine glandular gastric disease.
- Gastroscopy is necessary to determine presence and severity of equine gastric ulcer syndrome.
- Omeprazole forms the mainstay of treatment for squamous gastric disease
- Omeprazole monotherapy is unlikely to result in the healing of glandular gastric disease, and a combination with sucralfate is advised. Alternatively, glandular disease can be treated with long-acting intramuscular omeprazole or misoprostol.
- Management and husbandry practices must be addressed to treat and prevent the recurrence of ulcers.