Unravelling ulceration - The causes, treatment and prevention for squamous vs. glandular gastric ulceration

  Unraveling Ulceration    The causes, treatment and prevention for squamous vs. glandular gastric ulceration    By Emma Hardy, PhD   Gastric ulcers remain a common condition facing competition horses. This poses an ongoing and persistent challenge to trainers who face the negative effects of ulcers in terms of training and performance. To address the issue, the typical trainer spends a small fortune on scores of omeprazole and other ulcer remedies, only to find the problem isn’t resolved or simply comes back.  Meanwhile, researchers have been testing the very notion of “what is an ulcer?” The data casts doubt on whether go-to treatment approaches will actually work. A look at what the research now tells us about equine gastric ulcers may provide some new guidance for how best to address this nearly ubiquitous concern.   The two faces of gastric ulceration   While many people think of gastric ulcers as one specific disease, equine vets and researchers refer to gastric ulcers as a “syndrome” (Equine Gastric Ulcer Syndrome, or EGUS). The medical definition of a syndrome describes a set of symptoms and signs that together represent a disease process. In practical terms, this means that ulcers are really a clinical signs—truly a symptom—of underlying disease conditions.  A few years ago, articles began to appear in the scientific press highlighting differences in the healing of ulcers in two distinct regions of the stomach—the upper “squamous” area on the one hand, as compared to the lower “glandular” portion on the other. In recent years, researchers in Australia published a series of articles (Sykes et al, 2014) to “clarify the distinction between diseases in different regions of the stomach” (i.e., to describe the differences between ulcers in the squamous area of the stomach from those in the lower glandular area). The articles described significant differences between the two conditions, including prevalence, risk factors and response to treatment.   Squamous gastric ulceration   The upper region of the stomach is minimally protected from the corrosive effects of stomach acids. As such, squamous gastric ulceration (i.e., ulcers in the upper region of the stomach) is believed to result from the increased exposure to acid and other contents of the stomach. Ulcers in the squamous region are also more common, affecting upwards of 70% of Thoroughbred racehorses, as demonstrated in multiple studies over the past 20 years.   Glandular gastric ulceration   By contrast, ulcers in the lower glandular region of the stomach are believed to arise from a different set of conditions. The lower portion of the stomach is composed of numerous cell types including those that secrete gastric acid. Because horses secrete stomach acid continuously, the mucosal lining in this lower portion of the stomach is in direct contact with stomach acid at all times.  The lower portion of the stomach is also better protected—the glandular mucosa is lined with a thick layer of mucus that offers natural protection from acid. It is believed that glandular ulceration results from the breakdown of this protective lining. Although no research has conclusively shown exactly how this defence mechanism breaks down in horses, research in humans shows NSAID (non-steroidal anti-inflammatory drugs) use and bacterial agents are contributors.  Based on this, equine squamous gastric ulceration (ESGUS) is a specific condition distinct from equine glandular gastric ulceration (EGGUS).   Beyond the stomach   Until recently, little attention had been afforded to inflammation and ulceration developing beyond the stomach of the horse and, in particular, within the caecum and large colon. Studies have now shown how the hindgut can also be vulnerable to changes in the mucosal lining (i.e., ulcers and other types of inflammation) and should be an essential consideration in performance horse management.  The equine hindgut is vast. Thus, detecting ulcers or other colonic issues can be challenging. Visualization of gastric ulceration via 3m endoscopy has become a mainstream diagnostic procedure in many equine veterinary practices. Limitations in physical reach of the endoscope leaves it ineffective for visualizing anything beyond the proximal duodenum, and colonoscopy is simply not possible for the horse.  It could be suggested that the equine hindgut had been perceived as a bit of a “black box,” responsible for the lack of reliable diagnostic tools available for detecting issues there. But just because this part of the gut has been difficult to “see” doesn’t mean that issues don’t exist there.  Risk factors for hindgut dysbiosis and inflammation largely reside within the management and feeding practices associated with intensive exercise and management. NSAIDs can also be a significant causative agent. Extensive research involving the examination of horse cadavers has indicated that around 50% of those horses with confirmed gastric ulceration will also have some hindgut inflammation or areas of erosion. Thus, it is crucial to think of the health of the  entire  digestive tract and not only the stomach.   What this means for the trainer   Most racehorse trainers know first-hand the high cost of ulceration in their horses. There are obvious welfare implications derived from the discomfort and pain horses likely experience when suffering from ulcers and inflammation.  Ulcer-induced poor performance will often manifest as negative temperament changes, a poor attitude to work and stress-induced coping behaviors. There exists the potential for these performance-related “red flags” to be misinterpreted as bad behavior, particularly when clinical signs are vague. Thus, when responding to challenging behavior, it is always prudent to first consider that the horse may be conveying a “can’t” rather than a “won’t.”   Knowing where a problem exists streamlines recovery   If ulceration is suspected anywhere within the digestive tract, identifying where it is located is important from two aspects. Early and accurate detection is decisive in formulating an effective recovery plan, and identifying the source of the condition limits the possibility of significant long-term effects. Also, it is now appreciated that certain medications demonstrate greater efficacy depending on the diagnosis.  Omeprazole has long been the first-line treatment for all types of gastric ulceration but is now considered just one of several options. Indeed, a recent consensus statement regarding EGGUS reports that omeprazole alone may not be the most efficacious treatment since the causative factors for glandular injury are not primarily acid-induced. Instead, medications to support the health of the mucosal lining, such as the prostaglandin E analog, misoprostol may be more effective. Still, omeprazole (particularly the new injectable form) does remain a useful medication for squamous ulceration and, in conjunction with misoprostol for EGGUS, to allow acid injury to heal. Treatment duration is also markedly longer for EGGUS when compared to squamous ulceration.  A plethora of medications and approaches exist to support equine hindgut health. The success of a particular treatment will likely be dependent on the underlying cause, location and type of inflammation.   Different ulcers, different treatments   Every race trainer knows that omeprazole represents the “gold standard” treatment for equine ulcers. Omeprazole shuts down production of acid in the stomach, creating an environment where healing can occur. Not surprisingly, omeprazole has been shown to be most effective in treating squamous ulceration (ESGUS), since the corrosive effects of acid have been more clearly implicated as a contributor to ulcers there.  Studies have also shown, by contrast, that omeprazole is much less effective as a treatment of glandular gastric ulcers (EGGUS). Along the same lines, omeprazole is entirely ineffective as a treatment approach to colonic ulcers. In both cases, no “silver bullet” exists that can immediately mitigate the issue. Instead, approaches that seek to reduce or remove the causative stressors associated with the conditions may be the best option.  Finally, an appropriate strategy for resolution of hindgut disorders may include one or more of the following ingredients:  Linseed or flaxseed oil imparts an anti-inflammatory effect due to its high ratio of Omega-3 fatty acids to pro-inflammatory Omega-6 fatty acids.  Prebiotics derived from the walls of yeast cells such as mannan oligosaccharide (MOS) or fructo-oligosaccharides (FOS), a good bacteria food source help to support the proliferation of beneficial microflora. MOS also tricks pathogenic bacteria into binding to it, rather than binding to the wall of the intestine and colonizing.  Yea-Sacc, a live yeast culture ( Saccharomyces cerevisiae ) may help to populate a healthy microflora population, although proven benefits remain questionable.  Key amino acids, such as glutamine, threonine and arginine are important for the correct function and structure of numerous cells within the gut. They also help optimize blood supply, cellular turnover and tissue repair.  Psyllium is both high-fiber and coats the intestinal lining.  Sucralfate, a mucosal protectant, has been prescribed to treat right dorsal colitis successfully. Its mode of action is to coat areas of damage to enable healing.   Beware long-term use of acid-suppressing medications   The problems associated with excess acid are well established. However it is important to remember the important role acid plays within the normal digestive process. For example, gastric acidity helps maintain the correct pH in the gut to enable some digestive enzymes to function optimally.  While the use of acid-suppressing medications has become commonplace and inarguably effective in the short term, prolonged or repetitive administration may create aberrations further along the digestive tract, including intestinal dysbiosis and damage to the mucosal integrity.  Should acid-suppressing therapy be unavoidable, it is critical to include hindgut nutritional support at the same time to avoid the development of downstream issues; and long-term preventative measures should be implicated as soon as possible.   Prevention is always better than cure   Thus, we really have three types of ulcer syndromes, all potentially with different causes, reflecting different disease processes, and responding variably to different short-term treatments. Unfortunately, these problems will fail to dissipate in the long term so long as we merely continue the cycle of addressing issues with a treatment-oriented approach. Placing more emphasis on improving management and feeding practices will promote prevention and avoidance of these complaints altogether.  In an ideal world, we would radically change how we manage, feed and care for the animal to get closer to the way the horse’s digestive system naturally functions. This would incorporate the provision of continuous forage, unrestricted turnout, a “little-and-often” feeding regime, reducing the causes of stress and increasing socialization.  Grain and processed feeds in the horse’s diet would be kept to a minimum to ensure that simple carbohydrates are correctly digested in the foregut and do not reach the hindgut. While many yards do strive to achieve these goals, the extent to which they can achieve this may be limited. This ideal model of feeding and management is rarely conducive to meeting the physical and nutritional demands of the hard-working horse, and it’s difficult to practically implement on some yards. So, another approach would be to elevate our management of digestive tract health in order to help offset the gastrointestinal risks that challenge our competition horses. Supplementing the diet with targeted nutrients to help normalize digestion, repair and replenish the structure of the tract, and enhance its natural defences against injury and disease is the ideal adjunct to improve feeding and management practices.

By Emma Hardy, PhD

Gastric ulcers remain a common condition facing competition horses. This poses an ongoing and persistent challenge to trainers who face the negative effects of ulcers in terms of training and performance. To address the issue, the typical trainer spends a small fortune on scores of omeprazole and other ulcer remedies, only to find the problem isn’t resolved or simply comes back.

Meanwhile, researchers have been testing the very notion of “what is an ulcer?” The data casts doubt on whether go-to treatment approaches will actually work. A look at what the research now tells us about equine gastric ulcers may provide some new guidance for how best to address this nearly ubiquitous concern.

The two faces of gastric ulceration

While many people think of gastric ulcers as one specific disease, equine vets and researchers refer to gastric ulcers as a “syndrome” (Equine Gastric Ulcer Syndrome, or EGUS). The medical definition of a syndrome describes a set of symptoms and signs that together represent a disease process. In practical terms, this means that ulcers are really a clinical signs—truly a symptom—of underlying disease conditions.

A few years ago, articles began to appear in the scientific press highlighting differences in the healing of ulcers in two distinct regions of the stomach—the upper “squamous” area on the one hand, as compared to the lower “glandular” portion on the other. In recent years, researchers in Australia published a series of articles (Sykes et al, 2014) to “clarify the distinction between diseases in different regions of the stomach” (i.e., to describe the differences between ulcers in the squamous area of the stomach from those in the lower glandular area). The articles described significant differences between the two conditions, including prevalence, risk factors and response to treatment.

An example of a cherry ulcer

Squamous gastric ulceration

The upper region of the stomach is minimally protected from the corrosive effects of stomach acids. As such, squamous gastric ulceration (i.e., ulcers in the upper region of the stomach) is believed to result from the increased exposure to acid and other contents of the stomach. Ulcers in the squamous region are also more common, affecting upwards of 70% of Thoroughbred racehorses, as demonstrated in multiple studies over the past 20 years.

Glandular gastric ulceration

By contrast, ulcers in the lower glandular region of the stomach are believed to arise from a different set of conditions. The lower portion of the stomach is composed of numerous cell types including those that secrete gastric acid. Because horses secrete stomach acid continuously, the mucosal lining in this lower portion of the stomach is in direct contact with stomach acid at all times.

The lower portion of the stomach is also better protected—the glandular mucosa is lined with a thick layer of mucus that offers natural protection from acid. It is believed that glandular ulceration results from the breakdown of this protective lining. Although no research has conclusively shown exactly how this defence mechanism breaks down in horses, research in humans shows NSAID (non-steroidal anti-inflammatory drugs) use and bacterial agents are contributors.

Based on this, equine squamous gastric ulceration (ESGUS) is a specific condition distinct from equine glandular gastric ulceration (EGGUS).

Beyond the stomach….

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