Equine gastric ulcer syndrome is an umbrella term to describe gastric disease in horses. It encompasses equine squamous gastric disease (ESGD) and equine glandular gastric disease (EGGD).1,2 ESGD is further divided into primary and secondary diseases. ESGD prevalence is high (reviewed in Vokes et al),1 and Thoroughbreds in active race training have the highest prevalence, ranging between 80% and 100%.3–5 EGGD is also common with 25% and 65% prevalence in Thoroughbred racehorses and 55% and 64% in sport horses.5,6 EGGD, similar to ESGD, is associated with colic, poor body condition or inappetence, behavioral changes, and poor performance, although clinical signs are variable.5,7–11 The pathogenesis for primary ESGD is well understood and is caused by increased acid exposure of the squamous mucosa, which does not have adequate defenses against stomach acid.12–15 Proton pump inhibitors provide effective therapy for ESGD.16–18 In contrast, the pathogenesis of EGGD remains poorly understood, and antiacid treatments are less effective.19 Unlike the squamous mucosa, the glandular mucosa is designed to be in constant contact with gastric acid. Therefore, EGGD is thought to be a result of a failure of the normal glandular mucosal defense mechanisms.2 Stress could play a role in the breakdown of mucosal defenses, as horses with EGGD had increased adrenocortical responses to adrenocorticotropic hormone and novel stimuli.20,21 In humans, NSAID use can lead to gastric ulcers; however, studies22–25 in horses have not shown consistent induction of EGGD with NSAID treatment, and many horses with EGGD have not received NSAID treatment. Combined, these reports2 suggest NSAIDs at recommended doses may contribute to EGGD in individual animals but are unlikely to be the primary cause of disease at the population level. Helicobacter pylori infection is another known cause of gastric ulcers in humans,26–28 but Helicobacter-like pathogens do not appear to be associated with EGGD pathogenesis.2,29–31 Modest differences in the microbiome have been identified in association with EGGD, suggesting that bacteria may play a role in the development or persistence of glandular disease.31,32
In humans, the development of a subset of peptic ulcers has been linked with herpesvirus infections. The alpha herpesviruses varicella zoster virus, herpes simplex virus type 1, and gamma herpesvirus Epstein-Barr virus have all been associated with gastric ulcers in humans.33–39 Stress is a critical factor in the development of peptic ulcers and chronic gastritis in humans, and herpesviruses are known to be reactivated by stress.40,41 Stress appears to be a contributing factor to EGGD in horses. Additionally, the equine gamma herpesviruses EHV-2 and EHV-5 have been detected in the gastric mucosa of horses.42 We hypothesized that equine gamma herpesvirus infections are associated with EGGD.
Little has been done to compare endoscopy or postmortem findings with histopathological descriptions of the abnormal equine glandular mucosa.29,43–45 Further description of changes in the gastric mucosal tissue on a microscopic level with EGGD may provide insight into the pathogenesis of EGGD.
Our primary objective was to evaluate a potential link between gamma herpesviruses and EGGD. We did this by visualizing and quantifying EHV-2 and -5 by in situ hybridization (ISH) in gastric mucosal samples. We compared the viral load of these gamma herpesviruses in horses with versus without EGGD. In addition, we compared the viral load in EGGD lesions versus grossly normal tissue within individual horses. A secondary aim was to describe the histopathological findings of the abnormal glandular gastric mucosa observed during gastroscopy and postmortem examination.
Methods
Horses and case definitions
Samples were obtained from horses from 3 groups: (1) horses presented to hospital A (Cornell University Hospital for Animals) for gastroscopy examination between November 2018 and November 2020; (2) Cornell-owned horses euthanized for other reasons at hospital A between November 2018 and November 2020; and (3) horses donated to hospital B (Louisiana State University) for research between June and December 2018. Privately owned horses were included in the study with informed consent from clients. The study was approved by the IACUC at both Cornell (no. 2018-0107) and Louisiana State University (no. 18-053).
Horses were categorized as “normal” if no gross or endoscopic stomach lesions were observed. Horses were categorized as having EGGD if gross or endoscopic pathologic lesions, including hyperemia, erosions, hemorrhage, fibrinonecrosis, raised areas, or ulcers were observed.2 Tissue from EGGD horses was categorized as normal (EGGDN) or lesion (EGGDL) based on gross or endoscopic appearance. Horses with ESGD only were excluded from the control group, as ESGD could indicate underlying stress or other disease that might influence viral load in the glandular mucosa.
Biopsy
For client-owned animals, a routine procedure for sedated gastroscopy examination was performed by the attending clinician. The squamous mucosa along greater and lesser curvatures and the glandular mucosa at the pylorus were visualized. Endoscopic biopsies (2.3 mm) were obtained of normal pyloric mucosa and any lesions observed. The biopsy instrument was disinfected with a 10% bleach solution and rinsed with sterile saline in between each sampling site.
For necropsy samples collected at hospital A, gastric tissues were collected within 2 hours postmortem. Six-millimeter punch biopsies were obtained from grossly normal and abnormal tissue at the pylorus. Instruments were disinfected with 10% bleach solution and rinsed with sterile saline in between each sampling site. Postmortem samples at hospital B were collected by excision of grossly normal and abnormal tissues at the pylorus. Biopsies were fixed in 10% neutral buffered formalin and paraffin embedded.
Histology and ISH
Samples were evaluated using RNAscope ISH targeting the glycoprotein B (gB) gene of either EHV-2 or EHV-5, as previously validated.42 This assay detects both viral DNA and RNA and thus does not distinguish between latent and active infections. Positive (PPIB) and negative (DapB) control probes were applied for each assay and performed as expected. Slides were scanned digitally and the areas of the mucosa and lamina muscularis (LM) were measured using Animal Health Diagnostic Center web-based Pathology Center software. Cells with positive labeling were counted manually in the mucosa and LM separately. The entire slide was counted unless positive cells were too numerous to count, in which instances a smaller area was measured out and counted, including both a minimum area of 1.0 mm2 and a minimum of 100 positive cells. Individuals performing the counting of positive cells were blinded to horse and sample type (normal vs lesion). The number of positive cells per millimeter squared of tissue was calculated to determine viral load.
To differentiate between latent DNA and active replication when RNA is present, DNase pretreatment was applied on additional sections before labeling with EHV-2, EHV-5, and PPIB probes, as previously described.42 However, PPIB-positive control quality was poor, and the test could not be optimized within the cost and time constraints of this study. This analysis was, therefore, excluded.
To characterize the morphological changes in the glandular mucosa and verify our categorization of horses into normal and EGGD, H&E-labeled slides were evaluated by a board-certified veterinary pathologist (SPM), who was blinded to horse and sample type. Gastroscopic pinch biopsies were deemed insufficient for evaluation; therefore, only necropsy samples were assessed histologically. The glandular mucosa was described by severity, inflammatory cell type, depth, distribution, duration, fibrosis, glandular loss or dilation, erosion, ulceration, fibrinosuppurative inflammation, and any additional findings.
Statistical analysis
Viral load data (measured as the number of ISH-positive cells per mm2) was right skewed. The association between the presence of pyloric ulcers and the viral load with EHV-2 and EHV-5 in the pyloric mucosa and LM mucosa of normal and EGGD horses was evaluated using Wilcoxon rank-sum tests. The association between the amount of virus in EGGDN versus EGGDL tissues was assessed by Wilcoxon signed-rank test for nonparametric paired data. The analysis was performed with JMP Pro, version 17.0.0 (JMP Statistical Software). Significance was set at P < .05.
Results
Horses
At hospital A, 33 horses were examined. Twenty were included in the study, and 13 were excluded due to the presence of ESGD without EGGD. These 20 horses were considered to have normal stomachs (11) or stomachs with EGGD with or without ESGD (9). An additional 9 EGGD horses were included from banked tissues at hospital B. Horses with EGGD are denoted by number (eg, horse 1), and normal horses are denoted by letter (eg, horse A). There were 16 mares, 10 geldings, 2 stallions, and 1 horse of unreported sex. Breeds consisted of 8 Quarter Horses, 10 Thoroughbreds, 2 Warmbloods, 2 Saddlebreds, 1 Appaloosa, 1 Morgan, 1 Standardbred, 1 pony, 1 Morab, 1 draft cross, and 1 horse of unknown breed. Ages ranged from 2 to 24 years of age with an average of 12.2 years old. Historical data for diet, exercise, treatments, and feed supplements were unavailable for many horses. At hospital A, samples were obtained from 13 horses via necropsy and 7 horses via gastroscopy exams. At hospital B, samples were obtained from 8 horses via necropsy and 1 horse via gastroscopy exams.
Description of lesions
Endoscopic and gross lesions for EGGD were described according to the European College of Equine Internal Medicine2 consensus statement criteria (Table 1).
Gross description of equine glandular gastric disease in 18 horses.
| Description | No. of horses | No. of lesions |
|---|---|---|
| Severity | ||
| Mild | 8 | |
| Moderate | 9 | |
| Severe | 1 | |
| Distribution | ||
| Focal | 6 | |
| Multifocal | 10 | |
| Diffuse | 2 | |
| Epithelial appearance | ||
| Hyperemic | 17 | |
| Hemorrhagic | 9 | |
| Fibrinosuppurative | 5 | |
| Ulcerated | 4 | |
| Mucosal contour | ||
| Depressed | 4 | |
| Flat | 13 | |
| Raised | 6 |
For epithelial appearance and mucosal contour, some horses had more than 1 lesion described plus multiple descriptors per lesion.
Histologic evaluation was performed on postmortem samples only due to insufficient sample size of pinch biopsies. Five out of the 6 grossly normal horses had normal gastric glandular mucosa, while 1 had mild, multifocal, chronic lymphoplasmacytic gastritis and multifocal interglandular fibrosis.
All 15 horses that were considered to have EGGD based on postmortem evaluation were confirmed to have disease histologically (Figure 1 and Supplementary Table S1). Histopathology showed gastritis with an intact mucosal surface in 9/15 (60%) and an erosion and/or ulcer in 6/15 (40%). The erosions and ulcers confirmed histologically were seen as depressed or raised areas grossly. Frequently, the erosive areas were covered with a fibrinosuppurative layer. All horses with gastritis had lymphocytic or lymphoplasmacytic infiltrate, while neutrophils (27% [4/15]) and eosinophils (20% [3/15]) were noted in some. Fibrosis (20% [3/15]), glandular dilation (20% [3/15]), glandular loss (20% [3/15]), lymphoid aggregates (13% [2/15]), follicular lymphoid hyperplasia (7% [1/15]), suppurative adenitis (7% [1/15]), and submucosal mast cell tumor (7% [1/15]) were also observed. Horse 15 had multiple bots in the squamous portion of the stomach, and no other parasites were noted on gastroscopy. However, histopathology showed superficial nematodes, most consistent with Draschia megastroma, along with evidence of a mucosal barrier disruption with hair and plant material and lymphoplasmacytic infiltrate; eosinophils were not seen. Horse 18 had multiple bots at the margo plicatus near the lesser curvature, and a long thin white parasite was noted in the glandular mucosa in the cardiac region on gastroscopy, which was not biopsied.
Gross and histopathological findings of the glandular stomach in 3 horses examined at hospital A. A—Photograph of the pyloric region showing a flat, hemorrhagic (arrowhead) and a depressed, hemorrhagic (arrow) lesion. Horse 3; bar = 2 cm. B—Photograph of the lesser curvature and pyloric region showing deep pyloric ulcer (arrow) and other hemorrhagic ulcers. Horse 1; bar = 4 cm. C—Photomicrograph of normal glandular gastric mucosa showing the intact epithelial layer, gastric pits and glands of the submucosa and the deeper lamina propria. Horse L; H&E stain; bar = 500 µm. D—Photomicrograph of glandular gastric mucosa corresponding to the glandular lesion shown in A by the arrowhead. Focal gastritis is characterized by multifocal mild lymphoplasmacytic infiltrate with glandular dilation. Inset shows a higher magnification of the lymphoplasmacytic gastritis. Horse 3; H&E stain; bar = 500 µm; inset bar = 100 µm. E—Photomicrograph of the glandular mucosa corresponding to the glandular lesion shown in A by the arrow. Focal gastritis and erosion of mucosa are characterized by a fibrinosuppurative layer over the eroded mucosa and lymphocytic infiltrate in the submucosal region. Horse 3; H&E stain; bar = 500 µm. F—Photomicrograph of the deep glandular ulcer shown in B by the arrow. The ulcer is characterized by the lack of mucosa and submucosa layers, suppurative gastritis with submucosal granulation tissue, and severe medial hypertrophy of the submucosal arterioles. Horse 1; H&E stain; bar = 100 µm.
Citation: American Journal of Veterinary Research 85, 6; 10.2460/ajvr.23.12.0282
In situ hybridization findings
Postmortem and endoscopic biopsies were evaluated by ISH for viral load, although endoscopic biopsies included mucosa but not LM. All pyloric samples were positive for EHV-2, and all but 2 pyloric lesion samples were positive for EHV-5 (Figure 2). The distribution and proportion of infected cells were similar for EHV-2 and EHV-5. Infected cells could be observed primarily in the outer mucosal layer, with fewer horses showing infection in the deeper gastric glands and in the LM. Most cells showed nuclear hybridization. The proportion of positive cells was generally low, with occasional samples where nearly every cell was ISH positive. In the mucosa, gastric glandular tissues from normal horses had significantly higher median viral loads for both EHV-5 and EHV-2 than EGGDN or EGGDL tissues, although there was a large amount of overlap between groups (Table 2 and Figure 3). In the LM, gastric glandular tissues from normal horses had significantly higher EHV-5 viral loads than EGGDN (Table 3). Within an individual horse with EGGD, there was no significant difference in viral loads in EGGDN versus EGGDL tissues in either mucosa or LM (Supplementary Figure S1).
In situ hybridization (ISH) identifies equine gamma herpesviruses in gastric glandular epithelium and smooth muscle. A—Photomicrograph of normal glandular mucosal epithelium from a horse that had equine glandular gastric disease (EGGD). Positive hybridization (pink to red staining, arrows) is observed scattered through the tissue. Horse 2; equine herpesvirus 2 (EHV-2) glycoprotein B (gB) ISH; bar = 500 µm; inset bar = 100 µm. B—Photomicrograph of ulcerated glandular mucosal epithelium with hybridization located deep in the glands. Horse 2; equine herpesvirus 5 (EHV-5) gB ISH; bar = 500 µm; inset bar = 100 µm. C—Photomicrograph of normal glandular mucosa from a horse with EGGD. Hybridization is present in the lamina muscularis mucosa. The mucosal surface is at the bottom right of this image and submucosa on top left. Horse 1; EHV-5 gB ISH; bar = 500 µm; inset bar = 100 µm. D—Photomicrograph of ulcerated glandular mucosal epithelium. EHV-5 hybridization is present in the nuclei of the gastric glandular epithelium. Horse 1; EHV-5 gB ISH; bar = 100 µm. E—Photomicrograph of normal glandular mucosal epithelium from a horse without EGGD. EHV-5 hybridization is present in the nuclei of gastric glandular epithelium. Horse A; EHV-5 gB ISH; bar = 100 µm. F—Photomicrograph of ulcerated glandular mucosal epithelium labeled with a negative control probe shows no background. Horse 2; DapB ISH; bar = 100 µm. G—Photomicrograph of ulcerated glandular mucosal epithelium labeled with a positive control probe for the ubiquitously expressed gene PPIB showed widespread cytoplasmic hybridization, as expected. Horse 2; EGGD pyloric ulcer; PPIB ISH; bar = 100 µm.
Citation: American Journal of Veterinary Research 85, 6; 10.2460/ajvr.23.12.0282
Equine gamma herpesviral load in the pyloric mucosa of horses with and without equine glandular gastric disease (EGGD).
| Mucosa | |||||
|---|---|---|---|---|---|
| n | EHV-2 | EHV-5 | |||
| Normal | 11 | 9.6 | (0.12–310) | 7.3 | (0.078–370) |
| EGGDL | 18 | 0.82 | (0.087–410) | 0.87 | (0–33) |
| EGGDN | 18 | 0.43 | (0.0091–43) | 0.63 | (0.0087–41) |
| Normal vs EGGDL (P value) | .023a | .018a | |||
| Normal vs EGGDN (P value) | .026a | .021a | |||
| EGGDN vs EGGDL (P value) | 1 | .39 | |||
Median (range) in situ hybridization–positive cells/mm2. Viral load was compared between normal and EGGD horses by Wilcoxon rank-sum test. Viral load was compared between normal (EGGDN) and lesion (EGGDL) tissues within EGGD horses by Wilcoxon signed-rank test for paired data.
EHV-2 = Equine herpesvirus 2. EHV-5 = Equine herpesvirus 5.
Significant.
Equine gamma herpesviral load in the pyloric lamina muscularis mucosa of horses with and without equine glandular gastric disease (EGGD).
| Lamina muscularis | |||||
|---|---|---|---|---|---|
| n | EHV-2 | EHV-5 | |||
| Normal | 5 | 2.3 | (0–58) | 7 | (0.10–62) |
| EGGDL | 15 | 0.38 | (0–84) | 1.3 | (0–13) |
| EGGDN | 15 | 0.27 | (0–90) | 0.19 | (0–5) |
| Normal vs EGGDL (P value) | .41 | .081 | |||
| Normal vs EGGDN (P value) | .14 | .044a | |||
| EGGDN vs EGGDL (P value) | .93 | .89 | |||
Median (range) in situ hybridization–positive cells/mm2. Viral load was compared between normal and EGGD horses by Wilcoxon rank-sum test. Viral load was compared between normal (EGGDN) and lesion (EGGDL) tissues within EGGD horses by Wilcoxon signed-rank test for paired data.
EHV-2 = Equine herpesvirus 2. EHV-5 = Equine herpesvirus 5.
Significant.
Equine gamma herpesviral load is higher in horses without equine glandular gastric disease (EGGD) or equine squamous gastric disease. Viral load was determined by in situ hybridization, and positive cells per millimeter squared were determined separately for the mucosa (A and B) and lamina muscularis (LM; B and C) for equine herpesvirus-2 (EHV-2) and equine herpesvirus-5 (EHV-5). Normal horses without gastric ulcer disease versus EGGD horses were identified by gross pathology. For the box-and-whisker plot, the solid line within the box represents the median; the lower and upper limits of the box represent the interquartile (25th and 75th percentiles) range, respectively; the whiskers delimit the range. Viral loads for normal (EGGDN) and lesion tissues (EGGDL) in EGGD horses were compared to tissue from normal horses by pairwise Wilcoxon rank-sum test for nonparametric data. 0.01 < *P < 0.05.
Citation: American Journal of Veterinary Research 85, 6; 10.2460/ajvr.23.12.0282
Discussion
Our hypothesis that the presence of equine gamma herpesviruses in gastric tissues would be positively associated with EGGD was not supported. In fact, there appeared to be higher viral loads in horses with normal gastric mucosa instead. This is in direct contrast to studies34,36,39 in humans showing an association between the detection of herpesviruses in peptic lesions only.
EGGD more closely models human peptic ulcer disease than does ESGD. Efforts to identify causes of EGGD have considered common causes of human peptic ulcers, including NSAIDs and H pylori, however, these have not been well substantiated in horses. In this study, we explored a potential relation with herpesviruses. Most horses are infected with EHV-2 and EHV-5 within the first 6 months of life.46 These gamma herpesviruses can be detected in both healthy and sick horses in nasal and genital swab samples, conjunctiva, lacrimal gland, optic nerve, leukocytes, lymphoid, and nervous tissues.46–50 EHV-2 and -5, but not the alpha herpesvirus EHV-1, have been detected in gastric mucosa, and a small sample set was suggestive of a higher infection rate in horses with ulcers.42 Our larger dataset, albeit still a small number of horses with EGGD, confirmed the frequent presence of gamma herpesviruses in equine gastric mucosa but found no association with EGGD. This resembles recent investigations of equine keratoconjunctivitis and EHV-2, whereby 28.6% (22/77) of ocular swabs from horses without eye disease were positive by PCR and only 8.3% (4/48) with keratoconjuctivitis.51 However, positive clinical response to antiviral treatment suggests EHV-2 might still play a role in equine keratoconjunctivitis.
It is possible that the apparently ubiquitous nature of gamma herpesvirus infection is masking a disease effect or disease interaction. In this study, we detected viral DNA as well as RNA and could not confirm whether positive cells reflected latent or active infections. Although it is possible that reactivation occurs locally associated with EGGD lesions, this seems unlikely as we would have expected to have similar or higher viral loads in these lesions. In people with gastroduodenal ulcer disease, herpes simplex virus was detected by PCR in 9.5% of patients, and the virus was only detectable in lesions and not in normal tissue nearby.52
Few studies29,31,43,44,53 have compared the gross appearance of the glandular stomach of the horse during endoscopy exams or postmortem to histopathology findings. Here, we report on the histopathological findings in 18 horses with EGGD. Abnormal histopathology was noted for all the gross lesions. Of the horses in the EGGD group, 40% had erosion or ulceration and 60% had gastritis with an intact mucosal surface. Colloquially, clinicians describe EGGD lesions as “ulcers,” and this highlights the importance of classification as EGGD, as many of the lesions may not be true ulcerations but are instead associated with gastritis. Most cellular infiltrates were lymphocytes and plasma cells, and it has been postulated that this could be a form of inflammatory bowel disease or precancerous lesion. Recent data45 show an association between moderate to severe lymphoplasmacytic inflammation of the gastric glandular stomach and duodenum but not between the endoscopic appearance of EGGD and the presence or severity of small intestinal inflammation. A precursor to cancer is highly unlikely as gastric tumors are very rare in the horse and gastric lymphoma is exceedingly rare, with squamous cell carcinoma being most common and leiomyoma or leiomyosarcoma, mesothelioma, and adenocarcinoma also reported.54 The mast cell tumor observed in 1 case in this study is rare and has not been previously reported in horses to the authors’ knowledge, although mast cell tumors have been found in the stomachs of dogs.55 Alternatively, the lymphocytic infiltrate might also indicate a viral etiology, which was not confirmed here.
Using the European College of Equine Internal Medicine descriptions for the endoscopic and gross evaluation of the stomach,2 deep lesions were confirmed to be ulcers or erosions on histopathology, while flat lesions corresponded with erosions or gastritis and raised lesions corresponded with gastritis only. One horse that was categorized as normal on postmortem evaluation had mild, multifocal, chronic lymphoplasmacytic gastritis and multifocal interglandular fibrosis on histopathology. This finding suggests that visualization of the glandular mucosa during postmortem examination, and presumably endoscopically, can miss mild gastritis in the glandular region of the equine stomach. Gastroscopy can also miss glandular lesions due to the presence of feed or fluid in the stomach, inadequate insufflation of the stomach, or clinician experience.43 Gastroscopic biopsy can be a useful ancillary diagnostic tool for EGGD, although current limitations of pinch biopsy instruments (small samples, crush artifact) present a diagnostic challenge to the histopathologist where the mucosa to submucosal layers can be incomplete and might preclude the diagnosis of inflammatory infiltrate in gastric mucosal samples.53,56
The presence of nematodes in the gastric mucosa is a reminder that parasites might play a role in EGGD in horses. These parasites might be missed on the superficial pinch biopsies achievable through the endoscope. Draschia megastoma, a member of the Habronema genus, has a gastric form whose adults live in the wall of the gastric fundus and pyloric valve or freely on the surface.57,58 Various stomach pathologic conditions have been described in infected horses, including congested and hemorrhagic ulcer-like areas.59 Parasite control measures might be important for treating and preventing some cases of equine gastritis.
In summary, EGGD is characterized histologically by gastritis with a lymphoplasmacytic infiltrate and sometimes has disruption of the mucosal epithelium as erosions and ulcers. Gamma herpesviruses EHV-2 and EHV-5 are present in the stomachs of horses and in areas of EGGD but are unlikely to play a role in its etiology.
Supplementary Materials
Supplementary materials are posted online at the journal website: avmajournals.avma.org
Acknowledgments
The authors thank Mason Jager for training and assistance with the interpretation of ISH.
Disclosures
The authors have nothing to disclose. No AI-assisted technologies were used in the generation of this manuscript.
Funding
This study was funded by a resident research grant through the Harry M. Zweig Memorial Fund for Equine Research.
References
- 1.↑
Vokes J, Lovett A, Sykes B. Equine gastric ulcer syndrome: an update on current knowledge. Animals (Basel). 2023;13(7):1261. doi:10.3390/ani13071261
- 2.↑
Sykes BW, Hewetson M, Hepburn RJ, Luthersson N, Tamzali Y. European College of Equine Internal Medicine consensus statement-equine gastric ulcer syndrome in adult horses. J Vet Intern Med. 2015;29(5):1288–1299. doi:10.1111/jvim.13578
- 3.↑
Begg LM, O’Sullivan CB. The prevalence and distribution of gastric ulceration in 345 racehorses. Aust Vet J. 2003;81(4):199–201. doi:10.1111/J.1751-0813.2003.TB11469.X
- 4.
Lo Feudo CM, Stucchi L, Conturba B, Stancari G, Zucca E, Ferrucci F. Equine gastric ulcer syndrome affects fitness parameters in poorly performing StanHHdardbred racehorses. Front Vet Sci. 2022;9:1014619. doi:10.3389/fvets.2022.1014619
- 5.↑
Sykes BW, Bowen M, Habershon-Butcher JL, Green M, Hallowell GD. Management factors and clinical implications of glandular and squamous gastric disease in horses. J Vet Intern Med. 2019;33(1):233–240. doi:10.1111/jvim.15350
- 6.↑
Mönki J, Hewetson M, Virtala AMK. Risk factors for equine gastric glandular disease: a case-control study in a Finnish referral hospital population. J Vet Intern Med. 2016;30(4):1270–1275. doi:10.1111/jvim.14370
- 7.↑
Sandin A, Skidell J, Häggström J, Nilsson G. Postmortem findings of gastric ulcers in Swedish horses older than age one year: a retrospective study of 3715 horses (1924–1996). Equine Vet J. 2000;32(1):36–42. doi:10.2746/042516400777612044
- 8.
Vatistas NJ, Snyder JR, Carlson G, et al. Cross-sectional study of gastric ulcers of the squamous mucosa in Thoroughbred racehorses. Equine Vet J. 1999;31(29):34–39. doi:10.1111/J.2042-3306.1999.TB05166.X
- 9.
Bezdekova B, Wohlsein P, Venner M. Chronic severe pyloric lesions in horses: 47 cases. Equine Vet J. 2020;52(2):200–204. doi:10.1111/EVJ.13157
- 10.
Gough S, Hallowell G, Rendle D. Evaluation of the treatment of equine glandular gastric disease with either long-acting-injectable or oral omeprazole. Vet Med Sci. 2022;8(2):561–567. doi:10.1002/VMS3.728
- 11.↑
Franklin SH, Brazil TJ, Allen KJ. Poor performance associated with equine gastric ulceration syndrome in four Thoroughbred racehorses. Equine Vet Educ. 2008;20(3):119–124. doi:10.2746/095777308X282363
- 12.↑
Nadeau JA, Andrews FM, Patton CS, Argenzio RA, Mathew AG, Saxton AM. Effects of hydrochloric, valeric and other volatile fatty acids on pathogenesis of ulcers in the nonglandular portion of the stomach of horses. Am J Vet Res. 2003;64(4):413–417. doi:10.2460/ajvr.2003.64.413
- 13.
Nadeau JA, Andrews FM, Patton CS, Argenzio RA, Mathew AG, Saxton AM. Effects of hydrochloric, acetic, butyric, and propionic acids on pathogenesis of ulcers in the nonglandular portion of the stomach of horses. Am J Vet Res. 2003;64(4):404–412. doi:10.2460/ajvr.2003.64.404
- 14.
Andrews FM, Buchanan BR, Elliott SB, Al Jassim RAM, McGowan CM, Saxton AM. In vitro effects of hydrochloric and lactic acids on bioelectric properties of equine gastric squamous mucosa. Equine Vet J. 2008;40(4):301–305. doi:10.2746/042516408X293565
- 15.↑
Andrews FM, Buchanan BR, Smith SH, Elliott SB, Saxton AM. In vitro effects of hydrochloric acid and various concentrations of acetic, propionic, butyric, or valeric acids on bioelectric properties of equine gastric squamous mucosa. Am J Vet Res. 2006;67(11):1873–1882. doi:10.2460/AJVR.67.11.1873
- 16.↑
Birkmann K, Junge HK, Maischberger E, Wehrli Eser M, Schwarzwald CC. Efficacy of omeprazole powder paste or enteric-coated formulation in healing of gastric ulcers in horses. J Vet Intern Med. 2014;28(3):925–933. doi:10.1111/JVIM.12341
- 17.
Nieto JE, Spier S, Pipers FS, et al. Comparison of paste and suspension formulations of omeprazole in the healing of gastric ulcers in racehorses in active training. J Am Vet Med Assoc. 2002;221(8):1139–1143. doi:10.2460/javma.2002.221.1139
- 18.↑
Sykes BW, Sykes KM, Hallowell GD. A comparison of two doses of omeprazole in the treatment of equine gastric ulcer syndrome: a blinded, randomised, clinical trial. Equine Vet J. 2014;46(4):416–421. doi:10.1111/evj.12191
- 19.↑
Varley G, Bowen IM, Habershon-Butcher JL, Nicholls V, Hallowell GD. Misoprostol is superior to combined omeprazole-sucralfate for the treatment of equine gastric glandular disease. Equine Vet J. 2019;51(5):575–580. doi:10.1111/EVJ.13087
- 20.↑
Scheidegger MD, Gerber V, Bruckmaier RM, van der Kolk JH, Burger D, Ramseyer A. Increased adrenocortical response to adrenocorticotropic hormone (ACTH) in sport horses with equine glandular gastric disease (EGGD). Vet J. 2017;228:7–12. doi:10.1016/J.TVJL.2017.09.002
- 21.↑
Malmkvist J, Poulsen JM, Luthersson N, Palme R, Christensen JW, Søndergaard E. Behaviour and stress responses in horses with gastric ulceration. Appl Anim Behav Sci. 2012;142(3–4):160–167. doi:10.1016/J.APPLANIM.2012.10.002
- 22.↑
Pedersen SK, Cribb AE, Read EK, French D, Banse HE. Phenylbutazone induces equine glandular gastric disease without decreasing prostaglandin E2 concentrations. J Vet Pharmacol Ther. 2018;41(2):239–245. doi:10.1111/jvp.12464
- 23.
Richardson LM, Whitfield-Cargile CM, Cohen ND, Chamoun-Emanuelli AM, Dockery HJ. Effect of selective versus nonselective cyclooxygenase inhibitors on gastric ulceration scores and intestinal inflammation in horses. Vet Surg. 2018;47(6):784–791. doi:10.1111/VSU.12941
- 24.
Monreal L, Sabaté D, Segura D, Mayós I, Homedes J. Lower gastric ulcerogenic effect of suxibuzone compared to phenylbutazone when administered orally to horses. Res Vet Sci. 2004;76(2):145–149. doi:10.1016/j.rvsc.2003.10.004
- 25.↑
Andrews FM, Reinemeyer CR, Longhofer SL. Effects of top-dress formulations of suxibuzone and phenylbutazone on development of gastric ulcers in horses. Vet Ther. 2009;10(3):113–120.
- 26.↑
FitzGerald R, Smith SM. An overview of Helicobacter pylori infection. Methods Mol Biol. 2021;2283:1–14. doi:10.1007/978-1-0716-1302-3_1
- 27.
Tham KT, Peek RM, Atherton JC, et al. Helicobacter pylori genotypes, host factors, and gastric mucosal histopathology in peptic ulcer disease. Hum Pathol. 2001;32(3):264–273. doi:10.1053/hupa.2001.21136
- 28.↑
Bagheri N, Shirzad H, Elahi S, et al. Downregulated regulatory T cell function is associated with increased peptic ulcer in Helicobacter pylori-infection. Microb Pathog. 2017;110:165-175. doi:10.1016/j.micpath.2017.06.040
- 29.↑
Husted L, Jensen TK, Olsen SN, Mølbak L. Examination of equine glandular stomach lesions for bacteria, including Helicobacter spp by fluorescence in situ hybridisation. BMC Microbiol. 2010;10:84. 10.1186/1471-2180-10-84
- 30.
Contreras M, Morales A, García-Amado MA, De Vera M, Bermúdez V, Gueneau P. Detection of Helicobacter-like DNA in the gastric mucosa of Thoroughbred horses. Lett Appl Microbiol. 2007;45(5):553–557. doi:10.1111/J.1472-765X.2007.02227.X
- 31.↑
Paul LJ, Ericsson AC, Andrews FM, et al. Gastric microbiome in horses with and without equine glandular gastric disease. J Vet Intern Med. 2021;35(5):2458–2464. doi:10.1111/JVIM.16241
- 32.↑
Paul LJ, Ericsson AC, Andrews FM, et al. Field study examining the mucosal microbiome in equine glandular gastric disease. PLoS One. 2023;18(12):e0295697. doi:10.1371/JOURNAL.PONE.0295697
- 33.↑
Tsamakidis K, Panotopoulou E, Dimitroulopoulos D, et al. Herpes simplex virus type 1 in peptic ulcer disease: an inverse association with Helicobacter pylori. World J Gastroenterol. 2005;11(42):6644–6649. doi:10.3748/WJG.V11.I42.6644
- 34.↑
Milligan KL, Jain AK, Garrett JS, Knutsen AP. Gastric ulcers due to varicella-zoster reactivation. Pediatrics. 2012;130(5). doi:10.1542/PEDS.2011-3491
- 35.
Toll AD, Malik S, Tuluc M. Ulcerative gastritis secondary to Epstein-Barr viral infection. Dig Dis Sci. 2010;55(1):218–219. doi:10.1007/S10620-009-0710-Y
- 36.↑
Ryan JL, Shen YJ, Morgan DR, et al. Epstein-Barr virus infection is common in inflamed gastrointestinal mucosa. Dig Dis Sci. 2012;57(7):1887–1898. doi:10.1007/s10620-012-2116-5
- 37.
Gwak JW, Yoo J, Suh SO, Kim J, Oh IS, Bae JY. Benign gastric ulcer with Epstein-Barr virus infection mimicking malignant gastric ulcer. Korean J Gastroenterol. 2019;73(3):177–181. doi:10.4166/kjg.2019.73.3.177
- 38.
Chen ZME, Shah R, Zuckerman GR, Wang HL. Epstein-Barr virus gastritis: an underrecognized form of severe gastritis simulating gastric lymphoma. Am J Surg Pathol. 2007;31(9):1446–1451. doi:10.1097/PAS.0b013e318050072f
- 39.↑
Löhr JM, Nelson JA, Oldstone MB. Herpes simplex virus is associated with peptic ulcer disease. Trans Assoc Am Phys. 1989;102:213–223. doi:10.1128/jvi.64.5.2168-2174.1990
- 40.↑
Mehta SK, Cohrs RJ, Forghani B, Zerbe G, Gilden DH, Pierson DL. Stress-induced subclinical reactivation of varicella zoster virus in astronauts. J Med Virol. 2004;72(1):174–179. doi:10.1002/JMV.10555
- 41.↑
Yu W, Geng S, Suo Y, et al. Critical role of regulatory T cells in the latency and stress-induced reactivation of HSV-1. Cell Rep. 2018;25(9):2379–2389.e3. doi:10.1016/J.CELREP.2018.10.105
- 42.↑
Pennington MR, Cossic BGA, Perkins GA, Duffy C, Duhamel GE, Van de Walle GR. First demonstration of equid gammaherpesviruses within the gastric mucosal epithelium of horses. Virus Res. 2017;242:30–36. doi:10.1016/j.virusres.2017.09.002
- 43.↑
Andrews FM, Reinemeyer CR, McCracken MD, et al. Comparison of endoscopic, necropsy and histology scoring of equine gastric ulcers. Equine Vet J. 2002;34(5):475–478. doi:10.2746/042516402776117827
- 44.↑
Martineau H, Thompson H, Taylor D. Pathology of gastritis and gastric ulceration in the horse. Part 1: range of lesions present in 21 mature individuals. Equine Vet J. 2009;41(7):638–644. doi:10.2746/042516409X464816
- 45.↑
Banse HE, Piero F Del, Andrews FM, Garcia-Abarca N, Watanabe TTN. Characterization of gastrointestinal inflammatory cell type in equine glandular gastric disease. Am J Vet Res. 2023;84(12):1–8. doi:10.2460/AJVR.23.06.0129
- 46.↑
Murray MJ, Eichorn ES, Dubovi EJ, Ley WB, Cavey DM. Equine herpesvirus type 2: prevalence and seroepidemiology in foals. Equine Vet J. 1996;28(6):432–436. doi:10.1111/J.2042-3306.1996.TB01614.X
- 47.
Kemeny L, Pearson JE. Isolation of herpesvirus from equine leukocytes: comparison with equine rhinopneumonitis virus. Can J Comp Med. 1970;34(1):59–65.
- 48.
Roeder PL, Scott GR. The prevalence of equid herpes virus 2 infections. Vet Rec. 1975;96(18):404–405. doi:10.1136/VR.96.18.404
- 49.
Nordengrahn A, Merza M, Ros C, et al. Prevalence of equine herpesvirus types 2 and 5 in horse populations by using type-specific PCR assays. Vet Res. 2002;33(3):251–259. doi:10.1051/VETRES:2002013
- 50.↑
Lee SK, Lee I. The molecular detection of equine herpesviruses 2 and 5 in genital swabs from clinically normal thoroughbred mares in South Korea. J Equine Vet Sci. 2019;79:68–72. doi:10.1016/J.JEVS.2019.05.013
- 51.↑
Borchers K, Ebert M, Fetsch A, Hammond T, Sterner-Kock A. Prevalence of equine herpesvirus type 2 (EHV-2) DNA in ocular swabs and its cell tropism in equine conjunctiva. Vet Microbiol. 2006;118(3–4):260–266. doi:10.1016/J.VETMIC.2006.07.024
- 52.↑
Kemker BP, Docherty JJ, De Lucia A, Ruf W, Lewis RD. Herpes simplex virus: a possible etiologic agent in some gastroduodenal ulcer disease. Am Surg. 1992;58(12):775–778.
- 53.↑
Crumpton SM, Baiker K, Hallowell GD, Habershon-Butcher JL, Bowen IM. Diagnostic value of gastric mucosal biopsies in horses with glandular disease. Equine Vet J. 2015;47:9–9. doi:10.1111/evj.12486_18
- 54.↑
Taylor SD, Haldorson GJ, Vaughan B, Pusterla N. Gastric neoplasia in horses. J Vet Intern Med. 2009;23(5):1097–1102. doi:10.1111/J.1939-1676.2009.0356.X
- 55.↑
Ozaki K, Yamagami T, Nomura K, Narama I. Mast cell tumors of the gastrointestinal tract in 39 dogs. Vet Pathol. 2002;39(5):557–564. doi:versus 10.1354/vp.39-5-557
- 56.↑
Rodrigues NLF, Doré M, Doucet MY. Validation of a transendoscopic glandular and nonglandular gastric biopsy technique in horses. Equine Vet J. 2009;41(7):631–635. doi:10.2746/042516409X424144
- 57.↑
Al-Mokaddem AK, Ahmed KA, Doghaim RE. Pathology of gastric lesions in donkeys: a preliminary study. Equine Vet J. 2015;47(6):684–688. doi:10.1111/EVJ.12336
- 58.↑
Ouhelli H, Cabaret J, Pandey VS, Elkhalfane A. [Localisation of parasites in the stomach of horses of the region of Settat (Morocco)]. Rev Elev Med Vet Pays Trop. 1979;32(4):347–352. doi:versus 10.19182/remvt.8125
- 59.↑
Lyons ET, Tolliver SC, Drudge JH, Swerczek TW, Crowe MW. Parasites in Kentucky Thoroughbreds at necropsy: emphasis on stomach worms and tapeworms. Am J Vet Res. 1983;44(5):839–844.
