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EQUINE VETERINARY EDUCATION / AE / AUGUST 2019
Equine glandular gastric disease (EGGD)
The pathogenesis of EGGD is poorly described and the risk factors that contribute to disease are yet to be fully elucidated. In contrast to ESGD, which occurs because of increased acid exposure in a region with limited defence mechanisms, EGGD is believed to result from a breakdown of the normal defence mechanisms and consequent exposure of sensitive tissues to acid (Sykes et al. 2015a). However, the response to oral omeprazole monotherapy is poor with EGGD healing responses of only 9–32% with 28–35 days of omeprazole therapy at 4.0 mg/kg by mouth once daily reported (Sykes et al. 2014a,b, 2015b). The factors that contribute to the poor response rate are
not fully elucidated. The author proposes four mechanisms that likely contribute and that warrant review. Namely;
• Is adequate intraday acid suppression being achieved? • Are adequate durations of treatment being used? • Is adjunctive therapy such as sucralfate or misoprostol required?
• Is acid suppression the primary mechanism required for EGGD healing?
Intraday acid suppression In humans, good healing rates for gastroesophageal reflux disease, which is analogous to ESGD, are achieved when the percentage of time that pH exceeds 4 (%tpH >4) exceeds 66% (Bell et al. 1992), while a %tpH >3 of greater than 66% is required for healing of glandular disease (Bell et al. 1992). In a study measuring intragastric pH over 24 h periods using pH probes inserted retrograde into the indwelling gastric cannula in six horses fed ad libitum hay supplemented with a small grain meal twice daily a pH exceeding 4 was achieved, on average, for only 14 and 11 h on Days 2 and 7 of treatment, respectively, following the administration of a commercial, buffered, paste formulation of omeprazole at 4 mg/kg bwt by mouth once daily (Merritt et al. 2003). Similarly, it has recently been reported that following the administration of the same commercial, buffered, paste formulation of omeprazole the average %tpH >4 within the ventral stomach on Day 5 may be as little as 30–40% in horses consuming high roughage diets at the registered treatment dose of 4 mg/kg bwt by mouth once daily (Sykes et al. 2017b). This is below the threshold for healing reported in humans (Bell et al. 1992) and provides a potential explanation for the poor EGGD healing rates reported, especially in animals receiving ad libitum hay which is widely recommended for the management and prevention of EGUS (Sykes et al. 2015a).
Duration of treatment The duration of treatment required for the resolution of EGGD has not been well studied. Current treatment recommendations of a minimum of 4 weeks duration (Sykes et al. 2015a) are based primarily on existing recommendations for ESGD and clinical experience. Given the differences in pathophysiology between ESGD and EGGD, it is possible that, simply, a longer duration of treatment may be required for EGGD healing to consistently occur. In humans, the duration of treatment required for healing of NSAID induced ulceration was 8 and 12 weeks for 84% and 100% healing, respectively, in one study (Lancaster-Smith et al. 1991). If a similar effect was present in
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the horse, then longer treatment durations may be required. However, a recent study investigating the efficacy of a novel, long-acting, injectable omeprazole formulation reported an EGGD healing rate of 75% with 2 weeks of treatment (Sykes et al. 2017a). This suggests that EGGD healing is likely dependent on acid suppression, and that EGGD healing does occur within a short period of time if the magnitude and duration of acid suppression is adequate.
Adjunctive therapy The use of mucosal barrier protectants is logical given the proposed failure of mucosal defence mechanisms in the pathogenesis of EGGD. The use of sucralfate at a dose of 12 mg/kg bwt by mouth twice daily in addition to omeprazole at 4 mg/kg bwt by mouth once daily has been described in a UK sport and leisure horse population with a healing response rate of 63.2% reported (Hepburn and Proudman 2014). However, more recently, a study in a similar population reported a healing rate of only 22% over a
28 5 day period using omeprazole (4 mg/kg bwt by mouth once daily) and sucralfate (10 mg/kg bwt by mouth twice daily) (Varley et al. 2016) suggesting that the benefits of the addition of sucralfate to omeprazole monotherapy may be limited. Misoprostol has been proposed as an alternative, or adjunctive, treatment and a 73% response rate over a
28 5 day treatment period at a dose of 5 lg/kg bwt misoprostol by mouth twice daily has been reported (Varley et al. 2016). As such, misoprostol appears to warrant further consideration but detailed discussion is beyond the scope of this paper. The role of bacteria in the pathogenesis of EGGD is
controversial. However, no direct evidence supports the use of antimicrobials, and the addition of trimethoprim- sulfdimidine at 30 mg/kg bwt by mouth once daily to omeprazole at 4.0 mg/kg bwt by mouth once daily failed to improve the treatment response over omeprazole monotherapy (Sykes et al. 2014c). As such, and in line with the principles of responsible use of antimicrobials, the current recommendation is that their use in the routine treatment of EGGD is not justified (Sykes et al. 2015a).
The role of acid suppression Lastly, the role of acid suppression in the treatment of EGGD has not been fully validated. As such, it could reasonably be argued that acid suppression may not be, or at least has not been demonstrated to be, a critical factor in EGGD healing. However, as discussed above, a recent study investigating the efficacy of a novel, long-acting, injectable omeprazole formulation reported an EGGD healing rate of 75% over 2 weeks of treatment (Sykes et al. 2017a), suggesting that EGGD healing does occur if the magnitude and duration of acid suppression is adequate.
Factors affecting oral omeprazole efficacy
Consistently good rates of healing are observed for ESGD when appropriate magnitude and durations of acid suppression are achieved (Andrews et al. 1999; MacAllister et al. 1999; Lester et al. 2005; Sykes et al. 2015b). Similarly, preliminary data from a pilot study, in a small number of horses, suggest that good rates of EGGD healing can be achieved when prolonged acid suppression is achieved (Sykes et al. 2017a). As such, a key goal in the
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