Management of Eosinophilic Esophagitis
Not all cases of EO are suitable for dietary therapy. The child (or adult patient) may not be prepared to accept the dietary restrictions or may fail to respond to this approach. Furthermore, a subgroup of EO cases appears not to be sensitised to foods but to aeroallergens. These cases often tend to have a seasonal variability to their symptoms and will require medicines to alleviate symptoms. The mainstay of drug therapy is the topical administration of corticosteroids, although PPIs have a general role to play, and so in practice, combinations of drugs and diets are often employed.
In some cases, patients with oesophageal eosinophilia respond to PPIs. The term 'PPI responsive oesophageal eosinophilia' has been devised to account for these cases. The clinical response to PPIs may also point to a diagnosis of GORD, which can be further confirmed by oesophageal pH monitoring/impedance study, although the histological distribution of the infiltrate is characteristically of distal location. These alternative diagnoses have led to the recommendation of a trial period of PPI treatment (2 months at 1 mg/kg twice daily) prior to other EO therapies and the inclusion of prior PPI therapy in the diagnostic criteria for EO.
Although the mechanism by which PPI's influence oesophageal eosinophilia is not clear, regression of the eosinophilic infiltrate has been reported in a significant number of cases with typical EO phenotype following PPI treatment. PPI's may also be useful as 'co-therapy' in EO by alleviating symptoms of secondary GOR.
Topical corticosteroids have been shown to be effective in inducing clinical and histological response (and remission) in children and adults with EO. Thus far, two preparations have been assessed, namely, fluticasone and budesonide. Fluticasone can be administered by metered-dose inhaler. Since the aim is topical application, the doses are deliberately swallowed, with the recommendation not to eat or drink for 30 min thereafter. Alternatively, oral viscous budesonide, typically the type of preparation used for a nebuliser, can be used. The nebuliser budesonide suspension can then be mixed with sucralose (a food additive) to aid administration.
The efficacy of these approaches has now been confirmed by randomised controlled trials. For example, Dohil et al reported the effects of treating 24 children with EO with either oral viscous budesonide or placebo (divided dose of 1 –2 mg/day depending on the size) for 3 months (together with lansoprazole in all cases). Symptoms improved in 87% of oral viscous budesonide treated cases compared with no improvement in the placebo group. This was associated with a similarly significant difference in response to mucosal eosinophil counts.
The inflammatory process in EO is not confined to the epidermal layer and indeed some cases may present with severe dysphagia making topical therapy difficult. In such cases, conventional oral corticosteroids may have a role, with trial data demonstrating efficacy. The side effects of oral therapy, however, limit its use to short courses in severely affected cases.
Topical therapy has relatively few side effects although fungal infection (candida) is a recognised potential complication. Unfortunately, at the end of a treatment course, relapse is common, leading on to longer term therapy. Low-dose topical corticosteroids are an option in this scenario and have been evaluated with some success, both clinical and histological, when used as maintenance for 1 year. If this strategy is adopted for children, then careful monitoring for evidence of adverse effects, for example, on growth, will be essential.
Other medical therapies such as cromolyn sodium and leucotriene receptor antagonists have not been shown to be effective in treating EO. The same applies in the case of the small number of patients treated with azathioprine, 6-mercaptopurine, anti-tumour necrosis factor and anti-IgE monoclonal therapy. Anti-interleukin-5 therapy has also been evaluated, but results have been disappointing. Although the treatment resulted in a reduction in the mucosal eosinophil infiltrate, this was not associated with clinical symptom resolution.
Oesophageal strictures, which are a recognised complication of EO, can be effectively managed with oesophageal dilation. There have been concerns as to the risk of complications such as oesophageal perforation and haemorrhage. Large case series, mainly in adult practice, have now been reported with a relatively reassuring outcome. For example, Schoepfer et al described the outcome of 207 patients, concluding that the risk of complications was not excessive, although postprocedure pain was common. The underlying inflammatory process is not improved following dilation, and so concomitant medical therapy is still recommended.
Pharmacological Therapy
Not all cases of EO are suitable for dietary therapy. The child (or adult patient) may not be prepared to accept the dietary restrictions or may fail to respond to this approach. Furthermore, a subgroup of EO cases appears not to be sensitised to foods but to aeroallergens. These cases often tend to have a seasonal variability to their symptoms and will require medicines to alleviate symptoms. The mainstay of drug therapy is the topical administration of corticosteroids, although PPIs have a general role to play, and so in practice, combinations of drugs and diets are often employed.
Proton Pump Inhibitor Therapy
In some cases, patients with oesophageal eosinophilia respond to PPIs. The term 'PPI responsive oesophageal eosinophilia' has been devised to account for these cases. The clinical response to PPIs may also point to a diagnosis of GORD, which can be further confirmed by oesophageal pH monitoring/impedance study, although the histological distribution of the infiltrate is characteristically of distal location. These alternative diagnoses have led to the recommendation of a trial period of PPI treatment (2 months at 1 mg/kg twice daily) prior to other EO therapies and the inclusion of prior PPI therapy in the diagnostic criteria for EO.
Although the mechanism by which PPI's influence oesophageal eosinophilia is not clear, regression of the eosinophilic infiltrate has been reported in a significant number of cases with typical EO phenotype following PPI treatment. PPI's may also be useful as 'co-therapy' in EO by alleviating symptoms of secondary GOR.
Corticosteroids
Topical corticosteroids have been shown to be effective in inducing clinical and histological response (and remission) in children and adults with EO. Thus far, two preparations have been assessed, namely, fluticasone and budesonide. Fluticasone can be administered by metered-dose inhaler. Since the aim is topical application, the doses are deliberately swallowed, with the recommendation not to eat or drink for 30 min thereafter. Alternatively, oral viscous budesonide, typically the type of preparation used for a nebuliser, can be used. The nebuliser budesonide suspension can then be mixed with sucralose (a food additive) to aid administration.
The efficacy of these approaches has now been confirmed by randomised controlled trials. For example, Dohil et al reported the effects of treating 24 children with EO with either oral viscous budesonide or placebo (divided dose of 1 –2 mg/day depending on the size) for 3 months (together with lansoprazole in all cases). Symptoms improved in 87% of oral viscous budesonide treated cases compared with no improvement in the placebo group. This was associated with a similarly significant difference in response to mucosal eosinophil counts.
The inflammatory process in EO is not confined to the epidermal layer and indeed some cases may present with severe dysphagia making topical therapy difficult. In such cases, conventional oral corticosteroids may have a role, with trial data demonstrating efficacy. The side effects of oral therapy, however, limit its use to short courses in severely affected cases.
Topical therapy has relatively few side effects although fungal infection (candida) is a recognised potential complication. Unfortunately, at the end of a treatment course, relapse is common, leading on to longer term therapy. Low-dose topical corticosteroids are an option in this scenario and have been evaluated with some success, both clinical and histological, when used as maintenance for 1 year. If this strategy is adopted for children, then careful monitoring for evidence of adverse effects, for example, on growth, will be essential.
Other Medical Therapy
Other medical therapies such as cromolyn sodium and leucotriene receptor antagonists have not been shown to be effective in treating EO. The same applies in the case of the small number of patients treated with azathioprine, 6-mercaptopurine, anti-tumour necrosis factor and anti-IgE monoclonal therapy. Anti-interleukin-5 therapy has also been evaluated, but results have been disappointing. Although the treatment resulted in a reduction in the mucosal eosinophil infiltrate, this was not associated with clinical symptom resolution.
Oesophageal Dilation
Oesophageal strictures, which are a recognised complication of EO, can be effectively managed with oesophageal dilation. There have been concerns as to the risk of complications such as oesophageal perforation and haemorrhage. Large case series, mainly in adult practice, have now been reported with a relatively reassuring outcome. For example, Schoepfer et al described the outcome of 207 patients, concluding that the risk of complications was not excessive, although postprocedure pain was common. The underlying inflammatory process is not improved following dilation, and so concomitant medical therapy is still recommended.