Two expert group meetings were convened to discuss how the management of EoE in the UK can be improved and to consider new evidence since the British Society of Gastroenterology, United European Gastroenterology, European Academy of Allergy & Clinical Immunology, European Society for Paediatric Gastroenterology, Hepatology & Nutrition and European Consortium for Eosinophilic Diseases of the Gastrointestinal Tract guidelines were published.9 12 Figure 1 shows the integrated pathway for diagnosis and management of EoE developed following these meetings. This paper summarises the full guidance, which is also available at https://know-eoe.co.uk/payors

Presentation of EoE

EoE can present at any age, but the incidence rises during adolescence and peaks in early adulthood.7 9 12 It is more common in men, white people and those with an affected first-degree relative.7–9 12 Two-thirds of patients have other atopic diseases such as asthma, rhinitis and eczema.8 9

In about one-third of patients, acute food bolus obstruction requiring emergency hospital attendance is the first presentation of EoE.7 12 In the remainder, swallowing difficulty is of slower onset, with progressive dysphagia and repeat episodes of milder, self-resolving food bolus obstruction.1 2 7 12 Patients, aware of food travelling down their oesophagus, adapt eating habits by drinking large volumes of water and preferring soft foods such as soups over meat and bread.7 8 12 Patients avoid eating out because they are prolonged chewers, slow to eat and last to finish meals, resulting in social isolation, anxiety and reduced quality of life.7–9

Acute management of food bolus obstruction

Drug and conservative therapies (eg, baclofen, glucagon, salbutamol, benzodiazepines and fizzy drinks) are not recommended, as they do not reliably resolve food bolus obstruction and the risks may outweigh the benefits.8 12 14 Endoscopic removal has success rates >95% and minimal complications and is recommended for all patients within 24 hours to increase the chance of removal and decrease the risk of complications; it is urgently required in patients unable to swallow their own saliva.14 Endoscopy suction caps for upwards extraction make the removal of food boluses easier, quicker and safer.

Acute management of food bolus obstruction

Perform chest X-ray only in patients in distress and chest/abdominal CT only if patients have surgical emphysema or oesophageal perforation is suspected.12 43

Clear food bolus obstruction endoscopically and take six oesophageal biopsies if a diagnosis of EoE is not already made.

Perform immediate dilatation if indicated.12

Do not start PPIs or conservative treatments such as baclofen, glucagon, salbutamol, diazepam or fizzy drinks.8 12

Referral for suspected EoE

Accident and emergency clinicians often do not refer to gastroenterology or endoscopy, especially if food bolus obstructions resolve spontaneously.15 They may assume the obstruction is in the throat and refer to ear, nose and throat services, which are not set up to diagnose EoE.8 This can delay diagnosis, leading to repeated emergency attendances. Further food bolus obstruction typically develops within 3 months,16–19 and failure to follow-up predicts recurrence.20

Referral from accident and emergency

Do not discharge patients with food bolus obstructions without arranging further investigation or follow-up, even if obstructions resolve spontaneously.8 12 22

Refer urgently to gastroenterology.8 12

Before the patient leaves accident and emergency, request oesophago-gastro-duodenoscopy, including oesophageal biopsies:

within 6 hours if patients are distressed;

within 24 hours if patients have acute obstruction or cannot swallow their own saliva due to the high risk of aspiration;

within 2–4 weeks if obstruction resolves to ensure EoE is diagnosed before another event.

Avoid PPIs if biopsies cannot be obtained during acute management to avoid masking eosinophilia at later biopsy.23

Awareness of EoE is increasing among general practitioners, who may refer patients with a feeling of food stuck in their throat to gastroenterology for endoscopy. However, other conditions may be suspected initially due to the nature of the symptoms. Partial symptom relief with proton pump inhibitors (PPIs) in some patients may compound misdiagnosis.

Referral from primary care

Refer patients with symptoms of airway blockage, difficulty breathing, distress or continuous coughing as an emergency or to the ear, nose and throat department.

Refer all patients with dysphagia describing symptoms of food stuck in their oesophagus to gastroenterology for further investigation and endoscopy.

Book oesophago-gastro-duodenoscopy within 2–4 weeks at a service that performs biopsies.

Do not start PPIs.12

Stop PPIs 2–3 weeks before endoscopy to avoid masking eosinophilia.12 44

Give patients an information leaflet to explain the suspected diagnosis of EoE and that it is treatable, so they expect follow-up and understand the importance of endoscopy, even if the obstruction resolves.

Diagnosis

All patients with food bolus obstruction should have immediate arrangements for gastroscopy, as the diagnosis of EoE requires oesophago-gastro-duodenoscopy with biopsies.7 8 12 Endoscopic features include rings, furrows, white exudates and strictures.7–9 12 21 22 Histological features differentiating EoE from conditions such as gastro-oesophageal reflux disease include eosinophil surface layering, eosinophilic microabscesses and >15 eosinophils per 0.3 mm2 (formerly per high-power field) in the oesophageal squamous epithelium—the diagnostic criterion for EoE.1 7–9 12 22 23

Endoscopic findings are frequently subtle and unspecific and may go unnoticed.8 12 Inflammatory changes are often patchy, so multiple biopsies are needed7–9; sensitivity to identify EoE increases from 55% with one biopsy to approximately 100% with six biopsies.12 24 International guidance recommends ≥6 biopsies from two to three levels.9 25 Eosinophil counts are higher in areas with abnormal findings, particularly white exudates and longitudinal furrows.8 9 12 26

Diagnosis of EoE

Diagnose EoE through oesophago-gastro-duodenoscopy with biopsies, even if the oesophagus looks normal.7–9 45

Take ≥6 biopsies from multiple sites (ideally 3).7–9 24

EoE is confirmed by a peak eosinophil count of >15 eosinophils per 0.3 mm2 (equivalent to the previous threshold of >15/high-power field) of oesophageal epithelium.7 8

Induction of remission

Before budesonide orodispersible tablet—a corticosteroid formulation with oesophageal topical delivery—was licensed for EoE in the UK in 2018,27 28 numerous poorly effective approaches were used to manage symptoms, including elimination diets, off-licence PPIs and asthma corticosteroids, and investigative biologics targeting T-helper cell type 2 inflammation.8

Induction of remission

Discuss the efficacy and limitations of all treatment options for EoE with the patient.

Budesonide orodispersible tablet was developed specifically for EoE and is the only licensed treatment in the UK.28

Systemic steroids, swallowed fluticasone and other immunosuppressants are not recommended.9 10 12

PPIs have variable efficacy, and their use is off-licence.8–10 12

Dietary approaches are lifelong, of limited efficacy, burdensome for patients and involve multiple endoscopies.8–10 12

Monoclonal antibodies and biologics are reserved for clinical trials and are not routine practice for EoE in the UK.9 12

Budesonide orodispersible tablet allows targeted delivery of the glucocorticosteroid budesonide for patients with EoE, with very low systemic effects.29 The tablet disintegrates when placed on the tongue, dispersing budesonide in the mouth.29 Swallowed saliva loaded with budesonide lines the oesophageal mucosa and delivers budesonide to the oesophageal epithelium, where it inhibits the antigen-stimulated secretion of proinflammatory signal molecules, significantly reducing eosinophilic inflammatory infiltrate, with very low systemic effects.29 30

Budesonide orodispersible tablet is the most effective steroid therapy currently available for EoE.27 In the EOS-1 trial, 57.6% of patients achieved clinico-histological resolution with budesonide orodispersible tablet after 6 weeks compared with none taking placebo (p<0.0001) and 93.2% achieved histological resolution (figure 2).31 In the EOS-2 trial, 69.6% of patients achieved clinico-histological remission (histological 90.1%, clinical 75.1%) after 6 weeks of induction with 1 mg budesonide orodispersible tablet two times per day (figure 2) and mean peak eosinophil counts decreased by 89.0%.32 In patients in EOS-1 who did not achieve clinico-histological remission after 6 weeks or dropped out at ≥4 weeks due to lack of efficacy, prolonging treatment to 12 weeks led to clinico-histological remission in 84.7% of patients (figure 2).31 Accordingly, although the licensed treatment duration is 6–12 weeks,28 usual duration of induction in clinical practice is 12 weeks. In June 2021, the National Institute for Health and Care Excellence (NICE) in the UK recommended budesonide orodispersible tablet to induce remission of EoE in adults.33

Induction of remission—budesonide orodispersible tablet

Budesonide orodispersible tablet offers reliable efficacy and should be recommended for patients with frequent, daily symptoms.

If a patient opts to try budesonide orodispersible tablet, prescribe a sufficient supply of 1 mg two times per day until gastroenterology follow-up.

A repeat oesophago-gastro-duodenoscopy between 8 and 12 weeks may not be required in patients taking budesonide orodispersible tablets.

Arrange gastroenterology follow-up at 14 weeks to assess response and symptoms.

Arrange repeat oesophago-gastro-duodenoscopy for patients with persistent dysphagia and obtain consent for dilatation if required.

Figure 2

Induction of remission with budesonide orodispersible tablet in patients with eosinophilic oesophagitis (EoE): clinico-histological remission at weeks 6 and 12 in EOS-1 and at week 6 in EOS-2.31 32 ODT, oral dispersible tablet.

PPIs inhibit eotaxin-3 and/or reduce acid in 10% of patients with EoE and symptomatic gastro-oesophageal reflux disease.8 12 34 They are ineffective in maintaining remission in patients with histological responses12 but may improve reflux symptoms. In one study, PPIs resulted in histological remission in 49% of patients, deep histological remission in 38% and some improvement in 71%.35 In a long-term study, 35.5% of patients had an initial response to PPIs, but only 22% of these had a long-term histological response.36 PPIs have no proven effect on fibrosis and only partially improve symptoms in non-fibrotic EoE.12

Induction of remission—PPI

PPIs usually fail and should be a first-line treatment only in patients with mild, intermittent symptoms and according to patient preference.

If patients opt to try PPIs, prescribe double the usual dose (equivalent to 20 mg omeprazole two times per day) for 8–12 weeks,12 with sufficient supply until gastroenterology follow-up.

Book oesophago-gastro-duodenoscopy 12 weeks after treatment is started.

Arrange gastroenterology follow-up at 14 weeks to assess response and symptoms.

As EoE is thought to occur when the oesophageal mucosa reacts to environmental antigens, mostly in foods,3 8–10 12 dietary intervention seems logical,12 35 but it is variably effective. Eliminating milk and wheat, the most frequently implicated foods (two-food elimination), has a 30% success rate; eggs and soy can be eliminated if these are not successful (four-food elimination); and then nuts and seafood (six-food elimination).12 In a randomised trial, neither one-food nor six-food elimination diets restored normal histology or relieved symptoms of EoE.37 Six-food elimination resulted in higher histological remission rates than two-food or four-food elimination but with lower compliance and more endoscopies.12 38 Intensive support from experienced dieticians is required during elimination and reintroduction, with endoscopies at baseline and after each reintroduction.12 37 Diets must be maintained lifelong to maintain remission, but long-term adherence is poor.12

Induction of remission—diet

Diet usually fails and should be a first-line treatment only according to patient preference and with consideration of the burden in patients with mild, intermittent symptoms.

If patients opt to try diet:

Recommend a step-up approach (two-food to four-food to six-food).12 38

Arrange dietician support for elimination/reintroduction.10

Arrange oesophago-gastro-duodenoscopy 6–12 weeks after each food reintroduction.12

Book oesophago-gastro-duodenoscopy 12 weeks after treatment is started.

Arrange gastroenterology follow-up at 14 weeks to assess response.

If the patient has persistent symptoms, switch to budesonide orodispersible tablet and arrange for further gastroenterology follow-up.

Maintenance of remission

Maintenance therapy is recommended to reduce the risk of recurrent symptoms of dysphagia and food bolus obstruction,12 30 as relapse is common after treatment stops (figure 3).12 29 39

Figure 3

Relapse in patients with eosinophilic oesophagitis following cessation of treatment after induction of remission: symptom recurrence following oral viscous budesonide or fluticasone inhaler (A) and time to clinical relapse following budesonide orodispersible tablet or placebo bd, two times per day (B).39 40 ODT, oral dispersible tablet.

After 48 weeks of treatment in EOS-2, 73.5% and 75% of patients receiving budesonide orodispersible tablets 0.5 mg and 1.0 mg two times per day, respectively, were in persistent remission compared with 4.4% of placebo patients (p<0.001 for both budesonide doses vs placebo) (figure 4).40 After 96 weeks of treatment in patients still in remission after 48 weeks and relapsing patients in whom clinical remission was re-induced by 6 weeks of budesonide orodispersible tablet 1 mg two times per day, 86.1% of patients receiving maintenance budesonide orodispersible tablet 0.5 mg two times per day maintained clinical, histological and endoscopic remission (figure 4) and 78.8% of patients who received an optional biopsy were in deep histological remission (no eosinophils in any biopsy) (figure 4).41 No loss of efficacy or increase in side-effects was observed up to 3 years.41

Figure 4

Maintenance of remission with budesonide orodispersible tablet bd (two times per day) in patients with eosinophilic oesophagitis (EoE): clinico-histological at week 48 and clinical and deep histological remission at week 96 of EOS-2.40 41 ODT, oral dispersible tablet.

Although NICE approved budesonide orodispersible tablet for inducing remission of EoE in adults in 2021, the appraisal was published after maintenance of remission was licensed in March 2021.28 33 42 Until NICE undertakes a new appraisal of budesonide orodispersible tablet for maintenance and offers its opinion, the NHS is obligated to provide access to the only product licensed for EoE in line with its approved indication of induction and maintenance of EoE.28

Maintenance of remission

Budesonide is licensed for maintenance therapy in patients with EoE achieving remission on budesonide orodispersible tablet.28

The recommended dose for maintenance of remission is 1 mg/d budesonide as one 0.5 mg tablet in the morning and evening or 2 mg/d budesonide as one 1 mg tablet in the morning and evening.28

1 mg budesonide two times per day is recommended for maintenance in patients with long-standing disease or high oesophageal inflammation in acute disease.28

Duration of maintenance therapy is determined by the treating physician.28

Send a letter to the general practitioner to confirm oesophago-gastro-duodenoscopy results, treatment plan, patient-initiated follow-up is in place and timing of next gastroenterology review.

Repeat prescribing of budesonide orodispersible tablets should be undertaken by general practitioners if possible or via gastroenterology if not.

General practitioners should manage the repeat prescribing of PPIs.

Patients should have an annual follow-up with gastroenterology: