Eosinophilic oesophagitis (EO) - also abbreviated to EoE in American publications - is a disease characterised by oesophageal symptoms and infiltration of eosinophils in the oesophageal epithelium. Originally thought to be a type of gastro-oesophageal reflux disease (GORD), its failure in many (but not all) patients to respond to proton pump inhibitors (PPIs) and the recognition of eosinophilic infiltration on biopsy eventually led to EO being classified as a disease in its own right. Topical steroid therapy is the mainstay of treatment.
Initially thought to be a paediatric condition, EO is now known to be at its most common in middle-aged men. The average age at diagnosis is 30-50 years and the male-to-female ratio is 3:1. It is associated with allergic conditions.
The disease is most common in Caucasians. It has a wide geographical distribution, with cases reported in Europe, the USA, Canada, Brazil, Japan and Australia. It has a predominance in developed countries. The reason for this is unknown but it has been mooted that allergic diseases are more common in these countries or reporting of cases and data collection are better.
The prevalence has increased in recent years but it is not known if this is due to better diagnosis of the condition or whether there has been a true increase. A community study in Sweden reported a prevalence of 4 in 10,000. Thus, assuming a similar prevalence in the UK, a general practice with 5,000 patients would have 2 patients with OE on its list.
The oesophageal section of the British Society of Gastroenterology set up a National Registry in March 2010. 300 patients were registered in the first 18 months.
The presentation varies according to the age of the patient. In children the disease presents with failure to thrive and food refusal. Adolescents may experience chest pain, epigastric pain or vomiting. In adults, dysphagia and food bolus obstruction are common presenting symptoms, often accompanied by heartburn and chest pain. In fact, OE tends to be a late diagnosis and is often mistaken for GORD in the early stages. It may only be when dysphagia or food bolus obstruction develops that appropriate investigations are instituted and the true diagnosis revealed.
A personal history of allergy is common including:
Known causes of tissue eosinophilia need to be excluded. These include:
Diagnosis relies on demonstrating more than 15 eosinophils per high-power field on microscopy of an oesophageal biopsy.
Endoscopic abnormalities of the oesophagus may include:
- Diminished vascular pattern.
- Mucosal furrows.
- Thick mucosa.
- Rings - as in image below.
- Laryngeal oedema, vocal cord nodules, laryngeal ventricular obliteration.
Samir (own work) via Wikimedia Commons
Histological abnormalities may include:
- Abnormally long papillae.
- Fibrotic lamina propria.
- Eosinophilic granules.
- Increased extracellular major basic protein (MBP).
Other tests may be required to exclude other causes of tissue eosinophilia, depending on the clinical presentation.
Dietary manipulation is a non-pharmacological treatment which can be effective both in children and in adults. It can be used as an initial treatment or as an adjunct to pharmacological therapy. There are three main approaches:
- Elemental diet: this involves taking an amino acid mixture for six weeks. The mixture is often considered unpalatable and compliance is often poor but considerable improvement in symptoms and the histological picture has been noted.
- Exclusion of six food groups.
- Exclusion of food based on allergen tests.
It is essential to involve a dietician and sometimes an allergist if dietary manipulation is attempted.
This is the first-line medical treatment in adults and children. Fluticasone metered dose inhaler is usually used. The inhaler is sprayed into the mouth without inhaling and dry swallowed. Patients should be advised not to eat food or drink liquid for half an hour after a dose. Budesonide oral solution is an alternative, mixed with sucralose, chocolate syrup or honey. The treatment is effective in promoting histological remission but a systematic review suggested this does not always result in symptomatological improvement. Only 1% of steroid is absorbed so systemic side-effects are rare. Oral or oesophageal candidiasis are, however, common side-effects.
This is second-line treatment for adults and children when topical steroids and/or dietary manipulation fail. It is also used when oesophageal narrowing or stricture develops. Hydrostatic balloon dilatation or guided wire bougie dilatation may be performed. Dysphagia and quality of life are improved but eosinophilic infiltration is not affected. Repeated procedures may be needed. Mucosal tearing can lead to transient chest pain but there is no evidence that the histological changes predispose to perforation. The perforation rate (0.3%) is no greater than that seen in other oesophageal conditions.
Several novel approaches to therapy are being investigated, with varying degrees of success. These include:
- Anti-IgE therapy: the principle here is that some cases may be IgE-mediated. Omalizumab, an anti-IgE monoclonal antibody, was effective in some clinical trials but ineffective in others, suggesting that patient selection is important.
- Repairing the oesophageal epithelium: sucralfate slurry, which has been used in similar circumstances to heal peptic ulcers, is currently being investigated.
- Immunomodulators: azathioprine and 6-mercaptopurine have been useful in small trials but the condition recurred as soon as therapy was stopped, indicating that continued immunosuppression was required.
- Chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2) antagonist: this is manufactured by Th2 lymphocytes, eosinophils and basophil in many allergic conditions. Clinical trials have demonstrated moderate success in OE patients.
- Mast cell stabilisers: mast cells have long been suspected to act alongside eosinophils in causing epithelial inflammation. However, trials with the mast cell stabiliser cromoglycate have yet to prove significant beneficial effect.
- Immune modulators: immune modulators, such as IL-4, IL-5 and IL-15, TGFβ1, tumour necrosis factor and leukotriene, are all known to have increased activity in OE. Trials of agents which inhibit immune modulator action are currently in progress.
- PPI therapy: although failure to respond to PPI is one of the reasons for considering a diagnosis of OE, a small subset of patients does have some benefits from PPI therapy. This is thought to be related to both the acid-suppressive and the anti-inflammatory effects of PPIs.
OE is a chronic disease causing inflammation of the oesophagus. Complications may include oesophageal remodelling, fibrosis and stricture. Oesophageal malignancy has never been shown to occur. The condition is usually diagnosed several years after onset. Continued maintenance therapy with topical steroids and/or dietary manipulation helps to reduce complications, particularly in patients who have a history of food impaction, dysphagia or oesophageal stricture. Maintenance is also important in patients with a history of rapid histological and/or symptomatic relapse after stopping initial treatment.
Further reading and references
Furuta GT, Katzka DA; Eosinophilic Esophagitis. N Engl J Med. 2015 Oct 22373(17):1640-8. doi: 10.1056/NEJMra1502863.
Runge TM, Dellon ES; Do We Know What Causes Eosinophilic Esophagitis? A Mechanistic Update. Curr Gastroenterol Rep. 2015 Sep17(9):33. doi: 10.1007/s11894-015-0458-9.
Hruz P; Epidemiology of eosinophilic esophagitis. Dig Dis. 201432(1-2):40-7. doi: 10.1159/000357008. Epub 2014 Feb 28.
Gupte AR, Draganov PV; Eosinophilic esophagitis. World J Gastroenterol. 2009 Jan 715(1):17-24.
National Registry of eosinophilic oesophagitis; British Society of Gastroenterology
Papadopoulou A, Koletzko S, Heuschkel R, et al; Management guidelines of eosinophilic esophagitis in childhood. J Pediatr Gastroenterol Nutr. 2014 Jan58(1):107-18. doi: 10.1097/MPG.0b013e3182a80be1.
Ahmed M; Eosinophilic esophagitis in adults: An update. World J Gastrointest Pharmacol Ther. 2016 May 67(2):207-13. doi: 10.4292/wjgpt.v7.i2.207.
Murali AR, Gupta A, Attar BM, et al; Topical steroids in eosinophilic esophagitis: Systematic review and meta-analysis of placebo-controlled randomized clinical trials. J Gastroenterol Hepatol. 2016 Jun31(6):1111-9. doi: 10.1111/jgh.13281.
Singla MB, Moawad FJ; An Overview of the Diagnosis and Management of Eosinophilic Esophagitis. Clin Transl Gastroenterol. 2016 Mar 177:e155. doi: 10.1038/ctg.2016.4.
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