Eosinophilic Gut Diseases study day
This full study day for families and for health professionals was put together by the Academy for Paediatric Gastroenterology (APG), the gastroenterology department at Great Ormond Street Hospital (GOSH) and FABED, the support group set up by Amanda Cordell to help other families with children suffering from eosinophilic gastric disorders.
Classification of Eosinophilic disorders – Dr Mamoun Elawad, Consultant Paediatric Gastroenterologist, GOSH
There is really very little understanding of this condition or of the role played by eosinophils in the body.
Eosinophils are white cells and should appear in the body in small quantities; they are made in the bone marrow, pass into the bloodstream where they only remain for a couple of hours, and then on into the organs where they have a life of no more than 8 days.
Eosinophils should not lodge in the eosophagus, the lungs or the skin (so evidence of them in these areas suggest disease); they do lodge throughout the gut, normally in greater quantities in the left gut rather than in the right gut but very little is known as to what a 'normal' population of eosinophils may be. They appear to have both reactive and protective roles although very little is understood about what these may be.
However, if 'excited' the eosinophils in the gut (not elsewhere, it would appear) can burst, releasing toxins and causing significant inflammation. It is the release of these toxins and the subsequent inflammation that cause the pain and the many other symptoms of eosinophilic gut disease (EGD).
However, concentrations of eosinophils in the gut can be extremely patchy and can be situated anywhere from the eosophagus to the lower bowel. They can also be concentrated in all layers of the gut: the mucosa (skin), the muscles, the nerves or the outer bowel lining. EGD often presents with fewer eosinophils than normal in the bloodstream, possibly because they are being attracted into the organs.
The symptoms of EGD can be very similar to those caused by malignancies, drugs, parasites and other gastrointestinal conditions, making diagnosis particularly difficult. Eosinophils are also involved in other gastrointestinal disease such a IBD and connective tissue disorders.
EGD can affect any age group although most diagnosed cases are currently among children amongst whom the condition is equally spread across the sexes although in adults it appears to be male dominated. 70% of children with EGD are from atopic families; 10% have a first degree relative with the disease.
Classification is according to the site (oesophagus, stomach, small bowel, large bowel etc), the level (mucosal, muscle, nerve) or as affecting the autonomic nervous system – or affecting all three. When the muscles are affected it causes gut dysmotility (poor passage of food through the gut).
There seems to be a close connection between EGDs and IgE mediated allergy, usually food allergy and there is often an association between the two, but there are also many different presentations of the disease, even within the same family.
Neuro gastro eosinophilic symptoms can include:
Allergic Dysmotility – Dr Gloria Ortega, Clinical and Research Fellow, Paediatric Gastroenterology, GOSH
Underneath the mucosa (skin wall) of the gut lie layers of muscles, interspersed with nerves; the cells which lie between these are all essential to the functioning of those nerves. Excess eosinophils can lodge in the muscles, in the nerves and between the two.
Motility (the passage of food through the gut) requires coordinated contraction and relaxation of the muscles of the gut which work in tandem with the nerves. The enteric nervous system (the system of autonomous nerves which control the functioning of the gut) works independently of the central nervous system although it is affected by it, especially by allergic reactions.
In an allergic reaction, all parts of the gut can be involved as the gut decides what foods can safely pass through and what requires an allergic reaction to remove it. So muscles are very important in allergy as they release mediators, many of them hormones.
Muscle tone is very important at both ends of the gut. In reflux, the muscles may not be strong enough to keep the food in the stomach; in diarrhoea, constipation and faecal incontinence, the anal sphincter may not be strong enough either to move the food forward when needed or to keep it in the bowel if under pressure.
Gastrointestinal allergy, inflammation, immune dysregulation and gut dysmotility seem very closely related while high levels of mast cells and eosinophils affect nerve fibres and are probably the cause of the abdominal pain which appears to affect virtually all EGD patients.
An excessive population of eosinophils can damage both the nerves and the muscles of the gut. It is not known whether this pain and the disruption of the nervous system will have any lasting effect on the development of the enteric nervous system in young children.
Clinical picture of Eosinophilic Oesophagitis – Dr Neil Shah, Consultant Paediatric Gastroenterologist, GOSH
Eosinophilic oesophagitis (EE) is the best understood of the eosinophilic diseases.
Important diagnostic information includes atopic history of the parents, especially the father and especially in relationship to food allergy; do they eat 'normally' or do they 'not like' many foods? Although the condition does appear in babies it is most common in boys and teenagers.
As yet there is not enough known about eosinophilic diseases to make formal 'diagnoses' of the condition; merely 'descriptions'. It is also impossible to assess how common eosinophilic disease may be – nor, at this stage of knowledge, to say that eosinophils are the only things implicated in the condition, although it is unlikely that they are.
An attempt is always made to segregate eosinophilic disease from allergy although the conditions are very similar and many patients have both. Some children with eosinophilic disease may be sensitive to food without having an allergy, or may have other allergic conditions such as eczema, hay fever or rhinitis. Inhaled allergies are particularly common in EE.
Diagnosis of EE is easier than that of EGD as there should be no eosinophils in the oesophagus so their presence there indicates disease; eosinophils should be present in the gut but it is not known what concentration is 'normal' so it is very hard to assess the number at which disease becomes present.
Biopsies are used for diagnostic purposes but are not ideal as the eosinophils may cluster in any part of the oesophagus (or the gut) and there is no guarantee that a biopsy will catch the part in which the eosinophils are clustered. You may need four or five biopsies to get any serious understanding of the condition in that patient, and even then, symptoms and biopsies do not always match.
Although 70% of boys with EE have an atopic background or suffer from other allergies, skin prick testing is not helpful except to rule out allergens to which the patient could have an anaphylactic reaction.
Chronic EE or dysphagia (inability to swallow) may have long term complications in terms of scarring or permanent damage to the oesophagus. It is also possible that, as well as, or as a result of, releasing toxins eosinophils are eating away at the bowel or wherever they have lodged, thereby causing lasting damage.
The role of the allergist in eosinophilic disorders – Dr Helen Brough, Clinical Lecturer in Paediatric Allergy, King's college London
Tracing the links between allergy and eosinophilic diseases is really important. Research from 2002 suggests that:
The allergens to which eosinophilic patients are most likely to be sensitive are:
Exacerbating factors are:
Eosinophilic patients are also hyper-responsive to irritants so suffer more from coughing and itching. If their guts are really inflamed they will react to all food proteins.
It is important to assess the allergy status of a potential ED patient although neither skin prick not patch testing are very helpful in diagnosis, except for guarding against anaphylaxis.
Desensitisation is currently only used for aero allergens and does seem to work well for hay fever. If an eosinophilic patient also suffers from severe hay fever it may also alleviate the ED.
What is an eosinophil – and are they LIARS? – Dr Mona Bajaj-Elliott, Senior Lecturer, UCL Institute of Child Health, London
Ideally, to learn about how the body works, we should study healthy people, not sick people – but there is no funding for studying the healthy!
Food allergy is an immune reaction; food intolerance is a non-immune reaction; lactose intolerance is the dearth of an enzyme; reactions to toxins (such as caffeine) are pharmacological.
Eighty five per cent of allergy is to one small group of foods (milk, egg, wheat, soya, nuts etc) but why do only those foods cause a problem? Why not other foods? And why is it only the protein that is a problem? (For the record, the gut sees soluble and solid allergens very differently.)
And why have we had such a large rise in the incidence of food allergy in the last 100 years? It cannot be genetic so is it:
What is a eosinophil?
The word actually means 'acid loving cell'. Why are we creating too many? And what are they trying to block?
Eosinophils are present in white cells and organs but should not be in the skin, the lungs or the oesophagus all of which are squamous, sterile (eg bacteria free) environments. Is this relevant? Are eosinophils therefore important for dealing with bacteria – which is why they are not present where there are no bacteria to deal with?
Eosinophils appear to be important as a 'host defence against helminths and parasites' although that is unlikely to be their only role. Although destroying them when they over proliferate has to be the current goal of treatment, destroying all eosinophils could be unwise as we do not understand what other roles (some of them protective?) they may play. It may be one of LIARs – Local Immune And Remodelling/Repair.
The focus, maybe, should be on blocking the destructive function of eosinophils but not destroying them. However, this is not easy. Targeting eosinophils in the blood with drugs does not help, as they do not remain in the blood but lodge in the tissue and organs where they do the damage, and drugs cannot reach them in the tissue.
Dietary treatment of EGIDs – Claire de Koker, Specialist Research Dietitian, GOSH
Most research has, so far, been done on Eosinophilic Oesophagitis (EE) and one cannot necessarily extrapolate from that for the treatment for Eosinophilic Gastric Disease (EGD).
There are really only two dietary approaches: an elimination diet and an elemental diet, both of which can be used in combination with medication.
If a child is still symptomatic it will be treated with medication.
Standard therapies for EGIDs – Dr Neil Shah, Consultant Paediatric Gastroenterologist, GOSH
It is important to treat Eosinophilic Oesophagatis with drugs if diet does not work because of the danger of permanent damage to the oesophagus or of it becoming blocked.
The treatment for Eosinophilic Gastro Intestinal Disease (EGIDs) depends on the site and the primary focus is to remove the excess eosinophils; the difficulty is to know how many should be there in the first place.
EGIDs is a multi system inflammatory disease – and there are more inflammation systems in the gut than in any any other part of the body.
The target of treatment is to reduce the degranulation of mast cells and eosinophils, and to reduce the pain suffered by EGIDs children. It is clear that back-arching, screaming, irritable children are not suffering from reflux but from allergy/eosinophilic disease.
In eosinophilic gastrointestinal diseases diet remains the primary treatment but every effort is made to avoid using the elemental diet as, although the outcomes are good, it is so hard to get the children back onto eating food again.
Steroids are very successful in reducing inflammation but they do have side effects. It is also difficult to deliver the drugs to the bowel.
If you have food allergies or EGD as a child you have 2–3 times the likelihood of developing abdominal pain later in life.
Autoimmune nervous system
EGD also affects the autoimmune nervous system and can result in:
Symptom disassociation remains a major problem in EGD. A patient can have a clean biopsy yet remain multi symptomatic – yet one cannot diagnose without a biopsy or endoscopy.
Cinncinato Center for Eosinophilic Disorders – Sean Jameson, Program Manager at the Cinncinati centre
Sean Jameson described the history of and the work performed at the Cinncinati Center which focuses almost exclusively on Eoinophilic Oesophagitis.
Check in at their website at www.cincinnatichildrens.org for more details of their work.
You can see the whole day as a live webscast here on the PAG site.
For more on oesinophilic diseases contact FABED – the support group for Families Affected by Eosinophilic Disorders.
First published in September 2012
Click here for more articles on EGIDS