What is EGID?

Eosinophilic (E-o-sin-o-fil-ik) Disorders Information.

We encountered the world of EGID via Reflux symptoms initially. My whole family on my Dad's side had always suffered Gastro Oesophogeal Reflux to some extent (myself included) along with plenty of allergies, autoimmune problems and supposed IBS. I became very involved in supporting other parents dealing with infant reflux, and became aware that whilst other people's children seemed to outgrow their symptoms, ours waxed and waned, changed over time but certainly never went away. In 2010 our twins, who suffer most of all the children (I have 4, yes I'm a glutton for punishment!) were referred to Great Ormond Street Hospital and received diagnoses of EGID. It is highly likely that many family members suffer this autoimmune inflammatory disease to some extent.

I constantly read and attempt to make sense of the condition my children suffer with. I am not medically qualified, I merely include the information below to inform others and give them a platform from which to question and discuss. 

Eosinophilic disease is SOMETIMES the cause of reflux. One can be present without the other but when food intolerances, a complex set of symptoms and failure to respond to standard reflux medication present together then it is often considered. I have written a leaflet on Reflux in infants and children with Eosinophilic Disease here and also a more straightforward one on infant reflux which has been published and used in some hospitals in the UK. Increasingly, many patients with EGID diagnoses are also found to have Hypermobility Spectrum Disorder or possibly hEDS (Hypermonile Ehlers Danlos Syndrome). There is certainly some crossover between the two.

Eosinophilic disorders occur when eosinophils, a type of white blood cell, are found in above-normal amounts in various parts of the body. When the body wants to attack a substance, such as a food protein or airborne allergen, eosinophils respond by moving into the area and releasing a variety of toxins. This is a Type 4 Hypersensitivity, or delayed hypersensitivity. Many people with EGID will not test positive in skin prick tests or RAST allergy tests because it is a localised, delayed response.  It is still an immune response however and a true allergy. 

When the body produces too many eosinophils, they can cause chronic inflammation, resulting in tissue damage. This  inflammation can be localised or more widespread and can be due to autoimmune problems or an allergic response to allergens. (food seasonal, environmental etc) 

It is also suspected that increased levels of eosinophils increase gut permeability, which means foreign proteins cross over into the bloodstream. Once there they are treated as a foreign body (see below for more on this). Infant guts are designed to be permeable before six months to allow maternal antibodies to cross into the baby's bloodstream but after this time the gut should no longer be permeable.

Hyper allergic infants will often demonstrate symptoms of gut allergy before 6 months, but in any case it is recommended by the World Health Organisation that weaning is delayed until 6 months of age for precisely this reason. It does not stop allergies developing but makes them less likely.

When the gut responds to potential allergens (either appropriately or inappropriately) cells called mast cells release toxins. These are soaked up by nearby neurotransmitters which take the toxins to the central nervous system. This is why parents report behavioural changes in children with gut allergies, and children prone to sensory issues really struggle with a massive increase in sensory dysfunction when their gut is flaring.

An APFED video for children explaining what EGID is.

Eosinophilic disorders require allergens to be eliminated, but it is becoming clearer that these are not the only cause for the illness. There is little published research available, however it is now thought that it is an autoimmune response and seems to run in families suggesting genetic nature of the illness.

EGIDs are being recognized more and more around the world. In fact, recent studies in Cincinnati have shown that one type of EGID, eosinophilic esophagitis, is even more common than other well-known diseases that affect the gastrointestinal tract such as Crohn's Disease and Cystic Fibrosis.

What is Eosinophilic Disease?

An eosinophilic disorder is when a type of white blood cell called an Eosinophil is found in abnormal amounts in the Gastro-Intestinal (GI) tract (This is from the oesophagus down through the stomach and into the large and small bowel right through to the back passage). They are given diagnosis dependent on the area of the gastro-intestinal tract affected, these are:

Eosinophilic Oesophagitus - affecting the Oesophagus. More likely to include reflux symptoms.

Eosinophilic Gastroenteritis - affecting the stomach and small bowel.

Eosinophilic Colitis - affecting the large bowel / colon.

Eosinophilic Enterocolitis - affecting the small and large bowels.

Eosinophilic Gastroenterocolitis - affecting the stomach, small and large bowel.

An eosinophil is a type of white blood cell that is present in all people. It accounts for a very small amount of the total white blood cells, about 4%. When these are present in the body in normal amounts they actually help the white blood cells in fighting infection, parasites and allergens. When Eosinophilic patients’ bodies encounter an infection or allergen these eosinophils multiply in abnormal amounts. They have the opposite effect and actually cause inflammation and cause damage to tissue and nerves in the affected areas. If these disorders are left untreated they can spread and cause more serious damage to organs and enter the blood stream.

What are the symptoms?

The symptoms vary from patient to patient and can show in any order at any time and in any amount. Some of the symptoms that we have experienced, and this list is not exhaustive, are:

Stomach pains

Diarrohea

Constipation

Lethargy

Mouth Ulcers

Rashes, often with no obvious cause

Asthma attacks, possibly more directly related to reflux

Sore throat

Joint Pains

Headaches

Vomiting

Nausea

Failure to thrive

Sudden weight loss

Mood swings

Excessive sweating/body odour

Loss of colour in the skin

Dark rings under the eyes
Obviously, there are many other reasons why someone could have many of these symptoms.

Diagnosis

The most recognized way to diagnose an Eosinophilic Disorder is by analysing biopsies from the GI tract. More children are now being given a diagnosis on symptoms alone as Drs become more familiar with the obvious signs of the Disease. If eosinophils are present above the diagnostic threshold allergic reactions are more likely. If a child is already on an exclusion diet and is already medicated it may be more difficult to determine whether EGID is the cause of symptoms as eos levels will be lower.

This is a useful link explaining about gut cells and the immune system.

Once a diagnosis has been established, the consultant will discuss the treatment options. Currently there are 3 main treatment paths that are followed:

Elimination diet

The patient will have almost certainly already had allergy testing to rule out any more common illness. However not all may have been prescribed an elimination diet. Where this is recommended the patient removes all the offending allergens. After a period of time these will be re-introduced one at a time until a reaction is seen. The number of allergens taken from a diet can vary from patient to patient. Some of them most common allergens to be removed are:

Wheat, Dairy, Gluten, Egg, Soya.

Medication

There are no clinical guidelines in the treatment of Eosinophilic Disorders. A number of medications used in the treatment of other GI and/or auto immune disease have had a positive affect in the treatment of Eosinophilic disorders. These range from mild over the counter anti-histamines to powerful immuno suppressive medication in the most serious cases, some of those used are:

Anti-Histamine - These are used in most allergic conditions such as Hayfever, Asthma Eczma etc… They are used to help relieve the symptoms by stopping the body from reacting to allergens, Examples used are Ceterizine / Ketotifen

Sodium Cromoglicate - Used where a food allergy has already been determined. Given before each meal to prevent histamine being released which prevents the symptoms of the allergy. Given under the trade name of Nalcrom.

Leukotiene (luke-o-try-en) Inhbitors - Used primarily in the treatment of Asthma. Has proven to be successful in relieving the symptoms of other allergic conditions. They will not help to induce remission in Eosinophilic patients but does help to relieve allergic symptoms. Given under the trade name of Montelukast (Singulair).

Amino -Salicylates - This type of medication is used in the treatment of Inflammatory Bowel Disease (IBD), Crohns and Ulcerative Colitis (UC). They are anti-inflammatory drugs that help reduce the inflammation in the gut and prevent flare-ups. Most commonly given in liquid form called Sulphfasalazine. Because these medicines can cause a decrease in the normal number of blood cells in the blood, it is necessary to monitor the blood cell count by way of blood tests at least every 4 months.

Glucocorticoids (Steroids)- are used in many conditions to suppress inflammation. These are one of the most effective medications in the treatment of Eosinophilic Diorders. They are initially given in a high dose and then slow tapered off to a lowest possible dose where no adverse reaction is detected. Although the patient will require regular blood tests (approx 3 months) to check blood count, kidney function etc.. Bone density also needs to be closely monitored.

Immunosuppressant’s - Primarily used as a anti-rejection drug in transplant patients, these are used to reduce the activity of the cells in the immune system. These drugs reduce the production of the white blood cells, which reduces the ability of the immune system to attack the normal tissue. In Eosinophilic patients this can cause a remission in the illness. The full effect of this drug can take months to become apparent, but once working can be taken for a prolonged period without serious side effects. Blood counts do have to monitored very closely. Some of those used are, Azathioprine, Mycophenolate Mofetil or MMF and 6MP

Patients with an Eosinophilic condition commonly will have other allergic conditions such as, Asthma, Eczema, Hayfever, Rhinitis etc. Combined treatments will usually be used in the treatment of these associated illnesses.

Elemental Diet 

Where the illness persists or there is still failure to thrive, a elemental diet may be recommended to enable the body to absorb all the necessary nutrients without the need to swallow whole foods. A special formula is prescribed built of of Amino Acids (the building blocks for proteins), fats, sugars, vitamins and minerals. These can be given in the short or long term and require monitoring under the supervision of a qualified dietician. Elemental diets can be the sole source of nutrition or in conjunction with a elimination diet. If a patient is unable to take the formula orally, a feeding tube maybe required. If required for a prolonged period, the tube will be inserted through the stomach.

There is no cure for Eosinophilic Disorders.

They are manageable through diet and treatment, every case will vary in its severity. The illness can come and go, improve or worsen, this means that the patient can be in remission for months, even years but the illness can return at any time. Over the next few years it is hoped that public and professional awareness will be raised to a level where the exact causes for relapse is identified. There is currently too much ignorance in the medical profession over this disorder, with many pediatric consultants unwilling to diagnose and therefore worsening the condition of those patients who are awaiting answers. Professional opinion often conflicts and too often parents are suspected of exaggerating symptoms and accused of FII or Munchausen by Proxy. It's not easy diagnosis and brings little or no understanding.

One thing that is yet to be examined fully with this illness is the psychological effects on the patients, although leading experts in the field agree that there is a need for monitoring.

It is interesting to note that "leaky gut syndrome" has gained more credence since research into EGID has demonstrated how delayed Type IV sensitivities work and their effect on the permeability of the gut wall. This is also thought to be the reason hypermobile Ehlers Danlos Syndrome (hEDS)  often presents with food allergies- because collagen problems mean the gut wall is "leaky" and permits food proteins to cross into the blood stream and precipitate a local allergic response. This also gives some credence at least in theory to the notion that food allergies can precipitate autism and ASD behaviours. Many parents note how a normal child will appear extremely autistic when flaring with EGID. High histamine levels have also been noted in patients with EGID which is why antihistamines help, histamine is produced by mast cells. There is a useful Blog here discussing the role of histamine.

Read more on the US Cincinnati Children's Hospital Research Centre's Website here.
Read an interesting article "Life without food" about EoE and EGID here.