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Eosinophilic Gastrointestinal Disease
Eosinophils (e-o-sin-o-fills) are a type of white blood cell that are a normal part of the immune system. When triggered by allergies or infection, eosinophils increase in number and become active. In the short-term, this response is important and effective in clearing the body of pathogens. Certain tissues and organs throughout the body are accustomed to eosinophils, including some parts of the gastrointestinal (GI) tract. However, a disease state can occur when eosinophils are present in areas where they don’t normally occur on an ongoing basis, resulting in chronic inflammation. This prolonged tissue infiltration and inflammation can ultimately affect the function of that organ.
In recent years, physicians have been diagnosing a rare condition of unknown cause, called eosinophilic gastrointestinal disease (EGID), with increasing frequency in children and adults. EGID is characterized by chronic inflammation in the gastrointestinal (GI) tract caused by a greater than normal number of eosinophils without evidence of other causes (e.g., infections, allergy).
Physicians classify the disease according to where the eosinophils accumulate. Each type of the disease requires monitoring. There is currently no cure for EGID.
- eosinophilic esophagitis (EoE) is the most common type of EGID, in which large numbers of eosinophils are found in the esophagus, where normally there are no eosinophils. The esophagus is the tube that carries food from the mouth to the stomach.
- eosinophilic gastroenteritis (EG) affects the stomach and/or the small intestine.
- eosinophilic colitis (EC) is the rarest form of the disease and describes the occurrence of high levels of eosinophils in the large intestine.
EGID can affect people of all ages and ethnic backgrounds, although there appears to be associated sex and genetic factors. Research has found that 75% of individuals with EoE are male and 70-80% have other disorders such as asthma, eczema, and seasonal and/or food allergies. Most of the literature is based on EoE and the evidence base for interventions for EG and/or EC is poor and often adapted from EoE studies. Despite the advances in EoE familiarity and diagnostic criteria, there are likely many people living with EoE who are currently undiagnosed.
Symptoms/Diagnosis
Having too many eosinophils in the esophagus causes inflammation that makes swallowing difficult. The symptoms vary for each person and can include difficulty swallowing solids (often meats, rice, drier foods like bread), a feeling of food getting stuck after eating, vomiting, reflux, heartburn, pain on swallowing, and abdominal and/or chest pain. Many patients have adapted and learned to cope with their disease by modifying their eating behaviours (avoiding certain food that may trigger symptoms, avoiding eating out in restaurants, etc.). This can lead to isolation, fear, and social anxiety and can seriously restrict the quality of life.
Younger children might present with poor growth, vomiting, food refusal, and difficulties transitioning to more solid foods. Left untreated, EoE is usually associated with persistence of symptoms and inflammation and can progress to permanent damage to the esophagus by scarring and stricture formation (narrowing of the esophagus). This can result in a prolonged obstruction of the esophagus where food can get stuck (food bolus impaction) and needs removal by means of an emergency procedure. The disease course of EoE is chronic in most patients, with persistence of symptoms and esophageal eosinophilia if not treated properly. Quality of life can be improved with effective therapy.
Symptoms of EG are even more non-specific but may include diarrhea, abdominal pain, bloating, early satiety, swelling (edema), and/or iron deficiency anemia. Meanwhile, symptoms of EC typically involve bloody stools and diarrhea.
Unfortunately, many individuals with EGID can go years without a proper diagnosis, as the symptoms of EoE are similar to other well-known GI diseases such as gastroesophageal reflux disease (GERD), EG can resemble symptoms of functional dyspepsia, and the symptoms of EC are similar to Crohn’s disease, ulcerative colitis, and celiac disease. EGID is a relatively newer condition, having been first reported on in 1978, that has less general awareness and a diagnosis that isn’t always straight forward. You should not initiate treatment prior to consultation with a gastroenterologist, who can diagnose these conditions.
At present, the only way to diagnose EGID is through biopsies from an endoscopy and/or colonoscopy. During an endoscopy, a physician inserts a flexible tube with a light and a tiny camera at the end (an endoscope) through the mouth to examine the esophagus, stomach, and first part of the small intestine. For a colonoscopy, a physician uses a long, flexible tube (a colonoscope) inserted via the anus to view inside the colon. For a biopsy, the physician extracts a tiny piece of tissue for examination under a high-powered microscope. A pathologist reviewing biopsy samples will look for characteristic features of EGID but will also count the number of eosinophils. The combination of relevant symptoms and a high eosinophil count will lead to a diagnosis of EGID.
Treatment
Treatment will vary depending on the part of the GI system affected, but typically includes medication and adjustments to diet after a comprehensive review with a gastroenterologist. The multidisciplinary input of a dietitian and an allergist are often required to optimize management. The goal of treatment is to reduce symptoms as well as demonstrate improved endoscopic and histologic appearance, which means a reduction and ideally an elimination of the volume of eosinophils in the affected tissue. The treatments do have to be individualized, as what works for one person might not work for another.
In EGID, long-term treatment is required. If therapies are discontinued, as with other chronic diseases, the inflammation commonly flares up after a few months.
Dietary Therapy
Dietary therapy is one of the primary treatment methods. These can be effective whether or not you have a previously diagnosed allergic type condition.
While not intuitive, eliminating the most common food allergens is more effective than getting tested and removing foods based on the testing (called targeted elimination). The main reason for this is the testing used is designed for identifying immediate allergic reactions (IgE-mediated reaction), but allergy testing carries very low yield in management of EGID, and is not routinely recommended.
A variety of dietary therapy options are available. There are six food categories that make up the most common allergens: dairy, wheat, eggs, soy, peanuts/nuts, and fish/shellfish. Aeroallergens have also been implicated in a small group of patients with EGID.
Previous recommendations involved removing all six food groups and adding back foods stepwise if the diet is effective (after biopsy review), but evidence shows that starting with fewer may be sufficient and more sustainable. However, it is important to note that you must eliminate the foods for quite some time, typically 8 weeks, to know whether it is effective. Some sets eliminate single food groups such as dairy, or wheat as the first intervention. Another approach has been called the 2-4-6 step-up elimination diet. Step-up therapy involves removing the two most allergenic foods (dairy and wheat), then, if that is not sufficient, removing the four most allergenic (dairy, wheat, eggs, and soy), and if that is still not providing relief, removing all six.
While there isn’t a perfect way to do the eliminations, trial of food elimination followed by endoscopy and biopsies are a must.
The most effective dietary approach is an elemental diet, which involves only drinking a specialized balanced formula that has no intact proteins. This option is restrictive and difficult to follow because it involves receiving nutrition from an amino acid formula instead of eating food. Most individuals would require a feeding tube, as the taste of the formula is unpleasant. It is also extremely expensive. Elemental therapy is not meant to be a long-term treatment and is done under exceptional circumstances.
While dietary approaches may be appealing because they potentially offer effective treatment without medication, they also require massive restrictions on daily food choices and may impact quality of life. There are also important factors, such as affordability and cost, which those affected by EGID need to consider. Physicians do not recommend eliminating foods beyond the six food groups stated above, as this could result in poor nutrition. Being unable to afford to see a dietitian, or having to pay for the elemental diet formula, might be financially difficult, depending on your healthcare plan.
Dietitian counselling services in Canada can quickly become a huge cost to individuals who need ongoing advice. As the number of individuals with this disease continues to increase, it will be important to address the access issues to publicly-funded dietitian support to ensure patients are receiving adequate nutrition. Provincial governments should also reconsider their eligibility criteria for public coverage of all medically therapeutic formulas, such as elemental formula. For example, individuals living in Ontario aren’t eligible for this coverage if they are able to tolerate some solid food.
Medication
There are currently two medications approved by Health Canada to treat EoE. Budesonide (Jorveza™) is an orodispersible tablet that helps adults induce and maintain remission. This method of administration allows the medication to work locally in the esophagus to reduce the volume of eosinophils. Dupilumab (Dupixent®) is a subcutaneous weekly injection that is available for those 12 years and older who weigh at least 40 kg (88 lb). Dupixent® is also approved for severe asthma, dermatitis, and chronic rhinosinusitis, which sometimes co-exist with EoE. Both treatments reduce inflammation in the esophagus, but they use different methods: Jorveza™ is a corticosteroid and Dupixent® is a biologic.
For some individuals with EoE, proton pump inhibitors (PPIs) such as omeprazole (Losec®), lansoprazole (Prevacid®), pantoprazole sodium (Pantoloc®), esomeprazole (Nexium®), rabeprazole (Pariet®), pantoprazole magnesium (Tecta®), and dexlansoprazole (Dexilant®) can also be effective. In the past, physicians used PPIs to exclude a diagnosis of EoE, as they thought that positive response to PPIs meant that symptoms were a result of gastroesophageal reflux disease (GERD) rather than EoE. However, some research shows that PPIs might also treat EoE. There are multiple potential mechanisms for this, including anti-inflammatory effects from PPIs or reduced esophageal damage in those who have both GERD and EoE. While these drugs are approved for the treatment of GERD, they are not indicated specifically for the treatment of EoE.
Other medications that have been less studied, such as antihistamines (e.g., ketotifen), which are used frequently for conditions such as hay fever, asthma, and eczema, have also been used to help relieve the symptoms of EGID by stopping the body from reacting to allergens. Montelukast (leukotriene receptor antagonist) has also been used in patients with EGID.
Whether an individual can control the disease through diet and/or medication, it is important to note that symptoms frequently return after discontinuing treatment.
Outlook
Ongoing care for individuals with EGID is required, including the likelihood of additional endoscopies to assess how the digestive tract is responding to specific treatment. Untreated EGID may lead to malnutrition, poor growth, and anemia. In some individuals, EoE is complicated by the development of narrowing in the esophagus (strictures) and esophageal remodelling that can cause further issues with swallowing difficulty and food bolus obstruction. It is not clear how long EoE must exist before strictures form but generally it occurs gradually with years of uncontrolled inflammation.
The general principle is to control the inflammation to prevent complications such as strictures. If strictures are present and an individual has been on effective treatment (typically medication), esophageal dilation (stretching with balloon or dilator) may be indicated. It is important to keep in mind that dilation is not treating the underlying inflammatory condition but rather helps reduce symptoms and further risk of food impaction.
The long-term prognosis is unclear and there is much work required to find a cure, including plenty of research. To date, there is no evidence to suggest EoE increases risk of esophageal cancer. We need increased awareness of this condition, which is still not common at the primary care level to get individuals diagnosed in a timely manner. Once diagnosed, Canadian guidance and recommendations regarding diagnostic and therapeutic algorithms both in children and in adults could be of great benefit, because every gastroenterologist should be competent in managing this condition.