Eosinophilic gastroenteropathies are gastrointestinal (GI) diseases (enteropathies) in which one or more layers of the GI tract (most commonly the stomach and small intestine) are selectively infiltrated with a type of white blood cell called eosinophils, as part of an allergic response.
Eosinophilic gastroenteropathies are characterized by the accumulation of an abnormally large number of eosinophils (eosinophilic infiltration) in one or more specific places anywhere in the digestive system and associated lymph nodes resulting in nausea, difficulty swallowing, abdominal pain, vomiting and diarrhea, excessive loss of proteins in the GI tract, and failure to thrive. All gastroenteropathies are characterized by the presence of abnormal GI symptoms, eosinophilic infiltration in one or more areas of the GI tract, and the absence of an identified cause for the formation of an abnormally large number of eosinophils in the blood (eosinophilia). Some patients also suffer loss of protein from the body that often results in low blood levels of albumin and total protein (protein-losing enteropathy) due to increased GI tract permeability. As the GI tract wall becomes infiltrated with large numbers of eosinophils, its normal architecture is disrupted, and so is its function. Eosinophils are immune system white blood cells that destroy parasitic organisms and play a major role in allergic reactions. For this reason, the gastroenteropathies are often considered as food-related gastrointestinal allergy syndromes.
Eosinophilic gastroenteropathies have a specific name corresponding to the area of the digestive system where the highest numbers of eosinophils are found. They include the following:
Eosinophilic gastroenteritis (EG) is the best characterized gastroenteropathy. It is classified according to the layer of the GI tract involved, and mixed forms also occur. The walls of the GI tract have four layers of tissue, called mucosa, submucosa, muscularis externa, and serosa. The innermost layer is the mucosa, a membrane that forms a continuous lining of the GI tract from the mouth to the anus. In the large bowel, this tissue contains cells that produce mucus to lubricate and protect the smooth inner surface of the bowel wall. Connective tissue and muscle separate the muscosa from the second layer, the submucosa, which contains blood vessels, lymph vessels, nerves, and glands. Next to the submucosa is the muscularis externa, consisting of two layers of muscle fibers, one that runs lengthwise and one that encircles the bowel. The fourth layer, the serosa, is a thin membrane that produces fluid to lubricate the outer surface of the bowel so that it can slide against adjacent organs. The different types of EG are:
Eosinophilic esophagitis (EE) is characterized by the abnormal accumulation of eosinophils localized in the esophagus. In EE, high levels of eosinophils are detected in the esophagus but not in any other parts of the digestive tract. The presence of the eosinophils in the esophagus causes inflammation of its walls, which makes digestion extremely painful. Unlike that of normal children, the esophagus of an individual with EE does not have a smooth, uniform pink surface but displays lines (furrowing) and white patches. Children with EE have classic signs of gastroesophageal reflux (abdominal pain, difficulty swallowing, and vomiting) but fail to respond to antireflux medications. The danger of failing to diagnose this disorder is that children may be referred for unnecessary surgery because of their reflux symptoms.
Eosinophilic colitis (EC) is characterized by eosinophilic infiltration localized only in the large bowel, resulting in fever, diarrhea, bloody stools, constipation, obstruction/strictures, acute abdominal pain, and tenderness often localized in the right lower abdomen. EC often follows the onset of EG.
Eosinophilic duodenitis (ED) is characterized by eosinophilic inflammation of the small bowel that results in the production of leukotrienes, substances that participate in defense reactions and contribute to hypersensitivity and inflammation. Malabsorption of nutrients always results along with severe cramping, bowel obstruction, and intestinal bleeding with passage of bloody stools.
Other diseases feature enteropathies with symptoms similar to that of eosinophilic gastroenteropathies:
Although many factors have been identified as causing eosinophilic gastroenteropathies, some researchers suspect that undiscovered infections may also play a role. Thus, as of 2004, researches also believe an unknown mode of transmission may possibly be involved.
In the United States, eosinophilic gastroenteritis is very rare, and the incidence is difficult to estimate. However, since Kaijser's description in 1937, more than 280 cases have been reported in the medical literature. Although cases have also been reported worldwide, the exact incidence is unclear because of a lack of diagnostic precision. Cases of EG are reported mostly in Caucasians, with some cases occurring among Asians. A slight male preponderance has also been documented. People with a history of allergies, eczema, and seasonal asthma are more likely to have this disease. Eosinophilic esophagitis was long thought to be a variant of stomach reflux disease. It is as of 2004 known to be a distinct disorder predominately occurring in children. A study published in the New England Journal of Medicine in 2004 shows that EE rates have risen so dramatically in recent years that they may be at higher levels than that of other inflammatory gastrointestinal disorders. At Cincinnati Children's hospital, cases of EE were examined in patients from Hamilton County. Between 1991 and 2003, 315 cases met diagnostic criteria for EE. Only 2.8 percent of these cases were identified prior to 2000. Of the 315 cases, 103 resided within the county. Incidence rates of EE have not been reported in any other region of the United States, so national incidence rates are impossible to determine. However, if rates were the same as they are in Hamilton County, the annual occurrence of EE would be one in every 10,000 children, or approximately 22,000 children in the United States. The exact incidence and prevalence of EC and ED are not known, but these diseases are occurring or being diagnosed with increasing frequency and are especially prominent in children.
The eosinophil is a component of the immune system and is particularly involved with defense against parasites, but as of 2004 no parasite had been found responsible for any of the eosinophilic gastroenteropathies. The cause or mechanism of eosinophilic infiltration is also unknown, although some scientists suspect that the condition, first identified in Europe in the mid 1940s, is genetic, as it seems that in about 16 percent of known cases, an immediate family member is also diagnosed with an eosinophilic GI disorder. Various factors have been shown to trigger eosinophilic infiltration of the GI tract, and it has been shown that this, in turn, causes tissue damage by loss of cell granules (degranulation) and the untimely release of small proteins specialized in cell-to-cell communication (cytokines) that directly damage the GI tract wall. Examples of factors that are believed to have an incriminating role in triggering a flare-up include foods that trigger an allergic reaction (allergens) and immunodeficiency disorders caused by very low levels of immunoglobulins that result in an increased susceptibility to infection. Honey intolerance and bee pollen administration have also been suggested as a causative agent for EG. Researchers have confirmed a familial pattern to EE, which suggests either a genetic predisposition or a relationship to an unknown environmental exposure.
Gastroenteropathy symptoms vary depending on where the eosinophils are found and in what layer of the digestive system their numbers are highest. Symptoms therefore tend to be highly specific to each individual case. They may only appear when certain foods are ingested, or only during certain seasons of the year, or every few weeks, or in severe cases, every time any food is eaten. Infants with eosinophilic gastroenteropathies usually have acute reactions after food intake (within minutes to in one to two hours) that generally include nausea, vomiting and severe abdominal pain, later followed by diarrhea. These symptoms may occur alone or as part of a shock reaction. Symptoms vary depending on the type of gastroenteropathy (EG, EE, EC, or ED) and on the precise location of eosinophilic infiltration within the digestive system, as well as which layer or layers of the digestive system wall is infiltrated with eosinophils. Symptoms include, but are not limited to, the following:
Parents should call their healthcare provider to test for eosinophilic involvement if their child has recurrent symptoms of gastrointestinal disorder and feeding problems.
Eosinophilic gastroenteropathies are diseases that can be easily misdiagnosed. EE has long been misdiagnosed as gastroesophageal reflux, another digestive disease in which partially digested food from the stomach regurgitates and backs up (reflux). However, EE differs from esophageal reflux in the large numbers of eosinophils that are present in the GI tract. Diagnosis for eosinophilic gastroenteropathies is therefore only established on microscopic analysis of a tissue specimen (biopsy) revealing eosinophilic infiltration. Additionally, diagnosis is based on the following:
Treatment of eosinophilic gastroenteropathies is mainly symptomatic and supportive. Surgery may be necessary in severe EC cases in which there is obstruction of the intestines.
As of 2004 there is no known cure for eosinophilic gastroenteropathies, so medications are used to relieve symptoms and prevent full-blown attacks (or flare-ups). The only known medication to successfully stop eosinophilic inflammation is the corticosteroid drug, prednisone. Oral glucocorticosteroids are usually prescribed for those with EC or ED obstructive symptoms. Children with Pattern II EG may benefit from anti-inflammatory medications (for example, oral glucocorticoids or oral cromolyn) and specialized diet therapy, particularly in the case of food intolerance or allergy. Fluticasone propionate (Flonase, Flovent) is reported to be helpful in most cases of EG, if the medicine is swallowed so that it comes directly in contact with the esophageal tissues that are infiltrated by eosinophils. There is also reported success with use of a drug (Montelukast) that stops the production of the inflammatory leukotrienes associated with EC. Elemental formulas are also very effective. Cromolyn sodium (Gastrocrom) has been used with some success but does not work in all cases.
Parents may consider enrolling their EG diagnosed child or adolescent in a clinical trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). For example, in as of 2004 on-going omalizumab clinical study, participants undergo the following procedures:
As of 2004, a study is being conducted on the effectiveness of the membrane stabilizing drug sodium chromoglycate. More research is required to determine long-term safety and effectiveness of this drug. An experimental steroid called Budesonide may be helpful, but no clinical trials had been performed as of 2004. The severity of EG flare-ups has been reduced in some patients with antihistamines (such as Claritin, Allegra, or Zyrtec). A new class of asthma medications called leukotriene inhibitors has shown some mixed results in clinical trials for asthma patients and has been used experimentally in cases of EG but without conclusive results.
It is believed that whole food proteins are the most common triggers of an EG attack. Most infants with this condition are, therefore, put on a restricted diet and
Allergic reaction—An immune system reaction to a substance in the environment; symptoms include rash, inflammation, sneezing, itchy watery eyes, and runny nose.
Anemia—A condition in which there is an abnormally low number of red blood cells in the bloodstream. It may be due to loss of blood, an increase in red blood cell destruction, or a decrease in red blood cell production. Major symptoms are paleness, shortness of breath, unusually fast or strong heart beats, and tiredness.
Antibody—A special protein made by the body's immune system as a defense against foreign material (bacteria, viruses, etc.) that enters the body. It is uniquely designed to attack and neutralize the specific antigen that triggered the immune response.
Antigen—A substance (usually a protein) identified as foreign by the body's immune system, triggering the release of antibodies as part of the body's immune response.
Ascites—An abnormal accumulation of fluid within the abdominal cavity.
Biopsy—The surgical removal and microscopic examination of living tissue for diagnostic purposes or to follow the course of a disease. Most commonly the term refers to the collection and analysis of tissue from a suspected tumor to establish malignancy.
Complete blood count (CBC)—A routine analysis performed on a sample of blood taken from the patient's vein with a needle and vacuum tube. The measurements taken in a CBC include a white blood cell count, a red blood cell count, the red cell distribution width, the hematocrit (ratio of the volume of the red blood cells to the blood volume), and the amount of hemoglobin (the blood protein that carries oxygen).
Corticosteroids—A group of hormones produced naturally by the adrenal gland or manufactured synthetically. They are often used to treat inflammation. Examples include cortisone and prednisone.
Cytokines—Chemicals made by the cells that act on other cells to stimulate or inhibit their function. They are important controllers of immune functions.
Dysphagia—Difficulty in swallowing.
Enteropathy—A disease of the intestinal tract.
Eosinophil—A type of white blood cell containing granules that can be stained by eosin (a chemical that produces a red stain). Eosinophils increase in response to parasitic infections and allergic reactions.
Eosinophilia—An abnormal increase in the number of eosinophils, a type of white blood cell.
Gastroesophageal reflux disease (GERD)—A disorder of the lower end of the esophagus in which the lower esophageal sphincter does not open and close normally. As a result the acidic contents of the stomach can flow backward into the esophagus and irritate the tissues.
Gastrointestinal (GI) system—The body system involved in digestion, the breaking down and use of food. It includes the stomach, small intestine, and large intestine. Also known as the gastrointestinal tract.
Gastrostomy tube—A tube that is inserted through a small incision in the abdominal wall and that extends through the stomach wall into the stomach for the purpose of introducing parenteral feedings. Also called a gastric tube, gastrointestinal tube, or stomach tube.
Glucocorticoids—A general class of adrenal cortical hormones that are mainly active in protecting against stress and in protein and carbohydrate metabolism. They are widely used in medicine anti-inflammatories and immunosuppresives.
Immunodeficiency disease—A disease characterized chiefly by an increased susceptibility to infection. It is caused by very low levels of immunoglobulins that result in an impaired immune system. Affected people develop repeated infections.
Immunoglobulin G (IgG)—Immunoglobulin type gamma, the most common type found in the blood and tissue fluids.
Leukotrienes—Substances that are produced by white blood cells in response to antigens and contribute to inflammatory and asthmatic reactions.
Malabsorption—The inability of the digestive tract to absorb all the nutrients from food due to some malfunction or disability.
Melena—The passage of dark stools stained with blood pigments or with altered blood.
Protein-losing enteropathy—Excessive loss of plasma and proteins in the gastrointestinal tract.
Shock—A medical emergency in which the organs and tissues of the body are not receiving an adequate flow of blood. This deprives the organs and tissues of oxygen and allows the build-up of waste products. Shock can be caused by certain diseases, serious injury, or blood loss.
Stricture—An abnormal narrowing or tightening of a body tube or passage.
provided with elemental formulas containing no whole food proteins, such as Neocate or Elecare. For older children, physicians usually start by recommending a trial elimination diet that excludes milk, eggs, wheat, gluten, soy, and beef, because a link has been established with food intolerance and food allergy. Most patients improve significantly on diets avoiding foods to which they are allergic. Radioallergosorbent assay test (RAST) or skin testing can identify food hypersensitivity. If an exceptionally high number of food reactions are found, an amino-acid-based diet or elemental diet is often considered. Some patients with EE/EG/EC are even fed elemental formulas via a gastrostomy tube or are limited to TPN (blood-vessel feeding) if the disease is severe with many complications.
As of 2004 there is no cure for eosinophilic gastroenteropathies, and outcomes depend on the specific enteropathy. A small subset of patients are partly or totally disabled by the effects of the disorder, but most can have active and fulfilling lives. Eosinophilic gastroenteropathies are not known to be fatal, but some types cause such severe bleeding or nutritional deficiency that the condition may be life-threatening if not treated with appropriate medications and support measures. Some younger children who have been diagnosed at an early age are known to outgrow the most severe symptoms. Children with EG have a good prognosis. Mild and sporadic symptoms can be managed with observation, and disabling GI flare-ups can be controlled with prednisone. Most patients also respond well to oral glucocorticosteroids.
No specific prevention measures can be recommended for eosinophilic gastroenteropathies since their specific cause was unknown as of 2004.
Because of the high risk of misdiagnosis for eosinophilic gastroenteropathies, parents of infants who have persistent feeding problems and do not respond well to classical digestive disorder medications should request biopsies to test for possible eosinophilic involvement.
When diagnosis is confirmed, certain lifestyle changes are usually required, such as avoidance of certain foods or making sure that medication is taken every day. Parents should also be aware that commonly prescribed corticosteroid medications have side effects that are potentially serious. People who use them tend to become overweight, with swollen faces. Long-term use has also been shown to damage kidneys.
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Monique Laberge, Ph.D.
The following comments are not guaranteed to be that of a trained medical professional. Please consult your physician for advice.