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Monday, July 16, 2012
Advances, Summer 2012
Patients with food allergy have a sensitization to a specific food or foods and manifest a reproducible immune response whenever exposed to food-based allergens.
The true prevalence of food allergy in children is difficult to establish; however, research indicates the incidence is increasing in this population. Also, children are more slowly outgrowing food allergies—including milk and soy—resulting in a further ballooning of allergy prevalence. Compounding the incidence of actual food allergy, the tendency for physicians, as well as patients and families, to consider instances of food aversion or food intolerance as food allergy, together with the poor specificity of current testing, has led to an even higher perceived prevalence in pediatric patients. Between one-half and two-thirds of presumed food allergies in children and adults are not actual allergies.
Implications of Food Allergy
A food allergy impacts a child’s life medically, psychologically, and socially. The quality of life for a pediatric food allergy patient is detrimentally affected if the child has to avoid a basic food or foods, including milk, eggs, and wheat, for an extended period. This avoidance can lead to long-term nutritional problems if appropriate prevention steps are not well-considered. Food allergy can be complicated by food aversion in babies, which can prevent the successful introduction and continuation of solid foods.
Also, food allergy may lead to food-related anxiety as children get older. Fear of accidental exposure may prompt a child to manifest symptoms of severe anxiety in situations where a food allergen may be present. Also, the child may avoid social situations for fear of exposure. According to a study presented at the 2011 Food Allergy and Anaphylaxis Meeting sponsored by the European Academy of Allergy and Clinical Immunology (EAACI), 17 percent of allergic children avoid social situations, such as parties or picnics, because of food allergy.
Over the long term, anxiety and avoidance can promote frustration and resentment, isolate a child from his or her peer group, and encumber the child’s social interactions. A child may be the only one of his or her peers to have a food allergy and thus may feel conspicuously different. This may not only compound the child’s frustration but also expose him or her to ridicule stemming from a lack of understanding among peers.
Challenges with Diagnosis
Eosinophilic esophagitis (EoE) before (left) and after (right) treatment.
The cornerstone for effective food allergy treatment is accurate diagnosis. Without it, patients may avoid foods to which they are not clinically allergic or, conversely, consume foods that cause severe physical effects, including anaphylaxis. Accurately diagnosing a food allergy requires a detailed medical history, physical exam, and diagnostic testing. Diagnostic tools range from minimally invasive methods—skin and blood tests, for example—to exploratory options, including endoscopic biopsy. Children with food allergy may be allergic to multiple foods, and the diagnostic process may include a series of tests to capture the patient’s complete allergic profile. Each patient requires a customized diagnostic approach, keeping in mind the patient’s age, symptoms, and severity of allergic response. Depending on the nature and symptoms associated with suspected food allergy, a pediatric allergist/immunologist or gastroenterologist specializing in food allergy is an appropriate resource for accurate diagnosing. For many children with severe or complicated suspected food reactions, the use of multiple disciplines in the diagnostic evaluation is warranted (see the Food Allergy Center sidebar on page 11).
As previously mentioned, misdiagnosis is common with food allergy. This is concerning because a misdiagnosed patient may avoid a food to which he or she is not allergic, with potential implications for the child’s quality of life and nutrition. Also, an extended period of unnecessary food avoidance may reduce the patient’s eventual tolerance of the food should it be reintroduced.
Treatment for Food Allergy
There are no therapies available proven to prevent or cure food allergy. Patients diagnosed with a food allergy must avoid the food allergen. Medication, such as corticosteroids, can control symptoms but cannot address the underlying allergy. Because children with food allergy are two to four times more likely than children without food allergy to have comorbid conditions, including asthma, atopic dermatitis, and respiratory allergies, treatment plans must mitigate these other conditions.
Addressing Eosinophilic Esophagitis
One of the allergies studied and treated at the Mass General Food Allergy Center is eosinophilic esophagitis (EoE)—a chronic, immune-mediated inflammatory disorder most often triggered by one or more food antigens. Clinical symptoms of EoE include those of esophageal dysfunction (difficulty swallowing or food impaction) and eosinophilic inflammation (pain) of the esophagus.
EoE incidence rates range from 0.9 to 2.0 new cases per 10,000. Prevalence of EoE is thought to have increased since it was first detected in 1962, primarily due to enhanced disease recognition. The disease predominately afflicts males and has been shown to be hereditary, thus a detailed family history is paramount for supporting an accurate diagnosis.
Various foods trigger EoE, including cow’s milk, wheat, and soy. Possible disease indicators include food aversion and malnutrition in infants and toddlers, vomiting in preschoolers, and difficulty swallowing and abdominal pain in adolescents.
Endoscopy with esophageal biopsy is the only reliable methodology for diagnosing EoE. Repeat endoscopies may be necessary to fully verify the presence of allergy, and these can exert a significant physical and psychological toll on pediatric patients. Qian Yuan, MD, PhD, FAAP, and Aubrey Katz, MD, of Pediatric Gastroenterology and Nutrition at MassGeneral Hospital for Children are part of a multidisciplinary research team at the Food Allergy Center working to identify possible noninvasive biomarkers that can reliably predict the presence of EoE. Through an ongoing prospective research study, the team is selecting samples of blood, urine, saliva, and esophagus tissue and examining biochemical changes after introducing food antigens and/or new treatments. The goal of their research is to identify biomarkers within the biological fluids that can assist with diagnosis, assess therapy response, and monitor for possible relapse or disease alteration.
In addition to the biomarker study, less invasive imaging methods are being explored in collaboration with Guillermo Tearney, MD, PhD, associate director of the Wellman Center for Photomedicine, with the ultimate goal to perform a type of endoscopy on a fully conscious person using quick, well-tolerated mechanisms.
Endoscopy features of eosinophilic esophagitis (EoE) before treatment. Pictured from left: white patches; concentric rims; white patches and linear furrows; linear furrows.
Treatment of EoE is currently limited to avoiding allergy-producing food antigens or taking daily corticosteroids. A six-food or eight-food elimination diet that removes cow’s milk, soy, wheat, eggs, peanuts, tree nuts, fish, and shellfish for six weeks has resulted in clinical and histological remission for afflicted children, with a 2011 research study indicating remission for 85 percent of the children studied. Slow reintroduction of the six or eight foods—with sufficient time lapses (at least six to seven weeks) between introductions and careful monitoring for EoE recurrence—can narrow the possible antigens and uncover the allergy-inducing foods. In addition, patients engage in online surveys to provide details about their treatment, including the variety of food they consume and the quantity and frequency. Once a food is definitively proven to cause EoE, it is restricted from a patient’s diet.
An alternative to the six-food or eight-food elimination diet is a total elemental diet, which takes the form of a nutrient-rich drink that replaces solid food. While able to prevent allergic reactions, this intervention is limiting for patients, delays the successful introduction of solid foods, and has a negative emotional and social impact on young children.
The use of corticosteroids is an option for EoE symptom management; however, these drugs are not a cure for the disease. Although corticosteroids have realized up to a 90 percent response rate among food allergy patients, they only curtail symptoms: Recurrence appears to be inevitable if the patient is removed from the medication. Long-term topical corticosteroid use in this way may also be complicated by thrush or other problems.
To identify better treatment modalities for EoE, Food Allergy Center investigators, including Drs. Shreffler and Yuan, are currently involved in a retrospective study comparing the different forms of therapy, including the six-food and eight-food elimination diets, the elemental diet, and corticosteroid therapy. The study reviews the Food Allergy Center’s EoE patients and assesses their response to the various therapies.
The mechanisms for diagnosing, treating, and managing food allergy are still emerging as research continues to test new modalities. At the Food Allergy Center, multiple disciplines coordinate research and clinical treatment efforts, addressing the interrelated physical, psychological, and social needs of pediatric food allergy patients. While presently there is no cure for food allergy, current research will lead to a better understanding of the disease, resulting in the development of interventions with more lasting benefit.
Boyce JA, et al. (2010). Guidelines for the diagnosis and management of food allergy in the United States: Report of the NIAID-sponsored expert panel. J Allergy Clin Immun, 126: S1-S58.
Kagalwalla AF, et al. (2011). Identification of specific foods responsible for inflammation in children with eosinophilic esophagitis successfully treated with empiric elimination diet. J Pediatr Gastr Nutr, 53: 145-49.
Liacouras CA, et al. (2011). Eosinophilic esophagitis: Updated consensus recommendations for children and adults. J Allergy Clin Immun, 128: 3-20.e6.
Sherrill JD, Rothenberg ME. (2011). Genetic dissection of eosinophilic esophagitis provides insight into disease pathogenesis and treatment strategies. J Allergy Clin Immun, 128: 23-32.
Subbarao G, et al. (2011). Exploring potential noninvasive biomarkers in eosinophilic esophagitis in children. J Pediatr Gastr Nutr, 53: 651-58.
Food Allergy Center
The Food Allergy Center at Massachusetts General Hospital provides clinical services, patient education, and research related to food allergy. Led by Wayne Shreffler, MD, PhD, director of the center and section chief of pediatric allergy and immunology. The Food Allergy Center represents a collaborative effort among multiple disciplines—allergists, gastroenterologists, nutrition specialists, psychologists, and other specialists—to study and treat the spectrum of needs presented by a food allergy patient.
The center is primarily focused on the expeditious discovery of the food allergens causing a patient’s allergy, rather than the treatment of symptoms using drug therapy. This focus allows treatment teams to rapidly introduce targeted therapies for identified allergies. Because the center has experts in both pediatric and adult allergy treatment, patients can be seen and treated throughout the course of their lives.
In addition to supporting joint clinics between multiple disciplines, the Food Allergy Center serves as an organizational structure for different disciplines to coordinate clinical research protocols and translational research projects. More information about the Food Allergy Center can be found at massgeneralforchildren.org/foodallergy.
Current Trials Related to Food Allergy
The Food Allergy Center currently has several clinical studies under way relating to food allergies, including ones focused on treating immediate type allergies with oral immunotherapy (OIT)—introducing small, increasing amounts of an allergen in an attempt to protect a patient from allergic reactions and alter immune response to a specific food protein. In collaboration with investigators from the Mass General Hospital Center for Immunology and Inflammatory Diseases and Harvard Medical School, Food Allergy Center investigators recently won NIH funding to support research on OIT.
Current OIT studies encompass patients with single food allergies, such as peanuts or milk, but the Food Allergy Center is actively seeking funding to support treatment of multiple food allergies concurrently as well as to test novel therapies for immediate food allergies and eosinophilic esophagitis (EoE).
Massachusetts General Hospital for Children
MassGeneral Hospital for Children (MGHfC) is a full-service, family-centered, pediatric “hospital within a hospital.” MGHfC provides the entire spectrum of pediatric care—from primary care to a broad range of specialty and subspecialty pediatric services. With more than 250 physicians representing more than 60 pediatric specialties and subspecialties, MGHfC has the expertise and experience—as well as the state-of-the-art facilities and technologies—to provide exceptional care for infants, children, and adolescents, including those who are critically ill and/or have rare disorders. MGHfC provides patient care services at its main campus in Boston, as well as at a number of community locations.
To refer a patient, please call the MGHfC Access and New Appointment Center, Monday through Friday, 8 am to 5 pm, at 888-MGHfC11 (888-644-3211), or visit massgeneralforchildren.org
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