In recent years, clinicians and patients alike have experienced both significant interest in and confusion around food allergies/sensitivities and their manifestations in the gastrointestinal tract. A lack of clarity has led to frustration, inappropriate testing, and missed diagnoses.
Clifford Bassett, MD
Medscape contributor Akash Goel, MD, a clinical assistant professor of medicine at Weill Cornell Medicine, spoke with Clifford Bassett, MD, the founder and medical director of Allergy & Asthma Care of New York, a clinical assistant professor at NYU Grossman School of Medicine, a faculty member of the Weill Cornell Medical College in New York City, and author of The New Allergy Solution, about working toward a framework with which to approach diagnostic dilemmas around these food-related conditions.
Getting the Terminology Right
What defines a food allergy, and what kind of gastrointestinal symptoms do they produce?
Food allergies are due to an immunologic response to a food antigen culminating in a characteristic set of symptoms, ranging from mild to severe, with severe being multiorgan system anaphylaxis.
In the context of food, "allergies" traditionally suggest immediate-type hypersensitivity (type 1) involving antigen-specific immunoglobulin E (IgE) antibodies and histamine (among other mediators) release from mast cells and/or basophils. Type 1 food allergy signs/symptoms usually start within minutes to 1 hour after food ingestion and may include hives; itchiness; lip or tongue swelling; difficulty swallowing; throat tightening; chest tightness; trouble breathing; wheezing; and abrupt abdominal discomfort that may be associated with nausea, vomiting, and/or diarrhea.
In addition to immediate IgE-mediated food allergies, T cell–mediated and mixed pathophysiology food allergic disorders may present with more delayed and usually chronic gastrointestinal symptoms of emesis, diarrhea, blood in stool, poor growth, and/or weight loss. These disorders include eosinophilic esophagitis, food protein–induced enterocolitis syndrome, allergic proctocolitis, and enteropathy.
Recent evidence also suggests a putative role for T cell–mediated hypersensitivity in irritable bowel syndrome (IBS).
How does this differ from food sensitivities and food intolerances?
"Food intolerance" describes a large array of food-triggered complaints that do not involve the immune system, and its presence may be seen in up to one fifth of the population.
Typical symptoms are largely gastrointestinal and may include gas, distention, bloating, nausea, and/or changes in stool consistency. Lactose intolerance, with symptoms resulting from lactase deficiency and the consequent osmotic load caused by the inability to properly digest lactose, is a widely recognized example.
After eating certain foods, many people experience symptoms that are not thought to be related to food allergies or overt food intolerance. These are less specific, more diffuse, and less understood food-triggered symptoms and are often referred to as "food sensitivities." The exact mechanism is often unclear, although it appears that exposure to specific foods and/or chemicals or food additives may generate varied complaints. In many cases, gluten is suspected as the likely culprit. Thus, it is essential to first have a proper evaluation for celiac disease in such cases.
Food intolerances and sensitivities are more common than food allergies.
Food Allergies Are Increasingly Prevalent
Food allergies and intolerances seem to be on the rise. What's accounting for that?
Food allergy is a rising, global epidemic, with the greatest prevalence in the United States and other industrialized countries worldwide. Approximately 32 million people in the United States have at least one food allergy, including about 6 million children, and nearly 11% of people aged 18 or older — more than 26 million adults — have food allergies.
Recent data from the US Centers for Disease Control and Prevention have found that the prevalence of food allergy among children aged 0-17 years increased by 50% from 1999 to 2011.
According to a prior review, food allergic reactions necessitate a visit to emergency departments as frequently as every 3 minutes in the United States. That can be as many as a few hundred thousand persons who go to emergency departments for this problem.
The rise of food allergies is probably multifactorial, with changes in lifestyle and behavior playing a significant role. A big component is probably our prior misguided advice to avoid top food allergens early in life. Now, early introduction (as early as 4-6 months but at least within the first year of life) of a wide array of foods (eg, peanut, egg) with guidance by the pediatrician is recommended, with the intent of reducing the risk of developing food allergies.
This proactive approach is based on the dual-allergen exposure hypothesis, which posits that exposure to food allergens through the skin (especially in infants with atopic dermatitis) can lead to allergy whereas oral ingestion of foods at an early age usually results in tolerance.In other words, it appears that skin exposure sensitizes, whereas consumption of a food allergen induces a state of oral tolerance.
The hygiene hypothesis suggests that our environment has become "too clean." Some children's immune systems — left with decreased invaders to battle — may overreact unexpectedly to food proteins and create allergic responses.
Work currently being done on the role of our gut microbiome hopes to provide further insight on any association with IgE-mediated food allergy.
Identifying At-Risk Patients
How should gastroenterologists approach patients whose symptoms they suspect are due to a food allergy?
As with all diagnostic challenges, gathering a detailed history is paramount. Of prime importance is determining the acuity of the threat. If type 1 hypersensitivity is suspected, patient counseling about the signs and symptoms of anaphylaxis is crucial and, if encountered, prompt treatment with subcutaneous epinephrine and oral antihistamines or emergency department care should be readily available.
Evaluation for type 1 hypersensitivities includes maintenance of a detailed dietary log attempting to correlate ingestion of specific foods with onset of symptoms. The patient should be made aware that the culprit food does not necessarily need to be something new to the diet.
What kind of diagnostic questioning do you recommend?
When a food allergy diagnosis is uncertain, it is helpful to ask a series of pointed questions to gain clarity, such as:
What was the timing of a reaction to food ingestion?
Did the patient's symptoms respond to medications, such as an oral antihistamine and/or epinephrine autoinjector in suspected anaphylaxis?
Were the reported symptoms consistent with an immune mechanism? For example, headache, joint pain, and brain fog are not common symptoms of food allergy, whereas mouth and throat itchiness, hives, and wheezing are.
Have symptoms been consistently reproduced by food ingestion?
Were there any new foods introduced into the diet? Although new foods would be more likely culprits, this is not always the case.
Did the patient take aspirin and/or a nonsteroidal anti-inflammatory drug, consume alcohol, and/or exercise before or after the suspected reaction? These variables may increase the likelihood or severity of an allergic reaction.
As with many things in medicine, proper interpretation requires understanding the nuances to arrive at diagnoses that are not always black and white. This is where I spend much of my time sleuthing the details to arrive at a diagnosis.
The greatest value of the allergist lies in the selection of tests and interpretation of results to determine their clinical significance. A positive test result does not necessarily indicate a definite food allergy. Sorting through these issues is where the allergist's experience and training can be very helpful.
Weighing Testing Options
There are various types of testing. When should they be used, and how should they be interpreted by gastroenterologists?
I have found that a true collaboration with my gastroenterologist colleagues has led to greater patient satisfaction; better diagnostic accuracy; and improved co-management, including appropriate follow-up care.
Allergists strive to focus on choosing proper diagnostic tools as well as clinical correlation in the evaluation of food allergy. Another emphasis is the use of patient educational resources and in-depth counseling to mitigate exposure to the offending foods. Furthermore, using the skills of an experienced registered dietitian can optimize proper nutritional guidance for our patients.
To confirm that a true food allergy exists and to avoid unneeded food restrictions, it is preferable to have a consultation with an allergist.
When the pretest likelihood of a food-induced type 1 reaction is high (eg, classic immediate allergic symptoms, such as hives, wheezing, itching, or immediate emesis), an IgE food allergen test is indicated.
In most cases, a very sensitive method in type 1 IgE-mediated food allergy diagnostic testing is a reproducible food prick test, with either a commercial-grade allergenic extract or a fresh food. Prick food testing typically would be administered by the consulting allergist, who would interpret the results.
A negative food prick test generally has a very high predictive value, indicating a low likelihood of a true type 1 food allergy.
A positive food skin prick test or an in vitro IgE food-specific test may indicate allergic sensitivity; however, the individual's clinical response to a food, along with the characteristic signs and symptoms, is required for diagnosis of food hypersensitivity.It is important to note that the size of the food skin test does not necessarily correlate with severity of symptoms for that patient, but it does indicate a greater likelihood of a clinical allergy.
When it comes to the methods of diagnostic evaluation, food skin testing is generally preferred. Other diagnostic testing includes serologic food-specific IgE (ImmunoCAP) assays.
With both methods, a positive food test does not imply an individual has a clinical food allergy. A complete patient clinical history is necessary to properly interpret testing and consequent future recommendations.
Immunoassays are in vitro allergen antibody tests to measure food-specific IgE in the serum. A greater "likelihood" may exist of a food-induced reaction with higher levels of food-specific IgE values. However, the food-specific IgE level (ranging from low to high) does not automatically correlate with severity of a food-induced reaction.
To reiterate, this underscores the importance of an accurate patient clinical history to allow for proper test interpretation.
Testing can be particularly useful at times, because it is not affected by various medications an individual may be taking, such as antihistamines, in those with a history of severe anaphylaxis, nor by testing in a patient who has active urticaria and dermatographia.
Currently, food component IgE can be used in an adjunctive fashion in patients with suspected peanut, tree nut, cow's milk, or egg allergy by helping to define potential severity of a food allergic reaction, because it is testing for specific proteins in a food.
Allergists may also consider specific food predictive levels in children, depending on the clinical situation.
In some cases when the diagnosis is in doubt and the clinical suspicion for a true food allergy is relatively low, an oral food challenge may be considered under appropriate medical supervision.
Current and Future Treatment Options
What types of drugs, technologies, and assays are in the pipeline for food allergy and sensitivity testing?
In 2020, the US Food and Drug Administration approved the first biologic drug for oral immunotherapy for children and adolescents with a confirmed peanut allergy. Oral immunotherapy involves in-office initiation and every 2 weeks up dosing combined with an at-home process, whereby gradually escalating dosages of a food allergen are ingested over time until a steady maintenance dose is reached.
Researchers are looking at other routes of allergen delivery, such as sublingual immunotherapy and epicutaneous immunotherapy. The goal is to provide a form of allergen-specific immunotherapy to modify a food allergen response, allowing the individual to become more tolerant to a selected food and/or desensitization.
What's your perspective on the role of food as a driver of functional bowel diseases, like IBS?
Nearly 20 years ago, observations of inflammation in IBS challenged its traditional classification as a functional disorder. Half or more of those carrying this diagnosis report that foods can aggravate their symptoms. This association has traditionally been viewed as food intolerance, because testing efforts in search for type 1 and type 3 allergies have generally failed to implicate these allergic mechanisms.
Recent studies, however, resurrect a role for true food allergies. In one study, food-induced abdominal pain has been observed in association with local IgE production in response to food antigens, creating new potential therapeutic options.
Other studies (from 2013, 2018, and 2021) using skin patch testing implicate type 4 allergies in some cases. In these studies, participants with IBS are patch-tested to an extensive panel of type 4 food allergens. The foods that elicit allergic reactions in the skin are subsequently eliminated from the diet, and a significant percentage of those tested experience moderate to marked improvement or complete relief of their IBS symptoms.
It is theorized that a type 4 allergic reaction similar to that elicited in the skin by the patch testing occurs in the intestinal lining when the same foods are ingested, triggering IBS symptoms. Patch testing to a comprehensive set of type 4 food allergens may provide a new approach to the evaluation and management of IBS.
It is likely that IBS has several different underlying causes, some allergic in nature, all resulting in its well-characterized symptom complex.
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Cite this: The Gastroenterologist's Guide to Food Allergies, Intolerances, and Sensitivities - Medscape - Apr 11, 2022.
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