Episode Transcript
Hi and Welcome to Clerkship Ready - Pediatrics - A podcast aimed at helping you excel during your clinical clerkship in Pediatrics.
I am Dr.Jenna Zuzolo, and I am a Pediatric Resident at the University of Virginia.
Today, we will be reviewing what you need to know before a parent asks you about food allergy testing for their child.
A common question in multiple settings within the pediatric realm is, “I am worried my child has a food allergy, how do we go about testing this?”. Parents may ask you this during the outpatient annual visit, in the emergency department, or on the inpatient floor. In this podcast episode, we will discuss the definition of food allergies, clinical manifestations of food allergies, questions to ask families who are concerned about such allergies, as well as the testing available – all while emphasizing what can make you shine on your pediatric clerkship rotation. Of note, there are other types of allergies and testing, such as environmental allergies and drug allergies, but we will save that for a future podcast episode. And with that, let’s get into it!
Food allergies are a common topic in the general pediatrics world. Whether it is giving anticipatory guidance at the 4 month well child visit about introducing solid foods, including high risk allergy foods, or seeing a 9 month old for a sick visit after an infant broke out into a rash after trying eggs for the first time. For more information about the guidance you would give at the 4 month visit about introducing solids and high-allergen foods, check out episode #34, which specifically addresses this topic. First, it’s important to understand the difference between food allergies and food intolerance. Recall, that a food allergy is defined as, “an adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food” whereas food intolerance is defined as “nonimmune reactions that include metabolic, toxic, pharmacologic and undefined mechanisms” So basically – think of a true allergy as involving the immune system. A food intolerance does NOT involve the immune system response.
How common are food allergies? Well, according to multiple studies food allergies are only on the rise, as data over the past few decades suggests that food allergies are becoming increasingly prevalent, with some studies showing that up to 10% of the population is affected by food allergies. These food allergies are more common in children than adults.
Like all chronic disease processes, the expression of food allergy can be influenced by several factors such as environment, genetics, and genetic-environmental interactions. There are several different hypotheses as to what the underlying pathophysiology to food allergies comprises, but currently the underlying etiology is unknown and likely multifactorial.
Having a solid understanding of what food allergies are and what they look like is essential for a proper diagnosis. You must understand food allergies in order to diagnose them. Remember, allergies are not like other adverse reactions to foods, because allergies involve an immune response. You may be asked about food intolerances in our pediatric population, such as lactose intolerance or food poisoning, which is a toxic food adverse reaction. These ARE NOT food allergies.
Food allergies, as we mentioned before, are split up into two large umbrellas, IgE mediated or non-IgE mediated. We must understand the key features of these to define what testing might be appropriate to confirm, exclude, or monitor disease.
For IgE mediated food allergies, symptoms usually occur within minutes to up to 4 hours after food exposure (2). The common food offenders include peanut, tree nuts, fish, shellfish, egg, milk, wheat, soy and seeds. This can vary per individual. (1). A detailed history should be taken including factors pertaining to the most recent reaction, but it is also important to dive into what the typical diet is, any past reactions, and possible family history. We will talk about that in a few moments. The signs and symptoms of food allergies can affect multiple organ systems, and these reactions can range from mild to severe life threatening anaphylaxis.
So, what are these systems that can be affected and what does this look like? Cutaneous symptoms are the most common and can include hives, erythematous rashes, pruritus, and angioedema. Ocular involvement may be present with tears, erythema, or pruritus. Respiratory involvement like wheezing or coughing may be present. GI involvement can include abdominal pain, nausea, vomiting, or diarrhea. Note, that symptoms are usually immediate, and should occur within minutes to four hours if they are truly due to IgE mediated food allergies. There are also neurologic symptoms like dizziness or weakness which are very concerning, as are cardiovascular signs like tachycardia and hypotension. If two or more systems are affected after food ingestion, this meets criteria for anaphylaxis, which is rapidly progressive and potentially fatal if not given epinephrine autoinjector in a timely manner.
Don’t be fooled by symptoms of failure to thrive, constipation, bloody diarrhea, weight loss, emesis or diarrhea that occurs AFTER 4 hours after food ingestion as these are typically associated with non-IgE mediated food allergies. As for the non-IgE mediated reactions, there are several that the pathophysiology is not completely understood. I will list a few and their common clinical presentations, which may help you guide your history taking and allow you to brief parents on possible differentials prior to referring to an allergist/immunologist.
Eosinophilic esophagitis is a food-related inflammation of the esophagus that presents with dysphagia, patients may eat slower than their peers, require drinking liquids when eating foods, and struggle with certain foods and sensations of food being “stuck” in their esophagus.
If a patient has delayed allergic reaction symptoms from mammalian meats, they could have alpha-gal, which is a sensitization of IgE to the carbohydrate galactose-alpha-1,3-galactose and triggered by a tick bite. Some patients with alpha-gal may also experience reactions to otherwise tolerated foods, as well as ingestion to NSAIDs drugs, alcohol, exercise, menstruation, and illness.
FPIES, which stands for food protein induced enterocolitis syndrome, is a non-IgE food allergy which is often misdiagnosed. It is characterized by delayed profuse vomiting or diarrhea shortly after trying cow’s milk or other trigger foods. Dairy is the most common offender. This can be severe, and lead to hypotension and even shock, if concerns like this arise patients should be sent to the emergency department and given Zofran if age appropriate and consider IV fluid supplementation. If a patient is breastfed, a mom does not have to limit her diet.
FPIAP which stands for food protein induced proctocolitis, also known as cow’s milk protein allergy, is another non-IgE mediated food allergy. It’s different from FPIES as it typically presents in healthy infants with bloody, mucousy stools. The typical offenders include dairy, soy, wheat, egg, tree nuts, or legumes. If the patient is breastfed, the mother should limit her diet based on these symptoms. Usually, FPIAP resolves by 15 months of age, and if it does not allergists will typically refer them to GI to have them scoped to make sure nothing else is going on.
For the sake of time, I will stop here but know there are other non-IgE mediated food allergies and much more information to dive into for a future podcast.
And now that we feel comfortable differentiating between IgE mediated food allergies and non-IgE mediated food allergies, what should you do, as a medical student rotating through pediatrics when a concern for food allergies is brought up? Well – the most important thing (which will continue to be emphasized throughout this episode) is to take a very detailed, focused history to tease out what might be going on.
When talking about the most recent reaction, let’s go through some questions to ask:
1. Ask about what the presenting symptoms were and how long they lasted.
a. Remember, if you hear about any of those signs we talked about above: like hives, vomiting, diarrhea, wheezing, difficulty breathing, those are concerning for an IgE mediated food allergy. If they lasted a few hours this is more concerning for food allergy, versus if they lasted for several days upon weeks this could mean something else is going on.
2. Ask how long it took for symptoms to occur.
a. If it happened within a few minutes to up to four hours – also concerning for an IgE mediated food allergy.
3. Ask, how long was it between ingestion of the food and the symptom onset.
a. If someone tells you it took days for the rash to appear or other symptoms to occur, that does not align with a food allergy.
4. What foods were ingested immediately before the reactions, and has that patient had that food before and more than once?
a. Remember, the common food offenders include peanut, tree nuts, fish, shellfish, egg, milk, wheat, soy and seeds. It would be very unusual for a patient who has tolerated a food for most of their life to suddenly have a severe IgE mediated food allergy.
5. How much was ingested and were these symptoms ever noticed before? Was the food baked or uncooked?
a. If a patient has never this food before, this could be the first exposure. If they notice symptoms every time consistently, this is worrisome for food allergies.
6. Was the patient sick at the time, just performed a lot of physical activity, are they taking aspirin or NSAIDs?
a. Sometimes viruses can cause rashes that look just like food or other types of allergies. Sometimes patients get very flushed with activity and can break out into a rash or vomit. Aspirin and NSAIDs can mimic food allergies because they can lower the threshold for allergic reactions to food and increase IgE mediated mast cell and basophil activation (the cells involved in the immune inflammatory response). BUT this is not considered a true food allergy, because it doesn’t occur without NSAIDs or aspirin, and the immune response isn’t due to a new food allergy but due to the pharmacologic/immunologic effects of NSAIDs acting as a cofactor and making this happen.
7. Ask if the patient has had prior allergy testing, or if they have ever required an epinephrine autoinjector.
a. It’s important to know if they already have established allergies. If there is concern for food allergy, an epipen should be prescribed, this is the treatment for food allergies if a patient has anaphylaxis, and we’ll talk about this a little bit later.
8. Ask about family history, if parents or siblings have food allergies. Have they avoided foods in the past due to concerns for allergies in a family member?
a. If a family member has a food allergy to a specific food, it may be that the entire family avoids this food, thus the patient may not have ever had it before.
9. Does the patient avoid specific foods?
a. Same reason as above, it’s important to know if a patient avoids foods and accidentally had an exposure, for example if a family was vegan and the toddler accidentally ate something with eggs in it at daycare who had never had eggs before.
10. All of these are important to ask, and can help guide you to discover what truly may be going on.
Now, let’s move on to talk about testing for food allergies. If you are worried about a food allergy, you want to be prepared to let parents know what to expect for the next steps. Diagnostic approach to food allergies is not as simple as one might believe. There are many tests out there, not all of which are recommended for routine use by anyone. The following tests are NOT recommended for routine use: total IgE serum measurements, intradermal tests, atopy patch tests, as well as other tests that are unproved including applied kinesiology, allergen-specific IgG4 measurements, electrodermal testing, and others.
With so many tests, what should we do? Well, the most important “single test” for diagnosing food allergy is actually the clinical history itself. To be able to truly hone your questions on the history, have knowledge of clinical manifestations of food allergies and recognizing similar etiologies or “mimics” of food allergy is key. Let’s say you have a 2 year old coming in to clinic for a sick visit to discuss urticaria (hives) that developed within 30 minutes after they ingested peanut butter. For this example, we will say the patient has had pretty severe atopic dermatitis, and has tolerated large amounts of peanut butter before. Upon further questioning, you also learn that they have had symptoms of a viral infection, and the hives lasted for 6 days. Viral exanthems are a “mimic” of urticaria often seen in food and drug allergies. With the coinciding symptoms along with the duration of symptoms, and the fact that the patient has previously tolerated peanut butter, it is likely that this was a viral exanthem and not an IgE mediated food allergy to peanuts. Now let’s say in a similar but different scenario, the patient had eczema with previously resolved egg allergy and initially refused to try peanut butter that was offered in the past. This was the first time they had consumed peanut butter, that the parents had given them a Benadryl or other antihistamine and the rash dissipated, and did not return. Now this scenario would be highly convincing for an IgE mediated peanut allergy. By understanding the clinical details in the history, the first case would not require testing for peanut allergies, and the second case would likely undergo testing to confirm their allergy (1).
And that leads us to the answer to our question from parents or guardians, “how do we go about testing for food allergies?”. After deciding upon if the clinical history is concerning for food allergies, referring the patient to an allergy/immunology specialist is the next step as many primary care physicians feel uncomfortable interpreting laboratory tests when diagnosing food allergy (3). There are three main options for confirmation of suspicions: skin prick tests, serum IgE measurements to specific food allergens, and oral food challenges – all three of which are performed typically by allergists due to the importance of contextualizing the epidemiology, pathophysiology, and clinical history associated with each unique clinical scenario (1).
The gold standard for diagnosing food allergies is the oral food challenge. Patients are brought in under the supervision of an allergist/immunologist and they eat the suspected food and are monitored for several hours. A negative test occurs when the patient does not develop any objective symptoms during the challenge. A positive test occurs when there are objective symptoms – whether it be a cough and a rash, just a rash, vomiting, etc. The treatment options are present in case of reactions, which is why it is so important to be under the supervision of an allergist. As medical students on your pediatric rotation, you can prepare parents for what a food challenge may look like, and can reassure the families that a reaction from an oral food challenge does NOT result in increased sensitization (aka make the patient more likely to react) of whatever food is being tested. (3).
The most commonly used test is a skin prick or puncture test. This cannot be done if the patient has had an anaphylaxis reaction in the past 4-6 weeks or if the patient has had an antihistamine within 7 days of the test due to the potential for blunting skin reactivity. The skin is cleaned, a small drop of the allergen is inserted just under the skin, along both a positive control, histamine, and a negative control, water. The skin is marked and a timer is set for 15 minutes. After 15 minutes, the wheals produced are measured, a positive test is defined as at least 3mm larger than the negative control. (3) Although skin prick tests can help detect the presence of food allergen specific IgE, it is not a perfect test and false negatives can be seen. If the history is suspicious enough, diagnostic testing should be confirmed with other testing – and the use of skin prick testing ALONE in the clinic setting is NOT diagnostic and can result in overdiagnosis!
Serum IgE testing for specific allergen IgE antibodies in a patient’s blood can also be used. It is VERY IMPORTANT to understand that just because a patient has IgE antibodies that indicates sensitization DOES NOT automatically mean a patient has a clinical reactivity and has symptoms! Higher IgE levels may correlate with the probability of a clinical reaction, so if a patient has high levels an allergy specialist may recommend avoiding a food, or testing with a food challenge, or discuss other options. The sensitivity of IgE testing like this is greater than 90% but specificity is less than 50% due to possible cross-reactivity with different proteins (3).
There is not a clear “yes or no” result when it comes to correlating skin prick testing and serum IgE testing with clinical outcomes. Sensitivity is typically better than specificity and usually the larger the skin prick response size or the higher the serum IgE level, the more likely a patient is to have an allergy (1). But there are exceptions, including patients who have drastically high IgE levels or large wheals on skin prick testing and exhibit clinical tolerance to foods. To make things trickier, the exact opposite is true as well and some patients who have nearly undetectable IgE or skin prick testing to specific allergies results have symptoms of IgE mediated food allergies. This just goes to show the importance of really teasing things out in the history, that way you can be careful in selecting exactly WHAT allergens you will be referring patients to test for since the testing isn’t foolproof. And at the end of the day, remember that the gold standard is an oral food challenge.
It’s not uncommon parents will request multiple allergen tests, especially if they are worried about one food, why not “knock it out” and test for other foods. But because the number of exceptions and false positives and false negatives, because labs may not always correlate with clinical response, it’s important to emphasize to parents that we test ONLY the foods we are specifically concerned about from the clinical history. This is a great opportunity as a medical student to shine as you can prep parents for what to expect when testing for food allergies!
It's also reasonable for parents with children at high risk for food allergies to ask their pediatricians to be referred to an allergist to obtain testing prior to introducing highly allergenic foods – but know that widespread testing has poor predictive value. There are some cases when food allergy evaluation can be helpful – for example if a patient has another coexisting food allergy or if they have a sibling with a food allergy. This can be a discussion, and an allergy specialist can discuss the pros and cons to understanding a positive test result DOES NOT conclusively diagnose a food allergy.
As I briefly mentioned before, if you are concerned a patient has a food allergy, if the resources are available, it’s typically best to refer to an allergy/immunology specialist. Sometimes, wait times or scheduling issues can be tough. If you are worried about an IgE mediated food allergy, you should prescribe the family an autoinjector epinephrine, one for home and one for school to always have on hand. You should provide them with resources on how to use an epinephrine autoinjector if there is not a nurse at your location who can show them with an example epinephrine autoinjector. You should also tell parents to give their patient a SECOND generation antihistamine like cetirizine, levocetirizine, or desloratadine to patients 6 months and older if they think they are having an IgE mediated food reaction. Try to avoid Benadryl and first generation histamines in young infants due to the risk of making them too sleepy, the risk of toxicity, or the risk that the opposite effect can occur and kids can get really agitated. Also, tell the family to avoid the offending food for the time being until an allergy appointment can be set up! This way, there are no accidental exposures or risks that may cause serious harm to the patient.
And with that, I hope you will feel prepared during your Pediatric clerkship to discuss food allergies and testing available for our patients. Good luck, and don’t forget to have fun!
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