Oral Challenges for Food Allergy

One of the more common questions I am asked in clinic regards oral challenge testing for food allergy. The gold standard of food allergy testing is the oral challenge. Eating is the best test, as false positive allergy testing to foods occurs more often than we would like. The majority of the time, an oral challenge for food allergy is not necessary, though. I will try to take you through my thought process used in determining whether or not to offer an oral challenge to a patient.

The decision on whether or not to do an oral challenge involves two things. The first is the history. What is the history of the reaction to food? Was the timing of the reaction consistent with the food allergy reaction? Were the symptoms of the reaction (hives, wheezing, swelling, G.I. symptoms), consistent with a food allergy reaction? Did the patient use to eat the food without any problems then all of a sudden one time they had some symptoms that were not super typical for a food allergy reaction? Was the duration of a reaction consistent with a food allergy reaction (sometimes hives caused by a virus are falsely attributed to a food allergy).

The next consideration is what the allergy testing shows. Through some very nice research that has been done in the past, we have what are called decision points for oral challenges. For this reason, I tend to like using the Immunocap specific IgE concentration to the food in the blood to help decide on the necessity for the oral challenge. For a given food, based upon research, we have negative and positive predictive values for many of the most allergenic foods. For instance, a peanut specific IgE concentration of over 15 ku/L essentially shows that the patient has a 100% chance of reacting to peanut. For wheat, you would need to get to a level of 26 ku/L for a 75% chance that the patient would have a reaction.  So as you can see it is different for each food.  It is super important to note that the number does not denote the severity of the reaction, only the likelihood of a reaction. 

While these levels are really helpful to have, there is some nuance to this. Some newer research shows that for kids with very high total IgE levels, such as those with atopic dermatitis or eczema, many have falsely elevated specific IgE concentrations to foods that they can tolerate without issue. There is some even newer research showing that a ratio of the specific IgE concentration of the food to the total IgE can be helpful to use in addition to the traditional decision point for oral challenges, and for these kids with atopic dermatitis it can be useful to have this value as well.

There are three basic reasons to do an oral challenge in my mind. The first two are pretty straightforward and commonly encountered in the practice of allergy. The first reason is that someone comes in, usually a small child, who has a history of a positive allergy test to a food that was found incidentally. Usually, the positive test to the food was part of an allergy panel that was drawn for other reasons. If the child has previously been eating the food, I tell the parent that eating is the best test and that clearly the lab was a false positive. For these patients, an oral challenge is not necessary since they are already safely eating the food. But, sometimes there is no ingestion history one way or the other. At that point, we refer to the decision point data on the likelihood of an allergic reaction taking place. Based upon the negative or positive predictive values associated with the number, we decide whether or not to perform an oral challenge to see if the food can safely be consumed or to continue avoidance, consider the child food allergic and provide a food allergy action plan.

The second reason to do an oral challenge is where there is clearly a history of food allergy with corresponding positive allergy testing. But, several years have passed since a reaction has occurred, and generally there has also been a decline in the specific IgE concentration of the food in the blood to the point where we think the child might have outgrown the food allergy. This almost always happens in milk and egg allergy, thankfully. Also, about 20% of peanut allergic toddlers and 10% of tree nut allergic toddlers will "outgrow" these allergies over time so we follow these levels as well in the hope that this can take place. When the level has fallen to a decision point with acceptable risk, we proceed with the oral challenge.

The third reason to do an oral challenge is the least common. I call these oral challenges threshold challenges. This challenge generally happens when there is no history of a reaction, but the specific IgE level to the food essentially shows that there is a very high chance of reacting. Often times, the parent is skeptical that a food allergy actually exists because there has never been a reaction and they have not been particularly careful about avoiding the food (although there has also not been any overt ingestion). In these scenarios, I offer an oral challenge to essentially see what  threshold of allergen will cause symptoms in the patient. It is a useful tool to show parents or other caregivers the reality of the situation in a controlled environment. It also can be helpful in that we allow someone who is skeptical of his/her child's food allergy to see a food allergy action plan in action and to become more comfortable with it.

This is how an oral challenge works. We start with a very small amount of the food in question.  The starting dose is generally based upon the history of reactions and the likelihood of reaction. It can be as little as a few milligrams or as much as 100 mg of the food in question. Then, the dose of the food is essentially doubled every 15 to 20 minutes until either a full serving of the food is reached, or the first sign of an allergic reaction is noted. Generally, the symptoms of an allergic reaction are more mild than what is seen in real life as we try and use the least amount of food necessary to cause symptoms and treat the reaction immediately. The most common reaction is vomiting and G.I. symptoms. The second most common type of reaction is hives. Occasionally there can be wheezing. Oral challenges historically are very safe. To date, to my knowledge, there has never been a death associated with an oral challenge in an allergy clinic setting.

Hopefully, my explanation of oral challenges hasn't made things murkier for you. But as I hope you can see, an oral ingestion challenge is an important diagnostic skill in an allergist's toolkit.

Why I (still) perform oral immunotherapy to foods

You know what? I have been really pathetic with my blog. I just need to do it. Every week I need to try and crank something out. It's good to try and get my thoughts down on screen and get some feedback every now and then.

I've been asked to give an update on my oral immunotherapy (OIT) for food allergy program since beginning it towards the end of last year. OIT has changed my life, and I'm not even food allergic. It has become the single most rewarding part of my professional practice. It has also become the most time intensive part of my practice. The OIT program is mine, and mine alone. Because the parents and children in the OIT program put their faith in me and entrust me with so much, I basically do it all to ensure no errors are made. I'm available to them 24/7 by cell phone. I measure every bit of flour. I make the peanut solutions. I even make the labels on the bottles. I talk to the family and perform an exam prior to each up-dose.  As the program picks up steam, I probably will not able to keep up on all this and will eventually have to let go of some of my responsibilities.  I will not become less accessible, though.  That is the cornerstone of my OIT practice.  

But you know what? All of this extra work is worth it. These kids are amazing. These OIT families are amazing. The lengths that they will go, the commitments that they will make, to provide their child a life free of the anxiety that comes from being food allergic is inspiring to me as a parent.  The children's bravery at bucking the trend, at going along with something that their prior allergist might be against, is pretty awesome.  Here is a point of emphasis:  These kids are cool.  Really cool. 

I've also become much more adept at food challenges. Prior to my OIT life, the main reason to do a food challenge was to see if a child had outgrown their food allergy. Now, it is just as common for me to perform a food challenge to confirm the food allergy prior to undergoing such a time intensive process. As exciting as it is to see a food allergic kid progress through oral immunotherapy and tackle the food head on, it is just as exciting and rewarding to have a child pass a food challenge to something that they previously thought they were allergic to--and leave the clinic that day with complete and total freedom from that food's effect on their life. I have seen a kid with a peanut IgE of 12 and ara h2 IgE of 5 pass his challenge with flying colors.  I have also seen a kid with a walnut IgE of 0.6 fail a challenge on the first dose.

We have had minimal problems to date with the therapy, but the program is still in its infancy really. The most common side effects are some mild GI issues.  Probably the biggest one that I underestimated prior to starting this is the anxiety.  It is something that the kids, especially the older ones, can really struggle with.  The other thing I underestimated was how much peanut allergic kids seem not to like the taste of peanut (go figure).

My OIT practice is still small I think compared to most of the clinics around the country that are offering the therapy. I think I have around 15 patients right now. However, almost month-to-month, there is increased growth, excitement and interest in the program. Nearly every week now, I am either starting a patient on oral immunotherapy or performing a food challenge to see if a child would benefit from it.

OIT works. I don't think that any of the arguments that contend for more research prior to it being offered in practice, especially in regards to peanut, hold any water. Research should continue, don't get me wrong. Research on allergy shots for environmental allergies continues even while subcutaneous allergen immunotherapy is widely practiced in the community. The research is there to fine-tune the practice and answer questions as they arise. But fundamentally, I believe that oral immunotherapy to foods is safe and effective. 

I've always tended to believe that the most effective argument against oral immunotherapy was along the lines of the cold hard economics of it. The number of food allergic kids required to do food oral immunotherapy to prevent one food allergy related death is probably quite high (meaning the number needed to treat to prevent a death would maybe be too high to justify the price of the therapy, at least on a populational level). But, this economic argument that some allergists postulate no longer holds water either. Because a peanut flour pill has been fast tracked by the FDA. If one thought that the economics of OIT didn't make sense using run-of-the-mill peanut flour that can be bought anywhere, guess what will happen when we use "pharmaceutical grade" peanut flour that the patient is prescribed?  The cost of oral immunotherapy will be astronomical. Furthermore, when the peanut pill is eventually approved by the FDA, the same questions that hold many people back from offering OIT such as what's the most effective dosing protocol, desensitization versus tolerance induction, and side effects, will all still be out there. However, since the peanut flour will suddenly be "FDA-approved" using a more regimented protocol with likely less flexibility, will there be a clamor for it?  Likely so, but I guess it will be nice not to have any "stigma" associated with OIT any longer.  The peanut patch will probably also be out by then and represent a nice alternative for patients that are maybe not as good OIT candidates for one reason or another.

I really don't know what the future will hold. Maybe I'll be using pharma peanut flour, maybe not, or maybe I'll be using a combination of both; and of course there are still all those other food allergens to be dealt with.  But in any case I know I will still be here, working with these amazing families, using the best evidence available, to kick food allergy's butt.

A brief take on antibiotics

Don't get me wrong, antibiotics are important and life saving medications.  Modern medicine is nothing without the development and advancement of antimicrobial drugs.  But antibiotics are not a "no brainer."  Modern science is just scratching the surface of what the gut microbiome is.  We know antibiotics can really mess with this population of bacteria, and it can take a lot of time to recover.  Alterations in the gut microbiome have been implicated in the development of allergic disease as well as autoimmune and inflammatory diseases and potentially cancer.  The alteration of the microbiome because of antibiotic use in my mind is so important that I think we now have two reasons to be extra-judicious in the use of antibiotics (the other reason is to avoid fostering further resistance of disease-causing bacteria).  I can tell you that I prefer not to treat ear infections with antibiotics if possible (and Scandinavia has been doing this for quite a while).  I can also tell you that unless a person is toxic appearing or immunocompromised I am not going to treat a sinus infection with antibiotics.  A significant number of sinus infections are caused by viruses and not bacteria anyway, and the same goes for ear infections..  The next time you think you need antibiotics...take a little time and think twice, maybe you don't.

Why I perform oral immunotherapy to foods

After years of thoughtful and careful consideration, I have decided to pull the trigger and offer oral immunotherapy (OIT) to foods.  This decision was not undertaken lightly.  There are a number of reasons why the researchers who conduct OIT in academic settings state why it should not be offered in a real-world setting.  I am completely open to this criticism, and patients need to know that this is a big issue in the world of allergy.  Given this, the decision to offer OIT is wrought with controversy, and I wanted to explain how I arrived at it.  

There is the question as to whether or not OIT provides desensitization or immune tolerance.  If the patient is merely desensitized to the food, and if he/she stops ingesting the food for a period of time after the OIT protocols have been completed, then the patient will become re-sensitized to the food and have reactions if they are exposed to it.  If the patient becomes immune tolerant to the food, that means that after the OIT protocols have been completed if he/she is re-exposed to the food after a period of absent ingestion there would not be an allergic reaction, as the immune system has shifted away from an allergic pathway.  From my understanding of the current state of research, it seems that both outcomes are possible, and it is impossible  at the onset of therapy to identify a patient who would become desensitized from OIT vs. immune tolerant.  To me, this is a moot issue.  I am approaching the situation as follows: once the patient has completed OIT, he/she will be treated as if a desensitization has taken place and immune tolerance has not been reached.  If the patient does not continue eating the food as prescribed every day, then he/she will be brought into the clinic and an oral food challenge will be performed to sort out the issue.  

The second reason stated as to why not to perform OIT is that the therapy may fail.  I estimate that one in every four patients may not reach maintenance dosing for a variety of reasons, including allergic reactions.  This is no different from allergy shots, which all allergists routinely provide to their patients.

The third reason to not perform OIT to foods is the cost of the therapy.  This is certainly valid.  The current recommended treatment for food allergy is strict avoidance.  This, aside from maybe a yearly visit to the allergist and the cost of an epinephrine injector, is free.  There would also be the cost of allergy tests both for diagnosis and possible repeated tests every 1-2 years to monitor the trending of the specific allergy antibody to the food, in case the patient might "outgrow" the food allergy.  This certainly is much cheaper than OIT.  OIT will involve weekly office visits.  It will also involve prescriptions for epinephrine injectors, allergy testing charges, and an oral challenge at the onset of the protocol in many cases.  The cost in out-of-pocket dollars for OIT vs the cost of strict avoidance for treatment of the food allergy must be carefully considered by each family. 

In my mind, here is strongest reason why to perform OIT.  It is the psychological benefit.  Having a food allergy, or multiple food allergies, is difficult.  It is difficult for the child, for the parents, and for other members of the family such as siblings, grandparents, and aunts and uncles.  Multiple studies have documented this.  Studies have also shown that children with food allergies are bullied for having them.  This is the study that finally tipped me, and made me pull the trigger on offering OIT to my patients.  OIT improves quality of life.  Assuming maintenance dosing with OIT is reached, children are no longer afraid of the food or afraid of being bullied because they have a food allergy, and family members have peace of mind when the child is at school or away from home that they will not have a serious allergic reaction to the food when they are not around.  That is why we do it - so the family can take control of their life, and vanquish the fear.  

I promise to carefully lay out the pros and cons of OIT with each and every family.  It is not a miracle cure, and it is not easy, but I do think it can be life changing.  Don't hesitate to give us a call, shoot us an email, or make an appointment.