As reported in the Journal of Allergy and Clinical Immunology, team of UK researchers administered an estimated threshold dose of peanut in a blind challenge. Then participants with a confirmed allergy “underwent 3 open peanut challenges in random order: with exercise after each dose, with sleep deprivation preceding challenge, and with no intervention.” They concluded: Exercise and sleep deprivation each significantly reduce the threshold of reactivity in patients with peanut allergy, putting them at greater risk of a reaction. Adjusting reference doses using these data will improve allergen risk management and labeling to optimize protection of consumers with peanut allergy.
Food Allergy Corner
By Dr. Paul Ehrlich
With the age of prescription therapy for food allergies rapidly approaching, it’s not too early to start figuring out what patients will prefer among the options presented. Allergists and their patients have confronted similar dilemmas before, although simple preference doesn’t solve the problem. For example, we have been offering shots for a hundred years, and no one is terribly fond of them. To many, sublingual immunotherapy (SLIT) sounds like a dream, but experience teaches us that in the real world patients don’t like them in nearly equal measure. Taking a medicine every day is burdensome, and many patients don’t like the way the medicine feels and tastes in their mouths.
Thus, it was fascinating to read about Dr. Matthew Greenhawt’s presentation to the ACAAI meeting in Houston about patient and caregiver feelings concerning two modes of therapy that are rapidly nearing availability—Palforzia oral immunotherapy (OIT) and the Viaskin “peanut patch,” also called epicutaneous immunotherapy or EPIT. A total of 200 children aged 7-11 and 206 caregivers were surveyed with questionnaires replete with emoticons to express their feelings in addition to straight answers. Compliments to Matt and his team for their imagination in assaying patient emotions as part of the package.
Unsurprisingly their greatest concerns were over the prospect of medical emergency, but they were also deeply disturbed by things like touching, tasting, and smelling peanuts. Questioned about the prospective treatments, many rejected the oral approach. Many more were drawn to the idea of the patch.
Looking at the numbers, I began to think about my own experience over many years. The two key senses—taste and smell—have figured heavily in the lives of many patients whom I first met as children, and treated on into adulthood, and in many cases treated their own children. While there was no such thing as active treatment all those years, some of them did manage to outgrow their allergies, including to peanut. I would test them for IgE and do skin prick testing and urge them to try their allergens or do an office food challenge. But for some, the chance to eat the allergen just wasn’t enough to overcome that sensory aversion, although some do arrive at some remarkable strategies over time. The key is to associate food with the pleasure it is meant to give rather than regard it as medicine.
It’s early days for food immunotherapy, but it’s not so early that we can’t start figuring in the dimension of time. Longitudinal data for some of the earliest studies show that many subjects drop out. Medication fatigue is a real thing with all chronic disease management. It’s likely to factor heavily as OIT, the patch, and other non-curative treatments hit your allergist’s office. Those early aversions and fears at the front end have their analogues on the back end.
But maybe that’s not a bad thing. In a recent talk, one of the pioneers of private practice OIT observed that patients he had treated as little kids would come to him as they reached adolescence and inform him they were quitting. He was okay with that. He had helped them deal with their allergies long enough to come of age and could make their own decisions. They could negotiate the risks for themselves. I liked hearing this.
With a range of treatment options on the horizon, the allergist’s responsibility remains the same. To understand patient and caregiver needs and fears, to provide treatment when appropriate while explaining all the risks and offering lots of encouragement, and be just as considerate and well-reasoned when rejecting a treatment. One thing is sure: all those fears and aversions covered in Matt’s study are going to be a constant. We may have seen it all before, but it’s always new to the patient.
By Henry Ehrlich
Congratulations to Gwen Smith and the team from Allergic Living for the “Food Allergy Anxiety Guide.” This 90-page e-magazine will surely be the definitive guide to all aspects of the subject for years to come. As Gwen writes in her introduction, “The purpose of this e-magazine is to discuss the fears and the ‘what ifs’ with honesty, without sugar-coating, and to begin to understand this phenomenon as its own anxiety disorder.” Mission accomplished. It is an authoritative and polished product, complete with podcast, and should be on the desktops of patients, parents, and practitioners.
I wrote to Gwen and asked her a couple of questions:
AAC: What was the impetus for starting the project and how long did it take?
Gwen: I have a long interest in the anxiety issues surrounding food allergies. But the impetus for this full-on ‘Food Allergy Anxiety Guide’ stems directly from our decision earlier this year to transition to a digital publication. Doing so related to the future direction of publishing, but it also provided me an opportunity to stand back and assess: What could a digital Allergic Living be that was truly useful to the community? Coming from a current affairs (radio) and news magazine background, I’m always interested in taking apart and packaging big topics.
This led to my idea of a “big topic” special edition guide, and I had a sense from our community that a natural such subject/need was food allergy anxiety. We tested the idea on our social media channels by asking: “If you are stuck in food allergy stress, tell us your story.” (The Consulting Editor on this issue is Gina Clowes; she asked the same on Allergy Moms.) The outpouring in emails and posts was incredible, and people’s stories were so affecting. The need here, just as quality-of-life surveys have shown, is clear.
The edited-down reader quotes (preview publicly available here) are what led me to go slightly overboard and create a 90-page interactive publication. I felt compelled to do something exceptional on this topic. It’s almost more a book than a magazine. I honestly think this is the best work we’ve done in a dozen years of publishing. The reason is the importance of the topic and the fact that our writers and podcast moderator were able to get top food allergy therapists to give actionable strategies to show that you don’t have to stay locked in stress and fears.
We pulled it together four months. We burned lot of midnight oil. But we got there.
AAC: Wow. Tight timeframe. Were there any particular challenges?
Gwen: Even with Allergic Living’s big audience, getting enough people to know about the Guide and to understand it’s a significant and unique piece of work on the food allergy anxiety topic is taking a great deal of work. It’s also a bit of a challenge to communicate that while the Guide discusses anxiety, the real focus is on the steps toward stress control and better quality of life.
There were some hiccups at the beginning, but fortunately we got those sorted out quickly. Transitions always seem to come with learning curves.
What was NOT a challenge – finding people to speak on this topic. There are many wanting to talk, wanting to find a way through.
The finished product is worth the cost: $7.95. It’s not a one-time thing. Readers should go back again and again for the advice, for the inspiration, and for the exposure to multiple points of view. Print out pieces of it and show them to your uncomprehending friends and relatives. Get a grip. You are not alone.
Long-time readers of this website will remember an article by Dr. Eva Untersmayr linking use of antacids to adult onset of an allergy to Beluga caviar in an individual patient. He had eaten the delicacy at a party with no ill effects, but several months later had a severe reaction after eating more. The Dr. Untersmayr and her colleagues learned that he had been taking antacids during the first ingestion, reducing the crucial acid environment of his stomach. Poorly digested larger protein components found their way into the intestines and the blood, where the immune system went on alert and cranked out allergic antibodies in case it ever happened again. The same pattern was observed for patients with dyspeptic disorders treated using anti-ulcer medication. When Dr. Untersmayr popped up again recently as a co-author of an article in the journal Nature Communications entitled “Country-wide medical records infer increased allergy risk of gastric acid inhibition” which elaborates on the connection between anti-ulcer drugs and allergy, not just to food but to all kinds. She has generously agreed to answer some questions about the new article. – Henry Ehrlich
AAC: Eva, welcome back and thanks for volunteering your time. First, your methodology in this study was fascinating. You were able to access the medical records of 97% of the population of Austria between 2009 and 2013 because the country has near-universal health insurance. As an American I marvel at that all by itself. Simply put, you compared prescriptions of anti-allergy medicine to patients who had previously been taking H2 agonists—antacids–and proton pump inhibitors, or PPIs. How did you arrive that this approach? Also, I know it’s not as easy as it sounds. How did you construct the study? And what protections are there for patient privacy?
Eva: Henry, thank you very much for the invitation and your questions. You are right, our approach sounds straightforward, but it was made only possible within a network of excellent collaborations. The reason why we designed the study that way was to evaluate the impact of this medication on the entire Austrian population. We are very lucky to have compulsory health insurance ensuring nearly complete health care coverage, even paying for most of the medication Austrians are prescribed by medical doctors. In the health insurance databases, in- and outpatient data on medical services covered by the health insurance is available. And of course the study was performed in strict agreement with data protection and patient privacy law. Therefore, a pseudonymized data set was used and only after approval by our ethics committee of course. And in the end the analysis means a lot of statistical calculations and comparisons, which were done by the expert in our team.
AAC: The idea that digestion is impaired by these drugs so that allergenic protein components sneak through is familiar enough. But your study shows that they also activate Th2 mechanisms, which are more generally allergic, as indicated by patients needing medicines that don’t work on food allergies. How do these medicines affect the larger immune system? Could you particularly highlight their effects on the gut and oral microbiome?
Eva: I am not so sure that the concept of digestion impairment and higher risk for allergy development is familiar to everyone working in the field of allergy or gastroenterology. I still get a lot of questions from the audience when I present even our older data at scientific meetings. But you are right, our current data shows that the effect goes beyond food allergy, as we investigated use of anti-allergy medication, which is most frequently used for respiratory allergies and far less frequently in case of food allergies. One mechanism, which we also highlight in our paper, could be the direct effect on the immune response as immune cells have H2 receptors, PPIs can induce mast cell activation and the aluminum-containing Sucralfate might act as an adjuvant. Moreover, anti-ulcer drugs have an enormous effect on microbiota, which is even more prominent than the effect of antibiotics when considering the entire population due to longtime intake of this medication. So there are different layers of mechanisms that might explain our results.
AAC: These changes take place very quickly, don’t they? You mention as few as six days.
Eva: The change in the gastric milieu takes place very quickly. You are right that approximately 5-6 days of PPI intake elevates the gastric pH to around 5. But long-term use of anti-ulcer drugs seems to especially increase the risk for need of anti-allergy medication, which we could also prove in our current study.
AAC: I was particularly struck by how many young boys are on these drugs. Why? Is it because they eat a lot of junk? If so, why are their doctors prescribing these things and not focusing on improving their diets?
Eva: There is not really a difference between anti-ulcer drug prescription between boys and girls in childhood. Around puberty girls are more likely to get prescription for this medication and the female gender dominates until very old age.
AAC: Finally, the paragraph on “imprinting the next generation for allergy” was very troubling. I know that reflux is a big problem during pregnancy. I kind of hate to ask because mothers of food allergic kids are constantly worrying about what they did wrong, but I have to. How does antacid use “imprint” the next generation? Is this an epigenetic change or something else?
Eva: We and other groups have demonstrated this link in previous studies, both in experimental models and in human data. When the mother takes anti-ulcer medication during pregnancy, the child is more prone to become allergic due to skewing the immune response. Moreover, as mentioned above, anti-ulcer drugs affect the microbiota composition and we know how important our microbes are for immune health and how much the mother’s microbiota influences the colonization of the child. But I think much more research is needed until we fully understand all the mechanisms involved here. As an advice for pregnant mothers-to-be suffering from reflux (like I did with my second child): Lifestyle changes are also a good option and can prevent the need for medication. Do not eat too late and try to sleep with your upper body slightly elevated.
AAC: In your previous article, you wrote, “There is evidence that patients and doctors are trading long-term health for short-term comfort. In Europe, and I suspect elsewhere, the sales figures of acid-suppressive drugs are continuously on the rise and they are being used for long periods of time.” Do you have the feeling that patients and their doctors are taking better care of their digestion? Are they eating better? Are they using alkaline water instead of antacids and PPIs? Or is it business as usual?
Eva: Unfortunately I do not see a big difference in caring for a functional gastrointestinal digestion. Nevertheless, it is very important to raise awareness, to constantly inform medical doctors and patients. We once launched an awareness campaigns together with one of our health insurance companies here in Austria and we could really see an impact of this campaign on anti-ulcer drug prescription habits. Making important information available is very helpful!
AAC: Your biography says that you are a trained acupuncturist. The only doctors I know who address digestion as part of treatment for food allergies are also trained in Asian medicine—one in Chinese medicine and one in Ayurvedic medicine. Do you think that Western doctors have something to learn from these disciplines?
Eva: I am personally very keen on a broad approach in medicine. There are so many fields to learn from. Asian traditional medicine is one example, but we also should not forget traditional medical knowledge from our cultures, where much more attention was given to how, when and what to eat.
AAC: Thank you for your time.
Eva: Thank you Henry for your interesting questions and for highlighting our research!
Eva Untersmayr, MD, PhD, is Associate Professor and head of the Gastrointestinal immunology research group at Institute of Pathophysiology and Allergy Research at the Medical University of Vienna. She is a Clinical Immunologist especially interested in the connection between digestion, food allergy and the immune system of the gastrointestinal tract. Her work was continuously funded by several grants of the Austrian Science Fund, the Austria National bank, the EC Horizon 2020 and other funding agencies. Following her medical studies, Dr. Untersmayr also trained as an acupuncturist in Austria.
Fotocredits, © MedUni Wien, Felicitas Matern”
When IgE was discovered more than half a century ago, allergists had hopes that it would be the key to better diagnosis and treatment of allergies, but it has remained a riddle wrapped in an enigma, although there has been exciting research along the way. A new paper entitled “High-affinity allergen-specific human antibodies from single IgE B cell transcriptomes” by Stanford researchers Derek Croote, Spyros Darmanis, Kari R. Nadeau, and Stephen R. Quake has provided an exciting new glimpse of IgE’s nature that may lead to breakthroughs. We reached out to lead author Derek Croote of the Department of Bioengineering, who had recently followed us on Twitter. (Confession: another article by Hannah J. Gould and Faruk Ramadani was published in the same issue and as Derek suggested I used it as a cheat sheet for understanding the basic science.) – Henry Ehrlich
AAC: Thanks very much for taking time with our readers. Before we discuss the science in your paper, I’d like to ask you a few “process” questions. Can you tell us how you came to do this work? I’ve found that personal experience is the impetus for some researchers, either their own or a family member. Do you have a personal interest in food allergies or was it pure scientific curiosity?
Derek: This work began roughly three years ago actually. Professor Stephen Quake has always pursued clinically-relevant projects and at the time, techniques for studying single cells were maturing in the lab. These two factors, combined with Dr. Kari Nadeau’s clinical expertise and my interest in food allergies paved the way for our idea to study the rare B cells that produce IgE antibodies responsible for food allergies. I think my personal motivation also likely played a part–I have a severe milk allergy myself.
AAC: Would you give our readers some insight into how you think? What were the factors that led you to your hypothesis for this study? What previous research provided the building blocks?
Derek: From studies of humans and mice dating back decades, it has been known that B cells produce antibodies and that a specific class of antibodies, IgE, causes allergic reactions through interactions with other immune cells such as mast cells and basophils. However, studying the B cells that produce IgE antibodies has been a longstanding challenge due to their scarcity. By our estimates, B cells producing IgE antibodies can be as rare as one in ten million white blood cells! We thought that a new technique, called single cell RNA-sequencing, could allow us to capture these rare cells and study their antibodies.
AAC: This an extraordinarily rich paper—meaning there’s an awful lot I don’t understand—so I’m just going to focus on a few areas. B cells come in multiple subtypes including naïve and memory, which do not secrete antibodies, as well as plasmablasts and plasma cells, which do. As described in the Gould article, the IgE plasmablasts you discovered seem to learn their allergen specificity from other cells—on the job as it were, instead of at the factory. This gives them an advantage because they can go right to work pumping out new IgE when challenged. This is a good thing when there’s an infestation of helminths, which require a heavy-duty response. But it’s a problem when the target is a harmless allergen because it causes a reaction disproportionate to the threat. Am I correct in my description? Could you elaborate?
Derek: There are multiple interesting points there to unpack. In contrast to other antibody classes, such as IgM or IgG, most of the IgE B cells we found were plasmablasts, meaning- as you said- they were actively secreting IgE antibodies, many of them peanut-specific, into the blood when we isolated them. This is interesting because it suggests a bias in the fate of IgE B cells towards antibody-secreting plasmablasts. The question of where these IgE plasmablasts came from is more challenging to answer because we only have a single time point from each of the individuals in our study, but a large amount of research in mice and some in humans suggests that other antibody classes have a role in allergic “memory.” I think the method we developed using single cell RNA sequencing will help further answer these types of questions in humans going forward.
AAC: I think the most interesting thing about your paper is that it begins to explain how tendencies to specific allergens are inherited. You isolated identical gene sequences – converged sequences — from two unrelated patients with peanut allergens. I know that sickle-cell anemia started out as a defense against malaria, but it’s a disaster in those who have inherited the genes. Do food allergies have a parallel history? Does this mean that all these people (and millions more peanut-allergic patients) are somehow descended from some group that needed defenses against particular parasites, and that they are just waiting for a fight? Can we also infer that if you studied, say, milk allergies you would find a comparable set of convergent gene sequences?
Derek: We did find one instance of convergent evolution where two unrelated individuals produced antibodies derived from identical gene rearrangements, but unfortunately we cannot say more on the general importance of specific immunoglobulin genes in allergies because of the limited number of individuals in our study. Broader claims about genetics, inheritance, and the importance of specific genes will require further studies with more individuals and more allergen-specific antibodies.
AAC: You state that the different allergenic peanut proteins most associated with anaphylaxis—Ara h 1, 2, and 3—are very different from one another. Why do these generate a stronger immune response than other peanut proteins and how do they relate to the IgE antibodies you found?
Derek: How the immune system decides which proteins in foods are “harmful” is still poorly understood, but some proteins, such as Ara h 2, are clearly more allergenic than others. One surprising result of our work was that some IgE antibodies we found bind strongly to two distinct allergens- Ara h 2 and Ara h 3. When we dissected the features of these antibodies that gave them this ability to “cross-react,” we found that it was a result of affinity maturation, a process during which mutations to the antibody sequence give antibodies the ability to bind more strongly to a target. We think this molecular approach will prove useful going forward when studying other allergies, such as tree nut allergies, where individuals can be allergic to some tree nuts but not others.
AAC: This question of a particular food allergy being descended from an ancient defense mechanism does beg the question why don’t all people with that gene sequence become food allergic? Many more millions of people who have these sequences don’t present as allergic, so far at least. Here I’m going to draw on your co-author Dr. Kari Nadeau and her work on epigenetics—namely the science of how genes are expressed—which can be influenced by many environmental and societal factors. Could you tell us some of the latest thinking about the food allergy epidemic from the epigenetic standpoint? Is it just a matter of time and generations before more trends in diet, pollution, and behavior uncover the food allergies in us all?
Derek: Food allergies are increasing in prevalence at a rate that cannot be purely explained by genetics, and indeed, Dr. Kari Nadeau here at Stanford and others around the world are finding that the types and timing of environmental exposures play a key role in determining if and when allergies develop. While some trends are certainly worrying, I would say that there are numerous recent advances that are encouraging. For example, it appears that early childhood exposure to food allergens can be protective. Going forward I think this will be a major focus of clinicians as they seek to develop interventions to reduce the incidence all types of allergic disease.
AAC: Finally, let’s talk about hope for the future. IgG4 is a class of antibody that greatly increases in individuals undergoing immunotherapy and is believed to act as a “shield” to prevent the immune system from reacting to an allergen. In one individual, you found a B cell producing a peanut-specific IgG4 antibody and a separate B cell producing a peanut-specific IgE antibody. Could you, for example, “selectively breed” cells to produce more IgG4 rather than IgE or administer peanut-specific IgG4 to accelerate immunotherapy? And if I’m way off base, could you please explain why? What should we be thinking about?
Derek: I first want to be fully transparent and say that our study was focused on our basic understanding of allergies and a potential therapeutic is still far in the distance. That being said, IgG4 is an exciting future direction for the exact reasons you mentioned. For our work in particular, a potential therapeutic could be based on re-engineering our antibodies to retain their ability to bind peanut allergens, but modify them such that they belonged to the IgG4 antibody class. If these were then reintroduced into someone and that person accidentally consumed an allergen, these antibodies would ideally bind the peanut allergens and prevent the immune system from reacting to them.
AAC: Thanks for your time and your provocative research.
Derek: It was a pleasure, thank you.
Derek Croote is pursuing a Ph.D. in Bioengineering in the laboratory of Professor Stephen Quake at Stanford University. Broadly, his research interests include allergy, B cells, antibodies, genomics, and bioinformatics. His most recent research focuses on a fundamental understanding of the human immune system for translational applications in allergic disease. He is excited by today’s unprecedented capacity for generating biological data and can be followed on Twitter: @DerekCroote.
Graphic by GeekyMedics.com
By Dr. Paul Ehrlich
The 2019 new year brought heartbreak to a South Brooklyn family as an 11-year old boy died after reacting to the smell of fish being cooked in his home. As described by the New York Daily News, the family hooked him up to a “medical device”, and when that didn’t help they called 911. While the medical device wasn’t identified, I suspected that it might have been a nebulizer pointing to a history of asthma. A later report in the New York Post confirmed that he did have asthma, and also a fish allergy.
This tragedy is a reminder of the dangers of poorly controlled asthma more than a food allergy story. When the small airways are inflamed, the space through which the air flows is reduced. When a new trigger further shrinks the diameter due to mucous and swelling, the volume plummets. When the airways belong to a child, there just isn’t that much room to constrict.
Years ago I was asked to consult with the health authorities of a Caribbean country on the rapid increase in the incidence of asthma. We concluded that it was because people had shifted away from cooling their homes using natural air exchange and the installation of air conditioners, which trapped the allergens. This problem of reduced access to fresh air is also a problem in cold weather. In the winter months with windows shut, environmental allergens such as dust mite and cockroach are trapped in the home. Lungs become “twitchy” as the English put it. As a kind of double jeopardy, this condition can be exacerbated by breathing cold winter air.
Thus, the airways are primed for exposure to airborne allergens, in this case fish.`The literature contains examples of incidents like this, usually when people wander through a food court where shrimp are being boiled, or in restaurants. Roasting peanuts are another known trigger if being roasted in commercial quantities.
Every death is a tragedy, but it is also a warning. Respiratory anaphylaxis can be thought of as an asthma attack triggered via the blood. Control your asthma. Know your triggers. And minimize your exposures. In addition you can’t control environments where the odors are secondary to what others might be doing, such as cooking obviously but also sanding or spray painting. These irritants can also trigger an attack. If your child is susceptible to these, asthma control is the first line of defense. If a patient is using albuterol frequently, the asthma is not controlled.
Regardless, be sure to have an epinephrine auto-injector like the Auvi-Q, Epi-Pen, or one of the generics readily available. Epinephrine is both a Beta 1 agonist and a Beta 2 agonist. That is, it treats the respiratory system the way albuterol does for an asthma exacerbation (Beta 2), as well as the heart (Beta 1)–crucial for correcting plummeting blood pressure from anaphylaxis. It was the go-to treatment for asthma exacerbations before albuterol was developed.
Illustrations from Asthma Allergies Children: a parent’s guide
By Henry Ehrlich
In October, we wrote about a new horse in the epinephrine race and wondered if it would be the tipping point, based on the idea that it takes several competitors in a niche to drive down monopoly prices. Here it is, early December, and we read about still another, this one from Sandoz, the company that brought us LSD, but that was long ago and far away.
This one will not be an auto-injector, but a prefilled syringe instead. Sold under the name Symjepi, the price will be $250 for two, without insurance. People are so accustomed to auto-injectors adjusting to the pre-filled syringes will take some doing. Auto-injectors were developed by the military to administer nerve gas antidote under battlefield conditions. Anxious parents and teachers no doubt feel the same level of duress when a child is having anaphylaxis. Introducing another step into the process of deliver a life-saving drug will require additional training and enough practice to so without panic, although the unit appears to be well designed with clear instructions. But once that familiarity threshold is reached, Mylan’s market dominance may suffer a real blow. Maybe the invisible hand will reach out to help patients instead of picking their pockets at the same time.
A salutary effect on pricing is by no means a given. Generic drug makers are described as a price-fixing cartel, with its own private language. As reported in the Washington Post, “The ‘sandbox,’ …was the market for generic prescription drugs, where everyone was expected to play nice.
“’ Fair share’ described dividing up the sales pie to ensure that each company reaped continued profits. ‘Trashing the market’ was used when a competitor ignored these unwritten rules and sold drugs for less than agreed-upon prices.”
The investigation began as an an antitrust lawsuit agains two drugs in 2016 and now encompasses at least 16 companies and 300 drugs.”
By Henry Ehrlich
The first commercial oral immunotherapy product for food allergies has come through a phase 3 clinical trial, clearing the way for commercial release, possibly in 2019. The drug (made from peanut flour) received one of the highest honors in the world of medical publishing: publication in the New England Journal of Medicine. The co-authors are a food allergy all-star team, including several who have contributed to this website.
Although for the time being it is peanut only, Daniel C. Adelman, M.D. the head researcher for Aimmune Therapeutics, the company that made it, and lead author told me last year that it was the company’s ambition to be the largest maker of food immunotherapy products in the world. Dr. Brian Vickery, MD, Director, Food Allergy Program, Children’s Healthcare of Atlanta who led the international trial, said, “This was the largest clinical trial ever conducted in food immunotherapy, and the results suggest that the treatment could potentially protect peanut-allergic children from severe reactions due to accidental exposures, which would be life-changing for families. We are excited to be able to conduct research that could one day lead to new treatment options that improve the lives of families dealing with peanut allergies.”
AR101 performed well in children and adolescents 4 to 17 years of age compared to placebo. “Overall, 67% of the participants 4 to 17 years of age in the active-drug group could tolerate a single dose of at least 600 mg of peanut protein, the equivalent of approximately two whole peanut kernels, during the exit food challenge.” All had showed reaction symptoms at a challenge dose of 100 mg or less at baseline… no more than 30 mg of peanut protein, the equivalent of 1/10th of a peanut kernel. “A total of 50% of the participants 4 to 17 years of age in the active-drug group were able to complete the entire double-blind, placebo-controlled exit food challenge, which was capped by a 1000-mg single dose (the equivalent of approximately three or four peanut kernels).”
The bad news was that in participants 18 to 55 years of age the therapeutic effect was not significant.
So, we now have one on the board, an OIT protocol that will surely be offered much more widely than the “OIT underground” that has been treating patients for years. They will have to make the choice to perform, or at least authorize, more food challenges. As Dr. Andrew Bird (one of the co-authors) wrote on this website, the age of prescription food allergy treatment demands more rigorous diagnosis. They also must impress on patients and families that this is not a cure, but will require long-term maintenance and vigilance. And while it raises the threshold for eliciting a reaction, it doesn’t remove it altogether.
Another therapy, the DVB peanut patch is on its way.
Photos courtesy of Aimmune Therapeutics
Several years ago, Dr. Paul Ehrlich explained why he wouldn’t be taking up any of the new food allergy treatments that were coming into the medical marketplace. He wasn’t against it in principle so much as he wasn’t prepared to offer the kind of attention required when therapy consists of daily doses of the offending foods. He described such a practice in this way: If you are going to use this kind of therapy, the kind of practice you should go to, [is] one where current practitioners are either pioneers or who have worked directly with the pioneers.” We found one. Nikhila Deo Schroeder, M.D., who also holds a Masters in Engineering from MIT, started her own practice in Charlotte, North Carolina called Allergenuity Health whose aim is to safely teach and retrain the immune systems of allergic patients via a method called Sublingual Immunotherapy (SLIT) – the system of placing antigen under the tongue (via liquid or “drops”). After her Allergy & Immunology fellowship training at the University of Virginia, Dr. Schroeder worked for several years at Allergy Associates of La Crosse with Dr. Mary Morris, the standard bearer for the work done by her father Dr. David Morris, who attended a Sublingual Immunotherapy conference in the 1960’s and recognized the significant potential for this type of treatment in his mold allergic patients. Dr. Schroeder’s experience in La Crosse treating over 1000 patients with food and/or environmental allergies using Sublingual Immunotherapy gave her an in depth look at how the immune system responds to this type of allergen introduction and ideas for its further therapeutic potential. – Henry Ehrlich
AAC: Thank you, Dr. Schroeder, for taking time with our readers. First I’m intrigued by your background in engineering. What made you leave for medicine?
Nikhila: Thank you so much for the invitation to talk with you and your readers, Henry! I’m so happy to be here. I have always had a love for math, logic, and problem solving. Paired with my creative side, engineering was a very appealing career choice because it allowed me to use my skills to invent solutions for people. But being a doctor felt even more natural. My mom often shares the memory that when I was a really young girl, anytime someone was sick on our block, I would take them a can of chicken noodle soup from our pantry and keep them company. That’s just who I was and what I wanted to do from a young age onward. So in the end, I decided to go for both engineering and medicine and see what I could do with them together.
AAC: Does engineering inform the way you think about your allergy practice and your approach to patients?
Nikhila: Absolutely. My time studying engineering really cultivated my critical thinking skills and I apply that to my practice and my care of patients. Nearly every homework assignment or project at MIT was a complex problem that needed to be solved, and memorization or looking something up in our textbooks or on the internet was not going to cut it. Believe me, my friends and I tried. Though sometimes it was overwhelming, I’m so glad I pursued engineering first because it really taught me how to actively think and more importantly, to not be scared of doing so. Problems often have more than one solution, and that is a beautiful and extremely useful concept to remember in health. One solution may be the best overall for one person and a different solution may be best overall for another person with the same underlying issue. Being able to navigate, think, create, and adjust solutions to the individual person can help patients in ways that following a predetermined or standard solution simply can’t, so I’ve kept that idea central to my practice of medicine. Now that my husband and I have opened our own allergy clinic, we have incorporated these philosophies into not only our medical care but also into our overall health care process. Our clinic, Allergenuity Health, is in almost no way standard, and our approaches to everything from the care we provide to our business policies and price transparency are all designed to provide options and solutions to patients. It takes a lot of work, but it is worth it.
AAC: When you were doing your allergy training, was there much discussion of OIT and SLIT? What prompted you to pursue SLIT over OIT?
Nikhila: OIT and SLIT were essentially theoretical treatment possibilities during my fellowship training. They were an occasional topic of a research presentation or a Journal Club discussion. This makes sense to a large extent, since fellowship programs are designed to train budding allergists in the main diagnosis and treatment methods of the field, not necessarily in highly sub-specialized areas of the field. However, when I saw how much allergy patients and families were suffering and how inadequate the traditional therapies were in so many instances, I was motivated to look for or create something better and to further sub-specialize. I became very interested in immunologic signaling and how we could use that to help people with allergies. As I learned more about various types of immunotherapy, SLIT made a lot of sense to me. It actually made more sense overall than any other form of immunotherapy. It is scientific, uses a natural route of tolerance-training literally handed to us by our bodies, has been proven effective, and is safer than any other form of immunotherapy. Why weren’t we talking more about this? I still don’t know.
The safety aspect was the kicker for me that solidified my in-depth pursuit of SLIT. I had listened intently as so many patients and families shared their incredible stories, their worries, and their goals with me over the years. Safety, both in daily life and in treatment options, was overwhelmingly their main goal. What they desired most (other than a complete cure of course) was a treatment option that provided them with a safe way to build allergen protection, reduce chronic symptoms, and minimize the likelihood of anaphylaxis if they accidentally encountered their allergen(s). For example peanut-allergic patients and families made it more than clear that being able to eat peanut butter was not their goal, especially if they had to undergo a risky procedure to get to that point and then sustain a lifelong, daily risk to maintain it. And I completely saw their point. OIT’s risk of anaphylaxis for patients was and is still far too great for most specific patient situations, in my opinion. Some reports suggest that the average risk of anaphylaxis from OIT treatment may even be higher than the average natural risk of anaphylaxis in a food allergic patient. Though epinephrine is a life-saving medicine in anaphylaxis, it is not effective to rescue 100% of individuals from anaphylactic reactions even when used early and appropriately, so I take risk of anaphylaxis from a treatment extremely seriously. Given that SLIT can achieve many very useful and potentially life-saving results in a very safe way, without this substantial risk of anaphylaxis from the treatment itself, I knew that I personally would not be satisfied without seeing first-hand what SLIT could offer all of these patients looking for such an option.
AAC: So what did you find that Sublingual Immunotherapy (SLIT) could offer patients?
Nikhila: Essentially everything patients desire. SLIT checks off nearly all the boxes of an ideal allergen immunotherapy treatment.
- It is non-invasive. No shots, no pain.
- It can be used to treat environmental allergens and food allergens, and more than one allergen at once if needed.
- It can be used even in severely allergic patients.
- It is easy for patients and families to do.
- It is high reward for low risk, helping patients build substantial levels of protection without a significant risk of anaphylaxis from the treatment method itself.
- Its most common side effect is a temporarily itchy mouth.
- It can be done at any age, including as early as infancy.
- Depending on the method of SLIT, it does not require any significant exercise limitations, rest periods, or lifestyle restrictions. And missing an occasional dose when “life happens”, even during the buildup phase has no detrimental effects on the overall level of protection you have developed.
- It is non-intrusive. There is no need to find ways to get your child to eat something they may not like the taste of or that is anxiety-provoking.
- It saves families a lot of time and money in the long run – much less ER and other doctors’ visits, less testing, less medications.
- It can be done with infrequent appointments – nowhere near weekly or monthly like other forms of immunotherapy.
- It can dramatically improve a patient’s (and their family’s) quality of life with significant symptom relief and substantial allergen protection over time.
- Some patients can come off the treatment and have sustained results for some time. For those who have better relief and protection on the treatment than off or for whom it may be too risky to gamble with discontinuing, it is extremely easy to continue long-term.
- It is easy to travel with when needed, and treatment can be done and maintained long-distance if you’re on a trip, away at college, or move to a different state during the course of your treatment.
- It involves forming a simple habit just like brushing your teeth, but even easier.
Liquid antigen SLIT treatment is done by literally just holding a sweet-tasting liquid droplet – a very specially formulated one – in your mouth a few times each day. Like any form of allergen immunotherapy, achieving substantial, true immunologic change does take time and a commitment. But I have not currently come across anything better than SLIT to help most patients and families safely build towards their goals and improve their quality of life.
AAC: Is there anything that SLIT doesn’t offer patients that OIT does?
Nikhila: Yes, there is one main limitation of food SLIT compared to OIT. SLIT will not be able to give a patient or family real-time information on their exact level of developed tolerance or desensitization. For patients on food SLIT, the allergen amount a patient can tolerate if ingested is typically much higher than the SLIT dose being administered, but we don’t have an easy way to know exactly what that amount is at any given timepoint in the process (without doing an oral challenge) since the treatment does not involve someone actually ingesting the food like OIT does. With OIT, since you are ingesting a particular dose of an allergen each day, you know that if the next day you were accidentally to ingest up to that same amount of the allergen before you took your daily dose, you would probably be ok (unless you were exercising, hot, stressed, or ill at the time, so it is still not a guarantee). Though I wish this limitation didn’t exist, SLIT is not alone in this. It’s similar to allergy shots in which we cannot answer this question in real-time either. However, in the case of allergy shots and environmental SLIT, patients are naturally and repeatedly exposed to many of their environmental allergens, so they physically see their results at those times since those are essentially allergen challenges. With food SLIT, since you’re also avoiding the food at the time (at least initially), we can’t really use that method either unless you have an accidental exposure.
Here is what we do know though, which helps support patients through this limitation with SLIT:
- Studies that have challenged patients after even short SLIT courses have demonstrated substantial protection, with improvements in tolerance from their pre-treatment level of over 100-fold. The longer the time on SLIT treatment, the further this increases.
- Short-term studies have shown that successfully consumed doses in challenges have ranged from 250-2,500 or more times the SLIT treatment dose at the time. So we can make some educated estimates. (And again, the longer the time on SLIT treatment, the further this can increase.)
- Anecdotal experience with accidental exposures repeatedly shows significant protection gained already within the first year and even more in the subsequent years, and we get more than enough evidence of the power of SLIT to protect against allergen exposures from what we see with environmental allergy symptom relief to frequent natural allergen challenges.
- There are clues of the protective immunologic changes that we can see in test results as well (though we have a long way to go as a field in terms of getting access to much needed better tests in this area).
AAC: SLIT and OIT are often compared as if they approach “desensitization” via the same mechanisms. Is that true?
Nikhila: SLIT and OIT can be used similarly or very differently. That’s where a lot of confusion comes from, even by physicians. Not all procedures offered under the same name do the same thing. And one version of SLIT is certainly not the same as another version of SLIT, so it is important that patients research and interview providing physicians. The underlying knowledge of immunologic mechanisms, immunotherapy design skill, type of protocol, and experience of the providing physician can make a huge difference. This is probably similar with OIT, since both SLIT and OIT are sub-specialized treatments. I’d be happy to help explain the basics of these comparisons here.
AAC: So how can SLIT and OIT be used similarly to achieve desensitization?
Nikhila: Classic desensitization by OIT or SLIT is similar to what we offer in the hospital to desensitize penicillin-allergic patients if they really need penicillin treatment for a particular infection. The process involves introducing a particular allergen into the body in a fairly quick, increasing, step-wise manner. This essentially plays a trick on the immune system, which is why results are so quick and can be so high. But along with this type of result comes significant risk. There are two main parts to how this type of desensitization trick is achieved, which would take quite a bit of time to explain fully. But the basics of it are, one of the things that introducing allergen in small, increasing, repetitive ways can do is use up the system’s allergic mediators bit by bit by activating allergy cells in chunks until all the mediators have been released. This is of course not without risk of the patient developing some type of symptom along the way, and symptoms do commonly occur in classic desensitization procedures as allergy cells are activated. The hope is to stay under the threshold of anaphylaxis, but that unfortunately is not always the case because there is no way to know what that threshold is. The other thing that increasing, repetitive introduction of allergen can do is slowly flood the system with so much allergen that it gets a chance to bind in many more places than usual, including plugging up both binding sites on IgE antibodies, effectively blocking IgE antibodies from cross-linking with each other which is a main signal needed for activating allergy cells. So, both of these types of actions can occur as a person gets desensitized, rendering their allergy mediators either all used up or their IgE antibodies all blocked up, or striking some sort of balance in between. Regardless of exactly what occurs, once the short-term desensitization trick is achieved, the immune system is in a balanced state of “temporary tolerance” in which it still very much wants to react when it sees that allergen – it does not think the allergen is any less harmful than it did before – but it is just much more difficult for it to be able to do so. In order to keep the body in this type of desensitized state, a persistent and high amount of that allergen needs to remain in the system, at least for quite a long time if not indefinitely. It has been well-proven that in the short term, if the high allergen load is stopped, the patient’s immune system has a very good chance to replenish its allergic mediators to substantial amounts, and all the allergen plugging up the IgE antibodies gets a chance to be released such that these IgE antibodies can cross-link again. And when those things happen, allergic reactions to allergen exposures can again occur. For patients receiving drug desensitization to penicillin in the hospital, once the procedure is stopped, we make it a point to emphasize to them that they are still very allergic to penicillin and they should not take it again on their own for anything else even though they just took it for treatment at high doses.
Classic desensitization is an incredibly cool trick, but it is kind of like cheating on a test. The immune system appears to know how to handle an allergen, but in the short run it didn’t actually learn much about how to properly handle that allergen, and that can come back to haunt it. That’s not to say this type of desensitization is not without its uses, or that there aren’t potentially additional beneficial long-term effects if desensitization is carefully maintained (but our understanding of this is in its infancy since we do not maintain drug desensitization long term). What is very important is to understand this type of desensitization for what it is – a quick, high-dose, temporary fix that comes with risk, is high maintenance, and can fairly easily come undone. Since the main component of this desensitization is merely being able to get an allergen into the system repeatedly and at higher and higher doses, either OIT or SLIT can be used effectively for this purpose. OIT can more easily reach higher doses because you are using the actual food so you can consume as high of a dose as a person needs to institute this trick, but that comes with the disadvantages for some people in terms of not liking the taste of the food, as well as the risks of allergen ingestion and entrapment in the stomach. If a reaction begins after an OIT dose, it is not easy to remove the allergen from the body and minimize the reaction. SLIT can also reach substantially high doses because you need much less allergen (1000 times less or possibly even less) presented via the sublingual route to achieve similar results to the gastic route, but there are some limits to how much allergen can be physically held in the sublingual space as well as the expense of FDA-regulated, purified liquid antigens. However, if a reaction begins to occur with a SLIT dose, the antigen can be spit out and the mouth can be rinsed out to try to disrupt any further allergen capture, so risks and reactions can be better managed. The take-away here is that substantial desensitization of this type can and has been achieved with both SLIT and OIT methods. OIT can reach higher doses (if needed) more easily, but the safety with the SLIT route is overall better and the taste factor is a non-issue with SLIT since the allergen is in a purified liquid form.
AAC: And how can SLIT be used differently than OIT and other forms of immunotherapy?
Nikhila: This is the crux of why I personally find SLIT to be superior as an overall immunotherapy option and as the best place for most patients to at least start if not also finish. Sublingual Immunotherapy (SLIT) has the unique ability of exposing the immune system to its allergens via special highly tolerogenic (tolerance-promoting) immune messenger cells found only in the mouth. These cells are called oral Langerhans cells, and they are very efficient at capturing substances present in the mouth and then sending calming signals to the rest of the immune system via specific tolerance-promoting natural chemicals (cytokines such as IL-10 and TGF-b) and important T and B cell influences. In fact, this appears to be a main part of their job – to help the immune system learn to tolerate the exposures seen regularly and non-threateningly in the mouth. This has been supported in basic science studies, but it makes common sense too. Our vital substances all come through the mouth – water, food, air – and we need to overall be able to tolerate them in order to survive. These cells help teach the rest of our immune system what to tolerate. We can use them to help teach our immune system that “allergens” are harmless too.
Though the sublingual route can be used to attempt to achieve the classic type of desensitization I described before, it can also be used in a different way to try to retrain the immune system to think properly about allergens. This form of SLIT often includes many of a person’s allergens (not just one) and uses a lower and slower approach to allergen introduction. By purposefully giving low doses of allergen, especially at first, the allergen is mostly picked up by the special tolerogenic messenger cells I mentioned before (oral Langerhans cells), engaging those tolerance promoting mediators. Very little of the allergen in the treatment reaches the mast cells (allergy cells) in the mouth or elsewhere in the body, so very few allergic mediators are released and therefore symptoms are minimal and risk of anaphylaxis is essentially only theoretical when SLIT is done this way. (For example, I have not seen anything close to anaphylaxis from the SLIT treatment I have done in over 1000 patients now.) This type of SLIT method allows a skilled allergist to very safely direct the immunologic signals being generated in favor of tolerance-promotion rather than allergic pathway activation, thereby retraining the system towards realizing that all of these substances it thinks are dangerous allergens are truly harmless at baseline, and that activating allergy pathways is not a productive response. It is akin to giving the immune system a tutor to help it understand a concept that it had gotten confused about before. In the short term, fostering these calming signals can reduce inflammation and decrease the reactive cytokines released via allergic pathways. This lessens both symptoms of chronic allergic disease and a person’s immediate reactivity to their allergens. In the long-term, creating a persistent environment of these calming signals causes many favorable effects: a shift in the entire immune system away from desiring to produce IgE and towards producing other antibodies, downregulation of IgE receptors so any IgE produced becomes less able to cause detrimental actions anyway, and a change in the overall composition of immune cells away from those involved in creating and perpetuating allergic pathways and towards those found in tolerant, non-allergic individuals.
I have seen such good things come from this type of SLIT approach without significant inconvenience to families or safety risk to patients. And that makes this type of SLIT treatment extremely valuable and unique compared to all other forms of immunotherapy.
AAC: SLIT has been criticized for a lower reported efficacy than OIT. Can you help our readers navigate this comparison?
Nikhila: Of course. The efficacy comparison has been so oversimplified so frequently that it has led to a lot of perpetuated misinformation and confusion. But this is understandable because these topics are so complex that quick summaries by default miss and skew crucial points. I won’t even be able to get into the half of it here either without going on for hours, so I’m happy to talk more about it with anyone interested. The main thing it is really important for patients and families to know is that both OIT and SLIT are effective options to choose from. Risks of reaction to exposures generally improve by substantial levels with either method. SLIT does not only max out at “bite-proof” for everyone, and this has been clearly proven in peanut SLIT studies with many participants being able to eat anywhere from 1-20 peanuts after a relatively short SLIT course. It has also been shown in a milk SLIT study with participants being able to tolerate 1/8th-1 full cup of milk. And I have seen a wide range of incredible results in private practice as well to further confirm the potential with SLIT. Think about it – to be able to safely improve a peanut-allergic patient’s tolerance to even just 1 peanut, let alone potentially much more. That is what the vast majority of patients in the real-world want, so why isn’t SLIT being promoted more as an available, sub-specialized option? It doesn’t make much sense that it is not, except that the definition of efficacy has unfortunately strayed from what many patients truly desire to what type of high-dose result can be academically achieved.
The commonly used marker of “efficacy” in discussion is “high-dose tolerance as quickly as possible.” If that is the entire definition of efficacy, with no regard to safety or other factors, then a classic desensitization procedure via either OIT or SLIT would be the best route, with an advantage to OIT since the dose can easily be increased however high is needed to achieve the desired result for an individual. However, if we take into account what is desired by a particular family in their real-life in terms of what level of protection is effective for them – balanced with other factors like the risks of achieving that protection in a certain time-frame and the required maintenance to keep it up indefinitely – then “efficacy” takes on a whole different definition. Most patients are not looking to be able to fully eat a previously anaphylactic food. Many don’t even like the taste. They just want to be able to live their life as “normally” as possible with as much protection from accidental exposures, as minimal interference in their life, and as low of a safety risk from the treatment itself as possible. For these people, SLIT is the most effective option. And even for those who do want to be able to eat full servings of a previously anaphylactic food someday, SLIT may get them there, so it still is a great option to consider starting with given its other several benefits. If needed, OIT can be done afterwards with a more safe and smooth course thanks to the beneficial foundation laid by the initial SLIT course. So it’s also important to not think these treatments are mutually exclusive – the solution for a particular individual may involve both. In the end, overall efficacy of all of these treatments actually comes down to a family’s personal factors, and the simple, isolated comparison of “tolerated dose in a short time-frame” can really mislead a family trying to understand all of their options.
AAC: Who manufactures your drops at your clinic Allergenuity Health? Can they be combined to reduce the daily dosing burden or is each allergen treated separately? If so how many allergies can you treat simultaneously?
Nikhila: We formulate our own SLIT drops at Allergenuity Health, based off of my formulas and my direct, personalized management of the SLIT procedure course all along the way. We use FDA regulated antigens that come from the 3 major world-wide antigen companies who collect the allergen material and purify it into a liquid suspension. I absolutely treat multiple allergens at one time if possible for a patient, which greatly reduces patient burden and time to protection as well as has many other synergistic health benefits. We keep environmental and food allergens separate for logistic reasons, and in our typical dosage range I can fit up to 20 allergens in each bottle. That allows me to treat up to 20 environmental allergens and 20 food allergens with my most common method, and I have found that for most patients that is more than enough. Additional allergens or more concentrated high doses can be made available if needed, as I am always open to optimizing the treatment structure to each patient, so we get creative if need be to make a plan best suited to each patient.
AAC: Do you have any exclusion criteria for new patients such as uncontrolled asthma, EoE, or a history of frequent severe reactions?
Nikhila: This is a great question and the answer is – no! In fact, one of the wonderful features of the kind of SLIT I do is that I can actually use it to help all of these patients who are so often excluded from immunomodulatory treatments for safety reasons (which I’ve always found ironic since these are the patients who could benefit from immunotherapy the most). I use additional precautions in these patients to make sure that we really ease into allergen introduction to their body, but the beauty of this treatment method is that tolerance-generating mediators are released by the immune cells we are engaging with allergen, not allergic mediators. So, the allergen we’re introducing via the sublingual route is not significantly activating their allergic disease, but rather helping healing mediators be released. It’s pretty incredible that allergen particles can be both the problem and the solution, depending on the signal they send. But it makes sense because “allergens” are truly harmless themselves. SLIT has finally given me a fantastic and safe way to truly help all patients from mild to severe allergic disease so that no one is left out without an immunomodulatory option.
AAC: A few years ago we published an article about a Netherlands study that showed patient compliance with SLIT, which is better established in Europe than it is here, was lower than allergy shots. Last week I saw a presentation by a major figure in the field who showed similar data. She said the most important figure in getting good compliance is the doctor’s secretary who can call to remind patients. What is your experience with patient compliance? Also, she said that she doesn’t insist on SLIT patients carrying epinephrine. Where do you stand on that?
Nikhila: My experience with patient compliance with SLIT in private practice has been very good. I think that is because we make it a point to make sure that SLIT treatment is a good overall fit for the family before we start, and we make time up front to answer a family’s questions so that they understand how, when, and most importantly why they should properly take their doses. Additionally, we discuss what is and is not feasible for a family, and I take those factors as well as their medical situation into account as I formulate a personalized plan for them. As we go along, I tweak the plan as needed so that we can keep any symptoms from the allergen exposure in the treatment as minimal as possible. When the treatment is easy, families understand what they need to do and why, and the dosing doesn’t cause too many adverse effects, compliance is generally good. Families do have to take some responsibility for dosing properly on their own since the treatment is largely home-based unlike allergy shots, but most families we work with are motivated and we do our part as well to best set them up for success without too much inconvenience or stress. We certainly don’t have a secretary that calls and reminds patients to take their doses, and thankfully we have not found that to be needed at all. From what I have come across, compliance is lower when high doses are jumped into early on which leads to adverse effects and when proper education has not been allowed to take place. This often happens when treatments become standardized and patients are pushed through quickly. Thankfully, I have left that part of our health care system and am able to approach SLIT treatment in a completely different way for my patients.
My policy on epinephrine for SLIT patients is different for each patient. In an ideal world, I think every person, known to be allergic or not, should have epinephrine rescue readily accessible. Anyone can have a surprise allergic reaction at any time, not just those who have had one before. So I am always happy to prescribe it. For SLIT patients, for those who have epinephrine auto-injectors prescribed for their allergic conditions, I recommend that they bring them to their up-dose appointments. (They should anyway, because they should have them with them all the time.) However, for those on SLIT with no history or testing suggestive of severe allergic reaction risk, we discuss risks and the need for epinephrine and weigh all the factors. I will happily prescribe it, but that is not always what works best for a patient. It is my job to educate them and help them make the best decision for them. Carrying epinephrine in its current form certainly affects many aspects of a person’s lifestyle and routine, and it can be very expensive. So prescribing it just for it to sit in a drawer or never be picked up is also not useful if the patient’s risk for anaphylaxis is extremely low and they are not concerned. Since the method of SLIT that I do is overall so safe and nothing close to anaphylaxis from proper dosing has ever been an issue, I agree that from what I’ve seen, mandatory epinephrine carrying for certain types of SLIT treatment does not appear to be warranted and it should be discussed on a case by case basis.
AAC: Your website is quite detailed and clearly tilted in the interests of patients, including the creation of community. How did you arrive at this approach?
Nikhila: It’s just what we want to do. My husband and I see community and building strong relationships as the foundation of all good things in life, and we have both always been very service and community oriented. None of us do better alone than we do together with great and supportive people at our sides, and everyone’s health benefits from “TLC”. We were so tired of the often cold, competitive, and lonely nature of the standard, insurance-managed health care system in this country, both from the patient and physician perspectives. So when we decided to open our own clinic, we made sure to structure it based on our own values. Our patients become like family to us. We know our patients’ names, and their parents’ names if they are a child. We know about their favorite animal or toy if they’re a child or their hobby if they’re an adult. We give our young patients “superhero support” and “bottle buddies” to let them know that they are strong themselves but they are also not alone. We connect them to one another, and we have plans to do specific types of Allergenuity Health community events as we continue to grow. Knowing you are a part of a caring community can sometimes make all the difference, and we want our patients to never feel alone because once they’ve joined us, they never are.
AAC: Do you have any thoughts for your fellow allergists who are on the fence about offering new therapies or are firmly opposed?
Nikhila: My personal approach has always been simple – to make sure to keep an open mind about new or additional treatment possibilities that appear to make some scientific and common sense, and that has served me very well with my patients. But it has also not been easy to do so in this insurance-driven healthcare culture that so strongly restricts all of us to mass standardization and protocolization of healthcare and away from critical thinking, innovation, and personalization of care. So I completely understand why not all of my colleagues may embrace the same approach that I have. I guess I would encourage my colleagues to try hard to keep an open mind about reasonable therapies even if they are not interested in or willing to offer them, and to not dismiss a therapy or procedure based on summarized data without first trying to gain a better understanding of it. Though there are as many if not more terrible, unfounded therapies being pushed out there as there are great, underutilized therapies, if one or more of our allergist colleagues really stands behind a treatment, I would hope it would at least beg the question from fellow colleagues of “I wonder why?” and a subsequent “Let me reach out to my colleague and find out more.” The more we are open to listening to and learning from one another about things we have not thought deeply about or experienced ourselves, the better we can learn from our collective experiences and come together to help allergy patients. We don’t need to all offer the same highly specialized treatments, and in fact that would probably not be feasible because there are reasons that these treatments are highly specialized. But if we learn which of our colleagues is skilled at which treatment, and if we make an effort to understand what each treatment can offer patients, we can guide our patients to the best options for them whether or not we offer them, and that is what we are all here to do as the experts in our field.
AAC: Do you have final any thoughts for patients pondering their treatment options?
Nikhila: Choosing a treatment option is a very personal decision and there is no right or wrong. No single type of treatment is going to be the right choice for everyone, and thankfully there are several effective options available for patients and families to choose from (though some may require travel, as we have only been open a couple months and are honored to already be working with patients from 11 different states). SLIT offers significant benefits to the majority of allergic patients in a safe, easy, and convenient way, which is why I have chosen to specialize in comprehensive SLIT treatments and help make them more available to patients. But I also completely respect all the other treatments available and discuss them with patients regularly, including the option of avoidance, as each option has specific merits that may be a better fit for certain families.
In that light, I’ll share some final guidance here for families that may be trying to choose between starting with SLIT or OIT (or SLIT or allergy shots). Since each of these treatments has been proven effective to a substantial degree, it often really just comes down to thinking about your top priority/goal/concern and which treatment suits that best to start with:
- If you are concerned about a treatment’s risk of anaphylaxis, SLIT would be the better route for you.
- If your primary priority is being able to eat an allergenic food in large amounts as quickly as possible, OIT would be the better route for you.
- If you don’t like shots, SLIT would be the better route for you.
- If you have multiple allergens or some type of chronic allergic condition (eczema, asthma, seasonal allergies, etc), multi-allergen SLIT would be more helpful for you overall. SLIT would be a good initial foundation to calm down your immune system in general first if you are planning to later pursue OIT for one allergen in specific.
- If you need to know in real-time exactly what minimum amount of the allergen can likely be tolerated, OIT would be the better route for you.
- If your allergic child is very young, SLIT would be the better (and possibly only) safe immunotherapy option for you at this time.
- If your child doesn’t like the taste of the allergenic food, or if you cannot keep up with or don’t want to deal with the exercise, rest period, and other restrictions, SLIT would be the better option for you.
Thank you so much for the opportunity to speak with you and your readers.
Dr. Nikhila Schroeder is board certified in both Allergy & Immunology (adult and pediatric) and Pediatrics. She was born and raised in Wisconsin. She attended college in Cambridge, Massachusetts at the Massachusetts Institute of Technology where she obtained both Bachelor’s (2004) and Master’s of Engineering (2005) degrees in electrical engineering and computer science with concentrations in music biomedical engineering and music. She went on to medical school in Madison, Wisconsin and earned her Doctor of Medicine degree from the University of Wisconsin School of Medicine and Public Health in 2009. She then completed her Pediatrics Residency training program (2012) and Allergy/Immunology Fellowship training program (2014) both at the University of Virginia. From 2014-2017, she treated nearly 1000 patients with sublingual immunotherapy from all over the country. In 2018, Dr. Schroeder and her husband James Schroder decided to move their family to Charlotte, North Carolina and open Allergenuity Health Associates together in their vision, as a direct care comprehensive sublingual immunotherapy treatment center, to bring high-quality, scientific, comprehensive sublingual immunotherapy treatment regimens and a health care model that supports a strong patient-doctor relationship (including patients having direct access to their allergist) to the region. For more information go to http://allergenuityhealth.com/
Patient photo by permission of families, granted to Allergenuity
By Henry Ehrlich
A month ago we greeted the approval of TEVA’s entry into the epinephrine injector market with cautious enthusiasm. But we also questioned whether the new competition for EpiPen and Auvi-Q (and Adrenaclick, the perpetual afterthought) would be sufficient to drive down prices. Then we came across an article that posited it takes at least three competitors to take a meaningful bite out of the price tag. Thus we can welcome FDA approval of a low-dose version of Symjepi, which rounds out their product line—a high-dose version had already received a government okay, although we missed that. That would make three, or so it would appear. Unfortunately, this one is a pre-filled syringe instead of an auto-injector and would require special training for use.
Regardless, the competitive effects these new injectors represent are entirely notional for now since they are nowhere near the market. A time of shortage is not conducive to a price war. EpiPen, for generations the dominant player, is suffering from manufacturing problems and in short supply.
For the long-term, assuming EpiPen finds its footing again, we must wonder how many competitors there will be and whether that be enough to pressure Mylan. Much as we love Auvi-Q it is not a generic and must compete on the basis of coolness, ease of use, vocal capability, and for now ample supplies. Adrenaclick, like EpiPen, is manufactured by Pfizer, and like it is suffering from manufacturing problems that have led to shortages. So can we count it as one of the three competitors?
Thoughts on Shortages
The shortages are creating some interesting accommodations. For example, Walgreens has started offering Auvi-Q, the first time it has been offered at a retail pharmacy, instead of by mail.
Also, EpiPen has relaxed its 12-month replacement policy with the blessing of the FDA, extending it to 16 months. They are in effect admitting that the stricter standard was bogus. If it remains in place, instead of buying 10 injectors over a decade, the consumer would buy only about eight. That will be a big blow to the bottom line.
And as a reminder, the list of Chinese imports subject to tariffs included epinephrine the last time we looked. If there were a sudden rush to build strategic epinephrine manufacturing facilities the cost to consumers would skyrocket.