This summary was compiled from the tweets posted by allergists/immunologists who attended the 2013 annual meeting of the American Academy of Allergy Asthma and Immunology (AAAAI) (see the list at the end). The tweets were labeled #AAAAI. The text was edited and modified by me.
Wayne Shreffler @WayneShreffler: A strong message from Dan Rotrosen, Director of DAIT at NIAID of the NIH: we want more grant applications on food allergy.
Changing concepts in food allergy
Hugh Sampson, MD commented on the changing concepts in food allergy in the past 3 decades.
Questions regarding food allergy have become more sophisticated over time. As our understanding improves, we ask harder questions.
Food allergy has become a global issue, with increasing prevalence over time. 0.1-0.5% years ago, to 3-4% now. For example, peanut allergy has tripled since 1997. What changed since 15 years ago?
In Australia, 16% of children had sensitization to egg and half had a positive challenge. Highest in the world.
There has been a 50% increase in food-induced anaphylaxis over last decade. However, there are no good data on prevalence of fatal reactions.
Delayed introduction of solid foods was previously recommended. However, in some cases, early introduction is associated with less sensitization.
As dietary avoidance has become more stricter, we see a temporal association with increase in the time taken for food allergy to resolve.
We have also learned that many milk and egg allergic children can tolerate these foods when they are extensively heated, or baked. Apparently muffin is the food of choice for baked egg challenge - not cake.
Might the consumption of baked goods be providing children with a non-standardized oral immunotherapy to milk/egg? Does strict avoidance, even in those children who might pass a baked-good challenge, prevent children from gaining benefit?
Predictive values have been developed for food-specific IgE and likelihood of clinical reactivity. Editor’s note: Similar predictive values exist for the size of the wheal on skin testing.
8 foods cause 90% of food allergies (click to enlarge the image). The likelihood of a negative oral food challenge is shown in relation to the respective values of skin prick test (SPT) and serum IgE (sIgE):
IgE to Arah 2 in peanut allergy
Component resolved diagnostic testing can help tease out the likelihood of "true" reactivity vs. cross-reactivity for certain foods. Editor’s note: The only commercially available test in the US is for peanut and it costs $300 (not paid by most insurers). Skin testing and oral food challenges continue to have a very important role.
Nearly 100% of those with IgE to Arah 2 greater than 1.63 kU/L react to ingested peanut. It doesn't predict the severity of reaction or threshold dose. Ara h2 testing is superior to sIgE for whole peanut, and other components for diagnosis of clinically-significant peanut allergy. Source: JACI 2012.
There are suggested guidelines for use of component testing for peanut allergy - a nice article in the inaugural issue of JACI InPractice.
New questions: What are the basic underlying mechanisms of tolerance? What about non-IgE mediated allergy? Biomarkers/genetics?
Early dietary exposure to food allergens and development of food allergy
Mona Kidon, MD discussed early dietary exposure to food allergens.
Are there data to support timeline of ideal dietary introduction for various commonly allergenic foods? No.
Late dietary introduction does not appear to protect against allergic disease. In fact, early introduction of cow's milk (first 2 wks of life) appears to protect against cow's milk allergy (Israeli study).
Introduction of egg before the age of 4 months was associated with a lower rate of egg allergy than introduction after the age of 12 months.
Early complementary feeding may be associated not only with lower risk of food allergy, but also other of atopic diseases.
Early exposure to fish was associated with lower rates of fish allergy (if you're Chinese), but higher if not Chinese (Singaporean study).
Epinephrine usage is higher in northern hemisphere. Role for vitamin D?
Breastfeeding appears to protect against food allergy in some countries, but it is associated with food allergy in others. Role for genotype?
Food allergy (FA) is profoundly multifactorial. Food, environment, timing, genetics, breastfeeding, locale and more play a role. It is very complicated.
Food allergen sensitization and relationship to atopic dermatitis
George Du Toit, MD discussed food allergen sensitization and relationship to atopic dermatitis.
A significant percentage of children with atopic dermatitis are poly-sensitized to foods. Editor’s note: That does not mean they are allergic to those foods.
Onset of sensitization is likely in infancy. Egg allergy, eczema, eosinophilia and black race are risk markers for peanut sensitization. Avoidance of peanut during lactation may be associated with higher rates of peanut sensitization.
SLIT and OIT for food allergy
Wesley Burks, MD discussed SLIT and OIT for food allergy. There may be an analogy between aeroallergen IT and food allergy IT: they may need chronic treatment and to start with younger kids.
Dr. Burks believes these proactive therapies are not yet appropriate for routine implementation. Dosing and timing are yet to be worked out.
OIT - oral immunotherapy is swallowed, whole food.
SLIT - sublingual immunotherapy - extract is held under the tongue and then swallowed.
The paradigm is to begin at low dose, and escalate over time to maintenance dose. Sublingual doses are generally lower than OIT.
The amount of time on maintenance dose makes a big difference. Longer duration of OIT is more effective.
Immune tolerance and allergy - can we produce true tolerance?
Desensitization is not the same as tolerance. Tolerance infers protection after treatment has stopped.
Is food allergy associated with a defective T cell response? Several studies now indicate that food allergy is related to defective T regulatory response. Here is a model of T cell dysregulation : Foxp3 mutation --> IPEX.
Children who have outgrown non IgE-mediated milk allergy demonstrate detectable T regulatory activity. Both allergic and non-allergic individuals mount T and B cell responses following exposure to peanut, difference is in TH2/1 balance. Allergic individuals form peanut-specific IgE, non-allergic form peanut specific IgG - IgG is a normal response to a foreign protein.
What is true tolerance? This is different in different disease processes. Clinical tolerance and immunologic tolerance are not identical. Tolerance is not a lack of immune response. It is a DIFFERENT immune response.
Some studies suggest that when peanut tolerance develops, existing cells do not change, but rather, new populations of cells arise. Peripheral T cell tolerance is key.
Peanut OIT changes antigen specific Tregs and suppresses Th2 response to peanut.
Can we produce long-term tolerance? CoFAR Peanut SLIT study will try to answer that question. How long can maintenance dose be held before "sustained unresponsiveness" can be claimed? We still don't know.
Dr. Burks: We really don't know how long it'll take to develop true immune tolerance in peanut immunotherapy - 4 or 12 months?
41% patients appear to be tolerant after 1-3 years of peanut immunotherapy.
With peanut 10 g maintenance dose, after 4 months off OIT, there was a marked loss of unresponsiveness to food challenge. Interestingly, peanut-specific IgE levels decreased in all patients over time, even those who did not tolerate challenge at end of study.
In Burks' studies: OIT for peanut lead to passing a 5000 mg challenge while SLIT was only 1000 mg. Both of these peanut doses are well above "accidental" exposure levels though and Burks thus thinks SLIT is still useful in trials.
Hazelnut spread does not generally contain sufficient amounts of hazelnut protein for oral food challenge (@nmchase: #NoNutellaForYou).
Milk study: Patients started with SLIT lead-in, then split into 1) maintained SLIT, 2) low-dose OIT, 3) high-dose OIT. A dose-dependent response was noted.
Is desensitization a prerequisite to the development of long-lasting tolerance to foods? How long off therapy is long enough to claim tolerance? 1, 4, 12 months? Not all treated patients are able to stop therapy (OIT). Is tolerance the goal? Is it even possible in severely allergic patients? Might desensitization be sufficient? This is all up for discussion.
There is only 1 RCT of peanut OIT. There are not enough data to justify widespread use. For Milk OIT, for every 11 patients treated, 1 required epinephrine. Drop out rates during food OIT studies are 20-30%.
Critical knowledge gaps
Critical knowledge gaps include: 1. desensitization, 2. side effect profile, 3. mechanistic studies, 4. tolerance.
The critical gaps in OIT/SLIT for food allergy mean it is not ready for routine clinical use.
The end goal is to have an active treatment. Current dosing is based on educated guesses.
What do families really want? Most would be satisfied with desensitization, not necessarily requiring tolerance.
FAHF2 Chinese herbal formula
Food allergy herbal formula (FAHF-2) contains 9 herbs and is currently in trials. Clinical phase I trials of FAHF2 showed that is probably safe. Phase II trial is underway but requires 30 pills/day!
Japanese Experience with Anaphylactic Food Allergies
Motohiro Ebisawa MD PhD discussed OIT for Anaphylactic Food Allergies.
Common allergies in Japan are shellfish, fish, buckwheat, chocolate. Editor’s note: Chocolate allergy is vanishingly rare. The so-called “chocolate allergy” is typically due to allergy to some of the ingredients such as milk, soy or tree nuts.
The most important risk factors for anaphylactic food allergy include asthma, alcohol intake, and certain medications.
A recent fatal reaction to cow's milk of a Japanese schoolgirl again demonstrated the importance of anaphylaxis training for school staff.
Patients with elevated IgE to ovomucoid are unlikely to spontaneously outgrow hen's egg allergy.
A nationwide study of OIT in Japan included 49 participating institutions! There were 2 protocols (inpatient rush and outpatient slow). Over 400 patients were enrolled in the OIT study (multiple foods). There was a high rate of complications during the rush phase of protocol. There were better results with egg than cow's milk OIT. Wheat OIT was effective at inducing tolerance, but plagued with difficulty while updosing. Among all studied foods, cow's milk OIT was the most difficult to complete successfully. Those patients who reacted to oral food challenge post OIT tended to have severe reactions. There also existed a risk of severe reactivity in those patients who temporarily halted OIT due to viral infection.
A suppression of basophil activation was noted during OIT, but it was statistically significant only after longer-term therapy (longer than 24 mos). Allergen-specific IgG4 increased by month 12 of OIT for both wheat and peanut.
Oral Mite Anaphylaxis
Mario Sanchez-Borges MD discussed Oral Mite Anaphylaxis. (also known as pancake syndrome)
There was a recent case report of a patient with angioedema after eating pancakes made from wheat flour contaminated with storage mites (B. tropicalis). This is more common in tropical areas. There have been 135 published cases, but likely they are under-reported. It may be mistakenly diagnosed as wheat allergy.
Here is an abstract on oral mite anaphylaxis: http://www.ncbi.nlm.nih.gov/pubmed/15765735
Mites love traveling! Example: an allergist bought beignet mix in New Orleans. His severely-mite allergic daughter anaphylaxed upon eating them.
Flour can be contaminated, and mites are not visible to the naked eye. Corn flour can also be contaminated with mites.
Why is cooking/heating not reducing reactions? Some mite allergens are thermo-resistant (heat-stable).
Interesting tidbit: a large proportion (66-80%) of the patients with oral mite allergy have evidence of NSAID hypersensitivity.
What can we do to decrease risk? Store flour in refrigerator, use sealed glass/plastic containers, and keep ambient humidity below 50%.
Allergists are on Twitter - follow them
Allergists increased Twitter use 470% in one year - 25 allergists reached 250,000 individuals from the 2012 #AAAAI meeting (see the references here). This summary was compiled from some of the tweets posted by the following allergists:
This is a list of the allergists who used Twitter to post updates from the 2013 #AAAAI meeting. The list is open for edit, please feel free to add your own info.
I would strongly encourage you to post updates on Twitter from the CME conferences that you are planning to attend in the future. Here is how to do it: Twitter for Physicians: How to use Twitter to keep track of the latest news and scientific meetings, and share information with colleagues and patients.
Disclaimer: The text was edited, modified, and added to by me. This is one of a series of posts that will be published during the next few weeks.
Comments from Twitter and Facebook:
Sharon Wong: Thanks so much Dr. Ves!!! I was following along during the conference but like reading your summary so much more! Looking forward to more updates.
AllergyNotes: You're welcome. Yes, I like compiling the summaries of the tweets too - it puts the brief 140-character updates in context.
Sharon Wong: Did you have a workshop/seminar to show the doctors on how to use social media to share information? I think that's really great and have learned so much from the doctors who write blogs, answer general questions, and share information. Thank you!!!
Tricia Gavankar: Sharon Wong, did you pick up on the part about cow's milk? According to Burks of all the foods studied, cows milk proved the most difficult... it really makes sense to me-especially after what M went through. It said 1 out of 11 needed epi during milk OIT....
AllergyNotes: Yes, we did have a talk and a seminar on social media use by allergists. There were a lot of questions and strong interest in the topic. We also had the first international tweet-up of allergists which was one of the highlights of 2013 #AAAAI for many of us.
A Russell BSN RN AEC @AllergyEducator: Great #FoodAllergy Twitter summary from 2013 AAAAI meeting ow.ly/i8DCK by @DrVes
@DrVes: there are more summaries to come - my colleagues did a great job tweeting 2013 #AAAAI
A Russell BSN RN AEC @AllergyEducator: Great! Yes, they did an amazing job tweeting-substantive & fast. Also interesting 2 see what they viewed as noteworthy 2 share.
@DrVes: this is one of the greatest things about doctors tweeting a meeting - they self-select what they find useful, in real time.
A Russell BSN RN AEC @AllergyEducator: Yes, a fascinating aspect of reading it all-esp if @ same presentation! Thank you so much 4 being a great hcsm leader/expert Ves!
@AllergyNet: There is an amazing amount of info here. Thank you
@AllergieVoeding: Very good!!! and thx
Academic centers that have research programs involving desensitization to foods http://buff.ly/185849p and http://buff.ly/18584GB