You might think that people are kidding around when they tell you they have food allergies. And, it is true that some types of food allergies are only associated with minor symptoms. But others, such as seafood allergies and peanut allergies can be deadly.
“Cod was cooking on the stove when 11-year-old Cameron Jean-Pierre arrived at his grandmother’s home in New York.
Cameron, who had a known allergy to seafood, started to wheeze during the visit this week, so his father said he reached for his son’s asthma medication. But this time, the nebulizer machine that Cameron had used during allergy attacks in the past, did not seem to be working — the young boy could not breathe in the air, his father said.
He was rushed to a nearby hospital, where he was pronounced dead.”
This case is extreme. But it illustrates that even a vanishingly small amount of allergen suspended in the air can precipitate severe, even deadly anaphylactic shock.
The case of peanut allergy
Fish allergy, in fact, is quite uncommon. Peanut allergy, on the other hand, is becoming increasingly common. The reasons for this are unknown,
Between 1% and 2% of people in the U.S., the U.K., and several other countries are allergic to peanuts. This is roughly triple the rate in the mid-1990s.
Although fatal reactions to food allergies are rare, it is important that we learn in minute detail what causes these reactions so that we can intelligently devise effective treatments.
First, let’s explore the science behind serious food allergy reactions.
What is anaphylaxis?
Anaphylaxis is a serious allergic reaction that is rapid in onset. Untreated, it can lead to death. It typically causes more than one of the following:
- An itchy rash
- throat or tongue swelling
- shortness of breath
- low blood pressure
These symptoms typically come on in just over minutes to hours.
The discovery of anaphylaxis
Anaphylaxis was first described in 1902 when scientists Charles Richet and Paul Portier tried to immunize a dog with a toxic sea anemone extract.
They were surprised when the dog died 25 minutes after the second injection. They named this reaction anaphylaxis. Richet earned the Nobel Prize in 1913 for his work showing that immune responses could be harmful as well as beneficial.
It is only recently, however, that we started gaining a deeper understanding of what is happening on the molecular level. Basically, the process of developing an allergy to food (including peanuts) is made up of 2 phases:
- Sensitization to an allergen, and
- The allergic reaction that occurs once a person is sensitized.
So, how do people get sensitized?
There are specific cells, called dendritic cells, that reside in all the body surfaces that come in contact with the external environment. The skin is an obvious one, but so are the GI tract, the respiratory system, and the genitourinary tract.
The dendritic cells are basically sentries. Their role is to do the following:
- Send long extensions of their membranes to continuously sample the environment
- Trap all kinds of molecules, including certain foods and drugs as well as insect venom
- Fish out these foreign molecules from the microcirculation that lines the inner side of the skin, the gut, and the respiratory tree (trachea, bronchi, and the small branches called bronchioles).
Let’s say that a peanut particle is caught by the dendritic cells. A type of lymphocyte called T helper type 2, or Th2, that happens to be specific to peanut allergen will recognize its prey, bind to it, and carry it to another type of lymphocyte called B cell. This cell will then start producing a peanut-specific immunoglobulin (antibody) called IgE.
So now we have a peanut-sensitized individual, with peanut-specific IgE circulating and looking for the specific allergen (the peanut in this case) for which they were created.
And, here is how the allergic reaction is triggered.
The sensitized individual eats peanuts or anything that contains even minute amounts of peanut allergen.
Once peanut protein gets into the circulation it gets picked up by peanut-specific IgE. These antibodies, in turn, present their catch to specialized cells that line the blood vessels. These cells are called mast cells.
Unlike the Th2 cell that is smart, in the sense that it had specificity to it, the mast cell is dumb, it has no specificity to it. It will get activated by any antigen as long it is presented by an IgE-antigen complex.
But what the mast cell lacks in intelligence it makes up with firepower. It is loaded with histamine, leukotrienes, and prostaglandins. And it releases them into the circulation in an explosive bolus. These chemical mediators are inflammatory and have widespread effects on many systems.
What happens once the mast cell is triggered?
- Skin: the reaction causes itching, urticaria (hives), and angioedema (swelling).
- Gastrointestinal tract: it causes incontinence, diarrhea, and pain.
- Respiratory system: the reaction is manifest by shortness of breath and coughing.
The cardiovascular system effect is primarily due to profound vasodilation, causing hypotension and either rapid heart rate. Or, in the advanced stage of the reaction, a slowing heart rate and very faint pulse.
Acute reduction of blood supply to the brain is manifested in headache, confusion, anxiety, and loss of consciousness.
All these myriad effects take place rapidly and simultaneously. This is why they are so dangerous. And, it is why anaphylaxis is potentially fatal.
What can we do about anaphylaxis?
- If symptoms of anaphylaxis develop, don’t wait to see if things will get better. They usually get worse. Call 911 immediately!
- If you have an epinephrine autoinjector, such as EpiPen, available administer it intramuscularly into the outer mid-thigh.
- If wheezing develops use a bronchodilator inhaler.
You may also take an antihistamine, but don’t rely on them- they are too weak to counter the massive histamine release. And, they work too slowly.
At the hospital, the staff will probably administer epinephrine IV (if the severity of the reaction calls for it), hydrocortisone to suppress the widespread inflammation, and IV fluids to counter the drop in blood pressure.
How can we prevent a major food allergy reaction?
First and foremost, avoid coming in contact with the offending allergen, such as peanuts. But not only the nuts themselves, peanut butter, peanut butter sauce, even foods that came in contact with peanuts and contain vanishingly small amounts of it can precipitate a severe attack.
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Immunotherapy: fighting fire with fire?
For many years physicians had nothing to offer to peanut and other serious food allergy patients other than meticulous avoidance of the allergen.
This is in contrast to the treatment of non-food allergens, like bee venom or pollen of specific plants. Allergists have been successfully treating them with weekly injections of the allergens. This treatment, called immunotherapy, usually starts with minute doses of the allergen. Over time the dose is slowly increased.
The theory behind this treatment is that another class of antibodies called IgG4 is generated which counteracts the activity of IgE. This is the theory, however, the science is a bit hazy.
Still, for non-food allergies, this treatment works moderately well. What about food allergies? Brief testing decades ago indicated that shots for food allergies weren’t safe.
Around the mid-2000s, scientists began to feed children the allergen instead. Lab results showed that oral desensitization resulted in decreased mast cell reactivity, an increase in IgG4, and also an increase in IgA.
This immunoglobulin, IgA, is located in the gut wall and provides a barrier against the allergen entering the circulation. These are lab results, but reliable data of clinical outcomes are still unavailable. Therefore, until recently most guidelines called for treatment in medical centers only, and with great caution.
A breakthrough in the treatment of food allergies
In 2011, food-allergy researchers, physicians, and parents of children with food allergies sponsored a symposium at Harvard Medical School in Boston to standardize goals and strategy for oral immunotherapy efforts. About 60 people attended.
But no pharmaceutical company showed interest. So the group funded a start-up company, Aimmune, to develop oral immunotherapy for peanut allergy.
Researchers, sponsored by Aimmune, recently published the results of a phase 3 trial of oral peanut allergy desensitization using a peanut-derived investigational biologic oral immunotherapy drug called AR101. 496 of the 551 participants were children and adolescents 4 to 17 years of age, the rest were adults.
There were three phases to the trial:
- An initial dose-escalation phase
- An increasing dose phase
- A 24-week maintenance phase.
During the closely supervised one-day initial dose phase, participants ingested the AR101 in doses that increased from 0.5 mg to 6 mg.
In the increasing-dose phase, the dose was increased gradually every 2 weeks from 3 mg to 300 mg. And during the 24-week maintenance phase, participants took a single dose of 300 mg per day. This is equivalent to one solitary peanut.
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And the results?
Before participating in the desensitization study, subjects could consume less than half a peanut. After 1 year of treatment with AR101, two-thirds of them could consume a cumulative dose of approximately four peanuts.
In the control group, on the other hand, only 1 in 25 participants could consume this amount. In the 56 participants older than 17 years of age, no effect of AR101 treatment was shown.
Side effects during the intervention period that led to withdrawal from the trial occurred in 11.6% of the active-drug group and 2.4% of those of the control group. Epinephrine was used by 14.0% of the participants in the active-drug group as a result of reactions to treatment.
Food allergies: it’s not just peanuts
The EAT Study
These results encouraged researchers to cast a wider net and test for more allergenic foods. A paper published in 2016, describes a randomized controlled trial known as the EAT study. It was conducted in the UK where infants between the ages of 3 and 6 months continued breastfeeding with sequential introduction of these six allergenic foods
- cow’s milk
- hard-boiled hen’s egg
- whitefish (cod)
The control group continued breastfeeding without the introduction of allergenic foods.
The study fell short of its target because of variable compliance with the protocol regimen. However, it did allow the conclusion that early introduction, before 6 months of age, of at least some amount of multiple allergenic foods appears achievable and did not affect breastfeeding.
The PETIT study
A Japanese study published in 2017, known as the PETIT study examined the feasibility of early introduction of egg into the diet of infants with eczema (a skin condition indicative of allergic propensity).
Participants in the treatment group ate 50 mg of heated egg powder per day from 6 months to 9 months of age. And, then, they consumed 250 mg per day until 12 months of age.
Participants were aggressively treated for eczema at entry and maintained control without exacerbations throughout the intervention period. The control group did not receive egg powder but did receive the same treatment for eczema.
This trial was terminated on the basis of the results of the scheduled interim analysis of 100 participants. It showed a significant difference between the two groups. Four [9%] of 47 participants had an egg allergy in the egg group vs 18 [38%] of 47 in the placebo group.
Thus far oral desensitization does not purport to be a permanent cure. An allergic person may need to continue treatment ad infinitum, at least as far as we know now.
Follow up of long duration is needed to give us more confidence regarding the permanence of the immunologic tolerance induced by early introduction of allergenic foods.
The USDA 2020 Dietary Guidelines Report
The United States Department of Agriculture (USDA) recently published its 2020-2025 Dietary Guidelines Report for Americans (DGA) Report. It specifically addresses food allergies in children, stating:
“Strong evidence suggests that introducing peanut in the first year of life (after 4 months of age) may reduce risk of food allergy to peanuts [Grade: Strong]. This evidence is strongest for introducing peanut in infants at the highest risk (with severe atopic dermatitis and/or egg allergy) to prevent peanut allergy, but is also applicable to infants at lower risk.”
It also states that,
“Moderate evidence suggests that introducing egg in the first year of life (after 4 months of age) may reduce risk of food allergy to egg [Grade: Moderate].”
The report goes on to state that there is limited evidence to support the same for cow’s milk products, seafood, wheat, and soy. More research must be done to rule in or rule out the benefit of early antigen introduction for these foods.
The bottom line when it comes to food allergies
Food allergies, and peanut allergy, in particular, have been neglected diseases until quite recently. But the good news is we now have clinical trials that suggest that some people may experience improvement in their symptoms after oral desensitization therapy.
Additional Articles by the Author:
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Your Money or Your Life? The High Cost of Life-Saving Drugs
Published 3/17/19. Updated 10/25/20
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Dov Michaeli, MD, PhD
Dov Michaeli, M.D., Ph.D. (now retired) was a professor and basic science researcher at the University of California San Francisco. In addition to his clinical and research responsibilities, he also taught biochemistry to first-year medical students for many years.
During this time he was also the Editor of Lange Medical Publications, a company that developed and produced medical texts that were widely used by health professionals around the world.
He loves to write about the brain and human behavior as well as translate knowledge and complicated basic science concepts into entertainment for the rest of us.
He eventually left academia to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early-stage biotech company that developed products to improve post-surgical pain control.
Now that he is retired, he enjoys working out for two hours every day. He also follows the stock market, travels the world, and, of course, writes for TDWI.