Wine Allergy

Wine is made from grapes and like grape, true allergic reactions are, thankfully, rare. If a grape allergy is suspected, it can be easily ruled out or confirmed with an allergy skin test.

Many people do however complain of problems when they drink wine and yet are not allergic to grape. If these reactions to wine are not an allergy to grape then what is causing the problem?

In most cases, ill effects reported after drinking wine are the result of a sensitivity to preservatives in the wine or to alcohol.

Sulfite Sensitivity

Sulfites are routinely added in the winemaking process as a preservative to prevent the growth of bacteria and unwanted yeast. Without sulfites, most wine will turn to vinegar. These sulfiting agents – sulfur dioxide, sodium potassium sulfite, bisulfite, and metabisulfite – can be added at different times and in varying amounts depending on the type of wine being made. In general, white wine has a higher sulfite content than red and sweeter wines have more sulfite than drier wines.

All wine contains naturally occurring sulfites so finding a wine that is completely sulfite-free would be unlikely. However, some winemakers offer organic wines with no added sulfites. In the US, new regulations in place since 2012 require that all wines with sulfite levels greater than 10 mg/L (ppm) be labeled as containing sulfites. Similar guidelines have been adopted by the EU and Britain.

“Sulfite Free” actually means no sulfites were added to the wine

Exposure to sulfites has been associated with a number of symptoms in sensitive individuals including anaphylaxis and hives. Although asthmatic symptoms are uncommon in patients with sulfite sensitivity without a history of asthma, serious and potentially life-threatening asthmatic reactions can occur in patients already under treatment for asthma.

In addition to wine, sulfites are added to a variety of foods including fruits, vegetables, and seafood to preserve freshness and prevent browning. Similar to wine, the FDA requires labeling on any food or beverage with greater than 10 mg/L (ppm) of these preservatives.

Ethanol Sensitivity

In addition to grape juice and preservatives, wine (of course) contains alcohol, specifically ethanol. As discussed in more detail in an earlier post (here), some individuals develop serious symptoms when they consume any form of alcohol. This is caused by a deficiency in a liver enzyme called aldehyde dehydrogenase. Without this enzyme, high levels of the chemical acetaldehyde accumulate in the blood. Acetaldehyde can cause symptoms that resemble an allergic reaction including facial flushing, nasal congestion, respiratory difficulty, nausea, and headaches when they drink any form of alcohol.

Without the enzyme aldehyde dehydrogenase, acetaldehyde levels increase after drinking alcohol causing symptoms

Some reports suggest that wine may contain varying amounts of acetaldehyde in addition to ethanol. This may explain why some people are able to tolerate certain varieties of wine but not others.

What About Yeast?

Yeast is the engine that turns common grape juice into highly valued wine. The industrious yeast eat the sugar in the grapes and as a waste product produces ethanol. Although wild yeast found natively on the surface of harvested grapes has been used in winemaking for centuries, most winemakers today add yeast to ensure consistent results. Saccharomyces cerevisiae is the variety of yeast most frequently used in winemaking. It is also the yeast used in beer making and baking and is commonly called brewer’s yeast.

Saccharomyces cerevisiae yeast

Although brewer’s yeast is an allergen, there are few reports of allergy to the yeast causing problems drinking wine or beer or eating bread. It is, however, a significant cause of occupational allergy for those exposed to high levels of airborne yeast in the workplace such as a baker. As an interesting side note, this yeast also grows on our skin and can be a cause of yeast infections in women.

Why is brewer’s yeast a problem in the air and not in wine? Although wine production starts with living, growing, feasting yeast cells, rising levels of alcohol in the wine will eventually kill a large percentage of the yeast and are removed from the final product when they precipitate out.

Precipitated yeast in a wine bottle

How Do I Know What is Causing My Problems When I Drink Wine?

As mentioned above, allergy to grape can be determined with an allergy skin test. Allergy testing is also available for sensitivity to Saccharomyces cerevisiae yeast, although a positive test result does not necessarily mean that yeast in the wine is causing problems. Diagnosing alcohol and sulfite sensitivity is more challenging and requires a careful history by a physician experienced with these syndromes and a controlled food challenge.

Beer

Beer Allergy

Beer is the third most popular beverage, behind water and tea. In spite of this, true allergic reactions to beer are rare.

Beer contains four primary ingredients:  Water, malted barley, yeast, and hops.
Barely that has been partially sprouted and then dried is called malt. Malting develops enzymes that break down the starches in the grain to sugars that can be fermented by yeast.  Yeast eats the sugars and produces gas (CO2) and ethanol as waste products.  Hops is added for flavor and as a preservative.  

Nutritionally, beer is mostly water and sugar with a little protein.  A can of regular beer contains about 26 grams of sugar and 1.5 grams of protein. The rest is water.  

For the most part, all allergens (things that cause an allergic reaction) are intact proteins.   Most of the protein in beer is in the form of enzymes that are released from barley in the malting process. After the malting process, when the enzymes have done the work of breaking down complex carbohydrates to be used by the yeast, the mixture is boiled.  Boiling coagulates and precipitates a lot of the protein which is then removed by filtration from the final product. The protein that remains is likely to be in the form of heat resistant enzymes.  

For this reason, the intact protein profile, and hence the allergenicity, of beer is quite different from that of the grains the process started with.   
This may account for the fact beer, the third most widely consumed beverage on the planet, rarely causes true allergic reactions.  As discussed here, allergic-like reactions to alcohol is another story.

Sorting out the cause of a suspected allergic reaction to beer can be a challenge. Allergy skin testing to the most common beer ingredients including barley, malt, hops, and wheat is available and is the place to start. Frequently, a carefully controlled food challenge is required.

Alcohol Allergy

Can you be allergic to alcohol? 

The short answer is, “Yes”.  The full picture is a bit more complicated.

To start we need to distinguish true allergic reactions to alcohol from what we might broadly call “adverse reactions”. In an adverse reaction, bad things happen when you consume an alcoholic drink but the mechanism for the reaction may or may not be allergy.  

When we discuss the “alcohol” in the alcoholic beverages we drink we are referring to the chemical ethanol. There are other alcohols such as methanol (wood alcohol) that have a variety of applications, but most are too toxic to drink.  That brings up an important point.  

Alcohol is a Poison

Ethanol is a toxin. It’s primary toxic effect is to temporarily depress our central nervous system. This is where we get the term “intoxicated”.  Very high doses can cause respiratory depression, coma, and death. 

Ethanol is detoxified or metabolized in the liver.  If we do not detoxify the ethanol we drink, levels in the body will continue to increase until we lose consciousness.  This detoxifying process depends on an enzyme in our liver called alcohol dehydrogenase and produces the chemical acetaldehyde. Acetaldehyde is metabolized further by the enzyme aldehyde dehydrogenase.    We consume ethanol.  The ethanol is converted to acetaldehyde in the liver and the acetaldehyde is detoxified further by the enzyme aldehyde dehydrogenase.  This last part is important because without the enzyme aldehyde dehydrogenase, the body cannot get rid of the acetaldehyde and it will accumulate in the body. Acetaldehyde is not as toxic to the brain as ethanol, but high levels can cause facial flushing, nausea, headaches, and rapid heart rate. 

An estimated 30-50% of East Asians (Chinese, Japanese, and Koreans) do not make sufficient amounts of the enzyme aldehyde dehydrogenase and will get sick when they drink alcohol.

This reaction to alcohol has been called the alcohol flush reaction.   In addition to flushing, drinking alcohol can cause nasal stuffiness and asthma-like respiratory symptoms in individuals who have a deficiency in aldehyde dehydrogenase.  

Redness of the skin, nausea, nasal congestion and difficulty breathing – all this sounds like a typical allergic reaction.   It is not a true allergic reaction however because the mechanism is the accumulation of a toxin in the body of susceptible individuals because of an enzyme deficiency and not because of an immunologic allergic sensitivity.

People with a sensitivity to aspirin (aspirin-induced respiratory disease) may also experience an increase in respiratory symptoms after drinking alcohol, even if they have not taken aspirin. 

In addition to ethanol, some alcoholic drinks, particularly wine, may contain high levels of other chemicals such as sulfites and even acetaldehyde. (reviewed here)

All of these very unpleasant symptoms caused by drinking alcoholic beverages are either the direct effect of ethanol, metabolites or other chemicals present in the drink.   I review more about allergic reactions to beer, here, and to wine, here.

Macadamia Nut Ice Cream

Diagnosing Food Allergy: The Food Challenge

Fourteen year old Hanna was at the mall with friends when she discovered she was allergic to macadamia nut.  This fact became clear when she nearly died. She had only taken a few bites of the ice cream with macadamia nut from Cold Stone Creamery.  She had eaten a variety of nuts on numerous occasions without problems, her favorites being almond and hazelnut, but his was her  first time to try this macadamia nut.

By the time paramedics had arrived, she was covered in hives, felt dizzy, had vomited, and could not stand

Immediately her mouth began to burn and after a few minutes her face turned bright red.  She felt itchy all over, her eye lids and lips began to swell and she had a hard time breathing.  By the time paramedics had arrived, she was covered in hives, felt dizzy, had vomited, and could not stand.  The paramedics did not waist anytime:  A syringe filled with epinephrine was jabbed into her upper leg, an IV was started and connected to a larger bag of fluid and she was taken to the nearest hospital.  When she arrived at the emergency room she was feeling better, the hives were clearing and she could breath easier.   She was able to go home after several hours.

Trip to the Allergy Office

She was seen in our office the next week for allergy testing.  A small drop of macadamia nut extract was placed on the skin of her back and gently pricked. After 20 minutes the test was read by measuring the size of any swelling at the test site, the “wheal” as well as any redness or erythema.  The size of the test wheal is compared with a negative (saline) and a positive (histamine) control. A wheal that is 3-4 mm larger than the negative control is a positive test. Hanna’s macadamia test was over 20 mm!

For Hanna, the diagnosis of allergy to macadamia nut is clear.  She has a compelling history of typical allergy symptoms appearing within minutes of exposure and a strongly positive result on allergy skin testing to the allergen in question.  The recommendation is also clear.   No macadamia nuts…EVER. She will also need to carry an EpiPen in case of accidental exposure.  Having it nearby could be life saving.

Now let’s back up a notch.

Let’s suppose Hanna stayed home from the mall that day to study for a test and mom decided to make an appointment with an allergist to talk about Hanna’s itchy eyes and sneezing during the spring.   In this alternate universe, Hanna has never eaten macadamia nut.    During the visit mom mentioned that Hanna complained of itching of the mouth with almonds and hazelnuts when she was a child  but is now eating both nuts fairly regularly without problems.  She would like to check for tree nut allergy though, “just to be sure”.

Allergy testing is completed and the results show strongly positive reactions to spring tree and weed pollen.  Testing to the tree nuts showed an 8 mm reaction to almond, 6 mm reaction to Hazelnut, both moderately positive.  Macadamia nut showed a 20 mm skin test reaction.

What is the diagnosis?  Is Hanna allergic to almond and hazelnut?

To answer this important question, we need to start with how we define “allergy”.  The definition of allergy has two parts:

  1. A history of  symptoms (rash, abdominal pain, breathing difficulty, etc.) on exposure to an allergen
  2. A positive result to the suspected allergen on a skin or blood test for allergy

We like to have both to make a diagnosis of allergy. Even though Hanna’s allergy test is positive to almond and hazelnut, she has eaten both frequently without problems.  By definition therefore, she is not allergic to almond or hazelnut.

“Why are the almond and hazelnut allergy tests positive if  she is not allergic.”

There are a number of possibilities but it is most likely that the positive skin test reaction is the result of cross reaction between proteins in the tree nut and very similar proteins in the tree pollen that she is sensitive too. (To learn more about false positive allergy tests, go here.)

Although Hanna understands this explanation (“sort of”) she is still concerned about eating almond and hazelnut now that she knows that the allergy test was positive.  She asks if there is another test that will prove she is not allergic.

In fact, there is….

The Double Blind, Placebo Controlled Food Challenge

The double blind, placebo controlled food challenge is considered the gold standard for diagnosing food allergy.  In this test two foods are prepared, the test food and a placebo food made to look and taste like the test food.  Neither the patient nor those conducting the test  know which is the true food and which is the placebo until after the test is completed.  The use of the placebo removes the chance that symptoms may be related to the patient (or test giver) having symptoms caused by anxiety.

Because of difficulty associated with developing a suitable placebo for every test food, double blind, placebo controlled food challenges are infrequently done.   In stead, open, graduated challenges of the suspected food have become more popular.

Graduated Food Challenge

In this test, the patient is given a very tiny amount of the suspected food while being closely monitored for any signs of a reaction.  If there are no problems after 15-30 minutes, the dose of the food is increased.  This process is continued until a target dose is achieved or until any objective symptoms suggesting a reaction occur.

Allergy testing is always done prior to a food challenge.  If the allergy test is negative or if the patient has a clear history of having eaten the food without problems,  the chance of passing a food challenge is very high.   A food challenge is not recommended in someone who has a clear history of a severe allergic reaction to a food and has a positive allergy test.  Again, this patient is allergic by definition and a food challenge is not needed.

What about the macadamia nut?

More challenging is the question of conducting a food challenge in a patient who shows a strongly positive result on an allergy test and who has never eaten the food.  This is the case with Hanna and the macadamia nut.   Because she has never eaten macadamia nut, there is insufficient information to make a diagnosis of allergy.  On the other hand, the likelihood that she would fail a food challenge test is high because of the strongly positive skin test result.   In this case, the safest recommendation would be for her to avoid macadamia nut.   Although not perfect, cut off values for the size of skin test reaction likely to result in a failed food challenge have been published.

Delayed introduction of allergenic foods because of allergy testing may cause the problem that well-meaning parents are trying to prevent. 

There is increasing evidence that early introduction of allergenic foods to infants is associated with a decrease in food allergy.  For this reason, the unintended consequence of allergy testing of children to foods they have never eaten in hopes that it will be prevent them from having an allergic reaction, is that parents will be afraid to introduce foods that show positive on the test.  Delayed introduction of allergenic foods because of allergy testing may therefore cause the problem that well-meaning parents were trying to prevent.

A New (?) Treatment for Peanut Allergy

New Product to Treat Peanut Allergy

The Allergenic Products Advisory Committee of the Food and Drug Administration (FDA) recently voted to recommend approval of a new treatment for peanut allergy to the FDA.  The treatment was previously referred to as AR101 but it is expected to go by the brand name Palforzia,  If as expected,  the FDA gives the go ahead, it will be the first treatment for food allergy approved by the FDA.

A few important points about Palforzia

  1. It is not a medicine.

Palforzia is a capsule filled with a precise amount of peanut powder.  Thats it.

2. Palforzia is a form of oral immunotherapy

Oral immunotherapy is a process of feeding an allergic individual an increasing amount of the food they are allergic to with the goal of increasing the threshold that triggers a reaction. Immunotherapy for airborne allergens such as pollen, mold, and animal dander has been available by subcutaneous injection (allergy shots) for many years and is an effective treatment for seasonal allergies, allergy to pet dander, asthma, and eczema.  Recently, a sublingual (under the tonge) immunotherapy tablet has been approved by the FDA for the treatment of grass and ragweed pollen allergy.  Unfortunately, the grass tablet does not contain Bermuda grass and so is of limited value in Phoenix and other desert communities in Arizona.  This will be the first oral form of immunotherapy to be approved for the treatment of a food allergy.

3. It is not a cure

By increasing the threshold dose of food required to cause a reaction, it is hoped that treatment with Paforzia will decrease the risk of a  life threatening allergic reaction in the event that peanut is eaten by mistake.   It will not allow peanut allergic patients to enjoy a Snickers bar or PBJ sandwich.  With this treatment,  a child who was at risk of a trip to the hospital if he ate half of a peanut,  may be able to tolerate 3-4 peanuts before a severe reaction occurs.

4. It is for life

Patients must take the peanut capsule every day… forever!

5. There are risks

Patients receiving treatment with Paforzia  frequently have allergic reactions to the peanut powder. These reactions range from a stomach ache to anaphylaxis.   For this reason patients on Paforzia must carry self injectable epinephrine at all times.

Weighing the Risks versus Benefits

The challenge for doctors, patients and parents considering this new treatment will be in evaluating the  benefits versus the risks: Does the benefit of having some protection against a life-threatening reaction to an unexpected exposure to peanut outweigh the risk of frequent allergic reactions with the daily treatment?

There is No Such Thing as an Allergy Test

I have been teaching medical students in my office for the past several weeks. These first year University of Arizona students have recently completed a block of studies on the immune system and are spending time in an allergy clinic to learn how memorizing a million obscure names and pathways  applies to the real world of clinical medicine.

Each student spends only half a day with us so there is not much time to impart wisdom. Since this may be their only exposure to the specialty, I have tried to come up with a few important “pearls” for them to take with them.

Here is one of those pearls: “There is no such thing as an allergy test.”

Since we spend a lot of time in our practice testing patients to find out what they are allergic to, this statement is usually greeted by the students with a polite stare as if waiting for the punch line.

First year medical students are understandably a bit nervous when introduced to the real world of doctoring for the first time. They are quite sure of one thing: They do not know very much now and that somehow, over the course of just four years, they will be expected to know practically everything. They are also quite sure that they have no idea how this miracle of knowledge transfer is supposed to happen.

So the students typically smile politely and try not to say anything that would make them look any stupider than they feel. I try to reassure them and suggest that if there ever was a time to ask stupid questions, your first few years of medical school would be it.

The assumption that somehow you should know and that surely everyone but you knows is pervasive but also foolish and can be a serious hindrance to learning. Wisdom begins when we are able to put our pride in our pocket,  acknowledge our ignorance, and ask the stupid question. The other students, contrary to your assumption,  are also quite clueless,  and certain to be relieved when you do.

Back to the point. Why is there no such thing as an allergy test and why is this so important for medical students to learn?

The answer is in the definition of allergy.

Allergy is an adverse condition and symptoms caused by immunologic sensitization and exposure to an allergen.  An allergen, almost always a protein, is the thing (food, animal, pollen, mold, etc) that your immune system decides – arguable by mistake – you need to be defended against.  The resulting production of specific antibodies that react with the allergen is called sensitization.   Without it, you are not allergic.

Sensitization is the part that we learn from an allergy test.

However, having symptoms when exposed to the allergen you are sensitive to is also part of the definition of allergy. Without symptoms, you are not allergic. No matter what the results of an allergy test say.

A diagnosis of allergy cannot be made without a careful  history. In fact, when allergy tests alone are used to make a diagnosis of allergy – which is often the case when patients ask their family doctor to order an allergy test to find out what they are allergic to – the results can be confusing and misleading and even dangerous. In my experience, this is often the case.

Inappropriate diagnosis made on the basis of allergy tests alone have led to unnecessary restriction of foods, elimination of loving pets from the home, disruptive changes at home and at school, and prescriptions for insanely expensive medications such as Epipens.

On their own, blood tests and skin tests for allergy can give falsely positive results as often as 50% of the time. That means that if an allergy test is positive for peanut, and no consideration if given to the patient’s history, there is a 50% chance that the patient is allergic to peanuts and a 50% chance that they are not.

If history is not taken into account to make the diagnosis, an allergy test is about as good as flipping a coin.

Coupled with a thorough and accurate history, however, an allergy test is an essential tool for a making a diagnosis of allergy.

The history – listening! – is the most important skill for a physician to learn. And this is why it is important for medical students to remember: “There is no such thing as an allergy test”.

Chickpea Allergy

In the past few years I have discovered two foods that I really enjoy but did not eat growing up.   One is hummus and the other is falafel. In fact, I learned how much I enjoy both foods eating at the Pita Jungle in Ahwatukee. Their falafel sandwich with pita bread and hummus on the side is wonderful!   If you asked me a few years ago what hummus and falafel was made of I would have ( I am ashamed to say) drawn a blank. You of course know that both are made from the chickpea.

Chickpea is one of the earliest known cultivated plants. It is packed with nutrients providing high quality protein, carbohydrates and fiber, and is used in traditional dishes around the world. Because it is high in protein and low in fat, it’s popularity as part of a healthy diet has been increasing in the US over the past 10 years.

I recently learned that chickpea has other traditional uses. In some areas of India, for example, infants are bathed in a lotion made from chickpea flour. In fact, I recently saw a 10 year old girl in our office with a history of severe rash and itching of the skin after she was bathed in chickpea flower lotion as an infant.   Her family has had her avoid anything containing chickpea since that time but was concerned about cross reactivity between the chickpea and other foods.

Chickpea is a legume and therefore closely related to other common legumes used as food such as peanut, soy bean, and green pea. Because of this allergenic cross reactivity, many patients who are allergic to one legume will have a positive allergy test (skin test or blood test) to other legumes although they may be able to eat those foods without any problems.   Usually, people who are truly allergic to a legume (have had symptoms when eating the food) will have a larger reaction on an allergy skin test or a higher value on an allergy blood test, but this is not a reliable way to distinguish who is truly allergic from those who have a positive test because of cross reactivity alone.

As an example, the child who had the severe allergic reaction to chickpea flour as an infant tested positive to green pea, soy, and peanut on her allergy tests although she has been eating these foods all her life without problems.  I explained that the child had an allergic sensitivity to many legumes but was only allergic to Chickpea.  This is not an easy concept to grasp.

On the other hand, someone who grew up in the US with a severe peanut allergy may want to be careful before trying unfamiliar dishes in parts of the world where legumes, such as the Chickpea, are used extensively.

 

Don’t Let Your Babies Have Allergy Testing

This month, the National Institute of Allergy and Infectious Diseases published new guidelines for when peanut should be given to infants. The hope is that fewer children will develop peanut allergy as a result of these new recommendations

Screen Shot 2017-01-20 at 10.54.56 AM

The revision of its guidelines for the introduction of allergenic foods was prompted by the startling results of a study published in 2015 called the LEAP (Learning Early about Peanut Allergy) trial. In this study children between 4 and 11 months of age who were considered to be at high risk for developing allergy to peanut were divided into two groups. One group was given peanut to eat on a regular basis while the other group avoided peanut-containing food.   At 60 months of age both groups underwent a food challenge with peanut.

The peanut food challenge was positive in 13.7 % of the children that avoided peanut but only 1.9% in the group that ate peanuts regularly. In children that had a positive allergy skin test reaction to peanut before the study, the results were even more impressive. There was a 70% reduction in the prevalence of peanut allergy in the group given peanut compared with the peanut avoidance group.  In other words, children who were given peanut-containing foods to eat on a regular basis at a young age were significantly less likely to develop peanut allergy.

Here are the New Guidelines

  1. In children who have severe eczema, egg allergy (defined as a history of an allergic reaction to egg and a positive allergy skin prick or a positive oral egg food challenge result), or both, either a blood test or skin test for peanut should be performed. If the peanut allergy test is positive, the child should be referred to an allergy specialist for evaluation and possible oral food challenge with peanut.
  1. Children who have mild to moderate eczema (not severe) should have peanut-containing foods introduced at around 6 month of age
  1. In children who do not have eczema or history of food allergy, peanut should be introduced in an “age appropriate manner in accordance with family preferences and cultural practices”

Take Home Message

There is strong evidence that early introduction of allergenic foods such as peanut protects children from developing food allergy and delaying introduction of allergenic foods may increase the risk of severe food allergy.

Children who do not have severe eczema or a clear history of egg allergy SHOULD NOT have a blood test for food allergy.  The high rate of false positive results in these tests may delay the introduction of allergenic foods and can therefore cause the problem they are trying to prevent.

Children with a history of severe eczema or egg allergy (or any other food allergy) should be referred to an allergy specialist for further evaluation.

Brian Millhollon, MD

 

 

When is a Food Allergy Test NOT a Food Allergy Test?

Jason is now 15. He is taking AP calculus at Desert Vista High School, plays La Cross after school, is getting his driver’s permit next week, and plans to go to college and study electrical engineering after graduation. He is smart, tall for his age, and spends a little too much time playing video games.

He is also deathly afraid of peanuts.

He is afraid, in spite of the fact that he has never eaten a peanut. He has never enjoyed a Snickers bar, Reese’s Cup, or Kung Pao Chicken, and has certainly never eaten a peanut butter and jelly sandwich for lunch.

And yet, as long as he can remember, his parents have sternly warned him to stay away from peanuts.   He was not allowed to eat lunch with his friend’s at school because he had to eat at a special “peanut free” table and could not have snacks brought by other parents to baseball practice because they might be “contaminated” with peanut.

His parents have had to buy three sets of Epi Pens each year to keep at school, at home, and at his grandparents home, to be used in case he had a severe allergic reaction after eating peanut by mistake. This year his family spent more than a thousand dollars on the Epi Pens.

All in all, Jason’s life and the life of his family has been complicated by the serious threat of peanut allergy. And yet, Jason is not allergic to peanut.

The problem began when Jason was just turning two. He was spending the day at his grandparent’s house and developed a rash on his cheeks and vomited.   His parents became concerned that he may have had an allergic reaction to something he ate and so took him to his pediatrician who decided to run a food allergy panel just to be sure.

The test came back positive for peanut. The pediatrician suggested that it might be best for Jason to avoid peanuts since if was unclear if he may have eaten something that contained peanut at his grandparent’s house.   His parents read a story about a child with severe peanut allergy who died after being kissed by someone who had eaten a peanut and so requested an Epi Pen to keep on hand. All family members, friends, and teachers, were instructed on the importance of strict peanut avoidance when around Jason and on the use of an Epi Pen.

I saw Jason for first time six months ago.   His parents needed a refill of the Epic Pens and since his pediatrician was no longer practicing, they decided to make an appointment with an allergist.

After talking with Jason and his mother, it was clear that Jason did have allergies. He sneezed frequently, complained of stuffy nose and itchy eyes during the spring and fall, particularly while playing La Cross, and on occasion had wheezing and chest tightness after spending time around a friend’s cat.   Mom was not concerned about these symptoms, lot’s of people had them, but she with very concerned about his severe peanut allergy.

Because of his history, allergy testing to pollen, cat dander, and peanut was completed. The results showed very strong reactivity to grass, tree, and weed pollen as well as to cat dander. The skin test to peanut was also mildly positive.

How do we interpret these results? Most importantly, is Jason allergic to peanut?

To begin we rely on three sources of information to help us make a diagnosis of allergy: the patient’s history, laboratory tests, and a food challenge.

In Jason’s case, the history is not very strong for peanut allergy. In fact, it is not clear if he has ever been exposed to peanut.

What about the positive blood test and skin test for peanut allergy?

Both tests rely on the detection of a specific antibody produced by the body that reacts with peanut. When we find these antibodies, called IgE or immunoglobulin E, we can say that the patient shows sensitization to the food being tested. Both the blood test run when Jason was two and the recent skin test are technically not allergy tests, but tests for sensitization.

This distinction in terminology is important because many people have sensitization to a food (based on skin or blood tests) that they have eaten their entire lives without problems. Since food allergy by definition is adverse symptoms caused by exposure to a food that a patient is sensitized to, then without symptoms, there is no allergy.

If we define a perfect food allergy test as being reactive or positive in 100% of patients who have true allergy to the food and non-reactive or negative in 100% of patients who are tolerant of the food, meaning it is safe for them to eat it, then conventional food allergy testing is not very good. In fact, conventional food allergy testing has an approximately 50% false positive rate: Half of the patents that test positive to a food on these allergy tests are NOT allergic to the food. The test’s ability to rule out allergy is better, by some estimates more than 90%: There is less than a 10% chance that a patient with a negative test to a food will have an allergic reaction if they eat the food.

When we say that conventional allergy tests for peanut allergy have a 50% false positive rate we do not mean the test result is an error or mistake. The test accurately detects allergic or IgE antibodies to peanut. But as was mentioned, the presence of these antibodies does not always cause problems when the patient eats peanut and therefore is considered a falsely positive test for food allergy.

To understanding WHY we can have allergic antibodies to a food that we tolerate it is helpful to understand a few things about proteins. You can find a brief introduction to proteins here.

Peanuts, as well as most other foods, contain multiple proteins. The proteins in peanut are given numbered names beginning with Ara h (from the scientific name for peanut Arachis hypogaea). The peanut proteins Ara h1, Ara h2, Ara h3, Ara h6, Ara h8, and Ara h9 have been detected and allergic IgE antibodies have been found that react with each of these proteins.

Some of these peanut proteins, such as Ara h8, are very similar to proteins found in pollen produced by allergenic plants. In fact, if a patient is allergic to birch tree pollen, the anti-birch tree IgE antibodies they produce are likely to react with the Ara h8 protein in peanut. Patients with allergic antibodies to Ara h8 alone rarely have significant peanut allergy and yet will have a positive skin or blood test to peanut. One study showed that 79% of patients who had allergies to pollen reacted positively to peanut on an allergy test but were tolerant of peanut.

Other studies have shown that patients with high levels of allergic antibodies to the Ara h2 protein in peanut are more likely to have true peanut allergy. These observations have led to the development of component allergy tests were a patients blood can be tested for allergic antibodies to a specific food protein, not just the whole food.

Component testing for peanut allergy does show improved diagnostic accuracy compared with conventional blood tests, although it continues to have a high false positive rate and unfortunately can also be negative in patients who have true peanut allergy.

Component allergy testing for peanut was ordered for Jason and the results showed positive to Ara h8 only suggesting that the positive result on the skin test and earlier blood test occurred because of his strong sensitivity to pollen.

The results were discussed with Jason’s parents who asked if there was any other test that might be used to confirm that he is not allergic to peanut.

In fact, the most reliable and considered to be the gold standard for making a diagnosis of food allergy, is the double-blind, placebo-controlled food challenge. In this test, the patient is given a sample of the test food as well as a sample of a similar, non-allergic food as a placebo. Double blinded means that the doctor and technicians conducting the challenge as well as the patient, do not know which is the real test food and which is the placebo. The test is considered positive if the patient shows obvious signs of a reaction after eating the test food but not after eating the placebo.

There are a number of problems with the double-blind, placebo-controlled food challenge: It is difficult to perform, requiring significant time and recourses; A patient can have a severe allergic reaction to the food and therefore the study must conducted by trained personal in a setting that is capable of handling a severe emergency; and it is not always possible to find a suitable food to serve as a placebo.

Because a food challenge carries the very real risk of a severe allergic reaction it is rarely done if either the history or laboratory tests strongly suggest allergy. Open challenges to a food conducted in the allergist office is considered to be an alternative to a blinded, placebo-controlled challenger if the likelihood of significant allergy is considered to be very low based on history and previous tests.

Because of the weak history for peanut allergy and the results of component allergy testing, a peanut challenge in the office was offered to Jason and his parents.

When the food challenge was discussed with Jason he became very anxious and said that he did not see any reason to do it since he has done well staying away from peanut his whole life. He said he felt sick just thinking about it.

Hopefully, Jason’s fear of peanut allergy will subside with time and education and he will someday be able to enjoy a peanut butter and jelly sandwich or Snickers Bar.  And hopefully, improved testing methods as well as better understanding of food allergy will make such cases of unnecessary fear and anxiety over something to be enjoyed a thing of the past.

Brian Millhollon, MD

 

 

Food Allergy for Beginners: Sugars

What is a Sugar?

Sugar is one those loaded words that can have a variety of  meanings.  For example sugar can mean sucrose, the white granules you put in your coffee, or it can refer to the level of glucose in your blood, as in: “I need to up my insulin because my blood sugar is sky high after putting all that sugar in my coffee”.

Sugar can also refer to carbohydrates (“carbs”), one of the three categories of chemicals, along with fats and proteins, which make up the food we eat.

Carbohydrates can be single molecules or joined together to form large chains.  Single molecules are called monosaccarides and include glucose, galactose and fructose. Any two of these simple sugars combined are called disaccharides. For example, sucrose (table sugar) is a disaccharide combing the two simple sugars glucose and fructose. Lactose is a disaccharide containing glucose and galactose. Polysaccharides are long chains of monosaccharide joined together and are used in plants and animals for structure and storage. Sugar is stored as starch in plants and as glycogen in animals.

Monosaccaride - glucose

Monosaccharide – glucose

Disaccharide Sucrose

Disaccharide Sucrose

Polysaccharide

Polysaccharide Starch

Sugars can combine with proteins to form glycoproteins and with fats to form glycolipids.

It’s All About Glucose

Glucose is our body’s primary source of energy and also the primary product of photosynthesis, the process in plants that turns sunlight into food.  Most of the carbohydrates that we eat are converted to glucose during digestion. We crave sweet things because they usually contain lots of simple sugars that require very little or no work to convert to glucose. Most of the cells in our body can run on either glucose, fats, or proteins but the brain needs glucose to work.Glucose metabolism

Can You Be Allergic to Sugar?

The short answer is no. Simple sugars and disaccharides such as sucrose and lactose are not allergens and cannot cause true allergic reactions.

However, people have become allergic to glycoproteins, sugars combined with proteins. An example of this is allergy to galactose-alpha-1,3-galactose, also know as alpha-gal.   Alpha-gal is a common glycoprotein found on all animal cells except humans and primates and those sensitized can have allergic reactions to a variety of meats including beef, pork, and lamb.   Interestingly, a large number of alpha-gal allergic patients developed symptoms after being bitten by a tick, particularly the lone star tick found in the Southern and Eastern United States. Skin testing to meat and a blood test for allergic antibodies to alpha-gal can make the diagnosis.

Lactose Intolerance

Although sugars rarely cause true allergic reactions, they are a common cause of food intolerance. Because the cells in our body can only use glucose for fuel, all complex sugars (disaccharides and polysaccharides) have to be chopped-up or digested to make the glucose available. To do this, we produce enzymes that make the process of digesting the complex sugars possible.   Many of these enzymes are specific for a particular type of sugar. For example lactase is the enzyme that facilitates the break down of cows milk sugar (lactose) to yield glucose and galactose that is then easily absorbed into circulation to be used as fuel.

Without lactase the milk sugar passes intact into the colon where it provides nutrition for colonies of fermenting bacteria. These bacteria feed on the sugar and as a by-product, produce a large amount of methane gas and fluid retention causing intestinal bloating, cramping, and gas.   Treatment is avoidance of all mammalian milk and/or taking supplemental lactase (Lactaid) whenever milk products are consumed.

In summary, true allergic reactions to carbohydrates are rare while food intolerance, such as lactose intolerance, are more common.  Other problems associated with sugar (i.e., how to say,  “No thank you” to that cheese cake) is an important topic, although – except as a fellow victim- a bit out of my area of expertise.

Brian Millhollon, MD