This webinar was recorded on March 21, 2024

For most people, insect stings are a short-term annoyance. But for some, the venom in a stinging insect can cause an allergic reaction that can range from a mild local reaction to anaphylaxis. In this webinar, learn about how insect allergies are diagnosed and treated and how to be prepared for a potential allergic reaction.

Speaker:

  • David Golden, MD

David Golden, MD, is an Associate Professor of Medicine at Johns Hopkins University. He also has a private group practice in Allergy-Clinical Immunology in Baltimore and sees both adults and children. He is the Director of Allergy in the Department of Medicine, Sinai Hospital of Baltimore, and is the Chief of the Allergy Division of Internal Medicine at Franklin Square Hospital.

Dr. Golden maintains an active program of research studies on insect allergy and venom immunotherapy.

Golden completed his undergraduate, medical school, and Internal Medicine training at McGill University in Montreal, then pursued a fellowship training program in allergy-clinical immunology at Johns Hopkins University, where he began a career investigator pathway in insect sting allergy, with an interest in anaphylaxis in general, including latex allergy, food allergy and immunotherapy. He has published dozens of original research manuscripts as well as many review articles and book chapters.

He is a Fellow of the American College of Physicians-American Society of Internal Medicine, Fellow of the American Academy of Asthma Allergy and Immunology, and Fellow of the American College of Asthma Allergy and Immunology.

This Advances webinar is in partnership with the American College of Allergy, Asthma & Immunology. ACAAI offers CMEs for physicians and attendance credits for all others. You can create a free ACAAI account and obtain CME or attendance credits through the member portal for Advances webinars.

All attendees will be offered a certificate of attendance. No other continuing education credit is provided.


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Transcript: While this transcript is believed to be accurate, errors sometimes occur. It remains your responsibility to evaluate the accuracy and completeness of the information in this transcript. This transcript is not intended to substitute for professional medical advice.

Lynda Mitchell: Thank you all for joining us here today. I’m Lynda Mitchell, CEO of allergy and asthma network. Welcome to this noontime webinar on the East Coast. We are in for a real treat today with Dr. David Golden, who it is a real honor to have him here joining us. We have a few housekeeping items that we would like to go over before we get started. First, all participants will be in listen only mode and we will be recording this webinar. A copy of the recording will be available. After the webinar we do a follow-up email a day or two after the webinar with a link to the recording, so look for that and we will also find recording on our homepage if you just scroll down to the bottom of the page. This webinar is one hour long and that includes time for your questions. We will take those questions and I will ask Dr. Golden toward the end of the webinar when he follows up with his presentation. So just go ahead and add them during the session and then I will ask Dr. Golden your questions after he finishes. This webinar is in partnership with the American College of allergy, asthma and immunology. The ACAI offers CMEs for physicians and attendance credits for everyone else. You can create a free account on the ACAAI.org website to obtain CMEs and attendance credits for the advances webinars. All attendees will be offered certificates of attendance here as well. You will find that in the chat box and we will follow it up in the follow-up email as well. And like I said a few days after the webinar you will receive an email with some links to additional items of interest regarding the topic today along with some upcoming webinar dates that you can plan for. Today’s topic is insect and venom allergy diagnosis, treatment and preparedness. For many people come insect stings are a short-term annoyance but for some, the venom of a stinging insect can cause an allergic reaction that can range from mild, local reaction to severe anaphylaxis. In this webinar we will learn how insect allergies are diagnosed and treated and how to be prepared for potential allergic reaction. It is my pleasure to introduce our speaker, Dr. David Golden. Dr. Golden is an associate professor of medicine at Johns Hopkins University. He also has a private group practice in allergy clinical immunology in Baltimore and sees both adults and children. He’s is the director of allergy and the Department of medicine Sinai Hospital Baltimore and of the chief of the allergy division of internal medicine at Franklin Square Hospital. Dr. Golden maintains an active program of research studies on insect allergy and venom immunotherapy. He has published dozens of original resource manuscripts as well as many review articles and book chapters about anaphylaxis, latex allergy, food allergy and immunotherapy. He is a fellow of the American College of physicians, American Society of internal medicine, as made immunology and fellow of the American College of allergy, asthma and immunology. So thank you for being here with us, Dr. Golden. I know you’ve done some podcasts without — with us which were really helpful.

Dr. David Golden: Thank you so much, thanks for inviting me and thanks for that kind introduction. Let me make sure I can advance my slides. This is also by way of thinking the allergy and asthma network for putting on this program and for inviting me to participate. My disclosures. Some of which are relevant, but I think and hope you will find this to be balanced in presentation. And we are going to talk about insect sting allergy in general and talk about what we see and what you and your patients may experience regarding insect allergy and what do we do about it? How do we know what is going to happen in the future and how do we prevent reactions from happening? I will mention and invite you all to visit the website of the joint task force on practice parameters, which is a joint effort of the American College and American Academy of allergy, asthma and immunology, and much of what I’m going to be saying or pretty much all of what I’m going to be saying, I think, is from the last update on the insect sting practice parameter which is hard to believe that it is seven years old now. We are working on another newer update, and the very new, just published last month anaphylaxis practice parameter update, some of which is very relevant to what we are reviewing and I will be showing you some of that. There is such a thing, apparently, as insect sting allergy awareness week, which is coming up by a group called Bee Aware. It is usually in the month of May, and you may see some public outreach at that time. These are some of the number that they quote, which are pretty much on target. There are an awful lot of people, whether they know or appreciate it or not who are living with insect sting allergy , and as we will discuss, it is hard to know sometimes whether they are learning too little — worrying too little about their allergy or worrying too much about their allergy which is part of what we need to balance. Insect reactions account for to her 20,000 ER visits every year. Estimates of death have been, we believe, underestimated. They said 40 per year, I would say 60 per year which is what this group also says and we actually have estimates higher than that, which is not a big number compared to the number of people who are allergic, the number of people who get stung, but it does happen.

Some of us know unfortunately people in families where that has happened. The last three items are really important because these are things that many people don’t know, many doctors don’t know. Venom immunotherapy, at the bottom line says, venom immunotherapy exists and we will talk more about that but amazingly, almost all doctors that I’ve spoken to don’t know that venom immunotherapy exists and even if they do know anything about it, they would never guess a couple of items up from that that depending on which venom we are talking about, almost 100% of people who are on the venom immunotherapy have no reaction, no abnormal reaction when they get stunned, though he allergic reaction and after they stop immunotherapy. Again, they have a very, very low chance of reaction, so we sometimes avoid using the word cure, but it really is a cure for the majority of people who undergo venom immunotherapy. The second to last item is also very important. People don’t tell their doctor they have a reaction. I’ve been stunned many times so this must have been a fluke, and they don’t tell their doctor. And even when they do, the doctor doesn’t know that venom immunotherapy exists. So these are some of the problems we encounter with patient and with doctors regarding insect sting anaphylaxis.

So this is a honeybee. A little bit fuzzy on the thorax, hanging out in one of its favorite places. This is to introduce that we are talking about stinging insects, not biting insects. Biting insects almost never cause animal — anaphylaxis. People can get large swellings but almost never anaphylaxis except from stinging insects. In the stinging insects are all in the order hymenoptera. We deal mainly with honeybee allergies. Bumblebees can cause anaphylaxis, it just is a very unusual thing, other than we run into this in greenhouse workers, for example people who have a reason to be around bumblebees a lot eight disturb them, potentially, because it is very unusual to be stoned by a bumblebee, but it does happen. We also don’t have a venom available for testing although there is a blood test for bumblebee allergy. I call them wasps because in common terminology, all of these Yellowjackets are often referred to as wasps. Yellowjackets for on its are very closely related, and that is why put this line here, because among the vestments, the Reese — vespids, these three are virtually the same and allergy-wise, they are virtually the same. The paper wasps are cousins, if you will, to the Yellowjackets and Hornets. They are in the same group, but they are more distantly related, so allergy-wise, you can be allergic to Yellowjackets or wasps and you can show positive to both simply because there venoms are very similar. One of the problems we encountered is how do we know from their tests whether someone is actually allergic to two different insects or whether it is just the cross reactivity of the venom because they are so similar? The third group is stinging ants. They do, first of all. They may bite, but that is not the problem. They actually have a stinger, and they do sting. The most important group in the U.S. are the imported fire ants which infest the southeastern third of this country especially around the Gulf Coast but they are slowly spreading northward. There are other types of stinging ants in the U.S. besides these imported fire ants, and there are other families of stinging ants around the world that are not related to imported fire ants. So if someone is allergic to fire and U.S. and they are traveling to Australia where there are Jack jumper ants, should they worry about it? Well, not from an allergy point of view. I think it is a good idea to avoid all of these stinging ants, but they wouldn’t react to those other kinds because the allergy is different. Top left is a yellow jacket, and bottom right is a wasp. I point these out because they are kind of masqueraders. That wasp is often mistaken for a Yellowjackets to get the coloring and markings are so similar. To the trained eye, we can see the differences, but patients unless their entomologists and allergists unless they have been trained really are not very good at identifying particular insects. So when a patient tells me they know what they were stunned by, I listen but I’m not always sure whether to believe. This is the so-called Whiteface hornet. They build these big nests up in trees, and they are very vibration-sensitive. If you are using a lawnmower or a weed Wacker anywhere near them, they will swarm an attack. Vibration can disturb them and cause them to attack. And this is the imported fire ants. They are very small as you can see. They build these nouns and it is almost impossible to be outdoors in any of these infested areas and not get stunned. The attack rate, meaning the chance of getting stung each year is one in 10 for Yellowjackets. The average person get stunned once every 10 years, whereas for fire ants, it is 50% of the population did stung each year, or once every two years the average person in these areas it is for the hard to avoid these critters.

What do we mean by reactions? Normal reactions, itching, pain and swelling are normal, but large local reactions are large and they are local, so they always are in the vicinity of the sting. You can get stunned on your arm and wake up the next morning, because they are usually delayed with very large swelling, sometimes all the way up the arm and he can be scary and leads to emergency room as its where they usually call it an infection, which it is not, but we will come back to that a little bit later. They are allergic but they are not systemic. Systemic meaning it affects the whole system. A mild systemic reaction, we called it mild because it is not really anaphylaxis. Itching, hives, swelling of the face, even. Meeting even if you were stunned on the foot, the face could swell. It is a systemic reaction, but none of these are actually dangerous as long as they are only on the outside of your body. Very scary, but not dangerous. They are not technically anaphylactic. Moderate to severe will involve the breathing to some degree or the blood pressure to some degree or can lead to a near fatal anaphylaxis because of hypotensive shock. One pressure drops to zero, essentially. Or because of airway obstruction and respiratory failure. So there is a full spectrum of the reaction that we can see to insect stings. The systemic reactions are the same basically as any allergy, whether it is a food allergy, drug allergy. Anaphylaxis is anaphylaxis but I am pointing out here that my colleagues at Johns Hopkins many years ago who were working the pediatric studies noted that more than half of the children they receive systemic reactions had only these mild, so-called mild systemic reactions. Very scary to the parents, certainly, but it was interesting because in adults, they can happen but it is much less typical for there to be only continuous signs and symptoms. Conversely in adults, we see a fair number get low blood pressure, hypertension, dizziness or even loss of consciousness in children that is very uncommon. Those are the main differences between children and adults. In children it raised the question to my colleagues if they only have these mild reactions, do they really need to be in you nice? Which was the thrust of — immunized? Which was the thrust of the study. The timing of the reaction like any anaphylactic or systemic reaction is generally immediate. There are exceptions to that with certain allergies like what we now recognize as delayed in a flexes to red meat, but anaphylaxis at least used to be defined as an immediate hypersensitivity reaction. We see some data from many years ago when there was a registry of 3000 patients with insect allergy, and you can see that some 76% or so had the onset in under 20 minutes. It is up to 87% if we go up to 40 minutes. That is fairly immediate. But you can see that there are rare cases where even an hour or two or more after the sting, the reaction comes on. We are not always sure if there are milder symptoms that are not recognized or if it really doesn’t start until two hours or more. It is very hard to explain scientifically but we have to keep in mind that it is possible it has been reported. So how do we as allergists evaluate a patient?

Someone comes to CS because of concern about insect allergy. What can we do? The history is critical, as with almost everything we do. But it is not good enough to write down patient had allergic reaction to a sting. It can be very helpful at times to find out where they were, what they were doing, possible clues to a kind of insect it was, stings, where on the body, what was the time course of symptoms, what treatment did they use? All these things can be really important to making their judgments of what happened and what we should do next. And we would do testing to see if we could identify the allergy and which insect eye skin test or serum test. In component tests help us to zero in on exactly which insect was the main allergy. And there is a lot of attention now and no guidance in our guidelines about baseline serum drip — tryptase. We don’t have the ability to do baseline activation test because there is no FDA-platform for those tests, and we can do sting challenge test but it is not something you are likely to see done outside of a research study. So what does the history tell us? We find out more about this reaction and determine whether the reaction was mild — or mild or severe. We have done challenge studies, data from people who were not treated because they refused, and that is why we were allowed to sting them to see what would happen. You see that the stronger the history, the more the chance they are going to react to the sting. Severely reactors are more likely to react on the next sting and mild reactors. As just for chance of reaction. We talk about the frequency. Risk can be frequency, it can be severity. Those are two very different and very important questions. In this case, they history does predict the chance of reaction. It also happens to predict the severity, meaning people with severe reactions. This might sound like common sense but they are much more likely to have a severe reaction in the true than the mild or moderate reactors. I will talk much about the two different colored bars here. The main point with the different yellow jacket that I can’t tell apart, some are stronger than others, if you will. The red guys are the ones who nest underground and you run over with your lawnmower and they swarm into thank you. They are mean and they are potent. Those insects, the red Barber more likely to cause a reaction, especially severe reactions. But the person could have had a sting 10 years ago where they had a reaction and then they say but I got stung two years ago in have a reaction, so I’m OK, right? Well, maybe not. You see there is a much lower chance of reaction. They may not have reacted. But if they get stung again by the red Barb, they may very well have a reaction again. So there is some clinical used to know about this, and knowing that not having a reaction to a sting is on urgently not a guarantee that you won’t react again. So when do we perform the testing?

There are some things we have to remember when we do this that might help us to decide whether or not we are going to do the test. The negative productive value is very high. If the test is negative the chance of them having a reaction is extremely low. It should be zero, but no test is perfect. But the positive predictive value is actually very poor, and that is because like every allergy, there are many people who have the allergy in their system, but they don’t react. That is true for peanuts, cats, every allergy. A test is just a test. It doesn’t necessarily tell you what is going to happen, but we do have statistics that help us. But we have to remember that. We had better know what you’re going to do with the results. I did the test because I really wasn’t sure what to do, meaning they are kind of hoping it will be negative. If you’re hoping it will be negative, it won’t. I mean advice, but the more you hope it is going to be negative, the less chance, right you every time. And then you have a positive test or you’re still not sure what to do because you want sure in the first base. And I’m telling a positive test is not a guarantee of their reaction, because is it on the next slide? We will come back to more about that. But a positive test is not harmless. A positive test is going to cause a lot of concern, anxiety, fear. People might be afraid to go outside or even change their career or goals and this is very relevant because it has come up many times. A teenager wants to go into the military and they mention unfortunately that they think they have a reaction or their mother told them they had a reaction when they were a child and a pediatrician told them to carry the EpiPen for the rest of their lives. That person is not getting into the military. And it is going to take an expert allergist to certify that by history they may have had kind of a reaction that is not a concern. The point is that if someone did a test on that individual and it showed positive, then for sure they are not getting the military. So don’t even do the test of the person is a candidate for venom immunotherapy. That is the guidance that we now have in our practice parameters. And the only reason to go on the venom immunotherapy is if they have a moderate to severe anaphylactic reaction. Anything other than that, we recommend not even doing a test. Testing is based on the history. Even if the reaction was many years earlier, we still have to think about doing the test because a single sting with no reaction is not a guarantee. So there are other concerns that I’ve started to mention, and I already mentioned that there are many people who are positive but are not going to react to a sting. This is called asymptomatic. The point is of all the people listening to this webinar, 20% if you have a positive test for venom ige Someone who has been stunning in the previous two or three months, up to 40%. So all the test really tells you technically is that this person has been stung before. It is the history that tells you whether they are at risk for anaphylactic reaction.

Moreover, people who have had anaphylaxis and have a positive test, you would think that if they get stunned there was a 100% chance they are going to react. No, it is about 50% for a variety of reasons, some of which have to be insect and our bodies, but there is no one hundred percent. But 50% of a higher risk compared to 5% or 1%. Just to put it in context, that is a high-risk individual, someone we believe has a 50% chance of having a reaction. The testing, I mentioned the history predicts the frequency and severity. The test do not accurately predict severity. There are people with very strong tests who have no reaction or large local reactions. There are people with barely detectable IGE with near fatal anaphylaxis. Although there is a correlation, is not perfect. We don’t like for patients or doctors to make a prediction on severity based on testing alone. The testing is confirmatory, that is the way I put it. It is not diagnostic by itself. All approved by itself is that this person has been stunted, but I can confirm the risk of anaphylaxis. This shows you that the strength of the test, so this is a fairly strong test, it was positive at a low concentration. They have a higher frequency of — frequency of reaction that people with weaker test. The tests, however, do not predict severe reaction, as I just said. So which is better, the skin test with a blood test? This has been a hot button item for a while, and is still controversial. We recently had a pros and cons debate about this question at a college meeting in November. Truthfully, neither is the best, neither is perfect. They both have good sensitivity, they both have limited specificity because of what I set about a systematic sensitization. They both can be negative and wait a week or two after a sting reaction.

The most accurate results will be waiting a month or so after the reaction. I mentioned the frequency and severity, so they are really complementary and we are moving more and more toward doing at least, in some patients, both kinds of tests. What if the test is negative? If it is negative, do the other test. Neither test is perfect. If both are negative, do them again. Two or three months later, because they can vary for unknown reasons, and check the serum tryptase which I haven’t said much about yet but we will be coming back to that. A lot of people are positive to both honeybees and Yellowjackets, but many have only had one reaction, so which regularly allergic to? Practice parameters Sega should immunize people to everything positive. Because we can’t be sure whether they are going to react to whatever is positive. But we know that there were some cross-reactivity especially because of the carbohydrate determinants of these molecules and in laboratories, they can create recombinant allergies. They can build these allergens in a way that they don’t have these carbohydrates, so they would cross-react. That is one of the advantages of doing component-result diagnosis or component recombinant allergen testing. They mean the same thing. We are doing a blood test with the individual proteins from the venom. This shows you that there are a whole bunch of these proteins in honeybee venom. The nomenclature would be the generic name for honeybee, etc. So these in the top bar here are all unique allergies. If the blood test is positive, they are honeybee allergic. If it is positive to five, they are yellowjacket allergic. But there are these other components that cross-react so if someone could be allergic to honeybees, because it cross-react with this yellowjacket protein, the test for yellowjacket venom shows positive because they are not actually allergic to yellowjacket venom. This has only been available for a couple of years now and allows us to be short someone who would have been previously treated the honeybee and yellowjacket venom, now we can distinguish whether the really need both or maybe they only need one of the two to fully protect them. So what we are trying to do in counseling patients and treating patients is to be able to predict, as I’ve been saying, the frequency and severity, especially severity of future reactions. So here’s almost the entirety of the literature on what happens when people get stung who are considered to be at risk for a reaction because they had previous reaction and positive test. And although the bottom line is close to 50%, so that is where we get this number that is an approximately 50% chance of reaction to each sting, you see a wide range here, 30-65%. That is huge. And for many possible reasons. The late Bob Reisman, he broke it down this way to show us that the chance of having a reaction was almost twice as high in adults than in children, and he noticed that although he had previously used to say that the chance of reaction goes down with time, it turns out he believed didn’t see any difference and neither did the other studies. And he and we and others have noted that the reaction if someone gets stunned three or four times, the reaction itself isn’t different but it may or may not happen. They may not react to one and then they may react to the next. There are a lot of possible reasons for that. For example, it was Franken — actually, if we go back here, 1994. 220 eight patients, 90 of them had a reaction. Then they had the people who didn’t come back and do a second sting. We found the same thing and some old data.

A single state with no reaction is still not a guarantee. Take at least two stings. Something relatively new is the connection between in sexting allergy and disorders. Tryptase is another factor that is released. Baseline maintenance just an average day, they are not having a reaction. We measure that now for these reasons. A patient comes to see need to be evaluated. If I think they have anaphylaxis, I’m going to order a baseline because it is abnormal and up to 20% of patients, and more than 25% of the one to have low blood pressure, hypotension. So this is not uncommon. But what does it mean? It is associated with more severe reactions, more trouble with reactions to the venom immunotherapy injections, or chance that the treatment will not be fully protective, and more chance that when they stop the treatment, if they stop the treatment after five years like most people do, the allergy may return and in fact there for at least three cases of fatal reactions in people with disorders after they stopped immunotherapy so we now recommend venom immunotherapy for life in those people. In our anaphylaxis parameter, and this is not just in sexting allergy, we are recommending severe insect sting anaphylaxis, especially when there was hypotension or when they didn’t have a reaction. Believe it or not, that is a known connection to very severe anaphylaxis is not having hives in the reaction. But also, the people have unexplained anaphylaxis or other reasons for suspected –, the baseline serum tryptase should be measured and the second part of this would be the need for bone marrow biopsy when you would have to make a clear diagnosis of –. What we’re talking are clonal, Maxell disorders. That is almost like a malignancy in the bone marrow that causes the cells to be too many. That is having too many cells. But they are also more activated. They are more easily triggered so people can have anaphylaxis for little or no reason, and for any reason including insect stings. So people who have had moderate to severe sting anaphylaxis, especially Lome had hypotension and no hives, we would check the tryptase because it is usually elevated, but it can be normal. That is why if it is normal we would go one to check the blood test for the genetic mutation that is the cause and there is a special test we can do for that, a little bit less accurate than bone marrow biopsy but a lot easier to do. And in the end, we may have to do a bone marrow biopsy if we have to make a final diagnosis. Another condition that is very new, it was first reported in 2016, is an inherited condition.

Turns out that 6% of adults have an inherited condition or they have two extra genes. So if you have more than the usual number, you make more than the usual amount of tryptase. And they have levels greater than eight, so anytime someone that we are investigating has a baseline greater than eight, we have to go further, we have to find out if they have this HAT. Unfortunately is not covered by insurance so it means the patient has to pay about $160 to get that test if we want to confirm. And it is important because although it is present in 6% of the population, it turns up in almost three times as many of these severe sting anaphylaxis patients. Likewise for the patients that HAT is much higher in frequency. This is another one of those things that we have to look for because it is associated with severe anaphylaxis any of these Maxell disorders. If there are too many or they are overactive, a person can be much more susceptible, especially severe. And this all comes down to why we order the tryptase. We need to know if the person has these risk factors for severe anaphylaxis. This is all under the area of wanting to know who is going to have severe reactions. It has long been said, and it is true, that these medicines usually used for high blood pressure and heart conditions have been associated with more severe anaphylaxis. And it is actually right there in the package insert that these drugs are indicated in people anaphylaxis and vice versa. Immunotherapy is contraindicated in people who are on these medications. I say country that is in the package inserts, and it has been traditionally what has been said, we are going to back off that now. Because of this systematic review that show that although there was an increased severity, it is really more the underlying cardiovascular disease, the odds ratio was 3-5 times higher in relation to the cardiovascular disease than the relation of the medication.

If we are going to have a concern it is about the cardiovascular disease. Stopping or changing the medication may just put the person a higher risk for their cardiovascular disease. So we’ve really changed our thinking on this. This is the recommendations from the hot off the press anaphylaxis guidelines now that especially in sexting, we continue these medications or at least scouts that with the prescribing doctor and patient before it during immunotherapy. And in patients were on maintenance, if someone’s on maintenance venom immunotherapy and they say their doctor just put them on these medications, in the past, we would’ve gotten very concerned about that. Now we are going to say we are not that concerned about it, we don’t want your doctor to change her medicine. Visit Gary different approach not because there is no risk, but because the risk is much smaller than we thought. We do want to prevent insect stings, especially in people who have a risk of reaction, and we want to prevent reaction, so what kinds of things can we do? This is a table from the insect practice parameter and it may surprise you. Some of these things that are effective are not surprising. Don’t eat outdoors, avoid flowering plants. This is a very big item here, drinking from straws, cans or bottles. Yellowjackets are just the right size to fit in a straw or soda can and every year I hear people getting stung on that on or throat which is obviously not a good idea if you are allergic, so if you’re going to eat or drink outdoors at all, you really want to make darn sure there are no insects getting into your food or drink. It happens. Falling fruits, pet feces actually attract stinging insects. So these are kind of common sense. But it has been said that fragrances, brightly colored clothing, the entomologist tells of that is simply not true. Insect repellent stonework for stinging insects. Running and flailing your arms is going to attract them and make them angry. So these are some bits of advice we can give. The emergency department plays a big role. People go to the emergency department when they have a reaction. The guidelines for many, many years have been very clear going back to the 1980’s that is the job of the emergency department to advise people what might have caused the reaction, that they should avoid that allergen, and that they should see an allergist, that they should be provide epinephrine and they should be referred to an allergist.

Three things. Those are the three panels receding on the left. Food allergy on the right, insect allergy. Sunday Clark I believe. And what you are seeing is of the many emergency departments that they surveyed, other than their own, which is probably the last one here because you can see how well they are doing, emergency departments across the country are doing a terrible job eating these three basic requirements. They often do tell people what the offending allergen was, they are wrong half the time, but at least they try. They often don’t prescribe epinephrine and they rarely refer to an allergist. I can tell you there was an updated study 10 years later to look at are they doing any better, and the answer is no. This still needs to be worked on. Should everyone who has a concern about insect allergy get in epinephrine injector? Well, this is a very difficult argument or discussion both among allergist and physicians and between us and our patients. The way I look at it is there are high-risk individuals with course should have the injector. Until they are on venom immunotherapy for sure, and if they have high risk factors like a very severe history, frequent exposure like in beekeepers or landscapers, or if it had a reaction, these are some of the reasons that we see them as high-risk end of course have the pen on them, the injector. But what about the low risk people? 50% chance is high-risk. What if it is less than 5%, which it is in people with mild reaction. These are allergic reactions but the chance of having an injector is less than 5%. It is actually less than 3%. Or if they’re on venom immunotherapy, or after they stop venom immunotherapy. For what about their brother or uncle? Are they considered at risk, should they be tested? Those are all low risk individuals, and this is really a judgment call. I’m not going to say I’ve never prescribed it because if I can help them by prescribing it, then I will. But this study shows that that we are not always helping meant by prescribing it. The prescription for epinephrine is a prescription for fear. And to tell them that was not a bad reaction, you don’t need venom immunotherapy but here is your epinephrine injector? What they hear is I’m going to die. Besides, the emergency room already told them they are going to die from the next sting inserted their primary doctor in half their friends. What we see in this study is patients were randomized to get either pending immunotherapy or epinephrine injector. And this was a quality study. So they filled in a quality-of-life questionnaire for insect allergy and then what we see is that patients on venom immunotherapy had a much improved quality of life. They felt much better about their chance of not having a reaction. The people who got the injector had a decrease in quality of life. They are more impaired than they were before. Because they are just as scared as they were before, maybe even more so. They don’t feel this is going to protect them, and it won’t. Very interesting. But there are people who refuse to be randomized. And the people who chose the injector instead of immunotherapy did not have decreased quality of life. They were happy with that injector. They felt that it was a kind of insurance for them. This is a shared decision-making at its best. When it is done properly. I have that discussion with these patients who are low risk. I explained to them why they maybe don’t need the injector. I explore that with them. If they are comfortable, great. They are still scared to death and they would feel much better, great, I will prescribe them. But that is my approach and it is a lesson in shared decision-making as well, how we approach low risk patients.

So who needs venom immunotherapy? Well, really people who are at risk from having a moderate to severe enough electric reaction. A part of what — anaphylactic reaction. What are the chances they are going to get worse? Those are the mild reactions. I alluded earlier to the pediatric studies and turns out Journal 1990 reported that the chance of these children having a more severe reaction was very, very small. Zero, actually, in the 1990 publication, less than 3%, less than 2% in a later report. These are adults that we stunned and out of 81 adults with continued reactions, only two got worse. Again, less than 3% chance of a worse reaction. None of the moderate reactors got worse, interestingly. This whole thing that it is going to get worse every time, not true. Reactions usually are the same if they were before or less, and only occasionally do they get worse. So this really has a lot of bearing on who needs venom immunotherapy. The people who are at risk for moderate to severe reactions, sure. These are the ones that just been talking about. 5, 10, 50% chance they have a systemic reaction, of less than 5% is going to be epinephrine. Therefore, we say that an immunotherapy is not required. I didn’t say we don’t do it, it is not required. Not necessary. Because the risk is so low. But we do review with them, shared decision-making. We want to check if a have other high risk factors. We may want to know if they are on a beta blocker. Maybe they are beekeepers. Maybe there’s reasons to consider immunotherapy, including quality-of-life. If in the end I can persuade them that less than 3% risk is something they can live with, if they would feel immensely better in their daily life being on venom immunotherapy, yes. I said a bit about large, local reactions. They are usually delayed and can be very large. What if the chance of future reaction? 4%-10% has been the estimate for systemic reaction but less than 3% chance of anaphylaxis. So both epinephrine and immunotherapy are probably not necessary, but could be considered shared decision-making. This is from the new England journal of medicine and I’ve already mentioned the background. This is to remind me in case I haven’t already said. This was a 57-year-old man who presented to the emergency room with acute onset. They ruled out a heart attack, they have the endoscopy us come down to look at him to see if it was esophagitis, of when they went a little bit further, this is what they found. Reviewing the history, the chest pain all started when he was drinking from a soda can outdoors. So again, not a good idea to drink from straws and soda cans outdoors. If that person had been allergic to the insect it might have been a bad outcome. Been an immunotherapy actually does reduce large local reactions. So although that immunotherapy is not required to prevent systemic reactions in these patients, we’ve had patients who could study every year, they end up on steroids for the large locals. We can reduce by 50%-70% the size and duration of that swelling with immunotherapy. It really does work. And it is really only indicated for those individuals who frequent the struggle with these large local reactions.

I will skip some of the technicalities here. I’m already going to leave not enough time for questions. Allergist will want to know more about some of the ways in which we think we can streamline venom immunotherapy. You can use shorter treatment schedule that are very safe, over dosages this children are really quite effective. We can manage systemic reactions the same as we do with other allergy shots. We actually see last systemic reaction venom immunotherapy than Rast or Kathy therapy. — grass or cat immunotherapy. I’ve mentioned stopping venom immunotherapy. Five years is better than three, and is considered a good point to consider stopping. Testing is not helpful. It doesn’t give us any predictive value, but the past history and the tryptase are the two things that can tell us whether this person should or shouldn’t stop immunotherapy, aside from their personal values and preferences. That is shared decision-making. This table from the practice parameter summarizes that there are people, these five risk factors are reasons to continue venom immunotherapy indefinitely and there are other things that may make you want to extend it as well. I won’t go into all the details but it is mostly things I’ve already mentioned today. This is an estimate based on our data. It basically says if a person has any of the risk factors I just said, which is about one third of our population, one third had one or more of these risk factors, they have an estimated 45% chance of reaction based on treatment. The other two thirds to don’t have any of these risk factors in a less than 3% chance of reaction after stopping treatment. Pretty much the same as the general population. When we add this all up, there is a 70% chance, but now we’ve learned that we don’t stop treatment for the high-risk people and we feel very comfortable stopping treatment after five years in the low risk people. So in case I didn’t mention some of these, someone talks to their personal doctor or friends and relatives, primary doctor and get all of this misinformation. The next window tell you. No. The chance of dying is approximately one in 500,000. Almost the same range as getting it by lightning. It will always get worse? No. It’s very unlikely to get worse on the next sting. You will outgrow it? Maybe not. We published in a 2000 for a journal with children within sexting allergies. From that study, an estimated 30% chance or more that they will react again 20 years later even if they didn’t have any stings in between. We’ve addressed the it was a fluke question. No it was not a fluke you are allergic and you are going to react the next sting, 50% chance. And Benadryl will take care of it. We didn’t talk about anaphylaxis in general. I will promote them. No. When someone says Benadryl worked because there anaphylaxis got better, no. There anaphylaxis got better despite taking Benadryl. Benadryl us to do anything for anaphylaxis. It might help the itching and hives but first of all, it takes 30 plus minutes to work and by that time hopefully you are better because if you are not, then you are not. That is it for now. I invite questions always. I’m happy to answer emails. Happy to answer questions now. Thank you.

Lynda: Thank you so much. I get the take away is don’t use cans of soda or whatever outside with straws. So I will try to run through a lot these questions that are coming. Does there need to be a past exposure of a sting in order for a person to have an anaphylactic reaction or can it happen on first exposure?

Dr. Golden: Like every allergy you have to be sensitized, so there has to be a prior exposure, the people don’t always remember it. We are aware people who say they have never been stung before but that will be asked their older siblings or parents they said yeah, when he was two, he doesn’t remember. There has to be a prior exposure. But the first reaction could be severe or fatal.

Lynda: wow. Is there any role for a bluesman in treating insect stings allergies?

Dr. Golden: Interesting question. It is not FDA-approved for prevention insect sting anaphylaxis, is not approved for preventing any tenant anaphylaxis, it is as you know approved to raise the threshold for reaction in people with multiple food allergies, which is another way of saying we are trying to reduce the chance of severe anaphylaxis. Would it work for insect sting anaphylaxis? I certainly have opinions about that, but we don’t know. There are no data. The only thing that has been published, and this is off label, and there aren’t very many, but there are people who have great difficulty with repeated systemic reactions and although I didn’t mention it, aside from adjusting the regimen and pre-medicating, we can treat them with — Rick Smith usually but not always successful in allowing them to get that full dosage and be fully immunized, so yes, it does prevent reactions, and there are easily 100 published cases of what I just said. But no organized study and it is not FDA approved.

Lynda: is there any testing available for non–bee related stings like mosquitoes?

Dr. Golden: Mosquitoes are biting insects. Although there have been rare cases of anaphylaxis, there is not an accurate test. It is a shame really because the work has been done by a group in Canada who did all the molecular work in isolated the allergens and had a fabulous test. It takes a lot to get an allergy test to market in the U.S. So no, there is not an accurate test for mosquito or any other biting insect allergy.

Lynda: Is there an age restriction for insect immunotherapy for children?

Dr. Golden: No.

Lynda: The question I had is why isn’t bumblebee immunotherapy available in the U.S.? Is that the answer you just gave about being hard to get approved?

Dr. Golden: Well, if someone wanted to pursue it, that would be the question, yes. They would presumably have to do a full-scale trial challenged like was originally done. When this was developed in the 1970’s, bumblebee was not seen as a concern. It’s still a very, very low frequency event. In greenhouse workers that with the model. Rather than put the Met of a job, they actually created their own –. There is no commercially available treatment and I don’t see it coming which is too bad. I’ve had two patients with anaphylaxis. Have them try to stay away from stinging insects. I was going to speculate about other possible treatments but it would be speculation. There are rare cases that have to be treated individually and managed individually.

Lynda: If a patient tells you that they are guessing they reacted to a yellow jacket, how do you proceed? Do you have to check all the available?

Dr. Golden: We recommend to test with all the available denims. First of all because the patient is not necessarily correct. I’ve had several cases that were almost funny in the degree to which the patient was incorrect. And because you never know — so, I say there are people who are positive to honeybee and yellowjacket have only had one reaction. And maybe it was honeybee. But how do you know they are not going to have a reaction time they are stung by a yellowjacket? We’ve had patients where that was exactly what happened. They were treated with one of the Benham’s and then some years later they were stunned by that insect and had a reaction so the practice parameters recommend to test and treat with all venom’s. I didn’t really say, but fire and is tested and treated with a full body extract, it is not a purified venom but the approaches the same. In the one exception may be is fire and. And to some extent, honeybee. When a beekeeper gets stung attending the hives, it is probably a honeybee. When someone is walking barefoot in a fire ant infested area, it is probably a fire and allergy. Did those people even need to be tested with the other venom’s? Some experts have argued that don’t really need to, and others have said what I just said before, how do you know they are not allergic to another insect that they are going to react to in the future? That is a roundabout answer to say why we prefer to recommend to test and treat with all venoms.

Lynda: OK. Is there a window for measuring BST?

Dr. Golden: Yes. The baseline serum tryptase, no because it is baseline. That is what your level is everyday. I didn’t talk about acute tryptase and that is during the reaction. And we are recommending, and we wish the emergency physicians would read our guidelines, that the acute tryptase levels should be drawn as early as possible during an anaphylactic reaction, and there is a window there because it goes up and then it comes down over an hour or two or three, so if you wait too long you might miss it. Ideally it should be drawn within one or two hours after the onset of the anaphylactic reaction. And it is helpful in a number of ways. Mainly in that it can prove there really was or was not an anaphylactic reaction and you would be surprised how many times we are fooled by the patient and then we find the true answer from the acute tryptase level. That is where there is a window during the reaction but baseline is baseline. But you want to wait at least a few days and preferably a week or longer to get a true baseline level.

Lynda: Thank you very much. It is 1:00 so I think I have to cut that off and I know there was a few more questions. As Dr. Golden indicated, you can email him and ask a question if you would like to do so. Thank you so much, this was so informative. Really appreciate your time. What I’m going to do is move on to wrapping up and telling everybody about our next webinar is going to be on April 2, Dr. Katerina will be discussing food allergy approaches toward individual management. On April 9, are black people like me series will resume, and this is going to be about eczema in the black community, how it is different from that on white skin. So if you know patients and caregivers who would benefit from attending that, please spread the word about that. Really want to encourage as many patients and caregivers as possible to attend that. And we have some other ones coming up in May that will be going on in the future through emails and whatnot. You will receive an email from Zoom in a few days with a link to the recording and supplemental resources. Thank you from all of us here at allergy and asthma network. Join us as we work every day to improve the life and health of those working with allergies, asthma and related conditions. Thanks again, Dr. Golden. Dr.

Golden: My pleasure, thank you.