Otolaryngologist Anna Butrymowicz, MD, discusses the common – and growing – problem of environmental allergies, exploring reasons for the increase and looking at the impact allergies have on overall health and quality of life. She elucidates the challenging diagnostic process and how to select the right treatments. Includes a look at current and future approaches to immunotherapy – which can cure allergies.
you know, it really is a pleasure to talk with all of you guys today. Um when I joined UCSF here on the West Coast, I was, I was very surprised at kind of the the how allergy is allergy care is um is delivered to the community back on the East coast. It really was a mix of otolaryngologist and primary care physicians who did a lot of the testing and treatment for environmental allergies. And I really noticed that unfortunately here on the West Coast, most the majority of care was driven by our allergy, immunology colleagues or primary care colleagues. And so as an otolaryngologist that has, has trained an allergy, I really felt like my role and my job is to be a comprehensive kind of nasal um surgeon and physician and a huge part of that is treating rhino conjunctivitis uh and the vast majority of what causes that is allergies. And so that's why I'm happy to talk to you today. Not only to emphasize the fact that we, as otolaryngologist are happy to treat conditions of allergy in the upper airway, but also that, you know, I'm open to seeing any of your patients with any nasal complaints. And I'm an open door for all of you if there any questions. So I have no relevant financial um disclosures. So it's allergies interesting in this day and age because we seem to be stigmatized if we're sneezing in public at all. Right. And so we're spreading droplets. Not a great thing, but I titled this talk I think to not only to bring you guys in, but allergies are more than just a sneeze. And I'm hoping that through our conversation, you'll recognize why it's really important to recognize allergy and your patient cohorts and what it is that we should do to treat them either medically and or kind of taking next steps with allergy testing and treatment. Um So with that quick outline of Who are the people that really develop allergies and why do they develop allergies? Why do we treat them? What are the comorbidities that they're associated with? How do we diagnose it and how do we then treat it? And what are the future treatment modalities that we can anticipate happening in the next five or 10 years? So in regard to who develops allergy heck of a lot of people. The world allergy organization is warned that the prevalence of allergic diseases worldwide is rising dramatically in both developed and developing countries. Um And that's really interesting. One of the hypothesis is why about why allergies is increasing in developed countries and undeveloped countries is that um you know cena phileo or I. G. E. Is what drives allergic disease. So we teach to inflammatory response. Um Going back to our immunology days the same thing. Yes. NFL's and I. G. Also treat parasites. And as we see that um as we became urbanized and developed all over the world, the prevalence of parasites have gone down. And most people hypothesis that the emergence of allergy is really because um Houston affiliate and I. G. Have no longer spend all of their efforts fighting parasitic diseases. And now we are starting to become sensitized to relatively benign entities in our environment. And so sensitization rates are massive here in the United States. 40 to 50% of patients are sensitized. And what does that mean? If you allergy test 100 people then 40 to 50 of them will have some sort of sensitization and their allergy testing. But that doesn't necessarily mean they have clinical allergy. So clinical allergy is really estimated to be more 10 to 30% of the population. And that could be because of a couple of things you can be sensitized because perhaps the allergy testing is um is giving false positive results, which we can we'll talk about a little bit. But also just because you're sensitized doesn't mean you're going to be exposed to those things. So my prime example is um we often see that patients are allergic to cats when you do skin testing, but if you're not around cats, if you're not exposed to cats on a regular basis, you're not going to have a clinical disease that's consistent with allergic rhino conjunctivitis as a consequence of your cat allergy. So, sensitization alone is not the end. All be all you really have to be exposed to the allergies that a certain concentration and develop clinical symptoms that are consistent with allergic rhino conductive itis, But this is super common, six months 6th most common disease and adults. Um and we also see that allergy um the diagnosis of allergy usually manifest in different ways, depending on our age group. So when kids are born usually really don't manifest allergy until we get to about one year old where we start to see um eczema or a topic dermatitis as a consequence of allergy. We also see the peak and food allergy as we all know with peanut tree nut allergy. Um But that tends to go down and as we enter around age 56 this is where we see an increase in the incidence of allergic asthma, which then starts to drop as we get into our teen years. And that's really when we see the peak in our early twenties of allergic rhino conjunctivitis. Um And so this a topic marches seen throughout populations. And so it's often predictable that in patients who are one year old and have allergic eczema so that we can predict that they will become asthmatic if we don't control kind of environmental factors or treat them. Um systemically. The other reason it's important treat allergies because allergy is associated with so many comorbidities. So allergic rhino conjunctivitis essentially is inflammation of the upper airway. But as a consequence of that inflammation of the upper airway, we see a number of different things that can happen. Sinusitis, chronic sinusitis, 40 of patients will be sensitized to an allergen and likely that's contributing to the pan inflammation in the nasal sinuses, um inflammation of the U. Station tube from allergies can predispose us to use Station to dysfunction, chronic otitis media and other chronic inflammatory diseases of the year. We know that when you have poorly controlled upper airway allergy that can also exacerbate your asthma. And so we often see in our allergic patients that their asthma gets worse during their allergic season. If we control their their allergies or asthma will then in line become more controllable um nasal polyp poses, which is also an essential Philip driven process. Almost half of those patients will also be allergic. And once we treat the nasal polyps, treating the allergy can has the potential of decreasing the incidence of recurrence of these nasal polyps, we also know it affects your sleep. I'm sure anecdotally all of us either are allergic or have friends or family that are allergic and during their allergy season they always say that they're very tired and fatigued. Um And that's because the inflammation associated with allergy has central effects on our deep stage sleep. And we noticed that patients, when we compare allergic patients, do not allergic patients, that the deep stage sleep cycles are much shorter in our allergic patients. And so as a consequence your sleep is much less restorative. We really are dependent on that deep stage sleep. And not only that, but when we have a significant amount of nasal obstruction and their mouth breathing at night, we know that can affect not only our craniofacial skeleton in our mid face um development, but also can predispose us to inclusive issues or periodontal disease and increase in sense of cavities. So for a number of reasons I think it's very very important not only to recognize allergy but to treat it effectively to help prevent all of these consequences. We also know it's just very expensive to treat allergy $8 billion lost days of school meeting, childcare for the days that they are very allergic and can't go to school. What's hard to quantify is those indirect costs associated with present he is. Um So there are two kind of factors here. When we talk about kind of work, workplace functioning and efficiency, four million missed days of work. Now that's the absenteeism aspect present present is um is when you're allergic patients will go to work or will go to school but they aren't as effective or efficient in their work because they are tired because they are congested. Um And that is really really hard to quantify. But a huge aspect of what we try to follow in our allergic patients, Almost 50 if not more of allergic patients say it affects their quality of life. And we'll see that when we look at the ARIA criteria of how to quantify allergic disease, that that puts you in a severe category. Um so we'll talk about that again in a little bit and it's and again hugely prevalent. One in five americans diagnosed with allergies. Um in any of those aspects allergic asthma, rhino conjunctivitis, a topic dermatitis and all of your asthma. Asthma patients, two thirds of them will have allergies that may be driving and exacerbating their asthma. And so it's important that all of your asthma patients also be screened for allergic issues and potentially be tested for allergies. We know there's a heritability factor as well to patients to parents with allergies and your kiss Is 75 more likely to have allergies. Um So that's a big deal. And why do we develop them? So, we kind of talked about genetic predispositions, right? If you have two parents with it, then you're more likely to have it. There's also something called epigenetic factors. So if your grandmother smoked the smoking in, your grandmother will allow certain genes to be turned off in certain genes to be turned off. That's what's called epigenetic. And that epigenetic factor will then be heritable to your grandkids. So because your grandmother smoked grandkids are more likely to have allergies because of the epigenetic effects of that. And then we talk a lot about lifestyle functions, um and environmental factors, the most popular of which is really driven by the hygiene hypothesis. So, David Strahan, back in 1989, published this study, Hay fever hygiene and household size, where he basically had looked at a bunch of kids and um looked at those with allergies and look to see, you know, what are the factors that may predispose them to allergies? And they realize that firstborn kids or kids in families, only Children of only Children were more likely to have allergies than younger Children in a multi child household. He supposed that it was likely that the oldest Children are the only Children were less likely to have infections. And so that was the reason that they did not develop a topic disease. The conclusion was a bit of a jump. Um And that was what we um we defined as the hygiene hypothesis. Um That thought process has evolved a little bit in reality. The increase in infections did not have an effect on a topic disease at all, but rather what we saw is that younger Children in a group of multi multi child household, they were likely to be exposed to a higher diversity of microbes and that diversity lead not only from exposure but colonization of those microbes and that led to a decrease in N. A. T. P. One of the studies that helped us quantify that quite a bit was um in the nineties there were some immunologists that looked at populations from the eastern western block of europe. So before the iron curtain fell, western europe was really considered kind of urbanized. What significant medical care. Lots of antibiotic use, high population density. Where in East and the eastern Block it was more of an agrarian society, Lots of farms, large family households um drinking unpasteurized milk from the farm exposure to a lot of farm animals. So essentially these were these were patient populations that were genetically very similar but environmentally very dissimilar. And once the iron curtain came up there were some immunologists that looked and sampled Children from both of these populations and found when they looked at the microbiome and their feces, that they're, the diversity was very different. While patients from Hungary had a lot of high concentration of probiotic species, species like lactobacillus and a significant diversity of species, patients from Sweden actually had more pathologic species like Caronia bacterium. And there was much less diversity. So it really showed that it was a healthy and diverse microbiome that tended to um that was associated with a decrease in a topic disease. And that's really what we consider our hygiene hypothesis today. And so when we look at all of the factors associated with allergy that have come come to light, we can also kind of makes sense of why the microbiome is super important. So some of the protective factors that we've realized Children that are raised on farm with domestic livestock. If you have a dog at home, that decreases the likelihood you're going to develop allergic disease growing up. Um If you are if you gave birth via vaginal delivery, the exposure to all of the microbiome through the birth canal significantly decrease your likelihood of developing allergy, developing allergies later in life breastfeeding um and exposure of the microbiome within the breast milk in the breast tissue itself, drinking unpasteurized farm milk and inductive factors, things that will increase your likelihood of developing allergies later in life C section earlier for early formula feeding traditionally has been thought that way, but now we certainly do have more pro and prebiotic enriched formulas. And so it's unclear if those um will change uh the predictive, how often patients will develop a topic disease um and also exposure to antibiotics. So all very clear that microbiome has quite a bit of a of a role here in development of allergy. So now that we know that it's really important, we have to be able to recognize it. And here is the challenge with diagnosing allergy based on symptoms. The symptoms are all over the place. Um if you look at some of these you start to think, you know there's so many other disease processes that present like this. You know, one of my biggest challenges is an otolaryngologist is someone will come to my to my office and say I have a lot of nasal congestion and sinus pressure and sinus headaches. And I have to really make the distinction. Is this allergy or is this chronic sinusitis? That's really really hard to do unless you're doing imaging studies on a regular basis. And so I imagine it's also very hard for my Internal medicine colleagues to make that distinction. It is a full breath of presentation that patients will have um waking up at night, coughing headache, sore throat. Um I see a lot of adults with add New Chancellor hypertrophy who are treated with antibiotics chronically. And yet it's allergy that's driving the inflammatory process in their councils and adenoids, just a blocked nose, watery eyes, itchy nose, runny nose, snoring, itchy palate, very diverse presentation among all of these patients. And so it's really important that we recognize that our allergy patients aren't just itchy watery eyes and runny nose. We have to be able to distinguish. Um the diversity of complaints that are allergy patients will come into our office with and once we identify that the we should be able to categorize this in some way. Um And the way that most of the literature is defining um allergies is intermittent versus persistent and mild to moderate severe. The the a former kind of way of thinking of perennial versus these little allergy um is kind of frowned upon I guess at this point. Um And so we're really using this kind of um these kind of terms to help define and categorize allergy. So persistent more than four days a week for over four weeks um and intermittent, less than four days a week for less than four weeks, mild, essentially no effect to your quality of life, no effect to your to any of the things that you do moderate severe, Renecting your quality of life. So again, 50 of allergy patients will say it affects their quality of life. So 50 of patients by definition or moderate to severe. And so that's really important. And so when we look at kind of medical management of allergy, that really helps define how what our first steps and management should be. So, when patients present with symptoms and we categorize them and kind of moderate or mild, severe, persistent, um how do we confirm the allergy is a problem? Um We can do some blood testing which is readily accessible um In all of our clinics we can send them to quest and say give us a Northeast panel um and we will be able to define whether or not they have allergic sensitivities. Unfortunately, blood testing is not that sensitive and so it misses a lot of allergy. The positive is that there is absolutely no risk of anaphylaxis from taking some blood. And you can perform regardless of what medications they're on or what kind of skin reactivity they have. Unfortunately, in terms of health care costs, it's quite expensive. Um and inevitably the results are delayed. Skin testing is the most sensitive way for us to discover. Not only do patients have allergies, what are their allergies, it's often considered much less expensive. There are immediate results. The challenges is that there is a very, very small risk of anaphylaxis. Um And so we do kind of help, we do screen our patients that may be at risk for anaphylaxis. And those patients are active asthma, exacerbation patients on a beta blocker um active you are I and history of anaphylaxis. So some of these patients, we will then differ and say let's do blood testing instead. Um But skin skin protesting is our preferred modality. And then once you're diagnosed, how do we treat you again? You know, I don't often see the mild the patients that I see that are mild, it's often a secondary complaint to something else that's going on. Um And so if you imagine if patients are complaining, you know, for three days out of the year when the cypress trees are blossoming, um I noticed that I get itchy, watery eyes and runny nose. And so those three days when you know that your when you kind of sense in the morning that you're going to be allergic taking in Orlando histamine like Zyrtec, your Allegra I think is more than appropriate. Um But what I tend to see is more moderate to severe disease that's persistent. And again, if it's affecting your quality of life, your moderate to severe, if it's affecting your sleep, it's affecting your ability to function to exercise. Um then that's moderate to severe. And again, if it's happening more than four days a week, for more than four weeks, you're persistent. So I often see this category of patients. But overall, I think the message here, although this is a little bit of a messy flow chart. Um when we look at huge population studies and look to see what is our best single modality of treatment for allergic patients with allergic rhino conjunctivitis, intra nasal steroids, blow everything else out of the water. I'm an otolaryngologist. I would I wouldn't mind putting flown is in the water for everybody. But this is really a medication that is safe to use in the long term and should be utilized for the vast majority of patients with international complaints. And this doesn't have to be allergic rhinitis. Non allergic rhinitis. Um, response just as well to inter nasal steroids. So even if there is this kind of um if you're on the fence about what type of rhinitis is going on, what's causing their nasal obstruction trial of nasal steroids I think is the appropriate first step. And if those patients don't respond to inter nasal steroids and again, large studies looking at what is the next modality of treatment that we would add to? Inter nasal steroids. Um intra nasal anti histamines are the best next step. So something like as elastin oral anti histamines have very little role in my practice. Um I think they're only role is for mild intermittent disease. And once you have moderate and persistent symptoms, always starting with inter nasal steroids and then adding an international anti histamine, if the symptoms poorly respond, that's usually my line. So if if patients are treated with both modalities and they either fail to respond or they say I'm not tolerating this, then that's when I say, let's do some allergy testing and let's do some allergy treatment potentially. There are some other modalities that you can add. A petroleum is a great addition. If you're using both intra nasal anti histamines and inter nasal steroids. And they still seem to have a lot of running this either anterior early or with post nasal drip. Um, I think the acrobat nasal spray is a great addition, but essentially I am a Flonase as elastin then immunotherapy if that really doesn't work In regard to systemic immunotherapy. So this is really the only opportunity to potentially cure patients of their allergies. And that's a big statement right, 80 of patients who undergo systemic immunotherapy for the recommended duration will be cured of their allergies. And so that means none of that absenteeism from work. None of the wasted money of buying all of the nasal sprays and allergy rinses and etcetera. Um, I think that this is an important modality of treatment. Unfortunately it takes a long time to do 3-5 years and it's often pretty expensive the way that we deliver immunotherapy, the United States of America's two modalities. Allergy shots are the most traditional um and sublingual immunotherapy, which I'll be talking about as well, which happens less often here, but something that we certainly are providing to our allergy patients in our otolaryngology clinic. So subcutaneous immunotherapy allergy shots, we also call it skit, for short, it's the most established method in the United States of America, But this is kind of, I was so impressed by the statistic. Only five of patients with poorly controlled allergic rhinitis undergo skit. Now, why is that? It's expensive. It takes a long time. Not a lot of allergists perhaps are in communities of need. Um, and perhaps we don't recognize that patients should be offered a referral to either an allergy immunologist or do an otolaryngologist to discuss immunotherapy. So I think this is a very undertreated patient population But we know 80 of patients who actually undergo immunotherapy will improve significantly. But there is the risk of anaphylaxis again with allergy shots. And it's a significant costs for particularly in the first year while you're escalating therapy usually go into the clinic once a week. And so there are copays associated with that. Um And then you have to either miss work or school to be able to do that. And so that certainly is quite a commitment. Mhm. And in regard to sublingual immunotherapy, this is really the modality that when we when I came over to U. C. S. F. I was really motivated to start because I saw that there was very little done in terms of sublingual immunotherapy in the Bay Area. Um And this is the modality that we often treated patients with on the East Coast. Um For good reason you basically have a bottle of everything that would be otherwise in your allergy shot you get drops under the tongue, the first drops you take your in clinic, they monitor you to look for reactions when you take that bottle home for three months and you use it every day. It is the same duration of treatment, 3-5 years with essentially the same efficacy. And there is a although there is a very small risk of anaphylaxis much less than with subcutaneous immunotherapy. So it's safe. It's effective the challenges. It is not FDA approved. So it's considered off label use of Aquarius immunotherapy. What does that mean? That means it's an out of pocket cost. Um Across the country it costs a different amount of money depending on the clinic you go to. I've heard $400 I've heard $100. Um And most of the places in the Bay Area, it tends to be in the mid two hundreds for a three month supply, Which if you think about going every week to an allergy clinic for allergy shots and paying $20 for each of those copays. Um it's somewhat equivalent. The thing is you don't lose a lot of work days, you don't lose a lot of school days, you don't lose travel time and travel money. And so it tends to be financially, I think a moot point but still is quite a commitment of time and money, efficacy. Um Our allergy immunology colleagues are less eager to provide sublingual immunotherapy and they often cite the fact that it's not FDA approved. Um you know, I think there are lots of medications that we use off label and sublingual immunotherapy really has proven its efficacy. There are a number of meta analyses and reviews that really look at um Sublingual immunotherapy being just as efficacious. But what they're very, what there is very little of is direct head to head testing of sublingual immunotherapy to subcutaneous immunotherapy. Um So only for double blind randomized controlled trials that directly compare skit and slip And all. But one of the studies found no difference in control of symptoms and medication use of medications between the different modalities. One of the studies showed that the treatment effect of subcutaneous immunotherapy was better than slit, but that was only one year into treatment and it was about 30 patients. So it's hard to make really large conclusions about that. Um and essentially this review concluded that because of the heterogeneity of the studies and the small number of patients, it's really difficult to make broad conclusions. But what we certainly do know is sublingual immunotherapy is certainly safer than subcutaneous immunotherapy. And it's and it's long term efficacy over subcutaneous immunotherapy is hard to make conclusions about. So when we look at some of these randomized controlled trials, again, there's so many more studies looking at subcutaneous immunotherapy just because it's been around so much longer. Sublingual immunotherapy really only has been studied since the 90s. Um and so there's much more evidence to say that it's effective for asthma and rhinitis and conjunctivitis. Um and for sublingual immunotherapy, the evidence isn't as strong and again there aren't as many studies and it's very hard to compare when there is no head to head trial. But the future of therapy I think is something that truly is interesting. The Karolinska Institute in Sweden started doing some immunotherapy delivery straight into lymph nodes. Um and the reason that they were doing that is because the risk of anaphylaxis is because we have these peripheral inflammatory cells that can that can take in whatever allergy and you are providing and and create a systemic inflammatory response. But those are those kind of inflammatory cells are only at our periphery and they don't exist within a lymph node itself and the tolerance that we're hoping to achieve from memory T cells, all of that is happening within the lymph node itself. And so if we deliver allergy directly into the lymph node, we can prevent the systemic reactions while improving our delivery of allergy in to the location where we need it. Thus ideally making it more efficacious um sensitization and tolerance over time. So you're presenting a small amount of androgen into the lymph nodes and it bypasses the peripheral cells and we produce a higher concentration response to in response which leads to quicker tolerance. What does that mean? Traditionally subcutaneous immunotherapy? Sublingual immunotherapy is delivered over 3-5 years in inter lymphatic immunotherapy. We found efficacy after three injections in two months That mimics the sensitization that you get from 3-5 years of subcutaneous or sublingual immunotherapy. So this is massive. Um You know if you can now minimize the treatment of your allergic patients to three injections in two months now that will potentially increase the patients that you would be able to treat effectively. Um And it also decreases the the likelihood of these systemic anaphylactic reactions. So there is a group that was doing a safety trial in Austin um and they have I believe they just published the results to say that it's that it's a safe treatment. But in terms of randomized controlled trials, UCSF is hoping to start one of the first randomized controlled trials of intra lymphatic immunotherapy here in the United States of America. And I really do think that this is going to be a modality. That changes the way that we deliver allergy care in the United States of America probably within the next 5 to 10 years. So I'm eager obviously to deliver this news to everybody and keep your eye out for more information about this. But that's essentially everything. You know, I think more than anything else, I wanted to conclude that I think allergies truly important for a number of reasons and I think it's underdiagnosed and undertreated. Um I think they're really effective ways to treat allergy and improve patient quality of life and prevent associated diseases. But unfortunately right now it's a bit expensive and cumbersome. Um you know, our diagnostic techniques continue to improve and immunotherapy can potentially cure these patients and we may be able to even deliver immunotherapy and much more efficacious ways. Um, and so, you know, I'm happy to be the person to spread that news.
