Olfactory dysfunction has become even more common during the pandemic, yet its causes range widely from COVID-19 infections to neurological problems, including Parkinson’s and brain tumors, to simple aging. In this guide to understanding the condition and counseling patients appropriately, rhinologist Jose Gurrola II, MD, covering types of smell loss, the impact on patients’ lives, when to order labs or imaging, expected recovery times for COVID patients, and therapies worth trying.
Doctor Loftus and I have worked together to put together a uh topic of olfactory dysfunction to be given for our referring providers. Uh, it's rather, uh, practical at this point. It used to be several years ago. Um, it would be very difficult to get people to show up for a smell loss talk. Um, COVID has kind of put the world on its head in so many ways that this has gone from an area where many of us thought we could kind of generate, uh, Research, uh, interest on an orphan topic to now everyone is suddenly interested in it, um, from a rhihinology perspective as well as, uh, kind of multi, uh, impact in, in society. Um, so I will go ahead and start sharing my slides here. Um, and I do believe that once I start sharing this, I won't be able to, uh, see too many people. Uh, are they coming up OK for everyone right now? Yes, we can see all your slides. Perfect. Thank you all so much. So this is an olfactory dysfunction. I have no relevant disclosures. Um, a general overview and I will try to keep from, uh, completely, uh, getting in the weeds or otherwise, uh, as I would consider it nerding out on the aspects of smell that will drive all of you nuts, uh, for me to talk about. Um, we'll go over some of the Reasons why it's important, uh, that may not be so obvious to our patients. Talk a little bit about anatomy and then the relationship of smell to our, uh, other, uh, senses, and then go over the classifications that we use, uh, go over some etiologies, uh, how we evaluate, and then some of the treatment options. Um, I think we all realize that smell. is a primary driver of uh a lot of our quality of life. If we don't realize it, you can imagine when you have a cold, how miserable it is to not be able to smell, to not be able to um take in the different flavors and taste. It is triggered or it's related to uh so many other triggers for us, memories, uh, happiness, our social interactions, and then in many cases, um, our occupational ability, uh, whether that be, uh, smelling. Uh, fire or other components of things that may be, uh, not good for us or, uh, optimizing our ability to cook cause we're chefs or needing to take care of others who may need, uh, certain smell-related components of their care taken care of. Um, in terms of safety, uh, just day to day, realizing which food is good, which food is bad, whether or not we have toxins in the air, whether there's gas leaks, and then our daily hygiene. Um, I'll add, as I'm going through these that, uh, I do have a lot of slides. I don't need to, I think, get into the weeds, but if, uh, anyone has any particular, uh, interest in anything that I'm going over, um, I'm happy to come back to any of the slides, but I will try to keep it, uh, as relevant as possible. I think one of The important components of smell loss that relates to primary care and uh general internal medicine that many of us are probably aware of, but for those of us who aren't or otherwise for our patients who aren't, is that uh olfactory loss can be an early sign of a lot of different diseases. Um, this includes Parkinson's and Alzheimer's, which is, are some of the more commonly known ones, but also frontotemporal dementia, multiple sclerosis, and then in some cases, brain tumors. Um, Any of these can be rather gradual. When they're more uh sudden or when they aren't related to the other factors that we're seeing with things like Parkinson's and Alzheimer's, um, they can be very useful in terms of establishing an early plan of treatment for a lot of these patients. When it's related to brain tumors, we oftentimes see other, um, Other symptoms or other signs that things are going on and uh they're helpful, but we do use olfaction or the loss of olfaction and changes in olfaction as a uh another clinical sign that may be indicative of what's going on. Um, this is a little more in the weeds, but cranial nerve one is the olfactory nerve. Um, as we're looking up here, it sits right above the nasal cavity. Um, other components that, that we often associate with smell are often the scents that we get from things like camphor or menthol, uh, when we feel it in our nerves. Those are often transmitted by the trigeminal nerve. Um, when we're talking from a rhihinnology perspective about areas of import, the olfactory cleft is the space intranasal that is between the superior turbinate and the septum. The olfactory fossa, when we're talking about That or you're seeing things on a CT or MRI is above the nasal cavity and that is along the area where the um nerve itself actually exists. Um, so the cleft would be here and the fossa is above and intracranial. The neurofactory epithelium uh is this small area in the back that your sinus surgeon needs to be careful of and that patients feel like their COVID test is actually violating. It often doesn't go up that high, um, but this is along the area where if you get scarring, if you have inflammation, and it is obstructing, you will be blocking some of the 12 million receptors, um, that communicate between. The olfactory bulb and our external environment through our nose. Um, and I won't belabor, uh, many of these slides, but what we need to know is that the axons come through, and this is relevant more so in COVID is that historically, we've thought that when viruses attack this area, they're damaging the nerves. With COVID, it seemed as if it's dam uh damaging the supporting cells around this area. Um, and That prevents the full transmission of the odorant molecules being uh absorbed and interacting with these neurons transmitting directly and moving through our sensory system. Now, fortunately for the vast majority or for a strong majority of a lot of our initial COVID and the delta wave COVID patients, our basal cells along this olfactory epithelium tend to regenerate every Um, 4 to 8 weeks. It'll vary from patient to patient and with age and depending on the type of injury. But as these tend to recur, we tend to see people regaining their smell, uh, whether it's related to COVID or to other, um, Issues of loss of smell, whether it be another routine viral, um, or an infection of any sort. There is a relationship between smell and taste. There are tastes that patients, even if they lose their smell, will still have, and that is, uh, tends to be transmitted by our other cranial nerves, and those are sweet, sour, bitter, salty, and, uh, a mushroom or umami type flavor. Um, all of it's coordinated and runs through various pathways in our brain, um, but the vast majority of flavor, about 80% of it comes from our smell. So we lose a strong sense of flavor and differentiation other than salt, which is why as patients age, age and they lose their smell, or Alzheimer's patients who oftentimes want to put a tremendous amount of salt on our food. It's because there's a decreased sense of smell going on, so they lose their flavor and want to taste something. Um, in terms of prevalence, there are all kinds of numbers here as to how smell loss is increasing in our general population. I think the take-home here is that collectively, we're gonna encounter this, whether it be from a uh primary. care level, whether it be from our specialist uh level and examination or just even our families. Um, there's any number of variety of, uh, reasons that can be involved, but unfortunately, for a lot of the people who have smell loss, they won't necessarily notice it. They won't recognize it and it's particularly important when that's indicative of another change that may not be related to something as simple as a post-viral infection. Uh, the types of smell loss that or the way that we classify it is as follows. A decreased sense of smell is hiposmia. A complete loss of smell is gonna be anosmia or anosmia. And then, uh, hyperosmia is when you have an increased olfactory, uh, acuity, and it's often thought that it's due to a lower threshold. Um, some of those patients can be very interesting and they may think that they have a good sense of smell. They may just be rather sensitive, uh, to smell. I'm not sure why that's happening. So the dysosmia is a distorted sense of smell, and that can be associated when there is a smell that's present and it just smells differently to a person. It can be a complete hallucination when nothing is uh present, and oftentimes these are, uh, unfortunately not very pleasant smells when they're phantasms. Um, perrosmias, as we have listed here, uh, are linked to a, oops, excuse me, a number of different, uh, causes and things that can be happening, um, whether it's a shearing or a damage to the axon or a post-traumatic condition, uh, patients will know that they, um, oftentimes are smelling things that aren't there and nobody else is able to smell. That's how they usually will, uh, figure it out. So, uh, the majority of patients historically have been in their teens to 30s. Uh, it can be intermittent or persistent, and oftentimes patients will wonder or present to us asking if they're crazy as a result or what's going on. The vast majority of patients will present, um, Within a year, usually without treatment. This is showing the middle turbinate in a wide-open olfactory cleft region here. Um, recently, our group has shown that um distortions and phantassmias occur with post-COVID and it's mostly related to the recovery after they've lost, uh, all of their smell. So, Much like hearing loss, smell loss is considered or often broken down into conductive and sensory neuro. So the obstructive forms that we are often able to kind of get in and at least give other considerations other than just watching and waiting, uh, will be chronic nasal inflammation, polyps, and or, uh, sinus or sinonasal tumors. Uh, the sensory neural, uh, are a little bit more difficult to deal with in that we don't really have great treatments for a lot of these, and these can be post a viral. They can, when they're related to head trauma, there is a shearing at the skull base of the tiny axons that are coming through the bone, and that often can be difficult, uh, for us to do anything. We don't yet have an olfactory implant like we do for hearing loss. Medications can be a cause of what's going on. And then a number of different disorders, uh, whether they be endocrine-related or, uh, congenital. Of course, we're all aware of COVID. Um, and we, we put out a little series of different, um, publications on, on what all occurred, but smell and taste early on in the COVID pandemic were definitely a big driver, uh, as I think at this point, we all tend to know. Um, historically, post-viral, was the most common reason as to why we would see people for it. And it was thought, like I said, to reduce the number of uh the nerves coming down and it can often take weeks to months to recover. In COVID, uh, I won't belabor the point, but we think that it's the non-neuronal cells that are damaged, and these can often regenerate within a few weeks, which is why a lot of people were recovering without, um, Much, uh, dismay. There are, unfortunately, a, a number of either long COVID patients or patients who did not have the same type of recovery. Um, some of them, it can be a little bit more culturally impactful. Uh, I have several patients who were very big, uh, meat eaters, um, who loved, uh, all kinds of different flavors, and they now note that steak is a foul tasting. Um, food for them to have and, uh, cilantro now tastes like soap, and we may know a lot of patients who do note the cilantro tastes like soap, um, description that has, uh, been shown at least or suggested at least in some studies to be genetic. What's super interesting is that post-COVID, uh, some of these patients are describing a very similar presentation for, um, cilantro for them. Uh, the ACE2 receptors, uh, in the olfactory region are thought to be the reason why COVID was attacking this, uh, area. With the Omicron variant, we have not seen nearly as much. Um, and As of um the Delta variant, we saw that there were a number of different presentations and it can be rather high in some patients and particularly those who didn't get uh admitted to the hospital, their primary symptom would be uh smell and taste loss. Uh, more recent systematic reviews and meta-analyses show that about half of them, uh, would present with some form of smell loss. Um, and then, uh, it can occur in the absence of other symptoms as I suggest, it's often the healthy patients. Um, and then it was more common, um, for us to see that, uh, normosmia or normal smell. Um, for the patients who were admitted, uh, and having to undergo additional procedures or care. Um, This is just some of our own data, um, and we showed that with the changes in smell and taste and any number of myalgia, sore throat, and such, we were Predicting, at least for the outpatient, uh, survey responders that we had, uh, an ability of 82% to discriminate between positivity and negativity in COVID. Um, Egusia is a loss of taste and smell loss. You can see that those, uh, showed up with, uh, pretty strong predictive values, uh, that were clinically significant. Um, and this is just highlighting the nasal obstruction versus the anosmia itself, uh, and you see the difference, uh, between the COVID negatives and then also the COVID positives there. Excuse me. Um, when we looked at the, um, COVID patients for how severe the smell loss is, You can see that it tended to be uh closer to severe microsmia or severe smell loss, uh, and anosmia. There were several who came in with a moderate amount of smell loss as well. This is showing this in graph form, how the recovery goes from weeks. Um, about 80% are gonna recover to some mild smell loss to complete nomosmia after about 7 to 8 weeks. Um, And then I just explained some of this in terms of the taste that we've kind of gone over, that it comes from smell, that it's not a 1 to 1 correlation with if you lose your smell, but you're going to lose all of your taste. Oftentimes 1 may be more pronounced. You may notice that your smell has been hit harder, uh, whether or not it has, it has an impact on flavor, so you may notice the flavor of food is gone even though you think you still smell. Um. And it does not seem to be related to alterations in the saliva levels of, uh, or changes in saliva specifically. Um, so what we tell most of our patients is that, uh, with at least through Delta or with our patients who are coming in now, if they are having smell loss, that about 80% recover within a month. Uh, usually the most recover within about 3 weeks and then about 95% within about 6 months. Um, We're trying to figure out what to do with our long COVID patients and those patients who are, uh, not demonstrating return to baseline. Um, interestingly, prior to COVID, one of my, uh, primary research areas involved smell, and we had a specialized olfactometer or smell testing unit, uh, that we had made for us. Uh, we had it manufactured and we are now gonna utilize that to look at our patients, um, uh, that have altered smell loss, not necessarily complete smell loss, but who have things, a banana used to smell good or oranges used to smell good, and now it's smells um more like turpentine or it smells foul. So that is one of the things that we are looking to implement at UCSF, uh, very specifically through my research. I'm working on the IRB right now so we can get it going. It, it is not something that will necessarily impact the patients immediately, but I do find that the majority of them are, uh, encouraged by the fact that we're doing research and it does kind of hopefully shed at least a little bit of positivity that those patients won't be completely disregarded by our system. Um, we wanna make sure that the smell loss is COVID-related, that it's not related to injury, or that it didn't pre-exist. Uh, when they come in, when the patients come in, we do a full neuro exam, a nasal exam, and we want to rule out any kind of other sinus diseases. Um, we oftentimes we'll see the patients if they are still COVID positive or have not been cleared to kind of be about in the community, send them a smell test. So if you send them to me, Especially if they're coming from a little bit farther away, I will set them up with a video visit, ensuring them that we will do the vast majority of things that they would like to have done if they're going to come see me, but it will save them the parking and the effort to get out to see me. I will send them a smell test to get started. Um, these are, um, FDA approved certified instruments that are, uh, forced answer, scratch and sniff, uh, multiple choice test, and they give us a range of where the patients fit among the different populations and such. Uh, they are effective as a baseline. We do a physical exam and that exam usually includes a nasal endoscopy. This is going up looking towards that olfactory cleft in this region. And then as we come back, what you were seeing, uh, was the middle turbinate. Uh, as we start here, just to orient you, I'm trying to see if I get this stop. This is the inferior turbinate. Here's our septum. This is our middle turbinate, which is usually a little farther than we're able to see on anterior rhinoscopy. To the medial edge of this middle turbinate, we're gonna have uh the olfactory cleft and this is the middle meatus. And what this is indicative of or demonstrating at least is showing um nasal polyposis on either side of the middle turbinate. You can see how this would be a conductive block or an obstruction to that normal epithelia there and we're just showing that that is one of the things that can be causing a smell loss. Labs, we kind of do on an as-needed basis. If there's someone that you're concerned about or reasons that you may think they're particularly deconditioned, if they're alcoholic or have other things going on, we would consider uh some baseline level of labs in our polyp patients. I tend to get um a CBC with diff to look for the eosinophils and then an IGE. That's a different Talk that we tend to give. Um, we can look at different metallic toxin levels, but this often is gonna be led by our clinical, uh, history that we obtain. Imaging, um, I wouldn't reflexively get imaging on all these patients. Uh, I'd just as soon have the patients come in. The things that we kind of worry about as you can see here, um, there's some signs of chronic sinusitis going on. And that is something that we would be working up clinically. The patient will come to you and present oftentimes with, hey, there's a smell loss, particularly with COVID. So, um, another thing that we often ask about, particularly with idiopathic, is, is it really idiopathic or did that one fall or one hit or trauma, uh, basketball to the face or otherwise, have something to do with this? Um, Idiopathic itself, there's no preceding event, no disorder, and they tend to have a physical exam, uh, that is, uh, normal. Uh, in terms of MRI for, uh, idiopathic loss, cutting to the chase here, the rate of abnormal findings, um, is similar to that seen in the normal population. Uh, this can be unwarranted. The estimated cost per attributed abnormal finding if we got a, an MRI on every patient uh in order to get something that we would do is approximately $325,000. I don't think any of us thinks, thinks that's great. I'm happy to see these patients. I can screen, I can go over. I can assure them that I could see them every few months to make sure nothing new is coming through. Um, I'd, I am not enthusiastic about having our outside providers unless there's something they're concerned about or that we have a known, uh, neural or, uh, nasal mass going on. Uh, that's a little more disconcerting. Uh, new headaches that are rather severe that would make you get a CT or an MRI. Otherwise, fine, we may see something like this and that is something absolutely to work up. Uh, but it's, it's more using our, our discretion and considering our healthcare dollars in general that I think makes the most sense in this case. Um. Getting a little more in-depth into sensory neuro without doing too much. Um, you know, we wanna be able to make sure the patient's not comatose. Uh, if this is a post-traumatic issue where we're talking about a coma scale, there very well could have been shearing of the nerves, and I would say that oftentimes their olfactory loss is gonna be, uh, secondary to a lot of other things going on, um, particularly skull fractures, brain contusions, um, and other facial trauma or full body trauma that may be going on. Um, there are components of aging that I think are worth noting, and some of this is just as we have voice changes and hearing changes, uh, our smell is gonna change. We have decreased numbers of fibers. We have degeneration of the neuroepithelium going on. And we have decreased amount of growth. Um, so these are all things to kind of consider and discuss with our patients, particularly if they're getting all of the, uh, Presba issues, Presbycuis, uh, Presby laryngis, and then, uh, uh, Presba, I guess osmia is what it would be. I haven't actually heard that described, I kind of made that up right now. Um, but it can be, uh, an early sign for, like I said, Parkin Parkinson's disease, um, and there are Actually, awareness or public service announcements uh for us to be aware of things that are going on. So if you have other suspicions, asking about smell is actually not a bad thing to do. Um, In terms of Parkinson's disease, they will have some things that will be particularly difficult to recognize, as I mentioned, banana licorice uh is another, and then some of these other things. Um, and with Parkinson's specifically, it's a question of whether there might be, uh, some of the, uh, clumped alpha synuclein, uh, components or the tingles, neurofibrillary tingles that occur within the olfactory bulb. Um, More along the lines of what I typically treat, the olfactory, uh, region is obstructed by nasal polyposis or purulence or various masses of some sort. Uh, that can definitely contribute to a smell loss. Um, Less frequent, just kind of, uh, these are more kind of test answers. Coleman syndrome is the absence of olfactory bulbs. People won't smell anything. Uh, they may have a congenital anosmia, um, or a familial anosmia. I will be honest, I don't, doc, I don't, uh, diagnose many of these myself. I may notice the lack of the olfactory bulbs and then look into Coleman's, uh, but I don't typically see these and diagnosed. Medications. I ask patients about it or I look for anything that I, I don't recognize or that I may not be familiar with. Uh, it tends to be the anti-oplastic drugs that I see most frequently that I, uh, believe are related. Uh, when we talk about things to assist with day to day care with smell loss, um, working smoke alarms, gas stoves need to be, uh, evaluated, uh, more frequently than not, and then also labeling, uh, your perishable food and asking others for, uh, assistance with, uh, hygiene. Um, Prognosis, favorable factors, um, high residual smell ability, uh, female, young, non-smokers. Uh, you can imagine older male smokers, uh, everything just starts kind of going down, the more that you're gonna impact or, um, have adverse, uh, things that we would consider for general health issues as well. Um, When we do have inflammatory disease, surgery is often an option that we have. I would also suggest that when patients present with asthma and polyposis, it's gonna be things like aspirin avoidance that we have that are gonna be more important. Uh, if it's an overt obstruction, particularly after a recent trauma and the nose is kicked over, we can oftentimes do a septoplasty and improve the airflow. Um, people can get very big inferior turbinates where they have a complete obstruction. They would tend to notice that when we decongest their nose, they're able to smell better. So that's one of the things we would do in clinic as we're evaluating them. Olfactory training has gotten a lot more publicity after we've been trying to use it gradually for years. Uh, you take a number of different scents, usually about 4 from a few different groups, flowery, fruity, spicy, and resinous, and you just smell the uh essential oils several times a day. There are various companies and various kits you can use. Uh, we just like to get the patients to try doing it. Uh, they can change the scent after 12 weeks. It's been shown in randomized trials to improve on patients even when they are anosmic, they're better able to recognize. Uh, not completely sure why that works. What I do tell the patients is if they have a loss of smell, that in 3 to 3 months or 3 years, we're gonna wish we can come back and trial them on it. If it doesn't work after a prolonged period of time, I'm OK with them coming off of it, but I do recommend it for them. Um, like I said, it's been proved in a number of different studies, uh, to be useful. I am happy to get them started on it. I don't have, um, Any problem, and I tend to do it, I recommend it. I give them an instruction set on the video visit when I see them. So you can feel free to mention to any patient you're referring over that I'm likely gonna do a smell test and I will provide them with some treatment options even via video. Um, I will give them the instructions. Now, Steroid treatment can be complex cause, uh, you know, we all know that oral steroids patients may respond well to any number of different things. Um, but it, it can have a lot of negative effects and post-virally, uh, prior to COVID, we used to, for patients who presented within a month or two, if they were not diabetic, we would oftentimes give them A short course of a uh prednisone burst. Um, the supporting evidence is weak, uh, for overall smell loss, particularly if it's been a prolonged period of time. Topical sprays, um, there's good studies that actually show no positive benefit in postviral olfactory dysfunction specifically. I do recommend them for patients, uh, particularly who are congested. Or as they're trying to recover. I don't assure them that they will necessarily have an improvement in their smell. Now, steroid sprays, or steroid sprays are gonna be different than your steroid rinses. So a neti pot or a Neomed bottle or any equivalent where you put the salt packet in and then you then break in uh a budesonide or mometasone pill. is one of our go-tos right now, particularly with our COVID patients, and randomized controlled trials there have shown an improvement in smell recovery. I compare it to um the equivalent of using a spray bottle to spray at somebody versus using a water hose um or a giant bucket to throw in a direction. The spray is just gonna land whatever it hits first. The other one is gonna have an ability to penetrate further along. Um, and get towards that olfactory cleft region. I just got out of the OR right now with a patient who I started on steroid rinses. Um, he wasn't enthusiastic about it. Uh, he had a ton of pull-ups coming down. And when I got in there, he was still inflamed and he had a lot more posteriorly, but the anterior portion of his nose was surprisingly improved. Um, I almost regretted giving it to him cause I wanted a lot more surgery to be going on, but I think it benefited him overall. Um, so I can attest to the fact that these will definitely decrease inflammation, um, for a lot of our patients. Other treatments, uh, things that you or your patients, oops, may have heard about. Uh, one that I wanna Focus on is omega-three. There was a randomized trial out of Northwestern, uh, that where supplements were given to patients post-COVID. Um, I just talked to one of the, uh, authors on it. If you have to, if you're prescribing omega-threes for your patients, otherwise, I have no problem or qualms with that. What I would say is that it looks like there is not gonna be a necessarily positive. Finding related to the COVID symptoms, uh, coming out. So I just thought that was an important to kind of bring up. Um, there's not a consensus on a lot of these. What I would say is we will do the smell testing. We will give them steroid rinses, and then I will give them smell training instructions. If your patients want to do acupuncture, if they wanna do uh cupping or chakra realignment, I'm all for it if it helps them. Uh, acupuncture actually has been shown to improve on some people and has, uh, similar to the, um, upset that I, I mentioned, there's a sniffing sticks where you just smell markers, uh, a scented marker, and those scores were shown to improve in a number of patients. Uh, it's not as, um, Widely reported, uh, or widely used, but if it, if it works for your patient, I would say I, I'd be all for it. Um, so trying to wrap up as we go through all this, uh, information, uh, olfactory, uh, dysfunction is common. Uh, post-viral is the most, uh, frequent one that we see aside from overt sinonasal disease. Uh, however, a lot of times we can't find an overt cause or a, uh, primary diagnosis. for it. Smell loss from COVID tends to be different, uh, although the patients do tend to recover. Um, and as I mentioned, it's anywhere from 60, we usually say about 80%, uh, are gonna recover within the first month or two and 95% at about 6 months. Um, and like I said, oral steroids can be considered, but not when you have a mild case of the patient has, uh, COVID symptoms, uh, if they're not gonna get it otherwise. Um, we get a video visit, upset, history and physical. We do the endoscopy. I'll give olfactory training, initiate the rinses, and then I follow up with them. Uh, usually in person unless they request a video visit, and then I'll be going over the safety issues with them. Uh, so hopefully, it takes a lot of the other stuff off of your plate and they can know that this is something that we're focusing on, particularly, like I said, the patients who, uh, have some recovery, but it's either, uh, an off sense of smell or things aren't quite normal. We'll be looking to study them a lot more closely. Uh, in the very near future. Uh, this is Doctor Loftus here. Uh, Doctor Goldberg is another one of our colleagues, Matthew Russell, um, and then Doctor Fletcher are, and Doctor Muir are, our historic, uh, rhinologists who have been here. Doctor Loftus and I have a little less, uh, gray hair, uh, but are very enthusiastic and, uh, took on smell even before COVID.
