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BackTable / ENT / Article
Diagnosing Loss of Smell: Medical History, Testing & Imaging
Julia Casazza • Updated Sep 10, 2023 • 66 hits
When working up loss of smell, which questions should you ask? What studies should be ordered? How should patients be counseled regarding recovery? Dr. Zara Patel, rhinologist and internationally renowned expert on smell disorders, recently sat down with BackTable ENT and answered all of these questions. In this article, we review the contemporary workup for loss of smell, from the patient interview to prognostic counseling.
This article features excerpts from the BackTable ENT Podcast. We’ve provided the highlight reel in this article, and you can listen to the full podcast below.
The BackTable ENT Brief
• Damage to any structure in the olfactory pathway – from the nasal mucosa to the pyriform cortex – can cause loss of smell.
• A careful history and physical (with attention paid to previous infections and medications used) often identifies etiology of smell loss. For patients in whom this is not the case, neuroimaging using MRI may provide insight into olfactory function.
• High-risk medications for smell loss include cisplatin and zinc nasal spray. Just one application of zinc nasal spray can result in irreversible loss of smell.
• The University of Pennsylvania Smell Identification Test (UPSIT) requires patients to identify odors in a scratch-and-sniff booklet. Test results provide insight into the extent of smell loss.
• Rigid nasal endoscopy allows clinicians to examine the nasal mucosa and olfactory cleft for potential etiologies of smell loss. Extensive scarring of the olfactory cleft may portend difficulty recovering sense of smell.
• With the exception of patients whose presentation suggests an obvious systemic illness (such as hypothyroidism), labs are not necessary for workup of smell loss.
Table of Contents
(1) “Red Flag” Medications Associated with Loss of Smell
(2) Olfactory Function Testing to Diagnose Loss of Smell
(3) Rigid Nasal Endoscopy to Diagnose Loss of Smell
(4) Labs & Imaging Studies to Diagnose Loss of Smell
“Red Flag” Medications Associated with Loss of Smell
Due to their effects on the olfactory pathway, certain medications place patients at high risk for smell disturbances. When interviewing a patient with loss of smell, pay close attention to past and present medications. Chemotherapeutics such as cisplatin can kill delicate olfactory neurons. Neurologic/psychiatric medications alter neurotransmission, so while they may not directly target the olfactory system, they can alter its function. Zinc nasal spray – designed as a common cold remedy – is no longer sold in most locations, but is so damaging to olfactory neurons that even one application can result in irreversible loss of smell.
[Dr. Gopi Shah]
Tell me about the high red flag medications. Are there medications that you're always looking for on their list of medications? Then are there any nasal sprays that you found patients use that are at high risk for causing smell loss too?
[Dr. Zara Patel]
As far as the medication list, I would say that the two big things are any chemotherapeutic type of regimen. ENTs are, I think, very familiar with how chemotherapeutic agents can affect hearing, but smell is just like that. These are tiny, sensitive little neurons at the top of the nose, and they are sensitive to any of those agents that affect cell turnover and regeneration. Any chemotherapeutic agent, whether it's full-on traditional like cisplatin, or even the newer agents that a lot of people are on for breast cancer, things like that, those are all pretty impactful on smell.
Then of course, any neurologic type of medication, so antidepressants, anti-anxiety medications, seizure medications, all of those types of medications certainly can impact smell. It doesn't mean that everyone who's on it is going to have smell loss, but definitely anything that affects nerve transmission will affect smell potentially. As far as sprays, the classic example that thankfully is not sold over the counter anymore was Zicam nasal spray. This intranasal zinc spray unfortunately could just be one spray once in their life, causing an irreversible loss of smell. Such a tragic story, honestly, when you see patients who have had that happen.
Every so often, I will still get a patient who lives in a very rural area, they went to a store that hasn't changed what's on their shelves for 20, 30 years, and they somehow got their hands on that Zicam zinc nasal spray, and they still now can cause that dysfunction, and so the more public awareness that we can get out there that that's not okay. Really, honestly, I tell people that there are a lot of other over-the-counter nasal sprays that are not great for your nose, and that unless you've spoken with your physician, your ENT doctor, to really not put random things in the nose, you never know, especially in things that have not been studied, exactly how they might be impacting your olfactory system.
Out here in California, I have a lot of people who are just making some nasal spray on their own. They're taking some herbs or crushing up something they found in a naturopathic pharmacy and putting that in a liquid, and spraying it in their nose because they heard that that's going to help them prevent colds or get over a sinusitis infection. There's so many things that could cause damage to the system. It's actually a very sensitive system in some ways, even though it applies to the environment your whole life. I would say there's a lot of different things that can make it go bad if you put it in your nose.
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Olfactory Function Testing to Diagnose Loss of Smell
Assessment of olfactory function is challenging but important. Unlike hearing, no standard assessment of olfaction exists. Dr. Patel mentions the University of Pennsylvania Smell Identification Test (UPSIT) as an option to assess ability to identify odors. Sharing test results with patients suffering from hyposmia or anosmia can be a moment to build rapport, as results often validate what the patient intuits but cannot quantify. Patients undergoing treatment for their loss of smell (such as olfactory retraining therapy) should undergo repeat testing at six months.
[Dr. Gopi Shah]
Then tell me about, do you use questionnaires? Is there a small questionnaire that you're routinely using? Which small tests do you use, and why you're using? I guess to get an idea of degree, but exactly why and then how, and over time.
[Dr. Zara Patel]
As far as questionnaires, I use right now just our typical nasal sinus questionnaire and the SNOT-22, but I am going to incorporate soon, I'm getting the logistics of this ready, to start doing an actual olfactory questionnaire. The QOD is a very common one that I'll be incorporating for that specific patient population in clinic. It's been more of a logistic issue why I haven't done that up to this point with our clinic, but I'm hopefully going to be able to start doing that now. Then as far as the smell test, the smell test that I use in clinic as just a screening test to kind of just get one data point as to where people are is the UPSIT, that University of Pennsylvania smell identification test.
Like I mentioned before, it really is just one data point. We know that it doesn't tell us everything about a patient's smelling ability. I tell that to patients, because sometimes they'll be surprised at what their score was. Either they'll score better than they thought they would, or a lot lower than they thought they would. We know that patients' subjective feeling of how they smell does not correlate very well with these tests that we do.
Because that's just one data point, once I am actually enrolling patients in a study like a randomized controlled trial, which I often run on my smell patients, then I switch to a different, more granular type of test like the Sniffin’ Sticks so that I can get more data about every part of their smell, like the threshold, the identification, and discrimination. It does take a lot longer to do that test, which is why I don't use it as a screening test in my clinic because I just simply do not have the time. Even now my smell clinic is booked out until, I think, February or something like that.
I'm trying to get as many patients into my smell clinic as possible, and it just is not feasible to do a very long test. Even the UPSIT, you'll see some patients just take forever because they are really trying their best to smell it, scratch it and smell it, and then smell it again. They are really trying their hardest, and so it can take a really long time, even if they can't smell at all, to get the results of the test.
Rigid Nasal Endoscopy to Diagnose Loss of Smell
A focused physical exam can reveal causes of olfactory dysfunction and comorbidities such as sinusitis. Dr. Patel performs rigid nasal endoscopy on olfactory dysfunction patients using a pediatric 30-degree scope, as it optimizes patient comfort and ability to view important structures. She examines the most anterior portion of the nose without decongestion, decongests the nose, then performs a complete nasal endoscopy. Examining the nasal mucosa and olfactory cleft can inform treatment options and patient prognosis. In the instance that the olfactory cleft is extensively scarred, recovery of smell is less likely.
[Dr. Gopi Shah]
As we get to like the physical exam portion, I assume everybody would get a scope because we are looking for things like polyps, CRS, tumors, to see what the nasal cavity looks like. Do you decongest your patients? Do you not decongest? Do you scope twice? Tell me about that detail.
[Dr. Zara Patel]
In all my patients, whether they're just nasal, sinus, skull base, or olfactory patients, I basically use my endoscope to just look at the very front of their nose, see what their baseline is before any decongestion. Then I give them the spray that numbs them up and decongest them. Then I look further in with that endoscope, and I'm looking at everything. I'm looking at the turbinates down low. I'm looking all the way back to the nasopharynx. I'm looking at all the sinus drainage pathways. Specifically in our olfactory patients, I take a really good look at the olfactory cleft.
A lot of patients that I see in my clinic have already seen other ENTs and been told that they have a totally normal exam, but when you take some time to really examine the olfactory cleft, you can find things that other people haven't necessarily picked up on. Sometimes really the main thing that you see is just a lot of inflammation. You see swelling within the olfactory cleft, effacement of the cleft. If your olfactory cleft is closed off, you're not going to be able to smell very well. Just doing a high-volume stearate irrigation and making sure people are using the right head position to actually get that irrigation to the olfactory cleft can make a huge difference in the amount that people can smell.
Also, sometimes, especially actually after COVID-19, but in certain other circumstances also of chronic inflammation, you actually see scarring within the olfactory cleft. Sometimes people think that you can only see scarring from trauma or prior surgery, but really just chronic inflammation can create scar. It's not uncommon that I see scar bands at the top or back of the olfactory cleft just from chronic inflammation. That really does affect prognosis. When you no longer have the normal anatomy and you no longer are able to get odorants to the olfactory nerves in a normal fashion, then all these other things that we do are probably going to be less effective for those patients.
[Dr. Gopi Shah]
How do you maximize your view of the olfactory cleft? Are you using a 30-degree, a skinny scope, a flex? Then do you ever have to stick pledgets medial to the middle turbinate, and high? How do you get a good view of it?
[Dr. Zara Patel]
In just a regular screening scope exam, I don't use pledgets. I just use the spray. I do use, for all my patients, for all of our visits, we use a pediatric 30-degree nasal endoscope. That gives a really good view. You just gently maneuver that into position. You can really see all the way from the top and run down and look from the bottom. Just use your angle and move your angle around so that you're really getting a good view. You can get a really nice view that way. For patients that I'm doing injections in the olfactory cleft, like PRP injections that maybe we'll talk about later, then I do use pledgets to actually really numb up and decongest the cleft so that I have really good access to inject there.
Labs & Imaging Studies to Diagnose Loss of Smell
Carefully chosen labs and imaging studies can guide treatment of hyposmia and anosmia. Routine labs are not indicated in these patients. However, if a patient’s history suggests a particular etiology – such as hypothyroidism – labs should be ordered. In patients with comorbid rhinosinusitis, a sinus CT can identify obstruction or swelling contributing to olfactory difficulties. If a thorough history and physical examination fail to reveal an underlying cause, an MRI brain can be considered to look for neurologic causes of smell loss. Patients with hypertension, for instance, may have small vessel disease around their olfactory bulb and sulcus, contributing to diminished smell.
[Dr. Gopi Shah]
I can imagine how much of a difference it makes when you actually sit down and explain the pathophys even on the micro level, Patients want to know and for any of us, right? When we ourselves are patients about anything, regardless if we have a medical background or not, it's nice to understand what's going on and why, and how the decision-making is taking place. Tell me about workup. When are labs, and what labs are indicated? When do you consider imaging? The two big ones, CT and MRI.
[Dr. Zara Patel]
I almost never send labs. There aren't really any particular labs for most patients. Now, certainly if I get a history, very specific, like, oh, this patient sounds like they definitely have hypothyroidism, then certainly I'll send some thyroid labs. As far as imaging goes, if I have a history of people with chronic sinusitis or any sinus or nasal inflammatory issue, and they don't come in with imaging, then a CT, a CT sinus is typically a really good one to get because often that is the reason why they're having smell problem. That sometimes can correlate very well with your endoscopy, but sometimes, as you know, in our sinus patients, it's all in the sinus.
If you haven't had surgery, you don't actually see anything emanating out of the sinus outflow paths, and so the CT can be really helpful in those cases. If patients do not have any sinus or nasal history like that and they don't actually have any other good history, so there's no viral events, there's no other metabolic or endocrine, or medication, or work-related exposure, or anything else that I can pick up on that is a reason, truly an idiopathic patient, like I have no idea why this happened, then I will order an MRI. Because again, so often, you have the answer right there in your history.
For a COVID-19 smell loss patient, I don't need imaging. I know exactly why they have their smell loss and I don't need to get some MRI to show me that. If I really have no other idea, that's when you start thinking about, could there be a tumor there that I don't know about? Or could there be some other issue going on, especially in elderly patients? Sometimes you'll see extreme-- we often get MRIs in our patients and see in the report small vessel ischemic change, normal for a given age. That's a very common thing we see in our patients as they get older.
Sometimes you get much more small vessel ischemic change in and around the olfactory bulb and olfactory sulcus. That can give you an indication, maybe this patient's longstanding hypertension is actually the reason why these tiny little nerves don't work anymore. They're just not getting enough blood flow because of those tiny vessels not working. Or similarly, patients with diabetes, sometimes you can see that small vessel ischemic change in that area. That's something else you can try to pick up on an MRI. Then the last reason why sometimes I'll get MRI is for a prognostic factor.
Say, for example, there's a patient with COVID-19. I don't need imaging to tell me why they have this smell loss, but three years in, they really want to know what's my prognosis here. You can talk through all the different things that can impact their smell, like their age, their ration loss, things like that. What we can do is actually show you the volume of the olfactory bulb and the depth of the olfactory sulcus. Those can be prognostic factors as to how much smell is already gone, how much of that nerve tissue has regressed. Are we going to be able to get it back? That's another reason to order imaging sometimes.
Podcast Contributors
Dr. Zara Patel
Dr. Zara Patel is director of endoscopic skull base surgery and a professor of otolaryngology and neurosurgery at Stanford in California.
Dr. Gopi Shah
Dr. Gopi Shah is a pediatric otolaryngologist and the co-host of BackTable ENT.
Cite This Podcast
BackTable, LLC (Producer). (2023, August 1). Ep. 122 – Evaluation & Management of Patients with Olfactory Dysfunction [Audio podcast]. Retrieved from https://www.backtable.com
Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.
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