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BackTable / ENT / Podcast / Transcript #164
Podcast Transcript: Chronic Invasive Fungal Sinusitis: Diagnosis & Management
with Dr. Ashleigh Halderman
In this episode, Dr. Ashleigh Halderman, Rhinologist and Associate Professor at the University of Texas Southwestern Medical Center, discusses chronic invasive fungal sinusitis with hosts Dr. Gopi Shah and Dr. Ashley Agan, You can read the full transcript below and listen to this episode here on BackTable.com.
Table of Contents
(1) Fungal Sinusitis: Types & Symptoms
(2) Differentiating Chronic Invasive Fungal Sinusitis From Other Types of Acute Fungal Sinusitis (AFS)
(3) Challenges in Diagnosing Chronic IFS
(4) Diagnostic Workups for Chronic IFS Patients
(5) How Biopsies Help Confirm Chronic IFS
(6) Pre-operative Considerations & Management
(7) Treating AFS & Chronic IFS
(8) Surveillance & Management of Chronic IFS
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[Dr. Gopi Shah]
Hello everyone and welcome to the BackTable ENT podcast where we discuss all things ENT. We bring you the best and brightest in our field with the hope that you can take something from our show to your practice. My name is Gopi Shah. I'm one of your hosts today. I'm a pediatric ENT, and I'm here with my favorite person to host these podcasts with Dr. Ashley Agan. How are you, Ash?
[Dr. Ashley Agan]
Hey, Gopi. I'm so good. Excited to be here with you today and with our returning guest. We have the privilege of getting to check back in with Dr. Ashleigh Halderman today. If you guys missed her on episode 30, go back and check it out. She's back today. We're going to talk about chronic invasive fungal sinusitis. First, let me give her a quick intro, for those of you who don't know Ashley, she's an assistant professor in the Department of Otolaryngology at the University of Texas Southwestern Medical Center in Dallas.
After receiving her medical degree from Boston University, she completed her residency in otolaryngology at the Cleveland Clinic. She did her fellowship in rhinology and skull base surgery at Johns Hopkins University School of Medicine. She's the current president of the Texas Association of Otolaryngology. Welcome to the show, Ashleigh.
[Dr. Ashleigh Halderman]
Thank you so much for having me again. It's so good to see you both.
[Dr. Ashley Agan]
It's so great to see you. Tell us a little bit about the Texas Association of Otolaryngology. Congratulations on being the president of that by the way.
[Dr. Ashleigh Halderman] Thank you. It's a really great group of people. Obviously, it's comprised of otolaryngologists practicing in Texas.
[Dr. Gopi Shah] Yeehaw.
[Dr. Ashleigh Halderman]
Yes. It's a big state. There's a lot of ENTs, a lot of academic centers. It's just sort of a really great way-- For me being involved in it, it's been an incredible way to meet other otolaryngologists from across the state and become a resource for them. Working at an academic center, you have education at heart. That doesn't include just our residents and patients, being a source for other individuals taking care of patients in our state.
We just recently opened up membership to nurse practitioners and physician's assistants, which we're really excited about. We're really working to provide a lot of educational content. We're doing, I think in March, a webinar on post-nasal drip.
[Dr. Ashley Agan]
Nice.
[Dr. Ashleigh Halderman]
Yes.
[Dr. Ashley Agan]
It's really relevant actually.
[Dr. Ashleigh Halderman]
It is. The problem is no one wants to talk about it. We're trying to cover some of those high yield topics that you're not going to hear people talk about. Post-nasal drip will be coming up, I think, in March.
[Dr. Ashley Agan]
Very nice.
[Dr. Ashleigh Halderman]
We've also gotten into lobbying and legislation. We had our first legislative win, which was to include CMV in universal screening for babies who do not pass their hearing test.
[Dr. Ashley Agan]
Good job.
[Dr. Ashleigh Halderman]
We're really proud of that, thinking it was a positive win. It's been really cool to be involved in the different proxy areas that really impact the practice of medicine.
[Dr. Gopi Shah]
That's awesome, Ashleigh. Kudos. Before we get started, can you just tell our audience a little bit about yourself and about your practice?
[Dr. Ashleigh Halderman]
I've been practicing in Texas since 2016, and I am a subspecialist. All I do is rhinology and skull base surgery. My practice is about 50-50. I have a pretty high volume of skull base surgery. Until recently, I was covering Parkland, and Parkland is our county hospital, and we serve all patients, whether or not they can pay. Because of this unique sort of opportunity, we see very advanced pathology. I think that's permitted me the opportunity to get a very well-rounded experience in my time thus far, and to see some things that are real head scratchers and having to really think outside the box.
The number of times that I said, I've never seen this before in my first few years here, it was very uncomfortable and unnerving. I've come to find that that's just sort of part of the normal process, but I think we get a little bit more of it at Parkland than most places. Living in Texas, fungal sinusitis is endemic. It's interesting, actually, I never really thought about this until I was here and thinking about AFS being present in so many patients, but their incidence of acute invasive fungal sinusitis is actually higher in Texas.
If you look at some national database studies, you see the highest rates are in the South. I think that's just because, again, it's endemic, it's everywhere. My fellow last year was from the Northeast, and she trained in New York City. She was like, "You guys have way more cases than we ever did." I think there's really something to that. Fungus is among us, for sure.
[Dr. Ashley Agan]
For sure. As we dive into this, do you think it would be helpful to just lay out the different types of fungal sinusitis, and then we can go deep into the chronic invasive?
(1) Fungal Sinusitis: Types & Symptoms
[Dr. Ashleigh Halderman]
Absolutely. The way that I categorize fungal sinusitis, is, there's two main categories. There's noninvasive and invasive. In the noninvasive forms, you're going to have your fungal ball and allergic fungal sinusitis. Essentially, in a fungal ball, it's going to include usually one sinus, and we're not certain how or why it happens. One thing that seems to increase the risk is prior endodontal work. That might be changing, because I believe that they're no longer using the zinc as part of the amalgam. That was the thing that allowed this permissive environment, was theorized.
That is something that sort of increasing as people age, the incidence increases of fungal balls. There's not really any immune response to the fungus. In allergic fungal sinusitis, obviously, that is allergy-based, or so we think. There is an IgE sensitivity to fungus in these patients, which is helping to propagate and allow that disease to form. Otherwise, the immune system isn't really combating it, or ignoring it, I guess.
Then the invasive forms can be subcategorized into acute and chronic. Acute is the one that we all fear. It is very high mortality, between, I think the reports range anywhere from 20% to 80%. I think the biggest series maybe landed at 50% mortality rate. You're only going to see that in patients with fairly significant immune compromise. Either somebody with a hematologic malignancy who is on chemotherapy, who's had organ transplant, or is in diabetic ketoacidosis. Again, the diabetic ketoacidosis just sort of allows this permissive environment. The acidity is perfect for different fungus to grow and invade. There's immune issues within that state as well. It just gets a foothold and goes nuts.
Then the chronic forms, there's both chronic invasive fungal sinusitis, which is what we're going to talk about today and is pretty uncommon. Then you also have your chronic granulomatous invasive fungal sinusitis. The differences between those two, is that with chronic invasive, you're going to see some level of immune deficiency. It's usually not as profound as acute invasive, but it could be somebody who's on high-dose steroids for a while, or they have diabetes. I think most of the people that I've ever seen that have it have diabetes.
It's, again, very rare, but the mortality rate is real. It can be at a year, one paper said about 48% survival. It's landing there at about that 50%, like acute invasive. Then chronic granulomatous tends to be an immunocompetent patient. There's not really any evidence of any degree of immunocompromise. I am suspicious that this might be on a spectrum. We at UT Southwestern had five cases of allergic fungal sinusitis that converted to chronic granulomatous. Actually, when they've gone back and looked at pathology for allergic fungal sinusitis cases in a study, a couple of studies I think have been done. Around 21% of AFS patients show some granulomatous sort of inflammation.
All of our patients, they were all young Black men. Those are typically the patients who tend to see the most significant or severe disease when it comes to allergic fungal sinusitis. I wonder, is there something there? It can also happen in isolation not associated with allergic fungal sinusitis. It tends to be much more favorable. I think mortality is pretty low. It's highly treatable.
[Dr. Gopi Shah]
Just to recap, the invasive, they're all angioinvasive. When we talk about, obviously, acute IFS, we know it's invasive. We always ask, is there angioinvasion on PATH? Chronic invasive, it makes sense. It's angioinvasive on PATH. They're slightly immunodeficient, we said. Also chronic granulomatous fungal sinusitis is also invasive as well?
[Dr. Ashleigh Halderman]
I do not believe it's angioinvasive.
[Dr. Gopi Shah]
Okay, it's not angioinvasive.
[Dr. Ashleigh Halderman]
Correct.
[Dr. Gopi Shah]
Okay. Got it. Got it.
[Dr. Ashleigh Halderman]
I don't think so. It's a great question. I think that gets to the heart of why maybe it's less severe and less deadly. There can be orbital and intracranial extension of that, so perhaps at some level, but I'm not 100% sure.
[Dr. Gopi Shah]
Just to clarify, the thought is that the AFS is a spectrum and there may be a small percentage of AFS that turns into chronic granulomatous fungal sinusitis.
[Dr. Ashleigh Halderman]
Possibly, yes. That's important to pick up on, because typically with allergic fungal sinusitis, antifungal therapy is not part of the treatment paradigm. However, with chronic granulomatous, then you do need to have these folks on oral antifungals for a fairly extended period of time to fully clear up the disease. We don't really understand that. Is it everybody if it just gets too far advanced? Is it only certain people with certain characteristics that develop? My guess is that you have to have the right person, right place, right time for it to convert or to be present. It's just something to I think, keep an eye out for, especially if you run into a really severe case of AFS that's particularly recalcitrant.
(2) Differentiating Chronic Invasive Fungal Sinusitis From Other Types of Acute Fungal Sinusitis (AFS)
[Dr. Gopi Shah]
That's what sparked this conversation Ashleigh. Like several months ago, I was on call and there was a patient that came in that looked like one of these really impressive AFS cases. Then you and I started looking at it together and you said, what, this could actually be chronic invasive. Then I was like, well, you need to come on the show and talk to me more about this. Teach me more about this, because that wasn't on my radar. I guess we can start at presentation and just what does the typical patient look like that we need to be thinking about this diagnosis?
[Dr. Ashleigh Halderman]
It's always weird, for lack of a better term. Generally, the classic patient tends to be older. Most of the time they have diabetes and it's maybe not super well-controlled, but it's also not like DKA area. They're going to have symptoms for a very long period of time and they can be pretty nonspecific symptoms. The first case I treated or diagnosed chronic invasive fungal sinusitis on, was a woman in her 50s and she'd had a year of pretty severe left-sided facial pain. She had been treated for sinusitis, she had been treated with gabapentin, all these nerve-- They thought she had some type of neuralgia and nothing was really touching it. The pain was really severe throughout the whole trigeminal distribution. She went down the whole trigeminal neuralgia pathway. Then she went blind.
When she presented, there was pretty impressive destruction of the orbital apex and sort of the spheno-orbital area. Going back and hearing her story, it had been there this whole time for a year and they just missed what was causing it. That being said, there was bony destruction. It was pretty impressive. You could see some sort of soft tissue changes as well in the orbital apex area. I took her to the operating room and took tons of biopsies in the sphenoid area and along the lamina and whatnot, nothing. They couldn't find anything. I thought, this has got to be a cancer or something. There's got to be something there.
I think the next time I took her back, I actually went into her orbital apex and was getting tissue samples because that seemed to be the hot spot. I'd tried to avoid it before, because obviously you don't want to take out a person's optic nerve and I was still like very cautious. They saw some fungal elements on the frozen, which then they didn't see on the final pathology, but we had enough to go off of. She started on the antifungal therapy and her pain got way better. When you go into these cases, it's not necrotic. It's not necessarily slapping you in the face. It's like, this is blatantly abnormal. The tissue looked a little bit weird. It was maybe a little bit pale and thickened, if you will, but again, it wasn't necrotic.
We got her on antifungals and I sent the tissue for culture, nothing grew out. That's a common theme in these cases I find, is that sometimes it is hard to achieve a true diagnosis and get tissue to send for culture and to get it to grow out. We had to go just based off of a high level of suspicion. We hadn't found any cancer there. It had been going on for so long. She was diabetic. Her hemoglobin A1c wasn't awesome. She started getting better once we started treating her with the antifungals. I think here it was really sad too, because it had gone so long.
She did really well on her antifungals and then she just stopped taking them and disappeared for a little while. She came back with new facial pain and new headache again on that left side. That was very worrisome to me. It was already evolving her trigeminal nerve and her orbital apex. I already had a high level of concern that it had gone intracranial. I think by definition it had. I got imaging at that time and it had gone wild intracranially. She actually had sort of osteomyelitis type changes to the sphenoid wing. She ended up going with neurosurgery to get cleaned up, get cultures. We were able to get a positive culture at that time. She's just going to be on lifelong antifungals, but she's still alive.
[Dr. Gopi Shah]
Wow. In terms of your initial scope, Ash, what did you see when she first came to your clinic when you did endoscopy? Actually again, the patient that came to you guys on call, what are their scope care findings? Do you see polyps? You said you don't see that necrotic dead tissue. Are there any tip-offs?
[Dr. Ashleigh Halderman]
No. For me, it was purely symptoms and imaging. Again, it was limited to the sphenoid and the orbital apex. With the scope exam, you're not going to be able to see that area. You might be able to see the sphenoethmoid recess. I had another case recently that I was highly suspicious of chronic invasive and there was periolith. We were taking cultures, but sending-- Again, the perioliths was the only thing. The tissue just looked a little bit pale and thickened and inflamed a little bit, I guess, but not necrotic. That other case, Ashley, I guess I'm remembering her as sort of a mix between acute that transitioned to more of a chronic. Is that the same case?
[Dr. Ashley Agan]
I'm thinking of a young man that where I was thinking AFS, like allergic fungal. Maybe we can talk about that as a separate. Because that maybe is the possible conversion to chronic granulomatous invasive fungal, right?
[Dr. Ashleigh Halderman]
Even to chronic invasive.
[Dr. Ashley Agan]
Okay.
[Dr. Ashleigh Halderman]
There have been some reports, and this makes sense, that in individuals who have allergic fungal or have a fungal ball, if they then experience some immunocompromise, that can convert into any. It can convert into acute. It can convert into chronic depending on the level of immunosuppression. Probably in that setting, I think-- Did that individual have diabetes?
[Dr. Ashley Agan]
No, it was like a young, healthy, 20-something-year-old kid.
[Dr. Ashleigh Halderman]
That's right. Okay. Yes. That might've been then chronic granulomatous.
[Dr. Ashley Agan]
I think there was something on the MRI that suggested that maybe it was a little bit different than the classic AFS. They had been worked up CT and MRI at like an outside hospital, so they were coming in with all of that imaging.
[Dr. Ashleigh Halderman]
It's interesting, the chronic granulomatous, it's going to appear as a mass on imaging, whereas chronic invasive is going to appear as more infiltrative.
[Dr. Ashley Agan]
For your lady that had been sent for a workup for trigeminal neuralgia and everything, does that mean that her scans were clean? That there was no sinus disease that could be attributed to her symptoms and people were like, hey, it looks clean, let's send you to neurology?
[Dr. Ashleigh Halderman]
I think she had some mild findings in her sinuses, pretty mild. Maybe just a little bit of mucosal thickening. They did treat her for sinusitis, but it didn't make any difference. I think that they abandoned that and went for-- The pain was the predominant symptom. She wasn't really having any sino-nasal symptoms. I don't certainly blame anybody for that thought process. I think that the destruction of the orbital apex was a later finding. I think that if that had been present immediately, alarm bells would have been ringing.
[Dr. Ashley Agan]
Since it had been a year, maybe she got that CT early on, maybe there wasn't much there. Then it was MRI after MRI and you don't get great bony characteristics.
[Dr. Ashleigh Halderman]
Yes, predominantly intracranial MRIs, MRIs of the trigeminal. I can't tell you how many times you get one of those scans and there's no comments at all on the sinuses.
(3) Challenges in Diagnosing Chronic IFS
[Dr. Ashley Agan]
In patients who are presenting with predominantly like a facial pain complaint, I feel like it would be very easy to miss this because it's so rare that most of us probably aren't thinking of chronic invasive. Because patients coming in with sinus headache and facial pain are pretty common, and the percentage of them that are experiencing a chronic invasive fungal sinusitis is probably very, very low. Also you don't want to miss this. Any other questions that help tip you off, or is it just the chronic worsening nature of it? Walk me through your clinic visit to where we can make sure that we're catching these. Because these are mostly presenting in the clinic, not in the hospital, like an acute, right?
[Dr. Ashleigh Halderman]
No. The ones that I've seen have all presented in the hospital actually. It's because unfortunately by the time they get to us is they've gone blind, or they've developed some type of orbital symptoms, if you will, or the imaging is very concerning for like a mass or a tumor. That's how they typically end up with us. If you were just going off of facial pain alone, it is difficult and you're right, the majority of those patients are not going to have chronic invasive fungal sinusitis. Again, if they don't have any possible immune deficiency, like they're not diabetic, they haven't been on steroids, all of these things, then that further sort of is like probably not the case.
There's been a few studies that have looked at sort of the findings, and I think you just have to have a suspicious eye. I wish that I could give you something more solid, but I guess I would have to say that just based off of my experience and my learning through practice, I've been better at spotting these things. It's taken some trial and error a little bit. I wasn't perfect and I still am not. When I'm looking at a case, again, usually a lot of the groundwork has been done and there's some pretty abnormal findings on the imaging, like soft tissue involvement of the orbit, destruction of the bone, involvement of the pterygopalatine fossa structures.
They're presenting with symptoms like pain or paresthesias, which absolutely should be very concerning for anybody. Paresthesias needs further investigation for sure. It's just sort of that clinical picture of all of those things. I think in isolation, pain without findings in those areas, without sort of anything concerning, I don't think you need to be too worried.
[Dr. Gopi Shah] Do patients have like other sinus nasal symptoms? Runny nose, nasal congestion, parotid drainage?
[Dr. Ashleigh Halderman]
Not predominantly. You can never say never, but they tend to really present with headache, facial pain and orbital symptoms and sort of less so. I think chronic granulomatous may present more with nasal symptoms, but chronic invasive, not so much. I think everyone that I've ever diagnosed with chronic invasive has had either the facial pain, facial numbness and orbital involvement, so diplopia or vision loss, or orbital apex syndrome, things like that.
(4) Diagnostic Workups for Chronic IFS Patients
[Dr. Ashley Agan]
Just to review the imaging findings, so on CT, we said there's going to be more destructive lesions. Are you going to see erosion? You're not going to see expanse style changes. Walk me through some of the key CT and MRI findings. I know on MRI, you mentioned soft tissue changes, but just to have that organized.
[Dr. Ashleigh Halderman]
I was doing a little bit of reading last night just to make sure. The majority of the patients are going to show some findings, like I said, around the spheno-orbital and skull base region. Bony destruction and abnormalities, both in the soft tissue of the pterygopalatine fossa, orbital area, orbital apex is what I've seen. Also there was a case that was involving the maxillary sinus and this person has sort of abnormal findings along the lateral aspect of the maxillary sinus bone and like some soft tissue density there as well. That heightened my level of concern, especially because he was having like these sinus findings. They weren't really severe, but he was having paresthesias. I was like, "This is weird, we need to biopsy this. I think it might be chronic invasive."
As far as the MRIs, you're going to see some abnormal sort of signaling. I believe that most of the time it does enhance, but if it's pretty far gone, there might actually be a decrease in sort of uptake and like abnormal enhancement going the other direction. It's not enhancing like you would expect it to necessarily, if the tissue has been compromised. Then for chronic invasive, it is enhancing and it can be pretty impressive. I know that from a case that we had in residency.
[Dr. Ashley Agan]
Chronic invasive is enhancing?
[Dr. Ashleigh Halderman]
It can be. Yes. I think it depends on like how far into the course you are, right?
[Dr. Ashley Agan]
Okay.
[Dr. Ashleigh Halderman]
Because if we lose some of the tissue viability and the tissue is just in general not healthy, I think you're going to have a loss of that. I believe typically it is enhancing on two.
[Dr. Gopi Shah]
For most of these patients, it would be appropriate to start with a CT, and then if you're seeing bony erosion or if you're seeing something that looks like a tumor, but you're not sure, then you get an MRI.
[Dr. Ashleigh Halderman]
I think you also get an MRI based off of the symptoms that they're having. If they're having pain and numbness, then I want to know what their cranial nerves look like.
[Dr. Gopi Shah]
For the AFS patient, the allergic fungal patient that we're concerned could have some areas that have converted to a more chronic invasive. Is there something on the CT or the MRI that tips you off to that? Because for those patients, correct me if I'm wrong, but I assume some of their CT is going to look like the classic AFS with like that expansive sinus looking picture. Can you comment on that part?
[Dr. Ashleigh Halderman]
Yes. Expansile, but not invasive, and not infiltrative. Anybody who has AFS, but is again, presenting with facial numbness or facial pain that's sort of really acute or it just doesn't seem to-- Because most people with AFS don't present with facial pain. It's been a long ongoing process, and so that's just not usually part of it. They've sort of adapted, as everything is expanding and building up, pain is not usually something that's reported. AFS obeys boundaries to an extent. It's going to be this pushing border that's sort of smooth and is not actually invading the tissue.
When somebody who has maybe some atypical symptoms who has AFS, you get imaging, then I'm going to look at invasion. Is this no longer a pushing border and it's starting to infiltrate into the orbit or the pterygopalatine fossa or intracranially? You're going to look, do they have a V2 numbness? I'm going to look along the course of V2 and see, is it enhancing? Does that appear abnormal? Do I need to be concerned that something is happening along this nerve? It's these very subtle things, but that's what you would be looking for.
[Dr. Gopi Shah]
They could have some areas of imaging that look like classic AFS, and then some areas where it's like, oh, maybe this is actually starting to invade here.
[Dr. Ashleigh Halderman]
Absolutely. I think that the majority of these cases, there's a lot of clinical evidence. It's just the picture is not right. Something doesn't resonate right. The clinical presentation and the history is so essential in these cases. I would say that just every time I've seen something like this, something's just been off and it is a complete picture that you put together with all of these modalities, your sort of history, the clinical exam, imaging, and ultimately biopsy.
They have looked at sort of those markers that they can use for pulmonary fungal diseases and the answer is we have no idea how. It's just too early. It hasn't been looked at for fungal stuff. I would not bother ordering those, because I don't know how to interpret them.
[Dr. Gopi Shah]
What about just labs that evaluate their immune system? Would you want to look at like your ANC, like their hemoglobin A1C, or stuff like that?
[Dr. Ashleigh Halderman]
That's fair. There's no labs that are going to diagnose positive fungus here, other than tissue biopsy with culture and seeing the fungal elements. However, you can evaluate their metabolic state and BMP or CMP. You want to see if they're acidotic and if they're in a DKA, that's a huge piece of evidence. The hemoglobin A1C to get an idea of what their sugar control has been like over a three-month period. All of those are really important just to paint a fuller picture. Again, I think I've seen this develop in folks whose hemoglobin A1C was like a seven-point something. It doesn't have to be horrendous. I don't think seven-point something is great, but it's not 11 or 14 or–
[Dr. Gopi Shah]
We've seen worse, yes.
[Dr. Ashleigh Halderman]
Then as far as the classic other immune signs, for chronic, if a person does, and there was one study where patients had developed sort of chronic invasives in the setting of hematologic malignancy, so it is possible. I think that they actually found that an A1C level of greater than 1,000 was associated with improved survival. I think that the A1C is something I'm mostly going to be looking at in an individual who is on like chemotherapy or has a hematologic malignancy. Insofar as you can correct that and follow it, then yes, that could be really, really helpful.
(5) How Biopsies Help Confirm Chronic IFS
[Dr. Ashley Agan]
All right. Ashleigh, what's on our differential here? I know we've discussed tumor, we want to get biopsy. Usually we think path and biopsy or think in tumor. Do inverted papillomas have a similar presentation? What else is in your box of three to four things that may prove to have something similar to some of these findings?
[Dr. Ashleigh Halderman]
Like you said, malignancy, typically not just your run-of-the-mill sinus disease. Inverted papilloma would not be something I would expect, unless it had converted to a cancer, because then you can very easily see a lot of infiltrative changes then into the tissue. Again, that comes back to malignancy. I would say that it's some other things - Vasculitis, pseudotumor, some autoimmune process, those are going to be on my differential as well. IgG4 disease, I think those are the main ones just because this is so unusual.
[Dr. Ashley Agan]
All basically requiring some tissue pathology to figure out what's going on.
[Dr. Ashleigh Halderman]
Yes, and a multidisciplinary care team and approach to sort of evaluating everything and talking to your colleagues to see, hey, is there something that I'm missing? What do you recommend here?
(6) Pre-operative Considerations & Management
[Dr. Ashley Agan]
For the patient who's in the hospital, what's your order of operations? How quickly do you need to go to the operating room to get PATH? Is there anything that you do in the meantime while you're waiting as far as like starting medications?
[Dr. Ashleigh Halderman]
It depends how they present. Now if they've gone blind or are sort of losing vision, I think you need to act on things immediately. If they are started on antifungals before I get them to the operating room, that's okay by me, because preserving their functionality is goal number one. Then getting the diagnosis to sort of help support that is also a priority, but you need to do what you need to do to keep the patient as whole and well as possible. I feel like a lot of times we are not the front line. These aren't the people that they're not immediately coming to us.
There's been some stuff that's been done and you're just sort of walking into the situation and maybe a little bit later on the scene than some other folks, or infectious disease has been consulted and they're like, you need to get ENT involved. We arrive at some point. I always see my role in this as being the person that goes and procures tissue and sends that for the appropriate testing.
[Dr. Gopi Shah]
For tissue, this might sound like a silly question, but do you need a lot? Because when I think of sino-nasal biopsies, the lesion is very vascular. It's like get what you can and get out and pack. It doesn't sound like it would be too bloody. You could probably get what you need to, but how much tissue do you like to get? Because I feel like just a little Blakesley size, you're going to end up with, we don't have enough specimen or something. Does that ever pop into your head when you do these? I don't know. I'm always like, do I have enough? Do I have enough?
[Dr. Ashleigh Halderman]
Oh gosh, yes. I've been in the situation more than once, where they're looking and they can't find fungal elements. For that chronic invasive, and I think that our chairman who's a rhinologist has also said that he's had cases where like you just could not get pinned down fungus. I send a lot, any area that I can. In cases where they're pterygopalatine fossa or the orbital apex, I try to get to those areas and get samples, because disease is present and it shouldn't be there. I do chase these things a little bit. Not to the extent that like, if they're not blind, I'm not going to go blind them for the sake of like, but I am going to get a little bit into the orbit. I'm going to sample some of the orbital fat in a safe place. I do try to send as much as I can.
You of course always want to make sure that you send the tissue for culture. I can't emphasize that enough. This is sort of an interesting area where sending it for some of the like MRA analysis, of the 16S mRNA would probably be a great idea. The reason that I say that, is because it can detect it at such a smaller level, but it also can get the answer back to you, I think more quickly than routine standard cultures can. If you have that feasibility, this might be the case where you want to submit tissue for that sort of testing.
[Dr. Gopi Shah]
Are you doing frozens as well?
[Dr. Ashleigh Halderman]
I have. When I've done it, it's usually been on the second go around, because I'm wanting them to tell me that I've sampled something that can give them a diagnosis. As we know, in cases that are not fulminant acute invasive, it can be really hard to detect fungus in frozen section. I don't always rely on that. I think the second time around, usually I am, because I just want to know, did I get something? Please tell me there's something here so that I don't need to keep sending more, right?
[Dr. Ashley Agan]
Yes. Otherwise you're sending tissue for pass and then fungal culture.
[Dr. Ashleigh Halderman]
Yes, for permanent. Right. Because ultimately they need to be able to run like the GMS stains on it to really do a thorough job. It's going to take the special staining, that's what we're really relying on. If they can give me a preliminary, yes, there's fungus here, so that if we haven't started antifungals, we can start the person on antifungals, then that's really helpful. If I need to make decisions based off of that, then maybe I will send a frozen. It's a case by case situation.
(7) Treating AFS & Chronic IFS
[Dr. Gopi Shah]
In terms of empiric antifungals, when I think of acute invasive fungal sinusitis, the empiric is amphotericin. For chronic invasive fungal sinusitis, is the empiric antifungal also amphotericin or is this a voriconazole type? What do we usually start patients on?
[Dr. Ashleigh Halderman]
Typically, it's ampho and then they back off depending on speciation.
[Dr. Gopi Shah]
In chronic invasive, are we thinking mucor and the range from mucor to aspergillus to I've even seen just dematiaceous and acute invasive fungal sinusitis. Is it the whole gambit as well in chronic invasive?
[Dr. Ashleigh Halderman]
It's the whole gambit, yes. I think the majority of cases end up being aspergillus, honestly. I think that's the most common, but I've seen it due to dematiaceous as well. Mucor, I'm a little bit less certain about. I remember because I had another case here within the last year. I was corresponding with our IED doctors and I found a paper and I think everything was represented in this series.
[Dr. Ashley Agan]
For the patient who, for that AFS patient where they don't have any sort of neuropathy, they're not losing their vision, but maybe there's just some funny looking spots on the MRI or the CT where you're like, I'm a little bit concerned about this. Do you treat them different in as far as pre-op medications go? I think the patient that we had shared, instead of doing steroids, you had recommended an antibiotic. I don't remember exactly what, but that was part of it.
[Dr. Ashleigh Halderman]
No, maybe an antifungal.
[Dr. Ashley Agan]
I don't remember. Do you?
[Dr. Ashleigh Halderman]
Itraconazole maybe?
[Dr. Ashley Agan]
How do you think? I thought you gave them doxycycline.
[Dr. Ashleigh Halderman] Maybe. Yes. Okay. That would have been the case. To reduce inflammation. Yes. I've really backed away from doing high dose steroids in AFS patients prior to surgery. I think that's what you're talking about. The reason is because even though it's really rare, that conversion from just allergic fungal to invasive has been reported, and it's been reported in individuals on high dose steroids. I really don't do that anymore at all. Pre-op treat them with steroids.
There's been a few people-- This is interesting, but this is a little bit out there. This is not evidence-based, but we have had a few individuals who had really bad AFS and for whatever reason could not get surgery right away. One individual actually was diagnosed with a renal mass. We were like, we know your symptoms are really bothering you, but you need to have this figured out first. In the meantime, what we did, and I got this from Dr. Ryan, was treated them with steroids and itraconazole at the same time for a prolonged course of the itraconazole and a shorter course of the steroids.
Anecdotally, I had a young woman with AFS, who actually first presented with bronchopulmonary aspergillosis. She had been treated with steroids and I think voriconazole or one of the azoles for a really long period of time. They had initial imaging of her sinuses, I think just when she had started the treatment. Then we had gotten repeat imaging and it was remarkably better. It wasn't 100% clear, and you cannot clear this up with just sort of medical treatment. It's a surgical disease process. I actually took her to the operating room and there was still some fungal mucin in there, but it can sort of improve symptoms for people. That's always dicey. You have to balance that.
Obviously, both steroids and antifungals have a lot of side effects, and the antifungals can be damaging to other organs. That's not something that I like to pull out and use other than very specific cases. That has been something we've offered as a non-operative option for some individuals for a short period of time. If you really want to do something to help cut down inflammation, there's not data to really support this, but you could use like a doxycycline and it does exert some sort of anti-inflammatory effects.
Generally, I don't find that AFS cases bleed a whole bunch. They might at first, but once you start sort of getting in there and getting some of that fungal mucin out of there, unless they're acutely infected on top of the AFS, I just don't find that they really bleed that much. I don't think it's necessary to do steroids perhaps.
[Dr. Ashley Agan]
Even just that 2-week, 10-day or 14-day course of steroids, it could be enough to tip someone into chronic invasive?
[Dr. Ashleigh Halderman]
You just never know. The more I've sort of heard of and seen cases of it converting, I've just been like, I can't do this to people. It's like, I guess you have to ask yourself why you would do that, right? Are you doing it so that the surgery is a little bit easier for you? Not to say like that's a-- But like, if that's my only reason, is to make the surgery a little bit easier or maybe safer or something, I can't sort of do that in the face of like possibly causing them to convert. I think with AFS cases, look, if it's really, really hard and you are struggling, staging it as a complete and perfect option. Back out, go back in later, take some time. You know.
(8) Surveillance & Management of Chronic IFS
[Dr. Ashley Agan]
It's really interesting. For patients, let's say you have made the diagnosis, you got tissue confirmation, you have fungus that is invasive within the tissue and you say, okay, this is a chronic invasive fungal sinusitis. What do the next several months look like for that patient, as far as like how long do they need to be on antifungals and what's their surveillance like with you?
[Dr. Gopi Shah]
Also, do you have to go and do like a FESS? Is there any role of opening things up for irrigations or topicals or anything like that after the biopsy?
[Dr. Ashleigh Halderman]
Yes. I think I'll start with that, Gopi, because that's an important discussion point with chronic granulomatous and chronic invasive is how aggressive surgically do you get. I think that we're at this interesting time where in the past, people used to advocate for very aggressive surgical resection of all involved tissue. I've never done that and I don't think that really maybe needs to play a part anymore in the management of these patients. I think that way of thinking and that management was born out of necessity back when amphotericin was non-liposomal and it would cause kidney failure. It was just people couldn't be on it for more than a few days at a time because their organs would start failing. It was a really self-limited option.
Now that we have the liposomal amphotericin and it no longer causes immediate organ failure or in a really rapid time period, we've got a lot more time. I'd say that even more importantly, the azole and the development of those has led to improved medical management of these patients, which has reduced the necessity of being surgically aggressive. In these cases, because of where they tend to go, so orbital apex, orbit, sphenoid, surgical resection, pterygopalatine fossa. Surgical resection would be quite morbid and potentially fatal. You're really in a tough spot there.
We definitely take a more measured surgical approach. I don't think it ever hurts to open things up if this isn't concurrent with like fungal ball or allergic fungal sinusitis. I'm going to open those sinuses up to remove all of the fungal debris that's sitting there on the surface. If there's anything by chance that is necrotic or you're concerned about viability, you could always debride that as well. Mostly you're going in there just to get a diagnosis in my opinion. Some people might disagree and I think some people still go after that really aggressively, but that's just not something that we do here.
Then it's all about getting the specimen the speciation, knowing what it is and putting them on appropriate antifungals. Then the surveillance is imaging based. You're looking to see if this stuff clears up. In my experience, people have been on antifungals typically until maybe a little bit after the imaging sort of resolves. If the imaging never resolves, so long as they're not getting worse, that makes you think that maybe there's something else going on that you need to go back in there. Maybe it's a different fungus that's not being sort of controlled by their current oral antifungal medication. Sometimes like that person I started off talking about, that woman who had intracranial, they're going to be on it for the rest of their lives.
[Dr. Gopi Shah]
For that patient, do they just have like a PICC line or a port and they're doing IV infusion every day?
[Dr. Ashleigh Halderman]
No, that's the beautiful thing about the azoles, is that they're all oral. Voriconazole, itraconazole, propiconazole, all oral.
[Dr. Gopi Shah]
Got you. They're on amphotericin until it speciates and then you can convert to oral.
[Dr. Ashleigh Halderman]
Exactly. Yes. It's just like broad spectrum antibiotics until you can narrow it down.
[Dr. Gopi Shah]
What does that timeframe look like?
[Dr. Ashleigh Halderman]
Months and months and months.
[Dr. Gopi Shah]
How long do you think it usually takes to get that speciation and get them transitioned?
[Dr. Ashleigh Halderman]
Oh, that could take about a week or so. What I've been finding is that a lot of times they will transition them off the ampho quickly. They might be on that for like three to five days or something. Maybe even before they have the speciation with maybe some of the earlier information they can start to put them on. I think posiconazole has been a popular option. They might go ahead and do that. It probably depends on the infectious disease doctor and sort of what's going on with the patient overall as far as like renal function, all that.
[Dr. Ashley Agan]
Just going back to the initial presentation, it sounds like this is usually a unilateral presentation?
[Dr. Ashleigh Halderman]
I have not seen it bilateral, fortunately. I am not aware of any reports of it being bilateral.
[Dr. Gopi Shah]
After they're discharged, when do them back? When do you order that first surveillance imaging?
[Dr. Ashleigh Halderman]
I'll usually see them at about a week just to check in. Mostly that's sort of like a, hey, let's make sure that you've got your other follow-ups and that you're on your medications, and that you understand that you're going to need to be on these. Then typically the repeat imaging is up to ID, and I let them decide that. I probably wouldn't get it earlier than one month and would maybe go about 3 months, 6 to 12 weeks of treatment before doing that, and then go from there. It's a conversation with you and ID.
[Dr. Gopi Shah]
That's an MRI usually?
[Dr. Ashleigh Halderman]
Typically, yes.
[Dr. Ashley Agan]
Are sort of the three main things as opposed to any of the sino-nasal symptoms that they probably didn't have to begin with for this.
[Dr. Ashleigh Halderman]
Correct. Right. It's like the absence of sort of sino-nasal symptoms. I think in a few series of patients, like everybody presented with headache or facial pain.
[Dr. Gopi Shah]
Do those symptoms respond pretty quickly?
[Dr. Ashleigh Halderman]
They do actually. Yes. The woman that I had mentioned who had the severe facial pain for a year prior to presentation, her pain rapidly got better, which was very rewarding and she was grateful.
[Dr. Gopi Shah] Awesome. This has been a really informative, really great talk. As we round things out, anything that we've missed or anything we need to make sure that we touch on before we let you go?
[Dr. Ashleigh Halderman]
No. I think it's worth just sort of repeating the fact that the question of how aggressive surgically do you need to be is very up in the air right now. I can speak from experience when I say I've not regretted not being more surgically aggressive. I would say that in the majority of patients that I have treated, we've done limited debridement just to get the diagnosis and then really relied on the better antifungals that we have now and in a very prolonged course of treatment. We've not disfigured anybody unnecessarily or blinded them or removed an eye or anything like that and they've survived.
I would say if you're faced with one of these cases, don't swing for the fences necessarily. I think that that's something that we as a field need to really revisit, is the necessity of aggressive surgical treatment in these patients with the new age of antifungals.
[Dr. Ashley Agan]
Thank you so much, Ashleigh. If any of our audience wants to reach out to you, are you on any social media? If you're not, they can reach out to us on BackTable, we can relay the message.
[Dr. Ashleigh Halderman]
I don't have any social media, but I would be happy to, if you guys want to relay it to me, please feel free to contact the podcast with questions and I would be happy to correspond.
[Dr. Ashley Agan]
Awesome.
[Dr. Gopi Shah]
Thanks for taking the time Ashleigh.
[Dr. Ashley Agan]
Thank you, Ashleigh. This is great.
[Dr. Ashleigh Halderman]
Thanks for having me again. It's really good to see you girls.
[Dr. Gopi Shah]
It's so great to see you.
[Dr. Ashley Agan]
Podcast Contributors
Dr. Ashleigh Halderman
Dr. Ashleigh Halderman is an Assistant Professor and practicing ENT specializing in rhinology and skull base surgery in the Department of Otolaryngology at UT Southwestern in Texas.
Dr. Ashley Agan
Dr. Ashley Agan is an otolaryngologist in Dallas, TX.
Dr. Gopi Shah
Dr. Gopi Shah is a pediatric otolaryngologist and the co-host of BackTable ENT.
Cite This Podcast
BackTable, LLC (Producer). (2024, March 26). Ep. 164 – Chronic Invasive Fungal Sinusitis: Diagnosis & Management [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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