[SPEAKER_00]: Welcome back to Run the List.
[SPEAKER_00]: I'm your host Walker Redden and I'm thrilled to be here today with our guest, Matthew Pullen.
[SPEAKER_00]: Dr. Pullen is an assistant professor and infectious diseases at the University of Minnesota.
[SPEAKER_00]: He studies and dimming my co-sees, CryptoCocoman and Gitis, advanced HIV and COVID-nineteen.
[SPEAKER_00]: He has a super interesting background and bio-defense and bioterrorism, and now does work in clinical trials.
[SPEAKER_00]: We got together and we're thinking about how we could work to address the little bit of a gap that there is in the common understanding of endemic fungal infections such as blastomycosis.
[SPEAKER_00]: This is topic that's often only briefly covered in med school and there's groups of ID doctors who are really dedicated to studying these diseases in more detail helping to address that gap in some of our knowledge.
[SPEAKER_00]: So it's important for all clinicians to keep endemic mycosis in mind.
[SPEAKER_00]: And this case presentation, I don't want to build it up too much, but it's one of the more interesting case presentations we've ever done on the list.
[SPEAKER_00]: And I'm so excited for you to be here today Matt.
[SPEAKER_00]: Thanks for joining us.
[SPEAKER_01]: Of course, thank you very much for having me.
[SPEAKER_01]: I love talking about this.
[SPEAKER_00]: So, without any further ado, we're going to go ahead and run the list.
[SPEAKER_00]: Let's imagine you're seeing a forty-five-year-old man in clinic.
[SPEAKER_00]: He has a history of metabolic associated liver disease, hypertension, and he's initially presented to his dermatologist with several large purple black lesions, ranging in size from the size of a dime to a half-dollar, that have appeared on his trunk, flank, and thighs over the past month.
[SPEAKER_00]: These lesions aren't necessarily painful and peritic, but they do seem to be enlarging and new ones continue to show up.
[SPEAKER_00]: Over that same period of time, he has developed a sharp pinpoint area of pain in the lateral side of his right ankle.
[SPEAKER_00]: About two months prior to these symptoms developing, he developed a mild self-resolving respiratory illness.
[SPEAKER_00]: And this occurred while he was spending time at a relative's cabin in rural Pennsylvania, where he helped clear rotting pine trees.
[SPEAKER_00]: The time he was a bit distant, and he had a cough that was non-productive, accompanied by mild fever and chills.
[SPEAKER_00]: He didn't seem to respond much to over-the-counter-code and flu medications, but these symptoms gradually resolved over the following two weeks, and he doesn't currently have any respiratory symptoms.
[SPEAKER_00]: When you see him in clinic and do an exam, his vitals are stable, his well-appearing, the lesions described on his skin, or consistent with what he described on history, his right ankle's non-tender, but he does grim his son when standing and bearing weight on it.
[SPEAKER_00]: his lungs are queer to osculation.
[SPEAKER_00]: All right, so Matt, honestly, if I was seeing this patient, one of my first thoughts would be that I'd probably need to get the help of an infectious disease doctor.
[SPEAKER_00]: So we want to turn to you if ask, what are some of your initial thoughts when you hear about this case presentation?
[SPEAKER_01]: Yeah, so this is a pretty classic presentation for disseminated blastomycosis.
[SPEAKER_01]: The tricky part about this specific infection is that it can have a really varied presentation.
[SPEAKER_01]: About half of those infected with bloodstum ICs will remain asymptomatic and self-resolve, but the most common symptomatic presentation is the classic respiratory syndrome, typically called the pneumonia that doesn't improve with antibiotics.
[SPEAKER_01]: Beyond the lungs, the most common sites we see involved in disseminated disease are the skin, bones, genital urinary tract, and then the central nervous system.
[SPEAKER_00]: All right, so given that those symptoms can basically occur anywhere in the body and they're kind of non-specific, what are some other aspects of the history that you hone in on as an ID doc to help clarify what may be very relevant to the case?
[SPEAKER_01]: Yeah, so like with a lot of things in infectious disease, you should really think carefully about the exposure history.
[SPEAKER_01]: In this patient's case, he was working with rotting and waterlogged wood in the Ohio River Valley.
[SPEAKER_01]: That's the classic geographic region that we all learn about in med school when it comes to blasto.
[SPEAKER_01]: The soil spore connection is really key here.
[SPEAKER_01]: Blast of micees is what's called a thermally dimorphic fungus, meaning it exists in two forms since the dimorphic based on the temperature it exists in.
[SPEAKER_01]: It exists as a spore in the cooler soil and vegetation out the environment and then phase transitions into the pathogenic budding yeast form in warm environments like the mammalian respiratory tract.
[SPEAKER_01]: Classically, we used to call this the hunters disease because hunting dogs would get blast to my coasts.
[SPEAKER_01]: Even today, we see this pattern of someone coming in with respiratory symptoms that aren't resolving.
[SPEAKER_01]: And then they say, hey, you know, my dog had similar symptoms a couple weeks before me.
[SPEAKER_01]: A lot of that is because dogs, you know, they're sniffing around in the soil, they're disturbing soil and vegetation.
[SPEAKER_01]: So they likely get a higher burden of disease that they're inhaling.
[SPEAKER_01]: and they disturb the spores and kick them up into the air, which leads to their human being infected as well.
[SPEAKER_00]: That's so helpful.
[SPEAKER_00]: Just keeping in mind the example of dogs and how they may be able to get it in front of to their humans really is going to help me remember the soil spore connection.
[SPEAKER_00]: I also know that you've explained to me that the sort of classic geographic distribution we all learned about in med school has been shifting a bit.
[SPEAKER_00]: So could you speak to some of the epidemiologic data and how we sort of understand it these days?
[SPEAKER_01]: Yeah, a lot of the epidemiologic studies that are the basis of our medical school training where we talk about the Ohio and Mississippi River valleys.
[SPEAKER_01]: Those were performed in the nineteen sixties and nineteen seventies, which you know, understandably data was a little harder to come by.
[SPEAKER_01]: It was often incomplete.
[SPEAKER_01]: And it likely captured where people were diagnosed rather than with it, where they were exposed.
[SPEAKER_01]: So it kind of biases towards large medical centers, even today.
[SPEAKER_01]: More recent studies using Medicare data and multi-center studies
[SPEAKER_01]: has shown that the geographic range of last to my coasts as well as other endemics like histoplasmosis and coxidioidomycosis are expanding.
[SPEAKER_01]: Part of that is just, you know, revealing what was probably there the whole time that has a larger geographic distribution, but also the climate's changing.
[SPEAKER_01]: It's getting warmer and more humid everywhere, which is what these fungi love.
[SPEAKER_00]: So with that context in mind, did you just discuss the clinical presentation and a bit more detail?
[SPEAKER_00]: I know you said that the pulmonary blastos sort of how it initially starts, but could you speak more to what that's like and what the presentation may be like?
[SPEAKER_01]: Yeah, absolutely.
[SPEAKER_01]: So by far the most common symptomatic syndrome we see is the classic pulmonary blastomycosis kind of like all blastomycosis.
[SPEAKER_01]: This also has a pretty wide range of presentations.
[SPEAKER_01]: It can be anything from a mild, subacute subclinical pneumonia, all the way up to ARDS with the ARDS form carrying a nearly fifty percent mortality rate.
[SPEAKER_01]: So that's a pretty serious disease.
[SPEAKER_01]: Other than the kind of non-specific dyspnea and cough, you can often see fever, fatigue, hemoptosis, night sweats, weight loss, all of these things that we can see in bacterial pneumonia tuberculosis, even malignancies,
[SPEAKER_01]: which you often leads to the delayed diagnosis that's super common in Boston, my closest.
[SPEAKER_01]: It just looks like so many different things.
[SPEAKER_01]: Imaging findings similarly are pretty widely variable and often not very helpful.
[SPEAKER_01]: It can be everything from patchyopathies to cavitary lesions to the super unhelpful tree and bud appearance, which all of this also contributes to the frequent missed or delayed diagnoses in Boston.
[SPEAKER_00]: Thank you so much for walking us through that.
[SPEAKER_00]: I'm really picking up on a pattern here, which is that this can be a challenging diagnosis, which is why we're covering it today and really highlighting some of the subtleties here.
[SPEAKER_00]: So to that end, could you speak to some of the extra pulmonary manifestations of blastomycosis?
[SPEAKER_01]: About a quarter to forty percent of people will develop disseminated disease.
[SPEAKER_01]: Most often disseminating from their initial pulmonary source since that's the most common way you get infected.
[SPEAKER_01]: The most common site or dissemination by far is the skin.
[SPEAKER_01]: About forty to eighty percent of disseminated disease will be cutaneous.
[SPEAKER_01]: The next most common is osteomyolitis affecting five to twenty five percent of disseminated disease patients.
[SPEAKER_01]: And then the genital urinary tract at less than ten percent.
[SPEAKER_01]: Cutaneous disease usually starts as papial-pustular lesions that can progress to worty-veruchus plaques.
[SPEAKER_01]: They can develop central ulceration, can become violatious nodules or even develop underlying abscesses.
[SPEAKER_01]: Blasto mice's osteomyelitis usually presents as an abscess or sinus tract or septic arthritis in a seated joint or bone.
[SPEAKER_01]: And then the least common side, the CNS.
[SPEAKER_01]: It's usually in five to less than ten percent of disseminated disease.
[SPEAKER_01]: more often occurs in people with immunocompromising conditions or other syndromes or conditions that make them more prone to neurologic infection.
[SPEAKER_01]: This can present as a typical meningitis pattern, looking very similar to other fungal or bacterial meningitis diagnoses, or can present as a space occupying legion or abscess in the cranium or the spine.
[SPEAKER_00]: All right, so we have to keep in mind the skin, the bones, the genetic urinary tract, and the CNS.
[SPEAKER_00]: That's a lot to think about.
[SPEAKER_00]: And as we have gone through this case, we've already gotten a lot of relevant history.
[SPEAKER_00]: You have sort of described all the different aspects of the presentation.
[SPEAKER_00]: And so once this is in our differential, and we're trying to think about how to diagnose it, what are some of the tests we should be looking to perform to sort of coincide the diagnosis?
[SPEAKER_01]: So there are a few tests available to us.
[SPEAKER_01]: A lot of it kind of depends on
[SPEAKER_01]: where the disease is and what you have access to.
[SPEAKER_01]: In cases where you have skin disease, like in this patient or bone disease, the old adage of tissue is the issue applies.
[SPEAKER_01]: If you could buy up see something, buy up see it.
[SPEAKER_01]: You know, sometimes that can lead you to a quick diagnosis just by a preliminary pathology exam that shows buddy yeast.
[SPEAKER_01]: biopsies not always possible and you know getting tissue for fungal culture can often be slow.
[SPEAKER_01]: Cultures of fungus can take up to five weeks.
[SPEAKER_01]: So often it's just that preliminary pathology look that's really helpful.
[SPEAKER_01]: In pulmonary cases often we don't have anything to biopsy and that's where antigen testing is really key.
[SPEAKER_01]: Antigen testing can be done on blood on urine those two or by far the most common sources we use.
[SPEAKER_01]: But it can also be performed on CSF as well as BAL fluid.
[SPEAKER_01]: The turnaround time is fairly quick, even though it's a send out test.
[SPEAKER_01]: And one important thing to note is that there's broad cross reactivity between the blastobicis antigen and histoplasma toleromicis in paracoxidioidis antigen.
[SPEAKER_01]: So if there's a risk that they could have one of those infections, you should also order specific tests for those as well, just to kind of fair it out, which one is the actual infection here?
[SPEAKER_01]: There are some newer tests being developed, most of them PCR or next generation sequencing based.
[SPEAKER_01]: They're not really on the market yet, so keep your eye out for those.
[SPEAKER_01]: But right now, the focus is antigen testing and tissue biopsy.
[SPEAKER_00]: Perfect.
[SPEAKER_00]: So in this patient's case dermatology actually performed a punch by Opsi of one of the thigh lesions and that should broad-based but in yeast and Gamori methanamine silver staining.
[SPEAKER_00]: And so once we have the diagnosis, how do you approach treatment?
[SPEAKER_00]: I know it's really dependent on disease severity, so could you walk us through that?
[SPEAKER_01]: Sure.
[SPEAKER_01]: Treatment really depends on severity of the disease.
[SPEAKER_01]: The main break point is amphotericin or no amphotericin.
[SPEAKER_01]: From mild to moderate pulmonary disease, we typically don't use induction therapy with amphotericin.
[SPEAKER_01]: Instead, we go right to an oral easel.
[SPEAKER_01]: Typically, treating for six to twelve months, the easel of choice for Blasto, just because it's the most well studied.
[SPEAKER_01]: And as far as we know, most effective is itchricanasol.
[SPEAKER_01]: From mild to moderate, disseminated disease, but without CNS involvement,
[SPEAKER_01]: We take a similar approach using an oral asal right up front, usually treating for about twelve months, so a little bit longer than pulmonary disease.
[SPEAKER_01]: If patients have severe disease, which is typically based on clinical judgment, they may warrant induction therapy with amphotericin.
[SPEAKER_01]: So for severe pulmonary disease, severe disseminated disease, or any of those forms with CNS involvement, or if they're immunocompromised and have any form of blastomyosis,
[SPEAKER_01]: Then we would start out with one to two weeks of liposomal amphotericin as induction therapy.
[SPEAKER_01]: You can even extend it if you're not seeing signs of clinical improvement right off the bat.
[SPEAKER_01]: Once you finish that induction, then you step down to oral therapy, which, again, is oral atricanasal.
[SPEAKER_01]: In immunocompromise patients, you may want to continue lifelong suppression.
[SPEAKER_01]: If it's anticipated, they will continue to be immunosuppressed and potentially continually exposed to blastomyces.
[SPEAKER_01]: Ittriconazole, like all Asals, does have pitfalls and drawbacks.
[SPEAKER_01]: It has plenty of drug interactions.
[SPEAKER_01]: Patients can often report GI side effects and rash in absorption of the drug can be pretty variable.
[SPEAKER_01]: If someone isn't tolerating ittriconazole, we'll often switch to an alternative Asal, like Pozaconazole or Voryoconazole.
[SPEAKER_01]: But data is pretty limited and we often have to select the specific agent based on where in the body we're trying to treat.
[SPEAKER_01]: So in those cases, definitely get idea involved.
[SPEAKER_01]: That's what we live for.
[SPEAKER_00]: Love it.
[SPEAKER_00]: I always love to hear that.
[SPEAKER_00]: And thank you so much for stepping through all the aspects of how to diagnose and treat blasphemy courses.
[SPEAKER_00]: Before we wrap up as always, we just want to get the top three pearls that our listeners can take away from this discussion today.
[SPEAKER_00]: And then I also know that you just want to do include a quick reference to direct our listeners to one of the study websites that you have in case they have any of these cases themselves.
[SPEAKER_01]: Yeah, I would say that the three big takeaways are that bust on my coasts can mimic a wide variety of other conditions.
[SPEAKER_01]: So if your work up just isn't quite making sense with your working diagnosis and have a compatible exposure history, think bust on my coasts.
[SPEAKER_01]: It's the second point would be considering tissue in your diagnostics combined with antigen testing.
[SPEAKER_01]: And the third point would be that if your connoisseur is the most well studied oral therapy
[SPEAKER_01]: and should be preceded by induction therapy with glyphosomalonphoteros and in severe cases, CNS disease or any infection in an immunocompromised patient.
[SPEAKER_01]: And then, yeah, if you have any patients with blastomyocosis or histoplasmosis or coxidioidomyocosis, please send them our way.
[SPEAKER_01]: The website is fungalstudy.org.
[SPEAKER_01]: We're doing a large nationwide online study looking at patient-reported outcomes and treatment responses.
[SPEAKER_01]: All they have to do is answer online surveys and we'd love to hear from people out there that are being treated for these infections.
[SPEAKER_00]: Well, thanks so much for joining us again, Matt, and thanks to our listeners for tuning in.
[SPEAKER_00]: We'll catch you next time.
[SPEAKER_01]: Thank you.