[SPEAKER_01]: I think one has to be vigilant that on occasion this curious cell can indeed contribute to and cause tissue damage and it's up to us to be cognizant of that risk
[SPEAKER_05]: Welcome to the Coryham Thi-Pro's podcast, bringing you high yield evidence-based pearls.
[SPEAKER_05]: I'm Dr. Shrechevetti, and I'm joined by.
[SPEAKER_06]: Hi, I'm Hila Gershin, and I'm Colonel Medicine resident at Beth Israel's Deaconess Medical Center.
[SPEAKER_06]: Today's episode is all about peripheral eocinophilia.
[SPEAKER_05]: Yes, and to help us sort through this, we spoke to experts in the world of allergy and immunology, hematology and pulmonology, and to dig into this topic in a way that embias but I feel like is way more approachable than what I knew before.
[SPEAKER_01]: Hi, I'm Dr. Peter Weller, Chief of the Allerity Division at the former chief of the ID division at the B.I.
[SPEAKER_01]: Deaconess down at that long standing interest in E.S.
[SPEAKER_01]: and Affelia.
[SPEAKER_04]: Hi, I'm Jason Fried, a hematologist at Beth Israel Deaconess Medical Center in Harvard Medical School in Boston.
[SPEAKER_02]: will contribute to the death from pulmonary and critical care at University of California, San Diego, and I'm a professor of medicine there.
[SPEAKER_02]: I have a practice that focuses on esophorelect disease.
[SPEAKER_06]: And as always, please pause after each of the following pearls and test yourself.
[SPEAKER_06]: Because the more you test yourself, the deeper you're learning gains.
[SPEAKER_05]: Pearl 1, threshold and why we care.
[SPEAKER_05]: Why don't we care about use to failure and when does
[SPEAKER_06]: Pearl 2, use an affiliate in ATP.
[SPEAKER_06]: One can asthma allergic rhinitis or Xima explain eocinophilia, and one should you worry something more systemic is going on.
[SPEAKER_05]: Pearl 3, medications, which medications most likely cause eocinophilia, and one is at safe to monitor versus when you need to stop.
[SPEAKER_06]: Pearl 4, infections and parasites, how do travel immigration history and diet guide your infectious work up?
[SPEAKER_05]: And finally, a Pearl 5, steroids and malignancy, had steroids affect that yeast in health count, and why do we need to think about new plastic causes of yeast in Vilia before we treat?
[SPEAKER_05]: Okay, let's start a big picture here, Hila.
[SPEAKER_05]: And maybe the elephant in the room, why should we even care about Eosinophils to begin with?
[SPEAKER_06]: Shreya, I had the exact same question and that was a big motivation behind why wanted to learn more about this.
[SPEAKER_06]: So we care about Eosinophilia for two main reasons.
[SPEAKER_06]: First, if Eosinophils get high enough, they can cause direct organ damage, regardless of why they're so high.
[SPEAKER_06]: The second reason is that an elevated Eosinophil count can be that first clue that something more serious is going on in the body.
[SPEAKER_05]: I'm amazing.
[SPEAKER_05]: Okay, so before we get into the clues about what that use in Philly and might be telling us, let's make sure we're all in the same shared language.
[SPEAKER_05]: What is use in Philly and then when should we pause and particularly can you help me understand the numbers in the EMR, there's percentages, there's absolute values, there's decimal places.
[SPEAKER_06]: Definitely, Eosinophilia is an absolute Eosinaphil count, greater than 500 Eosinaphil's per microliter.
[SPEAKER_06]: Unfortunately, in most electronic medical record systems, this will not show up as 500, but rather 0.5.
[SPEAKER_06]: So since the units are different, you'll need to multiply by 1,000 anything you see in the EMR to get that Eosinaphil's per microliter.
[SPEAKER_05]: I'm so glad you said that because I also even get confused when I look at the percentage, or when I get the absolute one.
[SPEAKER_05]: And it's so sensitive.
[SPEAKER_05]: I'm looking at the absolute e-account and we kind of ignore the percentage.
[SPEAKER_05]: And then, yeah, I guess we just have to translate like decimal points.
[SPEAKER_06]: Right.
[SPEAKER_06]: So for absolute eocentifl account greater than 500 or greater than 0.5 in our electronic medical records system, we're starting to put on our detective hats.
[SPEAKER_06]: But when we're reaching an absolute eocinifal calculator than 1500 or 1.5, we get into hyper eocinifilia territory.
[SPEAKER_06]: And that's when we need to get vigilant and do more than just put on our detective hats.
[SPEAKER_04]: Hyperacinophilia just means their absolute use in a VilleCount is above 1500.
[SPEAKER_04]: That we just arbitrarily decide if it's above that, it's hyper.
[SPEAKER_04]: Okay, fine.
[SPEAKER_04]: But what's Hyperacinphylic syndrome?
[SPEAKER_04]: Hyperacinphylic syndrome means you have an absolute use in a VilleCount above 1500.
[SPEAKER_04]: And you have some end organ manifestation that is being caused by the elevated use in a VilleCount.
[SPEAKER_04]: It's pretty rare to have sort of end-organ manifestations with an absolute EIS NFL count less than 1,500.
[SPEAKER_04]: Between 1,500 and 5,000, it gets tricky because you can definitely have some life that, you know, that many manifestations in that category.
[SPEAKER_04]: And then when you get above 5,000, and especially like the higher you get, the more likely that you are to develop some serious end-organ manifestations from the non-specific effects and having super high EIS NFL count.
[SPEAKER_05]: Okay, so sounds like if the Eosinval count is high enough, particularly above 1,500 per mic leader or 1.5 in the EMR, then we worry about that directly causing some end organ damage of regardless of the cause.
[SPEAKER_06]: Exactly.
[SPEAKER_06]: Hybrid use in affiliate is just the number, just the absolute use in a full count greater than 1500 or 1.5.
[SPEAKER_06]: Now, hybrid use in a phylic syndrome, that's a clinical diagnosis.
[SPEAKER_06]: That's hybrid use in affiliate plus an organ damage, which is more likely to occur when that use in a full count is above 1.5.
[SPEAKER_05]: Okay, so it sounds like when there's too many eosophils, these crowded eosophils decranely in the blood and in the tissue, and that can lead to the end organ damage.
[SPEAKER_05]: And unfortunately, that end organ damage can be in any organ, the heart, the skin, the lungs, the GI system.
[SPEAKER_06]: Yeah, I once had a patient who presented with right-sided weakness and was found to have symbolic strokes.
[SPEAKER_06]: Her Eucinifel count was 17,000 or 17.0 on epic, and her triponence kept rising.
[SPEAKER_06]: She never had any chest pain, shortness of breath, but as part of her workup, we got a cardiac MRI.
[SPEAKER_06]: That showed signs of fibrosis, which was really concerning for Eucinifelic myocarditis.
[SPEAKER_06]: Because of all the inflammation in her left ventricle, she developed a thrombus that then
[SPEAKER_05]: Oh my, you know what I'm so struck by?
[SPEAKER_05]: Is that patient had no symptoms, right?
[SPEAKER_05]: That used to feel like my carditis was clinically silent.
[SPEAKER_05]: Gosh, like there was no symptoms related to that cardiac dysfunction.
[SPEAKER_06]: Exactly.
[SPEAKER_06]: And my takeaway from that is when patients have an eocinophile level above 1500 or 1.5, we need to be vigilant in evaluating for eocinophile like myocarditis regardless of the symptoms.
[SPEAKER_06]: We should get to reponents and EKGs.
[SPEAKER_06]: And I even spoke to some cardiologists who recommend getting an echo up front too to evaluate for that thrombus formation.
[SPEAKER_05]: So helpful.
[SPEAKER_05]: So trope, EKG, plus minus echo, when the EOS in a full count is greater than 1500 per mic leader or 1.5.
[SPEAKER_05]: Okay, what about the other organs, right?
[SPEAKER_05]: Do we do anything else to screen for other and organ damage in the body when the EO count is that high?
[SPEAKER_06]: We should definitely get a basic metabolic panel and liver function tests to evaluate for any renal or liver involvement.
[SPEAKER_06]: But the rest of the body, it's really having that vigilance, like you need to do a thorough review of systems to identify any no pulmonary or GI symptoms, do a physical exam to look for any rashes or any neuro signs.
[SPEAKER_05]: Okay, so that's helpful in the context of anyone who has an eocount career than 1500 or so, but I guess the other question is, does it matter how high the eocount is above that 1500 threshold?
[SPEAKER_05]: Like, is someone with an eocopal count career than 3000 more likely to have an organ damage in someone than 1500 eocopal is for my career.
[SPEAKER_06]: Oh, Shreyah, only it was that straightforward, though there is a higher risk with more elevated eocinophilia.
[SPEAKER_06]: There's not a one-to-one relationship.
[SPEAKER_06]: This number caught off a 1500, gives us an idea of a patient's risk of an organ damage, but peripheral eocinophil accounts, which is what we measure on a CBC, does not correlate with the damage that eocinophils can cause in the body.
[SPEAKER_01]: There's no perfect correlation between magnitude of blood eocinophilia and risk of cardiac damage or other eocinophile mediated grief with the imprecision of measuring eocinophile numbers and the fact that what we can sample is the circulating blood pool of eocinophiles.
[SPEAKER_01]: We don't know what's going on in the marrow.
[SPEAKER_01]: We don't know what's going on in tissues.
[SPEAKER_06]: Understanding the life cycles of use in a fills is really helpful to explain this.
[SPEAKER_06]: EOS spend only about 25 hours of their lifespan and peripheral circulation, but then spend days or even up to weeks in the tissues.
[SPEAKER_06]: They call it use in a fills tissue dwelling cells for a reason.
[SPEAKER_06]: So you can imagine the sample that you're getting in your AM labs is only a snapshot in time and misses the full distribution of use in a fills in the body.
[SPEAKER_05]: Yeah, man, that idea that the e-o count that we see at our EMR is just a snap shot and that these e-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-o-
[SPEAKER_06]: And at the same time, there can be peripheral eucinophilia without tissue damage.
[SPEAKER_06]: This adds another layer of complexity to the already complicated topic of eucinophilia.
[SPEAKER_05]: Oh, man.
[SPEAKER_05]: Awesome.
[SPEAKER_05]: I'm with you.
[SPEAKER_05]: I'm getting this.
[SPEAKER_05]: Thank you so much.
[SPEAKER_05]: He'll have for doing this.
[SPEAKER_05]: So maybe if I can summarize kind of our first chunk or first pearl, it's that we care about using a failure, particularly that's defined by greater than 500 EOS levels for micro leader or point five in the EMR.
[SPEAKER_06]: And the second reason we care is that the absolute useful account is a clue that something else more serious is going on.
[SPEAKER_06]: So let's put our detective hats on for the rest of these pearls.
[SPEAKER_05]: All right, so let's say we have a patient whose useful count is 750.
[SPEAKER_05]: So in the EMR, it would show up as 0.75.
[SPEAKER_05]: To be on the safe side, we think about end organ damage, there's no symptoms, there's no lab of remalonies, nothing scary.
[SPEAKER_05]: He like, can we just ignore this 750 use of L account?
[SPEAKER_05]: Can we just like close our eyes and hope it goes away?
[SPEAKER_06]: short answer, no, as we mentioned, even without an organ damage, Eosinophilia can still be a signal that's something else is going on.
[SPEAKER_06]: So we still need a framework to figure out why that Eosinophils are so high.
[SPEAKER_04]: There is a very popular nemonic for the causes of Eosinophilia that I have actually found very helpful in my practice.
[SPEAKER_04]: And that is NWACP.
[SPEAKER_06]: Okay, so NAACP is a helpful nomonic, but it misses an important ideology of Eosinophilia, and also includes a name for EGPA.
[SPEAKER_06]: We don't use anymore.
[SPEAKER_06]: So I propose a new nomonic, camp E or camp Eosinophilia.
[SPEAKER_05]: Awesome.
[SPEAKER_05]: Tell me more, Hila.
[SPEAKER_06]: So envision five tents around a bonfire in the woods of camp E or camp Eosinophilia.
[SPEAKER_06]: Each of these tents represents a different ideology.
[SPEAKER_06]: So see us for cancer.
[SPEAKER_06]: A is an extra large tent with room for both ATP, and adrenal insufficiency.
[SPEAKER_06]: MS for medications, P is for pathogens, and E is EGPA.
[SPEAKER_06]: The bonfire in the middle represents the inflammation that is caused by having too many circulating eucinophils.
[SPEAKER_05]: Uh, I love that, but also humbling, right?
[SPEAKER_05]: Because like everything from cancer or ATP, adrenal insufficiency, meds, Paris, I mean, I appreciate a good list, um, you know, keeps us from missing stuff.
[SPEAKER_05]: But lists are also just less.
[SPEAKER_05]: And how do we prioritize, you know, one thing from another?
[SPEAKER_06]: I feel you on that on such a deep level.
[SPEAKER_06]: So I thought it would be a really good idea to go through the most common causes of use in a failure and dig through some nuances with an each.
[SPEAKER_04]: when I'm seeing an outpatient for peripheral bloodiest in affiliate.
[SPEAKER_04]: One of the first questions I'm asking myself is, do they have a disease known to be associated with peripheral bloodiocinophilia?
[SPEAKER_04]: Number two is the acinophilia mild.
[SPEAKER_04]: And therefore I can just probably connect it to that disease known to be associated with acinophilia.
[SPEAKER_04]: And number three, is there anything else going on with them that needs to be explained or is this really just an incidental abnormality that we're trying to connect?
[SPEAKER_04]: And if it's just an incidental abnormality, they're doing fine otherwise, and we've got a diagnosis we can connect to.
[SPEAKER_04]: And it's mild, I'm usually done there.
[SPEAKER_05]: Okay, so for a mutation in clinic who has mild eocinophilia and then the conditions I'll be thinking about are the things that fall in that atopic bucket right allergic rhinitis asthma atopic dermatitis and one thing that I learned from our peer reviewer was that even eocinophilic GI disease is like eocinophilic esophageitis fall into the atopia umbrella.
[SPEAKER_03]: for relatively not high radius in the earlier, like in the kind of 500 to 1500 range, I'd say, you know, top things that they often are in those patients are some sort of a top thing.
[SPEAKER_03]: You know, ATP is very common in the population.
[SPEAKER_03]: So that's what, you know, common things being common.
[SPEAKER_06]: As I was learning more about this topic, I kept seeing this relationship between East Sinophil's and allergic conditions and I kept wondering why.
[SPEAKER_06]: Turns out, a topic diseases are driven by damage to the epithelium, which leads to inflammation.
[SPEAKER_06]: This inflammation leads to the migration of type 2 helpers cells and they produce a ton of IL-5.
[SPEAKER_06]: If you remember from boards, IL-5 is super important for you Sinophil maturation and their survival.
[SPEAKER_03]: So IL-5 is also produced by liposite CD4, type 2, liposites that, you know, those cells that are kind of canonically or classically regulated in allergic conditions.
[SPEAKER_03]: And that's why ESNFOs are up in these atopic conditions and many patients with ATP is that that's driven by the excess IL-5.
[SPEAKER_05]: IL5, well, I have not thought about that in a minute, but makes me think like, you know, if someone is a really bad algae flare or an asthma exacerbation, maybe their IL5 will like go crazy and then their Eosinival count will be proportionally that much higher.
[SPEAKER_05]: That's a good thought, but unfortunately no.
[SPEAKER_01]: You can be well controlled asthma and still have any astrophobia.
[SPEAKER_06]: You can have Xima or a topic dermatitis or eocinophilic gastritis that is relatively well controlled and still have eocinophilia.
[SPEAKER_06]: So eocinophilia is not a marker of disease activity, and IL-5 is not a helpful app to send.
[SPEAKER_05]: Uh, what a humbling cell in our bloodstream.
[SPEAKER_05]: I just wish it was like a one to one with the Eosinval account interpretation.
[SPEAKER_05]: I guess what I'm worrying about is that say I have a patient who has a mild Eosinval count and they have something in their chart like asthma, allergies, atopic dermatitis, then my worries, I'm just gonna write off that Eosinval count and not think of the other things in that campy pneumonic, right?
[SPEAKER_05]: Like, I don't want to misparasite.
[SPEAKER_05]: I don't want miscancer.
[SPEAKER_06]: I don't either, and I live with those same anxieties, but common things are common.
[SPEAKER_06]: What you do bring up, though, is a really great point that we need to keep a healthy dose of curiosity, because systemic conditions like EGPA or Yosinophilia granulomotosis with polyengitis often start with Yosinophilia and asthma.
[SPEAKER_01]: But I think one still has to keep in mind that is there something else developing an example would be what used to be called the Turks rose syndrome EGPA that can be processed where you know for adults that manifest by adult onset asthma sinusitis and then the vasculitis manifests later.
[SPEAKER_01]: So it's a situation where I think you can say, yeah, can you as my give you a center for you?
[SPEAKER_01]: Yes, but can you close the book necessarily in that individual?
[SPEAKER_01]: No, and if something else is developing, it makes you worried about a vast deletic process.
[SPEAKER_06]: So when there are multiple systems involved with signs of glomerular lymphritis and asymmetric neurologic findings, like monitoritis multiplex, it raises the possibility of vascularitis.
[SPEAKER_06]: And if those are present, you need to consider EGPA formerly known as Church Strauss Disease as a potential ideology.
[SPEAKER_01]: I had called it in Miku and we get night and it was a gentleman who ended up perforating his ball and in retrospect, it was a Vascularitis, it was a GPA.
[SPEAKER_01]: He had been referred, but a year and a half before, it probably has some abdominal pain, but he had a CT scan and he had a hypernephroma.
[SPEAKER_01]: So he was sent to us for a surgical resection.
[SPEAKER_01]: At that time, he had an E.S.
[SPEAKER_01]: in Ephilia.
[SPEAKER_01]: People said, hey, we're in the front white E.S.
[SPEAKER_01]: in Ephilia, it's no link, let it be.
[SPEAKER_01]: But in retrospect, he had Turkstraus syndrome, E.G.P.A.
[SPEAKER_01]: and what did a man with ultimately was a small bottle of ashillitis.
[SPEAKER_01]: The E.S.
[SPEAKER_01]: in Ephilia in retrospect was a clue to that.
[SPEAKER_01]: And probably, some of his abdominal pain,
[SPEAKER_01]: was is incipient GI vascularitis that then led to the CT scan, which gives you the diagnosis hypernafroma true, but not related.
[SPEAKER_05]: that case really highlights that mantra of staying curious.
[SPEAKER_05]: So I guess what I'm taking ways in a patient with asthma or sinusitis and other unexplained symptoms like that vague abdominal pain in the case we just heard or the classic kind of polypon exam or maybe there's unexplained opacity on lung imaging or abnormalities in their neurog exam or in their urine studies,
[SPEAKER_05]: We can think about EGPA, and Hela actually found this.
[SPEAKER_05]: There's this Euler criteria that can help us think through the diagnosis, and of course, we can always reach out to our rheumatology and allergy colleagues to help us make this very complex diagnosis.
[SPEAKER_06]: And so to recap, when someone has unexplained Eosinophilia without localizing symptoms, one of the first questions to ask is, do they already have a condition that's known to be associated with Eosinophilia?
[SPEAKER_06]: ATP really is one of the most common causes of use in a failure driven by damage to the epithelium and subsequent inflammation.
[SPEAKER_06]: But use in a full counts are not associated with disease activity.
[SPEAKER_05]: I still can't get over that.
[SPEAKER_05]: I wish I was a one to one.
[SPEAKER_05]: And then the other thing is that when you know, the explanation seems benign.
[SPEAKER_05]: I think we can all stay a bit curious.
[SPEAKER_05]: Make sure we're monitoring over time, watch out for any red flags that kind of come up.
[SPEAKER_05]: And of course, you know, Eosophilia might be a first clue that something bigger might be developing down the line.
[SPEAKER_06]: So we've talked about ATP as a potential source of eocinophilia, but our third pearl is truly something we see all the time.
[SPEAKER_06]: Medications.
[SPEAKER_04]: I think one of the most important things that you can do as a generalist is to take a very thorough medication history because medication-related eocinophilia is so extraordinarily common, both in terms of outpatients and both in terms of inpatients.
[SPEAKER_04]: And the diagnostic test for that,
[SPEAKER_04]: is a really good medication history which is not easy to do and it's actually like sometimes it's like so so easy to like click like click order order order you know echo order this order that order refer but like you know it's hard spending 15 minutes in the chart looking when they got each different antibiotic over the past two weeks and seeing which one might make sense timing wise as the cause of their dress syndrome.
[SPEAKER_04]: But
[SPEAKER_04]: Guess what?
[SPEAKER_04]: That's actually what's really going to solve the case, not necessarily sending off this million dollar work up for a bunch of things that don't make sense because if they acquired East and affiliate in the hospital, it is almost certainly related to a drug you gave them.
[SPEAKER_05]: And so doing a really good drug history is so essential.
[SPEAKER_04]: The group at MGH looked at 824 consecutive patients where they were going to be getting extended courses of ID antibiotics often about six weeks.
[SPEAKER_04]: And when they looked 25% of their patients developed some degree of peripheral blood isn't a failure.
[SPEAKER_04]: Absolutely, it's an evoke count greater than 500.
[SPEAKER_04]: They saw it isn't a failure with basically every antibiotic.
[SPEAKER_04]: You know, of course, Venko, Mison, Lanesalid, like, kind of silenced, but essentially, if you think about antibiotics are, their large natural products, they ended Mison, right?
[SPEAKER_04]: Like, we got them from microorganisms.
[SPEAKER_04]: And our bodies are sort of trained to treat such things as foreign, right?
[SPEAKER_04]: These like large macromolecules, like we, of course, want to be having an immune response to these large macromolecules.
[SPEAKER_04]: And so drug-related deacenephilia is really
[SPEAKER_06]: So antibiotics are a big cause of drug-related eocinophilia, but they're not the only ones.
[SPEAKER_06]: Some commonly implicated medications besides antibiotics include NSAIDs, anti-convulsions, and alloperonol.
[SPEAKER_01]: Homeopathic preparations at times have a listen to eocinophilia.
[SPEAKER_01]: The example, no, no example from some years ago is batches of contaminated elltryptafane that people took for a number of reasons for sleeping in this and that and they developed the ESMFLY and myologist syndrome.
[SPEAKER_01]: mechanism which is still not understood, it was the al-trip-defain that they were taking.
[SPEAKER_01]: And in some of those individuals, the medication history was not volunteered, as they weren't thinking about their nocturnal, al-trip-defain dose as a medication.
[SPEAKER_01]: Dr. Eden prescribed it, took it on their own,
[SPEAKER_05]: So yes, ask about supplements, ask about over the counter meds, or quote-unquote natural products, whatever will jog our patient's memory on the other things that they're taking.
[SPEAKER_05]: But I got to say, Hila, it seems like almost every medication can cause use in filia.
[SPEAKER_05]: And the hard part is to figure out which one, right?
[SPEAKER_05]: Like, I can imagine a situation where someone's on antibiotic, but also taking natural products.
[SPEAKER_06]: very fair and most of our patients are on more than one medication at a time.
[SPEAKER_06]: So you're right that any number of meds can be the culprit.
[SPEAKER_06]: And on top of that, it's sometimes tricky to pin down which one because drug-related use in affiliate isn't an immediate allergic reaction.
[SPEAKER_01]: In most cases, you know, the mechanism that drives the SNFelia elicited by a medications is really not well understood.
[SPEAKER_01]: It's not an IGE type allergic reaction, probably some manifestation of the self quotes sell me needed to be underneath.
[SPEAKER_01]: And it can develop after someone's been on a medication for a period of time.
[SPEAKER_01]: Me not become a parent right away.
[SPEAKER_06]: So because of the cell immunity, the time for when you start a medication to when you develop peripheral use in the philia can really vary by what medication it is and whether a patient has seen that medication before.
[SPEAKER_05]: That variation is so annoying to me because I wish again, it was like a clean timeline like drug exposure and then one week later, he is a philia.
[SPEAKER_06]: We have some rough guidelines from one of the studies that show that the median time from medication start to isolated peripheral eucinophilia is anywhere from one to 21 days, but even that's quite a big range.
[SPEAKER_06]: Right?
[SPEAKER_05]: So I guess maybe the practical kind of takeaway is to ask our patients, hey, what medications have you changed in the past month or so?
[SPEAKER_01]: if something were started recently and we know that didn't have any acidophilia a year ago, but now they have one, we've begins to point the finger potentially the newly started medication.
[SPEAKER_05]: Okay, so let's say the timing of a new medication starting and that trend of the absolute use of the account going up kind of works out and we have a good sense of okay, it was this medication doing it.
[SPEAKER_05]: Just that then mean automatically we have to stop
[SPEAKER_05]: Not necessarily.
[SPEAKER_04]: If they just have isolated peripheral bloodiest in the philia that is relatively mild, those patients can usually just be followed.
[SPEAKER_04]: And if that's really the best antibiotic for them, we'll often just continue the antibiotic.
[SPEAKER_04]: Because that's the safest course of action is to actually treat their infection, not which worry about an asymptomatic lab abnormality.
[SPEAKER_01]: As long as it's not yes and if immediate damage to tissues, I can continue to monitor that patient and follow them.
[SPEAKER_01]: Balance the need for the medication versus the easy choices terminating it.
[SPEAKER_01]: At times, hopefully patients were started on a medication for a reason, so that again comes up in patients who say on long-term anti-staphococcalatients, semi-sethetic penicins.
[SPEAKER_01]: They not infrequently will develop a log radius in a failure.
[SPEAKER_01]: They need it for what is potentially a life threatening and their periditis or whatever osteomyolitis and one would like to continue to ride with that.
[SPEAKER_01]: Is a reflection of ESFL media tissue damage?
[SPEAKER_05]: Okay, so isolated, asymptomatic use in Philia.
[SPEAKER_05]: We can often monitor.
[SPEAKER_06]: but that isolated qualifier really matters because what we're always watching for is dress, which stands for drug reaction with eocinophilia and systemic symptoms.
[SPEAKER_05]: And those systemic symptoms, the SS and dress is not subtle, right?
[SPEAKER_05]: Our patient's gonna are gonna be having fevers, more billy for a rash, facial, a de-mail, lymphedinopathy, hepatitis, achy, a whole storm.
[SPEAKER_06]: right, but it's just important to note because dresses treated very differently than isolated use in the philia.
[SPEAKER_06]: In dress, the offending agent has to be stopped immediately and patients often require further immunosuppression with steroids or other medications.
[SPEAKER_05]: Yeah, I think this is why that we have to like closely monitor right for end organ damage.
[SPEAKER_05]: And I think for space drop attention, right?
[SPEAKER_05]: We're going to be looking for triponins.
[SPEAKER_05]: We're going to get an EKG to see if there's any low voltage or any new arrhythmias.
[SPEAKER_05]: We're going to get LFTs.
[SPEAKER_05]: We're going to look at the kidney function.
[SPEAKER_05]: And of course, do a careful skin exam.
[SPEAKER_06]: And if you're suspecting a drug-related eocinophilia, I'm going to add that list a urine analysis.
[SPEAKER_06]: We're going to be looking for sterile pyuria or white cell cast that would be concerning for interstitial nephitis.
[SPEAKER_05]: Yeah, that's thanks for adding that.
[SPEAKER_06]: And so now that we're going through it, I'm really starting to understand why our patients on long-term antibiotics are in quote unquote safety labs.
[SPEAKER_06]: It's one of the reasons at least is to monitor for this development of dress syndrome from peripheral use in affiliates dress, we should just keep in mind develops around two to six weeks after medication initiation.
[SPEAKER_05]: Okay, so maybe to summarize the takeaways when it comes to medications causing Eosinphilia.
[SPEAKER_05]: I think we know our usual culprits that can do it, you know, antibiotics, interseesure meds, alipurinal NSAIDs.
[SPEAKER_05]: Those are the typical ones, and then it can happen days to weeks from starting.
[SPEAKER_06]: And it's important to remember that mild isolated Eosinphilia doesn't always require stopping the drug, but you really have to be vigilant and monitor for an organ damage or dress.
[SPEAKER_05]: Okay, so now on to my favorite problem, I think the most practice changing one for me, we did a-tipy, we did medications now onto the P of the camp e-numonic, P for pathogens, and here we're really talking about infectious causes.
[SPEAKER_06]: I'll be honest, Raya, before this episode, I thought I was doing such a good job with travel history.
[SPEAKER_06]: I'd ask any recent travel, get a no and move on.
[SPEAKER_05]: Oh, same, but Dr. Weller taught us that that is not enough.
[SPEAKER_01]: It in terms of travel history is we often will ask where they people have been recently.
[SPEAKER_01]: We also have to remember that we should ask about the immigration history.
[SPEAKER_01]: Is there a people that come from areas where some of the G.I.
[SPEAKER_01]: parasites may be endemic who have not gone back to their home?
[SPEAKER_01]: haven't been in Costa Rica for 10 years or Puerto Rico for 10 years.
[SPEAKER_01]: So travel histories negative.
[SPEAKER_01]: No, they have to include immigration history because especially strong employees, which can be a chronic.
[SPEAKER_01]: infection that uniquely auto-infect so it can perpetuate its life cycle at times subclinically or post-eclinically and that is germane and occasionally someone will develop disseminated strungel the diocese when they're immunosuppressed.
[SPEAKER_01]: and that distant immigration history has been overlooked in the nominal travel history last couple of years.
[SPEAKER_01]: No, I haven't gone back to my native country.
[SPEAKER_01]: So history is important.
[SPEAKER_05]: Okay, so a good travel history isn't just about, okay, did you have me travel recently?
[SPEAKER_05]: Especially because of a parasitic worm, strong employees, that can perpetually auto-infect.
[SPEAKER_06]: Yes, strong employees is special and that it can complete its whole life cycle in the human host.
[SPEAKER_06]: That's why the infection can persist for decades after the exposure, and it can cause this low-grade eucinophilia and immunocompetent patients.
[SPEAKER_05]: Yeah, and then if a patient does become immunosuppressed, then the strong authorities can turn into a very life-threatening hybrid infection.
[SPEAKER_06]: So we need to ask about where they were born, where they lived, and every stop along the way.
[SPEAKER_01]: One patient guy got called on in markedies in affiliate is a PhD student had been working in Madagascar, which curious, but markedies in affiliate and trying to think about the parasites that caused markedies in affiliate and Madagascar and nothing jumps right out, but it turned out he has spent time in West Africa.
[SPEAKER_01]: where some of the hilarious parasites are present.
[SPEAKER_01]: And indeed, he had what is low-alowa.
[SPEAKER_06]: And then there's another part of the history we often forget.
[SPEAKER_06]: Diet.
[SPEAKER_01]: A corollary of a travel history is a dietary history.
[SPEAKER_01]: If they've been traveling, or even if they haven't been traveling, anything that they might have consumed.
[SPEAKER_01]: Triconosis would be an example of a parasite that causes
[SPEAKER_01]: And if they had consumed, say, wild bear meat in Canada, in Maine, or in still in central Europe, they can develop tercanosis.
[SPEAKER_05]: Ah, that is a great point.
[SPEAKER_05]: We need to ask our patients, have they eaten any under cooked foods, like seafoods, wild meats, or anything else, right?
[SPEAKER_05]: This is not something our patients are going to volunteer, unless we directly ask them.
[SPEAKER_06]: So parasitic infections, especially helmets or warms, account for most infectious causes of use in affiliate.
[SPEAKER_06]: But it's really important to keep in mind that viruses like HIV and fungi can also cause use in affiliate.
[SPEAKER_01]: patient that I was called about, started on an antibiotic for pneumonia, had an esophelesia.
[SPEAKER_01]: So the question to me is, I have an antibiotic ex-caused esophelesia.
[SPEAKER_01]: So I started reading up, I didn't think so, but it couldn't find case reports, but it turned out what was not given to me was the patient's travel history.
[SPEAKER_01]: He's a middle-aged male, a resident town north of Boston, and lo and behold, he had recently come back from Arizona, where he was helping tidy up around his father's house, and he ended up coming to Broncosca Beach, and his diagnosis was not a parasite, coxidiotomycosis.
[SPEAKER_06]: That last story really highlights how easily it can be for us to anger on medications.
[SPEAKER_06]: Yes, it could be the antibiotics, but my take away is that even if there is a common cause of use in a failure, I should still do my due diligence and get a more complete travel history.
[SPEAKER_05]: Exactly.
[SPEAKER_05]: So,
[SPEAKER_05]: Think about the workup, then, of the infectious causes.
[SPEAKER_05]: It's going to be HIV testing, right for everyone, stool testing for open parasites.
[SPEAKER_05]: And then the rest of the workup is really guided by the history and specific travel destinations.
[SPEAKER_05]: So, for example, if the patient travels to West Africa and has Eocentphilia, then we should be getting specific tests super low, low,
[SPEAKER_06]: Yes, and in about the Oven parasites, the more days we have stool samples from, the better the sensitivity is for picking up helmets, but it's really important to know that Oven parasite is not the test of choice for strong goloidies.
[SPEAKER_06]: That's because strong goloidies has low and a regular larvae output in the stool, so that's why we really want to get the serology.
[SPEAKER_05]: Yes, exactly.
[SPEAKER_05]: Okay, to sum up this pearl, the next time we see Eos and Philia, we want to do a thorough infectious history.
[SPEAKER_05]: It's really about where were you born, where have you lived, where have you traveled, even if it was years ago, and did you have any stopovers?
[SPEAKER_06]: And we want to really think about what kinds of food have patients eaten.
[SPEAKER_06]: But were they exposed to any undercooked or wild meats?
[SPEAKER_06]: The CDC travel website I will link below for you guys is an amazing resource at linking what infectious exposures are related to where in the world and when you need to think about them.
[SPEAKER_05]: Oh, that sounds really helpful.
[SPEAKER_05]: And the last thing to run out, the P in the Camp E pneumonic, stands for pathogens, and, you know, we can say parasites perjade because helmets are worms are the majority of it.
[SPEAKER_05]: But we need to also remember that viruses and fungi, like, for example, coxioidies can also cause use in failure.
[SPEAKER_06]: So we covered the three big causes of eocinophilia, A to P meds and pathogens.
[SPEAKER_06]: Let's round out our discussion with some poporee of high yield points on eocinophilia.
[SPEAKER_01]: ESFL number fluctuates, the subtle fluctuation over the course of the day, which reflects the endogenous circulating rhythms of corticosteroids, and you start pumping out some steroids in the morning, ESFL tends to be lower, also stress can suppress ESFL numbers.
[SPEAKER_01]: There's an old study on medical residents presenting at ground rounds, and the ESFL levels
[SPEAKER_01]: they were at use in a panic.
[SPEAKER_05]: Ah, man, that is wild.
[SPEAKER_05]: So if the use of the levels actually fluctuate throughout the day, what about those six AM labs that were so used to, how do we interpret those?
[SPEAKER_06]: So those AM labs are probably when Eosinophils are at their lowest, because that's when we make most of our cortisol.
[SPEAKER_06]: The rule is more stress, more endogenous cortical steroid production, the lower the Eosinophil counts.
[SPEAKER_04]: all your patients with sepsis in the hospital of NutriVilk, Lukasitosis, they have suppressed eocentethyl counts.
[SPEAKER_04]: I mean, like, go to the ICU census, right?
[SPEAKER_04]: Like, you'll see everyone's got a suppressed eocentethyl count.
[SPEAKER_04]: Anyone who doesn't, there's probably some reason for that.
[SPEAKER_05]: So, here's the pearl.
[SPEAKER_05]: In a patient who's septic, a normal eocentethyl count, or a mildly elevated one, is actually abnormal, right?
[SPEAKER_05]: Even though our EMR is not flagging that for us.
[SPEAKER_05]: A normal or elevated eocount in a sick patient is a clue that there might be some other
[SPEAKER_01]: I remember doing an ID consult and a complicated guy who had motor vehicle accident in the capture was transferred down hair was in the make you pre-op and sick, February, and he had normally used in his stiff, as it is curious.
[SPEAKER_01]: You always teach that steps of stress, we suppress his yes and a felt.
[SPEAKER_01]: Yeah, until his CT scan showed that he'd blood into his dreamles.
[SPEAKER_06]: I love me good, Peter Waller, Eustinophilia story.
[SPEAKER_06]: So that patient in the ICU had a adrenal insufficiency.
[SPEAKER_06]: That brings us back to our camp Eustinophilia pneumonic, that A is stands for both ATP and adrenal insufficiency.
[SPEAKER_05]: Yeah, and so in this case, with adrenal insufficiency, there was a loss of cortisol, right?
[SPEAKER_05]: That room was that normal, suppressive effect that steroids have on the Eosinophil.
[SPEAKER_05]: So hence, his Eustinophil count was normal on the CDC.
[SPEAKER_06]: I'm so glad we talked about stress, steroids, and how those impact that use NFL levels.
[SPEAKER_06]: We spent a lot of time on causes, and so the next natural question for me is how do we actually manage use in a failure?
[SPEAKER_04]: One of the really weird things about use in a failure is that it's often easier to treat than it is to figure out what people actually have.
[SPEAKER_04]: Because honestly, steroids work for basically everything on that giant list of causes of use in a failure.
[SPEAKER_05]: Okay, so if steroids works so well on all your eosinophilia woes, then he'll know why do we spend this whole episode going over e-dialogy.
[SPEAKER_05]: I mean, I know we're good internal medicine doctors, but did that really bad?
[SPEAKER_06]: It does matter Shreya, we have two big reasons.
[SPEAKER_06]: First is infection, giving steroids to someone who has an undagnosed, strong gloidy's infection can trigger a hyper-infection syndrome and make our patients very, very sick.
[SPEAKER_06]: The second is diagnostics.
[SPEAKER_06]: Giving steroids can really muddy the data and interfere with our diagnosis of cancers like lymphoma.
[SPEAKER_06]: They can also lead to temporary improvement in eocinophils, which can masks and underlying malignancy that's going on.
[SPEAKER_05]: Ah, right.
[SPEAKER_05]: Yeah, cancer was that sea in the camp, e-new money.
[SPEAKER_05]: That's something I'm always worried about missing.
[SPEAKER_06]: I'm also worried about it, but the good news is that it's a really rare cause of eucinophilia.
[SPEAKER_06]: There's a subset of my Lord new plasms that we really don't want to miss, and it's one of the causes that does not respond to steroids.
[SPEAKER_04]: steroids will make the eSynophils go down for basically every single cause, except for this one thing, chronic eSynophilic leukemia, aka MHES.
[SPEAKER_04]: And that's because, in this case, these are actual, clonal eSynophils.
[SPEAKER_04]: The eSynophils are part of the malignant clone.
[SPEAKER_04]: They're no longer responding to growth signals or things that try and suppress their growth, meaning they will continue to grow and replicate independent of you trying to suppress them with their rights.
[SPEAKER_04]: And they will continue to grow and replicate independent of you cutting off their
[SPEAKER_05]: that is good to know.
[SPEAKER_05]: Stan, how do we think about the neotlassic workup?
[SPEAKER_05]: I mean, we're not going to be sending it off on everybody, of course.
[SPEAKER_06]: And you definitely shouldn't.
[SPEAKER_06]: You should really think about sending it, though, when the Eucinophilia is severe, like above 5,000 Eucinophiles per microliter or five in the EMR, and persistent.
[SPEAKER_06]: Eucinophilia, that does not respond to steroids, or Eucinophilia that initially improves with steroids, but then comes back with vengeance is also concerning from a ligmency.
[SPEAKER_06]: Ah, and this is where we're like, yes, hematology or allergy immunology colleagues, please help us.
[SPEAKER_06]: Yes, and just to give you a heads up of what their work up might include, they will probably send things like flow cytometry, fish testing for this mutation called PDGFRA.
[SPEAKER_06]: Next generation sequencing, B12 and triptace to look for systemic mastocytosis and full body imaging.
[SPEAKER_05]: And then I know sometimes bone marrow biopsies
[SPEAKER_04]: A bone marrow biopsy is not an essential part of the initial work up for isn't affiliate and you can proceed with just sending off all these tests off the blood.
[SPEAKER_05]: Okay.
[SPEAKER_05]: Nice.
[SPEAKER_05]: One less procedure in that initial work up for our patient.
[SPEAKER_05]: Wonderful.
[SPEAKER_05]: So I know we said hold off on steroids, right, especially if we're ruling out stronger loidies or cancer, but what are our patients really sick and, you know, maybe there's a concern of even endoring and damage like my patient who had that use in the field like myocarditis and stroke.
[SPEAKER_04]: But for like a sick patient in the hospital who's got like an elevated tropone in an abnormal EKG and you're like, this person could die of their e-cinephilia.
[SPEAKER_04]: I do not have a week to wait for all these tests to come back.
[SPEAKER_04]: So before I'm empirically giving steroids to someone who's really sick with peripheral bloodious in a philia, I want to make sure I have it CT torso that has identified any lymphatic nopathy or other possibilities of some other cancer that I want to go after biopsy before I give any steroids.
[SPEAKER_04]: I'm checking a trip tastes, but I'm not waiting for the results because the reality is that's unlikely to be helpful.
[SPEAKER_04]: I am sending off flow cytometry of the blood to look for LHES.
[SPEAKER_04]: And I often will also send off the testing for myeloperliferative hyperecinophilics and drum aka chronities in a vocalemia.
[SPEAKER_04]: And so that's going to be the translocations, the fish testing for the PDGFR translocation,
[SPEAKER_04]: as well as doing next generation sequencing for myloid type mutations to identify things like jack two mutations that may drive another subset of cases.
[SPEAKER_06]: That was some good space repetition for the hem workup of malignant neoplasms.
[SPEAKER_06]: So for clinically sick patients, we send off testing and start impaired steroids while we're still waiting for the results.
[SPEAKER_05]: Yeah, and then earlier we also discussed that giving steroids could precipitate like a disseminated hyper infection of
[SPEAKER_04]: My general approach is, I ask the question, are there any parasites or other pathogens that it makes any sense for this patient to have?
[SPEAKER_04]: And I just think about that epidemiologically in terms of their travel and exposure history.
[SPEAKER_04]: And if there are essentially none, then I treat them for strungaloidies because everyone in the US is at risk for strungaloidies with I've remacked in, and then I give them steroids.
[SPEAKER_04]: And I don't even wait, because that person has this life-wreatening situation.
[SPEAKER_04]: I just give them steroids, it's sort of like shoot first ask questions later.
[SPEAKER_05]: So, I guess with somebody is sick, you know, particularly with things about the patients that I see you, I think the order of management definitely changes.
[SPEAKER_05]: And so our main takeaway is when you come to steroids in malignancy, we know steroids isn't effective treatment for lowering the osinophils, but there's a worry of the hyper infection of strong employees and also reducing our diagnostic yields in real-class and like lymphoma.
[SPEAKER_06]: And one of my absolute favorite pearls is that in critically ill or septic patient, a normal use in a full count is actually really abnormal and should make you concerned about causes of hyper-eucinophilia.
[SPEAKER_06]: That could be anything that we just talked about, like drug exposures, adrenalin deficiency, et cetera, et cetera.
[SPEAKER_05]: coming back full circle, everything we just talked about.
[SPEAKER_05]: So that is a wrap for our episode.
[SPEAKER_05]: I hope you guys had fun taking a trip on Camp Eos de Filly with us.
[SPEAKER_05]: He let thank you so much for putting this together in the leadership.
[SPEAKER_06]: I learned a ton.
[SPEAKER_06]: Thank you so much, Shreya.
[SPEAKER_06]: And if you want to add any of your own tips, listeners, please leave a comment on a website page on Instagram or Facebook.
[SPEAKER_06]: Thank you so much to our peer reviewers, Dr. Pini's Corey, and Dr. Jonathan Barry.
[SPEAKER_05]: And always we love hearing feedback to these email us at hello at koreanpodcast.com.
[SPEAKER_05]: Our opinions expressed our own and do not represent the opinions of any affiliate institutions.
[SPEAKER_05]: Thank you and take care.
[SPEAKER_05]: I just kiss them.
[SPEAKER_05]: the deeper you're learning games.
[SPEAKER_05]: People meet me at conferences and then they'd like quote that to me the more you have yourself the deeper you're learning games.
[SPEAKER_05]: So it's embarrassing but then I'm like okay now if that's not a bad tag line if that I mean I'm such a nerd like that make your worst is oh well heal if you have other ideas I welcome and you're branding.
[SPEAKER_05]: No I love this.
[SPEAKER_05]: Okay.