Tuberculosis | Podcast

Welcome back to the Ninja Nerd podcast. Today we're talking all about tuberculosis. We're continuing on through our infectious disease playlist and tuberculosis. A scary one, huh? — Yeah. It's pretty [ __ ] scary. I'd be terrified to ever see this one. I actually, you know, I we didn't know, but they thought that we had a patient when I was on rotations, like a surgical rotation. They thought he might have had like a TV paritonitis — and so I wasn't like in the room and stuff but you heard about it and you wanted to go and see it but so that was the only time as I had heard about TV parathonitis once. I don't know I never got on it. Yeah, but like yeah it's a scary one. It's very scary. — For this episode it's going to be a new format. I love it. — I'm going to play the attending — and Zach's going to be my little resident. — He's going to be the guy under me. Go get some coffee. Yeah, — I take two cream in my coffee. He'll come back with a weird taste to it. That coffee if that's the case. — But anyway, — he's my res. — Dunkin Donuts. It's Dunkin' Nuts. — Oh boy. — There it was. If you couldn't catch on to what he was alluding to, you got it. — You got it. Now, — well, let's get into it here. We're talking all about tuberculosis. We've got some cases to go over and then Zach's going to basically be playing the resident, figuring out what's going on. What's my diagnosis and how do I treat? — Okay, cool. — All right, so we have case one, patient one, I should say. A 45-year-old male, immigrant from Southeast Asia, arrived six months ago. He comes to the ER complaining of a three-month history of cough, drenching night sweats, and he's lost 15 pounds. This morning, he coughed up a teaspoon of blood. — That's never a good sign. — Yeah. And just did he have the teaspoon ready? — Well, yeah. Yeah. It's already dished out for you. — I don't know. It's a little bit of blood. — Yeah. The quarter tablespoon of blood. — All right. Sorry. — We got immediate red flags. What's going on here? — Well, obviously we're talking about TB, so concern for TB. But when you talk about TB, the biggest things I think about is, as you discussed it, risk factors for exposure. Who would be expo who would be a person I'd be worried about being exposed to TB? Probably someone who was born into or traveled to an area of a high prevalence like region. So like you said, Southeast Asia, Africa, anything in that kind of like realm, I would probably be pretty concerned especially if they presented with symptoms like that. But another kind of concern that pushes you like so when a person is exposed, you can have a person exposed to the bacteria if they're immuno competent. They can kind of like they can put that pathogen into a dormant state where essentially it's still there. So you still have it. You're just not contagious and you're not symptomatic. the people who are like a little bit more like immuno compromised in a way or imunosuppressed or they just don't have that like super strong immune system that's capable of putting that pathogen into dormcy can progress to an active disease. So people who have things like HIV, AIDS, people who are on steroids, TNF inhibi, any kind of immunosuppressants, same thing, people who are solid organ transplants, usually when you get a transplant, you're on some type of imunosuppressive agent. So that's again a high risk, you know, category. And then probably even like people with like chronic illnesses, diabetes, chronic kidney disease. So those are like the two risk factors I look like is exposure and then what pushes them more into developing an active disease. So they had the immigration. Yep. — Did they have any I didn't hear like risk factors for like an immunosuppressed kind of event here. — It doesn't seem that way. Three-month history of cough, drenching night sweats, 15 pounds. There's no other thing in this history that would say there's some sort of immunompromised state. — Yeah. And sometimes that can be the case and you don't have you can have people who this can happen to. And that's why there's two different types. There's reactivation TB, which is a person who went into they had a latent TB infection and then maybe it was just like a malnourishment of some sort. Maybe they just got ill at one point and reactivated it. They have a little bit more of a slightly robust immune system if you want to think about it, but it's still not strong enough to maintain that pathogen into a dormant state. Usually the ones who are like super like imunosuppressed, they kind of they progress right away. They don't even get a chance to put it to dormcy. Either way, that's what I'm thinking is that they have some risk factors. The next thing is that when a person with those risk factors comes in with progressive symptoms that sound like pneumonia, like that just it's like a non-resolving pneumonia is the way I think about it. It's automatically on my differential. So, a productive cough, fever, you know, the night sweats and unintentional weight loss that starts to scare you a little bit and pushes you like, oh, could it be like malignancy

— right? Yeah. — But that's a part of your differential. But usually a productive cough, a like a fever, some like constitutional symptoms like night sweats and weight loss. You start to think about TB for sure. Those are like your your big four kind of the way I like to think about them. — Well, right now you your TB is coming across your mind. So, right, like you can't exclude that. He's sitting in the waiting room right now. He's with a whole bunch of other people. So, what's your very first move? Well, I mean, in this kind of case, if I have any concerns, you know, usually what you'll do is you you'll get them tested and even if you don't like no matter what you isolate them because it is very like if they're symptomatic, they're contagious and then if they cough, those respiratory droplets fly around, they get into another person's like uh respiratory tract, it can cause infection. So, for shores, skis is going to be like isolating them right away. That's — isolation, airborne precautions immediately. — Yeah. Even if you didn't have the prove it, if you have a high degree of suspicion for it, you definitely want to take precautions just because then that close contact exposure, that's a very high risk category. Usually the highest risk of getting exposed is you have someone who's right next to you or close to you who has active TB. — Yeah. And then also you can add on that you might have them isolated with negative pressure room N95 for the staff — and then you're not really waiting for labs. In this situation, it sort of is telling you right away, — yeah, — that there's a serious concern here. — Yeah. You act to isolate and then after you've done that and you all the proper precautions, then you can go through the steps of what we'll talk about chest X-ray and sputum samples and things of that nature. — So, let's say we do that now. He's isolated. Staff are all wearing N95s. You're good to go. — We then go and get a chest X-ray. That's your next move you just said. Yeah. — So you get a chest X-ray and it shows a cavitary lesion in the right upper lobe. — Okay. — So why the upper lobe? If we are talking about tuberculosis, why would it be upper lobe? — So this is a this looks like a classic reactivation TB. And that's why I think like they probably didn't put in there that the person was immuno compromised off the get-go now because reactivation theoretically you could have this happen in like children. You could have it happen in like someone who just hasn't been eating. You can have it if they just have a critical illness of some sort. They don't have to be imuno compromised. Their immune system is a little bit on the weakerish side, but they have something that triggers them to go from a dormant state to a reactivation of some sort. Whenever you reactivate the mcoacterium tuberculosis, it prefer it's an obligate a-obbe is what they call it. So it means it loves oxygen. The upper lobes are the highest oxygen tension. That's where the highest VQ, you know, perfusion ratio would be. So what they'll do is let's say that they started off, let's say that this person got exposed to TB. They created like a little area of a granuloma that they maintained it to become dormant in the upper lobe and then something happened. Whatever this person did, something happened to them where that basilli decided to come out of dormcancy and it decided to actually start breaking down a lot of that case material the granuloma and it starts liquefying that actual case necrosis and it forms like a cavity. Well, kind of a cavity. It's a cavity that's usually filled with that like necrotic material and then guess what happens? it starts to move and spread into the bronchi. And so all it takes is for them to cough a little bit and then that cavity becomes just filled with air rather than filled with the fibroacius liquefied material. So that's essentially what I would say is it's a loves the upper lobes because that's where the highest oxygen like tension is. — Well, you see this cavity but you need to prove it. So what diagnostic test do you have to order? So you get sputum samples at least you know like three of them ideally and you want to do them like 8 to 24 hours apart and you want to get at least like one or more of those in the early morning ideally. So I get three sputum samples follow those guidelines and then once you do that the sputum that you get you want it to kind of be a cough like an like you want them to induce like a cough and then collect a good sample. You'll send that to the lab and then usually when you do sputum cultures you do them for typical bacteria. For mcoacterium tuberculosis it's not a typical bacteria. So you do the first one oftent times is like the most rapid test to make you like be suspicious of mcoacterium species is an acidfasillus test and it looks at a smear. I'm not going to get into the micro but essentially you kind of you do all of these testing where you're trying to put acid alcohol and it's normally if it's not a mcoacterium species you'll put the acid alcohol and it'll remove any of the red stain that you put on these bacteria. But if you do that and it's mcoacterium, they resist that decolorization and they remain red or like pinkish red. So they would come up as a pinkish red basilli or rodshaped bacteria and that would be an acidfast bac bacillus smear, but it doesn't tell you it's TB. It just tells you it's a mcoacterium, which could be any of them. And the next test is since that one's super quick, you can get an answerish at that time frame, but it's

not definitive. The nucleic acid amplification test is another one. So it basically takes the sample it kind of basically you take the let's assume that the microbacterium tuberculosis is there it breaks it down it extracts the DNA from it makes a bunch of copies with it with the PCR and then essentially you kind of probe for specific genes that are in that DNA and if it comes up positive we know which genes are specifically present to make us suspicious for microacterium tuberculosis. So that's a pretty good like relatively definitive diagnosis from a rapid test which is pretty helpful because then you can kind of theoretically start treatment right then and there. So if I have a positive as acif basicus and a positive nucleic acid amplification test I can treat them. The reason why is a culture a microacterial culture takes like sometimes two to anywhere to eight weeks but we're still going to send it off for a culture. But if I got to wait two to eight weeks to treat this patient that's problematic. So, I go off of the smear and the nucleic acid amplification test and I wait for that smear to come back because the the I'm sorry, the culture to come back. The reason why is the culture is the gold standard conf like definitive diagnosis and it's the best when it comes to drug sensitivity. So, in other words, we'll talk about it, but there's a specific regimen you give for TB that culture will tell me if a patient doesn't have like the sensitivity to some of the drugs and we need to switch to other ones. So, that's the benefit. So, that's what I do. get the speedum sample, run those, and see if I get a hit on that. — All right. Well, let's just say the Sputum culture came back. You waited eight weeks, which is just mind-blowing to me. — Yeah, it's a slow grower. — Yeah. I don't know. Can we like expedite things here? Can we throw — It's a grower, not a shower. — Oh, okay. So, it's a growing pro. I'm thinking like you need like FedEx like an overnight shipping. — No, it's a it's a slow like replicating bacteria and it just takes so long and that's the downside. And that's why also the regimen for treating this thing is like you don't treat pneumonia for 6 to nine months. You know, this one's the same thing. It's like a super slowly growing bacteria. — Well, let's just say we do get this the sputum culture back. It's a gold standard and it does come back positive for miccoacterium tuberculosis. So, that's definitive. We have the gold standard. — Yeah. — Before we treat and before we get into all of that, I want you to first explain the pathology a little bit more. I guess I under I'm trying to understand when it reactivates — why was his immune system unable to kill this bacteria when he was first exposed now just saying he's healthy and I've heard a little bit about like sulfatides and things like that could cause that — so talk a little bit about that. — Yeah I mean generally these bacteria are pretty hardy so inherently with their nature they're pretty nasty stuff. You kind of brought it up they have things like sulfatides which is pretty cool. I mean it's basically like an enzyme that helps to inhibit the you have a fagosome and a loome in the macrofase when it engulfs the microbacterium and usually they fuse and it kind of the lysosal enzymes help to kind of chop up bacteria. These are like wizards or I don't know ninjas somehow and they release a sulfatide and it basically inhibits that fusion so they don't even get in contact with lysosomes. So it makes them pretty like resistant off the get-go. And then they have other things like they release something called chord factor which basically it just it pushes your immune system into a lymphocy macrofase like predominant reaction and it kind of pushes granuloma formation essentially. But yeah they're pretty nasty but like whenever a person gets put into a like a they try to put them into a dormant state it's primarily driven by your te- cell activity your TH1 cells they release something called interferon gamma. In a patient who has HIV AIDS which cell is most likely affected — T- cells. T cells and so the CD4 counts start dropping. Those TH1 cells drop, you lose the interferon gamma and that's like a 50 to 100fold risk. — Wow. — Yeah. So there's a pretty high risk of you know progressing or becoming reactivation TB. But usually for the most part uh other things that you would consider is like TNF inhibitors because another thing that happens is whenever the TE-C cells release interferon gamma they activate the macrofasages to make them better at trying to kill the miccoacterium and then those macrofasages say I ain't enough for the job I got to get more macrofasages and more lymphosytes. So they release something called TNF alpha and TNF alpha brings in more macrofasages and more lymphosytes. So if you have TNF inhibitors you're shutting down that pathway. If you're using amunosuppressants, ability of the immune system to tell you, hey, bring more cells in. So, you lose maintaining that granuloma. Basically, the prison for the microbacterium and it says, "All right, dudes, I'm out. " And then it's going to start doing some stuff. So, that's the concept, but this is there's a lot of things. It doesn't just have to be an immunosuppressive event. Like I said, you could have a person who's just like critically ill. They're malnourished. Sometimes we don't even know why. is we know that anything that really alters your immune system pushes you more towards not being able to maintain a dormant basilli and pushes it more into an active state but you can usually with these patients their immune

system is somewhat competent enough that it can actually cause liquefactive necrosis of all that case material so it's strong enough so that's why you see primary progressive TB is more likely to be in those severely immunosuppressed right off the get-go reactivation can occur for a lot of different things but their immune system is just a maybe a little bit more robust. But either way, tons of things that can cause that, but that's the justification behind it. — Well, we have active TB, right? What's your treatment regimen for this patient? — So, active TV is always the ripe regimen, which is rafampen, isid, pyroenomide, and ethanol. And I should be careful, it's not always. It just depends upon if that culture came back or the nucleic acid amplification said that their drug sensitive to that. So we get the results from that culture and it says oh they're resistant to rafampen they're resistant to isonia they're resistant to both I then have to change up the regimen but if it's like they're sensitive to it then I can be I'm okay I can just give them that regimen. So it's rafampen isid pisenomide and ethnbutl and we do that in two like phases. One is the intensive phase which you give them all of those drugs for two months and then usually during that process you're checking you know the sputum cultures and listening to them and see if they're you know they're improving and seeing if there's any signs of clinical failure or worsening. And so you check the sputum cultures at least, you know, one at month one and then another one around the as you're getting closer to month two and you're looking to see what those sputum cultures tell you. If it's persistently positive, if it's negative, if you develop some drug resistance along the way and if the person had some persistently positive cultures, I'd be concerned. And I probably would as long as it's still sensitive to that all the rafampen and isidin, it's we're good. Usually in that patient who's consecutive positive cultures, I would go for instead of doing rafampen and isized for four additional months, we push it to seven months. And so they'd be on that rafampen, is parisenomide, ethbutol for two months and then rafampen and isonia for seven months for a total of nine months. — And if they didn't have that persistently positive, it would be just four months, right? — Yeah. Then you would do rafampenized pisenomite and then for two months and then you would do the continuation phase of rafampeniz it for four months total of six months. — So we're talking either you're you could be looking at six months but in that case you could be looking at nine months. — Yeah. And that's just if it's like your for most TBs regardless if it's pulmonary or extra pulmonary because you can have TB in other sites of the body. It's pretty much that kind of range. There's only I think like a couple exception and that's if like it got into the bones or if brain. We are a little bit more cautious and we may go up to nine to 12 months. So that's the only times where it's a little precaution that they may be extended. — All right. Well, let's go to case two. However, it's the same patient. It's just kind of a continuation. — Okay. — So, you treat this patient. You started the ripe therapy. Let's just say he was sensitive to the ripe therapy. And you begin that. He comes back for his two-month follow-up. He feels okay, but he's still coughing a good amount. You check his repeat sputum culture, it's still positive. So, just like we just talked about this in this situation, he would qualify for an extension of therapy. Correct. — Yeah. If it's if at least if it's if they have So, the criteria says if there's apical cavitation on the chest X-ray and consecutively positive sputum cultures, at least two of them, yeah, you should definitely do that regimen. — And that was one thing I didn't mention. He had a cavity on his initial X-ray and his two-month culture is still positive. — Yeah. Then you do that whole seven month continuation. — So it's not four months. The continuation is now seven months. So our patient here is getting nine total. — Yeah. Which is insane. — That is that's — Yeah. It's a long time to be on antibiotics. — That's pregnancy. That's a full term. — Yeah, man. It's crazy. — Wow. All right. Well, that was that patient and unfortunately the treatment failure. He needed an extension of his therapy. — Yep. — All right, let's move on to case three. We have a 28-year-old female. You started on ripe therapy four weeks ago. She comes to the clinic complaining of nausea, vomiting, and right upper quadrant abdominal pain. Her eyes look a little bit yellow. — Okay. — What's going on? — Yeah. So, this is the common theme, right? So, whenever you give So, you can remember I like to remember rest in peace liver. So out of the ripe regimen, rafampen, isonized and purizenomide are kind of hpattoxic. Pyroisenomide being the most hpattoxic. And so when you're on these, you have to be careful especially you do tell them avoid alcohol because these can cause like a liver injury. So if you have that super, you know, imposed on top of alcohol consumption, that's going to raise it up as well. And this is also consider this in patients who have underlying diseases like cerosis or some types of like hpatic injuries of sorts. I'm thinking that they probably got an LFT bump which is extremely common with

this and but if it's enough that it's causing hepatitis or hepatomegaly that's causing pain it's causing associated nausea and vomiting and jaundice — then this is a pretty concerning feature and so symptoms are pushing me and then all I need to know is what does the kind of LFTs show me — and that's what we get next. So RIP to that liver I like that that's pretty clever. It's helpful to remember that. — Yeah. But her ALT and A are five times the upper limit of normal. — Yeah. — What do you do? — You just power through it. — Yeah. You say, "Ah, you're good, man. Just keep going. " — You should just those drugs will help you. — Oh my gosh. — Keep pushing through. — It's scary. But yeah, you got to hold them. — So you have to stop them. So at least the rip. Do you continue the E? — So what I would do is I would hold all of them first off. I would dis I would just stop them for now. And usually like a alt if you have symptoms, you only need it to be three times the upper limit of normal. If it's five times the upper limit of normal, you don't even have to have them have symptoms. You can just stop it. — Okay? — And that's why we check them. We prefer to check them and just keep an eye on it. But symptoms might push you to do it a little bit earlier. — But with this patient, yeah, I would stop them and then I would let the LFTs kind of like start to come down. I'd let the symptoms hopefully resolve. And then what I would do is probably as they're getting closer to like maybe two times the upper limit of normal. I would introduce like one at a time and then I would keep checking the LFTs and seeing which one was the primary offender because that's the one you may have to adjust. — Yeah, that's the you don't want to stop all of them. It's just kind of which one am I finding out as I introduce one time at a time back in is really triggering this. And then now when I find that one, I say, "Oh, that's the sucker. Let me find an alternative. " Gotcha. — So that that's the way I would kind of go about that. But it's not, you know, stop and never start them again. You know, in this case, we definitely need to, but we don't want to power them through it and put them into acute liver failure. — Well, we talked about the RIP. I'm I have a feeling the E isn't just going to be a, you know, no big deal. — No, — because she comes in and she says, "Hey, doc. I weird thing happened the other day. I was driving and all of a sudden I couldn't tell the difference between a red and green light. " — I don't mean to laugh. That's terrible. — Isn't that scary? — Yeah. So that at that point, — yeah, you're just running red lights. You're like, it was green. — I swear I thought So what do you think is happening when she says something like that to you? — Yeah. The E is the ethnut. So I have EI. — So I remember EI. Oh wow. — Yeah. You know, Ethanol affects the eye. And so it can cause some ocular like toxic particularly optic nuritis. And so they can get that red green kind of I forget the there's a specific very specific word for it. I can't remember. But yeah, they get optic nitis and they start to have some color changes and maybe some difficulty with the acuity of their vision and the clarity of it. So yeah, that's pretty common. — So similar to the other RIP drugs, would you do the same thing with ethbutol? Stop it immediately and then try and let that resolve. — Yeah, with this one, yeah, ethbutrol, it causes optic nitis and over time there is a concern that can lead to vision loss. So yeah. — So don't power through this one either. — No, no. You don't want them causing like an 18 car pile up. — No, we don't want that. We don't. — No, it's pretty serious. I I' I'd hold that one. — All right. Completely different scenario now. Wipe those clean. She comes in now saying, "Hey doc, I now have weird burning and tingling numbness in my fingers and toes. " — Oh yeah. — What's going on there? — So that's you remember isolated nerve. So they can get peripheral neuropathies and so you can prevent this. So this could have been prevented. — I was going to say could you have prevented? Yeah, ethnbutl is not you can kind of prevent it but you're more monitoring it with visual exams and that's why sometimes we monitor for abattoxicity with serial LFTs. — Yep. — With this you can prevent this with vitamin B6 or podoxine. — Okay. So within you should always give vitamin B6. — Yeah. I mean I think it's not it's pretty much a vitamin. It's a B vitamin essentially and so it's not going to cause any harm. There is times where they'll be like, "Oh, we should only do this in select risk, high-risisk people. " But it's a it's a B vitamin. — Yeah. It's not going to cause any like harm. — No. So, I would start puroxine with that empirically with the ripe regimen. — Okay. Periodoxy. Cool. All right. One last complaint. Completely different. Now, she says, "Hey, my big toe is swollen and red. — My big toe. " — Yeah. All right. So, that's You remember pureamide pyramid of urine. I mean, pir pyramid of uric acid. Pyinomide. — Yeah. Pyramid of purines. That's it. Pyramid of purines is the little easy way of doing. Okay. The uric acid extruction. — Uric acid is like it's generated from you know purines which is a nucleotide but anyway yeah it's — so gout uric acid's through the roof. — Yeah. So uric acid it causes hyperasemia and that hyper urmia increases the risk for things like gout but also increase the risk for uric acid crystals that can cause you know nefropathies and that can

lead to things particularly it could lead to maybe acute kidney injuries and it can even lead to nephrolithasis. So yeah that's another potential problem with that one. — All right case four. We have a 30-year-old nurse starting a new job at a hospital. She has no cough, no fevers, feels perfectly fine. She's good to go. Obviously, there's a loophole here. — Yeah, there's something coming. — Yeah. — Her like all of us going into a healthcare setting, you have to get a pre-employment PPD skin test for TB. She gets it done and she her skin test shows 11 millimeters of induration. — Now, there's different thresholds and cuto offs for your PPD and I would love to learn a little bit more about them and what they mean. — Okay. Yeah. So, I think whenever you look at these, it goes anybody greater than equal to 15 You got the TB. — It's concerning. Yeah. Okay. — Yeah. That's positive. It doesn't matter like — what kind of risk factors you got or not. Anything greater than equal to 15. Yeah. You got you probably have a high degree of suspicion that they have TB whether it's latent or active. Obviously, this person might be latent. — You got a bowling ball in your arm. — Yeah. — It's not good. — I probably like you. I've had mine done before and I it's gotten big. — Yeah. I'm like, "Oh, that doesn't look too great. " — Yeah. and you're like, "Oh crap. " You start getting scared. Do I got the TB? — Yeah. You read into it. — Yeah. It's got usually anything greater equal to 15, it doesn't matter your risk. It's positive. So, they're not she's not there, right? — But she has theoretically a higher risk like kind of exposure. So, hospitals, they keep a pretty like tight threshold. And so, anything in the health care workers, like prisoners, — immigrants, — well, yeah, immigrants too. And then I would even go as far as to say, you know, homeless. And those are also people that I would probably say we'll go with a we'll drop that threshold to be a little bit more careful. — Okay. — So, we'll go to anything that's greater than equal to 10 millimeters. And you have those high risk components. We don't want to let it we won't be like, oh, 15 is good enough. No, no. We want to catch make sure that this isn't something that's actually could be concerning. So, anything greater than equal to 10, which this one she had. — Exactly. She had 11. — 11. So it's just bigger than that. So that is concerning. And then anything where it's like greater than equal to five, we have to have a really good reason we would consider that to be positive. And that's a person who's like HIV. They are on significant amunosuppressants. They have some kind of immunosuppression or they tell you and they verbally say I had close I was sitting next to you know brother Derek next to me and he had active TB. — Brother Derek. Yeah. So like a very close contact exposure with an active TB patient or you have an immuno suppression, — you accept that smaller bump. — Yeah. — Anything greater than equal to five, it's considered positive. For hers, hers is positive. And that would push me to kind of consider what do I want to do with that next? — What do you So then the next thing is just to make sure like there's nothing kind of like causing like false reactions. And I don't think that there's anything in her history that concerns me. oftent times you get false negatives more often especially you can get what's called like energy which is seen in imunosuppressed individuals and things like that but she doesn't have that so I think this is probably an exposure at some point in time so the next goal is it latent or is it active and a chest X-ray is really the best way to go about that decision chest X-ray is crystal clear no symptoms you notice nothing — yeah so it's probably latent TV and that's what I would go with in this scenario is she has the concern of some type of the concept behind a PPD is actually kind of interesting when you think about this. You're taking 200 antigens of mcoacterium tuberculosis and introducing it into the dermis and you're counting on that person having tea cells, not naive like actually memory TH1 cells that actually remember this antigen. And if they remember it, they should mount the exact same immune response that they did in the lung, which is they release things like interferon gamma that pulls in macrofasages that amplifies the TNF alpha. And what does that lead to? It leads to kind of some swelling and a granuloma. And guess what happens to these people's arm? It gets swollen and it gets indrated. And if that happens and it's big enough with those particular exceptions of the rules, obviously that's when you're getting concerned. They have a memory of that TB exposure. That just doesn't mean that they're actively exhibiting the symptoms of it and contagious. The only way to determine that is symptoms, but also the chest X-ray. And so that's Yeah. — Yeah. Latent TB infection and we have to treat her, but she's not sick. So, do we use the ripe regimen here? — No. So, you So, now you don't got to be as aggressive, right? So, you can go with it depends upon the options. — It's just weird because like she's not sick. — Yeah. she's got nothing going on — and so all it takes is for her to get sick or have a something that kind of react. Yeah. — Yeah. So we just have to make sure that we take care of that. So we can kind of target these dormant

bacteria and so you have options you know rifomy like rafampen and rifentine are pretty good is also pretty good and so these are going to be better for your dormant ones. And so there's options. — Okay. The way I like to think about these is it only really comes down to two. This the simplest way, but we can talk about if we want to get a teensy bit more complicated. The two options is isid for six to nine months, which you'll give with B6 paradoxine. The other option is rafampen by itself and you'll do that for about four months. — Choose a shorter one. — Yeah. So that's what most people would do, right? — Yeah. And so that's oftentimes what we would go to, but it just depends as long as the person doesn't have any like contraindications or something concerning about being on rafampen or rifipentine, we're cool with that. Rafampen, rifin, any kind of rifomy, especially rafampen, they're cyp450 inducers. And so it's this fancy thing for saying they metabolize drugs quicker so they lower the actual efficacy of that drug. If a patient's taking warin and you lower the efficacy of it, what could you do? You can make them clot. — Okay? If you they're taking a lot of these patients who are on these probably have some degree of immune suppression like HIV and they're taking anti-retrovirals. If you give that drug with it you reduce the efficacy of those retro anti-retroviral drugs and again patients who oral contraceptives you're like I don't want to get prego you take that decrease the efficacy you know and you got that you know that bump there and so that's the kind of thing is you just consider that in the whole grand scheme of things. So people who have like those significant contraindications go to the isoniaid. The ones who don't you can go to the rafampant. A lot of the times people don't even like the four months and they offer other alternatives out there. And that's why I'm saying like it's not just those if you want to be picky. You could even do isid and rafampenant and you can drop it down to three months or you can do isid and another alternative called rifopentine and you could do that one weekly like a weekly and you can do that one for three months and so there is options it just depends upon adherence. — Sure. — And overall like risk factors but yeah in the simplicity of it it's those two. — All right well we got our nurse patient done and good to go. — Yep. — All right. Final case we have patient five. A patient with known pulmonary TB presents with a headache, stiff neck, confusion. Lumbar puncture confirms TB menitis or let's say they present with chest pain and signs of constrictive pericarditis. — Oh okay. — Well, what is that? This is this h how does this happen? So TV is pretty it's a nasty bacteria and so it can when it destroys tissue it accesses the bloodstream and it can get into spread all over. It can spread to the brain. bones. It could spread to the kidneys. adrenal glands. It could spread to did I say bones? I said bones already. It could spread to the plura, the paritinium, the liver, the spleen. You name it, it can potentially go there. And so because of that, it can manifest extra pulmonary tuberculosis manifestations as well. Anytime you see a person with a chest X-ray that shows like a milliary pattern, which means that they got a bunch of these like small lesions all over their chest X-ray, it's almost always disseminated for the most part. So they may have that milliary sign on their chest X-ray. You can probably be relatively confident that it's somewhere else in their body too because it's the way that they do that is hematogenous spread. So this person has TB menitis and potentially TB per paricarditis. TB menitis is a rough one. And this one again we already talked about it. You're going to treat them with the right regimen. You're just going to do it longer. TB paricarditis is actually pretty concerning as well. The reason why is with TB paricarditis you can get an acute paricarditis but TB stays around for a long time. So it'll keep causing inflammation, inflammation that eventually represents in fibrosis and constrictive paricarditis is pretty nasty because it can cause right heart failure symptoms. So they can have peripheral edema, a sites, hpatomegaly and on top of that they can even get jugular venus distension and it's a problematic disease. So the the whole point of this is that I think what we're getting to is what do we do differently about this? You treat them the same as you would for the active TB, the ripe regimen. You just may extend the total duration. Instead of six months, you may go to 9 to 12 months. And then you oftent times for those two, you add on a steroid like dexamethasone because it's been shown to reduce mortality, neurodeis, and tbmenitis and reduce the risk of developing constrictive paricarditis. But if this person's already getting to the constricted paricarditis, we might be a little late. — It just seems kind of like a conflict because normally you wouldn't

give dexamethasone or a steroid with an infection. — No, but with TB, this is one of those where it actually can be beneficial. — Wow. It's pretty amazing. Really, it is. — And there is some infections where you give dexamethasone. I think the concept behind a lot of those is, you know, especially in pneumonia, strep numo, it's been shown to reduce mortality as well. And it I think the concept behind it is just reducing the inflammatory results for whenever you give the antibiotic and it destroys the bacteria, it may cause like this inflammatory response and you may be shutting it down. The exact mechanism probably I don't know it but I know that it's probably somewhere along that logic is my guess. — Yeah, pretty cool stuff. Well, not TB, but that's very it is interesting. — Dude, TB cool. — Not cool. So, make sure you get those PPD tests done. — Yeah. Yeah. Let's just say you have a patient and they're on warrin for a history of DVT. Many, many people out there are on this. It's very common. Let's just say you have them their active TB and you start them on ripe therapy. Two weeks later, they have a massive pulmonary embolism. — Why? — Could be their revamp. Could be their revamp because any kind of rafampen is a cytochrome P450 inhibitor which inducer, sorry. And so because of that, it could theoretically decreased the Yeah, we talked about Yeah. decrease the efficacy. — Wow. — They could the clot burden could have progressed throughout the DVT, popped off and then, you know, got stuck in a pulmonary artery. — That's all speculation, but that's something to definitely consider. And so I would confirm that by, you know, obviously with Warfin, you check their INR levels and make sure that it's, you know, therapeutic, super therapeutic, and then make decisions on that obviously. But — for this person, — revamping. — Yeah. And so you might have to choose an alternative to revamping in scenarios like this or you may have to adjust the dose of your warfrin. It kind of just depends. I think this is a little bit more challenging to determine in these scenarios. But and there is alternatives to rafampen. You doesn't have to just stick with rafampen. There is a lot of other ones out there that we can utilize in place of rafampen, but they're pretty I don't really know a lot of their names because I've never really used them and I wouldn't say that they're — probably a good thing. — Yeah. But yeah, there is alternatives, but I it would kind of be a challenging decision to whether or not you monitor the war more closely and adjust that dose, continue the rafampen, or do you actually consider switching to another antibiotic instead of rafampen? — Awesome. Last quick little tidbit here, quick super simple differences between active TB, latent TB. — All right. Active TB is usually so it doesn't they don't have to be symptomatic, — right? They can be asymptomatic and a lot of times they are and that's really important. So signs and symptoms aren't always critical. But the other thing is that you're looking at those tests the tubercul we didn't talk about the other ones interferon gamma I'm sorry interferon gamma release assay and we actually use that sometimes in people who have like weird PPDs and we're not sure we can check that. — That's what I had. That was it. Yeah. For shorski. — Yep. — Oh yeah. because I had a huge freaking — I was you know I was — you freaking out. — Yeah, I was crapping myself and they oh well there's a very like good test we can do and it was that it was a blood test. — We use it more for people who probably like we have people who work with us over in Egypt. — So it's likely that more of those who live on the other side of the pond, they've experienced something called the BCG vaccine. And so those who get BCG vaccination when they get the tuberculent skin test it would give like false results. And so we use the BCG I'm sorry we use the interfering gamma release assay and those patients who usually have had some type of BCG vaccination. But it is very good. It's just it's a little bit less cost effective. — Yeah. I remember them telling me it's a very expensive test. — Yeah. I think just overall it's really good. It because what it looks at is it's very simple. Instead of you doing the reaction in the skin, you do the reaction in a test tube. — Oh. because you're just taking their blood. The blood has tea cells. If you have those memory TH1 cells and you expose them to like and that's another thing that makes it really good is you expose it to like very specific antigens like two antigens and then they see it they're like oh I've seen this before and then they pump out interferon gamma and so the higher the interferon gamma levels rise above the threshold boom you get a positive test. That's why it's a really good test. Yeah. Anyway, if you have those tests that are positive, the interferon gamma release assay, the tuberculin skin test, PPPD, the next thing that determines really truly the difference between active and latent is the imaging, chest X-ray, CT scan, whichever one you had to get. If you have a lesion, and that could look a bunch of different ways. It could be an apical cavitary lesion. It could be a consolidation with higher lympodinopathy. milliliary kind of like diffuse nodules all over the dang place. But that is and sometimes you can even see this other one really weird one call it tree butt. They get the point. There is imaging finding suggestive of TB and they have potentially a memory but be careful

because people who have active TB don't have to have a positive PPD or a positive interfering gamma release assay. And people who have very depleted immune systems like HIV or they're severely immunosuppressed, they don't have the immune system capable of generating that interferon gamma and tumor necrotic factor alpha production. So it looks as though they're not generating that response. It's just because you can think about it as their immune system is just like that. That's bro, I can't do much more. This is all you're going to get out of me and it's not going to be enough for me to give a positive test. So that doesn't mean that they aren't actually positive. It's like a false negative if you want to think about that. Key thing though is remember for the most part positive testing abnormal chest X-ray active TB with that little exception that it can have energy is what we call it. And then the patient with the latent is they have the evidence of an immune response tuberculos skin test interfering gamma release assay and they have a normal chest X-ray and that really is what it comes down to with those. And then side effects if you had to quickly summarize liver, eyes, nerves and gout. — Yeah. So I remember ripe and I remember ripe. So rafampen I always remember the R for rafampen is red orange tears. So always assure them, hey, if you're pissing and crying red orange like things, it's okay. You are not dying. — I would think I would be too. — Yeah. Usually just tell them, hey, don't put some contacts on if they got a lot of red, you know, orang-ish tears. But that's really the big thing to reassure them of rafampen. We know that it revs up the liver. So that's all the thing I add for the R. Revs up the liver. It's a cytochrome P450 inducer which means it enhances that enzyme and then metabolizes drugs quicker so they have less efficacy. And so that's the other thing which we talked about kind of going back to the Warframe. — Yep. — I in the IP is isid isolated nerve. So peripheral neuropathy combat that prevent that with paradoxine. P is for the pyzenomide is a pyramid of purine. So it's going to give you lots of uric acid that can cause gout maybe uric acid crystals that can cause nephrolithasis or acute kidney injury. And then E is ethnut I so optic nitis that kind of green red kind of changes and discolorate inability to kind of differentiate between the two and sometimes acuity of vision is kind of going down as well. So that's what I remember and then overall rest in peace liver rafampen isized and parzenomide have the highest risk of apattoxicity and those who monitor those LFTs. — All right well that's it for TB done. hey I hope that you guys learned a lot with this one. Obviously TB isn't something that you're probably going to be exposed to a lot in your medical career. You may though. Who knows? Depends upon what area of medicine you're planning to work on. Either way I hope that at the end of this you feel a little bit more confident. I hope that you feel like you were able to identify as you know Rob laid out the real true differences between things like active and latent TB really how to differentiate and discern what the findings of the kind of test like the tuberculin skin test and interfering game release assay tell you what the chest X-ray really helps you to determine and then also treating these patients how do I treat latent active and then the person who has active how do I really determine their actual positive cultures and positive tests that really confirm it with you know as we talked about the sputum samples and then how do you navigate some weird complications where a patient has active TB and they're showing symptoms from other areas of the body. How do I know which ones those are and how do I navigate that? And so I hope at the end of this you feel like you answered those questions. You feel like you know it. And if you guys did and you liked it, support us. You can hit the like button. You can comment down in the comment section. You can subscribe. You can go to our website and check out all the other things that we have to offer. But I love you. I thank you. And as always, until next time.