Decoding Leprosy Part II: Diagnosis & Treatment

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This is a podcast about One Health the idea that the health of humans, animals, plants and the environment that we all share are intrinsically linked.

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Coming to you from the University of Texas Medical Branch and the Galveston National Laboratory.

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This is Infectious Science, where enthusiasm for science is contagious.

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Welcome back to the Infectious Science Podcast.

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This is Dr Matthew Dasho, here with Camille Ledoux, and a real special guest who is joining us from Dallas, texas, a not only a friend of the podcast, but I would even say family of the podcast, because this is none other than Dr Mara Dasho, my sister, who is a practicing dermatopathologist and also someone who happens to have a great deal of expertise in Hansen's disease, which, as we know and we'll discuss in more detail, is caused by Mycobacterium leprosy.

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So, mara, welcome to the podcast.

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Hi Dr Dasho.

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From Dr Dasho.

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Maybe, to start, you can tell us a little bit about your background, how you got into working with Hansen's disease and what got you interested in leprosy to begin with.

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Yes, absolutely.

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My interest in Hansen's disease really started before I started residency.

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So I was a medical student in Galveston and I decided to do an international health and tropical medicine master's in Spain and it just so happened that I also had an interest in public health, infectious disease.

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And then I discovered an interest in leprosy, because we actually did have a dermatologist expert in leprosy who saw patients in her clinic that I ended up working with one-on-one.

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That was really helpful on the clinical side and I was able to do some research.

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But then in Galveston actually I did an elective and I ended up going to Baton Rouge, which is the center of Hansen's disease, the National Hansen's disease program in Baton Rouge.

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I ended up meeting the director there doing some research and I really just sort of fell into this interest, this niche, and so that sort of led to more research, which then led in my clinical years when I was doing my residency, ultimately in dermatology, discovered more of an interest, ended up doing more research, and then he, the director, ended up actually retiring early and he said oh, so you're now going to be following in my footsteps.

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By the way, I've been doing this for 25 years Now it's your turn.

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So now I'm reading pathology for the National Hansen's disease program from Dallas and I go there periodically and help run their laboratory.

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So that's kind of my side gig, but it's been really great.

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I've loved working with them.

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It is something that's rare, but it's not as rare as you think when we first were recording, we were talking about how this is such a slow growing pathogen that clinical presentations can really vary pretty widely.

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When you do see this in clinic, do you find that it's getting caught early?

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What clinical presentations do you see?

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Or is it people that are on a later?

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stage.

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Unfortunately it's across the board.

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So we call leprosy the great mimicker because it really can look like anything.

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If it's not on the brain you are probably going to miss it.

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It can range clinically from just a hypopigmented or light or white colored patch that may be a little anesthetic, all the way over to nodules and plaques and more severe presentations.

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So unless you're thinking about it, you may miss it.

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And I think that's one of the things that happens is that people go undiagnosed for a long period of time and they may not think of it because it's not usually itchy, it's not usually painful, and then they just have this rash that persists.

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So unless you see a dermatologist or you see someone that thinks to biopsy this or thinks about leprosy, you may miss it.

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The other thing that happens is that people can present with something called an immunologic reaction.

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So, depending on the type of leprosy you have, your body may mount an immune response to the antigen, so to the bacilli, and then it can present with neuropathy.

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It can present with systemic symptoms like fever and just really, really sick people.

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Their skin is really angry, they may have nodules and they may even have vasculitis and arthralgias.

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So you have to think about it.

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You also have to think to ask the questions about their exposures.

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In any past history we were talking about how people often think of armadillos when they think of leprosy.

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Do you find that in Texas that's a pretty common denominator for past exposures, or does it really vary where people have?

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been exposed.

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Well, we know that armadillos get highly infected with M leprae, and so we think that, because you can trace the region of the country, that you might see more of the nine-banded armadillo.

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You can sometimes see more Pantz's disease.

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The issue is that sometimes it doesn't always equate.

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And so then what?

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Is it still the armadillo, or is there something else going on?

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So there are more and more papers coming out on some of the other mechanisms of transmission that might be occurring.

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So there's a possibility that there's a soil-borne incidence going on here.

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So maybe it's something that's in the soil, maybe it's passed by another microbe that we don't know about that's able to transmit the mycobacteria.

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So we really don't have a clear-cut answer.

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But we know that the armadillo carries it, and if you do have exposure to armadillos, there's a possibility.

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But we just don't have that clear, clear, clear-cut answer why people are getting it but don't necessarily have exposure to armadillos.

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What's the prognosis for patients?

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So say, they've come in, someone was thinking about it and actually kind of went through a path to actually get a diagnosis.

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Then sort of what does it look like?

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Well, of course, the most important thing is to diagnose it and then what I try to do, at least from the pathology end, is help to identify what type of leprosy it is, because it exists along a spectrum and it can exist depending on your immunologic response and how you mount that response.

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Again, it could be you respond really really briskly to the mycobacterium and you just have a few lesions, and then some people don't mount a response and they have tons of lesions and they're covered and have a high burden, high load of mycobacteria.

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So I think that's something that you have to always think of again in the back of your mind, but just understanding that it exists along this spectrum.

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And when you diagnose them, then you also have to decide how you're going to treat them, because the tuberculoid or the type of leprosy where you're on the spectrum, where you're really mounting that good response, we would treat that in a different way than someone who is not mounting a very good response and they have tons of bacilli and they're highly infected and they may need more treatment for longer periods of time.

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Gotcha.

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Okay, that makes sense.

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And then I'm really curious.

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So I come from a bacteriology background and I've always heard that epilepary is not culturable.

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And so how then do you differentiate between, like the different types like you were talking about earlier?

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So you're right.

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So you can't culture it in media and it only grows really at that perfect temperature.

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I don't want to misspeak, but I want to say it's 32 degrees Celsius.

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I have to look again.

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I'm sorry about that, but basically it's difficult to culture in media and you can't culture it.

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So we rely on histology.

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Basically they're seeing the mycobacteria in H&E stain sections I'm sorry on fight stain sections, and then we also use PCR.

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So we, especially at the National Hansen's disease program, do PCR on all of the blocks that we receive and we do PCR for M leprae but also for M lepromatosis, which is another mycobacteria that causes leprosy and it manifests in a very clinically indistinguishable way.

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But it is distinguished just based on a couple of little biogenetic differences.

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So we do differentiate the two and again, pcr is the way to go.

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If you don't see it in stained sections then it doesn't mean that you don't have it, because it may be so rare that in the sections you may not even see it because you're cutting through the block and maybe the bacillus is not there.

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It may just take one to cause that type of reaction.

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So it can be challenging.

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But PCR you're looking at a hundred of those sections, so your chance of finding it is better.

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And I was also curious how large of the portion of our population that's actually immune to Hansen's disease, and it's quite high, and really it takes repeat exposures over many, many months with someone who's untreated to even potentially end up contracting M leprosy.

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What have you found?

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Do you think that if there's a genetic predisposition to it in certain families or in groups, or is it that someone has been around someone for an exceptionally long period of time?

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Yeah, that's a really good question because actually only 5% of the population could potentially get leprosy, so 95% of us will not get it.

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Our bodies are going to take care of the infection.

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So then you have to extrapolate those 5% of the population.

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What makes them similar and what makes them different?

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And even though we don't have, again, a clear-cut answer, we do see it more prevalent in certain groups and certain ethnic groups and certain populations that live in certain places, for example, micronesia.

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Leprosy is actually very prevalent and a lot of people are exposed in that area.

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And why?

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Well, it may just be genetically that they're predisposed, it may be environmental.

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There's a lot of potentials there.

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So I think that when you look at why someone's getting it and why someone's not, again, the chances are very, very good that you're not going to get it.

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But if there's a strong family history, if there's someone in your family that has been infected and you've been around them for long periods of time, you could get it Absolutely.

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But again it could also be that you're in the same family.

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Your dad may have lepromatous leprosy, which is again we're on that end of the spectrum where you get heavily infected and you may not.

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So I think the jury's still out there, but it's very interesting question and why we see it in certain groups.

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Now, Mara, I think you have the unique characteristic is that you have seen folks who are suffering from this condition and we don't see it that often, so don't always have a good idea of the clinical presentation and also the epidemiological background.

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There's certain populations that we know may be affected more disproportionately folks coming from endemic areas.

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There's the migration of folks from those endemic areas.

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So can you say a little bit more about what you've seen clinically and what the spectrum of disease looks like and what populations that you see are most affected by Hansen's disease?

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I deal mostly with the diagnosis of leprosy, but I still have encountered patients who have been dealing with leprosy and they're certainly very diverse.

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I've been involved in those cases, even though they may not be my patients, and it goes from people who are actually just born and raised in Florida, in central Florida or in Louisiana or in Texas, and they may not have a family history, but all of a sudden they develop a rash that hasn't been diagnosed and someone does a biopsy and it shows that it's positive.

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But it also could be people who have immigrated from other countries and do not have resources, and maybe they were diagnosed or maybe they were even partially treated in their home country, but then come to us and present either with a reaction, so they may present to an ER and no one knows their history.

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And then all of a sudden you have someone coming in that has diffuse rash, joint pains, very sick, and no one really knows what to do.

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They treat it as something else.

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So I think that these people, the people who are coming from other countries especially, who don't have resources, who don't have access to healthcare and to insurance, will come in, present to the ER and then they may get lost.

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And unless you have that, one member of the healthcare team that thinks to call someone, whether from the Hansen's program or a local Hansen's clinic, to say, hey, this might be leprosy, what do we do?

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These people may slip through the cracks.

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So I think it's really important that we're thinking about this disease, because there are people that are coming in who may or may not have been treated and they're potentially at a disadvantage because we're not thinking about it as clinicians either.

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I have two follow-up questions to that.

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That's very, very interesting.

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One is why do you think that the majority of cases in the United States are diagnosed in dermatology clinics versus something like an infectious disease clinic?

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Part of my PhD program is doing clinical encounters and so we go to infectious disease clinics and we shadow and they're trying to think of like anything and everything, but certainly when I was getting into the literature on this, it really seems like it's diagnosed oftentimes by dermatologists.

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So why do you think that is?

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And then also, how susceptible is the organism to antibiotics?

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So I think that most people are presenting to derm because there tends to be a rash involved.

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Typically there's a rash, not always.

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Actually, some forms of leprosy are pure neural, where you don't have a rash at all.

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And that's even more challenging because then they go to neurology and get this work up until someone potentially does a nerve biopsy.

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But most of the people who present to DERM have a rash and DERM does what DERM does best, which is biopsy.

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And then dermatopathologists if you're sending to a dermatopathologist who is trained to look at these biopsies and then come up with the diagnosis or at least a differential diagnosis stain the tissue to look for organisms.

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If they don't see organisms, then they may send it.

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There's a high possibility that this is leprosy, whether there's anesthesia.

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So if the lesions are anesthetic, that's also very important to think of.

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So it's not just rash.

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Are the lesions anesthetic?

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Are nerves enlarged?

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And you can even test for that.

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You can see.

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Sometimes when the nerves are enlarged or the ulnar nerve is enlarged you can say hey, oh, my goodness, maybe that nerve is inflamed.

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But in derm clinics we are trained to biopsy and as long as the dermatologist is doing a correct biopsy, which we always recommend a punch biopsy to get all the way down to fat so you can see the nerves.

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Then a lot of times at least the pathologist should have a suspicion that this could be and then know from there okay, stain it up, okay, maybe it needs to get PCR.

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So that's kind of the chain of events.

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But a lot of these people do go to germ.

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And then what was the second part of your question.

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I'm curious about how susceptible it is to antibiotics, particularly because when I think of mycobacterium I of course think of tuberculosis, and that is exceptionally long course of antibiotics.

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But for something like Lepre, is it a short course?

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Is it exceptionally long course of antibiotics?

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But for something like leprosy, is it a short course?

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Is it a long course?

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And then, based on that, how susceptible is it Like?

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Is there resistance to certain classes?

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So that's a great question.

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So the WHO will treat leprosy with something called multi-drug therapy.

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So Dapsone, rifampin and Clefazanine are the three drugs that are used, varying frequencies and durations.

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Typically, though, if you're following WHO protocol, the possebacillary or the tuberculoid form of leprosy is treated for a little bit less time six months to a year and then if it's multibacillary or lepromatous, where it's again that spectrum where there's high burden of bacilli and lots of lesions, then you're going to treat for longer and you're treated with three drugs.

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Now most clinicians are actually treating with a little bit of a different regimen and it's called ROM, but rifampin, ofloxacin, minocycline or moxifloxacin, and doing it for a little bit of shorter time periods because a lot of these medicines are not well tolerated A lot of laboratory issues and anemia etc.

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But the medicines are longer period of time, number one to treat fully.

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But in terms of resistance, that does occur.

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It does occur not often, but that's also something that we can test for genetically.

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So if you send your specimen to the National Hansen's Disease Program, you actually can have the tissue tested for resistance, and so we look at certain genes and look to see if those genes are expressed in different ways to determine if there's resistance.

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Okay, that's very cool.

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And then so, when someone has completed the course, how are they cleared?

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Is it that they've completed the six months to a year of antibiotics?

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Do they have to have a clear biopsy?

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Kind of no continuing symptoms?

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That's a really good question too.

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So if you complete the full treatment, so if you complete your multidrug therapy regimen, we do consider those patients treated.

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Now, the issue with leprosy is that the bacillus can remain in the tissue and typically does for many years after treatment, because even though the DNA may be present, the organism itself is dead.

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It just takes years and years for that organism to be broken down and removed from the tissues so it still can mount a reaction, it still can present lesions and still cause issues with morbidity.

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So neuropathy, nerve damage, lesions, it certainly can be longstanding.

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And that's really the big thing with Hansen's disease is that the sequelae, which are usually neurologic, which are usually the neuropathy and the loss of sensation, is really what causes the most disability over time.

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And that's the biggest problem.

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It's diagnosing it, yes, treating it, yes, but then what happens to these people?

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A lot of them end up at a great disadvantage because they're not getting their rehabilitation that they need, and that's another thing that the program does is occupational therapy, physical therapy, wound care to help these people who are dealing with the sequelae Gotcha.

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Yeah, no, that's definitely something I think that can often slip through the cracks Like oh, like we're treating this, but not necessarily all the downstream effects of it, and that's definitely really important to ensure that people have quality of life, and so people six months to a year on antibiotics, that's a very long time.

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Do you find that there's a lot of compliance with the regimen, because that's an exceptionally long time to take antibiotics?

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Do you think that that is a barrier to care, that a lot of people will take it and then drop off, or?

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I don't know if there's statistics or not yeah, I don't know about percentages, but absolutely, and a lot of people do directly observed therapy.

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So DOT and they'll have the patients come in for their monthly visits and have them take the medicine in front of them, especially if they're kids, for example, if you're treating a kid.

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But I think it really is on the clinician to be doing this follow-up for their patients and making sure that they're taking their medicines and seeing them regularly.

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And that can certainly be a challenge for people who don't have access.

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I mean, these people have to go to a free clinic and the Hanson's clinics around the country I think there are eight of them Uh, me on that but those clinics are government funded.

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They are free of charge, the medicines are free of charge.

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So if you get these people hooked in to the right places and to the clinics that exist, they are going to get the care they need and they'll get the lab monitoring.

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But it takes several steps, especially in our system, to get them there and they may not.

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So I think we're absolutely underdiagnosing.

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In the United States we typically diagnose about maybe 200 cases a year, but I think that number is definitely underestimated because we're missing patients that just can't get in or they're misdiagnosed.

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We had previously talked about that, where in infectious disease, anything it can get very like us versus them.

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Even if you look at the webpage, I think for the CDC it's like oh, most M leprosy infections are acquired outside the United States, but that's not necessarily true and I think what you were saying just kind of brings me into that important point.

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But it's stigmatizing to suggest that it's coming from outside borders, when borders are things that we've made up and it's definitely here.

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Totally Absolutely.

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It is here, and a lot of the cases are coming in from people who are from the United States that we see not all of them, but a good number of them and so we can't continue to think that this is just something that is coming from people from other countries and they're the ones who are getting exposed and bringing it into our country.

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That's not the case at all, especially leprosy.

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We just still have so much to learn and we certainly can't stigmatize those individuals.

00:21:23.133 --> 00:21:34.597
It still is a very stigmatizing disease, right, and so I think that dates back years and years and years and biblical times, and so I think that there's a lot to that, and culturally too.

00:21:34.597 --> 00:21:37.987
So people coming from other countries that you can't even say leprosy.

00:21:37.987 --> 00:21:43.152
That's why we call it Hansen's disease, because of the stigma that is associated with that word.

00:21:43.573 --> 00:22:06.644
That's definitely a major thing that we really discussed that this is still such a stigmatized disease and that can be a barrier to care but can also lead to negative health outcomes for people beyond the physical right, from a mental health perspective, especially because, if you think about it, when people say leprosy, the idea of that is that that was the original moral unclean disease and we've seen that later in other diseases as well.

00:22:06.644 --> 00:22:12.644
So I think in the 80s HIV was also viewed that way until there was a lot of activism and pushback.

00:22:12.644 --> 00:22:17.266
And so is there activism around Hansen's disease to change the perspective of it.

00:22:17.266 --> 00:22:21.982
Or do you think that there's not enough cases where that's being done or there's not funding for it?

00:22:22.503 --> 00:22:27.300
I think that certainly we need to bring more voice to this disease.

00:22:27.300 --> 00:22:50.209
The issue, of course, is that it's exceedingly rare, and so when you have a rare disease, it's not funded well and it's not given a lot of attention, and so you end up with some resources, not a lot, and so, unless you really can know where to look and know where these programs are and where these resources are, it's very nebulous.

00:22:50.209 --> 00:22:57.362
And then, on top of that, this is a government program that really funds the research and funds the clinical work.

00:22:57.362 --> 00:23:03.114
So I think that it's challenging to get the public eye involved in this disease.

00:23:03.114 --> 00:23:07.309
Most people don't even think it exists anymore, and so it's challenging.

00:23:07.309 --> 00:23:08.192
It really really is.

00:23:08.192 --> 00:23:13.933
It's hard to know what the next steps are, because it's so rare, but yet it's really important.

00:23:13.933 --> 00:23:17.503
And it's still relevant, but yet it's rare.

00:23:17.503 --> 00:23:30.232
So I think we have a lot of work yet to come and hopefully it will continue along these lines, but we'll also have more clinicians interested who will support us Absolutely.

00:23:36.460 --> 00:23:37.905
I think that everyone would want this disease to be eradicated.

00:23:37.905 --> 00:23:39.692
In fact, the WHO has put forth these goals for eradication that keep going on and on.

00:23:39.692 --> 00:23:42.923
We want to eradicate in 2000 and then 2010 and then 2020.

00:23:42.923 --> 00:23:55.027
I think that the lesson here is that it's still with us and although we want it to be eradicated, this is a much more complex issue than just medicines.

00:23:55.027 --> 00:24:16.132
This is really kind of identifying those at risk and then treating them, but then also following them and making sure that we are addressing all of the encompassing issues that come from this disease, and it's certainly very, very much socioeconomic.

00:24:16.132 --> 00:24:22.529
We're dealing with these psychological impacts, I think, down the road that also can affect someone's life profoundly.

00:24:22.630 --> 00:24:30.567
So I think we as clinicians really do need to keep this in the forefront of our minds and also just educate yourself on just basic presentations of leprosy.

00:24:30.567 --> 00:24:31.249
Think about it.

00:24:31.249 --> 00:24:34.101
Think about it if you see a rash or someone has a numb lesion.

00:24:34.101 --> 00:24:36.969
If you keep it in the back of your mind, then you're not going to miss it.

00:24:36.969 --> 00:24:39.946
All right, thank you, it is my pleasure.

00:24:39.946 --> 00:24:40.971
This was really fun.

00:24:40.971 --> 00:24:46.406
I hope we can do it again sometime in the future, but I would love for anyone else to contact me if they're interested or they have questions.

00:24:46.406 --> 00:24:48.270
I hope that conversations will continue.

00:24:54.420 --> 00:24:55.503
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00:24:55.503 --> 00:25:00.284
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