124. Moulds that cause chronic subcutaneous infections

• Sporotrichosis
• Mycetoma
• Chromoblastomycosis
• ...Entomophthorales.

Let's face it: you don't know anything about these diseases. 

That's OK: neither do Callum or Alyssa. That's why we've got a guest! Dr David Chandler is a Consultant Dermatologist, BSMM member and is a member of the Global Mycetoma Working Group. Listen on for everything you need to know about chronic subcutaneous infections caused by moulds! 

Transcript

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14. Moulds that cause chronic subcutaneous infections

0:00

Hi everyone. Welcome to the Idiots Podcast. That's infectious disease insights of these specialists. I'm Callum, and that's Alyssa. And we're going to tell you everything you need to know about fungal infection. Soon May the editing, editing come to discontinue Caspo fun gun. One day when the BDG is done, we'll take our leave and go.

Alyssa 0:22

Hi Callum. Hi David.

David 0:25

Hi.

Callum 0:26

Hello,

Alyssa 0:27

So we're really happy to be joined today by Dr. David Chandler, who's a consultant dermatologist at the University Hospital Sussex. And he's also an honorary research fellow in the Department of Global Health and Infection at Brighton and Sussex Medical School. His interest is in fungal infections of the skin, particularly tropical mycoses, such as mycetoma. And he's worked in many countries in Africa, India, and Latin America. In the UK NHS, he runs a specialist skin infection clinic, and he's also a member of the British Society of Medical Mycology who's supporting this series of episodes and the Mycetoma work, working with. So we are really happy to be joined by David. Thank you so much for coming on the show. And today we're gonna be talking about molds, the ones that cause subcutaneous infection,

David 1:22

Thank you, Alyssa. It's a pleasure to be here.

Callum 1:25

I'd say it's a double pleasure for David to be joining us, as a fellow Scott. And as I'm sure you have done David, where you wear your kilt to a special occasion or a wedding or whatnot. And recently I was at a wedding wearing my kilt and my sporran. I'd actually have recently learned this trick that I do And yeah, so it was a sporo Oh, sis.

David 1:53

that's, I wondered where that was going. That's, that was very good. That was very good.

Callum 1:58

Okay. That's me from puns. Take that box off. Listen, what are we talking about today? What do we mean when we talk about moles that cause subcutaneous infections, what does that include?

Alyssa 2:11

So we can be talking about

David 2:13

sporotrichosis,

Alyssa 2:15

Mycetoma, Blaser Mycosis C or below, mycosis and Baia below Mycosis. So these are really, we've already been through lots of moulds in this series of episodes and talked about how they can cause superficial and invasive infection. these moulds predominantly cause chronic subcutaneous infections.

Callum 2:37

And. David, Alyssa mentioned in your there that you have an interest in this area. How did that come about? what led you to becoming an interested and now really an expert in this field in the UK? That's

David 2:52

Oh, I guess at medical school, the things I was interested in would be, Dermatology and infectious diseases. So after foundation training, I took a year out to study tropical medicine at the London school and developed an interest in the fungal infections there. And during that course, I, I met someone who was the mentor of me. So Professor Rod Hay who really spurred on my interest in that area. So I guess it's the topic subject matter is one thing, but I guess also the person encouraged me, I encouraged my interest in, in that area.

Callum 3:27

a huge thing, isn't it? When you find a mentor, that's going to bring you before. And we all I guess, working, think about our mentors as we go along these journeys.

Alyssa 3:33

I was interested actually, David, about if you'd be able to tell us a little bit about your work abroad and how you came about, know, to spend time working abroad and, and if that also was something that led you to become interested in these infections.

David 3:48

Yeah I guess, my sotoma is probably what I've focused on mostly. And Brighton, Brighton Sussex Medical School. Now, the projects that I'm working on are so mostly focused on Mycetaema. And during my dermatology training, I took a year out and an OOPI out of program experience. And with that year, I spent most of it in Mexico and a little bit in Brazil. And that was mostly just to gain experience clinical experience, laboratory experience. But also to do some research as part of that. So that's where and when it started. That was roughly four years ago now. And a lot of the projects that I've done have stemmed from that. So that was mostly based in Mexico city at a referral hospital there in there's a dermatology and mycology center all in one but then I also did some sort of field work trips to rural parts of Mexico on the Pacific coast and the Guerrero state. Those were sort of rural clinics where we would try to find cases of myasthema but also just treat any sort of cases of skin disease that presented.

Alyssa 4:57

Yeah, when I've spent a little bit of time working abroad, so I spent some time in East Timor and some time in Panama saw lots of odd skin infections that I was never had a clue what they were. And I think at that time of my training, like these sorts of infections wouldn't have even been on my radar. And I guess one of the huge challenges in the places where I've been working was that there was. A real lack of laboratory diagnostics. I don't think even if we had come across one of these infections, we would have had much chance of chance of diagnosing it aside from clinical features. So maybe something we can talk about as we go through as well. Yeah. So

Callum 5:36

There's something hugely impressive about the ability of, I was thinking about this when you said that you'd sort dermatology, and that's how sad it was that we didn't manage to get you into ID, David. But, the of a dermatologist to turn up and look at a rash, and that just the clinical picture alone can give you so much information, that's hugely impressive. and even, in the UK in their immune compromised host population, for example, I was on at the weekend and just passed and there was a, what I thought was maybe a fungal infection, but, just having the words to label what the rash was and then even with advanced diagnostics, it can still be a real challenge. sometimes to diagnose fungal skin infections. So I guess you said that your primary focus is myositoma, but we're starting with spore trichosis. And I guess maybe because one that's, but more common in, we see it in the UK. and also it's slightly different group, I guess, from other ones, because this is a, correct me if I'm wrong, dimorphic fungus. So we were having a little bit of debate about whether this would sit in the episode about chronic fungal infections and the clinical grouping or with the taxonomic grouping and put it with the dimorphics. But I think it probably fits, better here, doesn't it? Should we just start off and talk a little bit about sporotricosis?

Alyssa 7:02

sporotrichosis is, a disease that's caused, I think there are two main species, aren't there? There's sporothrix schenckii, which is present in the uk and then there's also Brazil, which is more localized to Brazil and parts of South America. David, are you able to tell us a bit about spor truss caused by Sprott KY

David 7:27

Yeah the sporophytic strain curve, as you said, is the most common cause and it has quite a wide geographic distribution throughout the tropics and in Europe, that would be the species causing the infection if it was to occur here. Whereas Sporothrix basiliensis, as you mentioned, is largely in Brazil and neighboring countries. And then the other species of note is Sporothrix globosa, which is a common cause of Sporothricosis in Asia, parts of Asia. But in terms of the clinical features, in my experience, they don't vary too much according to species. They can present certainly in a very similar way. Sporothrix brasiliensis is recognized as being more virulent, so it can be clinically more aggressive causing more widespread skin disease. But the classical presentations can certainly be very, very similar for all of the causative species. I think it's, a good place to include it in this episode because the vast majority of infections are, skin and subcutaneous tissue there is this sort of systemic form of sporicosis as well, but that's, relatively uncommon compared to the skin infections that it causes.

Alyssa 8:47

and how do people get these skin infections?

David 8:51

Yeah I mean, that's one thing really that groups these infections all together is that they're referred to also as implantation Mycosis. So the mechanism of infection is by trauma. Often in many cases a thorn prick or a splinter of wood or just some minor trauma to the skin. And then the organisms which are environmental molds can then get into the skin and subcutaneous tissue and establish infection. So for Mycotoma, Chromoblastomycosis, all of these. subcutaneous fungal infections, the mechanism of infection is thought to be penetrating trauma to the skin, which introduces the the organism.

Callum 9:32

If you get this sort of penetrating trauma do we know what factors make it more or less likely that you go on to develop a chronic fungal disease? Do things like, irrigating or cleaning the wound. help or do we not know that sort of information?

David 9:47

It's a good question. I don't think we know because in some places minor. the skin is very common. If you ask people about thorn pricks or splinters and those sorts of injuries to the skin they get them all the time. But they don't develop my sotoma or spore dracosis every time. So I think what the factors are for why it infection. I think it's not clear. So probably the load, the inoculum probably host immune genetic factors, I guess, are also playing a role. Yeah. And I guess also whether the organism is, is there there might be trauma, but, it's not always going to be that the organism is present. on that organic material every time, but no, it's a good question, but it's, I don't think we know really why.

Callum 10:37

You mentioned that the mechanism of injuries quite similar. So focusing, I guess, on sport process. So after it's been inoculated, how would that present clinically in the UK or, or in other species?

David 10:50

Yeah so you usually you develop a skin lesion at the site of infection. And usually that will present as a nodule which increases in size. And then. usually becomes softer and ulcerates and discharges pus. That'd be a typical presentation. And in some cases the infection will remain localized to the site of infection, and that's referred to as fixed cutaneous sporic ricosis. In most cases, about three quarters of cases, the infection will spread via the lymphatics. So after that initial lesion appears, you will then get subsequent lesions appearing. So from distal to proximal along the lymphatic channels. So the hands or the extremities would be a common site of infection and you'd then get lesions popping up. Working their way up the arm towards the shoulder,

Callum 11:47

And people talk about this. Classic spread up the lymphatic system. There's this term of like sporotrichoid, so like sporotrichosis. So my reading of that was that this is, Maybe historically be much more, more common because I, it's certainly something that I've thought about and think about when I see patients with skin lesions that are a bit odd. And locally, we do occasionally diagnose it. Does it tend to come to probably like dermatology clinics more? I guess people don't really present with systemic upset and what other things are presenting that, you might term like, what's the differential for that pattern of of skin lesion.

David 12:24

Yeah so the difference, I mean in the UK if you, if a patient presented with that pattern of lesions, sporotrichoid lesions the most common cause for that would be a mycobacterial infection. So the classic one would be your fish tank granuloma. So mycobacterium marinum infection, and that can I had a patient currently actually that we're treating with that exact presentation there, which started on the thumb and then the lesions have spread up her arm almost as high as the shoulder. And that's a Mycobacterium marinum, so that would, I think, be the commonest cause of that presentation. Sporotrichosis would be much less likely, which is much more uncommon. The other thing to consider would be, if there was a travel history, then Cutaneous Leishmaniasis. Because that can, again, be pretty much indistinguishable. But I guess the travel history is the thing that would separate that.

Callum 13:19

Yeah, I was just thinking about that when you said a nodule that ulcerates which, is like I think most infection specialists would think about that when you put those two words together. But that's how it presents on the skin that can, my understanding is it can cause more invasive disease, but that's quite rare.

David 13:36

it is rare, yeah, it's a minority of cases that that have this systemic form and largely that is immunocompromised. Whereas the cutaneous form is something which occurs in, generally healthy, immunocompetent people. So yeah, in the systemic form you can get involvement of multiple organ systems. Bones and joints, tendons are often involved, so you have tenosynovitis I've seen it affect the eyes in different manifestations and actually from working in Brazil, something that we saw commonly in those cases was meningeal um, sporic fracosis so it was often HIV positive patients and then they had Meningial disease?

Alyssa 14:23

And did they often start off with cutaneous lesions and have that sort of classic cutaneous appearance and then it subsequently causes disseminated infection or, would you just find it from culture of the CSF

David 14:38

no. Yeah. I think that they don't tend to have that classical skin presentation first. yeah, the source of infection in those cases it might be that that's via inhalation of spores. So an an initial, much like the other systemic infections, the dimorphic initially a, a pulmonary infection, which disseminates. So it's not the case that it's beginning with skin disease and then disseminating. At least I don't think that's, I don't think that's common.

Alyssa 15:07

Okay.

Callum 15:09

And can that happen in, in spore trichosis shanky eye as well.

David 15:14

Yeah, absolutely. Yeah. It, it, it can do

Callum 15:17

I was not, I've thought about spore trichosis many times. I don't know if I've ever diagnosed a case though. And I had no awareness that it could cause systemic disease. And that's a really important learning point to think about. And the patients that you did find it in that was, it was more invasive, how were they diagnosed? Was that as Alyssa says on the sort of culture of CSF, or was that another marker?

David 15:39

no, I, I believe it was the it was CSF culture and they use serology quite frequently in those patients as well to particularly to monitor response to treatment, in those cases they were on treatment for such a prolonged periods and it was hard to know when to stop treatment. I think actually in a lot of those cases,

Callum 16:01

I imagine we've segued effortlessly into the laboratory diagnostics. I guess you've suspected that clinically you've got this classic cutaneous lesions or maybe more systemic disease. How would, what would this approach in general terms to diagnosing this be other than the pattern recognition of the clinical presentation?

David 16:21

yeah, so I mean, I guess, want to obtain, biopsies so histopathology is really useful for diagnosis generally you would perform direct microscopy with any tissue samples, but for sporic ricosis, that's not always that helpful. The yeasts are present in quite low numbers, so to, to see them on direct microscopy it can be quite difficult. So you would want to take skin samples for culture and for histopathology to try to identify the yeasts.

Alyssa 16:53

And just to recap again, because we are not including this in the Dimorphic fungus episode. So of the classical things about Dimorphic fungi is that they are molds in temperatures and then they're a yeast form in the host. So I guess you're gonna be looking for Yeah. Yeasts in your histo pathology samples and non-direct microscopy as opposed to the. To the mold, but then when you're culturing it, be, depending on what temperature you're culturing at you'd either be looking for yeasts molds.

David 17:30

Yes, absolutely right. So culturing it at lower temperatures, so under routine conditions, routine culture media, it would grow as a, as a mold, as you say. But then if you were to, once you've isolated the mold, if you then take a small piece of that and re culture it on an enriched medium at higher temperatures, say 37 degrees it will then grow as a yeast. And I think a lot of laboratories take that approach of growing a mold which is compatible with spo uh, morphologically and then converting it to a yeast form at a higher temperature in order to make the diagnosis.

Alyssa 18:07

And I guess another point that kind of differentiates spora threats from other dimorphic fungis, that these are ACDP category two pathogens, whereas I think the majority of the other dimorphic fungi are category three. So in a standard laboratory, we probably wouldn't. to grow these these fungi due to the risk of laboratory staff exposure. But, but sporothrex is a category two pathogen. we've talked about the role of histopathology. Is there a role for PCR at all in, in diagnosing sporotrichosis?

David 18:44

Yeah, there is I think in the problem with with a lot of these infections is that in many of the endemic areas. Those sorts of tools just aren't available unfortunately, but yeah, absolutely. Identifying the organism is usually by, cultural molecular methods if you, if you have them available. Yes, there is certainly a role for it.

Callum 19:06

And then once we've diagnosed and confirmed it, we've got our yeasts. From the patient, we've got hepatitis, histopathology and clinical syndrome. How do we go on treating this? You mentioned earlier on that these patients need long, long courses of therapy if it's invasive. Do, how do we treat both cutaneous and invasive disease?

David 19:23

Yes so, um, So, Itraconazole is certainly the first line most commonly used treatment. I mean, starting usually at a dose of 100 or 200 milligrams per day. But again, in more severe cases that can be increased up to, you know, 400 milligrams per day. And then in terms of treating skin disease, you're expecting to treat the patient for at least three months, but you essentially continue treating until you see a clinical resolution. So until you see those lesions healing and healing and scarring and the infection not looking active any longer. I

Alyssa 20:00

And are you aware of any issues of resistance of these? pathogens, or is itriconazole predominantly pretty, um, going to be effective against borothrex?

David 20:14

think it generally is quite effective, although in some cases it may need longer, longer duration. I think perhaps with sporothex brasiliensis it's, it's not always as effective. So certainly in some cases certainly some cases will be refractory and you'll need to consider a different azole. Or as a higher doses, or even in some cases sort of combination therapies and what's often what's commonly done as well is to use adjunctive treatments, physical therapies. Alongside it, you might supply cryotherapy. or thermotherapy to specific lesions. Or, also you can sometimes surgically excise or incise and drain particular lesions if they're not responding very well. Sometimes lesions will encapsulate or be quite cystic and resistant to treatments and so you might need to excise them or perform some sort of surgical treatment.

Callum 21:16

And then for more invasive disease, I guess that would be liposomal amphotericin B. You'd start that initially and then you would step down to oral atraconazole for again a prolonged period, several months, but then waiting for that sort of resolution of the disease.

David 21:34

Yeah, absolutely. I think that's a common approach is to start treatment with, say, liposome 1 for teratin B for two weeks or so and then to switch them on to oral intracortisol yeah, treatment durations are much longer in, in those cases, one to two years rather than a few months.

Alyssa 21:52

So my understanding, David, is that sporothoenix schenckii is a fairly ubiquitous worldwide distribution, whereas Brasiliensis is found predominantly in Brazil and South America. And is it that this is predominantly a disease of cats? that humans can then acquire through contact with cats. There's some link isn't there to cats with this.

David 22:18

Yeah, absolutely. I see. Earlier I said that, these are environmental molds and, and, and that's how infection occurs, but you're right, that, that with Brasiliensis, it is different. The infection is within the feline population. And, and that's, that's how the sort of epidemic of cases has developed in, in Brazil, mostly in Rio de Janeiro. The infection in these cases comes from either the bite or scratch from an infected cat. So the yeast is going to survive quite well in cat saliva, for example. It's a good temperature and pH. And yeah, either the bite or the scratch of a cat can then cause infection in human skin. I think part, in Brazil, it seems like part of the problem is that, There are a lot of cats family, it's quite frequent from what I saw for families to have, seven or eight or more cats. And they roam around as well. So there's a lot of transmission between that occurs. So it's a difficult problem to control. But yeah, that that's where that's the source of transmission in, in, in those cases.

Alyssa 23:28

So it's the inoculation injury is the, the cat, and then transmitting that environmental mold via, yeah, via the animal. Okay. And I guess that could lead to spreading beyond. know, to other countries if who are infected are moving between countries.

David 23:49

Yeah, absolutely. It has, it has spread to other countries in South America. It also occurred in the UK. I think it might, it must've been about probably a couple of years ago now, but there was a case of a cat imported from Brazil which I think was examined at the time of entry and thought to be healthy, but It then caused infection in someone in the UK. So it was a case of Sporysrix Brasiliensis infection from a cat imported from Brazil. It's quite an interesting case.

Alyssa 24:25

Wow, yeah, we would not want that spreading around

David 24:28

No.

Alyssa 24:29

population, so be wary of Yeah, cats coming from Brazil and South America, particularly if they've got skin lesions.

Callum 24:37

Yeah. It's particularly around the, like the nose. Isn't it in the face that you see them? Is that right?

David 24:41

Yeah, that's right, so that they get ulcerated, raw sort of skin lesions, yeah, as they often, on the face, around the nose.

Callum 24:49

was a session that ESCMID 2023, all about cutaneous fungal infections. And there was a speaker there, I forget his name, from Brazil speaking about their experience. And it was, scary. So I guess we'll need something to watch. But they showed a lot of pictures of cats. Faces and it was quite upsetting if you'd like cats. So, A picture of a cat in the show notes looking very bad. and it just seems like a real, as you said, problematic thing to control because these cats are roaming and the treatment is really difficult for humans, let alone for a cat that you can't explain the need for the treatment. So I guess is there anything else that we should say about Sporafix before we move on?

Alyssa 25:29

I think just one thing we haven't mentioned is that typically in, I know as I've gone through training, it's often referred to as rose gardeners disease, isn't it? And I think that's because the classic story is that you've got somebody who's an avid gardener who scratches themself on a rose thorn and that's the mechanism of inoculation. So that's another name for Sporotrichosis.

Callum 25:58

I yeah, I always find myself asking people weird questions like, do you do any gardening and then rosebuds, pets, and have they been imported? Just adding to your armamentary of odd questions you can ask your patient, which is what this is all about, I guess, isn't it? Should we move on and talk about the main event, Myositoma, then?

Alyssa 26:15

Yeah. So this is your main area of interest.

David 26:19

it is. Yeah. Yeah, this is certainly the research that I'm doing at the moment is. It's focused on Mycotoma.

Alyssa 26:27

And this is actually a WHO neglected tropical disease. Which I guess is good to have that label because it, gets recognized a bit more.

David 26:36

Yes, yeah, I was going to mention that just earlier actually, because it's WHO recognises this group of fungal infections, it's Mycotoma, Chromoblastomycosis, and other deep mycosis. They don't really specify what they mean by other deep mycosis, but That would also include things like Sporotrichosis and Lobomycosis, for example, in Central South America that entire group. But certainly Mycotamer and Chromoblastomycosis are the ones that are specifically listed.

Alyssa 27:06

So I've only seen one case of And it was in a a young man who I saw in Bristol, who was originally from Sudan. And he had had been walking barefoot, and cut his foot. And then he developed this really swollen area with skin breakdown and lots of sinuses. And initially I think he I don't know how he came into contact with health care services, but he initially was sarcoma route, osteosarcoma route, and there was concern that he might have osteosarcoma and biopsies sent. And then, there was thought about maybe surgical debridement of the area. And I can't remember at what stage infectious diseases um, came involved. But my senior reg at the time was also from Sudan. He recognized it immediately as Mycetoma or Madura foot. And we ended up diagnosing it on the grains that we managed to express. I think PCR was performed on the grains and it was more a clinical diagnosis, but that enabled us to work out what the organism was and then how best to treat it. So that was, yeah, that was a really fascinating case, but my only experience thus far with Mycetoma, so I'd be interested to, to hear a bit more from you about it.

David 28:26

Yes it's interesting that you said that, I think initially he was, Thought to maybe have sarcoma and then subsequently diagnosed with myasthema is also I guess this is the importance again of histopathology is that it can also work the other way around that in, in endemic areas where myasthema is more common there's a tendency to think it's another case of myasotoma because that is most likely, but you still can get sarcomas and bone tumours presenting in endemic areas. Again, just the importance of keeping that differential and taking a biopsy,

Callum 29:00

so I guess Alyssa mentioned there a case, so how does this sort of typically present over time? How does it, how did the Legion start and then how did they develop?

David 29:09

Yeah, so it's a slow, a slow onset. So again, the infection develops at the site of infection so it might be months or even years after the organism was introduced. And the key features are swelling, so a subcutaneous mass or swelling and then in most cases, the formation of sinus tracts. Sometimes there are skin nodules but certainly the key features are the swelling and the sinus tracts. And then from those sinus openings, you get typically a purulent discharge And that can contain the grains, which are the characteristic feature of the myasotoma. So the grains are the the morphological form that the organism takes on in, in human tissue. Going from its environmental mold phase, to then, in tissue, forming these grains, which are, like little small grains of rice, essentially. You can generally see them with the naked eye, but they're not as large as a grain of rice. Of rice?

Callum 30:14

So yeah, I guess maybe because they grow so slowly might lead to a delay in diagnosis. I guess you've got this sort of slow growing area, you've got the classical appearance and then imaging understand can that be useful as well as a diagnostic?

David 30:28

Yes, de definitely. It's an important part of the investigation. Mycetoma again, characteristic feature is that it does invade deeper tissues. So it can invade sort of tendons, deeper structures and particularly bone. It's quite common to get bone involvement some degree of bone involvement. As a minimum, a plain x ray is important. I think about a third of patients will have Destructive bone involvement, so he's cavitating destructive bone lesions but more patients will have a greater proportion of patients will have some evidence of bone involvement on x ray and MRI is also very sensitive. As well. You can see quite specific changes, of destructive bony change on MRI. So if that's available, it's a good investigation.

Callum 31:16

And would that help differentiate, cause you said one of the main differentials is things like sarcoma, but the imaging helped differentiate between those two possibilities.

David 31:25

I suppose it would I don't know too much about imaging of features of bone tumors or say sarcoma compared with Mycetoma, but I think the MRI features of. Mycotoma are fairly specific. You see this what's referred to as a dot in circle sign and Which I think is fairly specific to mycotoma.

Callum 31:48

And I guess, maybe moving on to other diagnostics. Thank you. What would differentiate them well what other diagnostics do we have

David 31:55

So Unlike sporodracosis and the direct microscopy and can be very helpful. So you can often confirm the diagnosis of mycotoma by expressing pus and examining it under the microscope straight away and you can visualize the grains. and make a diagnosis. It's important to obviously culture as well to try and identify the organism and say histopathology and imaging Molecular tests if they're available, but the simple tests say just direct microscopy can often confirm the diagnosis.

Callum 32:26

Hmm.

David 32:27

And in, in some cases, give you an idea of whether it's fungal or bacterial. And that's something to cover as well, actually, is that we're talking about fungal infections, but mycetoma has the fungal form, which is eumycetoma and the bacterial form caused by actinomycetes bacteria. And that's actinomycetoma. So you can distinguish between between the two fungal grains from bacterial grains on microscopy.

Callum 32:55

Hmm.

David 32:56

And on histopathology as well. It's easier with histopathology, you have a nice, a clearer image, but you can also do it on direct microscopy.

Alyssa 33:03

Guess that's really important when you come to think about treatment, because the treatment if you're branching bacteria is going to be different to your treatment of your, fungal pathogens.

David 33:15

Yeah, absolutely. And so that initial sort of rapid result that you can get from microscopy can, give you a diagnosis of bacterial or fungal, and then you know which treatment route to go down. You can start empiric treatment for one or the other whilst you're waiting for treatment. Culture, or if you have access to molecular tests.

Callum 33:36

Amazing power of a microscope. I guess in terms of etiological agents. So maybe we can focus on what you termed eumysotoma. So the fungal causes and is it called eumysotoma because fungal and fungi are, yeah. You, because you is Latin for like normal isn't it? So is that because that's like the classic because I'm thinking you mycotoma, I'm going to remember that because you carry it, so fungi cause it.

David 34:01

Yeah, the ewe bit was a true meaning, so the ewe mycotoma was a true mycotoma, as in reference to it being a fungal so true fungal mycotoma yeah, as opposed to actinomycotoma.

Callum 34:14

I just looked up what actino means, because I didn't know. I don't know if either of you know what it meant. Apparently Latin for branching, or radiating, pertaining to rays. So I presume that relates to the fact that actinomyces They're branching gram positive bacilli, so I guess that's another way to remember it. Actinobranch. In terms of the fungal causes of eumycetoma Alyssa, you've divided this up into ones that cause black grains and then those that cause pale grains. Is that, is that quite a good differentiator, David? Do you tend to see this species definitely causes black grains, this species definitely causes pale grains?

David 34:51

Yeah, it is really helpful. And again as a clinical clue before you even progress to microscopy that's really helpful because if you see black grains, then you know for sure that that's a fungus. So the bacterial grains are generally pale, white to yellow in color of this one species which will produce red grains, but they're generally white to yellow in colour. So yeah and then of the fungal causes they're either brown to black dark green mycotoma or pale green, which is again, white to yellow. So that, that is a helpful distinction, definitely.

Callum 35:26

We often do lists of organisms, I'm not sure if anybody finds them helpful, but it's quite fun to do them where we just read through the list. Okay, so black grains

David 35:35

Exela,

Callum 35:37

curvularia,

Alyssa 35:40

Scadosporium,

Callum 35:41

and then we've got pale grains,

Alyssa 35:44

madurai, Streptomyces

Callum 35:50

fusarium, and then on the actinomycetoma, so the bacteria, mostly bacteria, we've got pale grains,

David 36:02

nocardia species,

Callum 36:05

and we've got yellow to brown grains,

Alyssa 36:10

species.

Callum 36:12

And then red to pink grains.

David 36:15

that's action in Madura, pe

Callum 36:18

I've heard of some, but not all of these organisms. I think just looking through, the list there, we've, I think Liz and I, we've spoken before about Fum, aspergillus, gpo and then I think Jaye and I, a long time ago, did an episode in branching grandpa to Bai, and we talked about actino and nocardia. And a couple of other ones there, but is there any of those organisms, David, that's worth specifically talking about? Because I think Majorella is the most common, is that, is that correct? I

David 36:48

Yeah. Yeah, absolutely. Magella myomas is the communist cause. And yeah, it's, and then the others are all much less common compared to that. And then, I mean, out of the bacterial species and the cardia is, is very common That accounts for the majority of cases in parts of Latin America, Mexico,

Callum 37:08

always find Necardia such a fascinating organism because it is a bacteria, it's gram positive, but it grows aerobically rather than actinobacteria that generally grow anaerobically, then it has it's also partially acid fast, so seems to like encroach on everybody's territory, because it is a bacteria, but it this clinical syndrome, which is a bit fungal, and then it's partially acid fast, it's coming into that mycobacteria space as well, I think it should just stay in its lane, nocardia, so, Okay, so that's the list of organisms and you can, go and have a look at those and and other fungal episodes will pick up what those organisms are, but there's obviously a wide range of organisms that can cause it. So it makes it all the more important to get those laboratory diagnostics. off to try and focus in what you're going to treat it with. So how are we going to treat this in general terms rather than going into every specific organism? Because it will, depend on which organism you grow eventually

David 38:07

yeah, so treatment options are limited again, particularly in endemic settings. So, For the Eumysotema the main two agents are Itraconazole and Turbinafine. And I think probably the choice of drug is, more likely dependent on what's available. But certainly Itraconazole is considered first line. And so similarly to with Sporadrocosis, it's treating for prolonged courses until you achieve both clinical and treatment. mycological cure. you see, all of the clinical features resolving the sinus tract's not discharging. And if you repeatedly examine samples of the discharge, you should see that the grains are not there anymore.

Callum 38:53

And following treatment, what's the outcomes to patients have of the, I presume left with quite significant scarring and a disability despite this sort of microbiological cure, because you sent mentioned clinical improvement there too much of the lesions resolve?

David 39:10

So for actinomycetuma The treatment is more effective. So the cure rate is good, 80 to 90%. But for you, mitotamer, it's really not so good. It's more like 35%. And relapse, unfortunately, is very common. And so often amputation is necessary. The commonest area to have myostomies on the foot or lower leg. And as you were saying, it's a late presentation. If you've got a more advanced infection, more extensive it's been there for many years. It's not responding so well to antifungal treatment. It's likely that they will need quite radical surgery or amputation. Unfortunately um, 40 percent of patients end up having an amputation.

Callum 40:01

And is there any role for surgical excision or other surgical procedures earlier in the presentation? Or is that something that should be avoided?

David 40:09

Yes, so it should be avoided for actinomyocytoma because that can cause spread of the infection but for the eumycotoma there certainly is a role for it. If it's a small lesion, then often a surgical excision will be performed. early on followed by antifungal therapy. But for larger myositamines, five, 10 centimetres and above you would typically treat with antifungals first for six months or so then perform surgery. And then continue antifungal therapy.

Callum 40:44

Interesting. Okay. So it sounds like management's quite different depending on clinical syndrome. So we've got it. What about trachonazole or tribenophene for you, myasotoma? What about actinomyosotoma?

David 40:54

Yeah. So for actinomycetoma it's is usually treated with combinations of antibiotics. Quite a few different antibiotics are used. Often it's cotrimoxazole that's, it's commonly used and in combination with other antibiotics such as amoxicillin, cl, cla Dapsone and for More severe presentations, often the patients will be admitted for intravenous amikacin. And that will be given in cycles. So you'll have cycles of treatments including amikacin.

Alyssa 41:25

Sounds like treatments are, quite complicated. where people can get clinical advice about how best to approach these cases?

David 41:32

I guess the schools of tropical medicine and the hospital for tropical diseases in London would be good places to go to for advice. Yeah, if you do have a case, you're going to want to go somewhere for advice. I think that, yeah, schools of tropical medicine would be a good start.

Callum 41:48

And we mentioned right at the beginning, David, that you were doing the research in this area. I guess, you mind just talking us through what the current research questions are and what work is happening in this field? Because I guess with all these neglected tropical diseases, they are neglected and there isn't much data out there often on how to best manage these patients. what's the current, work that's being done?

David 42:12

Yeah, I mean, so there's research needed across the board really from sort of basic science through sort of public health. There is, there's an urgent need for, better treatments. And fairly recently there was the paper published in the Lancet ID on use of phosphorathiconazole for the treatment of eumycotoma. So that was published. Very promising that was randomized controlled trial or foster avoconazole against itraconazole. And it didn't show superiority, but it was comparable in its efficacy. But it's a once weekly treatment rather than daily for itraconazole. So there, there are potentially some advantages there, but that's, I think the first, RCT that's been conducted for eumycotomas, that was a very positive step. But yeah, there is there's basic science research ongoing professor Wendy van der Sande in the Netherlands runs a mycotoma dedicated lab where she, conducts research on in vitro testing antifungals against various, Myosoma causative agents using to animal models invertebrate models. And there's also more clinical work going on. So the work that I'm doing is more clinical epidemiological focused work in developing rapid diagnostic tests, point of care tests. So there is work on ongoing, but there's certainly room for a lot more.

Alyssa 43:37

And I guess one of the huge issues must be that in countries where Mycetoma is most common, there might be lack of access and ability to fund such lengthy durations of these antifungal and antibacterial therapies.

David 43:54

Yeah. I think drug availability is a real, issue. So particularly outside of clinical trial settings that is a real problem breaks in treatment. it was interesting in that RCT with fosforafilconazole the itraconazole performed, quite a bit better. then it was reported to, in the literature, the cure rate with nitroconzal was significantly better. And then the sort of 30 percent cure rate that's in the published studies having regular access to treatment is really important.

Callum 44:28

I've never heard of Fosuvaconazole before, I'll be honest, but maybe that's something that we can come back to Alyssa in our focused antifungal episodes So guess that's probably my isotoma. And we've got two more things left to talk about. So maybe now we can move on to chromoblastomycosis. So I guess the first question being, what is chromoblastomycosis? Because I think whilst a lot of people will probably heard of spirotricosis. Some people have heard of my isotoma or what? Commonly gets called Maduro foot. I suspect even less people will have heard of

David 45:05

Yeah. It's another of the subcutaneous infections in this case, it's caused by pigmented or melanized fungi or dermataceous fungi. And it's a very slowly progressive chronic infection of subcutaneous tissue. As with the other infections, it's usually on exposed body sites, extremities, and so feet and lower legs are a common site. And again, so in terms of the characteristic. Feature of the infection. It's the morphological form of the fungus in tissue. These pigmented fungi in tissue form what are called muriform cells or sclerotic cells, sclerotic bodies. which of the various organisms that can cause infection, they all produce that form. And that's what's diagnostic of this infection.

Alyssa 45:59

And you'd see that on microscopy, would you, with tissue or skin scrapings?

David 46:05

Yeah, absolutely. Absolutely. You can see that on direct microscopy or in deeper tissue samples, say on a skin biopsy. You can see those round, thick walled dark brown structures. You might also see, if you're doing skin scraping, as a very superficial sample, you might see pigmented hyphae in those superficial levels. But in deeper tissue, it's the muroform cells that you'll see.

Alyssa 46:30

And I guess just to recap the difference between fungi and Hyalohyphomycoses is that the Hyalohyphomycoses have clear fungal cell wall in hyphae, whereas the Dometiaceous fungi have pigmented, is it melanin, I think, in their cell wall. So when you look at them down the microscope, they, they have brownie, blackie. Cell, walls.

David 46:58

absolutely. Yeah. So there's pigmented moulds as you say,

Callum 47:01

And did we say where this occurs?

David 47:04

so it occurs, And throughout the tropics. But there are certain areas seems to occur more commonly in and humid areas or areas where there's a higher rainfall. In terms of reported case numbers. It's quite common in Mexico and parts of South America. Madagascar, I think, has the highest rainfall. Number of cases reported and there are parts of Asia as well in China where it's these sort of hyper endemic foci

Callum 47:34

yeah, I remember the talk that we had about it when I did the tropical medicine diploma and they showed a map of the country and said, it's here, but this isn't really useful because then they showed a map of the different regions and they were like breaking it down and actually were able to say it's really small localized areas within the country that were problematic and if you went just 10 miles down the road, it wouldn't be an issue. It was somewhere that was, quite mountainous and there was a lot of people that didn't have access to footwear and so there was a lot of, injuries. Is that right? This is god,

David 48:05

Yeah,

Callum 48:05

ten years ago now,

David 48:06

no, I think you are absolutely right. That's right for I think probably all of the infections with them within countries you see quite significant variation sometimes say for myasthema as well.

Callum 48:19

I

David 48:20

know, there will be some areas where eumysthema is quite common and other areas where axonomyasthema is much more common. And there are some towns or villages where sporic rucosis occurs and much more frequently. And sometimes that's the humidity, the altitude, the climate but it's not completely understood why they occur. I think, and the same with chromoblastomycosis. So you do see that variation in, numbers of cases, but also the causes of organisms, within countries.

Callum 48:52

Maybe just to briefly go through the etiological agents, there's a lot less here than there is in myosotoma. And this is already explained what we mean by that. And I don't actually know how to pronounce this first one. I was all ready to say it and I was about to say it What's the most common etiological agent, David?

David 49:08

Yeah, so Fonsecaia pedrozoi, you don't hear people say these names very often, do you? So it's,

Alyssa 49:14

No.

David 49:15

it can be quite easy to not be very sure of how to say them,

Callum 49:19

Glad you said it. yeah, And then we've also got, Cari.

Alyssa 49:28

Phyallophora varicosa.

Callum 49:30

So where are we with Chromoblaster? Have we done the clinical findings already?

David 49:35

Yeah, I think it's mentioned is it's very slowly progressive like Mycotema it, but even slower probably over many years. But the characteristic lesion is a verrucous plaque, so a rough warty plaque and as the infection advances, it becomes more extensive, so you can develop large areas of verrucous plaques extending across the skin. it doesn't invade deeper tissues in the same way that mysotoma does. so it's very much sort of skin subcutaneous where the infection remains localized.

Alyssa 50:10

And then can you get disseminated infection at all, like with sporothrex, or is this purely a cutaneous subcutaneous infection?

David 50:19

Yeah, I think this is purely skin and subcutaneous tissue. There are, I think, one or two reports of dissemination but I'm not sure if they were even convincing dissemination of infection or not. This is, in pretty much all cases remains localized to skin and subcutaneous tissue. But it can have, Quite high morbidity related to that, especially when it's more extensive you need to get. a range of complications, it causes quite significant scarring. So if that if that extends over a joint, for example, then you can get contractures of joints, fusion of the joints essentially. And not that it's involving the bone, the contracture can really prevent movement of the joints essentially. You can get it if it affects the The face, it can cause significant distortion. It can cause it tropion. And in chronic cases as with any sort of chronic inflammatory process in the skin, it can lead to the development of skin cancer. So squamous cell carcinoma. So you see that sometimes with the really chronic cases,

Alyssa 51:24

And do you have a, risk of secondary bacterial infection with these?

David 51:28

it can occur, but I think it's quite rare with all of them. I think secondary bacterial infection is not a common complication at all. Yeah. It depends partly on how severe it is. So if you've got early, very localized infection, then you may. You may opt to surgically excise the lesion as a very, complete way of treating it. If it's more advanced, that's not going to be feasible. So antifungal therapy is intracolonal again is the mainstay of treatment. But then similarly to sporotrichosis, you can then have other treatments alongside that. So again, your thermotherapy, heat therapy, and cryotherapy are often used. Alongside that, so there might be even if you have a large skin lesion that's responding to antifungal treatment, there might be parts of the lesion that aren't responding so well. And so treating those with cryotherapy just helps to get overall improvement.

Alyssa 52:26

And I had a really interesting lecture when I was doing my masters in medical mycology from Gordon Brown, who's director of the Exeter Centre for Medical Mycology and a fungal immunologist. And he became involved in research looking at the host immune response in chromoblastomycosis. And essentially, You might be familiar with this work as well, David, essentially discovered that these infections occur in healthy people, but occur when there's a defect of their toll like receptor pathway, which leads to an inability of their host immune system to recognize these pathogens. discovered that Omiquimod, which is a commonly used topical treatment for warts and BCCs and the like. Which is a toll like receptor ligand. can help activate this deficient pathway in these patients and clear the infection. And I think there's, I've put a link in the show notes this is subsequently being used in clinical cases as an adjunct to antifungal therapy to help clear these infections. Have you have you heard about this or had any experience of this at all?

David 53:41

Yes, I have heard of it. And I remember a patient, I think treated at St. George's Hospital, actually that was presented at one of our monthly dermatology meetings that have been treated with Imiquad and had a very good response. Yeah, as you say, it's something that we use in dermatology quite often for superficial skin cancers and pre malignant lesions, but I don't think it's commonly used in endemic areas but there is certainly some evidence from cases that have responded very well to it. And it's very interesting that mechanism of, let's say, being a toll like receptor agonist just how that works. It's very interesting.

Alyssa 54:22

And I guess this comes back to something we've talked about before, I think with Jeremy Day, who works with meningitis did a lot of work on repurposing of. drugs that are cheap and available and at how they could be repurposed for treating other infections that have limited treatment options.

David 54:41

Yeah. And I guess, It's a topical treatment as well there's advantages in that you're not, it has a lot of drug interactions, doesn't it? And so if you can use a topical treatment, and it's not going to cause problems in that way, that's an advantage.

Callum 54:56

I was just thinking, as you were saying earlier, Alyssa, about our WHO essential medicines list, which I guess is somewhat aspirational sometimes but in terms of treatments for these diseases that's on there. One of the difficulties I presume, about research in terms of maybe more of the fundings in that high income setting, but they're going to be using different antifungals and then you've got this data saying we use Posiconazole here, but that's not available in a lot of places. So you're stuck using Hitchoconazole, which is potentially less effective. Less well tolerated is my understanding,

David 55:27

Yeah, yeah, I think it's difficult when you've got, infections, which are generally quite rare caused by multiple different organisms which vary across different geographic areas, to try and set up a study. To evaluate treatments it is not the easiest thing.

Callum 55:47

Almost impossible. But I guess that doesn't mean we shouldn't try because we need the data, don't we?

David 55:52

yeah,

Callum 55:53

it's just how difficult it is to run a trial in a high income country on a relatively common disease with like clear diagnostics. I'm thinking about Staph aureus and how long it's taken us to get data for that. And now we're finally, we're getting good trials coming out. research has, we just say sometimes oh, there's no data, we need the research, but it's really hard really hard to study these things and get data that's actually useful, isn't it? Should we move on to talk about the next one,

Alyssa 56:20

so this is a group of the Entomophthorales, which are in the same kingdom as Mucorales in the Mucomycota kingdom. And my understanding is that these Moulds are mainly insect pathogens, but some of them cause diseases in humans. And these diseases include Kinetiobolomycosis and Basidiobolomycosis. Which are again, cutaneous and subcutaneous chronic infections. But I know very little about these infections or these pathogens.

David 56:58

yeah, these are, rare infections. I haven't seen cases of these myself. Yeah, and they are caused, as you say, they're caused by, the phylum that was the zygomycota, which is now being restructured. But in terms of the Organisms morphologically there's zygomycetes. So they again, talking about direct microscopy, if you were to look at them under the microscope they would look the same as the fungi that cause mucormycosis. So they're that group and they're very broad wide hyphae that have very specific features. And in terms of the actual infections, yeah, there are these two, two types, so you've got the one type which is referred to as rhinofacial zygomycosis, that's, or conidiobulomycosis so that's an infection that affects the facial subcutaneous tissue nasal subcutaneous tissue. Okay. nasal tissue and sinuses. And again, it's a slowly progressive infection which causes if you look at images of these cases, quite significant swelling and distortion of the facial tissues. And characteristically, they're quite hard, they cause a lot of fibrosis, fibrotic swelling, so woody, hard tissues so that's conidiobulomycosis and then the other form is basidiobulomycosis, which is a similar process, but it tends to affect a different part of the body. So it usually is around the thighs, the buttock sort of areas. There is some more fatty tissue but again, similar sort of clinical features with the hard swelling of the tissue.

Alyssa 58:37

And where are these do these infections predominantly occur? Is it mainly in tropical areas?

David 58:42

Yeah, it is mainly tropical. There are cases reported throughout Africa and and parts of Asia.

Alyssa 58:49

my colleague Dr. Jeremy Day, he spent Quite a few years working out in Vietnam and he had a fascinating case of c Mycosis in a young man who in with really severe disfiguring, ready, purplish, sw swelling of his. Of his face. And I think that, this poor man had, felt that he wasn't able to go out at all. Because he was so disfigured by this and ended up diagnosing it as committee or below mycosis. And due to lack of access to itroconazole or more that, that, that was prohibitively expensive. He used high dose fluconazole to treat him. And he's presented this several times and has shown the transition in this man's facial appearances from really disfigured facial swelling to complete kind of normalization of his face. So it resolved without any, any scarring or disfigurement. It was amazing.

David 59:50

Yeah, certainly. So you see some of the pictures of these cases you, you wouldn't imagine. That those sort of changes would resolve. So that's amazing.

Alyssa 59:58

And is it that mycosis, the Rhinoc facial form tends to happen in adults, whereas the city Blo mycosis, which is affects more the thighs and the buttocks, predominantly occurs in children.

David 1:00:12

Yes, that's right. Yes, conidiobulomycosis is more common in young adults and tends to be more common in male rather than females and basidiobulomycosis is more in children.

Alyssa 1:00:25

And we talked a bit about the diagnosis. So I guess it's in areas where this is clinically prevalent, it's mainly gonna be those clinical features, but also you said that these pathogens appear as MU's pathogens microscopically with the broad sort of past sparse septate hyphy. Are there any other diagnostic approaches? Would things like skin biopsy and histic pathology and culture be useful?

David 1:00:54

Yeah, I mean, I think that they are rare infections I think it is important to keep a broad distance. Differential in mind with your presentations like this. So I think a skin biopsy for histopathology is always going to be a good idea. And can certainly help in confirming the diagnosis, particularly if you're using fungal stains, silver stains and PAS stain, for example, to just to highlight the organisms that that can be helpful.

Alyssa 1:01:21

And what's the mainstay of treatment of these cases? these infections.

David 1:01:26

I believe the mainstay again is really was Intracornosal another option which can be used, not just for this, but for the other infections as well. For sporotrichosis, for example, is a potassium iodide that's quite commonly used in some areas. It's quite popular. It's quite popular in Brazil and it's inexpensive, which is another advantage.

Alyssa 1:01:46

And is that applied topically?

David 1:01:49

No, that's oral.

Alyssa 1:01:51

That's oral. Okay.

David 1:01:52

So I think the normal dose is four to six grams per day across across three doses, so it works out as a certain number of drops. Liquid drops per day.

Callum 1:02:03

Potassium iodide, yeah, understanding is that works by disrupting the fungal cell membrane and essentially it gets into the cell, there's release of free iodine ions, which then damage the fungal cell components. Although, it appears that the exact mechanism isn't known, is interesting. Some other people are suggesting it might the immune response. I guess, often fungi are so similar to us and they've got a lot of similar cellular processes, but maybe their mechanism of studying iodine is less, less effective than ours. So just to summarize what we've talked about there. So we've gone through The different molds that cause subcutaneous infections. So we started with Sporotrichosis and delved into Sporotrichosis Schenckii and also and talked about the the epidemiology of those both within the UK, but also globally um, the clinical syndromes and differential there being things like tuberculous mycobacterial infections predominantly as well as the fungal diagnostics, the diagnostics and the treatment. we talked about myositoma. This, chronic, subcutaneous disease, with the small granules and we talked about the difference between u mycetoma and actino mycetoma and the usefulness of the different, of the appearance of the grains that are coming from these lesions which are predominantly swelling with then sinuses and purulent discharge. The diagnosis being based on microscopy of the pus as well as histopathology PCR imaging also useful. And. Culture as well, and then the treatment involving different treatments between whether it's a fungal or bacterial cause and the role of surgery And then we talked about Chromoblastomycosis, which is, chronic cutaneous and subcutaneous disease with this varrocus lesions look warty or cauliflower in appearance. And the epidemiology of that and the etiological agents. Mostly being oh no, Fonsicchiae pedrosa, david, do you want to say it again?

David 1:04:15

Font's okay. At,

Callum 1:04:17

Thank you. For saving me there. We talked about the clinical appearances of that and laboratory with the usefulness there of skin scraping and microscopy. And treatment with, again, usually azoles, but some other adjunctive therapies and talk briefly about the importance of toll like receptor pathway. And then finally, we talked about the entomophorales which included things like conidiobolomycosis and basidiobolomycosis which are very rare and the differences in the presentation of those and treatment. So that's a summary of what we've talked about. Thank you so much again for listening. For joining us, David, do you have any sort of closing thoughts for our listeners?

David 1:04:57

Yeah. Thank you again for the invitation. it was great to come on. Talk about these infections. I think we did highlight importantly that they are collectively neglected tropical diseases, their skin and the treatment options are, you know, and there's a lot, improvement there hopefully for the future. I think we've covered most of the important points, on the importance of diagnostic tests, histopathology and. Approach to treatments, or as I said, antifungal options are limited, but hopefully that will change in the future. I

Callum 1:05:34

Anything you want to say, Alyssa?

Alyssa 1:05:36

I think,, this has got me keen to touch base with our dermatology department and think about how we can work more closely together, not just for these, this group of infections, but for our dermatophyte infections as well, that, supporting Yeah. diagnosis of these cases with effective culture and direct microscopy. and I think with this group of infections, with, we're only going to come across a handful in our career, but it's about being aware that there is this group of infections that's caused by fungal pathogens and just having an awareness of they appear, which areas of the world that they're prevalent in and, just making sure that we're thinking about culture and direct microscopy for these pathogens.

Callum 1:06:22

I like your point there, Alyssa, about touching base of your dermatology cause we are often asking them to biopsy strange skin things or give us opinion. And I find sometimes in infectious diseases that you referred patients with rashes as But you see a lot of, skin manifestations of infections and particularly cellulitis, you're looking at a lot. Sometimes you feel like a rash opinion service in the hospital because the dermatology colleagues are in my center are off site. And are also very overwhelmed with the amount of referrals are getting so, asked to see a lot of rashes So if you get an opportunity in training, maybe trying to spend some time in the dermatology department because it'll definitely be useful.

David 1:07:02

think it's a good area of overlap actually, it would be, it would also be good the other way around for dermatology trainings as well.

Callum 1:07:09

That's very true. If there's any dermatology trainees out there listening to this, there's a lot of opportunity for cross learning as we've had today from David.

1:07:16

Thank you for listening to The Idiots Podcast, the UK's premier Infectious Disease podcast. Questions, comments, suggestions. Why don't you send them into Idiots podcasting@gmail.com. Have a five star review in your pocket at Calm, and I would love to have it. Please drop it in your podcast player of choice. We tweet at idiot under pod, and if you want to donate to support the show, there's a link to do so in the description. But until next time, I'm Jane. I'm Callum. See you now. Now that the episode's done, we hope you learn and had lots of fun. So go forth and treat people with some of what you now know. Now that the episode's done, we hope you learn and had lots of fun. So go forth and treat people with some of what you now know.