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  • What are You Treating in a Foot Ulcer? Pathology and Treatment of Polymicrobial Infection
  • Lecture Transcript
  • Male Speaker: Speaker also not a stranger to us, Dr. Steven McClain who’s a pathologist and runs the McClain Laboratories who’s been a great supporter of ours in this special interest in dermatopathology which is in itself a great specialty and a great help to us. And so we’ve asked Dr. McClain to come to us to speak to us a little bit about knowing what you treat as podiatrist, making sure that your biopsying those crazy lesions that you see that are not responding the way that they should. And I think this is something that we as our profession needs to embrace much more, so I know. I don’t biopsy as much as I should and I’m sure Dr. McClain’s going to tell me why I should be biopsying far more commonly than I do, so I can make the accurate diagnosis. So let’s welcome Dr. Steve McClain.

    Dr. Steve McClain: That’s all I get? That’s a pretty weak response, come on. This is a great meeting. I am Steve McClain. I am a dermatopathologist from Long Island. I’ve been working in wound healing for about 21 years now ever since I’ve finished my training in dermatopathology. And I’ve come to see chronic wounds a little differently. Most of the speakers here when they talk about biofilm, they want you to think about bacteria. I want you to think about fungi. Fungi also produce biofilm. It’s not very well known. And so what I’d like you to think about what is it you’re treating in foot ulcer when you’re doing that good wound care. There are four objectives, I don’t have any conflicts or disclaimers. It’s one of the advantages of being poor I suppose. Normal feet are diverse by microbiomes. There’s all kinds of crad growing on normal feet. Everyone’s feet including yours. We’ve known since World War I that any infection, almost any bacteria in a wound will delay wound healing. Want to talk a little bit about clinical exam. I am a dermatopathologist so want you to think about the skin around the wound because that is important in treating the hole in the skin. And using the lab, I’m not trying to push McClain Laboratories, well of course I’m trying to push McClain Laboratories. But the point is use your local pathologist. They are available. You can talk with them. One of the test I’m going to talk about is just doing a simple stain of what is growing in that wound. Almost any bacteria not any one specific bacterium but any kind of bacteria in those wounds will delay healing. Okay. Our dogma is the chronic wounds are not infected. That’s nonsense. Complete and utter nonsense. There are bugs growing in these wounds. Well whether we call it bioburden, putrifaction, colonization or whatever all that blue crad on top of these edematous granulation tissue is microbial. There are fungi in there. There are bacteria in there. There’s a whole community of stuff in there. And the infection, the microbes love the vessels. Here’s one crawling right down into that thrombose vessel. Okay. All of that blue stuff growing right down into the vessels. This is what stalled healing is about. This is what those purple granulations are about that you need to debride. Okay. I’ve been studying these for about five years now. I finally got some podiatrist to simply send me some of your debridements. It was almost like I was asking them to – I don’t know change lives, change surgical techniques or something instead of just throwing the debridements. So I just say throw them into formalin. Send them to me. Okay. Well we don’t measure wounds very well. Maybe we throw a ruler and we take a picture of it. And so the question is what is that burden that thing that you’re treating in there? Well I use a dragon if you’re not going to find out what’s in there, then assume it’s a horrible dragon growing in there. And there are dragons are mysterious things and oftentimes and especially dragons we should never try and use a one magic bullet. Magic bullets don’t work on dragons. Let’s see. Here we go. Perhaps the best wound healer at least the best wound healing writer that we’ve ever known was Paul Brand. He was treating infection.

    [05:00]

    He says in all his videos, he says in his book treat the infection in the foot ulcer. Well if you’re not going to treat – if you’re not going to think of infection, let’s use the dragon hypothesis. So excise every spec of the dragon, the house meaning the callus and the root cellar, the part that goes down below where those vessels are. Chemically disinfect. Old school surgeons still use monocells in aluminum chloride. Those are fairly potent antimicrobials. They create a metal eschar when they contact collagen. Okay. Suppresory infection. He use gentian. He use the iodine. He also use peroxide. Peroxide is not an especially good disinfectant by the way. And he also was a big believer in soaking and cleansing all around the wounds, oiling nightly. I never understood the oiling part but I think maybe the next picture so we’ll show it. And offload, either cast it or get them off of it. Hippocrates first command on wound healing was bedrest for all leg sores. He recognized that 2300 years ago. Here’s a pretty typical heal ulcer. You’ll notice all of the flakes surround there. All dry skin is fungal. I’ve attributed that at the Harvey Lemont, that’s the first person I heard say it. But all of those flakes surround there need to be treated as well as the hole in the skin. Here’s an example of gentian triple dye and I have some of this dye available if anybody wants it. I have it for free. Just send me an email at info@mcclainslab.com. But when you’re going to use an antimicrobial like gentian or triple dye, you need to load it up. Put enough in it, 6 or 7 coats. Okay. Few more referrals from dermatology about bad reaction. There’s commonly an allergy to foot fungus and foot fungus of all kinds. This woman with the heels noticed the red around just above where the fungus is on the heels. And sometimes that goes all the way up to about three fingers breadths below the knee. Okay, normal skin. Not one chronic foot ulcer arises on normal skin. Usually all five toenails are pretty fungal and there’s dermatitis going up about three finger breadths below the knee. That dermatitis is part of the milieu of the leg. That’s a sick leg with these ulcers arising on. When you examine the patients, examine their hands, check out their face and their scalp. If they’ve got a big fungal loaded subderm and rosacea on their face, you know what their foots about before you even look at the foot. So when I mentioned about normal feet. On the left axis is fungal. On the right axis is bacterial. And the three of dots on the left, the top is plantar heel then the toe web and the toenail. There are more diverse, more numerous fungi on the heel than in the toe web. I wouldn’t have believed that. This is PCR data from the NIH. So the feet are adherently a microbial fungal community. Okay, is this going to work? Different colors. The green on the left is fungal for the feet of all different kinds. It’s not one particular microbe. It’s not one particular fungus. It’s not always dermatophytes. So microbes in normal skin. Well this is what it looks like. All your eccrine ducts are jammed full of microbes, fungi, bacteria, all kinds of stuff. You can disinfect the surface but pretty soon those will come right back up out of your eccrine ducts. IPKs and pressure lesions. I’ve started reading about Paul Brand during – when I was investigating IPKs. So now I’ve come to see that IPKs have about different parts. There’s the hard plastic part in the center, the one and then the skin looks like it’s got excessive we pronounced dramatic glyiphs. The ridges are pronounced. It’s Takeda seeing a callus. On the far right side below the number two, you’ll see more of those eccrine ducts. But down below the infected eccrine epithelium. The reason I mentioned this there is fungus on the lower left, that’s layer upon layer of PAS positive materials, some hyphae. And on the right is where that is merging with and that eccrine duct would probably be incorporated into that IPK if they’ve kept walking on it.

    [10:07]

    Well here’s one where there is a little brown nodule in the dermis underneath the IPK. Painful lesion and underneath there was this little ball of granulation tissue much like the PG that you see in an infected toe and an ingrown toenail onicocryptosis. And when I looked inside there, those pink blobs I thought were fibrin, the vessels look sick not really sure what to make of it. But when I studied for fungal antigens when I stained them red here, this is a trichophyte antibody in this granulation tissue. Fungal proteins in pyogenic granuloma in infected granulation tissue. Okay. There were hyphae up in the callous, they’re stained black here. Okay. So in conclusion they’re hard fungal pathologies can exert high pressure. They can in fact cause an infected granulation tissue below. This happened in a non-diabetic patients. When this happens in a diabetic patient, these things often goes south in a hurry. Their resistance is much lower. Well here’s that ulcer base in granulation tissue again. Let’s look at those vessels. I think I’ve got one more. Infected vessels and stalled healing. This is where all the exudates are coming from. The fluids coming out of the vessels. These are sick vessels plugged with fibrin but there is micro toxins, there is other toxins in here. There’s fungi that get down in here. Let’s talk about disinfection for a minute. I’ve got into this a few months ago. Amazing stories. The invention of disinfectants. Lis Franc, I couldn’t believe this when I read it. Read the bottom part there. Hence forward, there were no longer be any gangrene in hospitals. 1825, that’s how excited he was about bleach. Simple bleach, sodium hypochlorite. He also made kind of a putty-form with calcium hypochlorite and they would use that around the wounds. Okay. Fairly harsh chemicals. Samuel Weiss picked up on this and said, “The hands of the examiner must be cleansed with chlorine not only after handling cadavers but likewise after examining patients.” Okay. So he wasn’t talking about alcohol-based hand disinfectants, Samuel Weiss, he was talking about chlorinated disinfectants. Okay. Fungal osteo mycetomas and gangrene. We’ll move up a few years to 1860 or so. Mycetoma was described by Henry Vandyke Carter, 1860. I saw this case about four years ago. Someone plucked out what looked like a piece of drift wood bone out of proximal helix and there were fungi visible on the gram stain. Look at the far right, those are gram positives on top of the grain. On the bottom, it’s another grain that’s PSA positive. I couldn’t quite makes sense of it so others gram positive cocci, there’s fungi, fasciitis as osteomyelitis. But I kept reading about it because the grains are quite like those in mycetoma. What’s mycetoma doing in Suffolk County Long Island in 2010? This is Henry Vandyke Carter’s paper from 1861. And on page 207, he says, “I have a notion hospital gangrene is caused or aggravated by fungus.” This was before the invention of the gram stain. This was before the Civil War in fact. If you’ll notice on the far right, there are little grains in there, there are septate hyphae. Fungi are capable of doing this and yet we never talked about fungi in these wounds. Everyone talks about bio burden and biofilm and bacteria. Not one word about fungus. I’m having trouble advancing this. This foot would still be amputated today without much – so in my opinion mycetoma is a fungal foot ulcer with osteomyelitis. It’s the prototype. Lister used phenol. Lister was aiming to treat decomposition. He didn’t exactly understand it but he was right after Pasteur and he said, “They are particles of putrifaction which are getting into these wounds. And he treated them with phenol. And so that’s a very harsh chemical not if you diluted it out far enough. He was the master of dilution. You have to use the right strength according to what you’re treating.

    [15:00]

    By the time World War I came out there’s a big raging debate. Disinfectants are so harmful, they cause more harm than good, da, da, da back and forth. Much like we see today. Should you use something harsh in these wounds or not use something harsh. Lister had again two forms he used the liquid and he made it into a putty to use around the wounds. I never heard of using lime and linseed oil and phenol but that’s what he had compounded in the 1860s. He also thought that hospital gangrene maybe said to had been banished by the antiseptics system. They were pretty optimistic on what they were going to be able to do in the 1860s. Well this is truly amazing. Alexis Carrel, this book is available. Alexis Carrel on The Treatment of Infected Wounds. Probably the biggest wound study that’s ever been done. In World War I, there were 30 million casualties on both sides. 10 million deaths, 20 million injuries. The Rockefeller Institute, put forward all kinds of money several hospitals, there were more than 80 hospitals in France just for treating the wounded. Okay. Big effort. And in the midst of all is they still found time to do some basic research. This was included in the book. And so if you look the beginning on the 9th on the far left, the first three days we call that the inflammatory phase. The next couple days would be called granulation but where that breaks at day 5 or so that’s the end of the lag phase. And then the beginning of contractions, so they knew all about what normal wound healing was back then. They showed essentially the same occur for human wounds once the bacteria were gone. And when they treated with deacons, now when I say deacons I mean neutral hypochlorous acid. They’re the ones who invented it. They’re the ones who made it, they tested 250 different compounds during the war. Six times a day these wounds got treated. And who was the director of nursing? Alexis Carrel’s wife. And she was a scrub nurse, well-trained. She had only been married about a year when they got called into action in World War I. But it says, nurse using a pinchcock and so instilling antiseptic fluid. Okay. He used fenestrated catheters, superficial wound on the left. But look at that penetrating injury on the right. And that thing that’s layered around there is a felt dressing that was used to absorb the antiseptic. Okay. This is hypochlorous acid. You put too much of it obviously you get problems with maceration so they had to limit the moisture exposure but you had to get the disinfectant to all parts of the wound. Remember, they had no antibiotics. This was it. This is all they did to treat it. They put them all on bedrest by the way. But the real game was they defined just how many bacteria does it take to prevent wound closure and it takes only about two. Two per oil microscope field, that’s a thousand X lens. By the way this is available if you go advanced books search on Google, you can get this book for free. It’s about 260 pages or so. This particular field I’m showing you has more than 50 bacteria in those big things are neutrophils. And so they graft every patient got a graft so on the bottom, on the far left you’ll see a line. That’s about 70 bacteria per high powered field. And then you’ll see it breaks when they began using the disinfectant. And then it gets down below 1 and the wound’s healed. Bacteria came back up in the middle that’s wound reinfection. And they monitored these things. Everything that looked bad, look foul they would go and swab that. So the nurse, the Director of Nursing was also in charge of the laboratory, should say, “Oh there’s too many bacteria,” and so they would adjust the disinfectant. They also graft every wound every four days. Put a piece of cellophane over and plotted it out and use the planimeter to exactly measure wound areas. We should be doing this today, but we don’t. This going to work. Okay. This is what reinfection looks like. This is a 3-month wound.

    [20:00]

    Now let’s started it out with disinfection. There were high numbers of bacteria, put the disinfect in, went to low bacteria. The wound began to close rapidly. Remember, these were all fairly acute wounds in soldiers’ young men. And then it stalled. In fact, it goes up in the other direction. And there are excessive numbers of bacteria. Delayed healing with reinfection. By the end of the world, we were much better off than we were at the beginning. This is the first soldier injured in the French army lost both of his legs. They even healed some old foot wounds. This one had been present for more than six months. Now it started out, they had to disinfect it but once they did, it rapidly closed. So for some reason we say these wounds are not infected. In my experience that yellow stuff is just it’s fungal as a mycotic nail. It’s made out of the same stuff, four to five cells layered with PAS positive stuff and either candida or dermatophytes or sometimes just – I can’t tell what kind of fungi are in those. The crad goes out, put it in formalin, send it to your favorite pathologist. You’ll find there’s all kind of spores all over. They look like bacteria, layer upon layer of fungi. Big fungi, giant purple ones this is now you see in blue stains so we get carbohydrates plus used in there. In the center and in the necrotic stuff which is always on my debriding, we never look at that but look at – you see those purple threads in there. Fungi. Fungi will find that water. They will find the food and grow in there. So common treatable causes of delayed wound closure, any kind of foreign body of course, you know that. Infection of any kind, any kind of bacteria, and cancer. Let me show you another. So to the pathologist, I want you to send your debrided tissues. Strike up an alliance with your pathologist. Start looking at what’s in there or if you’re not sure what’s in there, you want to know if there’s bacteria in there. You want to know whether you should keep treating it. I guess if you’re using the silver compounds that looks like a pretty decent method. Almost any kind of disinfectant that you put into these wounds is beneficial. It doesn’t matter whether it’s chlorhexidine, silver, hypochlorous acid, gentian. It’s important that you clean out the wound completely and disinfect it. Other kinds of infections. This is tuberculosis. We don’t see much tuberculosis but it looks like a cancer almost, doesn’t it? Candida can do something quite similar especially – fungating candida is a pretty common. When you see that, you should think candida. Between the fourth and fifth toes are often loaded soft korns loaded with candida. The purple this is a PAS and now you see in blue stain. All the pink stuff, all the red and all the purple stuff is fungal. This is one I couldn’t hardly believe. There’s a big plaque of fungus growing on top. It’s not quite cancer but you can see a callous rim around it. I’ll show you. So much tissue I had to put it in two different sets. On the left, there’s all the superficial stuff and on the right is this – number two is this tissue. Looks almost like cancer. I have sent this onto the memorial just to be sure. I didn’t call it cancer. Pseudocarcinoma it is, okay. But this is what you have to clean all of that out of there. If you have the stalled healing at the edge there. Sometimes it’s candida either driving a wart or candida driving the healing epidermis but it can look just like cancer. We’ve talked about clinical exam. Id reaction. Think about adding a steroid to your antifungals. Here’s my recipe for ulcer. Symbiotic fungal infection on the nails with flakes, dermatitis and id reaction, the redness around those toes. And then some kind of breakdown. It doesn’t matter what sets into motion, the microbes will find the hole. They will find a way to that moisture. Now, when I sent this back and said it’s fungal the podiatrist says, “I’m worried about being infected,” so I’m going to treat them. I said, “Good.” She calls me back a month later and said, “You know, he’s not getting any better on bacterial.”

    [25:02]

    I said, “Bacterial?” She says, “Yeah, we both agreed it was infected.” I said, “Yeah, I told you it was fungal. I can’t say anything about bacterial.” Put some Lamisil the patient got better. Fortunately, this patient was not diabetic. If he had been, probably would’ve been gone. So fact, fungus infection in foot ulcer can invade like cancer. Just because you don’t study what’s in these debridements doesn’t mean it’s not fungal. If there’s an overwhelming fungal infection all the way around it, you have to think about the fungus getting in the ulcer. Okay. I already mentioned this. Reinfection is common and what they did during that war was to up to disinfection. They didn’t have any oral antibiotics to go to in 1915. And they got kinda creative about making sure that their disinfection got to all parts where the microbes were. So in summary, the normal feet are loaded with microbes. The clinical exam should include up to the legs especially that part three finger breadths below the knee. Because that dermatitis and that fungus growing on that dermatitis is going to be the causes of one of the stomp infections later on. You have to begin treating everything below the knee, in my opinion, with antifungals. One last thing here. Disinfection. The notion of disinfection is that it’s not specific, it’s broad spectrum. It’s generic. You’re using non-selective chemicals. They’re lethal to all microbes. Well you’re using things like mono cells, phenol, chlorine, PHMB, iodosorb. Another great product, okay. So any of these materials are pretty good at suppressing the microbial growth in there. I’m happy to look at any debridements you want to send me but the point is it also helps you to tell which you’re debriding down to. Are you getting down to normal tissue? You should know what normal is like. Now, Dr. Brown were alive today and he heard me talking say, “Oh that’s a mix fungal foot ulcer, I see.” So maybe I need an antifungal to the oiling or maybe I need to add an oral antifungal be it Terbinafine or fluconazole in the case of candida. Okay. I’m sure you could use those. If you needed them in the stalled wound. Whatever it’s stalled, you can be sure there’s a reason why there is not healing. So I’m going to make a plea. I’m going to ask you to stop treating dragons. I’m going to ask you to excise, completely disinfect and treat the infection that’s wounded preparation. That’s how you prepare a wound is to get rid of all the infection suppressed the microbial growth and once you do that, then the natural forces of wound healing will come in to play. You may have to do other things. You may have to use a wound – you may have to use a silver dressing. Whatever it takes don’t stop that one thing, add something else. If you’re going to add an oral, that’s fine. If you’re going to treat the whole leg from the knee down, treat the whole leg. You’ve gotta treat the skin around the ulcer as well as what’s in the ulcer. Okay. Thank you.