• The Infectious Components of the Chronic Foot Ulcer
  • Lecture Transcript
  • Male Speaker: Is the cheering going to start soon?


    Yes. Okay. Let’s see. This is actually a little bit of science. I know podiatrist by and large don’t like science but I snuck it in here on you. It’s true. More frequent debridement leads to faster wound closure and I’ll show you a paper on that. It’s a good paper. To segue into it, there are infectious components to chronic foot ulcer. I’ve been studying wounds for 25 years now but about 10 years ago, I began to work with podiatrists, because it seemed to me that the podiatrists were doing the bulk of the ulcer care in my community. I got no traction with the university but I did get traction with the private podiatrist. Okay. The objectives, I have to put these at the beginning but I have each one of these later on. There are some free references. You know what free means, right? You don’t have to pay anything for these references. One of the best ones was done during World War I. Alexis Carrel and Dakin were actually part of a big medical research team that was sponsored by Rockefeller. The whole thing. They paid for a ship even to make unlimited supplies of chlorine from seawater. They had unlimited supplies of Dakin’s solution. That book is available, "Treatment of Infected Wounds". It’s available on Google Advanced Search. For those of you who are not real big into antiseptics, there is an argument for using antiseptics in chronic wounds. There’s two of them here that I’ve given. One is by Kirsner if you want to write those names down, and Fumal. This is the paper by Fumal we’ll go into in depth. That talks about the paradox of using antiseptics in wounds and especially they were interested in the polymicrobial flora that were in leg ulcers. The paper by Keisha Findley, this is kind of a highfalutin one done by PNIH. Basically she showed that the feet have the greatest diversity of fungal populations of anywhere on the skin, especially the heel, the toe and the web space. The last is the paper that forms the title of this talk and that’s by James Wilcox, where they looked at 312,000 wounds. Okay. I did get my first microscope at age seven for Christmas. That’s a long time ago. I am from the University of Missouri where I graduated. Trained in pathology in Vermont. Paid off my medical school loans and then went back into an academic life with the dermatopathology with Bernie Ackerman. But since ‘94, I’ve been working with the wound research group at Stony Brook and there they study diabetic wounds, burns, any kind of complicated or some kind of new graft material. They’ll send me some material and say, “Does this have an affect in a wound?” We’ll put it on some animals and we’ll try and get 10 to the 6th or 10 to the 5th microbes. This is from some of the DAC technology and this is not antiseptics per se but it does bind to microbes. It binds to fungi. It binds to bacteria. It’s a little bit different kind of an antiseptic, one that inactivates microbes by binding to them. We started our own lab in 2004 and the goal was to provide reports with photographic proof. In this one, this is a proximal phalanx bone was sent in and you’ll notice in the bottom left or the bottom on the left too, there’s clearly fungus and that’s even on a gram stain. But all the other ones, there are grains of gram positives and PAS positives and PAS negatives and gram negatives. There’s all kinds of microbes in here and I thought, “Wow, that’s pretty strange.” But this is what my reports look like. I wanted to try and show what’s in the tissue. But the interesting part is the grains. The fungus is destroying bone. It has grains like mycetoma and yet it occurs today at Long Island. Now, we don’t think about mycetoma as a common disease today. It was described by Henry Vandyke Carter in 1860, wrote a second paper in 1861.


    If we zoom in a little bit, you’ll see that there’s actually some septations in there. Now today we say mycetoma is a bacterial disease. It’s caused by a filamentous microbe, [indecipherable] [05:12] Actinomyces, you name it. But none of those organisms have septate hyphae in them. It still remains a bit of a mystery. But in the second page of that second paper, Vandyke Carter says, “I have a notion, hospital gangrene is caused or aggravated by fungus.” That sort of jumped out of me when I read that even though it’s almost 150 years old. Now hospital gangrene referred to the gangrene that people got after they went in to the hospital. They had an operation. They had a surgical repair. Before Lister, before disinfection, people routinely got infected and it was called hospital gangrene. It was a common cause of death in the 1800s. Okay. I told you I’d talk about Keisha Findley’s paper. Normal feet are polymicrobial. This is one of the graphs out of that paper. Get it free, you can go to Nature, you can download this, no problem. On the left axis is fungal and you’ll see there’s fungal heel, toe web and toenail. Out to the right axis is bacterial and on the hands, hypothenar, volar forearm, etc. There’s more bacteria on your hands. There’s more fungi on your feet. All you really have to do to your foot is add water. The microbes are already in your skin. They’re living in your eccrine ducts, part of your calluses. They’re in your toenails. Many of us have it. All you have to do is add water. The second point, any wound infection delays healing, even polymicrobial infections, even small grain infections, where you don’t have 10 to the 5th organisms or you don’t have a predominant cause. We’ve known this since World War I. Hundred years ago, this was discovered. Let’s talk about that. What I found was, this is again Dakin and Alexis Carrel’s work. Only one or two bacteria per microscope field are enough to prevent wound closure. One or two bacteria. What they did in that study was to do essentially a gram stain. That was their wound method, their assessment of the wounds. One of two of their methods. They would graph. This is a graph. You’ll see that about where the red cross is, the bacteria were high and then the disinfection took hold and the bacteria went down to some low level. That low level that was critical to be considered surgically sterile was about one bacteria per three oil fields. That’s a thousand x field. Okay. That’s the highest power we have on the microscopes. The little bleep on there is a sign of reinfection. The treatment they did was Dakin’s Full Strength. Now the wound area from 1917, you see it goes up until a point of disinfection where the red cross is. The wound actually got worse for this patient and this is one patient. And then it goes down. Okay. The wound closes when the bacteria are gone. In fact, they said you can close the wound surgically by suture if you get it down to the surgically sterile levels for three days in a row. Okay. Now what can the pathologist do? Our last speaker was a very good speaker. I enjoyed his talk. But you notice he had the group therapy, right? Everybody’s involved in it. But there’s never a pathologists on those things and there wasn’t in his and I’m not blaming him but the same thing is true. Robert Frykberg can tell you the same thing. About six years ago, I said, “How come there’s never a pathologist on a wound healing group? Never.” Well, I guess I’m a talking pathologist. I want you to be able to see what biofilm looks like and what you’re trying to remove. If we look at the bottom of a wound, all that blue stuff that looks like it’s growing down is biofilm. Not too many bacteria. There’s just the sprinkling of them. Okay. The red is the thrombosis. The vessels beneath that biofilm in that granulation tissue are all plugged. Okay. There’s an effect on the endothelial cells. You can see a little bit of thrombose and a vessel wall. But the blue of the biofilm is down there. This leads me to Fumal’s paper talking about the paradoxical effect of using disinfectants on chronic wounds or polymicrobial.


    They described this necrotizing vasculitis instead it was related to the microbial load. Focal necrotizing vasculitis was related to the microbial load. These vessels are plugged. This is part of the reason why they won’t heal. Those vessels will not heal. Okay. They’re infected. Okay. Povidone-iodine increased the healing rate and reduced the time to healing. Now, the interesting part about this study and you probably can guess what the interesting part is, they actually use the pathologist as part of their team. They biopsied the wounds, they studied them under the microscope and they did bacteriology. Not only is it unique because they have pathologist, all patients had two wounds. One got treated with hydrocolloid. The other got treated with one of three disinfectants, either silver sulfadiazine, chlorhexidine or povidone-iodine. They found povidone-iodine was the best because it not only improve the healing rate, it reduced the time to healing far better than the silver or chlorhexidine. Okay. All three decreased the bacteria but the povidone was less toxic for wound healing. Okay. They noted the vasculitic changes went away. The microvessels themselves were not harmed but those thrombi went away. Did not impact the dermal dendrocytes or the fibroblast. It appeared to be their conclusion was an efficient compound in these respects exhibiting a positive and relevant clinical. What about more frequent debridement? I know ITs deal with that. This is from James Wilcox. It’s from Jim and it’s also available free. I think this is Graph 5 out of their paper. Basically, it’s a showing of three different types of debridement. One is debridement every two weeks, one is somewhere between one to two weeks and the other was on the order of one week or more frequently. If you zoom in down at the bottom and this thing runs out for about three years, this study did. I can’t show you but the left, the black one is the debridement once a week or more frequently. The two on the right, the green and the orange are one to two weeks or two weeks and beyond. Okay. At every point, more frequent debridement, you’ll get faster closure. If you went out at the top of the black curve there is 250 days. These really were chronic wounds. But at every time point, the black, the more frequent debridement led to faster closure. Statistically, that’s significant. There’s 3,000 wounds. This is from the Healogic Company I think. I have no interest in them. My goal, I would hope to get you to stop treating dragons and to biopsy some of these. That’s what I’ve been trying to be after some of my podiatrists is to get them to biopsy and let’s see what’s in these wounds. Why aren’t they healing? Now, if you want to treat dragons, that’s fine. Keep treating the dragons. If you don’t want to know what’s in here, that’s fine too. That’s a time-uttered method. We usually just debride it. We throw the stuff in the brown can. Think about a goal. The goal would be to excise that infection, to disinfect it and from my perspective, to treat fungal infection. I’ll say, “Well what? Nobody in there right minus Steve has talked about fungal infection.” Actually there are a few people who’ve talked about Candida and ulcers. But fungal infections are hard to diagnose. I wouldn’t ask you to send that if you don’t believe me, send the dragon in formalin to pathology and just say rule out infection, rule out cancer. Whether it’s a nonhealing wound, you can biopsy it. You can excise it. You can repeatedly debride it. Put it in formalin and send in to the lab, rule out infection, rule out cancer. How often is cancer a problem? Probably less than one in a thousand. But there’s a poster out there about squamous carcinoma that confounded some people. In chronic wounds, you should think about it. Bonus point. Just send your pathologist a clinical photograph, they’ll love you. Okay. Let’s talk about disinfection a little bit. If you ask me about, what is all that flaky stuff around that wound on this heel? We don’t often talk about what’s going on around the ulcer. We’re more interested of what’s in the ulcer.


    Here’s a simple disinfectant or an antiseptic that was applied. It’s called gentian triple dye. We used this on babies when I was in medical school. Every almost every baby, 4 billion Americans got treated with triple dye. It has three dyes in it. But the FDA still considers it a category two agent, needs more animal testing. I guess 4 billion humans is not enough. What about treating the infection around the ulcer? That comes into play and I’m going to show you. This is a picture of my father-in-law’s leg. Now, this is the way he was getting better. He fell on the bathroom. Sixteen-centimeter wound. Had it sutured up. He's concierge and he’s a wealthy guy by the way. Concierge’s doctor took out the stitches after two weeks. I would say to most of you no, not to take the stitches out too soon in 80-year-old man. But this doctor didn’t. The thing because it looked far worst than this. I came on the scene about two days before this picture and applied triple dye to it. Not only to the base but all around it. Now I want to point out the stuff around it. Those flaky things with the little rim of blue stuff, which is biofilm is all around the edge of the wound. Now he didn’t start out with a fungal infection but he has it on his toes. He has venous stasis on his legs. He’s got all kinds of flakes down there. This flaky stuff was all around the wound. Now a week later, just kept putting on the triple dye and cleaning it off just good wound care, all that flaky stuff went away and the wound begin to close. I’ll point out another one of my tricks. I hate to be on the green team. This was the sore back stuff. These are Avery 3/4 inch dots. If you’re going to serially photograph something, put a measuring tool at it and Avery 3/4 inch dot is exactly 19 millimeters. I used these dots. If you can’t tell if a wound is not calibrated, you can’t tell if it’s closing or not closing. But almost all that flaky stuff that went away. That was Candida growing up around there by the way. Okay. I want you to biopsy, debride and excise now in healing wounds, send it to the lab in formalin and say rule out infection, rule out cancer and we’re going to do a couple of things. Now in the time remaining to me, I’d like to talk a little bit more about the skin around the ulcer. I’ve already shown you how within a few weeks a dehisced wound can develop a Candida infection on the skin around it. The young woman there is not meant to be sexist, not meant to be anything other than an example of normal. You can imagine these legs do not belong to her. Okay. I think that’s pretty obvious. But how many of your patients with foot problems have this leg eggs in the problem and it often goes up to about three-fingerbreadths below the patella, about where you do a blow the knee amputation. If you look on the far left side, the patient’s left leg, there’s all kinds of flaky stuff on there. How about this? It’s pretty common. You see this over and over again and yet we just call it dermatitis instead of saying there’s a fungal component to this leg and to this ulcer we just tend to ignore that. Okay. Biocides. Biocides in the general class we’re talking about are antiseptics, disinfectants, preservatives, sterlings. They all have different durations of action. They’re all dependent on the active disinfectant getting in to the microbes. For my father-in-law, I actually used Dakin’s every four hours for the beginning and that cleaned it right up. I used povidone. I used iodosorb. I used iodoform and a sinus in there. I used plenty of triple dye. The triple dye lasted some of those places. It only binds to nonviable tissue. It binds the stubs. It binds the flaky stuff. It binds the biofilm, gram-positives, gram-negatives, fungi, you name it. That’s the triple dye. This is from Carrel’s paper. In World War I, they had no antibiotics. But they have a bunch of Dakin’s. They would put these tubes into the wound to ensure that the disinfectant got into every aspect of the wound.


    Okay. Now in those self-respect the dragon, fears of saint with only one weapon. For example, that dragon was named fungus and the spear was named penicillin, would you expect a response? Probably not. Okay. I studied the methods of Paul Brand because I thought of all the saints among us and all the people who have been good wound healers, Paul Wilson Brand was probably right up there. If he wasn’t the best, he was close to the best. He's certainly an inspiration for me. If you listen to Paul Brand’s videos, when he talked about treating these ulcers with total contact cast, he was talking about treating the infection. He was treating infection. Now I know it’s not politically correct to say these are infected. But the fact of the matter is one of the best wound healers of all time considered these all infected. His method was to excise every spec of the dragon in the house because we don’t know what dragon in the house are composed of. Chemically disinfect. How many of you use mon cells to stop bleeding for example? Mon cells, ferric subsulfate is a very potent antimicrobial. He used plenty of iodine. He used plenty of gentian. Again gentian and iodine are two fairly potent disinfectants. He’s a believer in soaking and cleansing around the wounds and oiling daily if he didn’t cast them. Of course many of the time he would cast them. And you know about no bed rest. Bed rest goes back to Hippocrates actually. Hippocrates was the first person to notice if you got a person off their feet, their leg sores would heal up. It’s still true today. Now some of my friends who are podiatrists have told me about the podiatry secret and I’ll pass this along. This is not in the literature. But when they run out of things to do and they don’t know what else to do, they’ve been known to try Lamisil. Believe it or not. Some people get benefit. Would you think about trying topical oxygen? Well now you would if everything else you’re doing is not working, I considered trying that. I’d also consider trying Lamisil. The recipe for ulcer in the time remaining, you know how common neuropathy is and there’s probably more of it or as much of it due to alcohol is there is due to diabetes mellitus and way more than is due to leprosy. But the neuropathy in terms of the concerns for foot ulcer is pretty much the same no matter what the cause. They can’t protect themselves. Their skin breaks down whether it’s due to pressure or a crack or a chilblain. Most patients will have some kind of symbiotic and fungal infection of the nail. I don’t think you can see it but in that middle toe, there’s all kinds of little flakes around there. The little flakes happen to be the infectious particles. There’s bacteria and fungi living on those. We've talked about the dermatitis. Now I have a minute 42 seconds. I want to show you a case I saw about three months ago. This is not a gangrenous toe. But this is a toe that kept ulcerating and after the third time the podiatrist said, ”I’m taking it off.” So we did. He sent it to me. This is the base of the toe you can see the ulcer callous. This is a slice through it. The nail is on top. You can see the joint in the middle. On the left at the distal part is where the ulcer was. There was an ulcer, there was onychomycosis, and there was osteomyelitis here. I’ll show you three different parts. This is Candida. I know Candida doesn’t grow in the toenails. Actually about 15% of what I see in onychomycosis is Candida. This is in the ulcer callous PAS on the left. This is a new stain we developed for Candida. It’s an antibody stain. The curious part was that in the bone, well away underneath the ulcer, about 3 or 4 millimeters away after they're healed, there were codified flakes that were jammed into the blood vessels. Let’s see. On your right, the red is actually an indicator of Candida. Okay. Those little blue dots on the left part where the arrow is, actually stain with candida. Some of these patients actually get a direct counting impact and drive callous bit into the distal toe. This is relatively hypovascular toe.


    Okay. I think that’s about it. Even though some of the evidence goes back to World War I, there’s still a need for disinfecting this feet. If you’re not sure, the patient’s not responding, then there’s several ways you can increase the disinfection. Number one is to increase the strength of the concentration. But number two, with Dakin’s you can increase the frequency addressing changes. It makes a big difference whether you dress them twice a day because Dakin’s only last about four to six hours. If you dress them twice a day, you’re getting twice the disinfection. The answer is not always to use the longest acting disinfectant although that’s one approach. One might be to use a stronger disinfectant or the other would be to continue using the one you're successful at but do it more frequently. This is a picture of my granddad from World War I when he went in the army. These leggings I’m convinced are part of the problems that they had with trench foot. The bindings that they had on their feet. Of course these guys were walking around in manure. They lived in manure. They lived with the war horses. He was actually a muleskinner in World War I. That’s my granddad. I’m pleased that you allowed me to present today. If there’s any questions, I’d be happy to take them. Thank you.