• Infectious Etiologies in Chronic Foot Ulcer - The Use of Long Acting Disinfectants for Wound Management
  • Lecture Transcript
  • Male Speaker: ____ you on now with Dr. Steve McClain talking about modern treatments of delayed wound healing and using a pathologic basis for surgery in antisepsis. So Dr. McClain is an MD dermatophatologist who did his fellowship at New York University. He’s a socio-professor of dermatology and emergency medicine at SUNY at Stony Brook. His research interests are in wound healing, malignant melanoma, and pathologic informatics. So please help me welcome Dr. McClain.

    Dr. Steve McClain: I’m waiting for my standing ovation. That’s pretty marginal. I am a pathologist. I have my own laboratory. I’ve been working in the field of diabetic and burn healing for more than 22 years now. Who put this on here [laughs]. Somebody slipped this on here.

    Female Speaker: Happy birthday.

    Dr. Steve McClain: Okay. The person on I guess it’s the right, the long-haired fellow is a rock musician. He’s the co-owner of McClain laboratories. The part I’m going to spend time on today has to do with the issue of the inflammatory phase of these wounds. We call it inflammatory phase but in my opinion it’s a smoldering infection phase. That’s the problem. This is a sample from a wound base. All the blue where you see a dipping down into the dermis, it’s not dermis anymore. That’s granulation tissue. The little red blobs are thrombosed vessels, but the blue is the biofilm. It’s the bio slime. It’s all the crud on top of the wound. It goes right down into that red zone which is a thrombosed vessel. This is the target. I won’t call it the enemy but it’s the target. It’s the part that has to be cleaned up. Now proving that’s infectious, proving there is an infection in here is a little bit harder. But after just a couple days, one debridement and bumping up the disinfection from quarter-strength Dakin’s to full-strength Dakin’s, that blue stuff went away. Now this is from a relative of mine. You got to wonder about anybody who’s got a pathologist for a relative I guess, but who have failed. He fell on the bathroom about eight weeks ago. Went straight to the hospital. Got stitched up. Spent three days in the hospital. Came home. His concierge doctor took the stitches out after two weeks. All my plastic surgeon friends say four weeks on the leg in an old man. I don’t know what your experience is but I tend to believe it. It dehisced and now he’s about six weeks after that and he’s got an infection. Okay. The objectives. Normal feet are polymicrobial. You should know that. There’s all kinds of data that the skin of the feet is probably the dirties area on the external surface of the body. We’ve known since World War 1 that any microbes in those wounds will delay healing. I’ll show you a little bit of that data. What do you need a pathologist for? I know you got a plenty of people on your wound team. Pathologist are helpful in seeing you and allowing you to see biofilm and how effective you are at surgically removing. I’ll spend a couple of minutes talking about the science behind this infection. My numbers just went up to 25 minutes. Did I get some bonus points in here somehow? I don’t know if I did. Okay. For those of you who are students and I know there’s two students right over here, write these down. These are references you should know. Alexis Carrel wrote on the treatment of infective wounds during World War 1. Robert Kirsner at Miami has written extensively on the controversy of antiseptics in wounds. This paper by Fumal was done at the University of Miami and showing basically that even though some of the chemicals we use in chronic wounds maybe relatively toxic to cells, they can and are capable of promoting healing. Keisha Findley, that’s the paper on topographical diversity in the skin which shows the heal actually has the greatest number of fungal species of any part of the foot. The heel, then the web space, and then the toenail. Last, James Wilcox did a study on some almost 400,000 wounds and on the frequency of debridement.


    Now all these references are available online and for free. You may have to search in Google advance book search to find the Alexis Carrel patent book. I did get my first microscope at age seven. I am an MD from Missouri. I did my pathology residency and so on. When I started my own lab in 2004, I did so because I wanted to be able to put pictures and reports. Where I work in the past they didn’t really want to support that. One of my reports would look something like this. It would include the gross image in the blue. Can somebody tell me whether that’s a left proximal hallux or a right? I don’t know which one. It says it’s from the left. But in this chunk of bone which came out in the office, there’s clearly fungal species in there. Then there were these grains staining gram positive in the upper or PAS positive in the lower right. There’s a whole gamish of organisms in the base of these wounds. So it woke me up that there could be fungus in these wounds. Certainly fungus here. People want to ignore the presence of fungus on the foot. I don’t think you can do that. Why is that? We want to ignore some of the principle organisms that are growing all over the feet and all over the legs. So if you want to ignore them and treat a dragon, that’s fine. But recognize that some of these organisms, especially fungi, have potential to impact these wounds. I personally think you should excise and disinfect and treat. Bring some treatment in towards the fungal infection. Not just the fungal infection in the wound but the fungal infection that’s all around the wound. From the toenails, the web spaces, the plantar, all the way up wherever there’s a leg dermatitis, I would expect you to treat those. If you want to help your pathologist out, you like a pathologist, put some of that dragon into formalin and send it to pathology and say rule out cancer or rule out infection. They will be happy to do so. Brief instructions for those of you who aren’t used to using pathology. Biopsy. Get some tissue whether you excise it, biopsy it, repeatedly debride it, and put it in the formalin. It’s not that hard. Send it to the lab. You just say rule out infection, rule out cancer. It doesn’t have to be any more technical than that. The cancer is one in a thousand, but it does happen. Fungus will grow on top of cancer. I’ve had two melanomas this year and three squamous cell carcinomas where it had a five millimeter thick callous growing on top of the cancer. You couldn’t even see the cancer until you removed it completely. Now in my lab if you want bonus points, then I give bonus pretty freely for sending clinical photographs. I have people texting me all the time. “Here, take this picture. I’ve got this biopsy coming.” How many toenails are fungal there? At least four you can see, right? Well, the point is that the mycotic nails and the ulcer callous, that yellows are made out of almost identical material. It’s made up of polymerized cornified cells, and there’s fungal hyphae and or a yeast in there. The reason for bringing up yeast is candida is a pretty common organism in the fungal callous that surround the ulcer. Here’s one of those. It was taken off. This is from three years ago. You can see the white part of the rim of the callous and then what looks like almost like the nictitating membrane of a cat’s eye as it creeps into the center. All those flaky parts in there, those are infectious particles of cornified cells and they’re loaded with all kinds of microbes. Not just bacteria but also fungi. The blue down at the bottom which you can barely see was all candida. The whole callous was infected. There are forms of fungal infection that we even pathologists don’t recognize very well. But that fungal pair of keratosis is common in the toenails and it’s common in the fungal callous. Those big purplish or almost black-looking blobs are giant hyphae. In the center of the wound, the muck in the center, and this is like a little, almost like a gelatinous plug that came out, you will see that there’s some little branching things that go down in there. There’s a white zone, the white circular one is fungal chitin.


    But all the little grape-like clusters, the purple thing that looks like branches, that looks like vines, that was all growing in the center of the ulcer. Then we get down to the bottom. Now in the prolonged inflammatory phase, the reason it’s prolonged, they’re responding in my opinion to this slimy infection that’s growing on the bottom of the wound base. Our names are not very good for it. In the old days we might have called it putrefaction. But in general, if it smells nasty and its draining, it’s infective. All those graphs that Dr. Lavery just talked about and most of the things have been talked about today, they are not going to work in a wound that’s slimy and filled with all kinds of microbes. The microbes love growth factors. They chew those up and they’re gone in a few minutes. You can’t put those high-end products on to a dirty wound. If it’s draining of it still smells, those products shouldn’t go on there. My opinion. This is Wilcox’s paper and this is a Meyer Kaplan. So right now you’re used to seeing all those things. There’s an early separation at the beginning. More frequent debridement leads to shorter healing times. Now what is it about more frequent debridement? Not only you’re debriding stuff, but each time you debride usually they get a pretty good dose of disinfected. The whole wound gets cleaned up in a surgical manner. If you do that more often than once a week, they heal faster. This is off the 250 as 250 days. Out to 250 days you can see the curve on the left, the black is more frequent debridement than once a week. The two other lines are less frequent debridement. As I said, put it in the formalin, rule out infection, rule out cancer. Now we have a variety of stains we can apply in the lab and we could even imply. Some people are even using molecular. You’ll find all kinds of organisms in there. Most important, if you got an infected pocket or a sinus, you can culture that but you can also gram-stain it because the presence of any bacteria at all is an indication for disinfection. Now that goes back to World War 1. Let’s see. In World War 1, all they had were biocides or disinfectants. The basic principle is that the disinfectant has to diffuse into the microbes. Each of them has a certain duration of action. I’ve listed a couple of these here, but Dakin’s only last about four hours. Yet we treat it once a day with wound cleansing and redressing. In the case of my relative’s thing, I came in, he was being treated with quarter-strength Dakin’s. So the first thing I did was bump it up to full-strength Dakin’s. In the sinus part, in the pocket, I actually began to use iodoform tape. With a matter of days, the bacteria disappeared. Iodine works. Acts a little bit longer. Triple dye or gentian violet last on the order of about two days. So most of these things need frequent retreatment in terms of disinfection. This is from Alexis Carrel’s book in 1917. Complicated thigh wound. They had three different tubes going in. They were treating this with full strength Dakin’s, .5% chlorine, in six times a day. They would instil it in for two hours. Let him rest for two hours and then they’ll start all over again. Six times a day Dakin’s was supplied, and they achieved healing in these wounds. Well I promised you something about infection and I’ll show you a little bit more but it will go through. This is tuberculosis from a pic drawing in a textbook from 1913. Why if it looks like this, you probably should be ruling out infection and ruling out cancer because I couldn’t tell the difference whether that was infection or cancer. In the tropics, especially in children, mycobacterium ulcerans or buruli ulcer is pretty common. In fact you see I think, some of you close up an, on the picture on the right, the blue one, there’s fungus growing all around that ulcer. You say well, that’s just growing around there. Well, I just wanted to point that it’s there.


    Mycetoma or chromomycosis. Pretty common. Step on a thorn, this gets up into the foot. This is interesting because it kind of runs counter. The toenail is infected and that’s probably a dermatophyte or T Rubrum, and yet there’s a chromomycosis growing on both sides of the foot. That’s the same foot believe it or not. A friend of mine from Turkey sent me that. This is Henry Vandyke’s drawing on mycetoma from 1860. So from a little puncture wound, these are invasive fungi. We think about fungis being a superficial infection, but once it gets into as you know, it can be a problem. Here’s another infection. Anybody want to guess what this is? Symmetrical plaques, distinct color? You two young women there. Who’s to know if they say ham-colored plaques? Palms and soles, thick syphilis. You should remember that forever because it will happen. You will see this. However, if it gets to be really rampant, fungus can actually grow on top of the syphilis. As the epidermis becomes necrotic, you’ve got a plaque of fungus growing on top, all that yellow on the right. Don’t you just love these powerpoint things where they zoom in and stuff? It’s true. All that yellow stuff on top of there is a secondary infection. This is candida. A 38-year-old woman. She’s had this three different times in her life over the past 10 years, and it keeps growing back. Note the toenails. Those also have candida as well. I know according to the jubilee of people candida onychomycosis, they can’t talk about it. But it’s true, it does happen and it does occur. This is another candida ulcer. This is a base of the first metatarsal. Some of these things are not quite cancer. They are so proliferative at the base. A little bit different from what I’ve been talking about but let’s see. This is the shavings, the curretings that were done by the podiatrist. You see, it almost looks like a cancer on the right there. We’ll zoom it in a little bit. But it’s pseudocarcinomatous. It’s not quite carcinoma and you have to treat this as if it’s cancer. You have to remove it completely and use harsh treatment at the base. Here’s another one. Candida in the soft corn between the fourth and fifth toe. This was loaded with candida. All the purplish-looking little red dots in there, that’s all candida. That’s not an infrequent sight. In fact it’s a difficult site to treat when that becomes ulcerated. As it go back through the history of wound healing, Dr. Paul Brand, the name comes up. He was the master healer for the 1900s. You know his story pretty well. How many of those toes are infected by fungus? There’s one of them starting to break down, but that’s the pressure point and that’s where it begins to break down. In fact, on the cap of that toe was a one millimeter thick callous. I thought it was a toenail when they send it to me. I got this one wrong. So hey, I thought this was infected. I said well, it looks like all the same thing but in fact the second samples she sent was from the cap, from the tip on the toe. But the components are neuropathy where you can’t feel yourself being injured, repetitive injury and infection. Those are the three main components at play here. Once the skin begins losing moisture, the fungi grow like mad. I like the dragon metaphor because if you don’t want to find out what’s in the ulcer, all you have to do is just ignore it and pretend it’s not there. You don’t have to send it to the laboratory. That’s not a standard of care. But if you’re going to treat dragons, you have to use more than one gun, more than one weapon. I think Dr. Freiberg mentioned it earlier today. He likes to use things in combination. There’s a reason for that. These things don’t all respond to one pointed weapon. So if we use the brand method for treating and in all of these writings, Dr. Bran said the first thing he was doing was treating infection. I know that that’s not our teaching in medical school. It wasn’t our teaching when I went. They say these things are not infective. But I’m here to say absolutely they’re infected. His method for treating was to excise every bit of the dragon and the house.


    Chemically disinfect. He used Monsel’s to achieve hemostasis. You put a strong chemical like that, like ferric subsulfate, that’s Monsel solution, or 35%, 25% aluminum chloride to achieve hemostasis. It also creates a metal eschar that’s relatively impermeable. So you leave a layer of this behind. Not only different materials you put on but in different order. So I say chemically disinfect the dragon eggs and you don’t have to believe in dragons but Monsel’s is a chemical agent which can be used as an antimicrobial. Afterwards, he would suppress it with iodine and or gentian violet, soaking it and cleansing around the wound, oiling daily. Bed rest. Everybody has mentioned bed rest. That goes back to Hippocrates 2300 years ago. Hippocrates noted you got to get them off their feet and put them to bed. There is a podiatrist secret. Some of my podiatrist know it and I’ll share it with you. Again, there is no clinical reports on this but if you get into a desperate moment and you don’t know what else to do, there is the pathologist secret weapon, Lamisil. A lot of my podiatrist friends will start their patients on Lamisil. Some of them they can’t get it on because they’re on statins, they’re on all kinds of drugs. Even in my relative, I didn’t start him on either Diflucan or Lamisil. Heel ulcers. Heel ulcers are a real problem. Now I want you to pay attention. Treating around the ulcer is just as important as treating in the ulcer because those flakes that get off the skin and go into the ulcer and they’re infectious. They’re carrying organisms back into these wounds. One method is one layer you can put is the gentian violet or gentian triple dye. But you got to remember to treat around the ulcer because it’s not just a hole in normal skin, it’s an infected hole that’s surrounded by fungally infected skin. You don’t believe me? Look at these legs. This is pretty common. People have a leg dermatitis or a leg eczema and we pretty much ignore it, but then wonder why their wounds won’t heal. Well, all three of those legs have signs of fungal infection. She’s the normal control in the study but all the flakes, if it’s red and it’s continuous with something else, it’s fungally infected right down to the toenails, then you should assume that that leg dermatitis is infected as well. Now my relative, I treated him with a disinfectant called PHMB, and cleaned up his legs. It was truly amazing now. Here’s his leg. This is two days after I started working on him. You’ll notice all this. Look how nasty it looks around there. All that black blue stuff is gentian triple dye. It’s staining around these fungal scales that go right up on to the wound edge. In fact if you see on the far right, I can’t point it out to you, that fungus went all the way down his leg, on his statis change he had fungal nails and so on. This is his biopsy two days after he’d been treated with Dakin’s and triple dye. He is closing but this is where he started out from. His wound had this slimy blue stuff all over there. Some bacteria, gram positives, gram negatives. I didn’t find any yeast. I didn’t find any hyphae in there. The infected vessels. Now I’m not the only one to recognize this. This is from the Fumal paper. Leg ulcer pathology. When this necrotizing vasculitis is in there, it was directly related in their studies to the microbial load. This was a sign not only that there was infection but there was a substantial infection in there. Infected vessels means stalled healing. The reason for this prolonged inflammatory stage has to do with this smoldering infection that’s going on. What they compared in this study, unique study done at the University of Miami, patients who had two ulcers.


    They treated one with some kind of hydrocolloid dressing. The other they chose one of three different disinfectants, chlorhexedine, silver sulfadiazine, and Povidone Iodine. All three of them reduce the microbial load. But only one of them increase the healing rate and that was Povidine Iodine. Not only decreased the time the healing but significantly increased the healing rate. So here’s an example of a disinfecting chemical which people will poo poo and say, “Well that’s harsh on cells.” The early phases of getting a wound to heal entail completely disinfecting that wound. So that’s the early phase and that’s the part that you have to pay attention. If you don’t do that part right, it will continue to smolder on and no amount of graft material or whatever will clean up those wounds. They don’t work when they’re loaded with microbes. All three disinfectants decrease bacteria. Povidine was better for wound healing. Did not alter the micro vessels. Did not change the number of dermal dendrocytes. Did not change the number of fibrocytes. There’s a lot of evidence from the cytotoxicity world in cell cultures but it doesn’t hold up in human data, in humans. So Povidone Iodine was lace toxic and they said, appeared to be an efficient compound in this respect exhibiting both a positive and relevant clinical effect. I’m hoping that you will consider biopsying some of these wounds. I enjoy studying them. I enjoy looking at not only the callous but also the part in the wounds. Let’s go back a second. See if we can go back here to Marvin’s slides. This one. This was after roughly four days treatment. It took yet another week probably to get all that scaly stuff off of there. I was treating him with a disinfecting ointment. Treated the leg one way. Treated inside the wound the second way. He’s now ready for grafting about two and a half weeks later. Cleaning up the infection is the principle task, the first task. Mechanically debriding all that stuff away is a good thing but following it up with a disinfectant is another. With the disinfectant, if it’s still oozing, if it’s still smelly, then you’ve still got a problem. The good part is disinfectants are adjustable. You could use quarter-strength Dakin’s. You can use half-strength Dakin’s. You can use full-strength Dakin’s. You can switch to iodine. You can switch to PHMB. There are plenty of choices for you to do this. I think there is one more. I would like you to think about not treating dragons anymore but consider what you’re doing is to treat infection. You’re not just treating the prolonged inflammatory phase, you’re treating the microbes in there that are delaying the healing. We’ve known that these microbes will delay healing. We’ve known that for more than a hundred years. Not that people who especially do the lab test anymore but maybe you should. The simplest lab test you could do in a wound is just to swab it and send it for a gram stain. That’s probably the cheapest one that I know of. If there’s still bacteria in there, it’s still infected. In summary, stop treating dragons. Excise and disinfect. Treat the fungal infection not only that’s in the wound but around it. I’m perfectly happy just to see the pathology when you do that. I think that’s about …