Female Speaker: Okay, so this lecture should be also titled, everything you wanted to know about tinea pedis but were afraid to ask. Okay, so just so you know, I'm an activist of principal investigator for both Merck and Valeant and has worked as an advisory board and speaker for PharmaDerm. Weâre going to talk today about how tinea is spread, describe the topicals that are out there and analyze the products used to prevent tinea. Just as a background, 26.5 million people are affected annually worldwide with fungal infections. Of that, weâre seeing more and more dermatophyte infections as we see in aging population, changing immune response, increased susceptibility. My current fourth year students actually just published an article on an online open access journal called Journal on Fungi, how ever you want to say it, talking about the immune response of the skin to T. rubrum. Itâs an interesting article, if you want to check it out. But certainly they take something thatâs really a complicated topic and water it down so that it makes sense, very proud of them for that because it really breaks down as to what's going on with the body with all of these. We also have another article thatâs about to be published talking about the environment with T. rubrum, both from a macroenvironment but also from a microenvironment. Itâs not just geographic variations which it can be, but itâs also clothing, shoes, hyperhydrosis. But also think about upstairs if you're staying in one of the hotel rooms in this particular building, think about the people who walked in that carpet before you. I know, right? I just ruined it for you. Certainly, we can pick up this very contagious agent from somites. But of course, we are more susceptible to it as we get older and if weâre male. Now, risk factors for it would be having the immune deficiency disease, patients who are currently receiving chemotherapy, steroids, being diabetic. Certainly, we see more dermatophyte infections in those as I mentioned with onychomycosis. They are three times more likely to develop onychomycosis in a nondiabetic. Patients who are obese and there is that genetic component, that autosomal dominant trait of the inability to mount cell mutated response to T. rubrum that exists no matter what you're talking about, whether itâs onycho or tinea. Letâs talk about how we spread things in the household. Well, Dr. Ghannoum, who's this really amazing mycologist took a look at 50 households where there was documented tinea pedis and basically just using PCR and strain differentiation, found 16 strains of T. rubrum across those 50 households. But basically what he found was the same strain of T. rubrum is in each house, which he would suspect. Certainly, weâre seeing it through families, again who are using the same showers, who are walking barefoot on the same carpets and in some cases like my patients themselves will say that they're sharing shoes that certainly we are infecting each other. What about reinfecting ourselves when we have a superficial fungal infection? Well, this was an open study of 86 patients. Now, I donât know if I could have thought of something like this but certainly, itâs a fascinating study. They had to have tinea pedis, they brought in a sock that they wore and they washed it once, just once. They didnât give any specifications whether it had to be in Clorox or hot water or what kind of detergent. They brought the sock in, put in a hermitically sealed bag and did some experiments on it and what they found was that after just that one washing, dermatophyte survive in socks. Itâs something to think about with our own patient population, that they might bathe, they might wash their socks and again, there was no control with this in how they washed it, but they can potentially keep reinfecting themselves. Just as inside, what are the types of tinea pedis that are out there? Well, everyone from an academic standpoint says that interdigital tinea is the most common and perhaps that is true but I feel that as a practitioner, I see moccasin more commonly than any set and certainly the least common would be the inflammatory type and Iâll go through these. Interdigital tinea is obviously is going to be in between the toe spaces and web spaces. Usually, the source between the fourth and fifth toes. Pruritus is extremely common, weâll see scaling, redness and certainly we can see maceration. We can see the scaling, the serpiginous scaling that we see commonly with tinea, extend plantarly on to the foot and to the sulcus. There's a dry type that we consider, again scaling, pruritus, low grade healing, and can be completely asymptomatic.
[05:06]
I mean, certainly we've all been in situations where weâre examining patientâs feet, they donât even realize that they have tinea pedis, whether itâs interdigital or moccasin. My favorite personally would be the webbed type only because it makes me break out the Woodâs lamp and my former students know how much I love Woodâs lamps. This is where we have our wet macerated interdigital spaces and certainly, we can see secondary bacterial infections. So if you use a Woodâs lamp with green fluorescence, you'll see Pseudomonas. With coral red, itâs usually Corynebacterium. What are our differential diagnoses? Certainly erythrasma, again that secondary bacterial infection, impetigo which would be more of a staph-strep situation. Pitted keratolysis, which I find endless fascinating. That's more of just the flesh colored pits that weâre going to see mostly on the plantar aspect of the foot. Certainly just again Pseudomonas wreaking havoc on these patients. What about moccasin? As I said before, to me moccasin, I see the most. Now, this is a much more difficult entity to treat. In fact, there is no set way of treating this. We donât know for how long. We donât know how often. Certainly, we don't know really what the optimal way of treating this is. Itâs actually something that we have a task force that I'm part of to figure out and define what moccasin tinea is because the FDA really doesnât recognize it. That said, every topical antifungal product thatâs out there is actually only indicated for interdigital tinea, nothing is indicated for moccasin. Moccasin again, how do we define it? Is it the whole foot, sort of the sulcus? How far does it go on to the sides of the foot. Thatâs something that we donât actually have a definition for, as simple as it may sound. But certainly itâs typically bilateral and again, we can see hyperkeratosis with it. We can see xerosis, but the quick and dirty way of telling it is if you see serpiginous scale, thatâs going to be tinea. Differential diagnoses, sore tinea and this is something that I am so [indecipherable] [07:16] I see so many patients get sent to me who've been misdiagnosed as having tinea and truly, they have psoriasis, they have some sort of eczematous reaction, pitted keratolysis, which again are those flesh-colored pits or simply a keratodermis, something that is genetic and that they were born with. The least common for is vesiculobullous. I tend to think of the vesiculobullous as almost being an allergic response to the dermatophyte. It is not a blistering reaction on the bottom of the foot. It is commonly something that starts interdigitally and they develop a blistering reaction on the dorsum of the toes. To me, that is truly what vesiculobullous tinea is. Our differential diagnoses would be bullous impetigo, contact dermatitis, dyshidrotic eczema and certainly the bullous disease is like epidermolysis bullosa. Again, our overall differential diagnoses for tinea would be contact dermatitis, candidiasis, just simply dry skin or xerosis, erythema multiforme, erythrasma, friction blisters, or bullouses, diabetic corn and psoriasis, which is my favorite. How do we tell this? Well, most of us can walk into a room and say, I feel it was pretty pure certainty that that is tinea pedis. Again, serpiginous scale, presence of onychomycosis, most likely itâs going to be tinea pedis. But there's times when patients have excoriated. Theyâve used products. You're seeing just a red scaly presentation that you really have to do a little bit more digging. Whether that means you do a KOH scraping, which will just simply tell you the presence of dermatophyte or not, hyphae or not. Or you do a biopsy. There have been cases where patients come in and itâs just really difficult to count and Iâll end up doing a punch biopsy. I do not do a shave biopsy for rashes because it does not go deep enough to tell me really what's going on pathology-wise. Again the most common dermatophyte or most common organism to cause tinea pedis would be a dermatophyte, T. rubrum specifically. But certainly we can see the other dermatophytes like microsporum and epidermophyte and causes as well, as well as some of the molds. Certainly I've seen more and more molds come back on culture in the last at least six years. T. rubrum is going to be the most common cause for all three types of tinea but certainly as you can see E. floccosum is also a member of that club that can cause all three. What's the problem with tinea? Well, most patients are going to go to the drugstore and find what I laughingly called Tough Actin Tinactin.
[10:00]
They're going to become frustrated and self-treat and eventually find their way to you. But the problem is itâs not just the over-the-counter stuff that really just doesnât seem to always do the job. Itâs some of the home remedies that they do. Now when I put a bleach on a slide, most people would perhaps do a bleach dilution. Not my patients in Philadelphia. They just take Clorox straight up and put it into a foot bath and then wonder why their skin is peeling and red and raw. Probably because itâs not wise to soak your feet in pure bleach. Now as far as vinegar goes, I have to say that when I was doing one of the clinical trials, we would soak the patientâs feet in just simply vinegar, prior to doing our KOH scraping because it reduces the bioburden of what's going on. To me, vinegar doesnât actually kill fungus, if a clinical trial protocol allowed us to do that. Of course, my least favorite, tea tree oil, which in its pure state actually can be a contact synthesizer so I donât recommend that to patients. What do we have prescription wise? Well of course, we have the orals which would be more for recalcitrant case or case where we've seen failure of the topicals. Topicals which is what the American Academy of Dermatology recognizes and recommends as their first line of defense. Again, things that we can use adjunctively to reduce say hyperkeratosis or some of the scaling that patients are complaining about, namely keratolytic agents like urea, salicylic acid or lactic acid. Oral antifungal agents, again this would be more for patients who have recalcitrant disease who have the vesiculobullous type and as well as moccasin that we just really canât seem to control with topicals. Terbinafine would certainly be probably the wisest thing to use because of its least amount of drug-drug interactions. That mainly is 250 milligrams for two to six weeks. I've heard all variations. I personally would use it for a month with my patients. Itraconazole which we donât use quite as often because of the drug-drug interactions, itâs not always accessible to our patients, would be 100 to 200 milligrams for again two to four weeks. You can use fluconazole if you feel that there's more of a Candidal component certainly and that's once weekly dosing. Griseofulvin is something that actually is truly indicated for tinea pedis, especially the ultramicrosize which would be easier on the stomach to digest. But itâs one of those things where the pills are quite large so itâs again not always accessible for patients to do. If we have a child who we need to use it for, we have to cut it up and put it in applesauce for them to swallow it a little bit better. As far as the topicals the ones that are FDA approved would be azoles, the allylamines, the benzylamines, thiocarbonates and the hydroxypyridones. Letâs go through those. Well, how do we want to choose before we go through those is talk about why we want to use a topical. Well, considerations. Number one, the type of tinea pedis that you're dealing with. As I mentioned before, a vesiculobullous I wouldnât even attempt to use a topical. An oral would be the way to go. The simplicity of dosing, a lot of the new agents are once daily dosing which we want to try to encourage patients to use. If I tell someone to use something twice a day, theyâll probably use it once a day. If I tell someone to use it once a day, theyâll probably use it every other day. Certainly, keeping things simple for patients at least hopefully ensures more adherence to using the regimen. We want to be as aggressive as possible. We want to make sure that we get the most bang for our buck with these medications so our patients can feel and see the difference. We also want to think about insurance coverage for those patients that thatâs an issue for and straightforward directions. Now the other thing I want to mention is the newer topicals really have a natural anti-inflammatory component to them. The need to use a topical steroid for these really itchy situations isn't necessary. In fact, again those who are my former students know that I am very, very anti-lotrisone. To me lotrisone is a cop out. You have a very strong topical steroid and kind of an antifungal. Well, using that you're sort of saying, âWell I'm not really sure what it is but I think Iâll cover both.â Well in reality, what you might be causing is tinea incognito where you're putting a steroid on top of a boiling pot of fungus. When you take that off, you can have an eruption of the fungal disease. I do not ever recommend using a topical steroid in conjunction with an antifungal. Treat what's in front of you. If itâs an inflammatory skin disease, itâs a steroid. If itâs a fungal disease, itâs an antifungal. Again, these medications will help reduce inflammation on their own. The other thing that we want to think about with these patients is tell them to go beyond the scale that you see at least one to two fingerbreadths beyond the scale because that dermatophyte is even though itâs a little slow and taking its time, itâs still past where you see the scale.
[15:11]
Now, we donât have comparative studies of these antifungals to each other. Itâs not something that pharmaceutical companies really would like to do. We do have more placebo and vehicle-controlled studies than anything. Also itâs one of those things where we donât have a lot of followup studies overtime to see recurrence. But certainly that's something that has been looked at. This has not been put in the literature. I know this is a very worthy slide, but this is just to say there's creams, there's gels, there's sprays, there's foams out there. The thing is over time, many of us in school were taught to not use a cream for in between the toes, to use a gel to dry things out. Well interestingly enough as I said before, all the topicals that are out there had been indicated and specifically approved FDA wise for interdigital tinea. For me, it was a paradigm shift when I was doing these clinical trials to use a cream for in between toes. Interestingly enough, patients actually didnât mind it and didnât cause the maceration that I certainly thought it would be from again learning that in school. I now can go between gels and creams for in between the toes. It seems to be again patient-wise doesnât seem to matter. Now going in to talk about the clinical trials, cure is sort of this interesting term. From an FDA standpoint, did we kill the fungus? From a patient standpoint, did we reduce the symptoms? We want to see that combination up for a complete cure. Did we kill the fungus? Did we reduce the symptoms to zero? Then there's all different ways of taking those statistics and messing with them and saying, did we kill the fungus but maybe they have a little bit of scaling left, that would be more of an effective treatment or did we just kill the fungus and did we just look at that. Each trial sort of has their own way of defining these things. You canât really compare them. Itâs like comparing apples to oranges. Letâs get into one of the newer agents which will be naftifine 2% gel. I was an investigator on this trial. Now, what was interesting about this, this is an allylamine so technically itâs fungicidal. Itâs a well-tolerated medication. It was during the trial with negative for tinea pedis, tinea cruris and tinea corposis. As a podiatrist, I was very grateful not to have to do the tinea cruris section because if you saw my clinical trial subjects, you would understand I was in no rush to scrape anyoneâs groin. Feet are just fine. But in one of these things what we did was we looked at both interdigital and we did moccasin. But we didnât have enough moccasin numbers in this trial to actually get it FDA approved. Thatâs something that certainly weâre going to present our data in a paper, however in the future again hopefully this sort of opens the door for people to look specifically at moccasin tinea. Now with naftifine 2% gel was used once daily for two weeks. During the clinical trials, and this is very standard for tinea pedis clinical trials, you treat that area for two weeks. You follow them for four weeks without using any medication and then you see them at week six for their final assessment where again you're doing KOH and culture, taking pictures, documenting and all of those different things. Again, complete cure would be defined as KOH culture negative and did you reduce the symptoms which would erythema, scaling and pruriritus. Now certainly erythema and scaling is something that I can assess. Pruritus is something thatâs subjective to the patient. Certainly there is that component to it with these particular trials. For naftifine versus the vehicle and the two studies that were done, parallel studies was 18% and 16%. Again, this is the most difficult number to achieve when you're doing trials. Mycological cure is a much easier number to achieve and that was 67% and 71%. Now again there's treatment effectiveness, clinical cure, clinical success which is all sort of saying, maybe we didnât go down to zero erythema. Maybe we have an erythema score of one or maybe you didnât get zero pruritus. Maybe there's a little bit of pruritus left. So that's kind of what those numbers are saying. Certainly, the whole take home messages is that after two weeks, these patients have success and four weeks after that of not using any medication, they still continued to have success. So itâs theorized that most likely with these patients, there's some sort of reservoir effect. Naftifine is staying within the stratum corneum and still working on even when youâve taken the drug away and you could really see that in a slide where you see week two is the dark blue and week six is the light blue and you can see that the response rate seems to continue to go up even again after removing the drug, after using it for two weeks.
[19:59]
Another topical agent, I was also the principal investigator for this particular trial was luliconazole 1% cream. As I mentioned before, this certainly made me change my thoughts about using a cream in between the toes because certainly thatâs not something I was taught. It was interesting to do this trial in once daily use for two weeks. Luliconazole is a drug that actually was approved in Japan years ago and then in order to get it approved here, we have to do clinical trials all over again. Same thing here with luliconazole, different drug class, itâs an azole versus an a allylamine with naftifine. But the antifungal effect still remained after you took the drug away after using it for two weeks. Again, we tend to see this reservoir effect where patients were still having benefit from the medication even when they're not using it. They can considered complete clearance would be 26% and 14% versus the vehicle. Clinical cure, which is just the visual cure is 29% and 15% and mycological cure was 62% and 56%. Again, how well did it kill fungus? Both drugs so far we've talked about do a pretty good job of killing fungus just after using it for two weeks. Again, the complete clearance where we've reduced the symptoms and youâve killed the fungus as you can see was superior to vehicle for both studies or both parallel studies. What about econazole? Now you're probably familiar with econazole as a cream once upon a time. But this was actually a foam so I was involved in this study as well, looking at a foam vehicle and the thing is the beautiful thing about dermatology is itâs not just about choosing the right drug, itâs about choosing the right vehicle thatâs appropriate for the patient. Again, foams are nice because they dried fast, they're easy to use your socks on afterwards because of their drying and some patients just prefer that technology versus just using a cream or a gel, just for some people just easier to use. Again, this is a broad spectrum antifungal. Itâs an azole and again, this was using a really nice vehicle that really has physiologic lipids and gets into the stratum corneum extremely well. So the actual vehicle itself really drives the active ingredient into the skin very well. So again, two parallel studies. This is consistently what is done. However, this was where it was applied once daily for four weeks. This was not a two-week regimen. This was a four-week regimen. Again, patients receive either the study drug or the vehicle. As you can see from the clinical trials, it had superiority over the vehicle. Two weeks after the end of treatment, again, it was a six weeks trial, four weeks of treatment, two weeks of no treatment at the end of that six week period. Patient still continued to have success. They looked at negative KOH culture as well as the clinical composite, meaning did you reduce the redness, scaling and pruritus. Now those are three prescription medications, right? Econazole foam, naftifine gel and luliconazole cream. What about the stuff thatâs over the counter? Well, if you go to England, you'll see a product called Lamisil Once. The first time I saw it in England, I said, âWhat is this and why donât we have it in the United States?â This is a single dose application of terbinafine. I find it kind of just really fascinating that this even exists. I think certainly for people in the military or people who are going away and wonât have access to medications like missionaries this might be a really good product for them, however you do have to get it from overseas. But you can buy anything on Amazon, right? Basically, what they did was they took a terbinafine spray versus Lamisil Once, which is the specific terbinafine cream. They just wanted to compare the two because both are once dosing, which is once dose and that's it. Basically found that the topical spray was not inferior to the Lamisil Once product but the no need to touch skin was a benefit for patients. Imagine some of our patients who canât reach over and touch their feet, they donât have someone to help them touch their feet, certainly this new terbinafine spray that should come out in the market eventually is appealing for some of those patients. What about the adverse events when it comes to these topical agents and certainly, we talked about adverse events with onychomycosis products. The same thing can happen with topical agents for tinea pedis. There's minimal systemic absorption and that's a benefit of using a topical over an oral. Generally, there's no major systemic side effects. The application site reactions that can happen and they do happen are possible, are usually more of an allergic content dermatitis situation. Have I seen these in practice? Absolutely I have definitely seen these in practice. You remove the agent, you treat the inflammation and then I usually move to a different class of antifungal, just make sure that either I'm dealing with something that is either a study drug or active drug wise or a preservative in them.
[25:15]
But usually, they're generally mild and transient. But what else can we think about besides over the counter and prescription. Well, how about non-pharmacologic interventions. Foot hygiene, I mean my patients always like to say, âDoc, I didnât wash my feet and I kept them real sweaty just so you could see what I'm dealing with?â And you're like, âThanks. Thanks for that.â But certainly, washing your feet is always a good thing. Shoe hygiene, how can we reduce the microenvironment of what is going on. They're going to keep reinfecting themselves. Shower hygiene, what can we tell them to use to disinfect their shower and what kind of preventative care can we give them. Certainly from a shoe hygiene perspective, I do recommend the ultraviolet light device that Iâll get into in a minute. Letâs talk about socks first. This is a very interesting article. Wasnât actually a study per se but certainly they could make something out of this in the future. In August 2010, there were 33 Chilean miners that were trapped. Unfortunately when you're trapped you're stuck in your shoes and socks or whatever you had on is what you're stuck in. Well, they were complaining to the people who were talking to them through very small tube of their feet were driving them crazy, itching, burning, all of those things. They sent some clotrimazole. Well, the clotrimazole didnât really do much. What they did was they contacted a company on the surface and said, âOkay, what can we do for these folks, clotrimazole is just not cutting it.â They sent them down some copper socks. So interesting, interestingly enough, they sent them three pairs that they could sort of use alternatively and when they were finally rescued at 69 days, only three of them had tinea, seven had some xerosis and three had what they considered dyshidrotic eczema. They gave them a questionnaire. Interestingly enough, copper seem to help calm the symptoms that they have. You might say, well copper is a natural antimicrobial agent but how do we get it into fibers. Well, there's actually plenty of different things that are out there. In fact, even at Target, you can purchase a pair of copper socks if you look hard enough. For me, I've seen on TV section. What about shoes? Well, a beautiful study that was done by Dr. Ghannoum again was okay, first of all, how can we infect footwear. Letâs take a regular sneaker and letâs see if we can actually inoculate it with T. rubrum and can we then get that isolate and then colonize it and put in a culture. They were actually first able to do that and then with the ultraviolet light device, what's called the SteriShoe commonly and did once cycle of that which is a 45-minute cycle and the shoe found that it absolutely reduced the fungal bioburden. Itâs something that from my patients where itâs accessible financially, I recommend them to purchase that because certainly itâs one way that we actually have proofs, we have data that it reduces the fungal burden of the shoes. Now what about patients who say, âYou know what Doc, I canât do anything everyday.â I'm like, âBut you eat everyday, you sleep everyday.â You know, have the cream on the side of the bed. Try to do it where you remember. But the truth of the matter is, is that weâre just creatures of habit that sometimes are in a habit of not doing things. For instance, in the adherence studies that are out there, they put on the study medication a little sensor that saw whenever the teenagers, and of course you're talking about teenagers here, right? Every time they opened up the jar to apply it on their face, did it match what they were seeing in their study diary. Well, they absolutely did not. Adherence definitely declined over time even in the clinical trial. The thing is adherence is completely low when it comes to topical agents. Patients think, well, I donât see benefits. Itâs not getting better right away. We especially as Americans want things better right away quickly. The challenge is especially with twice a day or even multiple day dosing and long-term treatment durations. Some of these patients we say that these products are used for two weeks, but in reality, they need them a lot longer than that. Certainly again, just even trying to reach the feet can be a challenge. Again, this is just showing you another study saying adherence to topical therapy just declines over an eight-week period. We do want to encourage our patients who want to educate them about the importance of using these products everyday. But we also want to talk to them about the consequences of if they donât follow through with their treatment. Certainly, if they donât have onychomycosis already, they certainly can develop it over time.
[30:01]
Persistent fungal infection, just having that itchy foot that just drives you crazy certainly be that. We can see the presence of dermatophytes complicate asthma and allergies believe it or not and contribute to refractory atopic eczema. Certainly, we want to make sure that these patients use their product because especially in the patients I've seen in Philadelphia, when I see that secondary bacterial infection in between the toes, that is nothing to sneeze at especially in our diabetic patients. We can see a cellulitis form and that can track up the leg and certainly be an issue. Just like with this patient. I mean I have to say that as a practitioner, superinfected tinea is always fascinating to treat. But certainly, itâs frustrating because you wonder how the patients let it go this long. Again, they start out with interdigital tinea. Itâs nice, wet, moist environment that bacteria also love to thrive on and then you end up with someone that you see at week one and then what I do with these particular patients is I treat them for the bacteria that they actually have present again. I use Woodâs lamp to help me diagnose, treat them with an antibiotic and then I treat them with the antifungal after that. I know some people use them concurrently. There's no set way of how you do it. Certainly, itâs your own protocol that you come up with but I find trying to keep things simple and direct is the way that I can get patients to follow through so I always use an antibiotic first, the antifungal second. Thatâs it for me. Thank you so much for your attention. Does anyone have any questions?