Female Speaker: This is always exciting for me. I love treating toenails as well as psoriasis and warts. For me, a day that doesn’t involve any sort of fungus, psoriasis or HPV infections is a day half lived for me. I’m excited to talk to you about all the different things that are out there with nails. I do again have a financial relationship with these particular entities. These are again people that I have done research with or have been involved with from a consultant basis. We’re going to discuss some treatment options for nails. This is not all about Lamisil, Sporanox or Penlac. We’re going to describe some cosmetic alternatives and talk about whether the nail disease that we’re looking at is internal or external. As someone who attends the Council for Nail Disorders on a yearly basis, one of the things that we always talk about is, is it fungus? And if it’s not fungus, where is it coming from? The easy way to do is to look at the pattern of what’s going on with the nail and does it follow the shape of the lunula? If it follows the shape of the lunula which is the half moon shape that you see, the visible portion of your matrix, it’s probably systemic. It’s probably internal. If it follows the shape of the proximal nail fold, it’s probably exogenous or it’s environmental or a condition that is external. The other thing that I look at besides the pattern of what’s going on with the nail is I look at their fingernails. I don’t just look at their toenails. Obviously, I want to see if there’s any other issues going on around the body, any other skin rashes, things like that, their past medical history, as well as the color and the quality of the nails that are infected as well as the quantity of nails that are infected. We all know what the current treatment options are for onychomycosis. I mean this is nothing new to you at all. Certainly, in my practice I might use more griseofulvin or fluconazole because I seem to culture out some very dramatic things that are out there that terbinafine or itraconazole just might not be able to handle or patients may not be able to medically go on itraconazole. Prescription wise, we’re all familiar with ciclopirox. Some of us have used ureas and certainly ureas are more difficult to get a hold of from a government perspective and from an insurance perspective. Amorolfine is used in Europe. We don’t have it here but my patients have somehow procured it from amazon.com which is always interesting. Then we have the topicals that are meant for dystrophic nails which are Genadur or Eco-Formula. Those are two different companies but it’s the same product. And a product called Nuvail which came out about a year ago. Certainly, we have debridement and we have a cosmetic covering called KeryFlex which I’ll get into. Now all of us know this is an infection, some of us would say disease. It’s embarrassing to our patients and that was never more evident to me when I was doing clinical trials. We would have patients fill out questionnaires and especially my male patients would say, “I don’t take my socks off. I don’t want my wife to see my nails. I don’t want to go to the pool. I don’t want to go on a cruise because I don’t want anyone to see my nail disease.” Certainly, we know it’s an embarrassing entity. It can cause ulceration of the nail bed beneath. Certainly if it’s very thick, if it’s painful and all of us have been in that situation when we’ve debrided the nail and that ooze comes out and that bloody mess from an ulcer that’s underneath the nail, we’ve seen that. It can seed infection to other places. If all of us put our pants on one leg at a time, if you’ve got athlete’s foot and onychomycosis, it might seed to your groin area and certainly can cause some tinea cruris. We know from Armstrong’s data that diabetics have a 60% chance of developing a foot ulcer. Certainly, something that we want to be proactive in treating. But we know it’s a $2 billion market with only 5% really seeking treatment. I put the slide here because this is an old standard and something that I prescribe on a daily basis in my own practice. Certainly I’ve seen it worked but it’s not always something that is appropriate for the patients depending on their medical history or their liver or what have you. We know that we can get clearing of the nail with oral terbinafine. But what’s on the pipeline? Oral posaconazole, it’s already available as an oral suspension. Dr. Luzzi [phonetic] and her team decided to look at it for the treatment of onychomycosis. It’s something that actually has been come out but the problem is, is that it’s an azole. We always worry about with different things with azoles and it’s fungistatic and it’s probably not cost effective to give that versus a generic itraconazole or something else. But what they evaluated was 200 milligrams given daily for 24 weeks or 400 milligrams given daily for 24 weeks and of course the 400 milligrams was the better dosage that had more efficacy. Oral itraconazole which is not available.

[05:04]

There are some clinical trials underway. It was used once weekly for 12 weeks just like we would use fluconazole. Fluconazole used once weekly for so many weeks. It might work for non-dermatophytes, but it seems like it's lost in pharma issues right now that they're looking for people to sort of partner with them to go further in clinical trials. Efinaconazole solution which is a trial that I was involved with as a principal investigator, just finished their phase 3 multicenter randomized double-blind study and show that it was effective and safe in using on patients with toenail onychomycosis. Hopefully, we'll see approval of that by the first quarter of 2014 or at least maybe the fall. We'll see how that goes. And then Anacor also has a novel new product that is a completely new class of antifungals. Their product is called tavaborole, and it has the unique product of having a boron ring within its molecule which targets leucyl-tRNA synthetase which basically blocks protein synthesis. It basically kills the fungus by creating this lipoprotein and it's not able to go on. They also have some really lovely data and hopefully that will be approved in the summer. Luliconazole, again, I had done the topical tinea pedis clinical trial with topical luliconazole for tinea pedis but they're also looking at it for toenails as well. They're just starting their trials and certainly it should be interesting to see where it goes and you should know luliconzole is already approved as a topical in Japan. I'm sure that approval will come here underway if they show that there is efficacy and safety. What was in the pipeline? This was a study that I was involved in. It was topical terbinafine and I think many people in their practice have taken crushed up Lamisil tablets and put it in various solutions or had used topical terbinafine. You could buy over the counter and have them use the cream on their nails. And also Novartis, I guess at one point, had looked at the topical terbinafine. Promius looked at this topical terbinafine. We actually ended the study before we could finish it because they really didn't have the efficacy data that they wanted. It's something that was tried but just didn’t seem to work. Certainly, if someone is able to come out with a different formulation or maybe a different vehicle, there could be a possibility but at this point it doesn’t exist. Something else that was in the pipeline which I thought that was really, really interesting was from a company called Nanovial [phonetic] and this was an emulsion. Basically it was a product that you would apply on the nail and around the nail that would saponify or just basically, just like soap, just lift away the molecule, had no antifungal properties to it. This company already uses this product for various different other diseases and have used it in the defense department for different medications or different diseases. The thought was is this could possibly work if you apply it around the nail. Unfortunately, it didn't really seem to go anywhere, it didn't really seem to do anything but you never know, maybe they’ll again create a different formulation or somebody else will pick it up. I think it's always important to educate our patients that fifth toenail dystrophy is not necessarily a mycotic nail. A lot of times, patients come in especially females saying, “You know what doc, like everything looks great but this baby toenail, it just looks terrible, always look terrible.” We all know it’s biomechanical. What do we really have to treat this nail dystrophy? The truth is, is there are some things that are out there that we can use. Of course, good old standby urea. There's a talk that urea might be taken off the market so certainly that will change the way we use these products and certainly for urea for topical cirrhosis and other kinds of conditions, I will miss urea if it is taken off the market. But it's not a cure for fungal nails, it just helps to debride them. There's a product that's over the counter that is known as Kerasal Fungal Nail Renewal Treatment. The study was done overseas and it's basically a combination of propylene glycol, urea and lactic acid. Looking at the study, those nails look pretty nice. It looks pretty great. I can say to you when it was first introduced to the American market, I suggested to some patients to use it. I said, “Well, if you want to use it in combination with oral medication or whatever else that I might be providing for you, let's give it a try.” Sadly, I didn't have any patients who were satisfied with this topical therapy. But again, it does exists, it’s something that if you wanted to utilize in your practice, you could, but I personally have not seen any efficacy with it.

[10:03]

These products I have definitely used more. This also can be used for dystrophic nails, Genadur and again Eco Formula. These are hydroxypropyl chitosan products. Basically, the shell of seafood we’ll say. But you can be seafood allergic and use these products. They did a study using it with psoriatic nails. With psoriatic nails, we see a lot of onycholysis and pitting and patients who had pitting and onycholysis with their nails did have improvement with this particular product. This is a product I’ve used extensively in my practice since it came out a year ago. It’s poly-ureaurethane 16% and it’s specifically FDA approved for dystrophic nails. What that means is it’s not necessarily fungal infected nails. It can be used for anything. I’m sure in the dermatology world, they’ll use it quite a lot for fingernails because a lot of patients who have their hands in water all the time have various -- careers where their nails are really getting hit hard, this is a great product. But for us, we can use this for that fifth toenail. We can use it for patients who’ve been on oral terbinafine and still have residual dystrophy. They can use this product on a daily basis. What Nuvail does is it penetrates the intercellular spaces and the nail surface ridges. It creates this very flexible polymer and it creates a nice structure but it’s also able to last throughout handwashing and showers. This particular product is something that we received from Germany a few years ago. It’s something that I teach the students at Temple how to do, just as the way of saying, “Okay, you can use this product as a cometic alternative. You can generate income in your practice by doing it.” It is not a gel nail. It is a cosmetic resin and it’s applied to the nail. It is cured with a UV light. However, it is not the same as gel nail. It’s been shown that gel nails really damaged the nail when you removed that. KeryFlex does not do the same thing. KeryFlex is a little bit of a process. Typically, what most people in practice are doing is the practitioner is doing the nail debridement and then they’re having their medical assistant apply the cosmetic nail resin. You can use this for patients who have onychomycosis. In theory, the resin once it’s cured cannot allow water to go into it. You’re suffocating the fungus in theory. You can also use this for patients who’ve had multiple nail procedures over the years, like multiple paronychia procedures. Their nails are just dystrophic and say they want to go a wedding or a prom or something like that, it’s a way of creating a nice covering, a nice even, smooth surface that nail polish can be used on top of it. It’s something that only is temporary. You have to have nail plate to do it. You have to have about 10 to 15% of nail plate to apply it. And it has to be usually reapplied in about six weeks depending on the patient’s nail growth. Again, it’s just a cosmetic alternative. It’s another thing to use in your toolbox for patients who perhaps want to go to an event or just don’t want to look at their nail fungus and don’t want to apply anything topically or use anything orally. Now there’s a lot of controversy out there with the laser and there’s a lot of interesting data that is out there. I was involved with the ultraviolet C light trial. Unfortunately, I don’t believe that that’s going to go to market. We don’t really see ultraviolet C penetrating the nail well. But the other products that are out there, generally 1064 nanometer YAGs which do seem to heat up the nail to a certain extent. The thing is, is we know that we have some clinical trials that are out there. We have some nice data but the mechanism of action is still yet to be elucidated. It would be really interesting in the future to see if we’re heating up the dermatophyte and destroying it that way or are we changing the keratin of the nail bed and making it inhospitable environment for the fungus that way. For nail psoriasis which -- I put this in here because I think sometimes we just don’t diagnose it enough. Certainly, if a patient has sausage digits or dactylitis, if they have enthesitis, they may not have any skin disease whatsoever but they might just have the nails involved and some joint issues. It’s important that we think about nail psoriasis and oftentimes it can look identical to onychomycosis. You can even have them intersect at the same time where you have nail fungus and psoriatic nail disease at the same time. It can be really challenging at times to treat. Certainly, classically we’re looking for pitting. We’re looking for salmon patches or oil patches. We’re looking for onycholysis and hypokeratosis of the nail bed.

[15:13]

All those things really are present and again look a lot like onychomycosis. But the other thing that we’ll see with these patients is the Koebner phenomenon where if we traumatize the area, we can have further spreading or further propagation of the disease. One of the things that I’ll see with these patients is they may not have all of their nails infected but those that are hammer digits that are biomechanically getting traumatized on a daily basis might exhibit the disease versus the nails that don’t. From a clinical trial standpoint, there’s something called the NAPSI scale which we won’t use in clinical practice but it’s a way that a lot of these studies have tried to sort of show how these products work for nail psoriasis. Now, one of the products that I have used classically for nail psoriasis is Tazorac which is tazarotene. Now Tazorac is a Retin-A and if you have any teenagers at home or you’ve ever used any topical acne products yourself, you might be familiar with this. I’ve used this Tazorac gel under occlusion, meaning a Band-Aid, for my patients to try to reduce some onycholysis and some pitting and that’s been okay. It’s worked for certain extent. In other markets, they’ve used clobetasol nail lacquer which we don’t have in the market here yet. I’ve also used something called calcitriol which is a vitamin D analog. That’s an ointment that’s known as Vectical that you can again use under occlusion on a daily basis. A lot of people agree that the standard should be something called oral acitretin or Soriatane but the problem is, is that patient selection really should be managed with this. This isn’t something I’m going to readily give to my females who are of childbearing age. There’s a lot of other things that have to go along with it just like if you were to put a patient on Accutane. It’s not something that you want to jump at prescribing at least from our perspective. I have used the pulsed dye laser on some of these nails and again I’ve not seen the changes that I’d like to see. Certainly a lot more research can go into looking at the laser for psoriatic nail disease. Some people have used infliximab or Remicade which is again a pretty significant drug to use on patients saying, “Alright, you’re going to go get your infusion every so many weeks and hopefully your nails will clear.” But this is something that I wouldn’t just use for nail psoriasis itself. It was something that if the patient had skin disease and joint disease that certainly would make more sense to put them on infliximab. What I have done sometimes is triamcinolone injections for my psoriatic nail patients. This was a patient who came to me saying, “Doc, they’ve put me on oral Lamisil twice. I feel that my nails just don’t seem to improve.” When I look at her nails, I said, “I have to ask you something. Do you have any skin rashes anywhere else?” And she said, “Well, yeah, I do. On the top of my butt, right below, right above in that area.” And I said, “Well, do you see a dermatologist for this?” She said, “Yeah. He treats me for my psoriasis.” I said, “Well, I think we’re really dealing here with nail psoriasis than anything else.” I started her on a series of triamcinolone injections where I inject in the proximal nailfold once monthly and she really did have a nice result and it’s something that can be used for inflammatory nail conditions. For onychocryptosis, it’s something obviously, you know, patients have painful nail borders but maybe they don’t want a nail procedure. What’s an alternative? There’s a Japanese dermatologist named Dr. Rye [phonetic] who has presented multiple times with the Council for Nail Disorders and has really interesting ideas about how can we buttress the nail from the skin. Now, podiatry might use cotton but she uses IV tubing and it’s an interesting thought, okay. Cut IV tubing and then literally glue it on the nail. She’s taking patients who have pretty significant granulation tissue that we hear would just jump in doing a nail procedure and certainly I would, my gut instinct would, but she says, “Alright, I’m just going to use this IV tubing, we’ll apply it to the sides and you can see how the nail grows out.” But it takes months and I think a lot of our patients here don’t have the patience to wait months for that granulation tissue to resolve or the pain. That’s it. Thank you so much for your attention.