Onychomycosis and the
`Role of Topical Antifungals
`
`Warren Joseph, DPM, FIDSA (chair), Richard Pollak, DPM, FACFAS, Tracey Vlahovic,
`DPM, Bryan Caldwell, DPM, Maureen Jennings, DPM, Scott Ashton, DPM, FACFAS,
`Bryan Markinson, DPM, FASPD, Alex Reyzelman, DPM, FACFAS, Jay Lifshen, DPM,
`FACFAS, Harry Goldsmith, DPM
`
`This supplement is supported by Valeant Pharmaceuticals
`
`Supplement to Podiatry Today® November 2013
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`

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`Table of Contents
`
`Onychomycosis: An Infectious Disease
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`Onychomycosis: Treatment Considerations
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`The Role of Efinaconazole 10% Solution in Onychomycosis Management
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` page 3
` page 7
` page 11
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`Panelists
`
`Warren Joseph, DPM, FIDSA (Chair)
`Dr. Joseph is a consultant in lower extremity in-
`fectious diseases and is a Fellow of the Infectious
`Diseases Society of America. He is affiliated with
`Roxborough Memorial Hospital in Philadelphia.
`
`Richard Pollak, DPM, FACFAS
`Dr. Pollak is a Diplomate of the American Board
`of Podiatric Surgery and Fellow of the American
`College of Foot and Ankle Surgeons. He is in private
`practice in San Antonio.
`
`Tracey Vlahovic, DPM
`Dr. Vlahovic is an Associate Professor and J. Stanley
`and Pearl Landau Faculty Fellow at the Temple Uni-
`versity School of Podiatric Medicine. She is a Diplo-
`mate of the American Board of Podiatric Surgery.
`
`Bryan Caldwell, DPM
`Dr. Caldwell is the Assistant Dean and Professor of
`Clinical Education and Clinic Operations at the
`College of Podiatric Medicine at Kent State Uni-
`versity. He is a Diplomate of the American Board of
`Podiatric Medicine.
`
`Maureen Jennings, DPM
`Dr. Jennings is the President of the Jennings Institute
`for Clinical Research in Brick, NJ She is an Adjunct
`Professor at Georgian Court University in Lakewood
`Township, NJ, and previously completed an NIH
`fellowship in clinical pharmacology at the Cornell
`University Medical Center.
`
`Scott Ashton, DPM, FACFAS
`Dr. Ashton is board certified by the American Board
`of Podiatric Surgery and the American Board of
`Quality Assurance and Utilization Review Physi-
`cians. He is a Fellow of the American College of
`Foot and Ankle Surgeons. Dr. Ashton is in private
`practice at multiple office locations in Texas.
`
`Bryan Markinson, DPM, FASPD
`Dr. Markinson is the Chief of Podiatric Medicine and
`Surgery in the Leni and Peter W. May Department
`of Orthopedic Surgery at the Mount Sinai School of
`Medicine in New York City. He is board certified by
`the American Board of Podiatric Medicine.
`
`Alexander Reyzelman, DPM, FACFAS
`Dr. Reyzelman is the Co-Director of the UCSF Center
`for Limb Preservation in San Francisco, and is an Associ-
`ate Professor at the California School of Podiatric Med-
`icine at Samuel Merritt College. He is board certified in
`foot surgery by the American Board of Podiatric Surgery.
`
`Jay Lifshen, DPM, FACFAS
`Dr. Lifshen is certified by the American Board of
`Podiatric Surgery. He is the founder and president of
`Podiatric Medical Partners of Texas, PA and is the po-
`diatric consultant to the Dallas Mavericks of the NBA.
`He practices in Irving, Tx.
`
`Harry Goldsmith, DPM, CSFAC
`Dr. Goldsmith is the CEO of Codingline. He is
`board-certified (administrative) by the American
`Board of Podiatric Surgery and is a certified surgical
`foot and ankle coder.
`
`
`The opinions expressed in this supplement are solely those of the authors. All participants received an honorarium for their contribution
`to the roundtable discussion.
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`Onychomycosis: An Infectious Disease
`Warren Joseph, DPM, FIDSA
`
`Onychomycosis is an infectious disease that should
`be treated with anti-infectives. Relatively rare 100 years
`ago, onychomycosis has become more common be-
`cause of changes in lifestyle (in particular urbanization,
`communal bathing areas, use of occlusive footwear, and
`increasing incidence of diabetes and HIV infection).
`The correlation between diabetes, tinea pedis and ony-
`chomycosis is well known. Also, people are involved in
`occupations and activities today that carry an increased
`risk, such as miners, soldiers and runners.1
`As an infection, onychomycosis has a genetic pre-
`disposition; an autosomal dominant trait with an in-
`ability to mount a cell mediatied response to T. rubrum.
`Left untreated onychomycosis is a progressive disease,
`spreading within the toenail to the rest of the toenails,
`and to other parts of the body. It can also spread from
`one person to the other. As a result, patients will often
`ask, “Is this contagious?” It can cause an immunologic
`response, affect quality of life (QoL), and as with any
`infection lead to recurrence or re-infection. This re-
`lapse can be a major issue because whenever a new
`product comes out for onychomycosis, people will ask,
`“Why should I treat it? It is just going to come back.”
`We are not curing the disease. We are putting it into re-
`mission, and this leads to the important question about
`how we manage onychomycosis long-term.
`Onychomycosis is progressive, recurring and re-
`quires treatment.2,3 There can be psychological issues
`if it impacts QoL, and it can be symptomatic caus-
`ing pain on ambulation.4 There are risks for further
`complications especially in our diabetic patients, those
`with peripheral vascular disease (PVD) and the im-
`munocompromised patient.5 Onychomycosis is a res-
`ervoir for infection, spreading to other nails and ana-
`tomical sites4 and other individuals.5 There can also be
`systemic or multi-system involvement. For example, it
`may be a trigger for asthma attacks in rare cases,6 and
`be a source of cellulitis.5
`Onychomycosis is a common nail disease with
`over 35 million people having it in the United States.
`It causes 11.2 million office visits and the number of
`patients diagnosed with onychomycosis is about 6.3
`million.7 There are a significant number of patients
`who have onychomycosis, but have never been to
`a physician to be diagnosed. There is an increase in
`incidence with age. In those patients who are diag-
`nosed, 59% are aged 55 and over, and only 20.5% of
`the diagnosed population are between ages 30 and
`45.7 In addition, podiatrists tend to see an older pop-
`ulation than dermatologists.
`
`Onychomycosis accounts for approximately 50% of
`all nail disease.8 In discussing the epidemiology of ony-
`chomycosis it is important to consider the host, the en-
`vironment and the pathogen (Figure 1). There is little
`that can be done about the host (age, genetic make up,
`co-existing diseases), and the key pathogens, T. rubrum or
`Trichophyton mentagrophytes are ubiquitous organisms that
`you can find in most places.
`Onychomycosis can be caused by dermatophytes,
`molds or yeast. While the most common are T. rubrum
`and T. mentagrophytes, variation exists worldwide.9 The
`role of molds as a pathogen is still not clear. Although
`they do not have the capability of digesting keratin,
`so it is unclear physiologically how they would cause
`infection. There appear to be 2-3 molds that can be
`pathogens and significant criteria do need to be met
`for diagnosis of a mold infection.
`In diagnosing onychomycosis, most studies suggest
`that periodic acid-Schiff (PAS) staining of nail clippings
`is probably the most sensitive and predictive test,10,11
`but it is not specific to the individual organism un-
`like mycological fungal culturing. Fungal culture is the
`only test that can confirm a specific pathogen, mode of
`infection and vitality of fungi.10,11 However, there are
`limitations. For example, it may take up to a month for
`cultures to grow, and the vitality of the cultures may
`be adversely affected by transport to a remote labo-
`ratory.12 There is a wide variability in KOH sensitivi-
`ty and this test is prone to false positive/false negative
`results.10 Molecular means of diagnosis is probably the
`future (especially polymerase chain reaction [PCR] and
`molecular sequencing). What are the best ways to make
`a diagnosis in your everyday practice, and what will the
`payors accept to confirm a diagnosis of onychomycosis
`are two important practical questions we face every day.
`As we have already discussed, onychomycosis can
`have a significant impact on QoL. A total of 258 pa-
`tients with confirmed onychomycosis were surveyed
`by telephone at three centers using a validated ques-
`tionnaire.13 Pain was found in 48% of patients, embar-
`rassment 7%, nail pressure 40%, shoe discomfort 38%
`and physician visits averaged 3.8/year.13 This research
`is important for two reasons – the incidence of pain
`and the number of physician visits. Any condition in
`which pain exists in almost 50% of our patients cannot
`be considered a cosmetic condition, and four physician
`visits a year has significant economic consequences.
`It is known that there is a genetic pre-disposition
`to T. rubrum in some families,14,15 with every affected
`child having at least one affected parent.15 In families
`
`
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`Onychomycosis and the Role of Topical Antifungals 3
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`Figure 1: Epidemiology of Onychomycosis
`
`Onychomycosis is the most common nail disease, accounting for approximately 50% of all
`nail problems1
`
`• Hygiene
`• Shoe gear
`• Hyperhidrosis
`• Communal habitat
`• Contagion (e.g., pool decks)
`
`Nail
`
`• Age1
`• Genetics1
`• Peripheral arterial disease
`• Diabetes4
`• Presence of tinea pedis
`•
`Immunocompromised
`(e.g., HIV-positive)
`
`•
`•
`•
`•
`
` Trauma3
` Infection
` Secondary infection
` Reinfection
`
`Onychomycosis
`
`1Faergemann J, Baran R. Epidemiology, clinical presentation and diagnosis of onychomycosis. Br J Dermatol. 2003;149(suppl 65):1-4. 2Rogers P,
`Bassler M. Treating onychomycosis. Am Fam Physician. 2001;63(4):663-672,677-678. 3Scher RK, Daniel CR, eds. Nails: Therapy-Diagnosis-Surgery.
`2nd ed. Philadelphia, PA: W.B. Saunders Co; 1997. 4Gupta AK, Konnikov N, MacDonald P, et al. Prevalence and epidemiology of toenail ony-
`chomycosis in diabetic subjects: a multicentre survey. Br J Dermatol. 1998;139(4):665-671.
`
`the most common primary T. rubrum infections pres-
`ent as tinea pedis with distal subungual onychomycosis
`(DSO) as a secondary infection.14 Patients predisposed
`to onychomycosis are also going to be predisposed to
`having fungal infections in other parts of their body,
`such as tinea corporis, tinea cruris and tinea pedis.
`Tinea pedis is inexorably linked to onychomycosis.
`Onychomycosis starts in almost every case as tinea pe-
`dis. The fungus infects the skin, minor trauma breaks
`the hyponychial seal and the fungus migrates beneath
`the nail. Maybe the patient doesn’t even recognize it
`is happening. Essentially, all patients with onychomy-
`cosis have or have had tinea pedis at one point, and
`you really need to treat both. If you treat patients with
`an oral antifungal for their onychomycosis it will treat
`their tinea pedis as well. But with a topical you have to
`treat the tinea pedis in addition, otherwise it will just
`act as a reservoir for re-infection of the tinea. Likewise
`if you only treat the tinea pedis the onychomycosis
`can re-infect the skin.
`Onychomycosis is very common in patients with
`diabetes, where the prevalence is 2.8 times greater than
`in patients without diabetes.16 Thickened fungal nails
`can develop serious bacterial infections and foot ulcer-
`ations.17 Patients with diabetic neuropathy tend to wear
`shoes that are too small, because they can’t feel that the
`shoe doesn’t fit well, leading to ulceration. Foot ulcer-
`ation has been reported in about 19% of diabetics, and
`in those with ulceration the prevalence of amputation
`
`ranges from 6%-43% depending on the severity of the
`ulceration.18,19 In patients who have had a unilateral am-
`putation the 5-year mortality rate is between 39% and
`68%.20 There is also a correlation between secondary
`gangrene infections in diabetics with onychomycosis.21
`DISCUSSION POINTS: Prevalence
`Jay Lifshen, DPM: Onychomycosis is very preva-
`lent in our practice; being in Texas with the Southern
`climate we see a lot more of these types of problems.
`From an economic perspective, our group has creat-
`ed our own lab to capture the technical component
`of the lab expense. In probably 15%-20% of all the
`patients we see, onychomycosis is their primary pre-
`senting complaint. Our practice has a lot of diabetic
`patients and many return for repeat foot care second-
`ary to their diabetes; many are considered high-risk
`patients in light of PAD and/or neuropathy.
`Bryan Caldwell, DPM: I have practiced in both
`Florida and Ohio, so I can concur about the prevalence
`of onychomycosis in Southern climates. In Ohio, we
`have 2 very different demographics, having a clinic in
`the suburbs and one in the city. The city clinic sees a
`predominantly African-American population. We see
`more onychomycosis patients here than in the suburbs.
`Indeed, almost every other patient we see has onycho-
`mycosis or at least a chronic tinea pedis leading to on-
`ychomycosis. I really believe that there is a genetic sus-
`ceptibility for the development of chronic tinea pedis
`
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`and onychomycosis, but also an increase in prevalence
`in the Southern states, so we have to consider environ-
`ment and genetics. Does someone who is genetically
`predisposed to onychomycosis assume a greater risk if
`he or she moves to a Southern climate? Diabetes is in-
`creasing for a variety of reasons, so it is no surprise that
`onychomycosis rates are increasing as well, given that
`there is a 3:1 susceptibility issue.
`Maureen Jennings, DPM: My podiatric practice is
`predominantly a medical practice in New Jersey, where
`patients are >55-years-old, have a high incidence of di-
`abetes and I probably see 65%-70% of the practice hav-
`ing onychomycosis, either primary or secondary. For a
`lot of my patients, it is embarrassment—they don’t like
`the way it looks. Pain relief is a definite consideration
`with the hope of improving nail appearance.
`Scott Ashton, DPM: As the presenting or at least
`secondary complaint, it is probably 30%-40% of the
`patients that I see. A lot choose not to have their ony-
`chomycosis treated; some don’t have the where with-
`al to treat it properly. But there are a lot of fastidious
`folks in North Dallas who want their toenails to be
`immaculate. It is a problem in populations that spend
`most of their time in sandals with their toenails visually
`exposed. I don’t see pain as the presenting complaint—
`dystrophy is the main issue, appearance and the fear of
`it spreading to other nails.
`Alex Reyzelman, DPM: I agree we see a lot of
`onychomycosis in these communities. It may be an
`interesting area to explore. They are likely to have
`more diabetes and alcohol-induced neuropathies. I
`also think we have to look at the different age groups.
`Embarrassment is a key psychological issue. Onycho-
`mycosis is certainly more recognized following pro-
`motion to patients.
`Richard Pollak, DPM: I used to think that ony-
`chomycosis was a “by the way disease” and not neces-
`sarily the primary reason patients were coming in to
`see us in the office. The Doyle data ties in with the
`public health issue and bears out our experience.21 The
`incidence of onychomycosis is clearly higher in the di-
`abetic patient population, or the underserved patient
`population. I can’t think of one patient I didn’t am-
`putate on (other than trauma) that didn’t have ony-
`chomycosis, or tinea pedis, meaning that these people
`have bad disease state. This is an underserved patient
`population, they are not being treated and they are just
`not taking care of themselves.
`Tracey Vlahovic, DPM: I am seeing patients with
`the absence of tinea pedis, but with the presence of nail
`disease due to pedicures. We are typically seeing this
`because they have been inoculated with a dirty un-
`sterilized instrument. I do a lot of education on appro-
`
`priate pedicures and looking for places that autoclave.
`Another concern I get in my practice is nail discolor-
`ation. They might have already been treated by anoth-
`er physician and been given oral terbinafine, but what
`they have is not fungal. I see a lot of misdiagnosis. I am
`telling patients that it is more likely they don’t have
`fungal disease than they do. It is my job to determine if
`it is really onychomycosis or not.
`Harry Goldsmith, DPM: Total annual Medicare
`reimbursement for routine foot care (eg, debridement
`and trimming of nails) is $350-375 million. Compared
`to overall Medicare expenditures, that’s a relatively small
`amount, but for podiatry, it is significant. CPT 11721
`(debridement of nails 6 through 10) is the #1 billed
`code to Medicare by podiatrists in just about every
`state. CPT 11720 (debridement of nails 1-5) consis-
`tently is listed in the top 10 codes billed by podiatrists.
`Debridement of nail codes are the #1 audited codes
`for podiatrists. Prior to billing these codes, Medicare
`does not require laboratory proof that onychomyco-
`sis is present; it only needs the doctor to document
`clinical findings consistent with onychomycosis. Some
`Medicare contractor policies will also allow the billing
`of these debridement codes because the nails are thick,
`dystrophic or misshaped. One should keep in mind that
`the performance of nail debridement, while reducing
`the “fungal load” in the nails, in and of itself does not
`mean that the nail has been or is actively being treated,
`unless you consider debridement a primary treatment.
`Typical qualifying conditions for billing either CPT
`11720 or CPT 11721 are either associated with “at
`risk” routine foot care or symptoms (ie, pain) associat-
`ed with nails. Regardless, payers have been increasingly
`aware that in addition to the debridement of nails, the
`identification and treatment of the nail fungus is crit-
`ical to the prevention of fungal spread to other nails
`and surrounding skin. The public as a result of years
`of direct marketing—pharmaceutical companies, laser
`manufacturers and podiatrists—are increasingly aware
`that a nail infected with fungus can be treated and that
`it wasn’t just an ugly nail anymore. Awareness is driv-
`en by market activity and market activity is driven by
`public awareness.
`Dr. Joseph: Dermatologists say that 50% of nail
`dystrophies are not onychomycosis. In a podiatric prac-
`tice more likely 75% of the nails we see are onychomy-
`cotic toenails.
`DISCUSSION POINTS: Diagnosis
`Dr. Pollak: I will often do a PAS stain to confirm
`the diagnosis of fungus. I occasionally will do a PAS
`stain to prove the negative. Often times, fungus may
`be misdiagnosed. Many patients would like treat-
`
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`Onychomycosis and the Role of Topical Antifungals 5
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`ment for fungus when they clearly have dystrophic
`nails and the etiology is trauma and not fungus. In
`practice, sometimes I will do a KOH in the office
`to verify if there is tinea pedis when I am consid-
`ering a topical medication for athlete’s foot. I rarely
`do a fungal culture in the office for onychomycosis.
`When I question the etiology, I prefer the PAS stain
`over the culture because of the high sensitivity of the
`PAS stain as well as it only takes a few days to receive
`the result from the laboratory.
`Dr. Vlahovic: I have predominantly Medicaid pa-
`tients, a lot of whom are formally capitated so I am
`forced to do KOH and culture (I have difficulty getting
`generic ciclopirox lacquer covered). I virtually never
`order a PAS because Medicaid won’t pay for it. Also,
`the patient may have seen several podiatrists before me
`so that is why I have started doing more of the PCR to
`see what kind of nondermatophyte mold I am dealing
`with. I use a dermatoscope that allows me to see pit-
`ting and other nail pathologies a little bit easier, which
`allows me to try to rule out melanoma.
`Dr. Lifshen: Cost is not an issue because if I
`am going to treat someone with oral terbinafine, I
`am going to get a PAS. There are a lot of patients
`who come in that have failed various treatments be-
`fore. You look at their nails and clinically they look
`like onychomycotic toenails, but they are not. Why
`would I subject them to another course of terbinaf-
`ine or switch them to itraconazole, if I don’t get the
`laboratory confirmation of onychomycosis? We have
`a standard protocol in our lab that if the PAS is nega-
`tive we will do a Gomori methenamine silver (GMS)
`stain. This stain can pick up some positives, even
`when the PAS is negative. If I am putting someone
`on a topical medication, I am not as strict. If patients
`say in advance that they are not interested in any oral
`medication, only topical, I would probably not do a
`PAS. Then if the topical doesn’t work, is it just that it
`was one of those 90% cases where it is not effective
`or is it because it was not a dermatophytic infection
`to begin with? You don’t know why it didn’t work
`and this can sometimes be a problem.
`Dr. Reyzelman: I tend to lean on the clinical di-
`agnosis a lot. If they have tinea pedis/multiple nails in-
`volved and fungal debris then I don’t necessarily get a
`PAS, only with high risk.
`Dr. Goldsmith: In the past, some Medicare con-
`tractor policies required the doctor to perform lab
`work to confirm the presence of onychomycosis or
`
`other pathology prior to allowing palliative care of
`the fungus nails. Those carriers found out in pretty
`short order that the volume of nail debridement did
`not significantly diminish. Rather the expenses as-
`sociated with these mandated laboratory tests were
`adding significant dollars to provide the debride-
`ment of mycotic nails benefit. Most of the Medicare
`carriers have dropped lab work requirements and
`leave it up to the doctor to clinically make and doc-
`ument the diagnosis. This is currently Medicare’s ap-
`proach in cases of palliative care. In cases of definitive
`treatment of onychomycosis (eg, use of anti-fungal
`medications), the need for laboratory confirmation
`and identification of the organism(s) is predicated
`on the standard of care. I encourage doctors treating
`onychomycosis to have a specific office protocol that
`will be followed for that treatment.
`Dr. Caldwell: When a new patient presents with
`fungal appearing nails we give them all the options
`straight away—we discuss debridement (you either go
`the infectious disease route or the pain management
`route and in the latter that is where debridement
`comes in regardless of reimbursement), topicals, laser
`and orals. We review the advantages of each, includ-
`ing the success rates and financial ramifications and
`let them choose. If they choose debridement we do
`not usually confirm with PAS stain or culture. If the
`patient chooses an oral treatment, or even topical/la-
`ser we will then do a PAS stain and a fungal culture.
`However, we don’t routinely test prior to topical ther-
`apy, but as new products come out we may modify
`our protocols depending on cost to patient. Do I be-
`lieve we are treating some non-onychomycosis with
`topicals as a result? Probably.
`Dr. Ashton: I rarely do KOH on a non-trial pa-
`tient, so I am looking at a PAS stain in just about every
`patient with what I think is onychomycosis. But if they
`refuse I will still give them oral therapy if I agree with
`it clinically, and document that they refused the tests on
`economic grounds. I rarely use ciclopirox and if I do, I
`wouldn’t do a PAS (although before it went generic we
`would to ensure coverage).
`Dr. Jennings: I give my patients a complete list of
`all of the options. I am a firm believer in education. If
`the choice was an oral agent, I would definitely do a
`PAS to confirm diagnosis. If using a topical and 95%
`sure it was onychomycosis, I probably wouldn’t do di-
`agnostic testing.
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`Onychomycosis: Treatment Considerations
`Warren Joseph, DPM
`
`There is a disconnect between how we approach
`onychomycosis, and what we know about the disease.
`There is a disconnect between how many patients have
`the disease, and how many are treated; what patients
`perceive of the disease, and the need to treated versus
`those who are actually treated; and between what po-
`diatrists see as being efficacious, and what we use, and
`the fear of risks of oral therapy versus the facts (that the
`risk is minimal).
`Overall, it is estimated that 35-36 million Americans
`have onychomycosis. Of these, only 6.3 million have
`been diagnosed by a physician, and only 2.5 million
`receive treatment each year. That leaves 33 million un-
`treated patients!
`Current therapies include prescription antifungals,
`soaking, debridement/avulsion and “over-the-counter”
`(OTC) medications. What is most striking is the 42% of
`patients who have tried OTC treatments, compared to
`12% who are receiving a prescription antifungal.22 Of
`course, there are going to be patients who come in to
`our practice who just don’t care; they have lived with
`their onychomycosis for years and don’t want to do
`anything about it, but the OTC group represent people
`who are actively doing something for their onychomy-
`cosis, because they want to get rid of it.
`Podiatric physicians’ treatment choices and their
`perceptions of treatment efficacy are quite different.
`For example, only 23% of podiatrists perceive that de-
`bridement is efficacious, and yet it is the #1 treatment
`recommended by podiatrists (in 75% of cases). Eighty
`percent of podiatrists perceive that oral antifungals are
`the most effective treatment, but they only recommend
`them in 30% of cases. Topicals are somewhere in the
`middle —perceived as effective by 7% of podiatrists yet
`fairly widely used (in 48% of cases).23
`Current approaches to treatment include mechan-
`ical/surgical (ie, debridement, P&A technique, nail
`avulsion),24 topical therapy, oral therapy and combi-
`nation therapy with debridement.25 Of course with
`ciclopirox, combining with debridement is in the
`package insert, but with newer products, this may not
`be the case. By combining debridement would you
`increase efficacy?
`Medical debridement has been the mainstay of the
`podiatric approach, and it does reduce thickness and
`length of the nail, causes decreased pain/pressure (one
`of the chief patient complaints) and may decrease the
`fungal load. It also makes the nail temporarily look a
`little bit better, but it does not address the fungus. De-
`bridement is not a treatment for fungal infection.
`
`The surgical approach (ie, removal of the nail) tends
`not to be used the same time as a topical, and tends to
`be used less currently as it can be painful and lead to
`secondary bacterial infection. If re-growth occurs, it is
`important to address the fungus.
`So what’s new in the world of onychomycosis? As
`of March 2013, 63 clinical trials were listed at www.
`clinicaltrials.gov with only 5 currently recruiting. Lots
`of treatment approaches are being looked at, includ-
`ing patches, iontophoresis with terbinafine (not being
`pursued anymore), itraconazole 200 mg once daily
`(now FDA approved), various lasers, micro drilling to
`increase the penetration of the topical and various new
`topicals are being investigated including luliconazole,
`amorolfine, transfersome and antimicrobial plasma.
`Ciclopirox nail lacquer is currently the only
`FDA-approved topical therapy for onychomycosis. Two
`products (efinaconazole and tavaborole) have recently
`completed their phase 3 trials and luliconazole is in
`phase 2/3.
`Based on the pivotal trials and FDA strict criteria,
`the cure and success rates were 8.5% and 12%, respec-
`tively, after 48 weeks treatment with ciclopirox nail lac-
`quer.26 A subsequent meta-analysis reported a clinical
`response rate of 52.4%±9.0%.27 These data and those
`from other studies that followed have brought up the
`whole debate of how we define treatment success in
`onychomyosis and what is an appropriate length of
`treatment (especially with the topical products).
`There are only two terms consistently applied in
`clinical trials—mycologic cure and complete cure.
`Mycologic cure is the lowest barrier, easiest to achieve
`and as a result reports the highest numbers. Complete
`cure is the highest barrier—how often is the nail 100%
`normal in appearance? Almost never, which is why the
`level of complete cure tends to be low. As a result a lot
`of intermediate endpoints (ie, clinical success, almost
`clear) have been reported in clinical trails, and different
`methodologies have been adopted to determine the
`extent of nail involvement. There is certainly confu-
`sion amongst podiatrists and comparing efficacy from
`different studies is difficult. Even the range of severity
`(percent nail involvement) varies amongst onychomy-
`cosis studies, however the mean values may be similar.
`So what is the role of topicals in the treatment of
`onychomycosis? They are generally used for mild to
`moderate DSO (although even here the severity terms
`are not well defined). They certainly represent an alter-
`native therapy for patients who cannot or will not take
`an oral therapy (and a lot of patients do come in and
`
`
`
`Onychomycosis and the Role of Topical Antifungals 7
`
`

`

`Table 1: Preventive Strategies to Control Recurrence of Onychomycosis
`
`say oral products are dangerous given what they have
`read about them on the Internet, or there is physician
`confusion about drug interactions). Topicals are poten-
`tial adjunctive therapy along with the orals (inside out
`and outside in) in moderate to severe disease; and a big
`area that has not been seriously looked at is their use in
`prevention of recurrence/maintenance therapy.
`Three oral agents are FDA approved: itraconazole,
`terbinafine and griseofulvin. Terbinafine is considered
`the gold standard in terms of cure rates (>70% success
`rate reported in a meta-analysis of the clinical studies).28
`There is almost no research into new oral agents, prob-
`ably because of the efficacy and the cost of generic ter-
`binafine. In a large randomized, open label multicenter
`study with oral terbinafine and aggressive debridement
`(IRON-CLAD), no clinically significant changes in
`liver transaminase levels were observed 6 weeks after
`treatment or after 12 weeks in those tested.29 So oral
`drugs are not so dangerous, but there is still a percep-
`tion out there that they are.
`Relapse (recurrence or reinfection) is a significant
`problem in the treatment of onychomycosis. As we dis-
`cussed earlier, because there is genetic predisposition to
`onychomycosis, we should be talking about remission
`rather than cure. Relapse of onychomycosis may be due
`to reinfection or incomplete eradication of the origi-
`nal fungus with treatment.2 It has been shown with
`orals that 22% of patients experience a relapse when
`followed up to 3 years after initial treatment.2 More re-
`cently, it was similarly shown that 4 years after an initial
`12-week treatment course, only 33%-35% of patients
`still exhibited evidence of a clinical cure and 28%-35%
`of patients remained completely cured.30
`In reality, the recurrence rate is 100% unless we
`manage the disease appropriately, and there are a num-
`ber of preventative strategies we can adopt to minimize
`
`recurrence. These include using maintenance treatment
`regimens as well as practical steps the patient can follow
`at home (Table 1).
`As mentioned earlier, comparing efficacy across
`studies is complex given the different degrees of nail
`involvement, patient age and demographic differences.
`Nevertheless, we can provide some guidance based on
`the pivotal studies and the common criteria of myco-
`logic and complete cure rates. As can be seen in Table
`2, reported mycologic cure rates range from 31% to
`70% and complete cure rates range from 5.5% to 38%.
`Use of lasers to treat onychomycosis has become
`more commonplace. However, there is very little data
`as to whether lasers work or not. There are only two
`published trials, and yet a number of lasers carry FDA
`clearance. The wording of the clearance is for tempo-
`rary improvement in the appearance of the nail. None
`are labelled for the actual treatment of onychomycosis.
`Another area of significant promotion is the wide vari-
`ety of OTC products claiming to be “effective 80% of
`the time” without defining what this means.
`DISCUSSION POINTS: Treatment Options
`Dr. Lifshen: I do not treat all cases of onychomy-
`cosis. Elderly patients who come in many times do not
`need to be treated. Usually, I just make sure they are
`comfortable and that they can get their shoes on, and
`that’s it. We also have to keep in mind the physical lim-
`itations of that age group. We have a