Onychomycosis and the Role of Topical Antifungals

16 Pages·2013·1.93 MB·English

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
Table of Contents
Onychomycosis: An Infectious Disease page 3
Onychomycosis: Treatment Considerations page 7
The Role of Efinaconazole 10% Solution in Onychomycosis Management page 11
Panelists
Warren Joseph, DPM, FIDSA (Chair) Scott Ashton, DPM, FACFAS
Dr. Joseph is a consultant in lower extremity in- Dr. Ashton is board certified by the American Board
fectious diseases and is a Fellow of the Infectious of Podiatric Surgery and the American Board of
Diseases Society of America. He is affiliated with Quality Assurance and Utilization Review Physi-
Roxborough Memorial Hospital in Philadelphia. cians. He is a Fellow of the American College of
Foot and Ankle Surgeons. Dr. Ashton is in private
Richard Pollak, DPM, FACFAS practice at multiple office locations in Texas.
Dr. Pollak is a Diplomate of the American Board
of Podiatric Surgery and Fellow of the American Bryan Markinson, DPM, FASPD
College of Foot and Ankle Surgeons. He is in private Dr. Markinson is the Chief of Podiatric Medicine and
practice in San Antonio. Surgery in the Leni and Peter W. May Department
of Orthopedic Surgery at the Mount Sinai School of
Tracey Vlahovic, DPM Medicine in New York City. He is board certified by
Dr. Vlahovic is an Associate Professor and J. Stanley the American Board of Podiatric Medicine.
and Pearl Landau Faculty Fellow at the Temple Uni-
versity School of Podiatric Medicine. She is a Diplo- Alexander Reyzelman, DPM, FACFAS
mate of the American Board of Podiatric Surgery. Dr. Reyzelman is the Co-Director of the UCSF Center
for Limb Preservation in San Francisco, and is an Associ-
Bryan Caldwell, DPM ate Professor at the California School of Podiatric Med-
Dr. Caldwell is the Assistant Dean and Professor of icine at Samuel Merritt College. He is board certified in
Clinical Education and Clinic Operations at the foot surgery by the American Board of Podiatric Surgery.
College of Podiatric Medicine at Kent State Uni-
versity. He is a Diplomate of the American Board of Jay Lifshen, DPM, FACFAS
Podiatric Medicine. Dr. Lifshen is certified by the American Board of
Podiatric Surgery. He is the founder and president of
Maureen Jennings, DPM Podiatric Medical Partners of Texas, PA and is the po-
Dr. Jennings is the President of the Jennings Institute diatric consultant to the Dallas Mavericks of the NBA.
for Clinical Research in Brick, NJ She is an Adjunct He practices in Irving, Tx.
Professor at Georgian Court University in Lakewood
Township, NJ, and previously completed an NIH Harry Goldsmith, DPM, CSFAC
fellowship in clinical pharmacology at the Cornell Dr. Goldsmith is the CEO of Codingline. He is
University Medical Center. 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.
2 Onychomycosis and the Role of Topical Antifungals
Onychomycosis: An Infectious Disease
Warren Joseph, DPM, FIDSA
Onychomycosis is an infectious disease that should Onychomycosis accounts for approximately 50% of
be treated with anti-infectives. Relatively rare 100 years all nail disease.8 In discussing the epidemiology of ony-
ago, onychomycosis has become more common be- chomycosis it is important to consider the host, the en-
cause of changes in lifestyle (in particular urbanization, vironment and the pathogen (Figure 1). There is little
communal bathing areas, use of occlusive footwear, and that can be done about the host (age, genetic make up,
increasing incidence of diabetes and HIV infection). co-existing diseases), and the key pathogens, T. rubrum or
The correlation between diabetes, tinea pedis and ony- Trichophyton mentagrophytes are ubiquitous organisms that
chomycosis is well known. Also, people are involved in you can find in most places.
occupations and activities today that carry an increased Onychomycosis can be caused by dermatophytes,
risk, such as miners, soldiers and runners.1 molds or yeast. While the most common are T. rubrum
As an infection, onychomycosis has a genetic pre- and T. mentagrophytes, variation exists worldwide.9 The
disposition; an autosomal dominant trait with an in- role of molds as a pathogen is still not clear. Although
ability to mount a cell mediatied response to T. rubrum. they do not have the capability of digesting keratin,
Left untreated onychomycosis is a progressive disease, so it is unclear physiologically how they would cause
spreading within the toenail to the rest of the toenails, infection. There appear to be 2-3 molds that can be
and to other parts of the body. It can also spread from pathogens and significant criteria do need to be met
one person to the other. As a result, patients will often for diagnosis of a mold infection.
ask, “Is this contagious?” It can cause an immunologic In diagnosing onychomycosis, most studies suggest
response, affect quality of life (QoL), and as with any that periodic acid-Schiff (PAS) staining of nail clippings
infection lead to recurrence or re-infection. This re- is probably the most sensitive and predictive test,10,11
lapse can be a major issue because whenever a new but it is not specific to the individual organism un-
product comes out for onychomycosis, people will ask, like mycological fungal culturing. Fungal culture is the
“Why should I treat it? It is just going to come back.” only test that can confirm a specific pathogen, mode of
We are not curing the disease. We are putting it into re- infection and vitality of fungi.10,11 However, there are
mission, and this leads to the important question about limitations. For example, it may take up to a month for
how we manage onychomycosis long-term. cultures to grow, and the vitality of the cultures may
Onychomycosis is progressive, recurring and re- be adversely affected by transport to a remote labo-
quires treatment.2,3 There can be psychological issues ratory.12 There is a wide variability in KOH sensitivi-
if it impacts QoL, and it can be symptomatic caus- ty and this test is prone to false positive/false negative
ing pain on ambulation.4 There are risks for further results.10 Molecular means of diagnosis is probably the
complications especially in our diabetic patients, those future (especially polymerase chain reaction [PCR] and
with peripheral vascular disease (PVD) and the im- molecular sequencing). What are the best ways to make
munocompromised patient.5 Onychomycosis is a res- a diagnosis in your everyday practice, and what will the
ervoir for infection, spreading to other nails and ana- payors accept to confirm a diagnosis of onychomycosis
tomical sites4 and other individuals.5 There can also be are two important practical questions we face every day.
systemic or multi-system involvement. For example, it As we have already discussed, onychomycosis can
may be a trigger for asthma attacks in rare cases,6 and have a significant impact on QoL. A total of 258 pa-
be a source of cellulitis.5 tients with confirmed onychomycosis were surveyed
Onychomycosis is a common nail disease with by telephone at three centers using a validated ques-
over 35 million people having it in the United States. tionnaire.13 Pain was found in 48% of patients, embar-
It causes 11.2 million office visits and the number of rassment 7%, nail pressure 40%, shoe discomfort 38%
patients diagnosed with onychomycosis is about 6.3 and physician visits averaged 3.8/year.13 This research
million.7 There are a significant number of patients is important for two reasons – the incidence of pain
who have onychomycosis, but have never been to and the number of physician visits. Any condition in
a physician to be diagnosed. There is an increase in which pain exists in almost 50% of our patients cannot
incidence with age. In those patients who are diag- be considered a cosmetic condition, and four physician
nosed, 59% are aged 55 and over, and only 20.5% of visits a year has significant economic consequences.
the diagnosed population are between ages 30 and It is known that there is a genetic pre-disposition
45.7 In addition, podiatrists tend to see an older pop- to T. rubrum in some families,14,15 with every affected
ulation than dermatologists. child having at least one affected parent.15 In families
Onychomycosis and the Role of Topical Antifungals 3
Figure 1: Epidemiology of Onychomycosis
Onychomycosis is the most common nail disease, accounting for approximately 50% of all
nail problems1
• Hygiene • Age1
• Shoe gear • Genetics1
Nail
• Hyperhidrosis • Peripheral arterial disease
• Communal habitat • Diabetes4
• Contagion (e.g., pool decks) • Presence of tinea pedis
• Immunocompromised
• Trauma3
(e.g., HIV-positive)
• 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- ranges from 6%-43% depending on the severity of the
ent as tinea pedis with distal subungual onychomycosis ulceration.18,19 In patients who have had a unilateral am-
(DSO) as a secondary infection.14 Patients predisposed putation the 5-year mortality rate is between 39% and
to onychomycosis are also going to be predisposed to 68%.20 There is also a correlation between secondary
having fungal infections in other parts of their body, gangrene infections in diabetics with onychomycosis.21
such as tinea corporis, tinea cruris and tinea pedis.
Tinea pedis is inexorably linked to onychomycosis. DISCUSSION POINTS: Prevalence
Onychomycosis starts in almost every case as tinea pe- Jay Lifshen, DPM: Onychomycosis is very preva-
dis. The fungus infects the skin, minor trauma breaks lent in our practice; being in Texas with the Southern
the hyponychial seal and the fungus migrates beneath climate we see a lot more of these types of problems.
the nail. Maybe the patient doesn’t even recognize it From an economic perspective, our group has creat-
is happening. Essentially, all patients with onychomy- ed our own lab to capture the technical component
cosis have or have had tinea pedis at one point, and of the lab expense. In probably 15%-20% of all the
you really need to treat both. If you treat patients with patients we see, onychomycosis is their primary pre-
an oral antifungal for their onychomycosis it will treat senting complaint. Our practice has a lot of diabetic
their tinea pedis as well. But with a topical you have to patients and many return for repeat foot care second-
treat the tinea pedis in addition, otherwise it will just ary to their diabetes; many are considered high-risk
act as a reservoir for re-infection of the tinea. Likewise patients in light of PAD and/or neuropathy.
if you only treat the tinea pedis the onychomycosis Bryan Caldwell, DPM: I have practiced in both
can re-infect the skin. Florida and Ohio, so I can concur about the prevalence
Onychomycosis is very common in patients with of onychomycosis in Southern climates. In Ohio, we
diabetes, where the prevalence is 2.8 times greater than have 2 very different demographics, having a clinic in
in patients without diabetes.16 Thickened fungal nails the suburbs and one in the city. The city clinic sees a
can develop serious bacterial infections and foot ulcer- predominantly African-American population. We see
ations.17 Patients with diabetic neuropathy tend to wear more onychomycosis patients here than in the suburbs.
shoes that are too small, because they can’t feel that the Indeed, almost every other patient we see has onycho-
shoe doesn’t fit well, leading to ulceration. Foot ulcer- mycosis or at least a chronic tinea pedis leading to on-
ation has been reported in about 19% of diabetics, and ychomycosis. I really believe that there is a genetic sus-
in those with ulceration the prevalence of amputation ceptibility for the development of chronic tinea pedis
4 Onychomycosis and the Role of Topical Antifungals
and onychomycosis, but also an increase in prevalence priate pedicures and looking for places that autoclave.
in the Southern states, so we have to consider environ- Another concern I get in my practice is nail discolor-
ment and genetics. Does someone who is genetically ation. They might have already been treated by anoth-
predisposed to onychomycosis assume a greater risk if er physician and been given oral terbinafine, but what
he or she moves to a Southern climate? Diabetes is in- they have is not fungal. I see a lot of misdiagnosis. I am
creasing for a variety of reasons, so it is no surprise that telling patients that it is more likely they don’t have
onychomycosis rates are increasing as well, given that fungal disease than they do. It is my job to determine if
there is a 3:1 susceptibility issue. it is really onychomycosis or not.
Maureen Jennings, DPM: My podiatric practice is Harry Goldsmith, DPM: Total annual Medicare
predominantly a medical practice in New Jersey, where reimbursement for routine foot care (eg, debridement
patients are >55-years-old, have a high incidence of di- and trimming of nails) is $350-375 million. Compared
abetes and I probably see 65%-70% of the practice hav- to overall Medicare expenditures, that’s a relatively small
ing onychomycosis, either primary or secondary. For a amount, but for podiatry, it is significant. CPT 11721
lot of my patients, it is embarrassment—they don’t like (debridement of nails 6 through 10) is the #1 billed
the way it looks. Pain relief is a definite consideration code to Medicare by podiatrists in just about every
with the hope of improving nail appearance. state. CPT 11720 (debridement of nails 1-5) consis-
Scott Ashton, DPM: As the presenting or at least tently is listed in the top 10 codes billed by podiatrists.
secondary complaint, it is probably 30%-40% of the Debridement of nail codes are the #1 audited codes
patients that I see. A lot choose not to have their ony- for podiatrists. Prior to billing these codes, Medicare
chomycosis treated; some don’t have the where with- does not require laboratory proof that onychomyco-
al to treat it properly. But there are a lot of fastidious sis is present; it only needs the doctor to document
folks in North Dallas who want their toenails to be clinical findings consistent with onychomycosis. Some
immaculate. It is a problem in populations that spend Medicare contractor policies will also allow the billing
most of their time in sandals with their toenails visually of these debridement codes because the nails are thick,
exposed. I don’t see pain as the presenting complaint— dystrophic or misshaped. One should keep in mind that
dystrophy is the main issue, appearance and the fear of the performance of nail debridement, while reducing
it spreading to other nails. the “fungal load” in the nails, in and of itself does not
Alex Reyzelman, DPM: I agree we see a lot of mean that the nail has been or is actively being treated,
onychomycosis in these communities. It may be an unless you consider debridement a primary treatment.
interesting area to explore. They are likely to have Typical qualifying conditions for billing either CPT
more diabetes and alcohol-induced neuropathies. I 11720 or CPT 11721 are either associated with “at
also think we have to look at the different age groups. risk” routine foot care or symptoms (ie, pain) associat-
Embarrassment is a key psychological issue. Onycho- ed with nails. Regardless, payers have been increasingly
mycosis is certainly more recognized following pro- aware that in addition to the debridement of nails, the
motion to patients. identification and treatment of the nail fungus is crit-
Richard Pollak, DPM: I used to think that ony- ical to the prevention of fungal spread to other nails
chomycosis was a “by the way disease” and not neces- and surrounding skin. The public as a result of years
sarily the primary reason patients were coming in to of direct marketing—pharmaceutical companies, laser
see us in the office. The Doyle data ties in with the manufacturers and podiatrists—are increasingly aware
public health issue and bears out our experience.21 The that a nail infected with fungus can be treated and that
incidence of onychomycosis is clearly higher in the di- it wasn’t just an ugly nail anymore. Awareness is driv-
abetic patient population, or the underserved patient en by market activity and market activity is driven by
population. I can’t think of one patient I didn’t am- public awareness.
putate on (other than trauma) that didn’t have ony- Dr. Joseph: Dermatologists say that 50% of nail
chomycosis, or tinea pedis, meaning that these people dystrophies are not onychomycosis. In a podiatric prac-
have bad disease state. This is an underserved patient tice more likely 75% of the nails we see are onychomy-
population, they are not being treated and they are just cotic toenails.
not taking care of themselves.
Tracey Vlahovic, DPM: I am seeing patients with DISCUSSION POINTS: Diagnosis
the absence of tinea pedis, but with the presence of nail Dr. Pollak: I will often do a PAS stain to confirm
disease due to pedicures. We are typically seeing this the diagnosis of fungus. I occasionally will do a PAS
because they have been inoculated with a dirty un- stain to prove the negative. Often times, fungus may
sterilized instrument. I do a lot of education on appro- be misdiagnosed. Many patients would like treat-
Onychomycosis and the Role of Topical Antifungals 5
ment for fungus when they clearly have dystrophic other pathology prior to allowing palliative care of
nails and the etiology is trauma and not fungus. In the fungus nails. Those carriers found out in pretty
practice, sometimes I will do a KOH in the office short order that the volume of nail debridement did
to verify if there is tinea pedis when I am consid- not significantly diminish. Rather the expenses as-
ering a topical medication for athlete’s foot. I rarely sociated with these mandated laboratory tests were
do a fungal culture in the office for onychomycosis. adding significant dollars to provide the debride-
When I question the etiology, I prefer the PAS stain ment of mycotic nails benefit. Most of the Medicare
over the culture because of the high sensitivity of the carriers have dropped lab work requirements and
PAS stain as well as it only takes a few days to receive leave it up to the doctor to clinically make and doc-
the result from the laboratory. ument the diagnosis. This is currently Medicare’s ap-
Dr. Vlahovic: I have predominantly Medicaid pa- proach in cases of palliative care. In cases of definitive
tients, a lot of whom are formally capitated so I am treatment of onychomycosis (eg, use of anti-fungal
forced to do KOH and culture (I have difficulty getting medications), the need for laboratory confirmation
generic ciclopirox lacquer covered). I virtually never and identification of the organism(s) is predicated
order a PAS because Medicaid won’t pay for it. Also, on the standard of care. I encourage doctors treating
the patient may have seen several podiatrists before me onychomycosis to have a specific office protocol that
so that is why I have started doing more of the PCR to will be followed for that treatment.
see what kind of nondermatophyte mold I am dealing Dr. Caldwell: When a new patient presents with
with. I use a dermatoscope that allows me to see pit- fungal appearing nails we give them all the options
ting and other nail pathologies a little bit easier, which straight away—we discuss debridement (you either go
allows me to try to rule out melanoma. the infectious disease route or the pain management
Dr. Lifshen: Cost is not an issue because if I route and in the latter that is where debridement
am going to treat someone with oral terbinafine, I comes in regardless of reimbursement), topicals, laser
am going to get a PAS. There are a lot of patients and orals. We review the advantages of each, includ-
who come in that have failed various treatments be- ing the success rates and financial ramifications and
fore. You look at their nails and clinically they look let them choose. If they choose debridement we do
like onychomycotic toenails, but they are not. Why not usually confirm with PAS stain or culture. If the
would I subject them to another course of terbinaf- patient chooses an oral treatment, or even topical/la-
ine or switch them to itraconazole, if I don’t get the ser we will then do a PAS stain and a fungal culture.
laboratory confirmation of onychomycosis? We have However, we don’t routinely test prior to topical ther-
a standard protocol in our lab that if the PAS is nega- apy, but as new products come out we may modify
tive we will do a Gomori methenamine silver (GMS) our protocols depending on cost to patient. Do I be-
stain. This stain can pick up some positives, even lieve we are treating some non-onychomycosis with
when the PAS is negative. If I am putting someone topicals as a result? Probably.
on a topical medication, I am not as strict. If patients Dr. Ashton: I rarely do KOH on a non-trial pa-
say in advance that they are not interested in any oral tient, so I am looking at a PAS stain in just about every
medication, only topical, I would probably not do a patient with what I think is onychomycosis. But if they
PAS. Then if the topical doesn’t work, is it just that it refuse I will still give them oral therapy if I agree with
was one of those 90% cases where it is not effective it clinically, and document that they refused the tests on
or is it because it was not a dermatophytic infection economic grounds. I rarely use ciclopirox and if I do, I
to begin with? You don’t know why it didn’t work wouldn’t do a PAS (although before it went generic we
and this can sometimes be a problem. would to ensure coverage).
Dr. Reyzelman: I tend to lean on the clinical di- Dr. Jennings: I give my patients a complete list of
agnosis a lot. If they have tinea pedis/multiple nails in- all of the options. I am a firm believer in education. If
volved and fungal debris then I don’t necessarily get a the choice was an oral agent, I would definitely do a
PAS, only with high risk. PAS to confirm diagnosis. If using a topical and 95%
Dr. Goldsmith: In the past, some Medicare con- sure it was onychomycosis, I probably wouldn’t do di-
tractor policies required the doctor to perform lab agnostic testing.
work to confirm the presence of onychomycosis or
6 Onychomycosis and the Role of Topical Antifungals
Onychomycosis: Treatment Considerations
Warren Joseph, DPM
There is a disconnect between how we approach The surgical approach (ie, removal of the nail) tends
onychomycosis, and what we know about the disease. not to be used the same time as a topical, and tends to
There is a disconnect between how many patients have be used less currently as it can be painful and lead to
the disease, and how many are treated; what patients secondary bacterial infection. If re-growth occurs, it is
perceive of the disease, and the need to treated versus important to address the fungus.
those who are actually treated; and between what po- So what’s new in the world of onychomycosis? As
diatrists see as being efficacious, and what we use, and of March 2013, 63 clinical trials were listed at www.
the fear of risks of oral therapy versus the facts (that the clinicaltrials.gov with only 5 currently recruiting. Lots
risk is minimal). of treatment approaches are being looked at, includ-
Overall, it is estimated that 35-36 million Americans ing patches, iontophoresis with terbinafine (not being
have onychomycosis. Of these, only 6.3 million have pursued anymore), itraconazole 200 mg once daily
been diagnosed by a physician, and only 2.5 million (now FDA approved), various lasers, micro drilling to
receive treatment each year. That leaves 33 million un- increase the penetration of the topical and various new
treated patients! topicals are being investigated including luliconazole,
Current therapies include prescription antifungals, amorolfine, transfersome and antimicrobial plasma.
soaking, debridement/avulsion and “over-the-counter” Ciclopirox nail lacquer is currently the only
(OTC) medications. What is most striking is the 42% of FDA-approved topical therapy for onychomycosis. Two
patients who have tried OTC treatments, compared to products (efinaconazole and tavaborole) have recently
12% who are receiving a prescription antifungal.22 Of completed their phase 3 trials and luliconazole is in
course, there are going to be patients who come in to phase 2/3.
our practice who just don’t care; they have lived with Based on the pivotal trials and FDA strict criteria,
their onychomycosis for years and don’t want to do the cure and success rates were 8.5% and 12%, respec-
anything about it, but the OTC group represent people tively, after 48 weeks treatment with ciclopirox nail lac-
who are actively doing something for their onychomy- quer.26 A subsequent meta-analysis reported a clinical
cosis, because they want to get rid of it. response rate of 52.4%±9.0%.27 These data and those
Podiatric physicians’ treatment choices and their from other studies that followed have brought up the
perceptions of treatment efficacy are quite different. whole debate of how we define treatment success in
For example, only 23% of podiatrists perceive that de- onychomyosis and what is an appropriate length of
bridement is efficacious, and yet it is the #1 treatment treatment (especially with the topical products).
recommended by podiatrists (in 75% of cases). Eighty There are only two terms consistently applied in
percent of podiatrists perceive that oral antifungals are clinical trials—mycologic cure and complete cure.
the most effective treatment, but they only recommend Mycologic cure is the lowest barrier, easiest to achieve
them in 30% of cases. Topicals are somewhere in the and as a result reports the highest numbers. Complete
middle —perceived as effective by 7% of podiatrists yet cure is the highest barrier—how often is the nail 100%
fairly widely used (in 48% of cases).23 normal in appearance? Almost never, which is why the
Current approaches to treatment include mechan- level of complete cure tends to be low. As a result a lot
ical/surgical (ie, debridement, P&A technique, nail of intermediate endpoints (ie, clinical success, almost
avulsion),24 topical therapy, oral therapy and combi- clear) have been reported in clinical trails, and different
nation therapy with debridement.25 Of course with methodologies have been adopted to determine the
ciclopirox, combining with debridement is in the extent of nail involvement. There is certainly confu-
package insert, but with newer products, this may not sion amongst podiatrists and comparing efficacy from
be the case. By combining debridement would you different studies is difficult. Even the range of severity
increase efficacy? (percent nail involvement) varies amongst onychomy-
Medical debridement has been the mainstay of the cosis studies, however the mean values may be similar.
podiatric approach, and it does reduce thickness and So what is the role of topicals in the treatment of
length of the nail, causes decreased pain/pressure (one onychomycosis? They are generally used for mild to
of the chief patient complaints) and may decrease the moderate DSO (although even here the severity terms
fungal load. It also makes the nail temporarily look a are not well defined). They certainly represent an alter-
little bit better, but it does not address the fungus. De- native therapy for patients who cannot or will not take
bridement is not a treatment for fungal infection. 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 recurrence. These include using maintenance treatment
read about them on the Internet, or there is physician regimens as well as practical steps the patient can follow
confusion about drug interactions). Topicals are poten- at home (Table 1).
tial adjunctive therapy along with the orals (inside out As mentioned earlier, comparing efficacy across
and outside in) in moderate to severe disease; and a big studies is complex given the different degrees of nail
area that has not been seriously looked at is their use in involvement, patient age and demographic differences.
prevention of recurrence/maintenance therapy. Nevertheless, we can provide some guidance based on
Three oral agents are FDA approved: itraconazole, the pivotal studies and the common criteria of myco-
terbinafine and griseofulvin. Terbinafine is considered logic and complete cure rates. As can be seen in Table
the gold standard in terms of cure rates (>70% success 2, reported mycologic cure rates range from 31% to
rate reported in a meta-analysis of the clinical studies).28 70% and complete cure rates range from 5.5% to 38%.
There is almost no research into new oral agents, prob- Use of lasers to treat onychomycosis has become
ably because of the efficacy and the cost of generic ter- more commonplace. However, there is very little data
binafine. In a large randomized, open label multicenter as to whether lasers work or not. There are only two
study with oral terbinafine and aggressive debridement published trials, and yet a number of lasers carry FDA
(IRON-CLAD), no clinically significant changes in clearance. The wording of the clearance is for tempo-
liver transaminase levels were observed 6 weeks after rary improvement in the appearance of the nail. None
treatment or after 12 weeks in those tested.29 So oral are labelled for the actual treatment of onychomycosis.
drugs are not so dangerous, but there is still a percep- Another area of significant promotion is the wide vari-
tion out there that they are. ety of OTC products claiming to be “effective 80% of
Relapse (recurrence or reinfection) is a significant the time” without defining what this means.
problem in the treatment of onychomycosis. As we dis-
cussed earlier, because there is genetic predisposition to DISCUSSION POINTS: Treatment Options
onychomycosis, we should be talking about remission Dr. Lifshen: I do not treat all cases of onychomy-
rather than cure. Relapse of onychomycosis may be due cosis. Elderly patients who come in many times do not
to reinfection or incomplete eradication of the origi- need to be treated. Usually, I just make sure they are
nal fungus with treatment.2 It has been shown with comfortable and that they can get their shoes on, and
orals that 22% of patients experience a relapse when that’s it. We also have to keep in mind the physical lim-
followed up to 3 years after initial treatment.2 More re- itations of that age group. We have a lot of patients who
cently, it was similarly shown that 4 years after an initial are unable to bend over and cut their nails or apply
12-week treatment course, only 33%-35% of patients medication to their toenails. Add to that the fact that
still exhibited evidence of a clinical cure and 28%-35% nails are generally more involved than we would see in
of patients remained completely cured.30 the 40-50-year-old population. They actually may be
In reality, the recurrence rate is 100% unless we more suited to an oral medication, but many patients
manage the disease appropriately, and there are a num- don’t want to take another medication orally regard-
ber of preventative strategies we can adopt to minimize less. It is a dilemma. It is going to be very difficult for
8 Onychomycosis and the Role of Topical Antifungals
Table 2: Efficacy of Topical and Oral Antifungals in Pivotal Studies
1Gupta AK, Fleckman P, Baran R. Ciclopirox nail lacquer topical solution 8% in the treatment of toenail onychomycosis. J Am Acad Dermatol.
2000;43(4 Suppl):S70-80.
2Anacor Pharmaceuticals press releases. January 28 and February 28, 2013 (www.anacor.com)
3Sporanox (itraconazole) [package insert]. Titusville, NJ: Janssen Pharmaceuticals Inc. 2012.
4Elewski BE, Rich P, Pollak P, et al. Efinaconazole 10% solution in the treatment of toenail onychomycosis: two phase 3 multicenter, randomized,
double-blind studies. J Am Acad Dermatol. 2013;68(4):600-608.
5Lamisil (terbinafine HCl) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp. 2012.
a company introducing a new topical antifungal with convinced about lasers. I believe it is important to take
practices that have already established a protocol of dis- notice of the clinical evidence.
pensing within their practice. I think podiatrists who Dr. Ashton: Patients are asking for laser treatment,
are dispensers and use combination therapy with oral but the real impetus behind the laser I feel at times is
terbinafine and a topical will continue to use an office the additional investigations (ie, they also do PAS stains,
based OTC product as their combination drug. If you etc.), and that generates a lot of traffic in the office. As
are using efinaconazole by itself as the only form of far as treating all comers with fungus, I have inquiries
treatment, and it does have significant efficacy results, all the time. Patients come in with their yellow/brittle
that is where you will see growth. toenails, and yes it is likely to be fungal but there are
Dr. Joseph: People did not want orals, and this is multiple medications, both oral and topical available. If
still true today. It doesn’t matter how much you educate there were a topical that was more effective, I would be
them; they are not willing to do it. They have their more inclined to use it except for a couple of things: all
family doctors telling them they are dangerous, the in- the clinical trials I have been involved in have selected
formation is on the Internet and a lot of podiatrists patients who don’t have total nail involvement, and a
don’t want to bother/risk it. lot of these elderly people do have total involvement.
Dr. Reyzelman: I treat those who want to be I don’t know how well a product priced similar to ci-
treated, unless they have significant comorbidities. I clopirox when it came out is going to go with these
educate my patients about the options that are avail- elderly Medicare patients. Theses people have a limit-
able, pros and cons and financial issues and help them ed income, and if they are going to come in because
decide the best solution for their problem. When they can’t manage the condition themselves and spend
thinking about severity, there is no specific classi- money, they will want to see results. I think the whole
fication. To me, severe would be total nail plate in- debate about OTCs comes down to one thing, and that
volvement; chronicity and duration are also important is a big switch to misrepresentation. The FDA does not
considerations. How much of the nail is infected is allow them to say they are treating onychomycosis spe-
an important guide, as well as the number of toes in- cifically; it may be treating fungus all over the toe, but
volved. I think efinaconazole is going to be used a lot not within the nail. OTC products may have a role as
and patients are going to drive the market. maintenance therapy to take steps to see that you don’t
Dr. Pollak: I ask people if they want to be treated. I get their onychomycosis back, especially something
don’t treat everyone unless it is bothersome in terms of that treats tinea pedis. Sequential prescription topical
appearance, or in rare cases it is painful. I use terbinafine might be the way to go?
in almost every case. I rarely offer my patients topicals Dr. Vlahovic: I am a big fan of oral terbinafine, and
because I have not been impressed with results I saw discuss with my patients the level of onychomycosis
with ciclopirox. If it is a one-fungus toenail, and really present, and if there are dermatophytomas, because they
dystrophic, I will suggest permanent removal. I am not are much more difficult to treat. I am a firm believer
Onychomycosis and the Role of Topical Antifungals 9
in matching the patient to the treatment. If they have —return on investment for patients. Is there a reason-
no cuticle involvement I might recommend a topical, able chance that using the medication will eliminate
it really depends on the patient. Can they reach their the fungus and make the nail “appear” more normal?
toenails? Maybe they don’t want to take an oral? I use Will the medication prevent the spread of the fun-
cosmetic nail resin applied on top of the nail and it gus to other nails? If the medication is a topical, how
mimics the look of the nail. The patient doesn’t have practical is the application—the ability to reach down
to think about it. In theory, you are sealing the nail and apply —process? How much will the treatment
and not allowing any more environmental dermato- cost overall? Will the fungus come back when I stop
phytes to get in, so I will do that for the patients who the treatment or can I continue treatment under a
can’t reach down to their toes and don’t want to take “maintenance” protocol? Historically, with patient
an oral. I have been waiting for a new effective topi- awareness through continuous marketing (television
cal agent such as efinaconazole to come out because I ads, radio and print media) and information patients
have a patient population who would benefit from its received from their doctors, issues related to pricing
broad spectrum and obviously from the efficacy. As far took a back seat to their desire to eliminate this infec-
as payment goes, something that is affordable is great tion in their nails. Consumer demand for a treatment
but I can tell you with certainty that my patients are so took off although acceptance of topical treatments al-
desperate to have clear nails they will find a way to pay. ways exceeded oral medication use. There is a good
I have been impressed by the depth people will go to market for an effective topical as you don’t have to go
to solve their nail problem. through a lot of thinking or effort to use it.
Dr. Caldwell: It is no shock to anyone that terbi- Dr. Markinson: There is a disconnect where the
nafine is the gold standard in treating onychomycosis, podiatrist is the driving force to OTC and topical, so
given the information (ie, success rates, the ease of tak- I believe for instance if you ask a typical patient, he
ing a pill). Many patients, even after you counsel them or she will tell you that the oral drug is dangerous
regarding the fact that there are very few cases of com- when there is no data to support it. We have not been
promised liver function with oral terbinafine, will tell responsive to try to dispel the myth. I don’t think we
you, “I don’t care. I am not taking anything by mouth. have said as a profession, with any enthusiasm, that this
I want the best thing I can apply to my toe.” Patients is a chronic disease, and it should be managed as such.
want a prescription topical solution that is covered by Sometimes a recurrence creates a bad impression of
their insurance, which will beat any other OTC if the the efficacy of a product but this can be wrong. You
cost differential is there. If there is a large co-pay there are obligated to tell the patient that nothing comes
could be a problem. close to terbinafine in curing the disease, but we don’t
Dr. Jennings: In our patient population, there is a do that. The only thing that drove the success of ci-
certain sophistication. They come into my office with clopirox was “you don’t have to worry about the liver.”
an armamentarium of things they have used in the That is what is driving the demand for OTC products
past or are interested in using and want my opinion. as well. We hear all the time from our patients what
I think the role of OTC products in podiatry is huge. they have used. I tell them there is only one FDA ap-
Safety and efficacy are important in the patient’s de- proved topical medication. Then I tell then the success
cision-making process. The public is becoming more rate and they are flabbergasted. I don’t think in-office
involved in the treatment of their own disease state. dispensing is an obstacle. The single driver of all this is
Dr. Goldsmith: Ciclopirox had the same issues the emphasis of podiatry that it is safe and that safety
when it was launched as efinaconazole will face: ROI outweighs efficacy all the time.
10 Onychomycosis and the Role of Topical Antifungals