f OURNAL OF THE AMERICAN PODIATRIC MEDICAL ASSOCIATION
`
`VOLUME
`
`NUMBERZMARCH/APRIL 2003
`
`
`
`ORIGINAL ARTICLES
`
`Bone Scintigraphic Findings in Patients with Foot Ulcers and
`Normal Plain Film Radiographs
`Arnold F. Jacobson and Joan E. Williams
`
`Clinical and Biomechanical Risk Factors of Patients Diagnosed with
`Hallux Valgus
`Thomas W. Kernozek, Abdulaziz Elfessi, and Steven Slerriker
`
`Subchondral Thickness Does Not Vary with Cartilage Degeneration
`on the Metatarsal
`Doreen Raudenbush, Dale Fl. Sumner, Parimal M. Panchal, et al
`
`Relationship Between “Growing Pains” and Foot Posture in Children
`Angela M. Evans
`
`Effect of the Low-Dye Strap on Pronation-Sensitive Mechanical Attributes
`of the Foot
`
`Jeffrey M. Whitaker, Kazuto Augustus, and Suzanne lshii
`
`The Influence of Geriatrics Education on Knowledge, Attitudes, and
`Career Aspirations of Podiatric Medical Students
`Hylton B. Menz
`
`Position of the Subtalar Joint Axis and Resistance of the Rearfoot to Supination
`Craig Payne, Shannon Munteanu, and Kathryn Miller
`
`Topical Treatments for Onychomycosis
`Myron A. Bodman, Lisa Feder, and Angela M. Nace
`
`Reliability and Validity of Center-of-Pressure Quantification
`Mark W. Cornwall and Thomas G. McPoil
`
`Implementation of Computerized Student-Patient Logs in Podiatric
`Medical Education
`Graham P. Shaw, Joel H. Clark, and Stephen J. Morewitz
`
`
`CLINICALLY SPEAKING
`
`Revisiting Epinephrine in Foot Surgery
`Philip Radovic, Robert G. Smith, and Don Shumway
`
`
`SPECIAL COMMUNICATION
`
`American Podiatric Medical Association Best Walking City Competition, 2002
`Allan H. Fisher, Jr., George P. Tzamaras, Allison J. Brewer, etal
`
`www.japmaonline.org
`
`Complete table of contents inside
`
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`

`
`EDITORIAL STAFF
`
`Warren S. Joseph, DPM
`Editor
`
`Glenn B. Gastwirth, DPM
`Executive Editor
`
`Annette Theuring
`Managing Editor
`
`Oedipa Anne Rice
`Editorial Assistant
`
`EDITORIAL ADVISORY BOARD
`
`Alan S. Banks, DPM
`Michael S. Downey, DPM
`Lester J. Jones, DPM
`
`Adam S. Landsman, DPM, PhD
`Stephen J. Miller, DPM
`Jeffrey M. Robbins, DPM
`
`William H. Sanner, DPM
`Ellen Sobel, DPM, PhD
`Gregg Young, DPM
`
`David G. Armstrong, DPM
`Bryan D. Caldwell, DPM, MS
`Thomas J. Chang, DPM
`Howard J. Dananberg, DPM
`Donna DeFronzo, DPM
`A. Lee Dellon, MD
`Vincent Giacalone, DPM
`Aditya K. Gupta, MD
`Howard Hillstrom, PhD
`Dennis Janisse, CPed
`Molly S. Judge, DPM
`
`CONTRIBUTING EDITORS
`
`Kevin A. Kirby, DPM
`Mark Kosinski, DPM
`Donald Kushner, DPM
`Leonard A. Levy, DPM
`Kieran T. Mahan, DPM
`Thomas McPoil, PhD, PT, ATC
`Hylton B. Menz, PhD, BPod(Hons)
`Gerit D. Mulder, DPM
`Benno M. Nigg, PhD
`Jeffrey C. Page, DPM
`Craig B. Payne, DipPod(NZ), MPH
`
`JOURNAL INFORMATION
`
`Robert D. Phillips, DPM
`Jane Pontious, DPM
`Douglas H. Richie, Jr., DPM
`Ronald L. Valmassy, DPM
`George F. Wallace, DPM
`Gerard V. Yu, DPM
`
`Clinical Pathology
`Harvey Lemont, DPM
`
`Publication Designer
`Jo Deckert
`
`The Journal of the American Podiatric Medical Association (ISSN
`8750-7315) is published bimonthly by the American Podiatric Medical
`Association, 9312 Old Georgetown Road, Bethesda, Maryland 20814-
`1621. Periodicals postage is paid at Bethesda, Maryland, and additional
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`
`Subscriptions
`
`A ($50.00) subscription to the Journal of the American Podiatric
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`Subscriptions for all others in the United States are $125.00 prepaid;
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`
`Editorial Content
`
`All expressions of opinion and all other statements are published
`on the authority of the writer(s) over whose signature they appear, and
`are not to be regarded as expressing the views of the American
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`Manuscripts should be submitted to Editor, Journal of the American
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`General Information
`The Journal is indexed in Index Medicus of die National Library of
`Medicine, Excevpta Medica, and CINAHL.
`Copyright ©2003 by the American Podiatric Medical Association. All
`rights reserved. No part of this publication may be reproduced,
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`mechanical, including photocopying or by any information storage or
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`Printed in the United States of America.
`
`A-4
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`
`Topical Treatments for Onychomycosis
`A Historical Perspective
`
`Myron A. Bodman, DPM*
`Lisa Feder, PhD1-
`Angela M. Nace, PharmD1-
`
`Topical treatment of onychomycosis, in contrast to systemic oral ther-
`apy, allows the patient to apply medication directly to the affected area,
`thereby decreasing the potential for adverse events and drug interac-
`tions. Historically, several topical antifungal agents have been used in
`the treatment of onychomycosis; however, the evidence for their effec-
`tiveness is based on very limited data or anecdotal reports. Recently,
`the development of new, effective topical agents has renewed interest
`in this form of therapy. As clinical experience with newer topical agents
`expands, they may be found to be an effective option for the treatment
`of onychomycosis. (J Am Podiatr Med Assoc 93(2): 136-141, 2003)
`
`
`Onychomycosis is the most common disease of the
`nails,‘ accounting for approximately 30% of all nail
`infections? It is estimated that this disease affects 2%
`
`to 13% of the general population?-7 with prevalence
`increasing with age. This fungal infection is caused by
`dermatophytes, nondermatophytic molds, or yeasts.”
`At least 80% of onychomycosis infections in temper-
`ate zones are caused by the dermatophytes Trich0ph—
`yton rubrum and Trichophyton mentagrophytesfm
`Common nondermatophytic molds in North America
`include Scopalariopsis brevicaulis, Aspergillus
`flavus, and Fusarium species, which account for ap-
`proximately l.5% to 6.0% of fungal nail infections.8v12
`Yeasts are responsible for 5% to 17% of all cases of
`onychomycosis, primarily affecting the fingernails,
`with Candida albicans isolated in more than 70% of
`
`patients?» 13
`
`*Cleveland Foot and Ankle Clinic, Ohio College of Podi-
`atric Medicine, Cleveland.
`TScientific Connexions, Newtown, PA.
`This article was supported by an unrestricted educational
`grant from Dermik Laboratories, Berwyn, Pennsylvania. Drs.
`Feder and Nace both received funding from Dermik Labo-
`ratories. Dr. Bodman has received monetary compensation
`for speaking engagements from Dermik Laboratories.
`Corresponding author: Myron A. Bodman, DPM, Cleve-
`land Foot and Ankle Clinic, Ohio College of Podiatric Medi-
`cine, lO5l5 Carnegie Ave, Cleveland, OH 44106.
`
`Diagnosis
`
`Clinically, onychomycosis is evident from hyperker—
`atosis of the nail bed, yellow to brownish discolora-
`tion of the nails, and separation of the nail from the
`nail bed (onycholysis).14 Diagnosis of onychomycosis
`is especially likely if tinea pedis caused by T rubrum
`is present. Trichophyton rubrum often invades the
`distal nail bed, resulting in the development of distal
`subungual onychomycosis. 15
`Accurate diagnosis by clinical presentation alone
`is possible in only 40% to 57% of cases.”- 15 Direct micro-
`scopic examination, fungal culture, or both are required
`to confirm the diagnosis and to identify the infecting
`organism.“v 17v 13 Direct microscopic examination for
`hyphal fragments is typically performed by preparing
`nail scrapings with potassium hydroxide (KOH).14~ 19
`Although direct microscopy cannot identify the spe-
`cific causative pathogen, it can determine whether
`the hyphae are characteristic of dermatophytes.” The
`most accurate test (85% sensitive) for the detection
`of mycotic nail infections is a routine histopathologic
`examination with periodic acid—Schiff stain.2° Fungal
`culture is required to identify the specific infecting
`organism; however, because more than 90% of ony-
`chomycosis infections are caused by dermatophytes,
`treatment is often initiated on the basis of a positive
`
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`KOH result. Further research may determine whether
`sensitivity is enhanced by combining periodic acid-
`Schiff staining with fungal cultures.
`
`Treatment Options: The Role of
`Topical Therapy
`
`Treatments for onychomycosis range from minimal
`intervention or palliative care to systemic therapy or
`nail avulsion by surgical or chemical means. The
`choice of treatment modality may depend on several
`factors, including the presentation and severity of the
`disease, the medical condition and current patient
`medications, physician and patient preference, and
`the cost of therapy? Because of the potential for drug
`interactions, use of systemic therapy may be inap-
`propriate in patients receiving multiple medications,
`such as those with human immunodeficiency virus,
`
`patients with diabetes mellitus, and the elderly.21'25
`Topical therapy allows for direct application to the
`desired area and minimizes the chance of adverse
`
`systemic drug reactions that can be associated with
`use of oral antifungal agents? This is also a good op-
`tion for patients with rnild-to—moderate disease and
`for those unwilling to take systemic medication.
`
`Topical Antifungal Agents
`
`Historically, several classes of topical antifungal
`medications have been used to treat onychomycosis,
`
`including polyenes (eg, nystatin); imidazoles (eg,
`clotrimazole, tioconazole, econazole, ketoconazole,
`miconazole, sulconazole, and oxiconazole), which
`have fungistatic properties in vitro; and allylamines/
`benzylamines (eg, naftifine, terbinafine, and butc-
`nafine), which have fungistatic and fungicidal prop-
`erties in m'tro.26 Few weH—designed clinical studies
`have evaluated the efficacy of these agents for the
`treatment of onychomycosis; therefore, most of the
`available data supporting their use are derived from
`small and poorly controlled studies.
`In an effort to improve outcomes, topical agents
`have been combined with 20% to 40% urea ointment
`
`to soften the onycholytic nail plate, thereby facilitat-
`ing debridement and antifungal penetration.2731 One
`of the most widely used antifungal~urea combina-
`tions evaluated in several small—scale trials is 1% bi-
`fonazole in combination with 40% urea ointment.27» 3033
`
`In one trial,” 28 patients with onychomycosis were
`treated with 40% urea—1% bifonazole cream once
`
`daily for 6 months. A “cure” was defined as normal
`nail growth throughout the 6- to 12-month follow-up
`period and negative culture findings. Cure rates of 81%
`for fingernails and 69% for toenails were achieved. In
`
`a study3° evaluating the efficacy of bifonazole—urea
`application in 25 children (aged 1.8 to 15.0 years) with
`onychomycosis, bifonazole—urea use resulted in a
`68% (17/25) therapeutic success rate (clinical cure
`and negative KOH and culture results), a 24% (6/25)
`improvement rate (important clinical changes, posi-
`tive or negative KOH results, and negative culture re-
`sults), and an 8% (2/25) failure rate (no clinical or
`mycologic [KOH/culture] changes or exacerbation of
`the process and positive KOH and culture results). In
`another study“ evaluating 50 patients with onycho-
`mycosis, application of bifonazole—urea cream result-
`ed in a 90% cure rate (negative culture results and
`negative clinical evaluation) 1 month after treatment.
`This response was maintained for 4 months after
`treatment. In a similar small—scale study32 evaluating
`
`daily use of 40% urea—1% bifonazole paste in 22 pa-
`tients with toenail onychomycosis, 63% of the nails
`were mycologically negative after 12 weeks of treat-
`ment, and 46% remained negative 24 weeks after
`tiating treatment. Adverse events observed in these
`trials included nail pain and dermatitis.27- 30 31 A 40%
`urea—1% bifonazole cream is commercially available
`in several countries outside of the United States.“ 35
`
`To date, two topical therapies have been approved
`for the treatment of onychomycosis in Europe: ciclopi—
`rox nail lacquer and amorolfine. Of these, only ciclopi—
`rox is approved for use in the United States. Ciclopirox
`nail lacquer 8% solution (Penlac, Derrnik Laborato-
`ries, Berwyn, Pennsylvania) is a hydroxypyridone
`derivative that differs chemically and mechanistically
`from other marketed antifungal agents (including irn—
`idazoles and allylamines).5 The mechanism of action
`of Ciclopirox is thought to be related to the chelation
`of polyvalent cations (Fe+3 or Al+3). It is a broad-spec-
`trum antifungal agent with activity against dermato-
`phytes such as T rubrum and T mentagrophytes,
`Candida species, and some nondermatophyte molds.
`Ciclopirox was introduced in 1975 and was first ap-
`proved approximately l0 years ago in France for the
`treatment of onychomycosis.5
`After repeated applications to the nail surface, ci-
`clopirox has been detected in all layers of the nail
`plate and the skin below.36» 37 Figure 1 illustrates the
`penetration of C14—labeled Ciclopirox in excised, my-
`cotically involved toenails. As expected, the concen-
`tration of the topical agent was highest in the upper
`layers of the nail plate,37 and at a depth of 0.4 mm, ci-
`clopirox exceeded the minimum inhibitory concentra-
`tions for the most common fungal species associated
`with onychomycosis (Table l).33» 39 Drug penetration
`of the nail varies, with more pronounced penetration
`observed in the damaged, friable areas of mycotic
`nails.37
`
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`Proximal subungual onychomycosis
`
`White superficial onychomycosis
`
`
`
`_ <___ Candida
`onychomycosis
`
`Distal subungual
`onychomycosis
`
`Figure 1. Penetration of C14-labeled ciclopirox in excised, mycotically involved toenails after a single application of
`ciclopirox nail lacquer 8% solution. (Reprinted with permission from Del Ftosso.‘5)
`
`The efficacy of ciclopirox in the treatment of ony-
`chomycosis of dermatophytic origin was recently
`demonstrated in two double—blind, vehicle—controlled
`US tn'als.4° These studies of 460 patients with mild—to—
`moderate onychomycosis included 231 individuals
`receiving ciclopirox and 229 receiving vehicle only.
`Ciclopirox or vehicle control was applied to all toe-
`nails and affected fingernails (including approxi-
`mately 5 mm of the surrounding skin) once daily for
`48 weeks. Efficacy was determined on the basis of
`the results of fungal cultures and KOH microscopy of
`nail specimens, an '1nVestigator—assessed global evalu-
`ation score, and planimetric measurement of the in-
`
`volved area. The primary efficacy variable in the stud-
`ies was treatment success, defined as simultaneous
`negative KOH and culture results and 10% or less
`area involvement of the target nail plate as deter-
`mined by planimetry. The most common causative or-
`ganism was T rubrum (96%). Treatment success was
`achieved in 6.5% (study 1) and 12% (study 2) of pa-
`tients treated with ciclopirox, compared with less
`than 1% for those in the vehicle groups (P < .05 for
`both studies). Significantly more patients treated
`with ciclopirox nail lacquer had negative culture re-
`sults (84% for both studies) compared with patients
`receiving vehicle (37% and 44%, respectively; P < .001).
`
`
`Table 1. Antifungal Efficacy of CiclopiroxT.
`Minimum Inhibitory Concentration (pg/mL)
`0.49
`0.98
`1.95
`3.92
`7.8
`15.6
`31.2
`
`Organism
`
`—
`—
`—
`2
`20
`14
`1
`Trichophyton rubrum (n = 37)
`—
`—
`—
`—
`2
`17
`10
`Trichophyton mentagrophytes (n = 29)
`—
`—
`—
`—
`—
`3
`2
`Epidermophyton floccosum (n = 5)
`—
`—
`—
`4
`13
`2
`1
`Microsporum canis (n = 20)
`—
`—
`—
`5
`11
`21
`—
`Candida albicans (n = 37)
`—
`—
`—
`—
`6
`6
`—
`Candida tropica/is (n = 12)
`—
`—
`—
`4
`5
`—
`—
`Candida pseudotropicalis (n = 9)
`—
`—
`—
`1
`8
`2
`—
`Candida krusei (n = 11)
`—
`—
`—
`5
`5
`—
`—
`Candida parapsilosis (n = 10)
`—
`—
`—
`3
`2
`1
`—
`Other Candida species (n = 6)
`—
`—
`—
`—
`1
`—
`—
`Scopulariopsis brevicaulis (n = 1)
`—
`5
`3
`10
`9
`1
`—
`Aspergillus species (n = 28)
`Scytalidinium hya/inum (n = 1)
`—
`1
`—
`—
`—
`—
`—
`Fusarium so/ani (n = 1)
`—
`—
`—
`—
`—
`—
`1
`
`Source: Data from Refs. 38 and 39.
`Note: Data are given as number of patients.
`
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`In addition, mycologic cure (defined as negative KOH
`and culture results) was achieved in 29% and 36% of
`patients treated with ciclopirox in each of the two
`studies, compared with 11% and 9% of patients re-
`ceiving vehicle, respectively (P < .01 for both stud-
`ies). Complete cure, defined as negative KOH and cul-
`ture results and a global evaluation score of cleared,
`was achieved in 5.5% and 8.5% of patients treated
`with ciclopirox nail lacquer and 0.9% and 0% of pa-
`tients receiving vehicle in study 1 and study 2, re-
`spectively. Statistically significant improvement for
`negative culture and mycologic cure was evident as
`early as week 12 of treatment and was maintained
`throughout the entire 48-week study. Efficacy was
`not related to the severity of nail disease: patients
`with 40% to 65% nail surface involvement demon-
`
`strated efficacy results similar to those with 20% to
`less than 40% nail involvement.4° The results of these
`
`trials led to the approval of ciclopirox for the topical
`treatment of Inild—to-moderate onychomycosis.“
`The efficacy of ciclopirox nail lacquer has been
`verified in numerous international trials that includ-
`
`ed patients with a broader Variety of causative organ-
`isms than the US pivotal trials, a wider range of treat-
`ment regimens (eg, alternate days or twice weekly),
`and a shorter duration of treatment (24 weeks versus
`48 weeks in the United States).4° The mycologic cure
`rates in these studies ranged from 47% to 86%.
`Amorolfine, available as a nail lacquer in many
`countries, is a morpholine derivative structurally and
`chemically unrelated to other antifungal agents. Its
`primary mechanism of action is inhibition of the bio-
`synthesis of ergosterol, a component of the fungal
`cell membrane. Amorolfine is fungistatic and fungici-
`dal, with greatest efficacy against dermatophytes and
`more variable activity against yeast and molds.“ Two
`multicenter studies evaluated the clinical efficacy of
`amorolfine therapy in patients with toenail or finger-
`nail onychomycosis. Application of 5% amorolfine
`lacquer once or twice weekly for 6 months produced
`mycologic cure (negative culture results) and clinical
`cure (no symptoms or signs or residual, slight erythe—
`ma or slight scaling) rates of approximately 45% to
`50% 3 months after the end of treatment.“
`
`Miscellaneous Topical Therapies
`
`Various miscellaneous topical therapies that have
`been suggested but not approved by the US Food
`and Drug Administration for the treatment of ony-
`chomycosis are summarized in Table 2.4449 Evidence
`for the penetration and efficacy of these treatments
`is lacking; advocacy of their use is based primarily on
`anecdotal reports and small-scale studies.
`
`Table 2. Miscellaneous Topical Agents Suggested but
`Not Approved for the Treatment of Onychomycosis
`Product
`
`Composition
`
`Mycocide NS“
`
`Fungoid Tincture”
`
`Surfactant, allantoin, benzalkonium
`chloride
`Miconazole nitrate 2% USP,
`phenylcarbinol, isopropyl alcohol
`(30%), water, acetic acid (glacial),
`laureth 4
`Clotrimazole 1% in polyethylene
`glycol
`Gordochom Solutionc Undecylenic acid 25%,
`chloroxylenol 3%
`Undecylenic acid 25%
`Terpinen-4-ol
`Source: Data from Refs. 44-49.
`Bwoodward Laboratories, Los Alamitos, California.
`”Pedino| Pharmacal, Inc, Farmingdale, New York.
`°Gordon Laboratories, Upper Darby, Pennsylvania.
`“Kramer Laboratories, Inc, Miami, Florida.
`
`Fungoid Solution”
`
`Fungi-Nail”
`Tea—tree oil
`
`Mycocide NS (Woodward Laboratories, Los Alami-
`tos, California) is a surfactant—based delivery system
`containing allantoin and benzalkonium chloride.4“ In
`a small, open-label study“ of 40 patients with toenail
`onychomycosis, patients underwent nail debride—
`ment followed by twice—daily application of 1 to 2
`drops of Mycocide NS. After 10 months, patients ex-
`perienced significant improvement in disease severi-
`ty based on subjective investigator and patient evalu-
`ations (P < .05).
`Fungoid Tincture (Pedinol Pharmacal, Inc, Farm-
`ingdale, New York), a nonprescription preparation
`not indicated for the treatment of onychomycosis,
`has been evaluated in only small-scale trials. Two
`clinical trials5°v 51 (vehicle—controlled) suggest that this
`product may have some activity in patients with dis-
`tal subungual onychomycosis of the toes after 12
`months of treatment. Both studies enrolled 20 pa-
`tients each, with 10 patients each randomized to
`tvvice—daily treatment with Fungoid Tincture or vehi-
`cle for 12 months. Although a greater number of pa-
`tients receiving Fungoid Tincture achieved negative
`results on KOH stain and culture and demonstrated
`
`clinical improvement (global assessment based on
`photographs) compared with those in the vehicle
`group, a statistical analysis was not conducted to de-
`termine the significance of these findings. Clinical
`improvement, assessed as the distance from the cuti-
`cle to the most proximal onychomycotic border and
`by percentage involvement, was either similar be-
`tween treatment groups or actually higher in the vehi-
`cle group.
`Tea—tree (Melaleuca altemifolia) oil, which con-
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`tains the active ingredient terpinen-4-ol, also has
`been reported to have antifungal properties.49i 52 In
`one trial,49 117 patients with distal subungual onycho—
`myeosis Were 1'3-nd0miZed to TeCeiVe tWiCe'd-any 313'
`pljcations Of either 1% clotiimazole solution or 100%
`tea.tree Oil for 6 months_ Physicians defined clinical
`improvement as “full” or «partial» resolution of Symp_
`toms based on the appearance of the target nail (the
`n3-11 Wltn tne greatest fungal burden at Study entry) at
`the end of therapy, There was no significant difference
`between clotrimazole and tea—tree oil with respect to
`.
`.
`.
`0
`.
`chmcal improvement (61%) and 60%, respectively) or
`negative culture results (11% and 18%, respectively).49
`
`Future Directions
`
`.
`.
`.
`.
`.
`One of the most effective Ways of improving clirucal
`Outcomes is to increase awareness of Current 0nyCn0'
`mycosis management among patients and health-care
`professionals Clinicians can play a key role in edu_
`cating patients about the nature of the disease, proper
`_
`_
`_
`techmqueS_tO prevent mfectloni
`the prospects
`for cure wlth current treatment optlons.” Promptly
`identifying patients who may be at risk for develop—
`ing more severe or less common types of onychomy—
`.
`.
`.
`.
`.
`C9513 ls 1mpO_rtant' For example’ pauent Populatlons
`Wlth concomltant dlsease States: along wlth the gen‘
`eral population, may experience recurrent fungal in-
`fections after successful initial treatment of onycho_
`mycosis.17v 21» 53 Future controlled trials evaluating the
`,
`,
`role of prophylactic topical agents (eg, 0HCe't’V9ek1Y
`CICIOPIFOX) may demonstrate 011111061 benefit In pI"e-
`venting reinfection in these patients.“
`In summary, there have been significant advances
`.
`.
`.
`.
`.
`in topical therapeutic options for onychomycosis.
`_
`_
`Untll recentlyv the use of toplcal agents Was based on
`limited evidence—primarily, small studies and anec—
`
`dotal reports. Despite this lack of confirmed efficacy,
`the demand for a nonsystemic treatment for 0nyChO_
`.
`f
`t
`d th .
`M
`tl
`h
`0WeV_er’
`mycosls _OS ere _
`elr use‘ Ore recen y’
`new toplcal 1'eglmens n3«Ve been deVel0Ped Wltn
`proven efficacy. Among these, ciclopirox nail lacquer
`is the only prescription topical therapy approved in
`the United States for the treatment of Onychomycos
`Sis‘ The availability of an agent with proven nail pen"
`etration provides clinicians for the first time with an
`effective topical treatment option for patients with
`mild—to—moderate onychomycosis.
`
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