581310

research-article2015
CMSXXX10.1177/1203475415581310Journal of Cutaneous Medicine & SurgeryGupta et al

Review

Journal of Cutaneous Medicine and Surgery

Toenail Onychomycosis—A Canadian 2015, Vol. 19(5) 440­–449

© The Author(s) 2015
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DOI: 10.1177/1203475415581310

Treatment: Development of a Clinical jcms.sagepub.com

Pathway

Aditya K. Gupta1, R. Gary Sibbald2, Anneke Andriessen3, Richard Belley4,

Alan Boroditsky5, Mariam Botros6, Robert Chelin7, Wayne Gulliver8, David Keast9,
and Mani Raman10

Abstract
Background: Onychomycosis is a difficult-to-treat infection whose current treatment paradigm relies primarily on oral
antifungals. The emergence of new topical drugs broadens the therapeutic options and prompts a re-evaluation of the current
Canadian treatment strategy.
Objective: To define a patient-centred Canadian treatment strategy for onychomycosis.
Methods: An expert panel of doctors who treat onychomycosis was convened. A systematic review of the literature
on treatments for onychomycosis was conducted. Based on the results, a survey was designed to determine a consensus
treatment system.
Results: First-line therapy should be selected based on nail plate involvement, with terbinafine for severe onychomycosis
(>60% involvement), terbinafine or efinaconazole for moderate onychomycosis (20%-60% involvement), and efinaconazole
for mild onychomycosis (<20% involvement). Comorbidities, patient preference and adherence, or nail thickness may result
in the use of alternative oral or topical antifungals.
Conclusion: These guidelines allow healthcare providers and patients to make informed choices about preventing and
treating onychomycosis.

Résumé
Contexte : L’onychomycose est une infection difficile à traiter dont le paradigme de traitement actuel repose principalement
sur les antifongiques administrés par voie orale. L’émergence de nouveaux médicaments topiques élargit les options
thérapeutiques et incite à une réévaluation de la stratégie actuelle de traitement au Canada.
Objectif : Définir une stratégie canadienne de traitement de l’onychomycose, axée sur le patient.
Méthode : Un groupe d’experts composé de médecins qui traitent l’onychomycose a été réuni. Une revue systématique de
la littérature sur les traitements de l’onychomycose a été effectuée. À partir de ces résultats, un sondage a été conçu dans le
but d’établir un consensus sur un système de traitement.
Résultats : Le traitement de première ligne devrait être choisi en fonction du degré d’atteinte de la tablette unguéale : la
terbinafine pour une onychomycose grave (> 60 % de l’ongle envahi), la terbinafine ou l’efinaconazole pour une onychomycose
modérée (20 à 60 % de l’ongle envahi) et l’efinaconazole pour une onychomycose légère (< 20 % de l’ongle envahi). Les
comorbidités, les préférences du patient et sa conformité au traitement, ou l’épaisseur de l’ongle peuvent donner lieu à une
substitution par d’autres antifongiques administrés par voie orale ou topique.
Conclusion : Ces lignes directrices permettent aux fournisseurs de soins de santé et aux patients de prendre des décisions
éclairées en regard de la prévention et du traitement de l’onychomycose.

Keywords
toenail onychomycosis, clinical pathway, transungual treatment

Background skin.1,2 This common nail infection often results in nail plate
damage, deformity, and toenail dystrophy that can interfere
Onychomycosis accounts for about half of all nail abnormali- with walking, exercise, or proper shoe fit.3 Fungal nail dis-
ties, and it complicates a third of the fungal infections of the ease can also coexist with other nail disorders.4 Onychomycosis
Gupta et al 441

Table 1.  Complete and Mycological Cure Rates for Drugs Approved in Canada Indicated for Onychomycosis.

Terbinafine Itraconazole Ciclopirox Efinaconazole

Dose 250 mg/d 200 mg/d 8% daily 10% daily
Treatment duration, wk 12 12 48 48
Assessment time point, wk 48 — 60 52
Complete cure rate, % 38 14  7 17
Mycological cure rate, % 70 54 33 54

is associated with detrimental psychosocial and physical
effects.5 The prevalence of onychomycosis is more common
as people age. Other conditions associated with increased
onychomycosis include immunosuppression (HIV infection,
transplants, or immunosuppressive therapy), diabetes, avid
sports participation, the use of commercial swimming pools,
wearing occlusive and tight footwear, occupations where
common showers are used, hot humid climate, and frequent
travel to endemic areas.6,7
Men are more affected, possibly due to more frequent
nail damage from sports and leisure activities.2 Toe nails
are about 7 times more frequently affected than fingernails,
partly due to slower toenail growth rate.2 Other predispos-
ing factors include walking barefoot, wearing ill-fitting
shoes, other nail trauma, peripheral vascular disease (PVD),
smoking, psoriasis, and diabetes.2 Fingernails can have a
decreased resistance to fungal infections from nail biting
(onychophagia) and through working with damaging chem-
icals. The dermatophytes cause approximately 90% of toe-
nail infections and 50% to 90% of fingernail infections.8,9
Nondermatophyte molds (NDMs) mainly affect toenails.8-10
Persons with onychomycosis may have 4 patterns of
involvement. Distal subungual onychomycosis is the most
common form. Proximal subungual onychomycosis is rare
and often indicates immunodeficiency, and superficial white
onychomycosis is often due to dermatophytes or yeast and
can be treated topically. These forms can increase in severity
until they present as total dystrophic onychomycosis,
involving the whole nail plate with matrix and lunular
involvement. The more severe forms of onychomycosis
may be resistant to treatment.
There are over 20 disorders that cause nail changes.
Therefore, a positive potassium hydroxide microscopic
examination or culture for fungus should be obtained before
systemic antifungal therapy is used.8,11 Fungal infection may
also exist with other disorders such as psoriasis or pincer
nails, and successful treatment of the fungus will not clear
the coexisting disorder. In Canada, ciclopirox 8% (Penlac;
Valeant Canada) is available as a lacquer applied to the nail
surface.12 Newer topical agents coming to the Canadian
market have been developed as solutions to increase tran-
sungual penetrance via decreased surface tension and kera-
tin binding.13 The topical nail preparations are indicated for
distal subungual and superficial white patterns of nail
onychomycosis.12,14
Objective
The objective of the project was to recognize features of
toenail onychomycosis and explore patient treatment
options. Onychomycosis prevention, treatment, and main-
tenance recommendations developed by the panel for a
Canadian treatment strategy are patient focused and
reflect the current therapeutic options available in Canada.
The current pharmaceutical options indicated for onycho-
mycosis that are available in Canada are terbinafine, itra-
conazole, ciclopirox, and efinaconazole (Table 1).12,14-16
Laser systems are also approved for “the temporary
increase of clear nail in onychomycosis.”17 They have a
wide range of clinical outcomes, from 0% to 100% myco-
logical cure, and their fungicidal effect is still under
investigation.18

1
University of Toronto, Toronto, ON, Canada, & Mediprobe Research Inc, London, ON, Canada
2
University of Toronto, Mississauga, ON, Canada
3
Malden and UMC St Radboud Nijmegen, The Netherlands
4
Département de Médecine Familiale et, Médecine d’urgence, Faculté de Médecine de l’Université Laval, Québec, QC, Canada
5
Vancouver General Hospital, Vancouver, BC, Canada
6
Women’s College Hospital, Toronto, ON, Canada
7
FAAFAS, Toronto, ON, Canada
8
Faculty of Medicine, Memorial University, St John, NF, Canada
9
General Practitioner, London, ON, Canada
10
FRCPC, Toronto, ON, Canada

Corresponding Author:
Aditya K. Gupta, University of Toronto & Mediprobe Research Inc, 645 Windermere Road, London, ON, N5X 2P1, Canada.
Email: agupta@execulink.com
442 Journal of Cutaneous Medicine and Surgery 19(5)

Table 2.  Panel Method.

Step Description
1 Panel members were identified and consensus meetings scheduled.
2 A systematic literature review was conducted using online databases. The reviewed literature was the basis for an interactive
group process to collect further information on Canadian toenail onychomycosis management.
3 A consensus meeting was held on November 30, 2013, in Toronto with the panel members. During the meeting, panel
members achieved agreement on core definitions and proposed approaches to patients with toenail onychomycosis.
4 After the discussion at the meeting, panel members were given an opportunity to vote on each proposed statement via
independent online SurveyMonkey. To reach a consensus, the panel had a predetermined agreement threshold of 80% or
higher agreement.
5 A patient-centred strategy for recognizing toenail onychomycosis patients and providing management was developed.
6 A publication was prepared, and the panel members reviewed its content.

Methods addressed included the importance of correct diagnosis;

The Expert Panel
A panel of dermatologists, general practitioners, podiatrists,
and chiropodists who practice toenail onychomycosis treat-
ment in Canada was established. The panel members were
chosen based on their Canadian practice in treating onycho-
mycosis and their publications on the subject. The panel also
included an advisor with an international clinical and scien-
tific background in this field. The panel adapted a modified
Delphi process for the development of the clinical pathway.
The process has been implemented previously to develop
clinical pathways and treatment algorithms. The panel
explored toenail onychomycosis and characterized individ-
ual case-based scenarios as a basis for treatment options. The
procedure is outlined in Table 2.
Systematic Literature Review
A systematic literature review was completed. The database
search sources were PubMed, Cochrane Library, Medline,
and Embase. Dates of the searches were November 2 and 3,
2013. Publication dates of the selected articles were January
1, 2000, to November 1, 2013. The search was limited to
systematic reviews, meta-analyses, randomized controlled
trials (RCTs), controlled studies, clinical trials, and new
research-based primary papers in the English language.
The following keywords were used: Candida, dermato-
phyte, itraconazole, nail lacquer, nondermatophytic molds,
onychomycosis, terbinafine, onychomycosis areas of treat-
ment, topical treatment, oral treatment, combinations of
treatment, and quality of life aspects.
Results of the Literature Search
The search identified 82 studies, of which 53 fit the selection
criteria (Table 3). The article types are shown in Figure 1.
Based on the results, a document was prepared with core
clinical pathway definitions and proposed approaches to
patients with toenail onychomycosis. Subjects that were
patient-centred considerations; when to use topical, oral, or
both types of treatment; how to prevent recurrences; and how
to include the healthcare system and societal perspective.
Panel Survey
Based on the discussions during the panel meeting, 10 ques-
tions were defined for the online survey. The questions
referred to the distal subungual pattern of onychomycosis.2
This pattern often starts with a distal streak pattern to a proxi-
mal location on the nail and may involve a variable amount
of the nail keratin.2 The panel members scored their answers
on a 7-point Likert scale, where 1 = strongly disagree, 4 =
equivocal, 7 = strongly agree. For each question, the partici-
pants indicated their level of agreement and then commented
in the box on how the statement could be improved. The
written comments were deemed most important for any
response of equivocal (4) or disagree with the statement (1-3
number anchors). A consensus was reached when more than
80% of the panel agreed or strongly agreed with the state-
ment. Eight health care professionals participated, and all
answered the questions.
Results
The panel reached a consensus for 7 of the 9 questions.
The most contentious question was whether the use of a
topical treatment required a positive direct microscopic
examination (DME). Figure 2 shows the responses of the
panel members; only 50% were in agreement that DME is
required. The panel concurred on the diagnostic classifica-
tion of distal subungual onychomycosis as mild, moderate,
and severe based on nail plate involvement (question 3). A
consensus was also reached on the definitions of clinical
efficacy and mycological cure (questions 4 and 5). The
definition for overall cure had 6 physicians in agreement,
1 physician with an equivocal response, and 1 physician
who strongly disagreed (question 6) (Figure 3). The panel
reached consensus on the first line of treatment for
Gupta et al 443

Table 3.  Selected Articles During the Literature Searches.

No. Authors & Journal Type

1 Elewski B. J Am Acad Dermatol. 2013;68(4):600-608. RCT topical

2 Gupta AK. J Eur Acad Dermatol Venereol. 2000;1:466-469. Review
3 Pierard GE. Mycoses. 2005;48:339-342. RCT
6 Kumar S. Investig Drugs. 2009;18:727-734. Review
7 Reich A, Szepietowski JC. Am J Clin Dermatol. 2011;12:313-320. Literature search
8 Finch JJ, Warshaw EM. Dermatol Ther. 2007;20:31-46. Review
9 Tavakkol A, Fellman S, Kianifard F. Am J Geriatr Pharmacother. 2006;4:1-13. Subanalysis
10 Arrese JE, Pierard GE. Dermatology. 2003;207:255-260. Review
11 Darkes MJ, Scott LJ, Goa KL. Am J Clin Dermatol. 2003;4:39-65. Review, oral treatment
12 Warshaw EM, Fett DD, Bloomfield HE, et al. J Am Acad Dermatol. 2005;53:578-584. RCT
13 Baran R. Br J Dermatol. 2007;157:149-157. RCT
14 Fungal nail infections: diagnosis and management [editorial]. Prescrire Int. 2009;18:26-30. Review
15 Gupta AK, Joseph WS. J Am Podiatr Med Assoc. 2000;90:495-501. Review
16 Baran R, Kaoukhov A. J Eur Acad Dermatol Venereol. 2005;19:21-29. Review
17 Lecha M, Effendy I, Feuilhade de Chauvin M, Di Chiacchio N, Baran R. J Eur Acad Dermatol Venereol. Consensus guidelines
2005;19(suppl):25-33.
18 Murdan S. Int J Pharm. 2002;236:1-26. Review
19 Baker SJ, Hui X, Maibach HI. Ann Rep Med Chem. 2005;40:323-334. Review
20 Werschler WP, Bondar G, Armstrong D. Am J Clin Dermatol. 2004;5:145-152. Review
21 Elewski BE. J Eur Acad Dermatol Venereol. Published online December 20, 2011. doi:10.1111/j.1468- RCT, 2 double-blind studies
3083.2011.04373.x.
22 Piraccini BM, Sisti A, Tosti A. J Am Acad Dermatol. 2010;62:411-414. CT, 7-year prospective study
23 Sigurgeirsson B. Arch Dermatol. 2002;138:353-357. CT, blinded prospective study
24 Tosti A, Hay R, Arenas-Guzman R. J Eur Acad Dermatol Venereol. 2005;19(suppl):13-16. Risk assessment
25 Sigurgeirsson B, Steingrimsson O. J Eur Acad Dermatol Venereol. 2004;18:48-51. Survey
26 Kaur R, Kashyap B, Bhalla P. Indian J Med Microbiol. 2008;26:108-116. Review
27 Baran R, Hay R, Haneke E, Tosti A, eds. Onychomycosis: The Current Approach to Diagnosis and Therapy. Review
London: Informa Healthcare; 2006.
28 Weinberg JM, Koestenblatt EK, Tutrone WD, Tishler HR, Najarian L. J Am Acad Dermatol. 2003;49: Review
193-197.
29 Shemer A, Trau H, Davidovici B, Grunwald MH, Amichai B. J Eur Acad Dermatol Venereol. 2008;22:182-185. CT
30 Scherer WP, Scherer MD. J Am Podiatr Med Assoc. 2004;94:356-362. Review
31 Roberts DT, Taylor WD, Boyle J. Br J Dermatol. 2003;148:402-410. Guidelines
32 Gupta AK, Ryder JE. Dermatol Clin. 2003;21:469-479. Review
33 Brown SJ. Ann Pharmacother. 2009;43:1684-1691. Review
34 Cathcart S, Cantrell W, Elewski B. J Eur Acad Dermatol Venereol. 2009;23:1119-1122. Review
35 Gupta AK, Ryder JE, Johnson AM. Br J Dermatol. 2004;150:537-544. Meta-analysis
36 Gupta AK, Lynch LE, Kogan N, Cooper EA. J Eur Acad Dermatol Venereol. 2009;23:256-262. RCT
37 Takahata Y, Hiruma M, Shiraki Y, Tokuhisa Y, Sugita T, Muto M. Mycoses. 2009;52:72-76. CT
38 Baran R, Tosti A, Hartmane I, et al. J Eur Acad Dermatol Venereol. 2009;23:773-781. RCT
39 Baran R, Coquard F. J Dermatolog Treat. 2005;16:52-55. CT
40 Landsman AS, Robbins AH, Angelini PF, et al. J Am Podiatr Med Assoc. 2010;100:166-177. CT
41 Hochman LG. J Cosmet Laser Ther. 2011;13:2-5. CT
42 Manevitch Z, Lev D, Hochberg M, Palhan M, Lewis A, Enk CD. Photochem Photobiol. 2010;86:476-479. CT
43 Gupta AK, Leonardi C, Stoltz RR, Pierce PF, Conetta B. J Eur Acad Dermatol Venereol. 2005;19:437-443. RCT
44 Baran R, Feuilhade M, Combernale P, et al. Br J Dermatol. 2000;142:1177-1183. RCT
45 Olafsson JH, Sigurgeirsson B, Baran R. Br J Dermatol. 2003;149(suppl 65):15-18. CT
46 Gupta AK, Lynde CW, Konnikov N. J Am Acad Dermatol. 2001;44:485-491. RCT
47 Piérard GE, Piérard-Franchimont C, Arrese JE. Dermatology. 2000;200:185-187. CT
48 Malay DS, Yi S, Borowsky P, Downey MS, Mlodzienski AJ. J Foot Ankle Surg. 2009;48:294-308. RCT
49 Grover C, Bansal S, Nanda S, Reddy BS, Kumar V. Br J Dermatol. 2007;157:364-368. RCT
50 Gianni C, Romano C. Dermatology. 2004;209:104-110. CT
51 Cribier BJ, Bakshi R. Br J Dermatol. 2004;150:414-420. Review
52 Rigopoulos D, Katoulis AC, Ioannides D, et al. Br J Dermatol. 2003;149:151-156. RCT
53 Gupta AK. Skin Therapy Lett. 2005;10(7):1-3. Review

Abbreviations: CT, controlled trial; RCT, randomized controlled trial.

444 Journal of Cutaneous Medicine and Surgery 19(5)

Figure 1.  Types of articles selected during the searches. CT, controlled trial; RCT, randomized controlled trial.

Figure 2.  Panel agreement with the requirement for a positive
microscopic examination prior to prescribing a topical antifungal
(question 2).
onychomycosis based on severity (questions 7 and 9). It
was also agreed that comorbidities, patient and provider
preference, cost, adherence to treatment, and nail thickness
could modify first-line recommendations (question 8),
prompting the use of a second-line therapy (question 9). In
Figure 3.  Panel response to the statement: Successful treatment
outcome for toenail onychomycosis is characterized by the
factors below: Overall cure (micro and clinical) is determined
by no clinical evidence of nail change with a negative potassium
hydroxide microscopic examination and culture for fungus
(question 6).
addition, the panel agreed that regular follow-up, treatment
of tinea pedis, and habits to reduce risk of reinfection
should be implemented to prevent relapse.
Gupta et al 445
Pathway to the Prevention and Treatment of
Toenail Onychomycosis Patients
The clinical pathway for the prevention and treatment of toe-
nail onychomycosis patients has 5 sections:
1. Etiology and differential diagnosis
2. Prevention strategies
3. Treatment strategies
4. Evaluation strategies
5. Maintenance strategies
The consensus on treatment will be divided into different
treatment sections for dermatophyte toenail infection, NDM
infection, and Candida infection. Section 1 of the pathway
defines toenail onychomycosis etiology and differential
diagnosis, and section 2 addresses the treatment of the
cause. This section also addresses patient-centred concerns,
including the provision of individualized patient education,
engagement of the patient and family in care planning, and
the exploration of potential barriers to treatment adherence.
Section 3 addresses treatment options. Section 4 addresses
evaluation of outcomes after first-line treatment. If the toe-
nail infection has not been eradicated after optimal first-line
treatment or did not progress toward the expected improve-
ment, re-evaluation should take place. Section 5 addresses
maintenance approaches. Maintenance for toenail onycho-
mycosis is not well researched, and further studies are
needed. The pathway to the prevention and treatment of toe-
nail onychomycosis patients with dermatophyte infection is
presented in Figure 4.
Conclusions
The panel members identified the following considerations
for performing differential diagnosis for onychomycosis: A
positive microscopic result for at least 1 toenail is needed to
confirm onychomycosis.9,11 This process is inexpensive and
relatively quick. In contrast, culture diagnosis can take up to
a month and time will be lost, especially if 3 successive
microscopic or cultures are recommended because the ini-
tial microscopic or culture results are negative but clinical
indicators are suggestive of fungus.9,19,20 A practical
approach would be “If it looks like fungus, smells like fun-
gus, it must be fungus,” keeping in mind that the confirma-
tion of the diagnosis is based on clinical presentation.4 Some
panel members suggested that a practical approach may be
to treat topically before testing, but if a patient is a nonre-
sponder, microscopic or culture confirmation of the fungal
diagnosis is needed.4,20 The issue of false negatives and the
involvement of neighboring toenails was discussed, and the
panel members agreed that the clinical presentation is key in
identifying the infection and its extent.20 The panel agreed
that classification of distal subungual pattern of toenail
involvement should be based on the percentage of clinical
nail involvement with suspected dermatophytes.20 This clas-
sification was used to define treatment options as proposed
in section 3. Topical treatment is often preferred to avoid
systemic side effects and the need for monitoring.21,22
However, before transungual efinaconazole 10% was intro-
duced, no topical treatment had been approved, as mono-
therapy and these older formulations often required frequent
nail debridement along with the topical application.21
The new nonlacquer transungual treatment containing efi-
naconazole 10% solution has demonstrated clinical effec-
tiveness when applied as monotherapy in patients with mild
to moderate toenail onychomycosis.13 The primary efficacy
endpoints (complete clinical cure and mycological cure)
were significantly greater than vehicle at week 52 (P < .001),
and clinical improvement continued after treatment was
stopped (week 48).13 When complete cure rates of oral treat-
ment with itraconazole (week 48, 14%) and terbinafine
(week 48, 38%) were compared, the performance of transun-
gual topical efinaconazole was 17% at week 52, demonstrat-
ing transungual treatment to be an effective option.13,15,16 It is
recognized that the results are not directly comparable since
patients with moderate to severe onychomycosis were
enrolled in trials with the oral agents, whereas those with
moderate onychomycosis were entered in trials where a topi-
cal agent was used. Despite these limitations, it is possible
compare the relative efficacy of the different agents in the
absence of head-to-head trials.23 As there have only been two
phase 3 clinical trials for efinaconazole, phase 4 reporting
and subsequent clinical trials for efinaconazole will help to
draw firm conclusions on efinaconazole’s relative efficacy to
oral drugs.
The transungual topical efinaconazole treatment is pro-
posed by the panel members as a valuable monotherapy
option for patients with less than 60% toenail plate involve-
ment.23 Efinaconazole has increased efficacy over ciclopirox,
but it is an affordable option with a comparable drug price
(2015 wholesale cost: Jublia [Valeant Canada] $10.76/mL
and Penlac $12.98/mL). Additionally, topical efinaconazole
may be used as monotherapy or combined with an oral anti-
fungal agent such as terbinafine in case of involvement of
more than 3 toenails.13,23 Topical efinaconazole would also be
an option with fingernail onychomycosis. Efinaconazole
could be considered in cases of early recurrence and possibly
as prophylaxis therapy in those individuals who are at a higher
risk for recurrence of onychomycosis. The panel members
went on to state that maintenance for toenail onychomycosis
is not well researched and further studies are needed. The pro-
posed measures for maintenance (section 5 of the clinical
pathway) are based on the clinical experience of the panel
members and what has been proposed in guidelines.
•• The panel explored and characterized individ-
ual patient case studies of those suffering from
446 Journal of Cutaneous Medicine and Surgery 19(5)

Figure 4.  Pathway to the prevention and treatment of toenail onychomycosis.

toenail onychomycosis and developed a patient-
centred management pathway.
•• Clinical diagnosis of toenail onychomycosis
remains important in determining treatment
approach.
•• Patients with mild to moderate toenail onycho-
mycosis may benefit from the application of topi-
cal transungual efinaconazole (10%).
•• Optimal prevention is a key factor in achieving a
successful treatment outcome.
Gupta et al 447
Appendix 1: Online Clinical Pathway
Questionnaire
1. Demographic Information
Please rank your agreement with the following statements on
a 7-point Likert scale where 0 = strongly disagree, 4 = equiv-
ocal, 7 = strongly agree.
2. Toenails that are being treated with topical antifungal  
agents should have a positive microscopic examina-
tion for fungus or a positive culture.
3. Classification of distal subungual pattern of toenail
involvement should be based on the percentage of
clinical nail involvement with the dermatophytes:
•• <20% of the entire nail = mild toenail
onychomycosis
•• 20%-60% of the entire nail = moderate toenail
onychomycosis
•• >60% of the entire nail = severe toenail
onychomycosis
4. Successful treatment outcome for toenail onychomy-
cosis is characterized by 1 of the factors below: a)
Clinical efficacy after 3-6 months of treatment:
•• 0% of nail plate involvement = complete clinical
cure
•• <5%-10% = clinical improvement
•• >10% = incomplete clinical response, reassess-
ment needed
5. Successful treatment outcome for toenail onychomy-
cosis is characterized by 1 of the factors below: b)
Mycological cure:
•• Positive or negative based on potassium
hydroxide/culture
•• Periodic acid-Schiff staining of a histological nail
biopsy may be inaccurate because we cannot
determine the viability of the observed fungal
organisms.
6. Successful treatment outcome for toenail onychomyco-
sis is characterized by the factor below: c) Overall cure
(micro and clinical) is determined by no clinical evi-
dence of nail change with a negative potassium hydrox-  
ide microscopic examination and culture for fungus.
7. First-line treatment for toenail onychomycosis based
on the percentage of nail involvement consists of
•• >60% = oral terbinafine (Lamisil; Novartis
Pharmaceuticals Canada)
•• 20%-60% = topical efinaconazole ± oral terbin-
afine (>3 nails)
•• <20% = topical efinaconazole
and this topical treatment
•• may also be indicated with selective debride-
ment (dermatophytoma = concentrated area of
fungus often clinically determined by a thick
nail plate)
•• may be used in conjunction with oral terbinafine
to improve clinical and microscopic cure
•• may also be indicated following oral terbinafine
when distal subungual onychomycosis changes
persist, especially if there is a positive micro-
scopic potassium hydroxide or culture (6
months)
8.   Treatment-modifying factors for toenail onycho-
mycosis include the following:
a) Benefit to risk ratio, where systemic treatment
may be contraindicated due to other medication
or the patient’s general medical condition/coex-
isting diseases
b) Patient preference, where the patient does not
want to consider systemic therapy or would con-
sider topical therapy first and would only use
systemic agents if the topical treatment was
unsuccessful
c) Healthcare provider preference, when health-
care professionals are reluctant to use sys-
temic agents due to side effects, coexisting
medical conditions, or drug-drug interaction
concerns
d) Cost, if the patient is not covered on a drug plan
or the plan does not cover the systemic or topical
agent
e) Adherence, when a patient is not reliable to fol-
low through on a treatment (eg, preference for
topical or systemic treatment and lifestyle
issues)
f) Special populations, such as patients with diabe-
tes mellitus or HIV
g) Special nail presentations, for example, derma-
tophytoma that needs to be debrided or clinically
removed and other types of nail dystrophies
(coexisting psoriasis, pincer nails)
h) Nail thickness—very thick nails may require
debridement in addition to topical or systemic
agents to treat onychomycosis
9. Second-line treatment for toenail onychomycosis
based on the percentage of nail involvement may be
determined as follows:
•• Mild toenail onychomycosis (<20%) may
respond to an alternate topical.
•• Moderate toenail onychomycosis (20%-60%)
may respond more completely to a combination
of oral agents (oral itraconazole or fluconazole is
less effective than terbinafine or topical transun-
gual efinaconazole).
•• Severe toenail onychomycosis (>60%) may
respond more completely to a combination of
oral agents (oral itraconazole or fluconazole is
less effective than terbinafine or topical
448 Journal of Cutaneous Medicine and Surgery 19(5)
transungual efinaconazole) with the option of
surgical debridement.
10. Maintenance for toenail onychomycosis is not well
researched and further studies are needed. The proposed
measures below are suggestions for further investiga-
tion. Your comments and agreement with the principles
listed are important and include the following:
a) Have regular follow-up.
b) Treat tinea pedis of the skin by using a topical
antifungal (eg, 2 times per week) to prevent
reestablishment of infection.
c) Treat toenails previously infected or reinfected
with a topical antifungal designed for nail appli-
cation once or twice a week.
d) Decrease risk of reinfection.
•• Sanitize shoes and socks (topical short chain
fatty acids; eg, Desenex [Novartis, Dorval
QC], Zeasorb [Steifel, Mississauga ON]).
•• Make lifestyle modifications: avoid being
barefoot in areas of high contagion (eg,
bathroom floors, health clubs, foot salons).
e) Conduct periodic self-examination.
Declaration of Conflicting Interests
The author(s) declared the following potential conflicts of interest
with respect to the research, authorship, and/or publication of this
article: Dr Gupta reports personal fees and nonfinancial support
from Valeant Canada during the conduct of the study and reports
grants, personal fees, and nonfinancial support from Valeant Canada,
grants from Allergan Canada, grants from Eli Lilly, personal fees
from Bayer, grants from Nuvolase, grants from Merck, grants from
NitricBio, grants from Polichem, grants from Bristol Meyers Squibb,
grants and personal fees from Janssen Pharmaceuticals, grants and
personal fees from Novartis outside the submitted work. Dr Sibbald
reports grants, personal fees, and nonfinancial support from Valeant
Pharmaceuticals during the conduct of the study. Dr Andriessen
reports grants and nonfinancial support from Valeant Pharmaceuticals
during the conduct of the study. Dr Belley reports personal fees and
nonfinancial support from Valeant Pharmaceuticals, personal fees
from Systagenix, personal fees from Shire, personal fees from
Healthpoint, and personal fees from Couidien during the conduct of
the study; Dr Belley is a primary investor in Applications Mobile
iTech. Dr Boroditsky reports nonfinancial support from Valeant
Pharmaceuticals during the conduct of the study. Dr Botros reports
nonfinancial support from Valeant Pharmaceuticals during the con-
duct of the study. Dr Chelin reports nonfinancial support from
Valeant Pharmaceuticals during the conduct of the study. Dr Gulliver
reports grants, personal fees, and nonfinancial support from Valeant
Pharmaceuticals during the conduct of the study. Dr Keast reports
nonfinancial support from Valeant Pharmaceuticals during the con-
duct of the study. Dr Raman reports nonfinancial support from
Valeant Pharmaceuticals during the conduct of the study.
Funding
The author(s) disclosed receipt of the following financial support
for the research, authorship, and/or publication of this article:
Valeant provided an unrestricted educational grant to organize a
consensus meeting and to prepare documentation used for the meet-
ing. There was no compensation paid to the panel members for the
online survey previous to the consensus meeting and the online
feedback on the manuscript, prepared for publication.
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