ACKNOWLEDGEMENTS: Medical writing support was provided by Prescott Medical Communications Group (Chicago, IL) with financial support from Ortho Dermatologics; Ortho Dermatologics is a division of Bausch Health US, LLC • Presented at Fall Clinical Dermatology Conference • October 21-24, 2021 • Las Vegas, NV

Therapeutic Recommendations for the Treatment of Toenail Onychomycosis in the US
Shari R Lipner, MD, PhD1; Warren S Joseph, DPM2; Tracey C Vlahovic, DPM3; Richard K Scher, MD1; Phoebe Rich, MD4; Mahmoud Ghannoum, PhD5; C Ralph Daniel, MD6; Boni Elewski, MD7 
1Department of Dermatology, Weill Cornell Medicine, New York, NY; 2Arizona College of Podiatric Medicine, Midwestern University, Glendale, AZ; 3Temple University School of Podiatric Medicine, Philadelphia, PA; 4Oregon Health and Science University, Portland, OR;  
5Case Western Reserve University, and University Hospitals Cleveland Medical Center, Cleveland, OH; 6Department of Dermatology, University of Mississippi Medical Center, Jackson, MS; 7University of Alabama at Birmingham School of Medicine, Birmingham, AL

SYNOPSIS
 � Onychomycosis—a fungal infection of the nail bed or plate—affects up to 14% of 
individuals in North America1,2

 � It is undertreated and treatment is challenging as toenail growth can take up to 12 months 
or more, the nail plate may prevent drug penetration, and disease recurrence is common3-6

 � National guidelines and consensus documents on onychomycosis diagnosis and treatment 
were last published more than 5 years ago in 2014 (British7) and 2015 (Canadian1)—around 
the time that both topical efinaconazole and tavaborole were first approved in the US in 
2014

• Since then, more clinical data, post hoc analyses, meta-analyses, and FDA-approved 
indications have become available for onychomycosis drugs

• As such, updated medical guidance is needed

OBJECTIVE AND METHODS
 � To provide recommendations for the diagnosis and therapeutic treatment of toenail 
onychomycosis following a roundtable discussion with the authors on March 15, 2021

 � Included here is a decision tree for choosing appropriate medications based on disease 
severity and patient characteristics, as well as an example handout intended for patients on 
best practices to mitigate disease recurrence

RESULTS

Diagnosis, Testing, and Clinical Presentation
 � Careful assessment and testing must be performed when diagnosing onychomycosis; nail 
dystrophy can be induced by other disorders, and many common conditions that can 
mimic onychomycosis should be ruled out (Figure 1)

 � Laboratory testing should also be performed to identify the infecting organism and 
exclude non-fungal conditions; Figure 1 shows common options that are used in 
conjunction with clinical diagnosis

Recommended Medications
 � The authors all agreed that treatment should be individualized for each patient based on 
nail involvement (number, surface area, thickness), infecting organism, patient 
characteristics (including comorbidities), current medications, biomechanics, cost/
availability/accessibility based on insurance, and patient preference

 � A decision tree to provide practical guidance on therapeutic recommendations in 
onychomycosis treatment developed by the authors is shown in Figure 2

 � Therapeutic recommendations by drug are also detailed in Figure 3 

 � Among oral medications, terbinafine is most commonly used as first-line treatment, 
followed by fluconazole

 � Among topical products, efinaconazole is ideal as first-line medication in pediatric patients, 
patients with less severe disease, and those with dermatophytomas

 � A topical medication was also recommended for use in combination with terbinafine or 
fluconazole and can be considered as maintenance therapy to prevent relapse

 � To improve outcomes, concurrent tinea pedis should be treated in all patients receiving 
topical therapy for onychomycosis

FIGURE 1.  Differential Diagnosis Decision Tree

NO YES

≥1 clinical sign(s) of possible onychomycosis?
• Longitudinal ridging/splitting
• Onycholysis
• Subungual hyperkeratosis
• Nail plate thickening/crumbling
• Nail discoloration (yellow, brown, black, white)

Use ≥1 con�rmatory test(s) for onychomycosis:
• Dermoscopy as a preliminary test to evaluate 
 nail dystrophy/roughness
• Histopathology (to distinguish other nail 
 diseases, such as psoriasis)
• Fungal culture 
• Periodic acid-Schiff (PAS) stain
• Potassium hydroxide (KOH)
• Polymerase chain reaction (PCR)

Differential diagnoses that can cause nail deformity:
• Nail psoriasis
• Chronic nail trauma/mechanical issues
• Onychogryphosis
• Lichen planus
• Onycholysis
• Tumor (subungual malignant melanoma, 
 Bowen’s disease, �broma, melanoma)
• Viral warts
• Chronic dermatitis or paronychia
• Bacterial infection
• Subungual exostosis
• Subungual hematoma

Unable to con�rm 
onychomycosis: 

recheck diagnosis

Con�rmed 
onychomycosis: 
begin treatment

(see Figure 2)

 From Lipner SR, et al. J Drugs Dermatol. 2021;20(10): doi:10.36849/JDD.6291.

FIGURE 2.  Decision Tree on Therapeutic Recommendations for the 
Treatment of Confirmed Onychomycosis

POPULATION

Pregnant/lactating

Adults

Clinical Presentation

Pediatric

Aged ≥65 years, concomitant
medications, or comorbidities

Aged <65 years and
relatively healthy

No current 
recommendations

Topical efinaconazole
(check entire family 

for infection)

Milda

topical 
efinaconazole

Patients aged 
≥65 years,diabetic, 
peripheral vascular 

disease, or 
immunocompromised
topical treatmentb 
+ oral terbinafine 
or oral fluconazole

Concomitant meds
topical treatmentb

+/- oral terbinafine
or oral fluconazole

Concurrent 
nail psoriasis

treat 
onychomycosis 
first by clinical 
presentation

Liver/kidney issues
topical treatmentb

Dermatophytomaa

topical 
efinaconazole

Moderatea

topical 
efinaconazole 

or oral terbinafine

Severea

oral terbinafine 
+/-  topical 
treatmentb

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Patient Characteristics

These are topline recommendations for treatment. All patient characteristics—including age, disease duration/severity, clinical presentation, concomitant 
medications, and comorbidities—must be taken into consideration when making treatment decisions, particularly for patients with more complex presentation. 
For all treatments, check prescribing information for potential drug-drug interactions and contraindications. 
aMild defined as <20% nail involvement; Moderate defined as 20%–60% nail involvement, Severe defined as >60% nail involvement and/or additional factors (ie, 
matrix involvement, 3 mm thickness great toenail, >1 great toenail involved, >3-4 toenails involved, total dystrophic nail); Dermatophytoma8-10 is a specialized term 
used by some dermatologists and can be defined as onychomycosis presenting as yellow or white streaks/patches in subungual space. 
bEfinaconazole preferred due to higher rates of complete cure and mycologic cure versus other topical treatments. 
From Lipner SR, et al. J Drugs Dermatol. 2021;20(10): doi:10.36849/JDD.6291.

FIGURE 3.   Therapeutic Recommendations by Drug

+/−

+

Treatment

Topical
monotherapy

Topical + oral 
(terbina�ne or 

�uconazole)

Oral
(+/- topical)

Ideal for the following:

• Milda or moderatea disease (e�naconazole)
• Pediatric patients (e�naconazole)
• Treatment of dermatophytomasa (e�naconazole) 
• Patients with liver/kidney issues 
• Consider for maintenance therapy to prevent relapse 
 (long-term, from once-weekly to once-daily)

• Moderatea or severea disease (terbina�ne)
• Fingernail with con�rmed Candida albicans infection 
 (�uconazole)
• Second-line for patients who fail terbina�ne (�uconazole)

• Patients aged ≥65 years
• Patients with diabetes
• Patients with peripheral vascular disease
• Immunocompromised patients
• Patients with certain concomitant medications (oral optional)
• Second-line for patients who fail topical monotherapy

These are topline recommendations for treatment. All patient characteristics—including age, disease duration/severity, clinical presentation, concomitant 
medications, and comorbidities—must be taken into consideration when making treatment decisions, particularly for patients with more complex presentation. For 
all treatments, check prescribing information for potential drug-drug interactions and contraindications. 
Efinaconazole preferred for topical treatment due to higher rates of complete cure and mycologic cure versus other topical treatments. 
aSee Figure 2 footnote for definitions. 
From Lipner SR, et al. J Drugs Dermatol. 2021;20(10): doi:10.36849/JDD.6291.

FIGURE 4.   Patient Education Handout

When to contact your doctor
• If family/household members have athlete’s foot or nail infections, 
 they should seek treatment and take precautions to prevent spread. 
• If you see signs of athlete’s foot or reinfection of the nail(s), 
 contact your doctor as soon as possible. 



• Wear properly sized shoes with adequate toe boxes. Avoid narrow-toed 
 shoes or high heels. Avoid non-breathable athletic shoes.
• Don’t walk barefoot in public facilities such as pools, spas, 
 locker rooms, showers, or gyms. Wear �ip �ops or shower shoes.
• When trying on new shoes, always wear socks.
• Use antifungal spray or powder in your shoes and/or a UV shoe 
 sanitizer everyday.
• Wear moisture-wicking socks or copper or silver antimicrobial socks.
• Alternate athletic shoes to allow each pair to dry thoroughly for 
 2–3 days between uses.
• Replace athletic shoes after 500 miles of use.

• Keep nails short and clean. 
• Only visit a licensed manicurist/pedicurist; bring your own 
 tools and clean them.
• Don’t pick your toenails or scratch your feet with �ngernails.
• Don’t use the same clippers/�les used on abnormal 
 nails on normal nails.
• Don’t share personal nail care instruments, soap, or towels. 
• Wash and dry your hands after contact with infected feet or nails.
• Dry feet thoroughly after washing.
• Wash towels, socks, and clothes after every use. Socks and other 
 contaminated clothing/towels should be washed at 140°F (60°C).

What to know about fungal nail infections
• Nail fungus may be in your shoes, carpet, bathroom, locker rooms, etc.
• Toenails grow slowly, so improvements could take 1–2 years to be noticeable.
• Even after the fungus is gone, the affected nail(s) may never look completely normal. 
• Once the fungus is cleared, it can return. 

Use treatment(s) recommended by your doctor and
follow the steps below to help prevent new infections:

Footwear

Personal Care and Laundry

From Lipner SR, et al. J Drugs Dermatol. 2021;20(10): doi:10.36849/JDD.6291.

CONCLUSIONS
 � These therapeutic recommendations, based on new clinical data, provide 
important updates to previous guidelines/consensus documents to assist 
healthcare practitioners in the diagnosis and treatment of toenail 
onychomycosis

 � Onychomycosis should be assessed clinically and confirmed with 
microscopy, histology, and/or culture

 � Terbinafine is the primary choice for oral treatment and efinaconazole  
10% for topical

 � Efinaconazole can be used for maintenance to prevent recurrence

 � For optimal outcomes, patients should be counseled regarding treatment 
expectations as well as follow-up care and maintenance post-treatment

REFERENCES
1. Gupta AK, Paquet M. J Cutan Med Surg. 2015;19(3):260-273.
2. Ghannoum MA, Hajjeh RA, Scher R, et al. J Am Acad 

Dermatol. 2000;43(4):641-648.
3. Rosen T, Friedlander SF, Kircik L, et al. J Drugs Dermatol. 

2015;14(3):223-233.
4. Gupta AK, Stec N. F1000Res. 2019;8.

5. Tosti A, Elewski BE. Skin Appendage Disord. 2016;2(1-2):83-87.
6. Narasimha Murthy S, Wiskirchen DE, Bowers CP. J Pharm Sci. 

2007;96(2):305-311.

7. Ameen M, Lear JT, Madan V, et al. Br J Dermatol. 
2014;171(5):937-958.

8. Burkhart CN, Burkhart CG, Gupta AK. J Am Acad Dermatol. 
2002;47(4):629-631.

9. Roberts DT, Evans EG. Br J Dermatol. 1998;138(1):189-190.
10. Wang C, Cantrell W, Canavan T, Elewski B. Skin Appendage 

Disord. 2019;5(5):304-308.

AUTHOR DISCLOSURES
Shari R. Lipner has served a consultant for Ortho Dermatologics, Hoth Therapeutics, and Verrica. Warren S. Joseph has served as consultant and speaker for Ortho Dermatologics. Tracey C. Vlahovic has served as 
investigator and speaker for Ortho Dermatologics. Richard K. Scher has nothing to disclose. Phoebe Rich has received research and educational grants from AbbVie, Allergan, Anacor Pharmaceuticals, Boehringer 
Ingelheim, Cassiopea, Dermira, Eli Lilly, Galderma, Janssen Ortho Inc., Kadmon Corporation, LEO Pharma, Merck, Moberg Derma, Novartis, Pfizer, Ranbaxy Laboratories Limited, Sandoz, Viamet Pharmaceutical Inc., 
Innovation Pharmaceuticals (Cellceutix), and Cutanea Life Sciences. Mahmoud Ghannoum has acted as a consultant or received contracts from Scynexis, Inc, Bausch & Lomb, Pfizer, and Mycovia. C. Ralph Daniel has 
provided clinical research support to Ortho Dermatologics and owns stock in Medimetriks Pharmaceuticals. Boni Elewski has provided clinical research support (research funding to University) for AbbVie, 
Anaptys-Bio, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Incyte, LEO Pharma, Lilly, Merck, Menlo, Novartis, Pfizer, Regeneron, Sun Pharma, Ortho Dermatologics, Vanda; and as consultant (received 
honorarium) from Boehringer Ingelheim, Bristol Meyers Squibb, Celgene, LEO Pharma, Lilly, Menlo, Novartis, Pfizer, Sun Pharma, Ortho Dermatologics, Verrica.

Patient Education
 � It is important to manage patient expectations when treating onychomycosis: optimal 
results can take over a year and clinical cure/normal nail appearance may not be possible

 � Patients should also be educated on the high recurrence rates (6.5%–53%)5; as such, 
regular follow-up visits with patients are recommended (3–6 months after oral or 1 year 
after topical treatment)

 � A physical handout (Figure 4) should also be provided to patients, explaining follow-up 
care/maintenance and highlighting that long-term treatment is more than just 
pharmacologic (eg, personal care, footwear selection/care, laundry)