Toenail Fungus Treatment Updates

Onychomycosis treatment is evolving past extended-duration monotherapy into multimodal precision regimens that target fungal DNA, biofilms, nail penetration, and more. These targeted newer options provide:

• Faster mycologic clearance

• Improved safety profile

• Lower recurrence rates

when applied in sequential combinations and monitored for efficacy.

Don’t rely on a single modality. Always stage treatment and consider maintenance.

Traditionally, toenail fungus was treated with oral antifungal agents as monotherapy. Combined regimens were more complicated, had questionable added-value, and were not always tolerated.

Now you’re likely to see:

• Next-gen topical triazoles

• Enhanced penetration/topical “lacquers”

• Laser-enhanced drug penetration

• Combination oral/topical/debridement regimens

• Specialized adjuncts to target biofilms

Old Treatments Fail Because…

As more options become available, it’s important to understand the situations where your patient may not respond to traditional therapies and talk about alternative treatments.

Oral Agents (Terbinafine, Itraconazole)

These are still going to be the most effective agent you have in your toolbox. However, in today’s practice, you have to be more diligent about:

• Monitoring for liver toxicity

• Checking for drug interactions

• Proper patient selection

As drug resistance becomes more prevalent, you may also see a decrease in response to terbinafine specifically. This can happen via mutations in the squalene epoxidase (SQLE) gene (L393F, F397L).

Older Topicals

Topical agents have poor penetration of the nail plate. Plus you must treat for at least 48 weeks ON A DAILY BASIS. Who’s going to do that?!

Maintenance and efficacy in real-world settings are two of the biggest hurdles for topical therapies. Fungal biofilms and efflux pumps can also play a role in limiting drug penetration in dermatophytes.

You Light My Lamp: Laser & Light Treatments for Onychomycosis

Laser therapy and light-activated medications are growing in popularity as supplement treatments.

Nd: YAG Laser

• Penetrates into the nail bed and plate.

• Thermally kills fungal cells.

• Usually administered in multiple courses.

Fractional CO₂ Laser

• Superficial laser that helps create microchannels in the nail plate.

Think of this laser as a “helper” to enhance topical absorption. Laser monotherapy shows mixed-results, but likely helps when combined with topical antifungals.

Photodynamic Therapy

Utilizes a photosensitizing agent along with light to create free radicals that kill fungus.

Cold Laser? There is some data using low-level laser therapy (battery powered “cold” lasers) that show symptomatic improvement with minimal discomfort.

Biochemical Stasis with the PRESSURE CO2 Laser

Hitting the Nail On the Head: Topical Delivery Advances

Topical treatments are constantly being improved to deliver higher concentrations of medication to the nail bed.

Enhanced Penetration

• Microporation

• Lipid nanoparticle delivery

• Vesicular transport

allows for longer contact time of the drug on the nail surface and better penetration into the nail matrix.

Sustained-Release Lacquers

Film-forming agents that allow for prolonged contact with the nail surface.

• Apply less often

• Increased overall therapeutic concentration

New agents like efinaconazole and tavaborole show better nail penetration than older generation topical agents like ciclopirox.

It’s Elementary: Systemic Treatment is Getting Better Too

Drug targeting and specificity are on the rise.

Novel Triazoles

Being developed with greater selectivity for fungal CYP51 and less impact on hepatic enzymes.

Targeted Drug Delivery

Delivery of antifungals specifically to the nail bed using lipid nanoparticles.

These treatments limit systemic absorption and concentrate medication where it’s needed.

There are currently injectable options and advanced oral nanoparticle technologies in late phase clinical trials showing promising tolerability and mycological cure rates.

Biofilm Busting & Beyond

New antifungals are being discovered every year.

Synthetic Antimicrobial Peptides

SAMPs are synthetic antimicrobial peptides that

• Can penetrate biofilms

• Interrupt fungal cell membranes

• Have less resistance potential

Antifungals that target biofilm formation are quickly becoming the standard of care. Check out our comprehensive guide on Dermatology Made Simple.

Enzymatic Nail Debridement

Using proteases and keratinases to digest the infected nail.

Allows for softer nails, better penetration of topical medications, and shorter treatment times.

When paired with an oral or topical medication, patients experience significantly better mycological clearance than medication alone.

Nail Growth 101: What does “cure” mean to you?

Ask yourself this: Did you send that patient home with expectations of what “cured” looks like?

Mycological Cure: Negative microscopy and/or culture.

Clinical Cure: Nail that appears normal.

Reminder: Healthy nails take time. Normal toenails grow ≈ 1–2 mm per month. Clear nails grow at the same rate.

One Step Forward, Two Steps Back: Stopping Recurrence

Antifungal therapy without continued maintenance is like hitting reset on a video game. It’s easy to get right back where you started.

Prevention Strategy	How
Oral pulse therapy	Take medication for a few weeks, under supervised lab monitoring.
Topical maintenance	Use medicated nail lacquer daily for 1-6 months after completion of treatment.
Shoe disinfection	Use UV nail sanitizer or antifungal spray.
Wash your socks	Hot wash and dry fully between wears.
Keep your feet dry	Rotate shoes, and stick to breathable materials.

Photoxing toenail fungus decreases recurrence risk.

Special attention should also be made to treat tinea pedis concurrently, and throw out old shoes (culture the shoes if you aren’t convinced!)

Last Resort: When to Refer To a Specialist

Know your limits. Not every patient is going to do well with medical management. At what point do you refer?

• Large areas of nail involvement (> 50%)

• If the matrix is involved.

• Immunocompromise (diabetes, HIV, immunosuppression, etc.)

• Lack of response to therapy after 3–6 months.

• Suspected drug resistance.

At WFAI, we like to confirm the diagnosis with microscopy and/or culture prior to offering treatment. Not only does this ensure you are treating the correct diagnosis, but it also helps us stage the treatment and offer tailored combination regimens to prevent recurrence and improve cosmetic outcomes.

Research into treatment of onychomycosis is constantly improving our understanding of how to best tackle toenail fungus.

Some key things to remember:

• New topical treatments are better at penetrating the nail.

• Combination therapy beats monotherapy every time.

• Resistance is possible with oral agents.

• Don’t forget about laser and light-based therapy.

• Maintenance is key to preventing recurrence.

Most patients will require staged combination treatment and some form of maintenance to truly beat toenail fungus.

FAQ

Q1: Are the newer topical medications better than the old ones?

A: Yes! New topical antifungals like efinaconazole and tavaborole have been shown to have better nail penetration and higher mycological cure rates than older treatments like ciclopirox. However, they still need to be applied daily for up to 48 weeks.

Q2: Will laser therapy clear up my toenail fungus?

A: Laser therapy can help reduce the fungal burden on your nail and give you a cosmetic improvement. However, most lasers do not completely eradicate the fungus alone. Your best bet for success is to pair laser treatments with an oral antifungal or medicated nail lacquer.

Q3: Are there any safer oral medications available?

A: Newer triazole derivatives and nanoparticle-based drug delivery platforms are currently being developed that show promise at decreasing hepatic complications and drug interactions. However, these drugs may not be available in your country.

Q4: How can I prevent my nail fungus from coming back?

A: Maintain therapy of the nail for a few months after you see it clearing. Disinfect your shoes, practice good sock hygiene, treat athlete’s foot right away, and rotate your footwear to decrease moisture buildup.

Q5: How long will it take for my nails to look normal?

A: PATIENCE! Remember that toenails grow slowly. Despite eradicating the fungus, it will take 9–18 months for your nail to completely grow out clear. Consistency with treatment and maintenance is crucial for long-lasting results.