Onychomycosis

Practice Essentials

Onychomycosis is a fungal infection of the toenails or fingernails that may involve any component of the nail unit, including the matrix, bed, or plate. Onychomycosis can cause pain, discomfort, and disfigurement and may produce serious physical and occupational limitations, as well as reducing quality of life. See the image below.

View Image

Proximal subungual onychomycosis. Proximal leukonychia. Image courtesy of Dr Antonella Tosti.

Signs and symptoms

Patients with onychomycosis may present with the following:

• Initially, complaints about the appearance of the nail, with no physical symptoms
• As the disease progresses, interference with standing, walking, and exercising
• Paresthesia, pain, discomfort, and loss of dexterity
• Loss of self-esteem and inhibited social interaction

Onychomycosis has 5 main subtypes, as follows:

• Distal lateral subungual onychomycosis (DLSO)
• White superficial onychomycosis (WSO)
• Proximal subungual onychomycosis (PSO)
• Endonyx onychomycosis (EO)
• Candidal onychomycosis

Patients may have a combination of these subtypes. Total dystrophic onychomycosis, the most advanced form of any subtype, presents as a thickened, opaque, and yellow-brown nail. Presentation varies by subtype.

Features of DLSO are as follows:

• Subungual hyperkeratosis and onycholysis, which is usually yellow-white in color
• Yellow streaks and/or yellow onycholytic areas in the central portion of the nail plate

Features of WSO are as follows:

• Confined to the toenails
• Small, white, speckled or powdery patches on the surface of the nail plate
• The nail becomes roughened and crumbles easily
• Molds produce a deep variety of WSO characterized by a larger and deeper nail plate invasion

Features of PSO are as follows:

• An area of leukonychia in the proximal nail plate that moves distally with nail growth
• In PSO caused by molds, leukonychia is typically associated with marked periungual inflammation

Features of EO are as follows:

• Milky white discoloration of the nail plate
• No evidence of subungual hyperkeratosis or onycholysis

Features of candidal onychomycosis are as follows:

• Develops in patients with chronic mucocutaneous candidiasis or immunodepression
• Affects several or all digits
• Total onychomycosis associated with periungual inflammation
• The digits often take on a bulbous or drumstick appearance

See Clinical Presentation for more detail.

Diagnosis

Direct microscopy of a 20% potassium hydroxide (KOH) preparation in dimethyl sulfoxide (DMSO) can screen for fungi. The technique is as follows:

• Before obtaining a specimen, the nails must be clipped and cleansed with an alcohol swab to remove bacteria and debris
• The preparation does not require heating or prolonged incubation if DMSO is a component of the KOH solution
• In DLSO, obtain a specimen from the nail bed by curettage; the onycholytic nail plate should be removed, and the sample should be obtained at a site most proximal to the cuticle, where the concentration of hyphae is greatest
• In PSO, the overlying nail plate must initially be pared with a No. 15 blade; then, a sample of the ventral nail plate may be taken
• In WSO, a No. 15 blade may be used to remove a specimen from the nail surface
• In suspected candidal onychomycosis, specimens should be taken from the affected nail bed closest to the proximal and lateral edges
• Nail fragments must be small enough for examination under low power
• Large pieces of nail plate may be pulverized prior to microscopy by using a hammer or a nail micronizer
• Counterstains, such as chlorazol black E or Parker blue-black ink, may be used to accentuate the hyphae

Fungal culture can identify the species of organism and guide therapy.^[1] Culture techniques are as follows:

• Two types of growth medium should be used, one for dermatophytes and one for nondermatophytes
• Medium with cycloheximide (dermatophyte test medium [DTM], Mycosel, or Mycobiotic) selects for dermatophytes
• Medium without cycloheximide (Sabouraud glucose agar, Littman oxgall medium, or inhibitory mold agar) isolates yeasts and nondermatophyte molds^[2]
• Cultures should be obtained from pulverized nail scrapings or clippings while the patient has abstained from antifungal medication for at least 2 weeks
• The specimen should be kept at room temperature with the cap placed loosely over the inoculated medium

See Workup for more detail.

Management

Medications for onychomycosis can be administered topically or orally. A combination of topical and systemic treatment increases the cure rate. Adjunctive surgical measures may also be used.

Topical therapy for onychomycosis is as follows:

• Ciclopirox olamine 8% nail lacquer solution
• Amorolfine or bifonazole/urea (available outside the United States)
• Efinaconazole 10% topical solution (the first FDA-approved topical triazole for toenail onychomycosis)
• Tavaborole 0.5% topical solution, an oxaborole solution (boron-containing compound)
• Can be used in WSO and DLSO limited to the distal nail
• Should be limited to cases involving less than half of the distal nail plate or for patients unable to tolerate systemic treatment
• Topical treatments may be useful to prevent recurrence in patients cured with systemic agents

Oral therapy for onychomycosis is as follows:

• Terbinafine
• Itraconazole
• Fluconazole and posaconazole^[3] are off-label alternatives
• Systemic treatment is always required in PSO and in DLSO involving the lunula region

Nonpharmacologic approaches include the following:

• Laser treatment
• Photodynamic therapy
• Mechanical, chemical, or surgical nail avulsion
• Chemical removal with a 40-50% urea compound in patients with very thick nails
• Removal of the nail plate as an adjunct to oral therapy

Laser treatment can be combined with topical antifungals.^{[4, 5]}

See Treatment and Medication for more detail.

• References

Background

Onychomycosis (OM) refers to a fungal infection that affects the toenails or the fingernails. Onychomycosis may involve any component of the nail unit, including the nail matrix, nail bed, or nail plate. Onychomycosis is not life threatening, but it can cause pain, discomfort, and disfigurement and may produce serious physical and occupational limitations. Psychosocial and emotional effects resulting from onychomycosis are widespread and may have a significant impact on quality of life.^[6]

The main subtypes of onychomycosis are distal lateral subungual onychomycosis (DLSO), white superficial onychomycosis (WSO), proximal subungual onychomycosis (PSO), endonyx onychomycosis (EO), and candidal onychomycosis. Patients may have a combination of these subtypes. Total dystrophic onychomycosis refers to the most advanced form of any subtype.

Special concerns

HIV disease

Onychomycosis in patients who are immunocompromised is associated with increased severity and morbidity. Lesions may appear atypical and require more aggressive management compared with the healthy population. Proximal subungual (ie, proximal subungual onychomycosis) involvement is much more prevalent in patients with HIV infection than in those without HIV infection. In this population, white superficial onychomycosis is more commonly caused by T rubrum, rather than T mentagrophytes.

Diabetes ^[7]

The diabetic foot may lead to serious complications associated with onychomycosis. Peripheral neuropathy and sensory loss may lead to increased trauma without pain in patients with diabetes. Bacterial colonization and vascular insufficiency may exacerbate the problem and may lead to serious sequelae.

Elderly age ^[8]

Onychomycosis in elderly people is complicated by diseases (eg, poor vision, arthritis) that prevent optimal foot care. Nail changes are much more common in elderly persons and often involve the fingernails and the toenails. The potential for drug-drug interactions is more evident and must be addressed before initiating oral therapy.

• References

Pathophysiology

The pathogenesis of onychomycosis depends on the clinical subtype. In distal lateral subungual onychomycosis, the most common form of onychomycosis, the fungus spreads from plantar skin and invades the nail bed via the hyponychium. Inflammation occurring in these areas of the nail apparatus causes the typical physical signs of distal lateral subungual onychomycosis. In contrast, white superficial onychomycosis is a rarer presentation caused by direct invasion of the surface of the nail plate. In proximal subungual onychomycosis, the least common subtype, fungi penetrate the nail matrix via the proximal nail fold and colonize the deep portion of proximal nail plate. Endonyx onychomycosis is a variant of distal lateral subungual onychomycosis in which the fungi infect the nail via the skin and directly invade the nail plate. Total dystrophic onychomycosis involves the entire nail unit (see the image below).

View Image

Distal subungual onychomycosis. Onycholysis and yellow streak. Image courtesy of Dr Antonella Tosti.

Nail invasion by Candida is not common because the yeast needs an altered immune response as a predisposing factor to be able to penetrate the nails. Despite the frequent isolation of Candida from the proximal nail fold or the subungual space of patients with chronic paronychia or onycholysis, in these patients Candida is only a secondary colonizer. In chronic mucocutaneous candidiasis, the yeast infects the nail plate and eventually the proximal and lateral nail folds.

• References

Etiology

Onychomycosis is caused by 3 main classes of fungi: dermatophytes, yeasts, and nondermatophyte molds. Dermatophytes are by far the most common cause of onychomycosis. Two major pathogens are responsible for approximately 90% of all onychomycosis cases. Trichophyton rubrum accounts for 70% and Trichophyton mentagrophytes accounts for 20% of all cases. Onychomycosis caused by nondermatophyte molds (Fusarium species, Scopulariopsis brevicaulis,Aspergillus species) is becoming more common worldwide, accounting for up to 10% of cases.^[9] Onychomycosis due to Candida is rare.^[10]

T rubrum is the most common pathogen in distal lateral subungual onychomycosis. Proximal subungual onychomycosis due to T rubrum infection is typical of immunosuppressed patients . Additionally, Proximal subungual onychomycosis with periungual inflammation is usually caused by molds

White superficial onychomycosis is usually caused by T mentagrophytes; nondermatophyte molds cause deep white superficial onychomycosis.

Candida albicans nail infection is observed in premature children, in immunocompromised patients, and in persons with chronic mucocutaneous candidiasis.

Risk factors for onychomycosis include family history, increasing age, poor health, prior trauma, warm climate, participation in fitness activities, immunosuppression (eg, HIV, drug induced), communal bathing, and occlusive footwear. Biomechanical problems with repetitive microtraumas to the nails cause onycholysis and other nail dystrophies that favor nail invasion by fungi.

• References

Epidemiology

United States

The recent proliferation of fungal infections in the United States can be traced to the large immigration of dermatophytes, especially Trichophyton rubrum, from West Africa and Southeast Asia to North America and Europe.^[11]

International

The incidence of onychomycosis has been reported to be 2-13% in North America.^[12] A multicenter survey in Canada showed the prevalence of onychomycosis at 6.5%.^[13] Onychomycosis accounts for half of all nail disorders, and onychomycosis is the most common nail disease in adults. Toenails are much more likely to be infected than fingernails. Thirty percent of patients with a cutaneous fungal infection also have onychomycosis. The incidence of onychomycosis has been increasing, owing to such factors as diabetes, immunosuppression, and increasing age.^[11]

Studies in the United Kingdom, Spain, and Finland found prevalence rates of onychomycosis to be 3-8%.

Race

Onychomycosis affects persons of all races.

Sex

Onychomycosis affects males more commonly than females. However, candidal infections are more common in women than in men.

Age

Studies indicate that adults are 30 times more likely to have onychomycosis than children. Onychomycosis has been reported to occur in 2.6% of children younger than 18 years but as many as 90% of elderly people.

• References

Prognosis

The goals for antifungal therapy are mycological cure and a normal looking nail. Mycological cure can be evaluated at the end of treatment, while clinical cure requires several more months owing to slow nail growth.^[14]

Clinical trials have repeatedly demonstrated higher efficacy for terbinafine compared with other antifungal treatments.^{[15, 16]} A meta-analysis of 18 studies on terbinafine, 6 studies on pulse itraconazole, and 3 studies on fluconazole for onychomycosis showed a mycological cure rate of 76%, 63 %, and 48 % respectively.^[17]

Yellow streaks along the lateral margin of the nail and/or presence of yellow onycholytic areas in the central portion of the nail (dermatophytoma) are associated with a poor response to treatment.

Residual nail changes persist in most patients as a result of the frequent association of onychomycosis with traumatic toenail dystrophies.

Onychomycosis caused by molds, particularly Fusarium species, are often not responsive to systemic therapy.

Recurrence (relapse or reinfection) of onychomycosis is not uncommon, with reported rates ranging from 10-53%.^[18]

Fungal infections of the fingernails have a much more favorable prognosis than toenail infections.

• References

Patient Education

Patients should be educated about the use of appropriate footwear, especially in high-exposure areas such as communal bathing facilities and health clubs.

Following treatment, patients must be advised that nails may not appear normal for up to 1 year, and prophylactic antifungal therapy may be required to prevent reinfection of the skin and the nails. Patients may use topical terbinafine cream twice daily for 1-2 weeks for early tinea pedis or a 1-week pulse of itraconazole (200 mg PO bid) at the first signs of onychomycosis.^[19]

For patient education resources, see the Psoriasis Center and Yeast and Fungal Infections Center, as well as Nail Psoriasis and Onychomycosis.

• References

History

Onychomycosis is usually asymptomatic; therefore, patients usually first present for cosmetic reasons without any physical complaints.

As the disease progresses, onychomycosis may interfere with standing, walking, and exercising.

Patients may report paresthesia, pain, discomfort, and loss of dexterity. They also may report loss of self-esteem and lack of social interaction.

A careful history may reveal many environmental and occupational risk factors.

• References

Physical Examination

The subtypes of onychomycosis may be distinguished on the basis of their usual presenting clinical features.

In distal lateral subungual onychomycosis, the nail shows subungual hyperkeratosis and onycholysis, which is usually yellow-white in color. Yellow streaks and/or yellow onycholytic areas in the central portion of the nail plate are commonly observed. Note the images below.

View Image

Distal subungual onychomycosis. Onycholysis and yellow streak. Image courtesy of Dr Antonella Tosti.

View Image

Distal subungual onychomycosis. Subungual hyperkeratosis onycholysis and yellow streak. Image courtesy of Dr Antonella Tosti.

Endonyx onychomycosis presents as a milky white discoloration of the nail plate, but, in contrast to distal lateral subungual onychomycosis, no evidence of subungual hyperkeratosis or onycholysis is present.

White superficial onychomycosis is confined to the toenails and manifests as small, white, speckled or powdery patches on the surface of the nail plate. The nail becomes roughened and crumbles easily. Molds produce a deep variety of white superficial onychomycosis characterized by a larger and deeper nail plate invasion. Note the image below.

View Image

White superficial onychomycosis. Image courtesy of Dr Antonella Tosti.

Proximal subungual onychomycosis presents as an area of leukonychia in the proximal nail plate that moves distally with nail growth. In proximal subungual onychomycosis caused by molds, leukonychia is typically associated with marked periungual inflammation. Note the image below.

View Image

Proximal subungual onychomycosis. Proximal leukonychia. Image courtesy of Dr Antonella Tosti.

Total dystrophic onychomycosis presents as a thickened, opaque, and yellow-brown nail.

In Candida onychomycosis associated with chronic mucocutaneous candidiasis or immunodepression, several or all digits are affected by total onychomycosis associated with periungual inflammation. The digits often take on a bulbous or drumstick appearance. Note the image below.

View Image

Candidal onychomycosis in a patient with chronic mucocutaneous candidiasis. Total onychomycosis and paronychia. Image courtesy of Dr Antonella Tosti.

• References

Complications

Skin injury adjacent to the nail may allow organisms to colonize, thereby increasing the risk of infectious complications. Reports of complications in elderly persons and persons with diabetes include cellulitis, osteomyelitis, sepsis, and tissue necrosis.

• References

Laboratory Studies

The clinical features of onychomycosis may mimic a large number of other nail disorders. Therefore, laboratory diagnosis of onychomycosis must be confirmed before beginning a treatment regimen. A negative mycological result does not rule out onychomycosis, because direct microscopy may be negative in up to 10% of cases and culture in up to 30% of cases.

Direct microscopy

A 20% potassium hydroxide (KOH) preparation in dimethyl sulfoxide (DMSO) is a useful screening test to rule out the presence of fungi. Before obtaining a specimen, the nails must be clipped and cleansed with an alcohol swab to remove bacteria and debris. The preparation does not require heating or prolonged incubation if DMSO is a component of the KOH solution.

In distal lateral subungual onychomycosis, a specimen should be obtained from the nail bed by curettage. The onycholytic nail plate should be removed and the sample should be obtained at a site most proximal to the cuticle, where the concentration of hyphae is greatest.

In proximal subungual onychomycosis, the overlying nail plate must initially be pared with a No. 15 blade. Then, a sample of the ventral nail plate may be taken. A No. 15 blade may also be used to remove a specimen from the nail surface in white superficial onychomycosis.

Specimens suspected of candidal onychomycosis should be taken from the affected nail bed closest to the proximal and lateral edges.

Nail fragments must be small enough for examination under low power. Large pieces of nail plate may be pulverized prior to microscopy by using a hammer or a nail micronizer. Counterstains, such as chlorazol black E or Parker blue-black ink, may be used to accentuate the hyphae. Shemer et al reported that drilling to obtain specimens and taking the sample from a more proximal site yield better results.^[20]

Culture

Direct microscopy cannot identify the specific pathogen involved in onychomycosis. A fungal culture must be used to identify the species of organism.^[1] Nondermatophyte molds may be resistant to the conventional therapy used for the more common dermatophytes.^[21] Therefore, 2 types of growth medium should be used, one with cycloheximide (dermatophyte test medium [DTM], Mycosel, or Mycobiotic) to select for dermatophytes and one without cycloheximide (Sabouraud glucose agar, Littman oxgall medium, or inhibitory mold agar) to isolate yeasts and nondermatophyte molds.^[2]

Cultures should be obtained from pulverized nail scrapings or clippings while the patient has abstained from antifungal medication for at least 2 weeks. The specimen should be kept at room temperature with the cap placed loosely over the inoculated medium.

• References

Other Tests

Polymerase chain reaction (PCR) assays have been developed to detect fungal DNA from infected nails.^[22] A highly sensitive nested PCR assay using species-specific primer pairs based on the 28S ribosomal RNA gene has been developed. This methodology permits detection of both dermatophytes and nondermatophytes.^[23]

• References

Procedures

Dermoscopy is useful to distinguish distal subungual onychomycosis from traumatic onycholysis. In distal subungual onychomycosis, the proximal border of the onycholytic area is jagged owing to the presence of yellow-white spikes that project into the proximal nail plate. See the image below. This patterned has been reported as the "aurora borealis" pattern.^[24]

View Image

Dermoscopy of distal subungual onychomycosis showing irregular margin of the onycholytic area with spikes projecting into the proximal nail plate, rep....

• References

Histologic Findings

Histologic examination of the nail is a very useful alternative to culture or KOH testing. Nail clippings may be sent to the laboratory for diagnosis in a formalin-filled container, or, as a last resort, an incisional nail biopsy (by punch or scalpel) may be performed to help confirm the diagnosis. Staining in the laboratory should be performed with periodic acid-Schiff stain (PAS) or methenamine silver stain to reveal fungal elements. A comparison of diagnostic methods revealed that a nail biopsy and staining with PAS is the most sensitive technique available to diagnose onychomycosis.^[25] Examining formalin-fixed, PAS-stained specimens has a higher probability (a higher negative predictive value) than KOH examination in determining that a patient is disease free if the test results are negative.

In addition to excluding other conditions (eg, psoriasis, lichen planus), the topographic distribution, the density, and the nature of the fungal elements may help guide treatment. Biopsy specimens of onychomycosis may show features of psoriasiform hyperplasia, including parakeratosis, thinned rete ridges, narrow suprapapillary plates, and dilated tortuous capillaries. As in direct microscopy, histopathologic diagnosis does not identify the species of causative pathogen.

• References

Staging

The onychomycosis severity index (OSI) has recently been proposed to grade the severity of distal subungual onychomycosis. The OSI score is obtained by multiplying the score for the area of involvement (range, 0-5) by the score for the proximity of disease to the matrix (range, 1-5). Ten points are added for the presence of a longitudinal streaking or a patch (dermatophytoma) or for greater than 2 mm of subungual hyperkeratosis. Mild onychomycosis corresponds to a score of 1-5; moderate, 6-15; and severe, 16-35.^[26]

• References

Medical Care

Treatment of onychomycosis depends on the clinical type of the onychomycosis, the number of affected nails, and the severity of nail involvement.^{[27, 28]} A systemic treatment is always required in proximal subungual onychomycosis and in distal lateral subungual onychomycosis involving the lunula region. White superficial onychomycosis and distal lateral subungual onychomycosis limited to the distal nail can be treated with a topical agent. A combination of systemic and topical treatment increases the cure rate. Because the rate of recurrence remains high, even with newer agents, the decision to treat should be made with a clear understanding of the cost and risks involved, as well as the risk of recurrence. Photodynamic therapy and lasers may represent future treatment options.^{[29, 30]}

Topical antifungals

The use of topical agents should be limited to cases involving less than half of the distal nail plate or for patients unable to tolerate systemic treatment. Agents available in the United States include ciclopirox olamine 8% and efinaconazole 10% nail solutions. Amorolfine and bifonazole/urea are available outside of the United States.

Topical treatments alone are generally unable to cure onychomycosis because of insufficient nail plate penetration. Ciclopirox and amorolfine solutions have been reported to penetrate through all nail layers but have low efficacy when used as monotherapy.^[31] They may be useful as adjunctive therapy in combination with oral therapy or as prophylaxis to prevent recurrence in patients cured with systemic agents. Daily application and a long duration of treatment (48 wk) are required for efinaconazole and ciclopirox.

Efinaconazole is indicated for toenail onychomycosis.^[32] Its approval was based on 2 phase III multicenter, randomized trials (N = 1655). Complete cure was seen in 17.8% and 15.2% of patients receiving the drug, versus 3.3% and 5.5% of subjects receiving the vehicle. Mycologic cure rates were significantly greater with efinaconazole (53.4-55.2%) compared with the drug vehicle (P< .001).^{[33, 34, 35]}

Tavaborole, a topical oxaborole antifungal (boron-containing compound) is indicated for onychomycosis of the toenails due to Trichophyton rubrum or Trichophyton mentagrophytes.^[36]  Its approval was based on two multicenter, double-blind, randomized trials involving 1194 subjects. After 48 weeks of treatment, complete cure was found in 6.5% and 9.1% in patients receiving tavaborole compared with 0.5% and 1.5%, respectively, of patients applying the vehicle alone.^[37]  Mycological cure was obtained in 31.1% and 35.9% for active treatment versus 7.2% and 12.2% for the vehicle.

Laser treatment can be combined with topical antifungals.^{[4, 5]}

Oral therapy

The newer generation of oral antifungal agents (itraconazole and terbinafine) has replaced older therapies in the treatment of onychomycosis.^{[38, 39, 40]} They offer shorter treatment regimens, higher cure rates, and fewer adverse effects. Fluconazole and the new triazole posaconazole^[3] (both not approved by the US Food and Drug Administration [FDA] for treatment of onychomycosis) offer an alternative to itraconazole and terbinafine. The efficacy of the newer antifungal agents lies in their ability to penetrate the nail plate within days of starting therapy. Evidence shows better efficacy with terbinafine than with other oral agents (see Prognosis).^[15]

To decrease the adverse effects and duration of oral therapy, topical treatments and nail avulsion may be combined with oral antifungal management.^[41]

• References

Surgical Care

Several laser devices have been used to treat onychomycosis, including Nd:YAG lasers and diode lasers. Evidence-based data on efficacy of the different lasers are still poor. Laser treatment can be combined with topical antifungals.^{[4, 5]}

Photodynamic therapy has been reported as effective in noncontrolled studies.^[42]

Surgical approaches to onychomycosis treatment can also include mechanical, chemical, or surgical nail avulsion. Chemical removal by using a 40-50% urea compound is painless and useful in patients with very thick nails. Removal of the nail plate should be considered an adjunctive treatment in patients undergoing oral therapy. A combination of oral, topical, and surgical therapy can increase efficacy and reduce cost.

• References

Activity

Activity does not need to be limited during treatment, but patients should be educated about avoiding direct contact with high-risk areas in public places.

• References

Long-Term Monitoring

Although hepatotoxic reactions are unlikely, periodic monitoring of patients undergoing oral antifungal therapy should include a CBC count and measurements of liver enzyme levels approximately every 4-6 weeks.

Treatment may be discontinued after standard dosing with terbinafine or itraconazole when no evidence of fungal infection (by microscopy or culture) is present. Nails may continue to look dystrophic after a cure is achieved in the laboratory.

After antifungal therapy, disease-free nail growth should be measured at every visit. Nails should grow at a rate of 1.5-2 mm per month and may take up to 1 year to look normal. A clinician may consider an additional dose of antifungal medication if the outgrowth distance slows or stops after discontinuing therapy.

• References

Guidelines Summary

In 2014, the British Association of Dermatologists published updated evidence-based guidelines for the management of onychomycosis.^[43] Treatment recommendations are given for both adults and children (ages 1-12 y).

Adult systemic treatment recommendations are as follows:

• Terbinafine as first line of treatment for dermatophyte onychomycosis and generally preferred over itraconazole; not recommended for patients with active or chronic liver disease (level A)
• Itraconazole as first line of treatment for dermatophyte onychomycosis (level A)
• Fluconazole may be a useful alternative in patients unable to tolerate terbinafine or itraconazole (level B)
• Griseofulvin is no longer a treatment of choice owing to lower efficacy and higher relapse rates compared with terbinafine and itraconazole (level C)
• Combination treatment recommended if response to topical monotherapy is likely to be poor (level D)

Adult topical treatment recommendations are as follows:

• Amorolfine or tioconazole are useful for superficial and distal onychomycosis (level D)
• Ciclopirox is useful for superficial and distal onychomycosis and for patients in whom systemic therapy is contraindicated (level D)

Adult other treatment recommendations are as follows:

• Surgical avulsion, debridement alone, and photodynamic therapy (PDT) not recommended

Children systemic treatment recommendations are as follows:

• Terbinafine as first line of treatment for dermatophyte onychomycosis and generally preferred over itraconazole (level A)
• Itraconazole is first line of treatment for dermatophyte onychomycosis (level A)
• Fluconazole considered as second line if itraconazole and terbinafine contraindicated or not tolerated (level B)
• Griseofulvin considered as second line if itraconazole and terbinafine contraindicated or not tolerated (level C)

In 2013, as part of the Choosing Wisely® initiative from the American Board of Internal Medicine Foundation (ABIM), the American Academy of Dermatology (AAD) released recommendations regarding low-value care that cautioned against prescribing oral antifungal therapy for suspected nail fungus without confirmation of fungal infection. The AAD concluded that about half of suspected fungal infections are not fungal infections and starting patients on treatment before confirming diagnosis could unnecessarily expose them to the adverse effects of antifungal therapy. Although the diagnosis of onychomycosis can be made clinically, it is important to confirm this with a nail clipping and with a periodic acid-Schiff or a fungal culture.^[44]

• References

Medication Summary

The goals of pharmacotherapy for onychomycosis are to reduce morbidity and to prevent complications.

• References

Terbinafine (Lamisil)

• Dosing, Interactions, etc.

Clinical Context:  Terbinafine inhibits squalene epoxidase, which decreases ergosterol synthesis, causing fungal cell death. Use the medication until symptoms significantly improve. More studies are needed to establish the efficacy of pulse regimens and the optimal duration of treatment.

• References

Itraconazole (Sporanox)

• Dosing, Interactions, etc.

Clinical Context:  Itraconazole has fungistatic activity. It is a synthetic triazole antifungal agent that slows fungal cell growth by inhibiting CYP-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes.

• References

Fluconazole (Diflucan)

• Dosing, Interactions, etc.

Clinical Context:  Fluconazole has fungistatic activity. It is a synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal CYP-450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes. Treatment should continue until the infection resolves.

• References

Class Summary

The goals of pharmacotherapy for onychomycosis are to reduce morbidity and to prevent complications.

• References

Ciclopirox (Penlac)

• Dosing, Interactions, etc.

Clinical Context:  Ciclopirox interferes with the synthesis of DNA, RNA, and protein by inhibiting the transport of essential elements in fungal cells.

• References

Efinaconazole (Jublia)

• Dosing, Interactions, etc.

Clinical Context:  Efinaconazole is a topical triazole antifungal agent. It inhibits fungal lanosterol 14α-demethylase involved in the biosynthesis of ergosterol, a constituent of fungal cell membranes. It is indicated for onychomycosis of the toenail(s) due to Trichophyton rubrum and Trichophyton mentagrophytes.

• References

Tavaborole (Kerydin)

• Dosing, Interactions, etc.

Clinical Context:  Tavaborole, a topical oxaborole antifungal (boron-containing compound), is indicated for onychomycosis of the toenails due to Trichophyton rubrum or Trichophyton mentagrophytes. It is available as 0.5% topical solution.

• References

Class Summary

Treatment of onychomycosis with topical antifungals is typically used as adjunctive therapy in combination with oral agents.

• References