Onychomycosis: Current Trends
`in Diagnosis and Treatment
`
`DYANNE P. WESTERBERG, DO, and MICHAEL I. VOYACK, DO
`
`Cooper Medical School ofRowan University, Camden, New Jersey
`
`Onychomycosis is a fungal infection of the nails that causes discoloration, thickening, and
`separation from the nail bed. Onychomycosis occurs in 10% of the general population, 20%
`of persons older than 60 years, and 50% of those older than 70 years. It is caused by a variety
`of organisms, but most cases are caused by dermatophytes. Accurate diagnosis involves physi-
`cal and microscopic examination and culture. Histologic evaluation using periodic acid—Schiff
`staining increases sensitivity for detecting infection. Treatment is aimed at eradication of the
`causative organism and return to a normal appearance of the nail. Systemic antifungals are the
`most effective treatment, with meta-analyses showing mycotic cure rates of 76% for terbinafine,
`63% for itraconazole with pulse closing, 59% for itraconazole with continuous dosing, and 48%
`for fluconazole. Concomitant nail debridement further increases cure rates. Topical therapy
`with ciclopirox is less effective; it has a failure rate exceeding 60%. Several nonprescription
`treatments have also been evaluated. Laser and photodynamic therapies show promise based
`on in-vitro evaluation, but more clinical studies are needed. Despite treatment, the recurrence
`rate of onychomycosis is 10% to 50% as a result of reinfection or lack of mycotic cure. (Am Fam
`Physician. 2013;88 (11) :762-770. Copyright © 2013 American Academy of Family Physicians.)
`
`; More online
`
`at http://www.
`
`aafp.orglafp.
`This clinical content
`conforms to AAFP criteria
`
`for continuing medical
`education (CME). See
`CME Quiz Questions on
`page 732.
`Author disclosure: No rel-
`evant financial affiliations.
`
`’ Patient information:
`A handout is available at
`
`http://www/aafp.org/afpl
`2013/1201/p762-s1.htm|.
`
`nychomycosis is a fungal infec-
`tion of the fingernails or toe-
`nails that causes discoloration,
`
`thickening, and separation from
`the nail bed. Onychomycosis occurs in 10%
`of the general population but is more com-
`mon in older adults; the prevalence is 20% in
`those older than 60 years and 50% in those
`older than 70 years.1 The increased preva-
`lence in older adults is related to peripheral
`vascular disease,
`immunologic disorders,
`and diabetes mellitus. The risk of onycho-
`mycosis is 1.9 to 2.8 times higher in persons
`with diabetes compared with the general
`population.2 In patients with human immu-
`nodeficiency Virus infection, the prevalence
`ranges from 15% to 40%.3
`toenails more
`Onychomycosis
`affects
`often than fingernails because of their
`slower growth, reduced blood supply, and
`frequent confinement in dark, moist envi-
`ronments. It may occur in patients with dis-
`torted nails, a history of nail trauma, genetic
`predisposition, hyperhidrosis, concurrent
`fungal infections, and psoriasis. It is also
`more common in smokers and in those who
`
`use occlusive footwear and shared bathing
`facilities}4
`
`Microbiology
`
`Onychomycosis is caused by various organ-
`isms, most often dermatophytes of the genus
`Trichophytorz. Other organisms include Can-
`dida, which is more common in fingernail
`infections (eFigure A) and in patients with
`chronic mucocutaneous candidiasis.1 Non-
`
`dermatophyte molds are a less common
`cause in the general population. Recent stud-
`ies, however, have demonstrated that they
`are the predominant organisms in patients
`with onychomycosis and human immuno-
`deficiency virus infection3 (eTable A).
`
`Classification
`
`Onychomycosis is divided into several classes
`based on morphologic patterns and mode
`of invasion of the nail (Table 1).5 Classifica-
`
`tion provides a framework for diagnosis and
`expected response to treatment, and can help
`predict the prognosis. The classes include
`distal and lateral subungual onychomyco-
`sis (Figures 1 and 2), proximal subungual
`
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`

`SORT: KEY RECOMMENDATIONS FOR PRACTICE
`
`Evidence
`
`Clinical recommendation
`rating
`References
`
`When preparing a nail specimen to test for onychomycosis, the nail should be cleaned with 70% isopropyl
`alcohol, then samples of the subungual debris and eight to 10 nail clippings should be obtained. The
`specimen should be placed on a microscope slide with a drop of potassium hydroxide 10% to 20%
`solution, then allowed to sit for at least five minutes before viewing under a microscope.
`Periodic acid—Schiff staining should be ordered to confirm infection in patients with suspected onychomycosis.
`Systemic antifungal agents are the most effective treatment for onychomycosis, but cure rates are much less
`than 100%. Terbinafine (Lamisil) is the most effective systemic agent available.
`When prescribing the topical agent ciclopirox, patients should be informed that it has some benefit in the
`treatment of onychomycosis, but also has a high failure rate.
`
`C
`
`C
`C
`
`C
`
`8, 11
`
`14
`23
`
`28, 31
`
`A = consistent, good—quality patient-oriented evidence; B = inconsistent or limited—quality patient—oriented evidence; C = consensus, disease—
`oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://wwvvaafp.
`org/afpsort.
`
`
`
`
`
`
`Table 1. Classification of Onychomycosis
`
`Onychomycosis
`class
`
`Distal and lateral
`subungual
`
`Endonyx
`subungual
`
`Proximal
`subungual
`
`Superficial
`
`Clinical features
`
`Begins distally at the hyponychium
`and spreads to the nail plate
`and bed; hyperkeratotic debris
`accumulates and results in
`onycholysis; nails thicken, chip,
`become dystrophic, and turn
`yellow-white or brown-black;
`infection can progress proximally,
`causing linear channels or "spikes"
`that can make treatment difficult;
`associated with paronychia
`
`Nail develops a milky white
`appearance, indentations,
`and lamellar splitting; no
`hyperkeratosis or onycholysis
`
`Debris accumulates under the
`proximal portion of the nail,
`causing onycholysis and a white
`color that spreads distally
`
`Nail appears to have powder-like
`patches of transverse striae on the
`surface
`
`Total dystrophic
`
`Complete destruction of the nail
`from long-standing infection; nail
`thickens, and nail structure is lost
`
`Causative organism*
`
`Epidermophyton
`floccosum
`
`Trichophyton
`men tagrophytes
`Trichophyton rubrum
`Fusarium species
`Scopulariopsis
`brevicaulis
`
`Scytalidium species
`Candida albicans
`
`Trichophyton
`soudanense
`
`Trichophyton
`violaceum
`
`I rubrum
`
`Aspergillus species
`Fusarium species
`C. albicans
`
`T. mentagrophytes
`I rubrum
`
`Acremonium species
`Fusarium species
`Scytalidium species
`
`Mode of infection
`
`Comments
`
`Most common form
`
`Fungal invasion through
`break in the skin at
`the lateral or distal
`undersurface of the
`nail
`
`Fungus invades the full
`thickness of the nail
`from directly under the
`skin without infecting
`the nail bed
`
`Fungus invades the
`proximal nail fold
`and cuticle; may also
`develop secondary to
`paronychia
`May appear on the
`superficial nail plate or
`emerge from under the
`nail fold; may be deep
`penetration of the
`superficial infection
`
`Rare; considered a
`subtype of distal and
`lateral subungual
`onychomycosis
`
`Suggests an
`immunosuppressive
`condition (e.g., human
`immunodeficiency
`virus infection)
`Previously known as
`superficial white
`onychomycosis, but
`some organisms
`produce black debris
`
`Can result from any
`of the other classes,
`although it is most
`often from severe distal
`and lateral subungual
`onychomycosis
`
`NOTE: Candidal onychomycosis was previously considered a class of onychomycosis. This condition, which more commonly involves the fingernails, has
`recently been excluded as a separate type because it was inconsistent to base a class on the organism alone.
`
`*—Dermatophytes are listed first, followed by nondermatophyte molds and yeast.
`Information from reference 5.
`
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`
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`

`Figure 1. Distal and lateral subungual onychomycosis.
`
`Figure 3. Proximal subungual onychomycosis.
`
`
`
`
`
`
`Figure 5. Total dystrophic onychomycosis.
`
`or curette, and subungual debris using a No. 15 surgical
`blade or a 2-mm curette. To improve accuracy, eight to
`10 nail shards should be collected.8 Diagnostic precision
`is enhanced if the sample is collected with a nail drill9
`
`Figure 2. Distal and lateral subungual onychomycosis with
`spike deformity.
`
`onychomycosis (Figure 3), superficial onychomycosis
`(Figure 4), and total dystrophic onychomycosis (Figure 5).
`A fifth class, endonyx subungual onychomycosis, is rare.
`Some nails have features from a combination of classes.
`
`Diagnosis
`
`Accurate diagnosis is crucial for successful treatment
`and requires identification of physical changes and posi-
`tive laboratory analysis. Only 50% of nail problems are
`caused by onychomycosis,6 and clinical diagnosis by
`physical examination alone can be inaccurate. Psoriasis,
`chronic nail trauma, and other causes must also be con-
`
`sidered. The differential diagnosis of onychomycosis is
`presented in Table 2,7 and an algorithm outlining a sug—
`gested diagnostic approach is shown in Figure 6.
`Laboratory analysis involves evaluation of nail clippings
`and subungual debris from the involved portion of the
`nail. Samples should be collected after cleansing the area
`with 70% isopropyl alcohol to prevent contamination.
`Clippings should be obtained with a sterile nail clipper
`
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`
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`

`Diagnosis of Onychomycosis
`
`Nail is discolored, deformed, hypertrophic,
`or hyperkeratotic, or has subungual
`debris; onychomycosis is suspected
`l
`Clean area with 70% isopropyl alcohol and obtain
`several samples of nail clippings and subungual debris
`l
`Office microscopy using KOH or KOH/
`dimethyl sulfoxide, or laboratory microscopy
`using KOH or KOH/calcofluor white stain
`
`Negative
`
`Positive
`
`l
`Begin treatment;
`consider studies to identify
`causative organism
`
`Obtain culture and/or histologic evaluations
`
`with periodic acid—Schiff staining
`
`Negative
`l
`Consider other
`nail disorders
`
`Positive
`l
`Begin treatment
`
`— F
`
`igure 6. Algorithm for the diagnosis and treatment of
`onychomycosis. (KOH = potassium hydroxide.)
`
`five to 30 minutes; heating the slide or adding a dimethyl
`sulfide 40% solution will enhance keratin dissolution.11
`
`Commercial laboratories may use KOH with calcofluor
`white stain, which binds to cellulose and enhances the
`
`fungal components in fluorescent microscopy.11
`Identification of hyphae, pseudohyphae, or spores
`confirms infection but does not identify the organism.
`To identify the organism, culture can be performed in a
`laboratory.” Samples should be sent in a sterile container,
`and results are usually available in four to six weeks. His-
`tologic evaluation can also be helpful for identification of
`the organism, and it can provide results within 24 hours.
`Periodic acid—Schiff (PAS) staining and methenamine
`silver stains are used. PAS staining is less expensive,13
`and in a study of 1,146 nail clippings comparing PAS
`histologic examination with KOH light microscopy and
`culture, PAS staining was the most sensitive test (82%
`sensitivity, compared with 53% for culture and 48% for
`KOH microscopy).14 Combining PAS staining with cul-
`ture increased sensitivity to 96%. In a review of cases
`in which treatment was initiated before specimens were
`
`Table 2. Common Conditions That Can Mimic
`Onychomycosis
`
`
`
` Condition Features
`
`Infections
`
`Chronic
`paronychia
`
`Viral warts
`
`Skin disorders
`Chronic
`dermatitis
`
`Lichen planus
`
`Psoriasis
`
`Twenty-nail
`dystrophy
`
`Trauma
`
`Footwear
`
`Manipulation
`(e.g., manicures,
`pedicures,
`rubbing)
`Tumors
`
`Chronic inflammation of the proximal
`paronychium; cross-striations of the
`nail; Streptococcus, Staphylococcus, or
`Candida found on smear and culture;
`common in children
`
`Localized in nail folds and subungual
`tissue; longitudinal depressed grooves in
`the nail plate
`
`Subungual dermatitis, hyperkeratosis,
`Beau lines, and pitting; thickened nail
`with corrugated surface
`Longitudinal grooves and fissures; usually
`affects fingernails
`Nail pitting, splinter hemorrhages, "oil
`staining," yellow-gray or silvery white
`nails (eFigure B)
`Dystrophy of all 20 nails; usually resolves
`in childhood; associated with the lesions
`of lichen planus (eFigure C)
`
`Oncholysis, ingrown toenails, subungual
`keratosis, nail plate discoloration and
`irregularities; caused by friction against
`the shoe
`
`Horizontal parallel nail plate grooves,
`inflammation from Staphylococcus
`aureus or Pseudomonas infection
`(eFigure D)
`
`Bowen disease
`
`Fibroma
`
`Squamous cell carcinoma; bleeding, pain,
`nail deformity, and nail discoloration
`Oval or spherical, white or yellow nodule;
`causes tunnel-like melanonychia; fibrous
`dermatofibroma or periungual fibroma
`Brown-yellow nail with dark pigment
`extending into the periungual skin folds;
`poor prognosis
`
`Melanoma
`
`Information from reference 7.
`
`and if it is taken from a more proximal location on the
`nail in patients with suspected distal and lateral onycho—
`mycosis.10 In those with suspected proximal subungual
`onychomycosis, the upper nail plate of the proximal nail
`is debrided, and underlying debris is collected. In those
`with suspected superficial onychomycosis, the superfi—
`cial aspect of the nail is scraped.
`Once the specimen has been obtained, office micros-
`copy can be performed by preparing the samples with
`potassium hydroxide (KOH) 10% to 20% solution. The
`KOH will dissolve keratin, leaving the fungal cell intact.
`The specimen should be placed on a slide with a drop
`of KOH solution, then set aside at room temperature for
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`Onychomycosis
`
`Table 3. Commonly Prescribed Medications for Treatment of Onychomycosis in Adults
`
`Cure rates (%)
`
`Mycotic
`
`Organisms targeted
`
`Potential adverse effects
`
`Medication
`
`Dosing
`
`C iclopirox
`8% solution
`(nail lacquer)
`
`Apply once daily to
`affected nails and to the
`underside of the nail
`
`Clinical
`
`6 to 921
`
`29 to 3621
`(77 when used in
`combination with
`debridement)22
`
`Candida species,
`dermatophytes
`
`4123
`
`4823
`
`Candida species
`
`Periungual erythema, erythema
`of the proximal nail fold,
`burning sensation, nail shape
`changes, ingrown toenails, nail
`discoloration
`
`Nausea, vomiting, abdominal
`pain, diarrhea, headache, rash
`
`Fluconazole
`(Diflucan)
`
`Itraconazole
`
`(Sporanox)
`
`Terbinafine
`(Lamisil)
`
`100 to 300 mg orally every
`week for three to six
`months (fingernails) or six
`to 12 months (toenails)
`
`Pulse dosing: 200 mg orally
`two times per day for one
`week per month, for two
`months (fingernails) or
`three months (toenails)
`Continuous dosing: 200
`mg orally once per day
`for six weeks (fingernails)
`or 12 weeks (toenails)
`
`250 mg orally once per day
`for six weeks (fingernails)
`or 12 weeks (toenails)
`
`7023
`
`63 (pulse dosing)
`69 (continuous
`dosingys
`
`Candida species,
`dermatophytes,
`nondermatophyte
`molds, Aspergil/us
`species
`
`Nausea, vomiting, hypokalemia,
`elevated transaminase and
`triglyceride levels, rash
`
`6623
`
`7623
`
`Some yeasts,
`dermatophytes,
`nondermatophyte
`molds
`
`Gastrointestinal upset, rash,
`headache
`
`FDA = U.5. Food and Drug Administration.
`*—Not all possible drug interactions are listed; see package insert before prescribing.
`t—Estimated retail price based on information obtained at http://wwwgoodrxcom (accessed March 4, 2013).
`
`information from references 21 through 27.
`
`obtained, PAS staining had the highest sensitivity, and
`culture had the least.14
`
`Polymerase chain reaction testing has been shown to be
`more accurate than culture, and results can be available
`
`in three days. However, it is not yet widely available”)16
`
`Treatment
`
`Onychomycosis is widely believed to be only a cosmetic
`problem, but it can be uncomfortable and can lead to
`cellulitis in older adults17 and foot ulcers in patients with
`diabetes.18 Eradication of the infection is key to improv—
`ing appearance and avoiding these complications, but
`it is not easily accomplished because nails are made of
`keratin, which is nonvascular and impermeable to many
`agents.19 Because of poor drug delivery to nails, results of
`treatment may not be apparent for a year.
`Treatment varies depending on the severity of nail
`
`changes, the organism involved, and concerns about
`adverse effects and drug interactions. Treatments also
`have varying effectiveness, based on cure parameters
`that are defined differently among studies. Mycotic
`cure denotes that no organism is identified on micros-
`copy and culture. Clinical cure refers to improvement
`in the appearance of the nail, often defined as a normal
`appearance in 80% to 100% of the nail. It is a subjec-
`tive measure that is difficult to compare across studies.20
`Complete cure indicates that mycotic and clinical cure
`have been achieved.
`
`ORAL AZOLES AND ALLYLAMINES
`
`Antifungals from the azole and allylamine classes are
`the most widely used oral medications for the treatment
`of onychomycosis. The azole class includes itraconazole
`(Sporanox), fluconazole (Diflucan), and ketoconazole;
`
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`

`Onychomycosis
`
`Potential drug
`interactions*
`
`—
`
`Benzodiazepines, calcium
`channel blockers, statins
`
`Benzodiazepines, calcium
`channel blockers, proton
`pump inhibitors, statins,
`warfarin (Coumadin),
`zolpidem (Ambien)
`
`Antiarrhythmic agents,
`beta blockers, selective
`serotonin reuptake
`inhibitors, tricyclic
`antidepressants, warfarin
`
`FDA
`
`pregnancy
`category
`
`Estimated
`monthly costt
`
`Comments
`
`B
`
`C
`
`C
`
`C
`
`$11 for3.3-mL
`bottle
`
`$13 for 30
`100—mg tablets
`($492 brand)
`
`$195 for 30
`100-mg
`capsules ($523
`brand)
`
`Indicated for use in immunocompetent patients with mild to moderate
`onychomycosis without lunular involvement; patients should not bathe
`for eight hours after applying nail lacquer; lacquer should be removed
`once per week, and as much of the damaged nail as possible should
`be removed using scissors, nail clippers, or a nail file
`
`Not FDA approved for treatment of onychomycosis in children or adults;
`prescribing guidelines recommend periodic monitoring of liver function,
`renal function, and potassium levels; use with caution in breastfeeding
`women and in patients with hepatic or renal disease or porphyria
`
`Liver function should be monitored in patients with preexisting hepatic
`dysfunction, and in all patients being treated for longer than one
`month; serum drug levels should be monitored because of erratic
`bioavailability with capsule formulation; renal function should be
`monitored; use with caution in breastfeeding women and in patients
`with hepatic or renal disease or porphyria; contraindicated in patients
`with ventricular dysfunction or congestive heart failure
`
`$4 for 30
`ZSO-mg tablets
`($607 brand)
`
`Liver transaminase levels should be checked before therapy is started;
`if treatment continues beyond six weeks, complete blood count
`and liver function testing should be performed; use with caution in
`breastfeeding women and in patients with hepatic or renal disease,
`psoriasis, or porphyria
`
`however, ketoconazole is rarely prescribed because of
`drug interactions and hepatotoxicity. The allylamine class
`is represented by terbinafine (Lamisil). These medica—
`tions and their dosing regimens are shown in Table 3.21‘27
`A meta-analysis of treatments for toenail onychomy-
`cosis determined that mycotic cure rates were 76% for
`terbinafine, 63% for itraconazole with pulse dosing, 59%
`for itraconazole with continuous dosing, and 48% for flu—
`conazole.23 Clinical cure rates were 66% for terbinafine,
`
`70% for itraconazole with pulse dosing, 70% for itracon-
`azole with continuous dosing, and 41% for fluconazole.
`Common adverse effects included headache, gastroin-
`testinal problems, and rash; these drugs also have been
`associated with Stevens—Iohnson syndrome, prolonged
`QT interval, and ventricular dysfunction. The use of
`these agents is discouraged in patients with liver, renal,
`or heart disease, and in those receiving medications with
`
`which there may be significant drug—drug interactions.25
`Liver function studies are recommended before begin—
`ning treatment and after one month of therapy.24 A meta—
`analysis concluded that the risk of asymptomatic eleva-
`tion oftransaminase levels in immunocompetent patients
`receiving oral antifungal agents was 2%, and that the risk
`of elevations requiring termination of therapy was 1%.28
`Although these medications are not approved for use in
`children, they have been used in children with positive
`results.29
`
`TOPICAL AGENTS
`
`Several topical agents are used for the treatment of ony—
`chomycosis. These agents have few contraindications
`and no drug-drug interactions.
`Ciclopirox 8% solution is the only topical prescription
`medication available in the United States for the treatment
`
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`

`Onychomycosis
`
`is a synthetic hydroxypyridine
`It
`of onychomycosis.
`antifungal formulated as a nail lacquer. Adverse effects
`include burning, itching, and stinging at the applica-
`tion site.30 It may be used in patients who cannot take
`oral antifungals and in those with less than 50% of the
`distal nail affected and no lunular involvement.21 It has
`
`been used in children, although it is not approved for use
`in patients younger than 12 years.29 When used alone,
`ciclopirox has a mycotic cure rate of 29% to 36%, and
`a clinical cure rate of 6% to 9%.21 A Cochrane review
`noted that the treatment failure rate was 61% to 64%
`after 48 weeks of use.31
`
`Ciclopirox has also been used in combination with
`oral agents to improve effectiveness. In one comparative
`
`study, a combination of ciclopirox and oral terbinafine
`had a mycotic cure rate of 88% and a complete cure rate of
`68%, whereas terbinafine alone had a mycotic cure rate of
`65% and a complete cure rate of 50%.32
`Nonprescription agents have also been used for treat—
`ment of onychomycosis (Table 4).“3'38 These therapies
`have been evaluated in only a small number of studies
`involving few patients. Topical mentholated ointment
`(Vicks Vaporub) was used in a small study involving
`18 patients.37 After 48 weeks, 28% had mycotic and
`clinical cure, 56% had partial clearance, and 17% had
`no improvement. Tea tree oil (Melaleuca alterm'folia)
`has been evaluated in two studies. Although one trial
`was favorable, combined data from both studies did not
`
`Table 4. Nonprescription Treatments for Onychomycosis
`
`Comments
`Administration
`Clinical cure rate (%)
`Agent
`Mycotic cure rate (%)
`
`Ageratina pichinchensis
`(snakeroot) extract33
`
`Cyanoacrylate, undecylenic
`acid, and hydroquinone
`(Renewed Nail)34
`
`71
`
`NA
`
`Apply every third day for
`the first month, twice
`per week for the second
`month, then once per
`week for the third month
`
`Soak and debride affected
`nails, then apply solution
`every two weeks for three
`to four visits; patients may
`also apply at home
`
`Dual-wavelength near-
`infrared laser (Noveon)35
`
`Treatment on days 1, 14,
`42, and 120
`
`Mild cases:
`65 (3 mm of nail
`clearance)
`26 (4 mm of nail
`clearance)
`Moderate to severe
`cases: 63 (3 mm
`of nail clearance)
`
`Mela/euca alternifo/ia
`(tea tree) oil36
`
`Mentholated ointment
`(Vicks Vaporub)37
`
`Apply twice per day
`
`Apply small amount with
`cotton swab daily
`
`NA
`
`28
`
`59
`
`50 to 65 (mild to
`moderate cases)
`35 (severe cases)
`
`30
`
`NA
`
`28
`
`Study of 110 patients;
`therapeutic effectiveness
`was similar to that in the
`control group, which
`used ciclopirox
`
`Study of 154 patients with
`cure rates reported after
`three months
`
`Toenails were evaluated
`on day 180
`
`Cochrane review found no
`evidence of benefit31
`
`Pilot study of 18 patients;
`56% had partial
`clearance, and 17% had
`no clearance
`
`One to three sessions four
`to six weeks apart
`
`NA
`
`Study of 37 toenails with
`onychomycosis
`
`Neodymium: yttrium-
`aluminum-garnet laser
`(Patholase Pinpointe)38
`
`61 (complete cure)
`19 (significant
`improvement)
`11 (moderate
`improvement)
`
`
`NA = not available.
`
`Information from references 31, and 33 through 38.
`
`768 American Family Physician
`
`www.aafp.org/afp
`
`Volume 88, Number 11 ’ December 1, 2013
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`Onychomycosis
`
`demonstrate significant benefit.”36 Snakeroot extract
`(Ageratina pichinchensis) is an antifungal derived from
`plants of the sunflower family. It was studied in a ran-
`domized trial involving 96 patients who applied the
`extract or ciclopirox for six months to nails with con-
`firmed infections.” Mycotic cure occurred in 59%
`of patients receiving the extract and in 64% of those
`receiving ciclopirox. Clinical cure occurred in 71%
`and 81% of patients, respectively. Differences between
`the two treatments were not statistically significant. A
`small study showed that a combination of cyanoacry—
`late, undecylenic acid, and hydroquinone (marketed
`as Renewed Nail) demonstrated mycotic cure in 78 of
`154 participants (50%).34
`
`PHYSICAL TREATMENTS
`
`Nail trimming and debridement are often performed
`concomitantly with other treatments and appear to offer
`benefit. Study groups that received nail debridement with
`oral terbinafine had higher clinical cure rates than those
`who received oral terbinafine alone.39 When debride-
`
`ment was performed with concurrent administration of
`ciclopirox, the mycotic cure rate was 77%, higher than
`that for ciclopirox alone.22 Improvement in nail appear-
`ance was reported, but clinical cure rates were not.
`Although they are expensive,
`laser and photody-
`namic therapies have become popular based on the
`success of in-Vitro studies. Several neodymiumzyttrium-
`aluminum—garnet (Nd:YAG) laser therapies have been
`approved by the US. Food and Drug Administration
`for treatment of onychomycosis.40 The Pinpointe Foot-
`laser, Cutera GenesisPlus laser, and Cooltouch Varia
`
`laser are short-pulse laser systems, whereas the Light
`Age Q-Clear laser is a Q—switched laser. However, there
`are only limited data about the use of these therapies in
`patients. In one study, Nd:YAG laser light was used to
`treat 37 nails, with one to three treatments given four
`to eight weeks apart. At 16 weeks, 61% were completely
`cured, 19% had significant improvement in the nail
`appearance, and 11% had moderate improvement in the
`nail appearance.38
`Another laser treatment, the dual—wavelength near-
`infrared laser (Noveon), is approved for dermatologic
`use, but not specifically for treatment of onychomy-
`cosis.41 This treatment was used on 26 nails on days 1,
`14, 42, and 120. After 180 days, 91% of nails with mild
`infection showed clinical improvement (3 to 4 mm of the
`nail free of clinical infection); however, only 30% had
`mycotic cure.42
`Photodynamic therapy using photosensitizing drugs
`and light to destroy fungal cells has shown some success
`
`in the treatment of onychomycosis, but further evalua—
`tion is needed.43
`
`Treatment Failure
`
`Despite the number of available treatments, not all
`patients with onychomycosis are cured. Numerous factors
`have been cited to explain the lack of response to therapy,
`such as nonadherence to treatment, incorrect diagnosis, or
`advanced disease. Factors contributing to poor response
`or nonresponse to treatment are listed in eTable B.
`For those who appear to be cured, recurrent infection
`is a risk, with a number of factors increasing the chance
`of recurrence. Risk factors include concomitant disease,
`
`dos—
`incorrect
`immunosuppression,
`genetic factors,
`ing or duration of treatment, moisture, occlusive foot-
`wear, older age, poor hygiene, tinea pedis, and trauma.44
`Recurrence can be caused by lack of mycotic cure or
`reinfection, and the reported rate of clinical recurrence
`of onychomycosis ranges from 10% to 53%, regardless
`of the treatment method used.45 Many patients tire of
`continued unsuccessful treatments or recurrences, and
`
`ultimately elect to undergo permanent nail removal.
`
`Data Sources: A PubMed search was performed using the term ony-
`chomycosis combined with prevalence, classification, diagnosis, and
`treatment. The search included meta-analyses and systematic reviews,
`including those from the Cochrane database. The initial search strategy
`was supplemented by searches for randomized controlled trials of specific
`treatments identified during the review of meta-analyses and systematic
`reviews. Search date: March 2012.
`
`Figures 1 through 5 provided by Robert T. Brodell, MD.
`
`The Authors
`
`DYANNE P. WESTERBERG, D0, FAAFP, is the founding chair of Family and
`Community Medicine at Cooper Medical School of Rowan University, and
`chief of Family and Community Medicine at Cooper University Hospital,
`both in Camden, NJ. At the time this article was written, she was chief of
`Family and Community Medicine at Cooper University Hospital, and vice
`chair of Family Medicine and Community Health at Robert Wood Johnson
`Medical School in Camden.
`
`MICHAEL J. VOYACK, D0, is an attending physician at Cooper University
`Hospital and a clinical instructor of family and community medicine at
`Cooper Medical School of Rowan University.
`
`Address correspondence to Dyanne P. Westerberg, DO, FAAFP, Coo-
`per University Hospital, 401 Haddon Ave., E&R Building, 2nd Floor,
`Camden, NJ 08103 (e-mail: westerberg-dyanne@cooperhealth.edu).
`Reprints are not available from the authors.
`
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`www.aafp.org/afp
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