Onychomycosis
Onychomycosis
John T. Swisher IV
Suzanne Hecht
Basics
Description
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A fungal infection of the toes and/or fingernails involving the nail bed, matrix, or plate
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Synonym(s): Nail ringworm; Tinea unguium
Epidemiology
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22–130 cases/1,000 population
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Accounts for 1:3 of integumentary infections
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Incidence of infection increasing worldwide
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Accounts for 50% of toenail dystrophies
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Adults 30× more likely to be affected than children
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∼2% prevalence in children
Risk Factors
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HIV
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Immunosuppressive states
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Diabetes mellitus (DM)
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Contact with infected individuals
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Peripheral vascular disease (PVD)
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Trauma
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Communal bathing
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Occlusive footwear
General Prevention
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Appropriate foot hygiene:
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Wear absorbent cotton socks.
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Wear breathable footwear.
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Protect feet in community areas.
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Keep feet dry throughout day.
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Discard old shoes that may harbor fungi.
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Control chronic health conditions.
Etiology
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Pathophysiology:
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Distal/lateral subungual onychomycosis (most common): Fungal invasion begins at hyponychium and spreads along nail bed proximally, concomitantly involving the inferior nail plate.
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White superficial onychomycosis: Fungal invasion develops from dorsal nail plate invasion.
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Proximal subungual onychomycosis (associated with immunocompromised state): Fungal invasion of cuticle and subsequent nail fold that penetrates dorsal nail plate
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Endonyx onychomycosis (least common): Fungal invasion of nail surface with eventual deep penetration
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Candidal onychomycosis: Yeast infection via onycholysis, paronychia, or chronic mucocutaneous disease
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Total dystrophic onychomycosis: End-stage fungal infection of entire nail unit that may easily fragment and lead to permanent scarring
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Etiology:
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Dermatophytes (>90% occurrence rate)
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Yeast
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Nondermatophytes
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Diagnosis
History
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Identify digits involved.
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History of predisposing factors: Trauma, tinea, and immunocompromised state
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Discuss bathing footwear habits
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Historical clues in regard to secondary infection
Physical Exam
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Distal/lateral subungual onychomycosis: Thickened/opacified nail with possible subungual hyperkeratosis and/or onycholysis
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White superficial onychomycosis: White patches on nail surface that can coalesce
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Proximal subungual onychomycosis: Nail fold leukonychia with white proximal nail plate
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Endonyx onychomycosis: White nail plate without subungual hyperkeratosis or onycholysis
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Candidal onychomycosis: Paronychia, onycholysis, and/or subungual hyperkeratosis
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Total dystrophic onychomycosis: Thick, opaque, yellow-brown nail involving entire plate/matrix
Diagnostic Tests & Interpretation
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Diagnosis made when both clinical and laboratory results are positive
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Essential that causative organism is identified
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Avoid topical antifungals for 2 wks prior to testing.
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Cleanse nail with alcohol swab prior to testing.
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Utilize potassium hydroxide (KOH) and fungal culture to determine therapy for initial screen.
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Owing to a high false-negative rate, you may need to repeat KOH or use histologic analysis with fungal culture.
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Histologic analysis with periodic acid–Schiff (PAS) is more sensitive than KOH or culture (1)[A].
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Lab
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KOH prep with light microscopy:
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20% KOH with 40% dimethyl sulfoxide (DMSO)
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Use a 1-mm curette to obtain most proximal sample
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Use a No. 15 blade scalpel for superficial fungi.
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Immediate results
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Fungal culture:
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Cycloheximide medium for dermatophytes and noncycloheximide medium for yeasts and nondermatophytes
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Nail clippings or scrapings for specimen
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May take weeks to grow on medium
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Species identification
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Histologic analysis with PAS:
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High sensitivity
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Prompt results
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Pathogen not identified
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Distal nail clipping from attachment to nail bed in formalin
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Immunohistochemistry:
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Identifies pathogen via labeled antibody to specific fungi
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Complicated and costly
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In vivo confocal microscopy:
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Uses light to penetrate nail to analyze reflection of fungi
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Inability to distinguish pathogen
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Costly
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Scanning electron microscopy:
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Expensive
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Detailed imaging of fungi elements
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Polymerase chain reaction (PCR):
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Fungal species identification by DNA sequence analysis
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Sufficient nail material required for testing
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Flow cytometry:
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Sorts by DNA, protein, cell size, and granulosity to identify fungi
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Complicated and costly
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Differential Diagnosis
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Eczema
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Endocrine disease
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Herpes whitlow
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Malignant melanoma
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Medications
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Paronychia
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Psoriasis
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Squamous cell carcinoma
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Trauma
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Yellow nail syndrome
P.417
Treatment
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Indications for treatment consist of pain, functional limitation, aesthetic purposes, and secondary infection.
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Discuss costs, side effects, and continuous/pulse dosing.
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Confirm past medical history to determine appropriate medication.
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Treat tinea pedis as soon as possible.
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Explain that it may take 12–18 mos for resolution of toenail infections and 4–6 mos for resolution of fingernail infections.
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Despite successful eradication of fungi, the nail may remain abnormal in appearance. This is not considered a treatment failure.
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Clinical cure is based on the absence of physical exam findings.
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Mycologic cure is when no fungal elements remain; however, the nail appearance still may be abnormal.
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Repeat testing may be required at completion of treatment to confirm cure.
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High recurrence (relapse/reinfection) rates: 15–20% within 1 yr
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Treatment failure may require repeat treatment.
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Return to play ± oral, topical, or surgical treatment is based on symptoms.
Medication
First Line
Terbinafine:
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Fungicidal against dermatophytes with fungistatic properties against some yeast and nondermatophytes
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Mycologic cure 76% ± 3%; clinical cure 66% ± 5%
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Fingernail: 250 mg/day × 6 wks (2)[A]
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Toenail: 250 mg/day × 12 wks (2)[A]
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Monitor pretreatment AST/ALT and every 6 wks for hepatotoxicity
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Contraindications: Hypersensitivity
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Precautions: Hepatotoxicity, GI upset, immunodeficiency, systemic lupus erythematosus (SLE), renal insufficiency, Steven-Johnson syndrome, and drug interactions
Second Line
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Itraconazole:
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Fungistatic against dermatophytes, yeast, and nondermatophytes
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Mycologic pulse cure 63% ± 7%; mycologic continuous cure 59% ± 5%; clinical pulse cure 70% ± 11%; clinical continuous cure 70% ± 5%
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Fingernail continuous therapy: 200 mg/day × 6 wks (3)[A]
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Toenail continuous therapy: 200 mg/day × 12 wks (3)[A]
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Fingernail pulse therapy: 200 mg b.i.d. × 7 days, off 21 days (2–3 pulses may be required)
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Toenail pulse therapy: 200 mg b.i.d. × 7 days, off 21 days (3–4 pulses may be required)
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Monitor pretreatment AST/ALT and every 6 wks for hepatotoxicity for continuous therapy; not required for pulse therapy
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Contraindications: Hypersensitivity, pregnancy, ventricular dysfunction, concomitant use of CYP3A4 drugs
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Precautions: Hepatotoxicity, GI upset, hearing loss, neuropathy, drug interactions
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Griseofulvin:
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Fungistatic against dermatophytes
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Mycologic cure 60% ± 6%; clinical cure 2% ± 2%
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Fingernails: 1,000 mg/day × 4 mos or more (3)[A]
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Toenails: 1,000 mg/day × 6 mos or more (3)[A]
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Contraindications: Hypersensitivity, porphyria, hepatocellular dysfunction, pregnancy
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Precautions: Penicillin allergy, photosensitivity
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Ciclopirox 8%:
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Mechanism of action unproven
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Mycologic cure 32%; treatment cure 7%
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Apply daily × 48 wks; remove lacquer once a week (2)[A].
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Consider when oral medication isn't indicated or nail plate has been removed.
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Contraindication: Hypersensitivity
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Precautions: DM, immunosuppressed state, and concomitant systemic antifungal use
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Surgery/Other Procedures
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Nail plate removal (total or partial)
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Chemical removal (40% urea)
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Use concomitant oral or topical antifungal with surgical approach (4)[C].
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Consider in recalcitrant cases.
References
1. Bell SS, Hall JB. Oral treatments for toenail onychomycosis (protocol). The Cochrane Collaboration 2009.
2. Gupta AK, Tu LQ. Therapies for onychomycosis: a review. Dermatol Clin. 2006;24:375–379.
3. Internet Resource: Thompson Micromedix Healthcare Series.
4. Blumberg M, Kantor GR. www.emedicine.com. Onychomycosis. 2007.
Codes
ICD9
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110.1 Dermatophytosis of nail
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112.3 Candidiasis of skin and nails
Clinical Pearls
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Not all nail dystrophies are due to fungi.
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Clinical and lab confirmation is essential for appropriate diagnosis and treatment.
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Oral is favorable to topical treatment.
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High recurrence rates exist.
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Advise patient on prevention techniques.