Onychomycosis

See Also

Definitions

Onychomycosis
1. Chronic fungal infection affecting the Toenail or Fingernail

Epidemiology

Prevalence
1. General population: 10% Prevalence (worldwide)
2. Age under 20 years: 3% Prevalence (U.S.)
3. Age over 60 years: 28% Prevalence (U.S.)
Most common Nail Disorder (accounts for 50% of Nail Disorders)
Rarely occurs in children unless predisposing factors
1. Immunosuppression (e.g. AIDS)
2. Extensive fungal skin involvement
3. Family History of Onychomycosis

Pathophysiology

Causes
1. Dermatophytes (70%)
2. Non-dermatophyte molds and yeasts (30%)
3. Mixed infection in up to 39%
Person to person transmission
Toenails are more commonly affected than Fingernails
1. Decreased blood supply and slower growth (compared with Fingernails)
2. Dark, moist environment

Risk Factors

Older age (especially over age 60-70 years)
1. Peripheral Arterial Disease
2. Decreased immune function
3. Slowed Nail Growth
4. Prolonged fungal exposures
Tinea Pedis or other fungal infection
Swimming pools, locker rooms or other use of shared bathing areas
Psoriasis
Nail deformity
Recurrent nail Trauma
Hyperhidrosis
Tobacco Abuse
Obesity
Immunodeficiency
1. Diabetes Mellitus (>1.9 fold increased risk)
2. HIV Infection (15-40% Prevalence)

Types

Distal Lateral Subungual (most common)
1. Affects distal and lateral Toenails and Fingernails (esp. first and fifth Toenails)
2. Starts distally (at Hyponychium) and spreads into nail plate and nail bed
3. Associated with hyperkeratosis with secondary Onycholysis and ultimately Dystrophic Nails with yellow or brown discoloration
4. Acquired through break in skin at nail undersurface (e.g. seocndary to Tinea Pedis, Paronychia)
5. Most common etiology: Trichophyton rubrum
  1. However any of the fungal organisms may be causative
Superficial or superficial white Onychomycosis (10% of cases, esp. children)
1. Most common etiology: Trichophyton mentagrophytes
2. Typically white (but sometimes black) powdery patches forming horizontal nail lines
Endonyx Subungual (rare subtype of distal subungual)
1. Etiologies
  1. Trichophyton soudanense
  2. Trichophyton violaceum
2. Direct infection of full nail thickness without affecting nail bed
3. May affect entire Toenails
  1. Starts as opaque, well demarcated milky-white spots
  2. Spots coalesce to involve entire nail
4. Associated findings
  1. Lamellar splitting and nail indentations
  2. No hyperkeratosis or Onycholysis
Proximal Subungual (uncommon)
1. Most common etiology: Trichophyton rubrum
2. Affects proximal Fingernails and Toenails
3. Fungi invade proximal nail fold to enter nail
4. Hyperkeratosis and debris form under proximal nail
  1. Results in Onycholysis that spreads gradually from proximal to distal nail
5. Predisposing factors
  1. Immunocompromised status (e.g. HIV Infection or AIDS)
  2. Local Trauma may also result in similar presentation
Candida Onychomycosis (rare)
1. Associated with Chronic Paronychia (Candida)
2. More common in Immunocompromised state
Total dystrophic Onychomycosis
1. Total nail plate destruction from above types (especially distal subungual)
2. Diffusely thickened and yellow nail
3. Nail crumbles and is friable
4. Associated with long-term infection that thickens the nail and ultimately destroys the nail structure
  1. Long-standing, progressive distal lateral subungual Onychomycosis
  2. Long standing, progressive proximal subungual Onychomycosis (esp. Immunocompromised)
Mixed-Pattern Onychomycosis
1. Combination of multiple subtypes
Secondary Onychomycosis
1. Superinfected secondary condition (esp. Psoriasis)

Signs
Nail plate changes

Discoloration
1. White or yellow
2. Green in cases of Pseudomonas superinfection
Deformed (hypertrophic or hyperkeratotic)
Opacification
Subungual debris
Onycholysis
Brittle nails that crumble with minimal force
Foul nail odor
Distribution based on type (see above)

Labs
Obtaining Nail specimens

Nail preparation
1. Wipe the nail with 70% Isopropyl Alcohol
2. Use sterile nail clipper to obtain 8-10 nail shards if possible (improves Test Sensitivity)
3. Obtain subungual material with 2 mm curette or #15 blade
4. Nail drill may be used for proximal nail location
Techniques for specific nail types
1. Distal subungual Onychomycosis
  1. Clip nail short
  2. Apply curette to nail bed near cuticle for sample
  3. Also scrape underside of nail plate
2. White superficial Onychomycosis
  1. Scrape nail plate surface white area for sample
3. Proximal superficial Onychomycosis
  1. Pare nail plate near lunula
  2. Curette sample from infected nail bed
4. Candidal Onychomycosis

Labs
Miscellaneous

Potassium Hydroxide (10-20% KOH): Subungual debris scraping
1. Test Sensitivity: 56-80%
2. Test Specificity: 72-95%
Periodic acid-Schiff Stain (PAS Stain)
1. Test Sensitivity: 82%
2. Performed with nail biopsy (see below)
Nail Fungal Culture
1. Test Sensitivity: 23-85%
2. Test Specificity: 82-99%
Nail Biopsy: Periodic acid schiff stain (effective, but expensive and not widely available)
1. Test Sensitivity: 81-96%
2. Test Specificity: 72-89%
Fungal PCR
1. Test Sensitivity: 83%
2. Test Specificity: 84%
3. Results in 3 days where available
4. Expensive and not widely available
References
1. Wilsmann-Theis (2011) J Eur Acad Dermatol Venereol 25(2): 235-7 [PubMed]

Differential Diagnosis

See Dystrophic Nail
1. Only 50% of Dystrophic Nails are Onychomycosis
Infection
1. Candida Paronychia (Chronic Paronychia)
2. Bacterial Paronychia (Acute Paronychia)
3. Periungual wart
  1. Associated with Onycholysis and longitudinal grooves
4. Herpetic Whitlow (Herpes Simplex Virus)
  1. Bleeding or purpuric nail lesions
Trauma
1. Ingrown Toenail
2. Local nail Trauma (e.g. tight footwear, manicures or pedicures)
3. Onychodystrophy
  1. Associated with Onycholysis, periungual keratosis
Skin conditions
1. Psoriasis
  1. Affects nails in >50% of cases
  2. Associated with Nail Pitting, Onycholysis, brown-red patches, subungual hyperkeratosis
2. Lichen Planus (especially Fingernails)
  1. Affects nails in >10% of cases
  2. Associated with longitudinal grooves, nail thinning, Pterygium on the dorsal surface
  3. Variant: Twenty-Nail Dystrophy (children)
3. Contact Dermatitis or other chronic dermatitis
  1. Associated with Nail Pitting, Beau Lines (transverse grooves)
Nail bed tumor
1. Fibroma or Dermatofibroma (benign)
  1. Smooth, firm Nodules that develop at nail folds
2. Subungual Melanoma
  1. Nail affected in up to 7% of cases
  2. Associated with Brown-yellow Nail Discoloration, subungual hyperkeratosis, onychorrhexis
3. Bowen Disease (Squamous Cell Carcinoma)
  1. Nail affected in 8% of cases
  2. Associated with Paronychia, poor Nail Growth, Onycholysis
Miscellaneous causes
1. Yellow Nail Syndrome
2. Trachyonychia
  1. Associated with longitudinal ridges, brittle nails, Nail Pitting
  2. Affects all nails
References
1. Allevato (2010) Clin Dermatol 28(2): 164-77 [PubMed]

Management
General Measures

Keep feet dry
1. Wear cotton socks and change 2-3 times per day
2. Wear shoes that are breathable
Reduce fungus exposure
1. Wear foot protection in shared showers (locker room) and other public areas
2. Treat Tinea Pedis
Optimize chronic disease management
1. Diabetes Mellitus
2. Tobacco Cessation
Anticipatory Guidance
1. Fingernails require 3-6 months to fully regrow
2. Toenails require up to 18 months to fully regrow
Antifungal Medications
1. Systemic Antifungals (esp. Terbinafine) are considered preferred treatment for Onychomycosis
2. Consider Topical Antifungal to treat periungual fungus or in mild cases (see indications below)
3. Consider longer Antifungal course in some patients
  1. Slow Nail Growth
  2. Extensive nail plate involvement
  3. Diminished blood supply
    1. Peripheral Vascular Disease
    2. Diabetes Mellitus
Surgical Management
1. Nail trimming and Debridement may be used as an adjunct to systemic and Topical Antifungals
2. Consider nail removal in severe Onycholysis

Management
Systemic Antifungal Agents and Laser

Indications
1. Immunocompromised patients
2. Secondary infection risk (e.g. Diabetes Mellitus)
3. Foot Pain
4. Cosmesis (warn regarding imperfect cure rates, and nails may remain dystrophic)
Background
1. Confirm Onychomycosis and not a mimic on differential diagnosis
  1. Onychomycosis is visually misdiagnosed in up to 50% of patients with Dystrophic Nails
2. Cure rates are listed in clinical cure (appearance) and mycologic cure (culture/microscopy)
3. Monitoring of liver transaminases is typically baseline and at 4-6 weeks after starting therapy
Terbinafine (Lamisil)
1. Indications
  1. First-line therapy due to best efficacy and low cost ($4 per month)
2. No further Liver Function Tests needed if baseline Liver Function Tests are normal and no systemic symptoms
3. See Terbinafine for Drug Interactions
4. Dosing: Daily
  1. See Terbinafine for dosing and lab monitoring
  2. Child 10 to 20 kg: 62.5 mg once daily
  3. Child 20 to 40 kg: 125 mg once daily
  4. Adult (and child >40 kg): 250 mg once daily
5. Dosing: Pulsed 12-4
  1. Take daily dosing for 12 weeks on, then 12 weeks off, then 4 weeks on
  2. Highest effectiveness, safety and cost of Terbinafine regimens in adults (as well as compared with other agents)
    1. Gupta (2023) Br J Dermatol 189(1): 12-22 [PubMed]
6. Dosing: Pulsed 4-4
  1. Take daily dosing for 4 weeks on, then 4 weeks off, then 4 weeks on
  2. Yadav (2015) Indian J Dermatol Venereol Leprol 81(4):363-9 [PubMed]
7. Duration
  1. Fingernails: 6 weeks
  2. Toenails: 12 weeks
8. Most effective oral Antifungal agent for treatment of Onychomycosis
9. Cure rate
  1. Clinical cure: 75% for Fingernails, 38-76% for Toenails
    1. Clinical relapse: 21% in severe cases
  2. Mycologic cure: 76% with negative culture/microscopy
    1. Mycologic relapse: 23% in severe cases
Itraconazole (Sporanox)
1. Indications
  1. Onychomycosis due to yeast or non-dermatophytes
2. See Itraconazole for dosing and lab monitoring
3. Fingernails
  1. Daily (continuous): 200 mg daily for 6 weeks
  2. Monthly (pulsed): 200 mg twice daily for one week per month for 2-3 months
4. Toenails
  1. Daily (continuous): 200 mg daily for 12 weeks
  2. Monthly (pulsed): 200 mg twice daily for one week per month for 3-4 months
5. Cure rate
  1. Clinical cure: 70%
  2. Mycologic cure: 69% with negative culture/microscopy (63% if pulse dosing)
  3. High recurrence rates in severe cases (roughly double Terbinafine relapse rate)
    1. Mycologic relapse: 53% (contrast with 23% for Terbinafine)
    2. Clinical relapse: 48% (contrast with 21% for Terbinafine)
Nd:YAG Laser (Neodymium:yttrium-aluminum-garnet laser)
1. Indicated in Onychomycosis refractory to systemic agents
2. Efficacy based only on small studies
3. 61% complete mycologic cure rates after 1-3 treatments at 4-6 week intervals
4. Kimura (2012) J Drugs Dermatol 11(4): 496-504 [PubMed]
References

Management
Less Effective Systemic Agents (generally avoid these for Onychomycosis)

Background
1. Avoid systemic agents listed here (Griseofulvin and Fluconazole) for Onychomycosis
2. Agents listed above (Terbinafine and Itraconazole) have better efficicacy
3. Griseofulvin has greater toxicity risk
Fluconazole (Diflucan)
1. See Fluconazole for dosing and lab monitoring
2. Dosing
  1. Child: 3-6 mg/kg (up to 150 to 300 mg) once weekly for at least 6 months, until entire nail grows out
  2. Adult: 150 mg once weekly for at least 6 months, until entire nail grows out
3. Cure rate
  1. Clinical cure: 76% for Fingernails, 31% for Toenails
  2. Mycologic cure: 48% with negative culture/microscopy
4. References
  1. Gupta (2004) Br J Dermatol 150(3): 537-44 [PubMed]
  2. Scher (1998) J Am Acad Dermatol 38:S77-S86 [PubMed]
Griseofulvin
1. Rare use due to long treatment duration, low cure rights, increased adverse effects
2. Low cure rates (30-45%) even when taken for up to 6-12 months at 500-1000 mg daily
3. Faergernann (1995) J Am Acad Dermatol 32: 750-3 [PubMed]

Management
Topical Agents

Indications for Topical Agents
1. No more than 3 nails affected
2. Superficial Onychomycosis
3. Distal lateral subungual Onychomycosis
  1. Affecting <50% of nail plate surface area
  2. Nail Matrix not involved
4. Prevention of Onychomycosis recurrence or reinfection
  1. See prognosis for protocol below
Avoid topical agents in moderate to severe Onychomycosis
1. Minimally if at all effective in significant Onychomycosis
2. Local irritation is common
3. If a topical agent is used, Ciclopirox (Penlac) would be preferred in combination with Debridement
Ciclopirox (Penlac) 8% nail lacquer
1. Applied daily for 48 weeks for Toenails, 24 weeks for Fingernails
2. Generic Ciclopirox costs $300 per year ($20/bottle) to treat two nails in 2020
3. Marginally better than Placebo
  1. Clinical cure rate 5-6% for Fingernails, 6-9% for Toenails (up to 36% with negative culture/microscopy)
  2. When used with Debridement may offer up to 77% mycotic cure rate (negative culture/microscopy)
4. References
  1. Gupta (2000) J Am Acad Dermatol 43(4 suppl) S70-80 [PubMed]
  2. Malay (2009) J Foot Ankle Surg 48(3): 294-308 [PubMed]
Efinaconazole (Jublia) 10% nail lacquer
1. Topical agent for Onychomycosis
  1. Appears more effective than Penlac
  2. Less effective than oral agents
2. Apply 2 drops daily to a great toe nail (or 1 drop for other nails) daily for 48 weeks
3. Very expensive ($650 for 4 ml - treats one great Toenail per 6 weeks)
  1. May cost $9000 for a year course for multiple nails
4. Clinical cure rate: 15 to 18%
5. (2014) Presc Lett 21(8): 47
Tavaborole (Kerydin) 5%
1. Similarly very expensive ($430/bottle) Topical Antifungal with low efficacy
2. Applied daily for 48 weeks
Cosmetic procedures
1. Laser Therapy (e.g. PinPointe)
  1. Treats only the cosmetic appearance of the nail (not the fungal infection)
Argentina pichinchensis (snakeroot extract)
1. Similar efficacy to Ciclopirox (Penlac)
2. Romero-Cerecero (2008) Planta Med 74(12): 1430-35 [PubMed]
Dual-wavelength near-infrared laser (Noveon)
1. Marginal benefits by study with atypical measures of clinical cure and 30% mycologic cure
2. Landsman (2010) J Am Podiatr Med Assoc 100(3):166-77 [PubMed]
OTC Nail Lacquers (e.g. Fungi-Nail)
1. Over-the-counter (otc) Antifungal agents that treat periungual fungus, but do not penetrate the nail to treat Onychomycosis
Vicks VapoRub
1. No proven efficacy in Onychomycosis
Tea Tree Oil
1. No proven efficacy in Onychomycosis

Prognosis

Recurrence rate after effective treatment: 20-25% within 2 years (up to 50% in some studies)
1. Decreased recurrence with Topical Antifungal applied twice weekly after treatment
2. Shemer (2017) Dermatol Ther 30(5): e12545 +PMID:28856784 [PubMed]
Factors associated with recurrence
1. Age >70 years old
2. Nail Trauma
3. Diabetes Mellitus

Complications

Cellulitis in older patients
Diabetic Foot Ulcer

References