ONYCHOMYCOSIS

ONYCHOMYCOSIS - Konstantinos Deligiannidis, MD, MPH; Stephen T. Earls, MD
BASICS
DESCRIPTION
• Infection of nail by fungi (mostly dermatophytes; also Candida, molds)
• System Affected: Skin/Exocrine
• Synonym(s): Tinea unguium; Ringworm of the nail
EPIDEMIOLOGY
• Predominant age: Dermatophytes common in adults; molds in older adults
• Predominant sex: Candidal: Adult women
Prevalence
In US, 22-130 cases per 1,000
ALERT
Geriatric Considerations
Mold onychomycosis more common
Pediatric Considerations
Rare before puberty
RISK FACTORS
• Dermatophytes
- Warmth, moisture, hyperhidrosis
- Tight-fitting shoes, rubber shoes
- Peripheral vascular disease
- Immunodeficiency
- Indirect contamination
• Candidal
- Direct contamination: Anovular, perirectal pruritus
- Chemical or mechanical damage to cuticle
- Maceration or occlusion
- Contact with substances containing sugar
- Hyperhidrosis
- Chilblain
- Cold hands (Raynaud phenomenon)
- Psoriatic onycholysis
- Diabetes mellitus
- Hyperparathyroidism
- Addison disease
- Malnutrition
- Malabsorption
- Dyscrasias
- Malignancies
- Postoperative conditions
- Immunodeficiency
• Molds
- Soil contamination
- Peripheral vascular disease
- Overlapping toes
- Onychogryphosis (deforming overgrowth of nails resulting in hooked or curved state)
Geriatric Considerations
• Predisposing diseases are more common.
• Hepatic/renal reserve is limited.
ETIOLOGY
• Dermatophytes (invade normal keratin)
- Trichophyton rubrum: Most common
- Trichophyton mentagrophytes var. interdigitale: 25% as common as T. rubrum (most common pathogen for white superficial onychomycosis)
- Epidermophyton floccosum, Trichophyton violaceum, Microsporum species less common
• Candida
- C. albicans, 70%
- C. parapsilosis, C. tropicalis, C. krusei (less common)
• Molds (invade altered keratin): Scopulariopsis brevicaulis, Hendersonula toruloidea, Aspergillus species, Alternaria tenuis, Cephalosporium, Scytalidium hyalinum
ASSOCIATED CONDITIONS
Immunodeficiency or chronic metabolic disease

DIAGNOSIS
SIGNS AND SYMPTOMS
• Dermatophytes: Commonly preceded by dermatophyte infection at another site; 80% involve toenails, especially hallux; simultaneous infection of fingernails and toenails rare. Four clinical forms occur
- Distal subungual onychomycosis: Spreads from hyponychium to nail bed to nail plate; subungual hyperkeratosis; subungual paronychia; onycholysis; nail dystrophy; discoloration  yellow-brown; bois vermoulu ("worm-eaten wood"); onychomadesis
- Lateral onychomycosis (common): Yellowish discoloration of lateral nail groove; onycholysis, proximal or distal
- Proximal onychomycosis (rare): Hands or feet; leukonychiabegins under posterior nail groove, spreading to nail plate and lunula; seen with immunodeficiency
- White superficial onychomycosis (rare): Hallux preferentially affected; infection of upper part of nail plate; opaque white spots on nail plate eventually merge to involve entire surface of the nail
• Candidal
- Hands, 70%, especially dominant hand
- Middle finger most common
- Pain mild, unless secondarily infected
- Increases on prolonged contact with water
- Primarily affects tissue surrounding nail
- Begins with cuticle detachment
- Dark yellowish to blackish-brown zone along lateral border of nail
- Secondary ungual changes: Convex, irregular, striated nail plate with dull, rough surface
- Onycholysis, especially on hands
- Distal subungual onychomycosis may occur
- Primary involvement of the nail plate is uncommon (thin, crumbly, opaque, brownish nail plate deformed by transverse grooves).
- Periungual edema/erythema may occur (club-shaped, bulbous fingertips).
- Superficial white onychomycosis: Young children
• Molds
- More common in those age >60 years
- More common in nails of hallux
- Resembles distal and lateral onychomycosis
ALERT
Pediatric Considerations
Candidal infection presents more commonly as superficial white onychomycosis
TESTS
Lab
• Potassium hydroxide (KOH) preparation
- Clip or file away some of nail plate as needed.
- Collect scales from stratum corneum of most proximal area (beneath nail or crumbling nail itself) with 1 mm curette.
- KOH (5%) plus gentle heat
- 100% sensitive if >2 preparations examined
• Cultures: Negative in 30% (secondary to loss of dermatophyte viability; improved by immediate culture on Sabouraud cell culture media)
• Histologic examination; punch biopsy: Proximal lesions with periodic acid-Schiff stain
• Discontinue all topical medication several days before obtaining sample.
Pathological Findings
Pathogens within the nail keratin
DIFFERENTIAL DIAGNOSIS
• Herpetic whitlow
• Eczema
• Pustular psoriasis
• Tumor
• Darier disease
• Pityriasis rubra pilaris
• Trophic changes, peripheral vascular disease
• Immunodeficiency
• Drugs; chemicals
• Trauma
• Alopecia areata
• Lichen planus
• Yellow nail syndrome (icterus, carotenemia, lymphedema, amyloidosis)
• White acquired nail disease (trauma, acute infection, chronic disease, thallium or arsenic poisoning, hepatic cirrhosis, chronic hypoalbuminemia)
• Brown-black pigment (melanotic, hematoma)
• Green dyschromia (Pseudomonas aeruginosa; molds, e.g., Penicillium)
• Connective tissue disorders: Dermatomyositis, scleroderma, Reiter disease
TREATMENT
STABILIZATION
Outpatient treatment unless secondary cellulitis/osteomyelitis
GENERAL MEASURES
• Avoid factors that promote fungal growth (heat, moisture).
• Treat underlying disease risk factors.
• Treat secondary infections.
Diet
No special diet
Activity
Restrictions based on promoting factors, underlying disease, or secondary infection
MEDICATION (DRUGS)
First Line
• Dermatophyteslocal: Cheaper, but less effective than systemic; apply under occlusive dressing; may mix with keratinolytic chemicals
- Allylamines: Terbinafine (Lamisil), Naftifine (Naftin); may be slightly more effective, but are more expensive than imidazoles. Recommended if imidazoles or undecylenic acid are not working. (1)[B]
- Imidazoles: Clotrimazole (Lotrimin, Mycelex), miconazole (Monistat), butoconazole, tioconazole, econazole (Spectazole), ketoconazole (Nizoral), sulconazole (Exelderm), oxiconazole (Oxistat); should be tried before allylamines for topical treatment. (1)[B]
- Unsaturated fatty acid derivatives: Propionic acid, undecylenic acid, tolnaftate (Tinactin); should be tried before allylamines for topical treatment. (1)[B]
• Dermatophytessystemic
- Terbinafine (Lamisil): 250 mg PO daily for 3 months; fewer drug-drug interactions, and fewer contraindications than imidazoles; terbinafine may be slightly more effective than itraconazole. (2,3)[A]
- Itraconazole (Sporanox): 200 mg PO 2 times a week for 1 week per month for 2 months for fingernails and 3-4 months for toenails (pulse therapy)
- Fluconazole (Diflucan): 300 mg PO weekly for 6 months (pulse therapy); overall, better tolerated than ketoconazole; expensive; reserve for extreme cases (disseminated disease, immunocompromised patient)
• Candida
- Imidazole derivative
- If bacterial infection is present, use antibacterial plus anticandidal; for example, nystatin (Mycostatin), topical amphotericin B (Fungizone), or itraconazole (Sporanox) 200 mg PO daily for 3 months, or fluconazole 300 mg PO weekly for 6 months
• Mold: 1% iodinated alcohol, benzoic acid (Whitfield ointment), silver nitrate, glutaraldehyde, imidazole derivatives, itraconazole
• Contraindications
- Griseofulvin: Porphyria, hepatocellular failure, serious side effects (leukopenia, persistent anemia), pregnancy
- Ketoconazole: Hepatocellular disease, pregnancy
- Fluconazole: Hepatocellular failure, pregnancy
• Precautions
- Topical agents: Use with caution on broken skin or in vascular compromise or decreased sensation.
- Griseofulvin: Monitor for hepatic, renal, hematopoietic side effects; photosensitivity; lupuslike symptoms; or exacerbation. Take with meals to enhance absorption.
- Ketoconazole: Hepatotoxicity (may be severe or fatal); anaphylaxis may (rarely) occur with 1st dose; decreased testosterone levels
- Fluconazole: Decrease dose in renal failure, hepatotoxicity.
• Significant possible interactions
- Griseofulvin: Warfarin, barbiturates, alcohol, oral contraceptives
- Ketoconazole: Warfarin, rifampin, cyclosporine, phenytoin, terfenadine
- Fluconazole: Phenytoin (Dilantin), cyclosporine, oral hypoglycemics, oral anticoagulants, rifampin, hydrochlorothiazide
- Itraconazole and ketoconazole require gastric acid for absorption; effectiveness reduced with antacids, H2 blockers, and proton-pump inhibitors.
• Drug choices are limited in pregnancy.
Second Line
• Dermatophyteslocal
- Ciclopirox (Loprox, Penlac): 8% topical lacquer for patients without lunula involvement
- Amorolfine (Loceryl): 5% lacquer
- Butenafine with tea tree oil
- Cationic surfactants, for example, benzalkonium chloride (Cetylcide), cetrimide, cetylpyridinium chloride (Ony-Clear, Fungoid)
- Halogenated/chlorinated/iodinated derivatives (chloramine, tincture of iodine)
- Dyes (malachite green, crystal violet)
- Mercury derivatives (thimerosal)
- Phenols
- Glutaraldehyde
• Dermatophytessystemic: Griseofulvin (Fulvicin, Gris-PEG, Grisactin) ultramicrosize; usual adult dose is 250-500 mg b.i.d. with meals for 6-12 months; however, terbinafine 250 mg PO daily was statistically significantly more effective for 4-6 weeks. (3)[A]
ALERT
Geriatric Considerations
Decreased ability for topical self-treatment
SURGERY
Nail removal to remove infected keratin
• Mechanical: Soften with occlusive dressing with 40% urea gel; detach from nail bed with tweezers or file with abrasive stone.
• Chemical: Protect peripheral tissue with adhesive strips; apply ointment of 30% salicylic acid, 40% urea, or 50% potassium iodide under occlusive dressing.
• Surgical avulsion: For involvement of a few nails
FOLLOW-UP
PROGNOSIS
• Relapse is common; prognosis is poor if 1 hand, 2 feet, or multiple nails are involved.
• 20-40% of nails fail to respond.
• 40-70% of patients show long-term relapse.
COMPLICATIONS
Secondary infections with progression to cellulitis/osteomyelitis
PATIENT MONITORING
• Topical agents: Slow response expected; visits every 6-12 weeks
• Griseofulvin: CBC and liver function tests initially, then every 3 months
• Ketoconazole: Liver function tests every 3 weeks for the 1st 3 months, then monthly
• Itraconazole and fluconazole: Liver function tests at start and at 4 weeks
• Terbinafine: Liver function and hematologic tests at start and at 4 weeks
• Treatment duration (months): Fingernails (6-9), toenails (9-12), great toenail (12-24)
REFERENCES
1. Crawford F, Hart R, Bell-Syer S, Torgerson D, et al. Topical treatments for fungal infections of the skin and nails of the foot. [Systematic Review] Cochrane Skin Group. Cochrane Database of Systematic Reviews. 1, 2006.
2. De Keyser P, De Backer M, Massart DL, Westerlinck KJ. Two week oral treatment of tinea pedis, comparing terbinafine (250mg/day) with itraconazole (100mg/day): A double blind multicentre study. Br J Dermatol. 1994;130(Suppl 43):22-25.
3. Bell-Syer SEM, Hart R, Crawford F, et al. Oral treatments for fungal infections of the skin of the foot. [Systematic Review] Cochrane Skin Group. Cochrane Database of Systematic Reviews. 1, 2006.
MISCELLANEOUS
• Definitions
- Onycholysis: Detachment of nail plate from nail bed
- Dystrophy: Thickening, deformation, crumbling
- Onychomadesis: Shedding of nail
- Leukonychia: Yellowish white spots
• See also: HIV infection and AIDS