Onychomycosis – Causes, Symptoms, Diagnosis, Treatment and Ongoing care

Basics

Description

Chronic fungal infection of fingernails or toenailsCaused mostly by dermatophytes, also yeasts, moldsToenails more commonly affected than fingernailsSystem(s) affected: Skin/ExocrineSynonym(s): Tinea unguium; Ringworm of the nail

Epidemiology

Prevalence

2–8% in general populationPredominant age: 14–28% in adults >60 years of ageRare before puberty

Risk Factors

Older ageTinea pedisCancerDiabetesPeripheral vascular diseasePsoriasisCohabitation with others with onychomycosisImmunodeficiencySwimmingSmokingPeripheral vascular diseaseChildren with Down’s syndrome

Etiology

Dermatophytes: Trichophyton (T. rubrum most common), Epidermophyton, MicrosporumYeasts: C. albicans (most common), C. parapsilosis, C. tropicalis, C. kruseiMolds: Scopulariopsis brevicaulis, Hendersonula toruloidea, Aspergillus sp., Alternaria tenuis, Cephalosporium, Scytalidium hyalinumDermatophytes cause 90% of toenail and most of fingernail onychomycoses.Fingernail onychomycosis more often caused by yeast than toenailDermatophytes invade normal keratin, whereas molds invade altered keratin.

Commonly Associated Conditions

Immunodeficiency or chronic metabolic diseaseTinea pedis or manuum

Diagnosis

Physical Exam

Dermatophytes: Commonly preceded by dermatophyte infection at another site; 80% involve toenails, especially hallux; simultaneous infection of fingernails and toenails is rare. 4 clinical forms occur: Distal or lateral subungual onychomycosis (most common): Spreads from distal or lateral margins to nail bed to nail plate; subungual hyperkeratosis; subungual paronychia; onycholysis; nail dystrophy; discoloration—yellow-brown; yellow streaking laterally; bois vermoulu (“worm-eaten wood”); onychomadesisProximal subungual onychomycosis (rare): Hands or feet; leukonychia—begins under posterior nail groove, appearing to occur from the proximal underside of the nail (or direct invasion of the nail plate from above); spreads to nail plate and lunula; seen with immunodeficiencySuperficial white onychomycosis (rare): Hallux preferentially affected; infection of outer surface of nail plate; opaque white spots on nail plate eventually merge to involve entire surface of the nailCandidal: Hands 70%, especially dominant handMiddle finger most commonPain mild, unless secondarily infectedIncreases on prolonged contact with waterPrimarily affects tissue surrounding nailBegins with cuticle detachmentDark yellowish to blackish brown to green zone along lateral border of nailSecondary ungual changes: Convex, irregular, striated nail plate with dull, rough surfaceOnycholysis, especially on handsDistal 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).Molds: More common in those >60 years of ageMore common in nails of halluxResembles distal and lateral onychomycosis

Pediatric Considerations

Candidal infection presents more commonly as superficial white onychomycosis.

Diagnostic Tests & Interpretation

Accurate diagnosis requires both laboratory and clinical evidence.If onychomycosis is suspected clinically and initial diagnostic laboratory tests are negative, they should be repeated.

Lab

Initial lab tests

Direct microscopy with potassium hydroxide (KOH) preparation: Clip away diseased, discolored nail plate.Collect debris from stratum corneum of most proximal area (beneath nail or crumbling nail itself) with 1-mm curette or scalpel.Larger sample improves sensitivity.KOH (5%) plus gentle heat.High sensitivity if >2 preparations examinedCultures: False negative in 30% (secondary to loss of dermatophyte viability; improved by immediate culture on Sabouraud cell culture medium)Histologic examination of nail clippings; punch biopsy: Proximal lesions; stain both with periodic acid–Schiff (PAS) stainDiscontinue all topical medication for some time before obtaining sample.

Pathological Findings

Pathogens within the nail keratin

Differential Diagnosis

Psoriasis (most common alternate diagnosis)Traumatic dystrophyLichen planusOnychogryphosisEczematous conditionsHypothyroidismDrugs and chemicalsYellow nail syndromeNeoplasmsOnly 50% of dystrophic nails are due to onychomycosis.

Treatment

Medication

Pregnancy Considerations

Oral antifungals and ciclopirox are pregnancy Category B (terbinafine, ciclopirox) or C (itraconazole, fluconazole, and griseofulvin). Because treatment of onychomycosis usually can be postponed until after pregnancy, treatment typically should be avoided during pregnancy.

First Line

Oral antifungals are preferred due to higher rates of cure, but have systemic adverse effects and drug–drug interactions.Terbinafine 250 mg/d p.o. × 6 weeks for finger-nails and 3 months for toenails, most effective in cure and prevention of relapse, most cost-effective with higher patient satisfaction compared with itraconazole pulse. It has similar tolerance to terbinafine pulse (500 mg/d × 1 week per month for 3 months), and fewer drug–drug interactions (1)[C],(2)[A].Itraconazole pulse 400 mg/d p.o. or 200 mg p.o. b.i.d. × 1 week, then 3 weeks off, repeat for 2 cycles for fingernails and 3–4 cycles for toenails (lower cost and lower pill burden than itraconazole continuous, more effective than terbinafine for Candida and molds, do not need to monitor liver function tests (1)[C],(2)[A]Itraconazole continuous 200 mg/d p.o. × 6 weeks for fingernails and 3 months for toenails (may be more effective than itraconazole pulse, more effective than terbinafine for Candida and molds) (1)[C],(2)[A]

Second Line

Fluconazole pulse 150–300 mg p.o. weekly × 6 months (less frequent dosing but lower cure rate) (1)[C],(2)[A]Griseofulvin 500–1,000 mg/d p.o. for up to 18 months (lower cure rate, needs to be continued until the diseased nail is completely replaced) (1)[C],(2)[A]Ciclopirox 8% nail lacquer: Apply once daily to affected nails (if without lunula involvement) for up to 48 weeks, and every 7 days, remove lacquer with alcohol, then file away loose nail material and trim nails (low cure rate, avoids systemic adverse effects, less cost-effective). Application after p.o. treatment may reduce recurrences (3)[A].Contraindications for oral antifungals: Hepatic diseasePregnancy (see Pregnancy Alert)Current or history of congestive heart failure (CHF) (itraconazole)Porphyria (griseofulvin)Precautions/adverse effects: Oral antifungals: HepatotoxicityNeutropeniaHypersensitivityPhotosensitivity, lupuslike symptoms, proteinuria (griseofulvin)Chronic kidney disease (avoid terbinafine for patients with CrCl <50 mL/min, decrease fluconazole dose)CHF, peripheral edema, pulmonary edema (itraconazole)Ciclopirox: Rash, nail disorders; avoid contact with skin other than skin immediately surrounding nail; use with caution on broken skin or in vascular compromiseSignificant drug–drug interactions: Terbinafine (inhibits CYP2D6): ß-Blockers, cimetidine, cyclosporine, dextromethorphan, monoamine oxidase inhibitors (MAOIs), rifampin, selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), warfarinItraconazole, fluconazole (inhibit CYP3A4): Antiarrhythmics, benzodiazepines, cisapride, ergot alkaloids, HMG CoA reductase inhibitors, alfentanil, buspirone, calcium channel blockers, carbamazepine, cimetidine, corticosteroids, cyclosporine, haloperidol, hydrochlorothiazide, hypoglycemics, losartan, oral contraceptives, phenytoin, pimozide, protease inhibitors, rifamycins, sirolimus, tacrolimus, TCAs, theophylline, tolterodine, vinca alkaloids, warfarin, zidovudine, zolpidemGriseofulvin: Barbiturates, oral contraceptives, cyclosporine, salicylates, warfarin

Additional Treatment

General Measures

Avoid factors that promote fungal growth (i.e., heat, moisture, occlusion).Treat underlying disease risk factors.Treat secondary infections.

Complementary and Alternative Medicine

Melaleuca alternifolia (tea tree) oil has a 10% mycologic cure.

Surgery/Other Procedures

Nail debridement to remove infected keratin (efficacy not well studied):

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; used by some for pain control

Ongoing Care

Follow-Up Recommendations

Formation of new fingernail takes 4–6 months and new toenail takes 12–18 months.Cure defined as (4)[C]: 100% absence of clinical signs and/orNegative mycology with =1 of the following clinical signs: Distal subungual hyperkeratosis or onycholysis leaving <10% of the nail plate affectedNail plate thickening that does not improve with treatment because of comorbid condition

Patient Monitoring

Topical agents: Slow response expected; visits every 6–12 weeksTerbinafine, griseofulvin: Baseline and as needed liver function tests (LFTs) and CBCItraconazole continuous: Baseline and as needed LFTs

Patient Education

Advise patient to: Keep affected area clean and dry.Avoid rubber or other occlusive footwear.Avoid tight or ill-fitting footwear.Wear absorbent cotton socks; avoid synthetic fibers.Change clothing and towels frequently, and launder them in hot water.Cure of all toenails may not be attainable.Nail may not appear normal after cure.

Prognosis

Complete clinical cure in 25–50% (higher mycologic cure rates)10–50% recur (relapse or reinfection).Poor prognostic factors (4)[C]: Areas of nail involvement >50%Significant proximal or lateral diseaseSubungual hyperkeratosis >2 mmWhite/yellow or orange/brown streaks in the nail (includes dermatophytoma)Total dystrophic onychomycosis (with matrix involvement)Nonresponsive organisms (e.g., Scytalidium mold)Patients with immunosuppressionDiminished peripheral circulation

Complications

Secondary infections with progression to soft tissue infection or osteomyelitisToenail discomfort or pain that can limit physical mobility or activityAnxiety, negative self-image

References

1. Finch JJ, Warshaw EM. Toenail onychomycosis: current and future treatment options. Dermatol Ther. 2007;20:31–46.

2. Hinojosa JR, Hitchcock K, Rodriguez JE. Clinical inquiries. Which oral antifungal is best for toenail onychomycosis? J Fam Pract. 2007;56:581–2.

3. Crawford F, Hollis S. Topical treatments for fungal infections of the skin and nails of the foot. Cochrane Database of Systematic Reviews. 2007, Issue 3. Art. No.: CD001434. DOI:10.1002/14651858.CD001434.pub2.

4. Scher RK, Tavakkol A, Sigurgeirsson B, et al. Onychomycosis: diagnosis and definition of cure. Journal of the American Academy of Dermatology. 2007;56:939–44.

Additional Reading

de Berker D et al. Clinical practice. Fungal nail disease. N Engl J Med. 2009;360:2108–16.

Welsh O, Vera-Cabrera L, Welsh E et al. Onychomycosis. Clin Dermatol. 2010;28:151–9.

Codes

ICD9

110.1 Dermatophytosis of nail112.3 Candidiasis of skin and nails

Snomed

414941008 onychomycosis (disorder)403058003 onychomycosis of fingernails (disorder)403059006 onychomycosis of toenails (disorder)

Clinical Pearls

Psoriasis and chronic nail trauma are commonly mistaken for fungal infection.Diagnosis should be based on both clinical and mycologic laboratory evidence.Oral antifungals generally are well tolerated and more effective than topical antifungals, with terbinafine the most effective.LFT monitoring is necessary for most oral antifungal regimens.Patient should understand that treatment is long term, recurrence is common, and nails may not appear normal even after treatment.