Onychomycosis

Description
  • Common fungal infection of the nails with toenails being primarily affected (80% of cases) but can also involve fingernails
  • Not life-threatening, but causes discomfort and nail deformities which can affect quality of life
  • In susceptible patients, may progress to cellulitis or diabetic foot infections
  • Ninety percent of onychomycosis (OM) cases are caused by the dermatophyte , T. rubrum. Candida albicans is involved in up to 5% of infections, most commonly in fingernails.
  • Risk factors:
    • Older age
    • Gender – 2.4 times more common in males than females
    • Tinea pedis infection (co-infection very common)
    • Diabetes
    • Peripheral vascular disease
    • Immunodeficiency
    • Psoriasis of the skin
    • Nail trauma
    • Occlusive footwear
    • Sports or other activities involving bare feet
    • Smoking
  • Images:
Signs and Symptoms

Three major subtypes of OM:

  1. Distal and lateral subungual onychomycosis (DLSO) – infection is located under the tip and side of nail, as seen here.
    • Most common type (90%)
    • Nail thickening with white-yellowish discoloration
    • Brittle, friable nail plate which may crumble leaving yellow debris
    • Typical presentation is  “butter”- coloured spikes descending vertically from the distal end (top) of the nail
    • Onycholysis (separation of nail plate from nail bed) is common
    • No change in shape of nail

2. Superficial white onychomycosis (SWO) 

    • Up to 7% of OM cases
    • More common in children than adults
    • Chalky, white patches on top surface of nail plate
    • Entire nail plate may become roughened and crumbly

3.  Proximal (bottom of the nail) subungual onychomycosis  

    • Up to 6% of cases
    • White discoloration at proximal nail fold beneath nail bed
    • Infection spreads from bottom of nail up towards the tip.
    • Often a marker of immunosuppression disorders
Differential Assessments

Onychomycosis is responsible for only 50–60% of cases of abnormal-appearing nails. Other conditions which can resemble OM must be ruled out before proceeding with treatment. 

  • Atopic dermatitis – Transverse ridges (run horizontally across nail), affects nail fold, history of eczema.
  • Bacterial paronychia – Infection around a nail – painful, red, swollen area, often with pustules.
  • Contact dermatitis– History of exposure to nail polish, artificial nails.
  • Drug-induced nail disorders - onycholysis (nail separating from nail bed): cancer chemotherapy, psoralens, retinoids, gold, thyroid hormone; discolouration of nails: tetracyclines, gold, antimalarials.
  • Lichen planus – Longitudinal grooves and ridges, nail atrophy (thinning); often associated with lichen planus lesions (purplish, flat-topped bumps) in other areas of the body – oral mucosa, wrists, shins, torso.
  • Onychogryphosis (senile) – Curved, thickened claw-like nails frequently seen in older adults with vascular insufficiency.
  • Psoriasis - Pitting of nails, symmetrical nail involvement. History of psoriasis, typical lesions (silvery scales) in other areas of body, e.g. knees, elbows.
  • Squamous cell cancer - Papilloma or warty involvement of paronychia (area where nail and skin meet), erosions and scaling.
  • Subungual melanoma - Vertical pigmented bands in the nail bed
  • Systemic disorders such as iron deficiency (brittle, spoon shaped nails), hypothyroidism (brittle nails) or hyperthyroidism (onycholysis) – usually most or all nails are involved.
  • Trauma to nails – Single nail, deformed shape, history of injury.
  • Yellow nail syndrome – Yellow-green thick, curved slow-growing nails. Associated with defective lymphatic drainage in lungs and pulmonary infection.
When to Refer
  • If the patient has not been previously diagnosed. Guidelines recommend microscopy (KOH examination of nail scrapings and, if negative but OM still suspected, culture to confirm diagnosis before beginning treatment)
  • Involvement of more than 50% of nail – oral antifungal therapy is recommended
  • Lunula (crescent-shaped area at the base of the nail) involvement or onycholysis – oral antifungal treatment is required
  • Symptoms suggest possible cellulitis or carcinoma
  • Suspected drug-induced or disease-induced condition
  • Patient is immunosuppressed due to disease or medication
  • Poorly controlled diabetes; patients with peripheral circulatory conditions
  • Poorly controlled skin conditions such as psoriasis or dermatitis
  • Symptoms not typical of OM; cannot confirm patient’s self-diagnosis
Treatment

General Measures

  • Avoid factors that promote fungal growth (i.e. heat, moisture, and occlusion):
    • Wear stockings and shoes that keep humidity to a minimum
    • Dry feet and spaces between toes thoroughly after washing
    • Use protective footwear when in shared public spaces such as swimming pools
    • Keep nails clean and cut short
    • Don’t share nail clippers or footwear
    • Protect toenails from trauma – avoid restrictive footwear; being fitted for orthotics may be helpful
    • Protect fingernails with rubber gloves if hands are immersed in water for long periods of time
    • Treat or refer patients for treatment of secondary infections that might be contributing to OM e.g. Tinea pedis


Non-prescription medications

  • Apply emollients on cracked skin to reduce further entry points for fungus
  • Ensure underlying disease risk factors are being appropriately addressed and/or refer patient
  • Home remedies like vinegar, Listerine, vitamin E or thyme oil have no proven benefit (Rxfiles)
  • Mentholated ointments (e.g. Vicks vaporub) - very limited evidence
  • Undecylenic acid (e.g. Fungicure 25%) – no proven benefit for OM
  • Propylene glycol/urea/lactic acid combination (Emtrix):  66.4% propylene glycol, 20% urea and 10% lactic acid
    • Patients with < 50% nail involvement: 27% mycological cure with Emtrix vs. 10.5% with placebo after 26 weeks; significantly more patients reported improvement in nail condition with Emtrix

 

Prescription medications

Topical

Efinaconazole Solution

  • Indicated for topical treatment of mild to moderate onychomycosis of toenails without lunula involvement due to T. rubrum and T. mentagrophytes in immunocompetent adult patients
  • Mycologic cure rate nearly 50% and complete cure rate (mycological + 0% nail involvement) 15% after 48 weeks in patients with nail involvement of < 50%
  • NNT for mycologic cure = 3; NNT for complete cure = 7 to 11
  • Not evaluated for more extensive OM (when > 50% of the nail is involved)
  • Safety in pediatrics (less than 18 years of age), pregnant and lactating women has not been evaluated
  • Apply once daily to affected nail(s) for 48 weeks
  • No debridement required
  • Available in a 6 ml container which provides 80 applications

Ciclopirox 8% nail lacquer (not appropriate for pharmacist prescribing)

  • Ciclopirox is not approved for pharmacist prescribing due to limited effectiveness and cost
  • Limited efficacy for toenail onychomycosis
  • Requires weekly nail trimming and removal of lacquer build-up
  • Requires monthly debridement by podiatrist /physician

Oral

  • Terbinafine and itraconazole are more effective than topical treatment when there is extensive nail involvement. Refer patients with nail involvement of > 50% to a podiatrist or their physician for consideration of oral therapy
  • Fluconazole can also be used but appears to be less effective than terbinafine or itraconazole
  • Ketoconazole is the preferred treatment for infection caused by Candida
General Advice / Monitoring
  • General measures to prevent spread or reinfections (See above)

  • Directions for use of efinaconazole:
    • Clean toenails with soap and water and dry prior to application
    • Do not apply until ≥10 minutes after showering, bathing, or washing
    • Place one drop on each affected toenail and spread evenly using the built-in brush applicator over entire toenail including cuticle, folds of skin next to side of nail, toenail bed, hyponychium (thickened skin layer underneath tip of toenail) and under surface to toenail tip. If big toenail involved, apply a second drop at the end of the toenail
    • Allow solution to dry on toenails before covering with footwear
    • Nail polish and other cosmetic products for nails should be avoided during treatment
    • Wash hands with soap and water after applying the drug

  • Onset of effect:  It may take a few months before improvement in nail(s) is noticeable.

Monitoring:

  • Benefit:
    • Expect slow response to topical treatment; growth of diseased area of nail should stop in 12 weeks for toenails, 6 weeks for fingernails: nail should appear normal in 12 to 18 months
    • Follow-up with patient in 8 weeks
    • Have patient measure distance of disease-free nail outgrowth monthly (normal growth rate is 1.5–2 mm/month) to ensure that nail remains disease-free
    • Refer patient to podiatrist or physician If new lesions appear or if no benefit to diseased nail(s) at 8 week follow-up 
  • Adverse effects:
    • Similar to placebo in studies
    • Minimal irritation after application – should disappear in a few days. If irritation is severe or worsens, stop therapy

  • Treatment and resolution of Tinea pedis if present (See guidelines for Tinea pedis)
  • Treatment and control of comorbidities such as diabetes, peripheral circulation problems
  • Advise patient to watch for and report any signs of secondary infections e.g. cellulitis (swelling, warmth, pain, draining around nails)
Prescribing and Billing Details
  • May prescribe sufficient quantity of Efinaconazole to treat onychomycosis for 48 weeks.
  • Only products with an official indication from Health Canada for onychomycosis are considered for these guidelines.  Only the active ingredients in the "products" section are approved for pharmacist prescribing. 
Products

Detailed information on contraindications, cautions, adverse effects and interactions is available in individual drug monographs in RxTx - CPS from CPhA, RxTx (Internet), Lexi-Comp, AHFS, www.drugs.com or other reliable drug monograph references. For comprehensive drug comparisons, see RxFiles charts (www.rxfiles.ca).

This information should be routinely consulted before prescribing.

TABLE 1: APPROVED PRODUCTS FOR ONYCHOMYCOSIS PHARMACIST PRESCRIBING

DRUG

RECOMMENDED DOSE

EFINACONAZOLE 10% SOLUTION

APPLY ONCE DAILY FOR 48 WEEKS

Treatment Flowchart
Pharmacist Assessment Documents
References / Suggested Reading
  1. Onychomycosis. In DynaMed [database online]. EBSCO Information Services. Available at https://dynamed.ebscohost.com. (Subscription required). Updated Dec. 2014. Accessed March 23, 2015. (Note – Saskatchewan pharmacists have access through SHIRP www.shirp.ca )
  2. Miller P. Skin Disorders: Fungal Nail Infections.  In: Gray Jean, editor. e-Therapeutics+ [Internet]. Ottawa (ON): Canadian Pharmacists Association; c2015 [revised Aug 2014; cited Mar 2015]. Available from: http://www.e-therapeutics.ca. Also available in paper copy from the publisher. (Note – Saskatchewan pharmacists have access through SHIRP www.shirp.ca ).
  3. Miller P. Dermatologic Conditions: Fungal Nail Infections (Onychomycosis) In: Gray Jean, editor. e-Therapeutics+ Complete - Minor Ailments. [Internet]. Ottawa (ON): Canadian Pharmacists Association; c2015 [revised Mar, 2013; cited Mar 2015]. Available from: http://www.e-therapeutics.ca. Also available in paper copy from the publisher. (Note – Saskatchewan pharmacists have access through SHIRP www.shirp.ca ).
  4. Goldstein A. Onychomycosis. In UpToDate online. [Revised Aug 2014; cited Mar 2015.] Available at www.uptodate.com (by subscription).
  5. Drug-Induced Nail Disorders: Prevention Is Best. In Medscape Specialty online. Available at http://www.medscape.com/viewarticle/406421_4. Accessed Mar 2015.
  6. Emtestam L, Kaaman T, Rensfeldt K. Treatment of distal subungual onychomycosis with a topical preparation of urea, propylene glycol and lactic acid: results of a 24-week, double-blind, placebo-controlled study.  Mycoses 2012;55:532–540.
  7. Elewski B, Rich P, Pollak R, et al. Efinaconazole 10% solution in the treatment of toenail onychomycosis: Two phase III multicenter, randomized, double-blind studies, J Am Acad Dermatol 2013;68:600-8.
Written by Karen Jensen, BSP, MSc
Reviewed by Carmen Bell, BSP; Terry Damm, BSP
Posted Feb 2018