A Simple Algorithm for the Treatment of Dermatophyte Toenail Onychomycosis

A. K. Gupta, MD, PhD, MBA, FAAD, FRCPC^1,2; E. A. Cooper, HBSc²

1. Division of Dermatology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
2. Mediprobe Research Inc., London, ON, Canada

Background

Onychomycosis infections of fingernails and toenails may be caused by many types of fungi or yeast species. In practice, almost all infections are produced by the dermatophyte fungi Trichophyton sp. (especially T. rubrum and T. mentagrophytes), Microsporum sp., and Epidermophyton sp., with toenail infections typically being more severe and more difficult to eradicate than fingernail infections. There has been much discussion about the optimal treatment for onychomycosis, particularly now that topical nail lacquers have become available. This new therapeutic option offers reduced risk of adverse effects compared with standard oral therapies. We propose a simple algorithmic approach to aid in the selection of therapy for dermatophyte toenail onychomycosis (Tablle 1), and present a balance between efficacy and risk of therapy.

Treatment Options for Onychomycosis

Oral Therapies Approved in Canada

• Terbinafine 250mg/day for 12 weeks
• Itraconazole pulse therapy: for dermatophyte onychomycosis
  • 1 pulse = 200mg twice daily for 1 week on, 3 weeks off
  • 3 pulses are standard for toenail onychomycosis
• Oral therapies provide access to the nail bed and matrix of all toes; both terbinafine and itraconazole may persist in nails for long periods after treatment.
• Oral therapy can also treat concomitant skin infections such as tinea pedis.
• Consult current prescribing information for contraindications and monitoring requirements.
• Liver function testing should be done prior to therapy, and periodically during therapy.

Topical Therapies Approved in Canada

• Ciclopirox nail lacquer 8%, once daily for 48 weeks1
• Adverse events are few, with mild localized reactions at the application site.
• May not provide adequate penetration where nails are thick or have severe onycholysis.

Other Therapies

• Mechanical or chemical debridement: lessens the burden of infection and may benefit any degree of onychomycosis; can be performed in office, or by other healthcare professionals.
• Nail avulsion (chemical or mechanical): typically a last resort, as there is some risk for permanent nail damage.

Combination Therapy

• Dual therapies: oral/topical, oral/debridement, or topical/debridement. In practice, nail avulsion is typically followed by topical or oral therapy to combat the remaining infection.
• Triple therapies: oral/topical/debridement2
• Oral therapy combined with topical therapy can provide penetration of the nail plate from inside and out, which may increase the overall amount of antifungal medication reaching the infection, particularly where the nail is thickened, shows extensive onycholysis, has lateral or matrix involvement, or is a dermatophytoma.³
• Debridement may increase access to the infection by topical medications.

Nail Presentation	Assumptions	Treatment Options
Table 1: Simple treatment algorithm for dermatophyte toenail onychomycosis Onycholysis = separation of the nail plate from the nail bed Matrix = the base or root of the nail, from which the nail grows

Variables to Consider in Treatment Decisions

Nail Disease Variables

• Number of nails affected
• Percentage of affected nail plate area
• Is it DLSO, or another presentation?^4-6
• Infection confirmed as dermatophyte?
  (i.e., Trichophyton sp., Microsporum sp., or Epidermophyton sp.)
• Thickness of nails
• Matrix (proximal nail fold) area involved in infection?
• Lateral streaks or central spikes (dermatophytoma) present?

Patient Variables

• Presence of peripheral vascular disease
• Diabetes
• Age of patient
• Obesity
• Other co-morbid conditions, e.g., liver disease
• Oral drugs patient is using
• Compliance
• Drug insurance status
• Patient preference

Physician Variables

• Physician preference and experience

Other Treatment Considerations

Efficacy of Therapy

• Efficacy should consist of both mycological eradication and outgrowth of the infected nail.
• Mycological cure is suggested by negative microscopy exam and negative culture in successive samples.
• For clinical success, the infected toenail must be grown out and replaced by a healthy nail (average time: 9-16 months); success of treatment is typically assessed around month 12; for some patients, trauma or medical conditions may prevent the nail from returning to a ‘normal’ appearance, and thus, success will only be a nail appearance as normal as possible for the individual patient condition.
• ‘Booster’ therapy may be provided to the patient: extra courses of oral therapy may be given following completion of the standard oral regimen (4 wks terbinafine; 1 pulse itraconazole).⁷

Special Patient Populations

• Elderly: slower nail growth, reduced immune response.8
• Diabetics/peripheral vascular disease: higher rates of onychomycosis, requires adequate antifungal therapy to prevent spread of infection, concomitant foot trauma, ulceration, amputation.9 Use caution when performing debridement, sampling, to avoid injury to skin.
• Children: no treatments have been specifically approved for use in children.
• Fingernail infections: fingernails grow at a faster rate than toenails and typically show higher cure rates.

Non-DLSO Presentations

• Superficial white onychomycosis infections may be treated adequately using topical therapy and debridement of infected areas with a curette or scalpel.
• Proximal subungual onychomycosis, due to the deep-seated nature of infection, is most adequately treated with oral therapy; may be associated with immunocompromised status.

Nondermatophyte Infections

• Nondermatophyte infections are difficult to identify, but need to be recognized accurately, as standard antifungal therapies may not be as effective in nondermatophyte moulds as for dermatophytes.¹⁰
• Recommended treatment may be specific to the organism causing infection.^11,12

References

1. J Am Acad Dermatol 43(4 Suppl):S70-80 (2000 Oct).
2. Gupta AK, Lynch L. Cutis 74(1 Suppl):5-9 (2004 Jul).
3. Gupta AK, Baran R. J Am Acad Dermatol 43(4 Suppl):S96-102 (2000 Oct).
4. Baran R, et al. Br J Dermatol 139(4):567-71 (1998 Oct).
5. Scher RK, et al. J Am Acad Dermatol 56(6):939-44 (2007 Jun).
6. Gupta AK, et al. J Drugs Dermatol 3(1):51-6 (2004 Jan-Feb).
7. Gupta AK, et al. J Eur Acad Dermatol Venereol 16(6):579-86 (2002 Nov).
8. Tavakkol A, et al. Am J Geriatr Pharmacother 4(1):1-13 (2006 Mar).
9. Gupta AK, et al. J Eur Acad Dermatol Venereol 20(10):1188-93 (2006 Nov).
10. Gupta AK, et al. Int J Dermatol 42(4):272-3 (2003 Apr).
11. Tosti A, et al. J Am Acad Dermatol 42(2 Pt 1):217-24 (2000 Feb).
12. Tosti A, et al. Dermatol Clin 21(3):491-7 (2003 Jul).