J Korean Med Assoc.  2019 Jul;62(7):385-391. 10.5124/jkma.2019.62.7.385.

Treatment of onychomycosis

• Lee YW

• KMID: 2452641
• DOI: http://doi.org/10.5124/jkma.2019.62.7.385

Abstract

Onychomycosis is a fungal nail infection caused by various fungal species, including dermatophytes, non-dermatophytes, and yeast. It is one of most bothersome nail problems, because it may cause permanent deformity of the nail, local pain, paresthesia, and difficulties performing activities of daily living and engaging in social interactions. Additionally, the treatment of onychomycosis is considered to be challenging because of the long duration of treatment, high recurrence and treatment failure rates, and drug interactions. In this article, we review the prognostic factors for onychomycosis treatment, the treatment options that have been approved, and off-label therapies and devices. Furthermore, we describe preventive therapy for recurrence and emerging methods to achieve a high cure rate. For successful treatment of onychomycosis, the risk factors should be clarified according to the patient's status and the clinical characteristics of onychomycosis. Recently, combinations of various treatment options, such as systemic therapy with simultaneous topical antifungal agents and boost therapy, have been reported as effective treatments of onychomycosis. In addition, laser therapy, photodynamic therapy, and plasma therapy have been proposed as emerging curative options. Providing patient-specific treatment based on an understanding of these treatments plays a pivotal role in achieving better treatment results. This article suggested the updated treatment options for onychomycosis to help clinicians make proper plans and achieve better results.

Keyword

Onychomycosis; Antifungal agents; Laser therapy; Therapeutics

MeSH Terms

Activities of Daily Living
Antifungal Agents
Arthrodermataceae
Congenital Abnormalities
Drug Interactions
Interpersonal Relations
Laser Therapy
Onychomycosis*
Paresthesia
Photochemotherapy
Plasma
Recurrence
Risk Factors
Treatment Failure
Yeasts
Antifungal Agents

Reference

1. Elewski BE, Hay RJ. Novel treatment strategies for superficial mycoses: introduction. J Am Acad Dermatol. 1999; 40(6 Pt 2):S1–S2.

2. English MP. Trichophyton rubrum infection in families. Br Med J. 1957; 1:744–746.

3. Piraccini BM, Alessandrini A. Onychomycosis: a review. J Fungi (Basel). 2015; 1:30–43.

4. Gupta AK. Onychomycosis in the elderly. Drugs Aging. 2000; 16:397–407.

5. Gupta AK, Drummond-Main C, Cooper EA, Brintnell W, Piraccini BM, Tosti A. Systematic review of nondermatophyte mold onychomycosis: diagnosis, clinical types, epidemiology, and treatment. J Am Acad Dermatol. 2012; 66:494–502.

6. Baran R, Faergemann J, Hay RJ. Superficial white onychomycosis: a syndrome with different fungal causes and paths of infection. J Am Acad Dermatol. 2007; 57:879–882.

7. Hay RJ, Baran R. Onychomycosis: a proposed revision of the clinical classification. J Am Acad Dermatol. 2011; 65:1219–1227.

8. Carney C, Tosti A, Daniel R, Scher R, Rich P, DeCoster J, Elewski B. A new classification system for grading the severity of onychomycosis: Onychomycosis Severity Index. Arch Dermatol. 2011; 147:1277–1282.

9. Scher RK, Tavakkol A, Sigurgeirsson B, Hay RJ, Joseph WS, Tosti A, Fleckman P, Ghannoum M, Armstrong DG, Markin-son BC, Elewski BE. Onychomycosis: diagnosis and definition of cure. J Am Acad Dermatol. 2007; 56:939–944.

10. Roberts DT. Onychomycosis: current treatment and future challenges. Br J Dermatol. 1999; 141(Suppl 56):1–4.

11. Tosti A, Piraccini BM, Stinchi C, Colombo MD. Relapses of onychomycosis after successful treatment with systemic antifungals: a three-year followup. Dermatology. 1998; 197:162–166.

12. Gupta AK, Studholme C. How do we measure efficacy of therapy in onychomycosis: patient, physician, and regulatory perspectives. J Dermatolog Treat. 2016; 27:498–504.

13. Del Rosso JQ. The role of topical antifungal therapy for onychomycosis and the emergence of newer agents. J Clin Aesthet Dermatol. 2014; 7:10–18.

14. Gupta AK, Ryder JE, Baran R. The use of topical therapies to treat onychomycosis. Dermatol Clin. 2003; 21:481–489.

15. Tabara K, Szewczyk AE, Bienias W, Wojciechowska A, Pastus-zka M, Oszukowska M, Kaszuba A. Amorolfine vs. ciclopirox: lacquers for the treatment of onychomycosis. Postepy Dermatol Alergol. 2015; 32:40–45.

16. Elewski BE, Ghannoum MA, Mayser P, Gupta AK, Korting HC, Shouey RJ, Baker DR, Rich PA, Ling M, Hugot S, Damaj B, Nyirady J, Thangavelu K, Notter M, Parneix-Spake A, Sigurgeirsson B. Efficacy, safety and tolerability of topical terbinafine nail solution in patients with mild-to-moderate toenail onychomycosis: results from three randomized studies using double-blind vehicle-controlled and open-label active-controlled designs. J Eur Acad Dermatol Venereol. 2013; 27:287–294.

17. Ruiz-Lopez P, Moreno-Coutino G, Fernandez-Martinez R, Espinoza-Hernandez J, Rodriguez-Zulueta P, Reyes-Teran G. Evaluation of improvement of onychomycosis in HIV-infected patients after initiation of combined antiretroviral therapy without antifungal treatment. Mycoses. 2015; 58:516–521.

18. Gupta AK, Fleckman P, Baran R. Ciclopirox nail lacquer topical solution 8% in the treatment of toenail onychomycosis. J Am Acad Dermatol. 2000; 43(4 Suppl):S70–S80.

19. Elewski BE, Rich P, Pollak R, Pariser DM, Watanabe S, Senda H, Ieda C, Smith K, Pillai R, Ramakrishna T, Olin JT. Efinaconazole 10% solution in the treatment of toenail onychomycosis: two phase III multicenter, randomized, double-blind studies. J Am Acad Dermatol. 2013; 68:600–608.

20. Scher RK, Nakamura N, Tavakkol A. Luliconazole: a review of a new antifungal agent for the topical treatment of onychomycosis. Mycoses. 2014; 57:389–393.

21. Watanabe S, Kishida H, Okubo A. Efficacy and safety of luliconazole 5% nail solution for the treatment of onychomycosis: A multicenter, double-blind, randomized phase III study. J Dermatol. 2017; 44:753–759.

22. Elewski BE, Aly R, Baldwin SL, Gonzalez Soto RF, Rich P, Weisfeld M, Wiltz H, Zane LT, Pollak R. Efficacy and safety of tavaborole topical solution, 5%, a novel boron-based antifungal agent, for the treatment of toenail onychomycosis: results from 2 randomized phase-III studies. J Am Acad Dermatol. 2015; 73:62–69.

23. Gupta AK, Sauder DN, Shear NH. Antifungal agents: an overview. Part II. J Am Acad Dermatol. 1994; 30:911–933.

24. Breckenridge A. Clinical significance of interactions with antifungal agents. Br J Dermatol. 1992; 126(Suppl 39):19–22.

25. Van Cauteren H. The toxicological properties of itraconazole. Recent Trends Discov Dev Eval Antifung Agents. 1987. 263–271.

26. Munoz P, Moreno S, Berenguer J, Bernaldo de Quiros JC, Bouza E. Fluconazole-related hepatotoxicity in patients with acquired immunodeficiency syndrome. Arch Intern Med. 1991; 151:1020–1021.

27. Sigurgeirsson B, Paul C, Curran D, Evans EG. Prognostic factors of mycological cure following treatment of onychomycosis with oral antifungal agents. Br J Dermatol. 2002; 147:1241–1243.

28. Sigurgeirsson B, van Rossem K, Malahias S, Raterink K. A phase II, randomized, double-blind, placebo-controlled, parallel group, dose-ranging study to investigate the efficacy and safety of 4 dose regimens of oral albaconazole in patients with distal subungual onychomycosis. J Am Acad Dermatol. 2013; 69:416–425.

29. Moore JN, Healy JR, Kraft WK. Pharmacologic and clinical evaluation of posaconazole. Expert Rev Clin Pharmacol. 2015; 8:321–334.

30. Watanabe S, Tsubouchi I, Okubo A. Efficacy and safety of fosravuconazole L-lysine ethanolate, a novel oral triazole antifungal agent, for the treatment of onychomycosis: a multicenter, double-blind, randomized phase III study. J Dermatol. 2018; 45:1151–1159.

31. Gupta AK, Versteeg SG. A critical review of improvement rates for laser therapy used to treat toenail onychomycosis. J Eur Acad Dermatol Venereol. 2017; 31:1111–1118.

32. Hashimoto T, Blumenthal HJ. Survival and resistance of Trichophyton mentagrophytes arthrospores. Appl Environ Microbiol. 1978; 35:274–277.

33. Gupta AK, Ahmad I, Borst I, Summerbell RC. Detection of xanthomegnin in epidermal materials infected with Trichophyton rubrum. J Invest Dermatol. 2000; 115:901–905.

34. Sotiriou E, Koussidou-Eremonti T, Chaidemenos G, Apalla Z, Ioannides D. Photodynamic therapy for distal and lateral subungual toenail onychomycosis caused by Trichophyton rubrum: preliminary results of a single-centre open trial. Acta Derm Venereol. 2010; 90:216–217.

35. Heinlin J, Maisch T, Zimmermann JL, Shimizu T, Holzmann T, Simon M, Heider J, Landthaler M, Morfill G, Karrer S. Contact-free inactivation of Trichophyton rubrum and Microsporum canis by cold atmospheric plasma treatment. Future Microbiol. 2013; 8:1097–1106.

36. Arrese JE, Pierard GE. Treatment failures and relapses in onychomycosis: a stubborn clinical problem. Dermatology. 2003; 207:255–260.

37. Pierard GE, Pierard-Franchimont C, Arrese JE. The boosted oral antifungal treatment for onychomycosis beyond the regular itraconazole pulse dosing regimen. Dermatology. 2000; 200:185–187.

38. Lipner SR, Scher RK. Onychomycosis: treatment and prevention of recurrence. J Am Acad Dermatol. 2019; 80:853–867.