Abstract
Onychomycosis should be considered a medical problem, rather than a cosmetic one. In most cases, except the mildest one and in children systemic treatment is needed. Choice of treatment is based on several factors such as the organism isolated, type of onychomycosis, concomitant disorders and possibility of drug interactions. Terbinafine is the drug of choice in patients with dermatophyte onychomycosis. Patients with negative prognostic factors can be more difficult to treat and may need modification of the treatment such as surgery and/or booster treatment. When patients have been cured, it is important to prevent recurrences.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Scher RK. Onychomycosis is more than a cosmetic problem. Br J Dermatol. 1994;130(Suppl 43):15.
Roseeuw D. Achilles foot screening project: preliminary results of patients screened by dermatologists. J Eur Acad Dermatol Venereol. 1999;12(Suppl 1):S6–9; discussion S17.
Szepietowski JC, Reich A, for the National Quality of Life in Dermatology Group. Stigmatisation in onychomycosis patients: a population-based study. Mycoses. 2009;52(4):343–9.
Reich A, Szepietowski JC. Health-related quality of life in patients with nail disorders. Am J Clin Dermatol. 2011;12(5):313–20.
Roujeau J-C, Sigurgeirsson B, Korting H-C, Kerl H, Paul C. Chronic dermatomycoses of the foot as risk factors for acute bacterial cellulitis of the leg: a case-control study. Dermatology. 2004;209(4):301–7.
Björnsdóttir S, Gottfredsson M, Thórisdóttir AS, et al. Risk factors for acute cellulitis of the lower limb: a prospective case-control study. Clin Infect Dis. 2005;41(10):1416–22.
Arenas R, Domínguez-Cherit J, Fernández LM. Open randomized comparison of itraconazole versus terbinafine in onychomycosis. Int J Dermatol. 1995;34(2):138–43.
Bonifaz A, Paredes V, Fierro L. Onychocryptosis as consequence of effective treatment of dermatophytic onychomycosis. J Eur Acad Dermatol Venereol. 2007;21(5):699–700.
Connelley LK, Dinehart SM, McDonald R. Onychocryptosis associated with the treatment of onychomycosis. J Am Podiatr Med Assoc. 1999;89(8):424–6.
Milobratović D, Janković S, Vukičević J, Marinković J, Janković J, Railić Z. Quality of life in patients with toenail onychomycosis. Mycoses. 2013;56:543–51.
Drake LA, Patrick DL, Fleckman P, et al. The impact of onychomycosis on quality of life: development of an international onychomycosis-specific questionnaire to measure patient quality of life. J Am Acad Dermatol. 1999;41(2 Pt 1):189–96.
Wise F, Sulzberger MB. Urticaria and hay-fever due to trichophytin (Epidermophyton interdigitale). J Am Med Assoc. 1930;95(20):1504.
Weary PE, Guerrant JL. Chronic urticaria in association with dermatophytosis. Response to the administration of griseofulvin. Arch Dermatol. 1967;95(4):400–1.
Platts-Mills TA, Fiocco GP, Pollart S, Hayden ML, Jackson S, Wilkins SR. Trichophyton allergy in a 24-year-old man with “intrinsic” asthma. Ann Allergy. 1986;56(6):454–5. 70-1.
Gumowski P, Lech B, Chaves I, Girard JP. Chronic asthma and rhinitis due to Candida albicans, epidermophyton, and trichophyton. Ann Allergy. 1987;59(1):48–51.
Ward GW, Karlsson G, Rose G, Platts-Mills TA. Trichophyton asthma: sensitisation of bronchi and upper airways to dermatophyte antigen. Lancet. 1989;1(8643):859–62.
Kivity S, Schwarz Y, Fireman E. The association of perennial rhinitis with Trichophyton infection. Clin Exp Allergy. 1992;22(4):498–500.
Ward GW, Woodfolk JA, Hayden ML, Jackson S, Platts-Mills TA. Treatment of late-onset asthma with fluconazole. J Allergy Clin Immunol. 1999;104(3 Pt 1):541–6.
Klein PA, Clark RA, Nicol NH. Acute infection with Trichophyton rubrum associated with flares of atopic dermatitis. Cutis. 1999;63(3):171–2.
Wilson BB, Deuell B, Mills TA. Atopic dermatitis associated with dermatophyte infection and Trichophyton hypersensitivity. Cutis. 1993;51(3):191–2.
Woodfolk JA. Allergy and dermatophytes. Clin Microbiol Rev. 2005;18(1):30–43.
Baran R, Hay RJ, Garduno JI. Review of antifungal therapy and the severity index for assessing onychomycosis: part I. J Dermatolog Treat. 2008;19(2):72–81.
de Sá DC, Lamas APB, Tosti A. Oral therapy for onychomycosis: an evidence-based review. Am J Clin Dermatol. 2013;15:17–36.
Scher RK, Tavakkol A, Sigurgeirsson B, et al. Onychomycosis: diagnosis and definition of cure. J Am Acad Dermatol. 2007;56(6):939–44.
Fromtling RA. Overview of medically important antifungal azole derivatives. Clin Microbiol Rev. 1988;1(2):187–217.
Heykants J, Van Peer A, Van de Velde V, et al. The clinical pharmacokinetics of itraconazole: an overview. Mycoses. 1989;32(Suppl 1):67–87.
Debruyne D, Coquerel A. Pharmacokinetics of antifungal agents in onychomycoses. Clin Pharmacokinet. 2001;40(6):441–72.
Cauwenbergh G, Degreef H, Heykants J, Woestenborghs R, Van Rooy P, Haeverans K. Pharmacokinetic profile of orally administered itraconazole in human skin. J Am Acad Dermatol. 1988;18(2 Pt 1):263–8.
Matthieu L, De Doncker P, Cauwenbergh G, et al. Itraconazole penetrates the nail via the nail matrix and the nail bed – an investigation in onychomycosis. Clin Exp Dermatol. 1991;16(5):374–6.
De Doncker P, Decroix J, Piérard GE, et al. Antifungal pulse therapy for onychomycosis. A pharmacokinetic and pharmacodynamic investigation of monthly cycles of 1-week pulse therapy with itraconazole. Arch Dermatol. 1996;132(1):34–41.
Gupta AK, Sauder DN, Shear NH. Antifungal agents: an overview. Part II. J Am Acad Dermatol. 1994;30(6):911–33; quiz 34–6.
Janssen-Cilag. Sporanox – summary of product characteristics (last revision 23/04/2013). 2013.
Cleary JD, Taylor JW, Chapman SW. Itraconazole in antifungal therapy. Ann Pharmacother. 1992;26(4):502–9.
Grant SM, Clissold SP. Itraconazole. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in superficial and systemic mycoses. Drugs. 1989;37(3):310–44.
Chang C-H, Young-Xu Y, Kurth T, Orav JE, Chan AK. The safety of oral antifungal treatments for superficial dermatophytosis and onychomycosis: a meta-analysis. Am J Med. 2007;120(9):791–8.
Elewski B, Tavakkol A. Safety and tolerability of oral antifungal agents in the treatment of fungal nail disease: a proven reality. Ther Clin Risk Manag. 2005;1(4):299–306.
Ahmad SR, Singer SJ, Leissa BG. Congestive heart failure associated with itraconazole. Lancet. 2001;357(9270):1766–7.
Sigurgeirsson B, Olafsson JH, Steinsson JB, Paul C, Billstein S, Evans EGV. Long-term effectiveness of treatment with terbinafine vs itraconazole in onychomycosis: a 5-year blinded prospective follow-up study. Arch Dermatol. 2002;138(3):353–7.
Evans EG, Sigurgeirsson B. Double blind, randomised study of continuous terbinafine compared with intermittent itraconazole in treatment of toenail onychomycosis. The LION Study Group. BMJ. 1999;318(7190):1031–5.
Sigurgeirsson B, Billstein S, Rantanen T, et al. L.I.ON. Study: efficacy and tolerability of continuous terbinafine (Lamisil) compared to intermittent itraconazole in the treatment of toenail onychomycosis. Lamisil vs. Itraconazole in Onychomycosis. Br J Dermatol. 1999;141(Suppl 56):5–14.
Arca E, Taştan HB, Akar A, Kurumlu Z, Gür AR. An open, randomized, comparative study of oral fluconazole, itraconazole and terbinafine therapy in onychomycosis. J Dermatolog Treat. 2002;13(1):3–9.
Arenas R, Fernández G, Domínguez L. Onychomycosis treated with itraconazole or griseofulvin alone with and without a topical antimycotic or keratolytic agent. Int J Dermatol. 1991;30(8):586–9.
Bonifaz A, Carrasco-Gerard E, Saúl A. Itraconazole in onychomycosis: intermittent dose schedule. Int J Dermatol. 1997;36(1):70–2.
Bräutigam M, Nolting S, Schopf RE, Weidinger G. Randomised double blind comparison of terbinafine and itraconazole for treatment of toenail tinea infection. Seventh Lamisil German Onychomycosis Study Group. BMJ. 1995;311(7010):919–22.
Chen J, Liao W, Wen H, Wu J, Yao Z. A comparison among four regimens of itraconazole treatment in onychomycosis. Mycoses. 1999;42(1–2):93–6.
De Backer M, De Vroey C, Lesaffre E, Scheys I, De Keyser P. Twelve weeks of continuous oral therapy for toenail onychomycosis caused by dermatophytes: a double-blind comparative trial of terbinafine 250 mg/day versus itraconazole 200 mg/day. J Am Acad Dermatol. 1998;38(5 Pt 3):S57–63.
Degreef H, del Palacio A, Mygind S, Ginter G, Pinto Soares A, Zuluaga de Cadena A. Randomized double-blind comparison of short-term itraconazole and terbinafine therapy for toenail onychomycosis. Acta Derm Venereol. 1999;79(3):221–3.
Elewski BE, Scher RK, Aly R, et al. Double-blind, randomized comparison of itraconazole capsules vs. placebo in the treatment of toenail onychomycosis. Cutis. 1997;59(4):217–20.
Haneke E, Tajerbashi M, De Doncker P, Heremans A. Itraconazole in the treatment of onychomycosis: a double-blind comparison with miconazole. Dermatology. 1998;196(3):323–9.
Havu V, Brandt H, Heikkilä H, et al. Continuous and intermittent itraconazole dosing schedules for the treatment of onychomycosis: a pharmacokinetic comparison. Br J Dermatol. 1999;140(1):96–101.
Havu V, Brandt H, Heikkilä H, et al. A double-blind, randomized study comparing itraconazole pulse therapy with continuous dosing for the treatment of toe-nail onychomycosis. Br J Dermatol. 1997;136(2):230–4.
Piepponen T, Blomqvist K, Brandt H, et al. Efficacy and safety of itraconazole in the long-term treatment of onychomycosis. J Antimicrob Chemother. 1992;29(2):195–205.
Odom RB, Aly R, Scher RK, et al. A multicenter, placebo-controlled, double-blind study of intermittent therapy with itraconazole for the treatment of onychomycosis of the fingernail. J Am Acad Dermatol. 1997;36(2 Pt 1):231–5.
Odom R, Daniel CR, Aly R. A double-blind, randomized comparison of itraconazole capsules and placebo in the treatment of onychomycosis of the toenail. J Am Acad Dermatol. 1996;35(1):110–1.
Tang WY, Chong LY, Leung CY, Ho HH, Wong TW. Intermittent pulse therapy with itraconazole for onychomycosis. Experience in Hong Kong Chinese. Mycoses. 2000;43(1–2):35–9.
Wang DL, Wang AP, Li RY, Wang R. Therapeutic efficacy and safety of one-week intermittent therapy with itraconazole for onychomycosis in a Chinese patient population. Dermatology. 1999;199(1):47–9.
Heikkilä H, Stubb S. Long-term results in patients with onychomycosis treated with terbinafine or itraconazole. Br J Dermatol. 2002;146(2):250–3.
Hiruma M, Matsushita A, Kobayashi M, Ogawa H. One week pulse therapy with itraconazole (200 mg day-1) for onychomycosis. Evaluation of treatment results according to patient background. Mycoses. 2001;44(3–4):87–93.
Bahadir S, Inalöz HS, Alpay K, Agaoglu C, Cimsit G, Parlat P. Continuous terbinafine or pulse itraconazole: a comparative study on onychomycosis. J Eur Acad Dermatol Venereol. 2000;14(5):422–3.
Haneke E, Abeck D, Ring J. Safety and efficacy of intermittent therapy with itraconazole in finger- and toenail onychomycosis: a multicentre trial. Mycoses. 1998;41(11–12):521–7.
Ginter G, De Doncker P. An intermittent itraconazole 1-week dosing regimen for the treatment of toenail onychomycosis in dermatological practice. Mycoses. 1998;41(5–6):235–8.
Wu J, Wen H, Liao W. Small-dose itraconazole pulse therapy in the treatment of onychomycosis. Mycoses. 1997;40(9–10):397–400.
Heikkilä H, Stubb S. Long-term results of patients with onychomycosis treated with itraconazole. Acta Derm Venereol. 1997;77(1):70–1.
Jones HE, Zaias N. Double-blind, randomized comparison of itraconazole capsules and placebo in onychomycosis of toenail. Int J Dermatol. 1996;35(8):589–90.
De Backer M, De Keyser P, De Vroey C, Lesaffre E. A 12-week treatment for dermatophyte toe onychomycosis: terbinafine 250 mg/day vs. itraconazole 200 mg/day – a double-blind comparative trial. Br J Dermatol. 1996;134(Suppl 46):16–7; discussion 38.
De Doncker P, Van Lint J, Dockx P, Roseeuw D. Pulse therapy with one-week itraconazole monthly for three or four months in the treatment of onychomycosis. Cutis. 1995;56(3):180–3.
Walsøe I, Stangerup M, Svejgaard E. Itraconazole in onychomycosis. Open and double-blind studies. Acta Derm Venereol. 1990;70(2):137–40.
Gupta AK, Ryder JE, Johnson AM. Cumulative meta-analysis of systemic antifungal agents for the treatment of onychomycosis. Br J Dermatol. 2004;150(3):537–44.
Ryder NS. Specific inhibition of fungal sterol biosynthesis by SF 86-327, a new allylamine antimycotic agent. Antimicrob Agents Chemother. 1985;27(2):252–6.
Ryder NS, Dupont MC. Inhibition of squalene epoxidase by allylamine antimycotic compounds. A comparative study of the fungal and mammalian enzymes. Biochem J. 1985;230(3):765–70.
Ryder NS. Terbinafine: mode of action and properties of the squalene epoxidase inhibition. Br J Dermatol. 1992;126(Suppl 39):2–7.
Ryder NS, Favre B. Antifungal activity and mechanism of action of terbinafine. Rev Contemp Pharmacother. 1997;8:275–88.
Petranyi G, Meingassner JG, Mieth H. Antifungal activity of the allylamine derivative terbinafine in vitro. Antimicrob Agents Chemother. 1987;31(9):1365–8.
Rinaldi MG. In vitro susceptibility of dermatophytes to antifungal drugs. Int J Dermatol. 1993;32(7):502–3.
Chiritescu MM, Chiritescu ME, Scher RK. Newer systemic antifungal drugs for the treatment of onychomycosis. Clin Podiatr Med Surg. 1996;13(4):741–58.
Shear NH, Gupta AK. Terbinafine for the treatment of pedal onychomycosis. A foot closer to the promised land of cured nails? Arch Dermatol. 1995;131(8):937–42.
Faergemann J, Zehender H, Denouël J, Millerioux L. Levels of terbinafine in plasma, stratum corneum, dermis-epidermis (without stratum corneum), sebum, hair and nails during and after 250 mg terbinafine orally once per day for four weeks. Acta Derm Venereol. 1993;73(4):305–9.
Dykes PJ, Thomas R, Finlay AY. Determination of terbinafine in nail samples during systemic treatment for onychomycoses. Br J Dermatol. 1990;123(4):481–6.
Balfour JA, Faulds D. Terbinafine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in superficial mycoses. Drugs. 1992;43(2):259–84.
Hazen KC. Fungicidal versus fungistatic activity of terbinafine and itraconazole: an in vitro comparison. J Am Acad Dermatol. 1998;38(5 Pt 3):S37–41.
Schatz F, Bräutigam M, Dobrowolski E, et al. Nail incorporation kinetics of terbinafine in onychomycosis patients. Clin Exp Dermatol. 1995;20(5):377–83.
Novartis pharma. Lamisil – summary of product characteristics (last revision 21.05.2013). 2013.
Katz HI, Gupta AK. Oral antifungal drug interactions. Dermatol Clin. 1997;15(3):535–44.
Baran R, Hay RJ, Garduno JI. Review of antifungal therapy, part II: treatment rationale, including specific patient populations. J Dermatolog Treat. 2008;19(3):168–75.
Hall M, Monka C, Krupp P, O’Sullivan D. Safety of oral terbinafine: results of a postmarketing surveillance study in 25,884 patients. Arch Dermatol. 1997;133(10):1213–9.
Bangsgaard N, Saunte DM, Folkenberg M, Zachariae C. Serious adverse events reporting on systemic terbinafine: a Danish register-based study. Acta Derm Venereol. 2011;91(3):358–9.
Kanzler MH. Reevaluating the need for laboratory testing in the treatment of onychomycosis: safety and cost-effectiveness considerations. JAMA Dermatol. 2015:1–2.
Russo MW, Galanko JA, Shrestha R, Fried MW, Watkins P. Liver transplantation for acute liver failure from drug induced liver injury in the United States. Liver Transpl. 2004;10(8):1018–23.
Baran R, Belaich S, Beylot C, et al. Comparative multicentre double-blind study of terbinafine (250 mg per day) versus griseofulvin (1 g per day) in the treatment of dermatophyte onychomycosis. J Dermatol Treat. 1997;8(2):93–7.
Billstein S, Kianifard F, Justice A. Terbinafine vs. placebo for onychomycosis in black patients. Int J Dermatol. 1999;38(5):377–9.
Drake LA, Shear NH, Arlette JP, et al. Oral terbinafine in the treatment of toenail onychomycosis: North American multicenter trial. J Am Acad Dermatol. 1997;37(5 Pt 1):740–5.
Faergemann J, Anderson C, Hersle K, et al. Double-blind, parallel-group comparison of terbinafine and griseofulvin in the treatment of toenail onychomycosis. J Am Acad Dermatol. 1995;32(5 Pt 1):750–3.
Goodfield MJ, Andrew L, Evans EG. Short term treatment of dermatophyte onychomycosis with terbinafine. BMJ. 1992;304(6835):1151–4.
Hofmann H, Bräutigam M, Weidinger G, Zaun H. Treatment of toenail onychomycosis. A randomized, double-blind study with terbinafine and griseofulvin. LAGOS II Study Group. Arch Dermatol. 1995;131(8):919–22.
Kejda J. Itraconazole pulse therapy vs continuous terbinafine dosing for toenail onychomycosis. Postgrad Med. 1999; Spec No: 12–5.
Warshaw EM, Carver SM, Zielke GR, Ahmed DD. Intermittent terbinafine for toenail onychomycosis: is it effective? Results of a randomized pilot trial. Arch Dermatol. 2001;137(9):1253.
van der Schroeff JG, Cirkel PK, Crijns MB, et al. A randomized treatment duration-finding study of terbinafine in onychomycosis. Br J Dermatol. 1992;126(Suppl 39):36–9.
Tosti A, Piraccini BM, Stinchi C, Venturo N, Bardazzi F, Colombo MD. Treatment of dermatophyte nail infections: an open randomized study comparing intermittent terbinafine therapy with continuous terbinafine treatment and intermittent itraconazole therapy. J Am Acad Dermatol. 1996;34(4):595–600.
Tausch I, Bräutigam M, Weidinger G, Jones TC. Evaluation of 6 weeks treatment of terbinafine in tinea unguium in a double-blind trial comparing 6 and 12 weeks therapy. The Lagos V Study Group. Br J Dermatol. 1997;136(5):737–42.
Svejgaard EL, Brandrup F, Kragballe K, et al. Oral terbinafine in toenail dermatophytosis. A double-blind, placebo-controlled multicenter study with 12 months’ follow-up. Acta Derm Venereol. 1997;77(1):66–9.
Pollak R, Billstein SA. Efficacy of terbinafine for toenail onychomycosis. A multicenter trial of various treatment durations. J Am Podiatr Med Assoc. 2001;91(3):127–31.
Sigurgeirsson B, Elewski BE, Rich PA, et al. Intermittent versus continuous terbinafine in the treatment of toenail onychomycosis: a randomized, double-blind comparison. J Dermatolog Treat. 2006;17(1):38–44.
Haugh M, Helou S, Boissel JP, Cribier BJ. Terbinafine in fungal infections of the nails: a meta-analysis of randomized clinical trials. Br J Dermatol. 2002;147(1):118–21.
Trivedi NA, Shah PC. A meta-analysis comparing efficacy of continuous terbinafine with intermittent itraconazole for toenail onychomycosis. Indian J Dermatol. 2010;55(2):198–9.
Honeyman J, Talarico FS, Arruda L, et al. Itraconazole versus terbinafine (LAMISILR): which is better for the treatment of onychomycosis? J Eur Acad Dermatol Venereol. 1997;9(3):215–21.
Havu V, Heikkilä H, Kuokkanen K, et al. A double-blind, randomized study to compare the efficacy and safety of terbinafine (Lamisil) with fluconazole (Diflucan) in the treatment of onychomycosis. Br J Dermatol. 2000;142(1):97–102.
Scher RK, Breneman D, Rich P, et al. Once-weekly fluconazole (150, 300, or 450 mg) in the treatment of distal subungual onychomycosis of the toenail. J Am Acad Dermatol. 1998;38(6 Pt 2):S77–86.
Welsh O, Vera-Cabrera L, Welsh E. Onychomycosis. Clin Dermatol. 2010;28(2):151–9.
Elewski BE. Once-weekly fluconazole in the treatment of onychomycosis: introduction. J Am Acad Dermatol. 1998;38(6 Pt 2):S73–6.
Ling MR, Swinyer LJ, Jarratt MT, et al. Once-weekly fluconazole (450 mg) for 4, 6, or 9 months of treatment for distal subungual onychomycosis of the toenail. J Am Acad Dermatol. 1998;38(6 Pt 2):S95–102.
Drake L, Babel D, Stewart DM, et al. Once-weekly fluconazole (150, 300, or 450 mg) in the treatment of distal subungual onychomycosis of the fingernail. J Am Acad Dermatol. 1998;38(6 Pt 2):S87–94.
Scher RK, Daniel R. Nails diagnosis, therapy, surgery. Oxford: Elsevier Saunders; 2005.
Rich P, Scher RK, Breneman D, et al. Pharmacokinetics of three doses of once-weekly fluconazole (150, 300, and 450 mg) in distal subungual onychomycosis of the toenail. J Am Acad Dermatol. 1998;38(6 Pt 2):S103–9.
Laufen H, Zimmermann T, Yeates RA, Schumacher T, Wildfeuer A. The uptake of fluconazole in finger and toe nails. Int J Clin Pharmacol Ther. 1999;37(7):352–60.
Savin RC, Drake L, Babel D, et al. Pharmacokinetics of three once-weekly dosages of fluconazole (150, 300, or 450 mg) in distal subungual onychomycosis of the fingernail. J Am Acad Dermatol. 1998;38(6 Pt 2):S110–6.
Barchiesi F, Silvestri C, Arzeni D, et al. In vitro susceptibility of dermatophytes to conventional and alternative antifungal agents. Med Mycol. 2009;47(3):321–6.
Pfaller MA, Diekema DJ, Gibbs DL, et al. Results from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2007: a 10.5-year analysis of susceptibilities of Candida Species to fluconazole and voriconazole as determined by CLSI standardized disk diffusion. J Clin Microbiol. 2010;48(4):1366–77.
Brown SJ. Efficacy of fluconazole for the treatment of onychomycosis. Ann Pharmacother. 2009;43(10):1684–91.
Drake LA, Scher RK, Smith EB, et al. Effect of onychomycosis on quality of life. J Am Acad Dermatol. 1998;38(5 Pt 1):702–4.
Chen X, Hiruma M, Shiraki Y, Ogawa H. Combination therapy of once-weekly fluconazole (100, 150, or 300 mg) with topical application of ketoconazole cream in the treatment of onychomycosis. Jpn J Infect Dis. 2004;57(6):260–3.
Gupta AK, Gregurek-Novak T, Konnikov N, Lynde CW, Hofstader S, Summerbell RC. Itraconazole and terbinafine treatment of some nondermatophyte molds causing onychomycosis of the toes and a review of the literature. J Cutan Med Surg. 2001;5(3):206–10.
Montero-Gei F, Robles-Soto ME, Schlager H. Fluconazole in the treatment of severe onychomycosis. Int J Dermatol. 1996;35(8):587–8.
Gupta AK, Drummond-Main C, Paquet M. Evidence-based optimal fluconazole dosing regimen for onychomycosis treatment. J Dermatolog Treat. 2012;24:75–80.
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;69:416–25.
Barchiesi F, Arzeni D, Camiletti V, et al. In vitro activity of posaconazole against clinical isolates of dermatophytes. J Clin Microbiol. 2001;39(11):4208–9.
Elewski B, Pollak R, Ashton S, Rich P, Schlessinger J, Tavakkol A. A randomized, placebo- and active-controlled, parallel-group, multicentre, investigator-blinded study of four treatment regimens of posaconazole in adults with toenail onychomycosis. Br J Dermatol. 2012;166(2):389–98.
Warrilow AGS, Hull CM, Parker JE, et al. The clinical candidate VT-1161 is a highly potent inhibitor of Candida albicans CYP51 but fails to bind the human enzyme. Antimicrob Agents Chemother. 2014;58(12):7121–7.
Warshaw EM, Fett DD, Bloomfield HE, et al. Pulse versus continuous terbinafine for onychomycosis: a randomized, double-blind, controlled trial. J Am Acad Dermatol. 2005;53(4):578–84.
Darkes MJM, Scott LJ, Goa KL. Terbinafine: a review of its use in onychomycosis in adults. Am J Clin Dermatol. 2003;4(1):39–65.
Sigurgeirsson B, Paul C, Curran D, Evans EGV. Prognostic factors of mycological cure following treatment of onychomycosis with oral antifungal agents. Br J Dermatol. 2002;147(6):1241–3.
Tuccori M, Bresci F, Guidi B, Blandizzi C, Del Tacca M, Di Paolo M. Fatal hepatitis after long-term pulse itraconazole treatment for onychomycosis. Ann Pharmacother. 2008;42(7):1112–7.
Doncker PD, Gupta AK, Marynissen G, Stoffels P, Heremans A. Itraconazole pulse therapy for onychomycosis and dermatomycoses: an overview. J Am Acad Dermatol. 1997;37(6):969–74.
Bruch-Gerharz D, Ruzicka T. Dermatomykosen im Kindesalter. Monatsschr Kinderheilkd. 2008;156(2):132–8.
Irvine A, Hoeger P, Yan AC. Harper’s textbook of pediatric dermatology. Chichester/Hoboken: Wiley-Blackwell; 2011.
Baran R, Hay R, Haneke E, Tosti A. Onychomycosis. The current approach to diagnosis and therapy. 2nd ed. Abingdon: Informa healthcare; 2006.
Gupta AK, Chang P, Del Rosso JQ, Adam P, Hofstader SL. Onychomycosis in children: prevalence and management. Pediatr Dermatol. 1998;15(6):464–71.
Sigurgeirsson B. Onychomycosis. In: Ólafsson JH, Hay RJ, editors. Antibiotic and antifungal therapies in dermatology. Switzerland: Springer; 2016.
Baranov AF, Konopikhina TA, Uglova SV. Combined treatment of onychomycoses with griseofulvin in combination with topical therapy. Vestn Dermatol Venerol. 1966;40(1):46–9.
Olafsson JH, Sigurgeirsson B, Baran R. Combination therapy for onychomycosis. Br J Dermatol. 2003;149(Suppl 65):15–8.
Lauharanta J, Zaug M, Polak A, Reinel D. Combination of amorolfine with griseofulvin: in vitro activity and clinical results in onychomycosis. JAMA SEA. 1993;9(Suppl 4):23–7.
Baran R, Feuilhade M, Combernale P, et al. A randomized trial of amorolfine 5% solution nail lacquer combined with oral terbinafine compared with terbinafine alone in the treatment of dermatophytic toenail onychomycoses affecting the matrix region. Br J Dermatol. 2000;142(6):1177–83.
Sigurgeirsson B, Olafsson JH, Steinsson JT, Kerrouche N, Sidou F. Efficacy of amorolfine nail lacquer for the prophylaxis of onychomycosis over 3 years. J Eur Acad Dermatol Venereol. 2010;24(8):910–5.
Jaiswal A, Sharma RP, Garg AP. An open randomized comparative study to test the efficacy and safety of oral terbinafine pulse as a monotherapy and in combination with topical ciclopirox olamine 8% or topical amorolfine hydrochloride 5% in the treatment of onychomycosis. Indian J Dermatol Venereol Leprol. 2007;73(6):393–6.
Baran R, Sigurgeirsson B, de Berker D, et al. A multicentre, randomized, controlled study of the efficacy, safety and cost-effectiveness of a combination therapy with amorolfine nail lacquer and oral terbinafine compared with oral terbinafine alone for the treatment of onychomycosis with matrix involvement. Br J Dermatol. 2007;157(1):149–57.
Rigopoulos D, Katoulis AC, Ioannides D, et al. A randomized trial of amorolfine 5% solution nail lacquer in association with itraconazole pulse therapy compared with itraconazole alone in the treatment of Candida fingernail onychomycosis. Br J Dermatol. 2003;149(1):151–6.
Lecha M. Amorolfine and itraconazole combination for severe toenail onychomycosis; results of an open randomized trial in Spain. Br J Dermatol. 2001;145(Suppl 60):21–6.
Baran R. Topical amorolfine for 15 months combined with 12 weeks of oral terbinafine, a cost-effective treatment for onychomycosis. Br J Dermatol. 2001;145(Suppl 60):15–9.
Avner S, Nir N, Henri T. Combination of oral terbinafine and topical ciclopirox compared to oral terbinafine for the treatment of onychomycosis. J Dermatolog Treat. 2005;16(5–6):327–30.
Gupta AK, Onychomycosis Combination Therapy Study Group. Ciclopirox topical solution, 8% combined with oral terbinafine to treat onychomycosis: a randomized, evaluator-blinded study. J Drugs Dermatol. 2005;4(4):481–5.
Sergeev AY, Sergeev YV. Pulsed combination therapy: a new option for onychomycosis. Mycoses. 2001;44(Suppl 1):68–9.
Gupta S, Jangra RS, Gupta S, Mahendra A, Kumar A. A painless, minimally invasive technique for debulking onychomycotic nails. J Am Acad Dermatol. 2017;76(1):e17–e9.
Zhou BR, Lu Y, Permatasari F, et al. The efficacy of fractional carbon dioxide (CO2) laser combined with luliconazole 1% cream for the treatment of onychomycosis: a randomized, controlled trial. Medicine (Baltimore). 2016;95(44):e5141.
Ellis DH, Marley JE, Watson AB, Williams TG. Significance of non-dermatophyte moulds and yeasts in onychomycosis. Dermatology. 1997;194(Suppl 1):40–2.
English MP. Nails and fungi. Br J Dermatol. 1976;94(6):697–701.
Tosti A, Piraccini BM, Stinchi C, Lorenzi S. Onychomycosis due to Scopulariopsis brevicaulis: clinical features and response to systemic antifungals. Br J Dermatol. 1996;135(5):799–802.
Nolting S, Brautigam M, Weidinger G. Terbinafine in onychomycosis with involvement by non-dermatophytic fungi. Br J Dermatol. 1994;130(Suppl 43):16–21.
Gianni C, Romano C. Clinical and histological aspects of toenail onychomycosis caused by Aspergillus spp.: 34 cases treated with weekly intermittent terbinafine. Dermatology. 2004;209(2):104–10.
Tseng SS, Longley BJ, Scher RK, Treiber RK. Fusarium fingernail infection responsive to fluconazole intermittent therapy. Cutis. 2000;65(6):352–4.
Daniel CR, Daniel MP, Daniel CM, Sullivan S, Ellis G. Chronic paronychia and onycholysis: a thirteen-year experience. Cutis. 1996;58(6):397–401.
Daniel CR, Daniel MP, Daniel J, Sullivan S, Bell FE. Managing simple chronic paronychia and onycholysis with ciclopirox 0.77% and an irritant-avoidance regimen. Cutis. 2004;73(1):81–5.
Seebacher C. Fungal flora of diseased and healthy toenails. Mykosen. 1968;11(12):893–902.
Daniel CR, Gupta AK, Daniel MP, Sullivan S. Candida infection of the nail: role of Candida as a primary or secondary pathogen. Int J Dermatol. 1998;37(12):904–7.
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):S70–80.
Elewski BE, Ghannoum MA, Mayser P, et al. 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. 2011.
Baran R, de Doncker P. Lateral edge nail involvement indicates poor prognosis for treating onychomycosis with the new systemic antifungals. Acta Derm Venereol. 1996;76(1):82–3.
Sigurgeirsson B. Prognostic factors for cure following treatment of onychomycosis. J Eur Acad Dermatol Venereol. 2010;24(6):679–84.
Gupta AK, Konnikov N, Lynde CW, et al. Onychomycosis: predisposed populations and some predictors of suboptimal response to oral antifungal agents. Eur J Dermatol. 1999;9(8):633–8.
Scher RK, Baran R. Onychomycosis in clinical practice: factors contributing to recurrence. Br J Dermatol. 2003;149(Suppl 65):5–9.
Roberts DT, Evans EG. Subungual dermatophytoma complicating dermatophyte onychomycosis. Br J Dermatol. 1998;138(1):189–90.
Lecha M, Effendy I, Feuilhade de Chauvin M, Di Chiacchio N, Baran R, Taskforce on Onychomycosis Education. Treatment options – development of consensus guidelines. J Eur Acad Dermatol Venereol. 2005;19(Suppl 1):25–33.
Carney C, Tosti A, Daniel R, et al. A new classification system for grading the severity of onychomycosis: onychomycosis severity index. 159. Prognostic factors. Arch Dermatol. 2011;147(11):1277–82.
Gupta AK, Daniel CR. Factors that may affect the response of onychomycosis to oral antifungal therapy. Australas J Dermatol. 1998;39(4):222–4.
Geyer AS, Onumah N, Uyttendaele H, Scher RK. Modulation of linear nail growth to treat diseases of the nail. J Am Acad Dermatol. 2004;50(2):229–34.
Zheng Y, Wu Y, Chen H, Zhu Z, Liu L, Zeng J. Analysis of the factors influencing the therapeutic effects of onychomycosis. J Tongji Med Univ. 2001;21(3):259–62.
Reszke R, Pełka D, Walasek A, Machaj Z, Reich A. Skin disorders in elderly subjects. Int J Dermatol. 2015;54:e332–8.
Baran R. The nail in the elderly. Clin Dermatol. 2011;29(1):54–60.
Gupta AK, Jain HC, Lynde CW, Macdonald P, Cooper EA, Summerbell RC. Prevalence and epidemiology of onychomycosis in patients visiting physicians’ offices: a multicenter canadian survey of 15,000 patients. J Am Acad Dermatol. 2000;43(2 Pt 1):244–8.
Cozzani E, Agnoletti AF, Speziari S, et al. Epidemiological study of onychomycosis in older adults with onychodystrophy. Geriatr Gerontol Int. 2015;16:486.
Fiallo P, Cardo PP. Age as limiting factor of the efficacy of itraconazole for treatment of onychomycosis. Mycoses. 2001;44(5):191–4.
Elewski BE, Tosti A. Risk factors and comorbidities for onychomycosis: implications for treatment with topical therapy. J Clin Aesthet Dermatol. 2015;8(11):38–42.
Heikkilä H, Stubb S. The prevalence of onychomycosis in Finland. Br J Dermatol. 1995;133(5):699–703.
Veer P, Patwardhan NS, Damle AS. Study of onychomycosis: prevailing fungi and pattern of infection. Indian J Med Microbiol. 2007;25(1):53–6.
Sergeev AY, Gupta AK, Sergeev YV. The Scoring Clinical Index for Onychomycosis (SCIO index). Skin Therapy Lett. 2002;7(Suppl 1):6–7.
Shuster S, Baran R. Recurrence of fungal nail disease and the dissociation of relapse from re-infection. Acta Derm Venereol. 2001;81(2):154–5.
Yin Z, Xu J, Luo D. A meta-analysis comparing long-term recurrences of toenail onychomycosis after successful treatment with terbinafine versus itraconazole. J Dermatolog Treat. 2012;23(6):449–52.
Tosti A, Piraccini BM, Stinchi C, Colombo MD. Relapses of onychomycosis after successful treatment with systemic antifungals: a three-year follow-up. Dermatology. 1998;197(2):162–6.
Ko JY, Lee HE, Jae H, Oh DH, Kim JS, Yu HJ. Cure rate, duration required for complete cure and recurrence rate of onychomycosis according to clinical factors in Korean patients. Mycoses. 2011;54(5):e384–8.
Piraccini BM, Sisti A, Tosti A. Long-term follow-up of toenail onychomycosis caused by dermatophytes after successful treatment with systemic antifungal agents. J Am Acad Dermatol. 2010;62(3):411–4.
Elewski BE, Rich P, Tosti A, et al. Onchomycosis: an overview. J Drugs Dermatol. 2013;12(7):s96–s103.
Sigurgeirsson B, Steingrímsson O. Risk factors associated with onychomycosis. J Eur Acad Dermatol Venereol. 2004;18(1):48–51.
Ajello L, Getz ME. Recovery of dermatophytes from shoes and shower stalls. J Invest Dermatol. 1954;22(1):17–21; discussion, -4.
Broughton RH. Reinfection from socks and shoes in tinea pedis. Br J Dermatol. 1955;67(7):249–54.
Ghannoum MA, Isham N, Long L. Optimization of an infected shoe model for the evaluation of an ultraviolet shoe sanitizer device. J Am Podiatr Med Assoc. 2012;102(4):309–13.
Feuilhade de Chauvin M. A study on the decontamination of insoles colonized by Trichophyton rubrum: effect of terbinafine spray powder 1% and terbinafine spray solution 1%. J Eur Acad Dermatol Venereol. 2012;26(7):875–8.
Hammer TR, Mucha H, Hoefer D. Infection risk by dermatophytes during storage and after domestic laundry and their temperature-dependent inactivation. Mycopathologia. 2011;171(1):43–9.
Amichai B, Grunwald MH, Davidovici B, Farhi R, Shemer A. The effect of domestic laundry processes on fungal contamination of socks. Int J Dermatol. 2013;52:1392–4.
Gudnadóttir G, Hilmarsdóttir I, Sigurgeirsson B. Onychomycosis in Icelandic swimmers. Acta Derm Venereol. 1999;79(5):376–7.
Hilmarsdottir I, Haraldsson H, Sigurdardottir A, Sigurgeirsson B. Dermatophytes in a swimming pool facility: difference in dermatophyte load in men’s and women’s dressing rooms. Acta Derm Venereol. 2005;85(3):267–8.
Daniel CR, Jellinek NJ. Commentary: the illusory tinea unguium cure. J Am Acad Dermatol. 2010;62(3):415–7.
Gupta AK, Jain HC, Lynde CW, Watteel GN, Summerbell RC. Prevalence and epidemiology of unsuspected onychomycosis in patients visiting dermatologists’ offices in Ontario, Canada – a multicenter survey of 2001 patients. Int J Dermatol. 1997;36(10):783–7.
Sigurgeirsson B, Steingrímsson O, Sveinsdóttir S. Prevalence of onychomycosis in Iceland: a population-based study. Acta Derm Venereol. 2002;82(6):467–9.
Chiacchio ND, Suarez MV, Madeira CL, Loureiro WR. An observational and descriptive study of the epidemiology of and therapeutic approach to onychomycosis in dermatology offices in Brazil. An Bras Dermatol. 2013;88(Suppl 1):3–11.
Sigurgeirsson B, Baran R. The prevalence of onychomycosis in the global population: a literature study. J Eur Acad Dermatol Venereol. 2014;28(11):1480–91. https://doi.org/10.1111/jdv.12323. Epub 2013 Nov 28.
Buxton PK, Milne LJ, Prescott RJ, Proudfoot MC, Stuart FM. The prevalence of dermatophyte infection in well-controlled diabetics and the response to Trichophyton antigen. Br J Dermatol. 1996;134(5):900–3.
Al-Mutairi N, Eassa BI, Al-Rqobah DA. Clinical and mycologic characteristics of onychomycosis in diabetic patients. Acta Dermatovenerol Croat. 2010;18(2):84–91.
Gulcan A, Gulcan E, Oksuz S, Sahin I, Kaya D. Prevalence of toenail onychomycosis in patients with type 2 diabetes mellitus and evaluation of risk factors. J Am Podiatr Med Assoc. 2011;101(1):49–54.
Leelavathi M, Azimah MN, Kharuddin NF, Tzar MN. Prevalence of toenail onychomycosis among diabetics at a primary care facility in Malaysia. Southeast Asian J Trop Med Public Health. 2013;44(3):479–83.
Gupta AK, Lynde CW, Jain HC, et al. A higher prevalence of onychomycosis in psoriatics compared with non-psoriatics: a multicentre study. Br J Dermatol. 1997;136(5):786–9.
Güleç AT, Demirbilek M, Seçkin D, et al. Superficial fungal infections in 102 renal transplant recipients: a case-control study. J Am Acad Dermatol. 2003;49(2):187–92.
Moreno-Coutiño G, Arenas R, Reyes-Terán G. Clinical presentation of onychomycosis in hiv/aids: a review of 280 mexican cases. Indian J Dermatol. 2011;56(1):120–1.
Gregory N. Special patient populations: onychomycosis in the HIV-positive patient. J Am Acad Dermatol. 1996;35(3 Pt 2):S13–6.
Rodwell GEJ, Bayles CL, Towersey L, Aly R. The prevalence of dermatophyte infection in patients infected with human immunodeficiency virus. Int J Dermatol. 2008;47(4):339–43.
Ozkan F, Ozturk P, Ozyurt K, et al. Frequency of peripheral arterial disease and venous insufficiency in toenail onychomycosis. J Dermatol. 2013;40(2):107–10.
Kulac M, Acar M, Karaca S, et al. Venous insufficiency in patients with toenail onychomycosis. J Ultrasound Med. 2005;24(8):1085–9.
Gupta AK, Gupta MA, Summerbell RC, et al. The epidemiology of onychomycosis: possible role of smoking and peripheral arterial disease. J Eur Acad Dermatol Venereol. 2000;14(6):466–9.
English MP. Trichophyton rubrum infection in families. Br Med J. 1957;1(5021):744.
Ghannoum MA, Mukherjee PK, Warshaw EM, Evans S, Korman NJ, Tavakkol A. Molecular analysis of dermatophytes suggests spread of infection among household members. Cutis. 2013;91(5):237–45.
Gupta AK, Sibbald RG, Lynde CW, et al. Onychomycosis in children: prevalence and treatment strategies. J Am Acad Dermatol. 1997;36(3 Pt 1):395–402.
Zaias N, Tosti A, Rebell G, et al. Autosomal dominant pattern of distal subungual onychomycosis caused by Trichophyton rubrum. J Am Acad Dermatol. 1996;34(2 Pt 1):302–4.
Pickup TL, Adams BB. Prevalence of tinea pedis in professional and college soccer players versus non-athletes. Clin J Sport Med. 2007;17(1):52–4.
Chan MKT, Chong L-Y, Achilles Project Working Group in Hong Kong. A prospective epidemiologic survey on the prevalence of foot disease in Hong Kong. J Am Podiatr Med Assoc. 2002;92(8):450–6.
Caputo R, De Boulle K, Del Rosso J, Nowicki R. Prevalence of superficial fungal infections among sports-active individuals: results from the Achilles survey, a review of the literature. J Eur Acad Dermatol Venereol. 2001;15(4):312–6.
Gazes MI, Zeichner J. Onychomycosis in close quarter living review of the literature. Mycoses. 2013;56:610–3.
El Fekih N, Belghith I, Trabelsi S, Skhiri-Aounallah H, Khaled S, Fazaa B. Epidemiological and etiological study of foot mycosis in Tunisia. Actas Dermosifiliogr. 2012;103(6):520–4.
Jang KA, Chi DH, Choi JH, Sung KJ, Moon KC, Koh JK. Tinea pedis in Korean children. Int J Dermatol. 2000;39(1):25–7.
Fletcher CL, Hay RJ, Smeeton NC. Onychomycosis: the development of a clinical diagnostic aid for toenail disease. Part I. Establishing discriminating historical and clinical features. Br J Dermatol. 2004;150(4):701–5.
Walling HW. Subclinical onychomycosis is associated with tinea pedis. Br J Dermatol. 2009;161(4):746–9.
Gupta AK, Ryder JE. How to improve cure rates for the management of onychomycosis. Dermatol Clin. 2003;21(3):499–505. vii.
Gupta AK, Lynde CW, Konnikov N. Single-blind, randomized, prospective study of sequential itraconazole and terbinafine pulse compared with terbinafine pulse for the treatment of toenail onychomycosis. J Am Acad Dermatol. 2001;44(3):485–91.
Watson A, Marley J, Ellis D, Williams T. Terbinafine in onychomycosis of the toenail: a novel treatment protocol. J Am Acad Dermatol. 1995;33(5 Pt 1):775–9.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
12.1 Electronic Supplementary Materials
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG, part of Springer Nature
About this chapter
Cite this chapter
Sigurgeirsson, B. (2018). Systemic Therapy of Onychomycosis. In: Rubin, A.I., Jellinek, N.J., Daniel, C.R., Scher, R.K. (eds) Scher and Daniel’s Nails. Springer, Cham. https://doi.org/10.1007/978-3-319-65649-6_12
Download citation
DOI: https://doi.org/10.1007/978-3-319-65649-6_12
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-65647-2
Online ISBN: 978-3-319-65649-6
eBook Packages: MedicineMedicine (R0)