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  • REVIEW ARTICLE

    Toenail onychomycosis: an important global diseaseburden

    J. Thomas* BPharm MPharmSc, G. A. Jacobson* BPharm (Hons) PhD, C. K. Narkowicz* BSc(Hons) PhD, G. M. Peterson* BPharm (Hons) PhD MBA FSHP FACP AACPA MPS, H. BurnetDip App Sc (Pod) and C. Sharpe BPod*School of Pharmacy, University of Tasmania, Hobart, Tasmania and Department of Podiatry, RoyalHobart Hospital, Hobart, Tasmania, Australia

    SUMMARY

    Onychomycosis is a fungal infection of the nail

    plate or nail bed. It does not usually cure itself

    and it can trigger more infectious lesions in other

    parts of the body. The reported prevalence of

    onychomycosis is increasing in Western coun-

    tries, presumably due to lifestyle changes and the

    ageing of the population. Approximately 10% of

    the general population, 20% of the population

    aged >60 years, up to 50% of people aged

    >70 years and up to one-third of diabetic indi-

    viduals have onychomycosis. Care should be

    taken for the accurate diagnosis and timely

    treatment of toenail onychomycosis to prevent

    complications. Current treatment options have

    relatively limited therapeutic success, particularly

    long-term. Oral medications are associated with

    high recurrence rates and treatment failure, and

    are not suitable for many cases due to potential

    adverse effects. Topical medications are recom-

    mended only for mild to moderate cases. The cost

    of therapies may also be prohibitive in some

    cases. In the light of these issues, more research is

    warranted for the investigation and development

    of more effective and economical options for the

    treatment and prophylaxis of toenail onychomy-

    cosis. In patient populations such as diabetic

    individuals, where onychomycosis can provoke

    lower extremity complications, professional

    podiatry care of toenails and feet should be

    encouraged.

    Keywords: dermatophytes, diagnosis, epidemiol-

    ogy, onychomycosis, toenail, treatment

    INTRODUCTION

    Onychomycosis is a fungal infection of the nail

    plate or nail bed, leading to the gradual destruction

    of the nail plate. Onychomycosis has been referred

    to as the most prevalent of the nail ailments and

    accounts for about 50% of all diseased nails and

    about 30% of cutaneous fungal infections (1). It is

    caused by dermatophytes, yeasts or non-dermato-

    phytic moulds (2). The dermatophytes Trichophyton

    rubrum and Trichophyton mentagrophytes are the

    main causative pathogens, responsible for 8090%

    of cases (36). Non-dermatophytic fungi such as

    Acremonium spp., Alternaria spp., Aspergillus spp.,

    Fusarium spp., Scytalidium spp. and Scopulariopsis

    spp. have been found to be involved in 211% of

    the onychomycosis cases reported. Yeasts, inclu-

    ding Candida spp., account for 210% of fungal nail

    infections (5, 711). Dermatophytes are normally

    transmitted through infected moist floor areas and

    are less often transmitted via direct personal con-

    tact. Non-dermatophytic fungi have been fre-

    quently associated with the infection of

    traumatized nails in aged patients (11).

    Onychomycosis is associated with less noticeable

    symptoms than foot ulceration due to tinea pedis,

    and is often considered a cosmetic problem and

    overlooked (12). Tinea pedis can lead to onycho-

    mycosis and has been associated with onychomy-

    cosis in 3059% of cases (13, 14). The secondary

    spread of fungal organisms may lead to the infec-

    tion of web spaces, toes, nail plates, sole, heel and

    across the whole foot (14, 15).

    Received 18 May 2009, Accepted 18 May 2009

    Correspondence: J. Thomas, School of Pharmacy, University of

    Tasmania, Private Bag 26, Hobart, Tasmania, 7001, Australia.

    Tel.: +61 (3) 6226 1069; fax: +61 (3) 6226 2870; e-mail: jackson.

    thomas@utas.edu.au

    Journal of Clinical Pharmacy and Therapeutics (2010) 35, 497519 doi:10.1111/j.1365-2710.2009.01107.x

    2010 The Authors. JCPT 2010 Blackwell Publishing Ltd 497

  • HISTORY OF ONYCHOMYCOSIS

    In 1853, onychomycosis was first described and

    reported by Meissner, a German medical student

    (16). The history of onychomycosis is analogous to

    that of T. rubrum, the major causative fungal

    pathogen involved in the pathogenesis of onycho-

    mycosis and tinea pedis (17). T. rubrum was until

    recently, limited to Southeast Asia, Indonesia,

    Northern Australia and West Africa (18). People

    living in these regions are reported to have suffered

    from chronic tinea corporis; however, tinea pedis

    was not found among them. This was presumably

    due to the lack of footwear among the local pop-

    ulation (17, 18). However, the use of occlusive

    footwear by European colonists and soldiers

    provided a highly favourable environment for

    T. rubrum to grow and cause pedal fungal infec-

    tions (17, 18).

    The incidence of tinea pedis was rare in Europe,

    before the arrival of T. rubrum. Increased popula-

    tion mobility that resulted from world wars, mass

    migration and recreational travel led to the trans-

    location and subsequent distribution of T. rubrum

    from its original endemic regions to new ecological

    environments in Europe and America (17, 19). The

    first reported clinical case of tinea pedis in the

    United States was encountered soon after World

    War I. In the same country, the first documented

    case of onychomycosis is said to have been repor-

    ted in 1928 (17, 20). World War II and the Korean

    and Vietnam wars, increased participation in fit-

    ness activities, the use of occlusive footwear and

    periodic and migratory movement of populations,

    have contributed towards the increased prevalence

    of tinea pedis and onychomycosis in the 20th cen-

    tury (21). After the Vietnam War, T. rubrum sur-

    passed T. mentagrophytes as the most commonly

    isolated dermatophyte worldwide (21). In the

    United States, it has been found that dermatophytic

    fungi can be isolated from the plantar surface in

    about 70% of the population (18, 22).

    EPIDEMIOLOGY

    In post-industrialized countries, more than 10% of

    the general population is reported to have ony-

    chomycosis (23). A few other studies reported a

    similar prevalence for onychomycosis worldwide;

    a Finnish study (n = 800) reported a prevalence of

    84% and two large Canadian studies (n = 2001;n = 15 000) reported a prevalence ranging from

    65% to 91% for onychomycosis (2426). Manyauthors believed that onychomycosis started as an

    insignificant medical problem (27, 28). It has been

    suggested that the prevalence of onychomycosis

    has steadily increased over the past few decades

    (17, 27, 28). Results from several population studies

    support this. A 1979 United States study

    (n = 20 000) reported the overall prevalence of

    onychomycosis to be 218% (29). A United Statesstudy in 1997 (n = 1038) revealed a much higher

    prevalence of onychomycosis (87%) (30) and alarge-scale multicentre North American study

    published in 2000 (n = 1832) estimated the preva-

    lence of onychomycosis to be 138% (31).An Indonesian study has demonstrated a similar

    pattern: the study concluded that the average

    incidence of onychomycosis has increased from

    35% in 19971998 to 47% in 2003 (32). A survey(Achilles project, 1999) conducted among the

    general population visiting physicians in Europe

    (Belgium, Netherlands, Luxembourg, Switzerland,

    Hungary, Great Britain, Poland) (n = 22 760) and in

    East Asia (China, South Korea, Taiwan)

    (n = 43 914) demonstrated a substantial onycho-

    mycosis prevalence of 26% and 22%, respectively.

    The Achilles project concluded that 2 out of 10

    patients of the studied population showed signs of

    onychomycosis (33).

    RISK FACTORS

    A summary of various predisposing factors for

    onychomycosis is given in Table 1.

    Age and gender

    Onychomycosis is reported to be more prevalent in

    the elderly and appears to occur more frequently in

    males (21, 30, 31). Early studies have shown that

    there is a correlation between age and onychomy-

    cosis. Approximately 20% of the population aged

    >60 years and up to 50% of the subjects aged

    >70 years are reported to have onychomycosis (5,

    20). The correlation between increasing age and

    onychomycosis may be attributed to reduced

    peripheral circulation, inactivity, suboptimal

    immune status, diabetes, larger and distorted nail

    surfaces, slower growing nails, difficulty in

    2010 The Authors. JCPT 2010 Blackwell Publishing Ltd, Journal of Clinical Pharmacy and Therapeutics, 35, 497519

    498 J. Thomas et al.

  • grooming the nails and maintaining foot hygiene,

    frequent nail injury and increased exposure to

    disease-causing fungi (2, 5, 11, 34).

    Gupta and colleagues postulated that the gender

    difference may be attributable to the differences in

    hormone levels (progesterone and other related

    hormones) that result in a different capacity to

    inhibit the growth of dermatophytes (24, 35, 36).

    Increased use of occlusive footwear and nail inju-

    ries may also contribute to the higher incidence of

    onychomycosis in males (37). Onychomycosis is

    seen in only a small proportion (approximately

    04%) of children (1, 38). The lower prevalence ofonychomycosis in children compared to adults

    may be due to r