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Kruithoff, C.; Gamal, A.; Mccormick, T.S.; Ghannoum, M.A. Dermatophyte Infections Worldwide. Encyclopedia. Available online: https://encyclopedia.pub/entry/53391 (accessed on 17 November 2024).
Kruithoff C, Gamal A, Mccormick TS, Ghannoum MA. Dermatophyte Infections Worldwide. Encyclopedia. Available at: https://encyclopedia.pub/entry/53391. Accessed November 17, 2024.
Kruithoff, Caroline, Ahmed Gamal, Thomas S. Mccormick, Mahmoud A. Ghannoum. "Dermatophyte Infections Worldwide" Encyclopedia, https://encyclopedia.pub/entry/53391 (accessed November 17, 2024).
Kruithoff, C., Gamal, A., Mccormick, T.S., & Ghannoum, M.A. (2024, January 03). Dermatophyte Infections Worldwide. In Encyclopedia. https://encyclopedia.pub/entry/53391
Kruithoff, Caroline, et al. "Dermatophyte Infections Worldwide." Encyclopedia. Web. 03 January, 2024.
Dermatophyte Infections Worldwide
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This entry is adapted from the peer-reviewed paper 10.3390/life14010001

The increase in the incidence of superficial fungal infections combined with the emergence of antifungal resistance represents both a global health challenge and a considerable economic burden. Dermatophytes, the main culprit causing superficial fungal infections, have started to exhibit antifungal resistance. This can be observed in some of the most common species, such as Trichophyton rubrum and Trichophyton mentagrophytes. Importantly, the new subspecies, known as Trichophyton indotineae, has been reported to show high resistance to terbinafine, a first-line treatment for dermatophyte infections. Compounding these issues is the realization that diagnosing the causative infectious agents requires using molecular analysis that goes beyond the conventional macroscopic and microscopic methods. 

incidence terbinafine dermatophytes trichophyton

1. Introduction

Superficial fungal infections (SFIs) affect approximately 20 to 25 percent of the global population [1]. They can result in a myriad of dermatologic clinical presentations depending on both the organism involved and the area of the body affected [1]. Factors such as age, gender, and geographical location play an important role in the prevalence of these infections [2]. In a 2004 study in partnership with the American Academy of Dermatology, the prevalence of SFIs was reported to be 29.4 million cases. Between 1995 and 2004, there have been approximately 51 million patient visits for these infections [3][4]. Furthermore, between the years of 2005 and 2014, dermatophyte infections were responsible for 4,981,444 outpatient visits in the United States, as reported by the Centers for Disease Control and Prevention (CDC). Moreover, the direct medical cost caused by these infections was approximately USD 845 million dollars in 2019. The worldwide increased incidence of fungal infections and the growing trend of resistant organisms have attracted global concern [5][6].

2. Epidemiology of Dermatophyte Infections

Dermatophytes are the most prevalent pathogenic fungi in the United States and among the most common causes of skin diseases worldwide [7]. Dermatophytes can be classified based on their habitat into anthrophilic (growing on humans), zoophilic (growing on animals), and geophilic (growing in soil) [8]. They belong to seven clades from A to G: clade A contains the Trichophyton species, clade B contains Epidermophyton floccosum species, and clades C and F contain the Microsporum species [9][10]. There are over 40 species of dermatophytes known to infect humans, primarily causing SFIs [11]. As a keratinophilic fungus (i.e., exhibiting affinity to keratin), dermatophytes infect the keratin structures of the skin, hair, and nails, resulting in an inflammatory host response and clinical conditions known as tinea [12]. These dermatophytes can also colonize human hosts without causing disease [11]. While the prevalence of dermatophyte species varies across different regions of the world, Trichophyton rubrum is responsible for the majority of dermatophyte-associated infections reported [11][12].
As dermatophytes thrive in hot, humid environments, many tropical and developing countries are facing an increase in dermatophyte infections [5]. Specifically, India has encountered an enormous challenge due to an alarming increase in the number of chronic and recurrent dermatophyte infections. The tropical and subtropical climate of the country is particularly favorable for dermatophytes [13]. Furthermore, overcrowding, shared living spaces, and urbanization are all contributing factors to the increasing prevalence of dermatophytosis [14]. In addition to the rapidly rising rate of infection, treatment efficacy has been suboptimal due to a lack of antifungal stewardship in clinical practice [15]. Importantly, it is essential to consider non-dermatophyte molds as causative organisms as well, especially in treatment-resistant conditions. These molds are commonly found in African and Asian countries, as well as the Caribbean islands, Central America, South America, and parts of the United States [16]. T. mentagrophytes has been reported to be the most common cause of tinea infection in India, followed by T. rubrum and T. interdigitale [14]. While in North America and Europe, T. rubrum is the most common dermatophyte pathogen implicated in tinea, closely followed by T. interdigitale [17].
T. rubrum has been reported to be the main cause of chronic dermatophytosis infection [18]. A reason for this could be the uncontrolled use of antifungal medications, which can result in selective pressure, allowing a resistant strain to prevail within a population. In one study, T. rubrum was shown to develop resistance to fluconazole and itraconazole upon prolonged drug exposure. Analysis of minimum inhibitory concentration (MIC) values confirmed the inclination of T. rubrum to acquire resistance against fluconazole when compared with itraconazole. This research also reported patterns of cross-resistance between these two azole antifungals. The underlying mechanisms that can contribute to the development of T. rubrum resistance include increased drug efflux, decreased drug uptake, structural target site modifications, and the production of biofilms [19].
T. tonsurans, on the other hand, was initially native to Southeast Asia and Australia but quickly expanded to the rest of the world through colonization, migration, and sports-related travel. T. tonsurans can live on household items and easily transmit infections through shared objects [20]. Interestingly, the prevalence of T. tonsurans is now increasing worldwide. In the United States, T. tonsurans is the primary cause of tinea capitis [21]. Additionally, in Germany, there is presently an increasing prevalence of tinea capitis caused by T. tonsurans and fellow anthropophilic pathogens T. violaceum and T. soudanense [22]. One possible explanation for this is the inadequate treatment of infections such as tinea capitis. For example, using griseofulvin, which is more effective at inhibiting Microsporum spp. than Trichophyton spp., in management of such cases may result in treatment failure, chronicity, and spread of infection [23].

3. Clinical Perspectives of Tinea

From a clinical perspective, dermatophyte infection, known as tinea, is further classified based on the anatomical region of the body affected (Table 1) [6]. Additionally, tinea infections can be transmitted from both humans and pets [24]. T. tonsurans and Microsporum canis are mainly known to cause tinea capitis infections [11]. Furthermore, tinea corporis (ringworm) is most commonly caused by T. rubrum, T. mentagrophytes, and T. tonsurans [25]. Tinea corporis can also be caused by contact with infected pets, though the most common causative organism in this scenario is M. canis [24]. T. rubrum is the most common cause of tinea cruris (jock itch) around the globe, though T. mentagrophytes infections have been increasing in certain areas [26][27][28]. Trichophyton organisms have been found to affect male and female children equally. However, M. canis more commonly affects males [24].
Table 1. Clinical classification of tinea infections [29].
Tinea Infection Body Area Affected Most Common
Causative Pathogens
Tinea Capitis Head and scalp T. tonsurans,
Microsporum canis [11]
Tinea Corporis Trunk and extremities T. rubrum, T. mentagrophytes,
T. tonsurans [25]
Tinea Cruris Groin, pubic region,
intertriginous anogenital region		 T. rubrum,
T. mentagrophytes [26][27][28]
Tinea Faciei Face T. rubrum,
T. mentagrophytes [30][31]
Tinea Barbae Beard and mustache area T. verrucosum, T. rubrum,
T. mentagrophytes [32]
Tinea Manuum Hands T. rubrum [33]
Tinea Pedis Feet T. rubrum, T. mentagrophytes, Epidermophyton floccosum [18][34][35][36]
Onychomycosis
(Tinea Unguium)		 Nails T. rubrum,
T. mentagrophytes [37][38]
Similarly, onychomycosis is commonly caused by dermatophytes (60–70% of the cases) and less commonly by other non-dermatophytes (mold and yeast). Several studies have shown that the majority of onychomycosis cases are caused by T. rubrum, followed by T. mentagrophytes [37][38]. Interestingly, in a study conducted in Iran that included 1284 microscopically positive onychomycosis cases, the main causative organism was Candida albicans. This was followed by Trichophyton interdigital and Aspergillus flavus. This may suggest a regional factor that can affect the prevalence of this type of infection [39].
The socioeconomic status of individual countries was reported to have an impact on the type of dermatophyte infection encountered in clinical practice. For example, tinea capitis is more prevalent in developing countries, while the prevalence of tinea pedis and onychomycosis is higher in developed countries [40]. Tinea pedis is a common fungal infection seen worldwide, with the most prevalent dermatophytes isolated in these cases being T. rubrum, T. mentagrophytes, and Epidermophyton floccosum [18][34][35][36]. This infection has been growing over recent years, yet the underlying pathogenesis is not definitively known [41][42]. However, tinea pedis was shown to be more prevalent in the adult-aged population, especially in males [34][35]. While tinea pedis and onychomycosis are prevalent around the globe, these infections are less common in India and rural Africa [36].
In the United States and the United Kingdom, T. tonsurans is the most common causative organism of tinea capitis infection [43][44]. Additionally, T. tonsurans can cause a type of tinea corporis infection known as tinea gladiatorum, which is common in athletes participating in direct contact sports, such as wrestlers. The average prevalence of tinea gladiatorum among wrestlers in the United States, Iran, and Turkey is 34.29% [20].

4. Standard Treatment of Tinea Infections and Current Limitations

The standard treatment of tinea infections is largely topical with azoles or allylamines. Tinea capitis and onychomycosis are more difficult to treat and typically require systemic oral therapy. Systemic therapy may also be utilized in chronic, refractory, or severe tinea infections (Table 2).
Table 2. Clinical viewpoints: systemic and local therapies for tinea infections.
Tinea Infection Systemic Therapy Local Therapy
Tinea Capitis
[24]		 Terbinafine or Griseofulvin. If kerion is present, add steroids. Not recommended. Itraconazole or Fluconazole may be used in some cases.
Tinea Corporis
[45][46]		 Indicated for severe infection caused by T. rubrum. Terbinafine, Itraconazole, Fluconazole, or Griseofulvin. Terbinafine is indicated for Majocchi Granuloma. Azoles or Allylamines
Tinea Cruris
[27][47]		 Indicated for chronic or recurrent infection. Terbinafine, Itraconazole, or Fluconazole. Azoles or Allylamines
Tinea Faciei
[30][48]		 Indicated for severe or refractory infection or involvement of vellus hair Azoles or Allylamines
Tinea Barbae
[32]		 Terbinafine, Itraconazole,
Fluconazole, or Ketoconazole		 Azoles or Allylamines as adjunct therapy
Tinea Manuum
[33][49][50]		 Indicated for co-infection of the nail, two feet-one hand syndrome, and chronic or recurrent infection. Terbinafine or Itraconazole may be effective. Azoles or Allylamines
Tinea Pedis
[6][50][51][52][53]		 Indicated for treatment-resistant infection. Terbinafine, Itraconazole, Fluconazole, Ketoconazole, or Griseofulvin. Indicated for uncomplicated or mild interdigital infection. Azoles or Allylamines. Luliconazole or Naftifine may be used for interdigital infection. Initial treatment with topical corticosteroids may be beneficial.
Onychomycosis
(Tinea Unguium)
[54][55][56][57][58][59]		 Indicated for moderate to severe infection. Terbinafine or Itraconazole. Avoid Griseofulvin (lower efficacy) and Ketoconazole (hepatotoxicity). Indicated for mild to moderate infection. Efinaconazole, Ciclopirox, or Amorolfine.
Medications that are commonly used to treat infections caused by T. rubrum include terbinafine, itraconazole, amorolfine, and ciclopirox [60]. Terbinafine, available as both a topical and oral medication, has long been a standard drug of choice for the treatment of tinea infections [61]. The topical form is available as terbinafine 1% cream and is used as the first-line treatment for most tinea corporis, tinea cruris, and tinea pedis infections [6]. On the other hand, oral therapy is mainly used for more resistant conditions, such as tinea capitis and onychomycosis, or for areas of extensive skin infection. This is especially true for patients who fail topical therapy or are immunocompromised [62]. In adults, oral terbinafine 250 mg once daily is the recommended first-line treatment for onychomycosis. Itraconazole and fluconazole, available as oral medications, are other alternatives used as second-line agents for conditions that require systemic treatment [6].
In a Cochrane review conducted in 2017, comparing a terbinafine treatment group to an azole treatment group, terbinafine was shown to be more effective at treating onychomycosis compared with azoles. Additionally, both groups had similar adverse reactions of headache, nausea, and viral infection [63]. For terbinafine, the side effects that are commonly observed include GI disturbance, headache, and taste alteration [64]. Hepatotoxicity, while rare, is a potentially life-threatening complication of both terbinafine and itraconazole [64][65]. Beside the above complications, drug-drug interactions may influence serum itraconazole levels and must be acknowledged before prescribing the medication [66].
The FDA has only approved oral terbinafine and itraconazole for the treatment of onychomycosis. However, fluconazole is also used as an off-label alternative treatment for onychomycosis. Pulse-dosing regimens and booster therapy may also be utilized in the treatment approach, particularly with itraconazole. On the other hand, for topical treatments, only ciclopirox 8% nail lacquer, efinaconazole 10% solution, and tavaborole 5% solution have been approved by the FDA for management of onychomycosis [67].

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Subjects: Infectious Diseases; Dermatology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Caroline Kruithoff
,
Ahmed Gamal
,
Thomas S. McCormick
,
Mahmoud A. Ghannoum
View Times: 382
Revisions: 3 times (View History)
Update Date: 09 Jan 2024
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