Dermatophytoses

Dermatophytoses

Peiying Feng1, Macit Ilkit2, Ruoyu Li3, Murat Durdu4, Kyung Jo Kwon-Chung5 and Sybren de Hoog6

1Department of Dermatology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China; 2Division of Mycology, University of Çukurova, Adana, Türkiye; 3Department of Dermatology and Venereology, Peking University First Hospital, Beijing, China; 4Department of Dermatology, Dr. Turgut Noyan Application and Research Center, Başkent University, Adana, Türkiye; 5Laboratory of Clinical Immunology and Microbiology, National Institutes of Health, Bethesda, MD, U.S.A.; 6Radboudumc-CWZ Centre of Expertise for Mycology, Nijmegen, The Netherlands

Latest update: 4 July 2024

Introduction

Dermatophytoses are infections of keratinized tissues of epidermis, hair, and nails, caused by a group of specialized fungi, the dermatophytes. This group includes fungi in the family Arthrodermataceae (order Onygenales) with different types of mammal association. All these genera are referred to as dermatophytes, even though in some of them an infection of a warm-blooded host occurs only exceptionally. With this definition, members of recognized dermatophytes are found in the genera Arthroderma, Epidermophyton, Lophophyton, Microsporum, Nannizzia, Paraphyton and Trichophyton (de Hoog et al., 2017). The infectious potential differs significantly between species. The recommended collective disease name to indicate dermatophyte infections is ‘dermatophytosis’ (de Hoog et al., 2024) rather than dermatomycosis, because the latter would also cover agents of skin infection outside the Arthrodermataceae. An older name is ‘ringworm’, which was coined to describe the circular lesion produced by dermatophytes on the skin (Leung et al., 2020).

Infected hosts are mainly mammals. Among the approximately 60 species of clinically relevant dermatophytes, only Lophophyton gallinae has repeatedly been associated with infections involving the skin and wattles rather than the plumage in birds (Yamaguchi, 2019; Murata et al., 2013Miyasato et al., 2011). In furred animals, the presence of dermatophytes is often limited to fur colonization and hair invasion. The human host differs rather fundamentally because it lacks a dense fur, and fungal growth consequently often involves the glabrous skin. Human infections are mild to severe, depending on specific virulence and on the immunological response of the host. Subcutaneous or deep infections are mostly associated with dysfunctional acquired cellular immunity.

Ecology, transmission and evolution

Dermatophytes are divided into three approximate ecological groups: geophilic, zoophilic and anthropophilic, depending on their natural lifestyle, i.e., their life cycle in their environment versus mammalian habitats. Among the main traits, the three types follow one another in the evolutionary history, thus the genera broadly match these concepts. The combination of ecology, phylogeny and medical significance has led to a more stable taxonomic system (de Hoog et al., 2017) than the previously used generic circumscriptions, which were based solely on microscopic morphology. Humans have played a significant role in this evolutionary history, since geophilic dermatophytes reside in natural habitats, zoophilic dermatophytes are particularly common among domesticated animals, and anthropophilic dermatophytes are adapted to Homo sapiens.

Geophilic dermatophytes

Similar to the numerous members of the order Onygenales, geophilic dermatophytes live in soil. Their unique source of nutrients comprises degradation of keratinous remains of terrestrial animals. As a consequence, members of Arthrodermataceae are commonly found in mammal burrows and shelters. An elaborate sexual state is produced in the adjacent soil. Since sexuality is part of the natural life cycle, mating and ascospore production are common. Additionally, in vitro, such species easily produce sexual fruitbodies. The genus Arthroderma contains numerous geophilic species for which a sexual state is known. The conidia are distributed asymptomatically in the fur of the animals inhabiting the burrows; in general, the terrestrial animals are not infected. Human infection is extremely rare in most geophilic species, due to absence of contact with contaminated soil or the inhabiting mammal. Knowledge of these fungi is limited, but a certain degree of host-specificity likely occurs, which is determined by the animal habitat. For example, Arthroderma redellii is associated with bats (Lorch et al., 2015), and A. eboreum with badgers and rabbits (Campbell et al., 2006), both of which are burrow-building animals. Not all dermatophytes are unambiguously classified in one of the ecological categories. For example, Nannizzia gypsea is traditionally treated as a geophilic species, but this species is also frequently reported to cause human infections. The occasional case reports mention infection directly from soil rather than from an animal carrying the fungus (Alsop & Prior 1961). Dogs with an outdoor access, especially in rural areas, are exposed to geophilic species, such as Nannizzia gypsea. The fungi are easily transmitted to humans (Chermette et al., 2008Moriello et al., 2017) through direct contact with the hair coat of the infected animals.

Diagram of hypothetical life cycles of dermatophytes. A. Geophilic dermatophyte. Clonal distribution via conidia in fur of terrestrial animals, sexuality with fruitbody production in soil. Infections in humans are very rare. B. Zoophilic dermatophyte. With respect to domesticated animals, the sexual cycle in soil is mostly interrupted. Host shifts to other domesticated animals occur, and human infection is common but usually does not lead to transmission. C. Anthropophilic dermatophyte. Sexual cycle is impossible, direct transmission via contagious humans, potentially leading to epidemics.

Zoophilic dermatophytes

Animal domestication, creating the novelty of farm and pet animals, has led to interruption of the alternating sexual-clonal lifecycle of the previously geophilic dermatophytes, leading to a preponderance of the asexual form of propagation with conidia being carried in animal fur. Under these conditions, there is much more contact between animal species, which is unlikely to occur in nature. Infection of a non-preferred host often leads to inflammatory infections (Weitzman & Summerbell, 1995), but with repeated events the fungus is able to adapt to the new host, known as a host shift, which is accompanied by a decrease in virulence (Chollet et al., 2015). A shift in the importance of preponderantly innate to more efficient acquired cellular immunity has been noted; for a review, see Deng et al. (2023). Host shifts from several animal hosts to humans have taken place, which has led to a large number of species adapted to Homo sapiens; the human host is unique in carrying a large number of adapted species, known as the anthropophilic dermatophytes. These evolutionary events include Microsporum canis (from cat) to M. ferrugineum (Zhou et al., 2023), Trichophyton benhamiae (from guinea pig) to T. concentricum (Pihet et al., 2008), and Trichophyton equinum (from horse) to T. tonsurans (Kandemir et al., 2020). New adaptations are expected with new animals being introduced in close proximity to humans.

Zoophilic dermatophytes are also known in non-terrestrial wild animals, such as Trichophyton simii in monkeys (Boehringer et al., 1999). Human infections by this species originated from infected monkeys (Krajden et al., 2022). Trichophyton mentagrophytes caused infections among American troops in Vietnam, and the source of this outbreak was traced to the rats trapped near the army living quarters (Allen & Taplin, 1973). The majority of classic zoophilic dermatophytes have been reported to infect farm animals, and human infections from these animals are frequent. Trichophyton verrucosum is prevalent in cattle (Łagowski et al., 2019), and also T. mentagrophytes is common in ruminants (Dalis et al., 2022); T. bullosum is found in horses (Lyskova et al., 2015). Farmers and members of their families who handle cattle frequently acquire Trichophyton verrucosum infection from infected animals (Papini et al., 2008) or from troughs and stalls used by infected animals. Sources of human infection due to Lophophyton gallinae (Yamaguchi, 2019) and Nannizzia nana (Bonifaz et al., 2019) have been shown to be chickens and pigs, respectively.

Under urban conditions, pet animals are a main source of human infections by dermatophytes (Paryuni et al., 2020), with Microsporum canis being the most prevalent species (Neves et al., 2018). Infections transmitted from rodents with a dense fur, such as guinea pigs, mostly belong to the Trichophyton benhamiae complex. Recently, novel popular pets such as the African pygmee hedgehog were infected by Trichophyton erinacei (Walsh et al., 2021). In animals, non-inflammatory arthroconidia often form a thick layer around infected animal hair shafts but without cutaneous involvement.

Anthropophilic dermatophytes

A small number of dermatophytes are nearly exclusively found on humans. Propagules are shed in the domestic environment, but assimilative growth of the fungus occurs only after infection. Transmission proceeds from infected hosts which are contagious. Anthropophilic species are not or are rarely found on domesticated animals, but most likely have their evolutionary origin in these animals. Throughout history, humans have enlarged the spectrum of tamed animals in their close vicinity, and as a result the human host carries an exceptionally large number of adapted dermatophytes. Trichophyton concentricum possibly emerged from T. benhamiae (Čmoková et al., 2020), T. tonsurans from T. equinum (Kandemir et al., 2020), T. interdigitale from T. mentagrophytes (Tang et al., 2021), and Microsporum ferrugineum from M. canis (Zhou et al., 2023). For T. rubrum and allies and for T. schoenleinii, no ancestral species are known.

Infections are transmitted indirectly through fallen hairs and desquamated epithelium more often than through direct bodily contact. Use of contaminated barbershop instruments, combs, hairbrushes, and hats is a common method of transmission (Winge et al., 2009). Presence of infectious propagules has also been reported in clothing (Jazdarehee et al., 2022). Infections can also be transmitted by contact with contaminated bedding and seats or other furniture (Kane et al., 1988; Ilkit et al., 2010). Evidence indicates that infections due to anthropophilic dermatophytes can be transmitted by shared towels or clothing even after domestic laundry (Hammer et al., 2011). Transmission within families is common (Tuknayat et al., 2020). A major source of tinea pedis is the contaminated floors of homes or public bathing facilities (Makhdoumi et al., 2021). The incidence of species such as Trichophyton rubrum and T. interdigitale dramatically increased in developed countries after public bathing facilities for sport activities became available (Lacroix et al., 2002; Shemer et al., 2016). Direct personal contact as the means of transmission also occurs; a well-known example is transmission of T. tonsurans with wrestling (Wang et al., 2023). Trichophyton concentricum is transmitted from diseased mother to child soon after birth. Malnutrition (Schofield et al., 1963) and genetic predisposition influencing skin microbiota (Er et al., 2022) also plays a role (Gnat et al., 2021). CARD9-related immunodeficiency frequently leads to severe dermatophytosis (Lanternier et al., 2013; Ansai et al., 2024).

Clinical manifestations

Dermatophytes not only affect the entire skin from head to toe, but also skin appendages such as nails and hair. Skin involvement may be localized to a certain anatomical area on the body or can spread throughout the body. While dermatophytes generally cause superficial infections affecting the horny layer of the skin, they can spread to the dermis and deeper tissues in immunosuppressed patients or due to external or metabolic factors.

Characteristic features of superficial dermatophyte infections according to their location.

Hair invasion

Mammal hair can be affected by dermatophyte growth in different ways (Tang et al., 2023). In humans, hair invasion frequently accompanies tinea capitis, where damage is macroscopically visible by short, broken hairs. Two basic types can be recognized, which can be visualized with potassium hydroxide (KOH) and cytologic stains:
Ectothrix. Hyphae are formed at the outside of the hairs, breaking up into small (2-3 µm) cubical to spherical arthroconidia which are clumped around the damaged region of the hair shaft. The hair cortex is mostly swollen and damaged, and broken hairs terminate with a loose, broom-like appearance. Potassium hydroxide (KOH) digestion is required to dissolve excessive keratin and cytologic staining for visualization. Breakage is a few millimeters above the hair follicle, leading to the clinical picture known as ‘gray patch‘ (Aritonang et al., 2022).
Main causative agent: Microsporum canis.
Endothrix. Fungal cells invade the hair shaft and eventually fill the inside with arthroconidia which are 5-8 μm in diam (Peixoto et al., 2019). The cuticle remains intact; the hair may burst, break, crumble and curl at the surface of the follicle opening, leaving hairless follicles, a picture which is clinically known as ‘black dot‘.
Main causative agents: Trichophyton tonsuransT. violaceum.
Vellus hair infection. Human thin body hair infection leading to breakage and absence of hair (Zhou et al., 2024). Accompanying cutaneous symptoms are scaling and local inflammation.
Main causative agents: Microsporum canis, Trichophyton mentagrophytes.

Superficial dermatophytoses

This category contains those disorders in which living parts of outermost skin layers, genitalia or external ears can be affected by dermatophytes. Skin lesions are often circular with slightly raised, red margins, containing numerous scales and surrounded by reddish, itching skin. This characteristic type of infection is classically known as ‘ringworm‘, a term that is often applied to the total of dermatophyte infections.
The fungus remains restricted to the stratum corneum. As a result of keratinolytic activity, metabolites are produced, which provoke inflammation. The horny layer deteriorates and becomes scaly. The affected areas expand gradually, and tissue may heal at the center. The lesions are classified according to their localisation on the human body: the involvement of the scalp, face, hand, groin, palm, plantar region and the remaining other skin areas are called tinea capitis, tinea faciei, tinea manuum, tinea cruris, tinea pedis and tinea corporis, respectively.
Tinea pedis (athlete’s foot). Dermatophyte infection of the feet and the interdigital spaces of the toes (Ilkit & Durdu, 2015). The disorder has emerged with rural habits of wearing closed shoes (Sasagawa, 2019). The disorder is commonly observed in the elderly population, more rarely in children (Tullio et al., 2007). It is estimated that about 15% of the world population carries this infection. The moist skin between toes is infected, particularly between the fourth and fifth toes; the horny layer is damaged, and painful fissures may develop. Symptoms are often slight but can also be severe and then include malodor, and pruritus. In the toe webs, scaling, fissuring, maceration, and erythema (‘interdigital type‘) may be associated with an itching or burning sensation (Al Hasan et al., 2004). Adjacent infection of the sole often extends up the lower sides of the foot, known as ‘moccasin type‘ (chronic hyperkeratotic type). This type is a prolonged, chronic form of tinea infection. The sole appears hyperkeratotic and often covered with fine scales; fissuring may occur. Except for the toes, the dorsum of the foot is spared. The ‘acute ulcerative type’ has rapidly expanding vesiculopustular lesions and ulcerations with severe inflammation. The infection is mostly located in the toe web spaces. Secondary bacterial infection is often observed and may lead to cellulitis, lymphangitis or pyrexia. This type is commonly seen in immunocompromised and diabetic patients. A ‘vesiculobullous type‘ of tinea pedis is characterized by pustules or vesicles on the plantar surface of the feet (El-Segini et al., 2002). This infection has an acute onset with intense inflammation leading to multilocular pruritic vesicles or bullae. Infection is limited to the toes, instep, and lateral aspects of the foot. The infection tends to worsen during summer, and relapses are frequent. With bacterial superinfection, erythema increases, and this may become associated with edema, cellulitis, lymphangitis, adenopathy and hyperhydrosis; this aggravation is painful. All types of tinea pedis often lead to satellite infections elsewhere on the extremities when not treated properly (Zhan et al., 2010).
Main causative agents: Trichophyton rubrumEpidermophyton floccosum.
Tinea manuumThis is the hand-affecting counterpart of, and frequently associated with, tinea pedis. Mostly the dominant hand is involved. Small lesions between the fingers with scaly rash may finally affect larger parts of the palm which becomes hyperkeratotic (Veraldi et al., 2019). The infection involves the epidermis and causes erythema, which is particularly noted in palmar wrinkles. The skin becomes scaly, and sometimes lesions are pustular (Choi et al., 2019). Symptoms may remain absent, but patients may also experience an itching, stinging, or burning sensation. Outside self-inoculation from the feet, the infection often originates from pet animals, particularly the African pygmee hedgehog (Coronado-Aguilar et al., 2018; Walsh et al., 2021).
Main causative agents: Trichophyton rubrum, T. erinacei.
Tinea faciei. Circinate erythematous plaques (Meymandi et al., 2003; Khaled et al., 2007) or erythematous macules resembling impetigo (Kimura et al., 2014) on exposed parts of the face (Lin et al., 2004). Cutaneous lesions are eventually covered with golden-yellow scales or crusts which can be readily removed (Zhang et al., 2022). Patients often complain of itching. Infections may be transmitted from animals (Hsieh et al., 2010; Tan et al., 2020), particularly pet animals which transfer the disorder upon cuddling (Kim & Dyer, 2024). Such infections are mainly found in children (del Boz et al., 2012); in neonates the infection is very rare (Alkeswani et al., 2018). Infections can be promoted by maceration, e.g., by prolonged mask wear (Agarwal et al., 2021). Infections in patients with constitutional disorders are also known, such as excess of growth hormone associated with metabolic complications (Merad et al., 2021). Infections limited to the eyebrows also occur (Zhuang et al., 2007) which may extend to the skin (Ishizaki et al., 2012). Infection of the eyelashes is referred to as ‘tinea ciliaris’, or ‘tinea blepharo-ciliaris’ when associated with blepharitis (Wang & Sun, 2018; Sahin et al., 2014). Depending on the infectious agent and the immune status of the host, lesions can be recalcitrant (Fukada et al., 2024). Also cases are known with expansion from other parts of the body (Vazheva & Zisova, 2021). Cases of tinea faciei and t. corporis with atypical presentations are often referred to as ‘tinea incognito‘.
Main causative agents: Microsporum canisTrichophyton interdigitaleT. tonsuransT. rubrum, T. erinacei.
Tinea barbae (tinea sycosis) concerns infections of the skin and hair follicles of the bearded area of the face (Bonifaz et al., 2003; Xavier et al., 2008). Two types are known. The superficial type, characterized by erythematous patches with pustular folliculitis, is mainly caused by anthropophilic dermatophytes, mainly in the Trichophyton rubrum complex. The affected hairs are sometimes easily extracted. The deeper type presents as inflammatory nodules with kerion-like swellings, pustules and draining sinuses on the surface. Hairs are loose or broken, and the follicle may be involved. Because of its deep skin involvement, this type is often indicated with the adjective ‘profunda’ (Wendrock-Shiga et al., 2017). The infection is mostly transmitted from cattle (Wollina et al., 2018) and is rather common among farmers (Sabota et al., 1996).
Main causative agent Trichophyton verrucosum.
Tinea corporis. Lesions on exposed, hairless skin of arms or trunk (Machnikowski et al., 2017; Tanabe et al., 2023). Infection of the body often occurs concomitantly with and may result from lesions on nails, scalp, groin, or beard (Szepietowski et al., 2006), but the term tinea corporis is properly applied to lesions originating on the glabrous skin. Lesions initiate as erythematous, dry and scaly plaques that extend to circular, sharply circumscribed patches with slightly elevated borders of increased inflammation and scaling. Subsequent central healing leads to the characteristic annular outline known as ‘ringworm’ (Akhoundi et al., 2020). The ringworms may be single, multiple, or confluent. In in patients with underlying immune disorders, numerous lesions join and cover large parts of the body (Gorani et al., 2002). Tinea corporis in patients with advanced HIV infection users is often widespread without circular forms (Pihet et al., 2008; Costa et al., 2015; Mariyani et al., 2022). Such undetermined forms are sometimes difficult to recognize in clinical practice and have therefore been indicated as ‘tinea incognito‘. Lesions may remain low inflammatory lesions with minimal scaling and erythema, while highly inflammatory lesions, occurring particularly with geo- or zoophilic etiologic agents (Chollet et al., 2015), are composed of pustules, vesicles, and marked erythematous macules resembling impetigo (Shimoyama et al., 2016). Central clearing usually occurs but is often incomplete and may be associated with hyperpigmentation (Diep et al., 2020). Tinea corporis is frequently observed in children (Starace et al., 2021).
Main causative agents: Microsporum canisTrichophyton interdigitaleT. verrucosumT. tonsuransT. violaceum.
Tinea imbricata (tokelau) is an unusual form of tinea corporis (Leung et al., 2019). Concentric rings (Roslan & Abdul Hadi, 2022; Veraldi et al., 2014) or dense labyrinthoid (Leung et al., 2018) superficial scaling with low inflammatory response and minimal erythema, spreading out peripherally over many years, creating a distinctive appearance. The chronic disorder is generally linked to Trichophyton concentricum; if similar lesions are caused by another dermatophyte species, the terms ‘tinea indecisiva‘ (Sonthalia et al., 2015) and ‘tinea pseudoimbricata‘ (Suzuki et al., 2021) have been applied.
Causative agent: Trichophyton concentricum.
Tinea cruris (jock itch). Pruritic lesions on and around the groin affecting the warm, moist areas of the body. The infection begins as a small erythematous rash in the groin fold, usually on both sides, extending with circular lesions to the inner thighs (Firooz et al., 2021). The lower abdomen can be involved, and frequent extension to the perineum and perianal areas is observed. Ring-like lesions may also appear on the buttocks. The genital areas, especially the scrotum, are rarely involved. Particularly when the infection is caused by a dermatophyte with increased virulence such as Trichophyton indotineae, extension with tinea corporis is observed (Uhrlaß et al., 2022; Sardana et al., 2023). Early infections by this emerging dermatophyte had a sexual transmission route (Kupsch et al., 2019Luchsinger et al., 2015Nenoff et al., 2020). Causative agents of tinea cruris are anthropophilic dermatophytes and therefore infected patients are contagious, or the infection is transmitted by autoinoculation from a reservoir on the hands or feet. Approximately one half of patients with tinea cruris have coexisting tinea pedis. With underlying immune disorders, erythematous, oozing, crusted plaques may appear (Bhagra et al., 2013; Reddy et al., 2022). Secondary bacterial or viral involvement may occur (Mathur et al., 2023).
Main causative agents: Epidermophyton floccosumTrichophyton interdigitale, T. indotineaeT. rubrum.
Tinea genitalis (white dot). A variant of tinea cruris occurs on the scrotum of male patients. Whitish, dry, cottony superficial growth is observed with limited inflammation with or without itching. Pale yellowish crusts and scales are firmly attached to the scrotum and show erosion when removed (Lu et al., 2009; Chen et al., 2013; Yin et al., 2019).
Main causative agents: Nannizzia gypsea, Trichophyton rubrum.
Tinea unguium. This condition refers to onychomycosis caused by a dermatophyte, a condition under the general term often caused by Candida albicans. Tinea unguium is an extremely common (Perea et al., 2000; Aman et al., 2001) chronic infection of the nail bed and nail (Asz-Sigall et al., 2017), mostly of the toenails. It is the prevalent nail disorder in adults, accounting for 15-40% of all nail diseases (Ameen et al., 2014). Dermatophytes account for about 90% cases of onychomycosis of the toenails and at least 50% of fingernail infections (Thomas et al., 2010). Predisposing factors tinea pedis, diabetes, immunosuppression, poor peripheral circulation, trauma and advanced age. The infection expands from the periphery towards the centre; the nail may eventually be released due to lateral hyperkeratosis which lifts the nail distally. The distal nail bed and hyponychium gradually break and crumble, and the subungual region shows yellowish brown discoloration. This condition is known as ‘distal and lateral subungual onychomycosis‘ (DLSO), a term that also covers non-dermatophyte agents such as Candida albicans (Subramanya et al., 2019). Adjacent nails usually remain unaffected. Trichophyton rubrum is the prevalent dermatophyte. ‘Superficial white / black onychomycosis’ (SWO / SBO) is an invasion of the superficial layer of the nail plate, visible as small, white, speckled or powdery patches on its surface. The nail becomes roughened and crumbles easily. The most common etiologic agent is Trichophyton interdigitale, while T. rubrum is prevalent in the HIV-positive population. The term also covers non-dermatophytes such as species of Aspergillus, Acremonium and Fusarium for the white variant. Agents of black onychomycosis (melanonychia) mainly caused by T. rubrum or the non-dermatophyte Neoscytalidium dimidiatum (Rodríguez-Cerdeira et al., 2024). ‘Proximal subungual onychomycosis’ involves the proximal nailfold and adjacent nail plate, resulting in subungual hyperkeratosis, proximal onycholysis, leukonychia, and destruction. Trichophyton rubrum is the principal causative agent, periungual inflammation may also be caused by non-dermatophytes such as Fusarium, Aspergillus and Scopulariopsis. ‘Endonyx onychomycosis’ presents as a milky white discoloration of the nail plate, but no evidence of subungual hyperkeratosis or onycholysis is observed. Main etiologic agents are T. soudanense and T. violaceum. ‘Total dystrophic onychomycosis’ is the final stage of any of the described types of onychomycosis, the entire nail presenting in a thickened, opaque, and yellow-brown condition.

Deep dermatophytoses

Tinea folliculorum (Majocchi’s granuloma, granuloma trichophyticum) is defined as perifollicular granulomatous inflammation (Sun et al., 2018; Durdu et al., 2019). Infection of hair follicles can lead to a deep dermal inflammatory reaction very similar to kerion of the scalp. Fungal elements are present in the hair follicle and in the perifollicular infiltrate of the dermis, due to the rupture of the follicle wall. The lesion becomes pustular, well circumscribed, elevated and crusted. Infections mostly are seen at the lower extremities (Coelho et al., 2009), with epilation (Mazur et al., 2018) and the use of topical steroids (Liu et al., 2015) as risk factors. Recurrent cases may be linked with chemotherapy-induced neutropenia.
Main causative agent: Trichophyton rubrum.
Deep dermatophytosis. This is a severe and sometimes life-threatening condition, characterized by extensive dermal and subcutaneous tissue invasion, with frequent dissemination to the lymph nodes and sometimes to the central nervous system. The disorder is nearly always associated with immunosuppression because of solid organ transplantation (Wu et al., 2013; Rouzaud et al., 2018) or inherited immune disorders such as CARD9 (Boudghene Stambouli et al., 2017; Lanternier et al., 2013; Stambouli et al., 2017; Ansai et al., 2024) or other causes of lymphocytopenia (Song et al., 2023).
Main causative agents: Microsporum canis, Trichophyton mentagrophytes, T. rubrum.
Tinea capitis. Tinea capitis is a rather common infection occurring predominantly in children (Hay, 2017; Wang et al., 2023), often being acquired from pet animals. Manifestations are highly variable. As the term mainly refers to the localization of the infection, tinea capitis encompasses several clinical types. Depending on the etiologic agent, hair invasion is prevalently of the endothrix or ectothrix type, respectively. Initial infection is in the perifollicular epidermis, due to hyphae affecting the hair extending downwards from the follicle, via the cuticle, and then reaching the hair cortex. ‘Gray patch‘ (tinea alba) (Pratiwi & Setyaningrum, 2020) is the most common non-inflammatory form of tinea capitis (Farooqi et al., 2014). Poorly defined, grayish, dry, finely scaling patches are visible on the scalp; lesions sometimes extend widely (Lozano-Masdemont et al., 2019). Typically, the lesions start around the hair shaft, and lead the hairs to break off 2–3 mm above the scalp. Invaded hairs show an ectothrix infection and characteristically green fluorescence under Wood’s ultra-violet light. Patients may recover spontaneously without scars in the adolescent period. In ‘black dot‘, a subtype that is more often seen in adult patients, the hair crumbles and breaks off at the skin surface leaving hairless follicles (Keisham et al., 2015). Invaded hairs show endothrix infection; fluorescence remains absent under Wood’s ultra-violet light. The lesion may leave patchy atrophic scars after recovering. In more advanced stages of infection, perifollicular inflammation leads to complete degeneration of the hairs. This provokes further intense inflammation that progresses into the subcutaneous tissue and the perivascular area (Elmas & Durdu, 2023). Suppurating reactions are common, leading to kerion or favus, described below. Fungal metabolite production during hair infection causes more severe, inflammatory reactions than on hairless skin. The inflammatory and pustular plaques provoke extensive, permanent alopecia. Epidemiology and spectrum of etiologic agents was reviewed by Chen & Yu (2024).
Main causative agents:  Microsporum audouiniiM. canis (from cats / dogs), M. ferrugineum, Trichophyton verrucosum (from cattle), T. mentagrophytes (from horses / dogs), T. tonsuransT. schoenleiniiT. violaceum, T. soudanense.
Kerion. A subtype of tinea capitis with scattered pustules, folliculitis, or plaque with massive purulent discharge. Areas of hair loss with painful, boggy, thickened scalp, which may progress to severe hair loss with scarring alopecia. Regional lymphadenopathy is common. Due to local oozing of pus, yellowish crusts are formed, and the skin feels soft to the touch. Both ecto- and endothrix hair infection is observed (Deng et al., 2024), usually leading to extensive hair loss (Fernandes et al., 2013; Tshudy & McCann, 2023). The source of infection is mostly an agricultural or pet animal.
Main causative agents: Microsporum audouinii, M. canis, Trichophyton mentagrophytes, T. soudanense.
Favus (tinea capitis favosa). Hyphae create air spaces in the hair during decomposition. This is a chronic infection (Ilkit, 2010) characterized by the presence of sulfur-yellow, circular, cup-shaped crusted lesions (scutula) emerging around hair follicles (Iwasa et al., 2019). The scutulae have a distinctive mousy odor. The hair does not break but is lost completely and permanently due to degeneration of the follicle. Subsequent loss of hair causes a sharply delimited bald spot on the haired skin. The adjacent skin is invaded, crusty and scarred.
Causative agent: Trichophyton schoenleinii.
Disseminated dermatophytosis. Extracutaneous spreading to other organs is rarely observed in patients with severe underlying diseases (Marconi et al., 2010). The term is somewhat misleading in that infection is mostly not disseminated beyond the skin but is widespread over large body areas, often beginning in childhood and expanding over decades. The skin becomes nodular, thickened, and scaling, without purulence or crusting.

Therapy

All dermatophyte infections should be treated comprehensively. Pharmacological treatment depends on the anatomical location of the infection and on the causative agent, either topical formulation or oral therapy, or these in combination. Systemic therapy is given in cases of tinea capitis and recalcitrant tinea unguium, and topical therapy is mostly sufficient with skin infections; however, systemic therapy may also be considered in cutaneous cases with extensive disease, significant hyperkeratosis or relapse or topical treatment failure. The aim of treatment should be to decrease signs and symptoms, but also to eradicate the infection to prevent relapse and transmission. In 2014, guidelines for the management of onychomycosis and tinea capitis were published by the British Association of Dermatologist, providing evidence-based recommendations for practical use (http://www.bad.org.uk).

Therapy of tinea capitis

Topical treatment alone is not recommended for the management of tinea capitis but can be applied as an adjunct to oral use of antifungals to eradicate the fungus from the infected site, to reduce transmission, and support cure and mitigation of symptoms. Basic rules for prevention involve, in addition to oral therapy, wash and clean the infected area, cut the infected hair, and disinfect. Various topical agents are available for adjunctive therapy, for example shampoos with selenium sulfide 1%, ciclopirox 1% and ketoconazole 2% shampoos, and application of povidone–iodine, which all have shown efficacy (Fuller et al., 2014). Use of these shampoos twice a week as adjunctive therapy or with griseofulvin substantially reduces the period of active shedding (Chen et al., 2010).

Therapy of cutaneous tinea

Topical treatment is valuable in managing tinea infections of the skin, particularly tinea corporis, t. cruris and t. manuum. Systemic treatment may be needed for recalcitrant, severe or extensive infections. Several groups of effective antifungals are available for topical application, such as the azoles (clotrimazole 1%, ketoconazole 2%, miconazole 2%, tioconazole 1%, bifonazole 1%, econazole 1%, oxiconazole 1%, sertaconazole 2%), allylamines (terbinafine 1%, naftifine 1%, butenafine1%), amorolfine, cyclopyroxolamine, tolnaftate, benzoic acid and undecenoic acid. In main traits, fungicidal allylamines perform better than fungistatic azoles in providing and maintaining mycological cure. Some of these are available as over-the-counter drugs in most, but not all countries. Topical agents should be applied once or twice daily, with a minimum duration of treatment of 2 to 4 weeks. A meta-analysis of tinea pedis involving 19 randomized controlled trials (n = 1,937) comparing azole and allylamine antifungals with placebo (Rotta et al., 2012) for mycological cure and sustained therapy showed that azoles and allylamines are both effective, but a similar study (Crawford & Hollis, 2007) of 9 RCTs (n = 1003, 4-6 wk) indicated better results with allylamines (terbinafine and naftifine 1%) than with azoles cream (clotrimazole 1-2% , bifonazole 1%). Another study (Rotta et al., 2012) of 6 RCTs (n = 298) showed that terbinafine was already effective with 1-2 wk treatment. Combination of azoles with corticosteroids were slightly more effective than azoles alone for clinical but not for mycological cure (van Zuuren et al., 2015). However, this combination may stimulate emergence of resistant genotypes and is therefore not recommended in view of public health (Singh et al., 2019).

Therapy of tinea unguium

Treatment of dermatophyte nail infections is modified by clinical type, affected area, and causative agent. Tinea unguium requires longterm treatment with systemic and topical antifungal agents or device-based methods to be effective. Topical treatment alone should be limited to DLSO with the involved part covering less than 50% of the nail, and to SWO/SBO without paronychia (except in transverse or striate infections). In these milder cases, no matrix should be involved, and less than four nails be affected. Topical therapy is also required when systemic antifungals are contraindicated. Amorolfine 5% or ciclopirox 8% olamine nail lacquer (approved in the U.S.A. and Canada), twice weekly, are most commonly used and proved to be effective in around 50% of cases of distal fingernail and toenail onychomycosis (Zaug & Bergstraesser, 1992). Amorolfine belongs to the morpholine group of synthetic antifungal drugs and exhibits broad-spectrum fungistatic and fungicidal activity. For the onychomycosis with matrix involvement, the lacquer is preferably used in combination with oral antifungal therapy. Five trials have underlined the effectivity of oral therapy: one using griseofulvin, three terbinafine, and one itraconazole (Zaug, 1995; Baran et al., 2000, 2007; Lecha et al., 2002; Jaiswal et al., 2007). Side-effects following amorolfine lacquer treatment are rare and are limited to local burning, pruritus or erythema.

Ciclopirox is a hydroxypyridone derivative with broad-spectrum antifungal activity against Trichophyton rubrum and non-dermatophytes. Ciclopirox 8% nail lacquer can be used once daily for 48 weeks in cases of mild to moderate onychomycosis. Two open label studies demonstrated clinical improvement of onychomycosis in 63-89% diabetic patients with diabetes (Seebacher et al., 2001; Brenner et al., 2007), although the number of patients was relatively low. Combination with oral antifungals would result in higher efficacy (Shemer et al., 2010). Other topical formulations are in use, including tioconazole 28% nail solution, efinaconazole10%, butenafine, bifonazole urea, salicylic acid, over-the-counter mentholated ointment, ozonized sunflower oil and undecenoates, but there are limited data to support their effectivity (Ameen et al., 2014).

Technologies that enhance the penetration of topical antifungals into the nail plate are currently under investigation. These include device-based therapies, such as laser devices (Kozarev & Vižintin, 2010; Landsman & Robbins, 2012), photodynamic therapy (Sotiriou et al., 2010) and iontophoresis (Amichai et al. 2010). Several laser systems have been FDA-cleared for onychomycosis. However, these techniques are still in their infancy, and clinical trials are required prior to wider application.