Dermatophytes

Essentials of Diagnosis

• Characteristic pattern of inflammation on glabrous skin surfaces. The active border of infection is scaly, red, and slightly elevated.
• Wet mount preparation with potassium hydroxide (10-20%). Skin scraping from the active border shows branching, translucent, rod-shaped filaments (hyphae) in keratinised material under low-power microscopy (10-40x). Hyphae are uniformly wide and regularly septated.
• Wood's light examination (UV light at 365 nm) shows blue-green fluorescence for Microsporum canis and Microsporum audouinii. Trichophyton schoenleinii is pale green, and tinea versicolor shows white-yellow fluorescence.
• Culture should be performed using hair, nail, and skin specimens from particularly inflammatory lesions to establish a definitive mycological diagnosis.

General Considerations

Dermatophytes are moulds that infect keratinised tissues, including skin, hair, and nails. Although 40 dermatophyte species are known to infect humans, only about 15 are common causes of disease. These organisms belong to three genera: Microsporum, Trichophyton, and Epidermophyton. Because these fungi have similar infectivity, morphology, and pathogenicity, they are often categorised according to the clinical syndrome and their preferred anatomical site, such as tinea capitis, tinea pedis, etc. The term "tinea" comes from the Latin word meaning worm or moth. These superficial mycoses often produce serpiginous skin markings.

Although tinea versicolor (caused by Malassezia furfur or Pityrosporum spp.) is not formally considered a dermatophytosis, it is also discussed in this chapter because it affects the superficial layers of skin.

Epidemiology

Dermatophytes are found in three distinct environmental niches and show specific adaptation to these sites: animals, humans, and soil. Therefore, they are classified as anthropophilic, zoophilic, or geophilic organisms. As these names imply, infection occurs after exposure to infected humans, animals (such as cats, dogs, or cattle), or soil.

Dermatophytoses occur worldwide and vary in presentation according to the site of infection. Improved living standards in the United States since the end of World War II have decreased the incidence of tinea capitis. By contrast, dramatic increases in the incidence of tinea pedis and tinea cruris due to Trichophyton rubrum, an anthropophilic dermatophyte, have been observed in recent years in developed nations. T rubrum is the most common dermatophyte pathogen worldwide, affecting up to one-third of the population of industrialised countries. Tinea pedis occurs almost exclusively among people who wear shoes, because shoes provide warmth and moisture-conditions preferred by the causative organisms.

Transmission of zoophilic dermatophytes occurs through direct contact with infected animals or via fomites, such as troughs and stalls used by infected animals. Geophilic dermatophyte infections occur through direct contact with soil and are seen in greenhouse workers, but infections with these organisms are relatively less common than those caused by anthropophilic dermatophytes.

Microbiology

Dermatophytes belong to three anamorphic (asexual or imperfect) genera, Epidermophyton, Microsporum, and Trichophyton, of the Deuteromycota (Fungi Imperfecti). Members of the Epidermophyton genus have macroconidia that are smooth-walled and occur singly or in clusters, but these fungi have no microconidia. Members of the Microsporum genus have macroconidia that are fusiform or cylindrical with roughened walls. There are fewer microconidia, and they are found singly along the hyphae as pear-shaped structures. Trichophyton species have macroconidia with smooth cylindrical walls. Their microconidia are numerous and spherical or pear shaped; they appear in clusters along the hyphae.

Conidia form the basis for dermatophyte speciation. Because dermatophytes form only hyphae and arthrospores in the nonviable keratinised tissue of infected humans, they must be cultivated in the laboratory to develop conidia for identification. Colonies form at room temperature on Sabouraud's agar; their colour, texture, and morphology are also useful for species identification.

Pathogenesis

Host factors that enhance the development of dermatophytoses include genetic susceptibility markers; abraded skin; occlusive clothing, footwear, or dressings; and the presence of other cutaneous diseases such as atopic dermatitis. Dermatophytes invade the keratinised layers of skin by producing keratinases, enzymes that digest keratin. As they adhere to and invade host skin, dermatophytes elicit a diverse range of clinical responses. Most lesions are confined within an anatomical boundary and may even be self-limited, but widespread dermatophyte infection has been observed in patients with AIDS, patients receiving immunosuppressive drug regimens, and those with endocrinopathies such as Cushing's disease. The pathogenic features of superficial dermatophyte skin infections are broad and depend on both the fungus and the host response.

Trichophyton is also the name of a crude extract from certain dermatophytes that produces a tuberculin-like response in most adults. Two moieties of the galactomannan peptide are responsible for the antigenic response. The carbohydrate portion causes an immediate response, and the peptide portion is associated with a delayed response and probably with immunity as well. Resistance to infection is T cell mediated and may be acquired after infection, but it varies in duration and degree depending on host factors, the fungal species, and the site of infection.

Clinical Findings

Superficial mycoses are named according to the site of infection, which usually corresponds to the site of local inoculation. The degree of inflammation is often dictated by the nature of the environment from which the fungus originates. For example, anthropophilic dermatophytes elicit a milder immune response in humans than zoophilic fungi. The anthropophilic M audouinii causes minimal inflammation compared with the zoophilic M canis. Table 1 lists the microbiological differential diagnosis for each clinical syndrome discussed below.

Tinea Capitis

Tinea capitis, or scalp ringworm, mainly affects prepubertal children aged 4-14 years. It is most commonly observed in crowded living conditions and in areas of poverty. Infection of the hair shaft distinguishes this disease from other dermatophytoses that involve glabrous skin. Tinea capitis is often classified according to one of three patterns of fungal invasion noted microscopically: endothrix, ectothrix, or favus. Endothrix infections invade the inside of the hair shaft, and the cuticle is not destroyed; clinically, this appears as simple scaling of the scalp. It may resemble seborrhoeic dermatitis or dandruff. There may be grey patches of alopecia with minimal or no inflammation, or "black dot" alopecia, in which hairs break off at the roots.

Ectothrix infections present with grey or scaling patches of alopecia with minimal or no inflammation. A "black dot" appearance may also be seen. Kerions and prominent inflammatory lesions may occur because the dermatophytes that cause ectothrix infections invade both the inside and the outside of the hair shaft and follicles. Kerions are boggy, suppurative, and usually painful. Kerions are most commonly seen with M canis and rarely with Trichophyton mentagrophytes or Trichophyton verrucosum.

Favus infection leads to crusting and matted hair on the scalp, with such severe invasion that permanent alopecia often results. It is seen primarily in Eastern Europe and Africa.

Tinea Barbae

Tinea barbae, like tinea capitis, affects hair follicles and shafts, but in the facial area. It is often diagnosed only after it fails to respond to several courses of antibacterial agents. Affected hairs are easily removed, unlike those in bacterial folliculitis, which resist removal. The zoophilic dermatophytes T mentagrophytes and T verrucosum are the most common causes of tinea barbae. The condition often begins with a small clump of follicular pustules, then develops into a boggy, erythematous, tumour-like abscess.

Tinea Corporis

Tinea corporis, or ringworm, refers primarily to lesions affecting non-hairy or glabrous skin, but it may also result from extension of scalp or groin infections. Lesions are usually sharply demarcated and ring-like, with a raised border. Infections can range from mildly to highly inflammatory, with pustules, vesicles, and marked erythema. The central area may become brown or hypopigmented and less scaly as the active border progresses.

Tinea Cruris

Tinea cruris, or jock itch, is more common in men and may involve the perineum, perianal area, and thighs, but it rarely affects the scrotum. (By contrast, Candida infections typically involve the scrotum.) Tinea cruris typically presents with bilateral asymmetric erythematous plaques that spread distally from the groin. There is often central clearing and an active erythematous border, which may have vesicles or papules. Pruritus and burning are common complaints.

This infection is usually transmitted from the patient's foot to the groin. Tinea cruris often occurs in the summer months after sweating or wearing wet clothing, or in the winter months after wearing many layers of clothing, which leads to the warm, moist conditions that predispose to fungal growth.

Tinea Pedis

Tinea pedis, also known as athlete's foot, is the most commonly diagnosed dermatophyte infection overall and is usually caused by the anthropophilic organism T rubrum. Occlusive footwear promotes warmth and sweating, which provide an ideal environment for fungal growth. Tinea pedis presents in four general patterns: (a) interdigital infection with erythema, maceration, and scale formation; (b) "moccasin foot" with erythema and thick hyperkeratotic scales; (c) inflammatory infection with vesicles, usually on the medial foot; and (d) a less common ulcerative infection affecting the web spaces of the toes, sometimes superinfected with bacteria and often seen in immunocompromised patients. If tinea unguium is present, tinea pedis may persist because of constant reinfection from the nails.

Tinea Unguium

Tinea unguium, or onychomycosis, is an infection of the fingernails or toenails. Infections typically begin along the leading edge of the nail or the lateral border and involve the nail plate; the result is opaque, chalky, or yellow nail discolouration. The nail may also become thickened and brittle. Inflammatory changes of the skin around the nail, including paronychia, are not seen with tinea unguium. Toenails are involved more frequently than fingernails, and the incidence of this infection increases with age.

Nondermatophytic moulds such as Scopulariopsis and Scytalidium spp., Acremonium, Fusarium, and Candida spp. cause ~ 5% of fungal nail diseases. This prevalence varies by geography, and these moulds may account for up to 50% of fungal nail infections in Southeast Asia. It is important to distinguish these fungi, because not all respond to the same therapy.

Tinea Incognito

Tinea incognito refers to dermatophyte infections that are disguised, often because they are treated with topical steroids and then lose some of their characteristic clinical features. Steroids may temporarily reduce inflammation, but the fungus can grow unchecked because of the impaired immune response. The rash changes so that scaling margins disappear, borders become irregular, and a once localised process may expand. The diagnosis is easily made once steroids are stopped for a few days and scaling reappears, and hyphae can be seen on microscopy. Tinea incognito is most often observed in the groin, face, and hands.

Dermatophytid

Dermatophytid, or the "id" reaction, is an allergic response to tinea processes that causes sterile dermatitis at distant sites. The most common presentation is a patient with tinea pedis who develops itching and burning on the hands, usually on the sides of the fingers near the crease. Vesicles may appear and enlarge to bullae. Desquamation of the palms and soles occurs less commonly, without inflammation. The lesions persist until the primary process resolves.

Tinea Versicolor

Tinea versicolor is a common fungal infection of the superficial layer of skin caused by members of the Malassezia genus, especially Malassezia furfur, formerly known as both Pityrosporum orbiculare and Pityrosporum ovale. These organisms are lipophilic and use medium-chain-length fatty acids. They are part of the normal skin flora, but certain conditions promote proliferation, such as excess heat, humidity, pregnancy, oral contraceptives, malnutrition, burns, Cushing's disease, corticosteroid therapy, or other forms of immunosuppression.

Clinically, tinea versicolor has a characteristic distribution and set of lesions. It begins as small circular macules of various colours (hence the name "versicolor"), such as white, pink, or brown, that expand radially. The varied colour of this rash stems from the host's pathological response. For example, reddish macules or patches are related to a hyperaemic inflammatory response; hypopigmented lesions are caused by alterations in melanosome formation and transfer of pigment to keratinocytes; and tan or dark macules or patches are also related to alterations in melanosome formation. In each individual, lesion colour is uniform. The upper trunk is most commonly affected because the organism is present in highest numbers in areas of increased sebaceous activity. Lesions often become more obvious in summer, when hypopigmented areas contrast more sharply with unaffected tanned skin. Lesions are usually asymptomatic, but they may itch if inflammation is present.

Diagnosis

In addition to clinical recognition and diagnosis on clinical grounds, three specific techniques are useful in the work-up and more definitive diagnosis of superficial mycoses: UV light examination, direct microscopy, and culture. Direct examination of the patient's skin in a darkened room using UV light (a Wood's lamp) is useful only for infections-primarily tinea capitis or corporis-caused by certain species, including M audouinii, M canis, and T schoenleinii. These infections give off a blue-green colour.

Specimens for diagnosis by microscopy or culture can be collected using a razor or scalpel to scrape keratinised or flaking material from the leading edge of the newest lesion. Nail scrapings are best obtained by scraping underneath the nail plate, first to clean it and then to collect a specimen onto a microscope slide or to inoculate culture. A few drops of 10-20% KOH solution are placed on the slide to dissolve keratin. Heating accelerates the process. This enables visualisation of hyphae seen with dermatophytes, or hyphae and spores seen in candidal and tinea versicolor infections.

Because KOH wet mounts cannot differentiate among dermatophyte species, organisms should be cultivated to reveal the distinguishing conidial forms. From a clinical perspective, it is usually not necessary to identify the dermatophyte species, because topical and oral agents are active against all of them. Species identification is important for scalp infections, severe or inflammatory skin infections, and some nail infections because systemic treatment is required for scalp infections, treatment may be prolonged and expensive, and species identification may enable prevention of zoophilic infections. Some nail infections may be caused by a mould (eg, Scopulariopsis spp.) which, despite being indistinguishable from dermatophytoses on gross visual inspection, will not respond to the same therapy. Culture is usually performed using Sabouraud's agar slants, which are incubated at room temperature for 1-3 weeks. The specific dermatophyte is then identified by colony colour and texture, as well as by light microscopy, which reveals specific morphological patterns.

Diagnosis of tinea versicolor is made by Wood's light examination, which shows irregular whitish-yellow areas of fluorescence, although some lesions do not fluoresce. Potassium hydroxide wet mount preparations show short, broad hyphae and clusters of budding cells, which are often described as having the appearance of "spaghetti and meatballs". Cultivation is possible but rarely indicated, and it requires addition of oil to the fungal culture media because the organism is lipophilic.

¹ Anthropophilic. ² Zoophilic. ³ Geophilic.

Treatment

The principles of treatment are outlined below according to the specific clinical presentation. Most tinea infections involving the skin can be treated with topical agents, such as an imidazole, twice daily for 2 or 3 weeks. Terbinafine is also available in both topical and oral formulations and appears to be more potent, requiring shorter treatment courses with longer-lasting clinical responses. Terbinafine and newer related drugs block ergosterol synthesis at an earlier step than the azole drugs.

If the infection is widespread, involves a large surface area, or is particularly inflammatory, systemic drugs are indicated. For infections of hair and nails, debridement is important before systemic treatment. Several oral medications, including itraconazole, fluconazole, and terbinafine, can be dosed daily or in so-called "pulsed" regimens for effective treatment of infections of keratinised tissues. Pulse dosing takes advantage of drug deposition in the nail so that the total dose can be reduced; higher amounts of drug are given repeatedly for short intervals corresponding to the time it takes for a finger- or toenail to grow. For example, a slightly higher daily dose is given for 1 week each month for the estimated time required for the infected nail to regrow.

Treatment of tinea versicolor involves a 2.5% selenium sulfide suspension applied to the entire skin surface from the lower posterior scalp down to the thighs for 10 minutes each day for 7 days. Another common regimen is to apply the lotion and wash it off after 24 hours, repeating once a week for a month. Antifungal creams are useful. Single-dose oral treatment with ketoconazole, itraconazole, or fluconazole has also been shown to be effective. Other important adjunctive measures to minimise reinfection include discarding or boiling frequently worn garments that are in contact with the skin. Lesions may take months to clear because they result from depigmentation, which persists despite eradication of the fungus.

Prevention & Control

Several interventions have been shown to be useful in the prevention and control of dermatophytes, depending on their type and anatomical location. In general, keeping the body surface clean and dry; avoiding occlusive gloves or shoes that may promote tinea unguium, manus, or pedis; and avoiding sweat-dampened clothing that allows tinea versicolor to thrive all help to control infection. Regular cleaning of showers and changing areas at public pools with bleach is thought to help control some infections, as is the individual use of chemicals such as foot powders.

Prevention and control of dermatophytoses

Prophylactic measures

• Identify and avoid exposure to animals or fomites suspected of harbouring dermatophytes.
• Boil or wash clothing using a commercial facility.
• Disinfect public shower and bathing areas.

Isolation precautions

• None.