Dermatophyte

Pathogenesis

In order for dermatophytoses to occur, the fungus must directly contact the skin. Likelihood of infection is increased if the skin integrity is compromised, as in minor breaks.

The fungi use various proteinases to establish infection in the keratinized stratum corneum. Some studies also suggest that a class of proteins called LysM coat the fungal cell walls to help the fungi evade host cell immune response.

The course of infection varies between each case, and may be determined by several factors including: "the anatomic location, the degree of skin moisture, the dynamics of skin growth and desquamation, the speed and extent of the inflammatory response, and the infecting species."

The ring shape of dermatophyte lesions result from outward growth of the fungi. The fungi spread in a centrifugal pattern in the stratum corneum, which is the outermost keratinized layer of the skin.

For nail infections, the growth initiates through the lateral or superficial nail plates, then continues throughout the nail. For hair infections, fungal invasion begins at the hair shaft.

Symptoms manifest from inflammatory reactions due to the fungal antigens. The rapid turnover of desquamation, or skin peeling, due to inflammation limits dermatophytoses, as the fungi are pushed out of the skin.

Dermatophytoses rarely cause serious illness, as the fungi infection tends to be limited to the superficial skin. The infection tends to self-resolve so long as the fungal growth does not exceed inflammatory response and desquamation rate is sufficient. If immune response is insufficient, however, infection may progress to chronic inflammation.

Immune response

Fortunately, dermatophytoses soon progress from the inflammatory stage to spontaneous healing, which is largely cell-mediated. Fungi are destroyed via oxidative pathways by phagocytes both intracellularly and extracellularly. T-cell-mediated response using TH1 cells are likely responsible for controlling infection. It is unclear whether the antifungal antibodies formed in response to the infection play a role in immunity.

Infection may become chronic and widespread if the host has a compromised immune system and is receiving treatment that reduces T-lymphocyte function. Also, the responsible species for chronic infections in both normal and immunocompromised patients tends to be Trichophyton rubrum; immune response tends to be hyporeactive. However, "the clinical manifestations of these infections are largely due to delayed-type hypersensitivity responses to these agents rather than from direct effects of the fungus on the host."

Diagnosis and identification

Usually, dermatophyte infections can be diagnosed by their appearance. However, a confirmatory rapid in-office test can also be conducted, which entails using a scalpel to scrape off a lesion sample from the nail, skin, or scalp and transferring it to a slide. Potassium hydroxide (KOH) is added to the slide and the sample is examined with a microscope to determine presence of hyphae. Care should be taken in procurement of a sample, as false-negative results may occur if the patient is already using an antifungal, if too small a sample is obtained, or if sample from a wrong site is collected.

Additionally, a Wood's lamp examination (ultraviolet light) may be used to diagnose specific dermatophytes that fluoresce. Should there be an outbreak or if a patient is not responding well to therapy, sometimes a fungal culture is indicated. A fungal culture is also used when long-term oral therapy is being considered.

Fungal culture medium can be used for positive identification of the species. The fungi tend to grow well at 25 degrees Celsius on Sabouraud agar within a few days to a few weeks. In the culture, characteristic septate hyphae can be seen interspersed among the epithelial cells, and the conidia may form either on the hyphae or on conidiophores. Trichophyton tonsurans, the causative agent of tinea capitis (scalp infection) can be seen as solidly packed arthrospores within the broken hairshafts scraped from the plugged black dots of the scalp. Microscopic morphology of the micro- and macroconidia is the most reliable identification character, but both good slide preparation and stimulation of sporulation in some strains are needed. While small microconidia may not always form, the larger macroconidia aids in identification of the fungal species.

Culture characteristics such as surface texture, topography and pigmentation are variable, so they are the least reliable criteria for identification. Clinical information such as the appearance of the lesion, site, geographic location, travel history, animal contacts and race is also important, especially in identifying rare non-sporulating species like Trichophyton concentricum, Microsporum audouinii and Trichophyton schoenleinii.

A special agar called Dermatophyte Test Medium (DTM) has been formulated to grow and identify dermatophytes. Without having to look at the colony, the hyphae, or macroconidia, one can identify the dermatophyte by a simple color test. The specimen (scraping from skin, nail, or hair) is embedded in the DTM culture medium. It is incubated at room temperature for 10 to 14 days. If the fungus is a dermatophyte, the medium will turn bright red. If the fungus is not a dermatophyte, no color change will be noted. If kept beyond 14 days, false positive can result even with non-dermatophytes. Specimen from the DTM can be sent for species identification if desired.

Often dermatophyte infection may resemble other inflammatory skin disorders or dermatitis, thus leading to misdiagnosis of fungal infections.

Transmission

Dermatophytes are transmitted by direct contact with an infected host (human or animal) or by direct or indirect contact with infected shed skin or hair in fomites such as clothing, combs, hair brushes, theatre seats, caps, furniture, bed linens, shoes, socks, towels, hotel rugs, sauna, bathhouse, and locker room floors. Also, transmission may occur from soil-to-skin contact. Depending on the species the organism may be viable in the environment for up to 15 months.

While even healthy individuals may become infected, there is an increased susceptibility to infection when there is a preexisting injury to the skin such as scars, burns, excessive temperature and humidity. Adaptation to growth on humans by most geophilic species resulted in diminished loss of sporulation, sexuality, and other soil-associated characteristics.

Classification

Dermatophytes are classified as anthropophilic (humans), zoophilic (animals) or geophilic (soil) according to their normal habitat.

• Anthropophilic dermatophytes are restricted to human hosts and produce a mild, chronic inflammation.
• Zoophilic organisms are found primarily in animals and cause marked inflammatory reactions in humans who have contact with infected cats, dogs, cattle, horses, birds, or other animals. Infection may also be transmitted via indirect contact with infected animals, such as by their hair. This is followed by a rapid termination of the infection.
• Geophilic species are usually recovered from the soil but occasionally infect humans and animals. They cause a marked inflammatory reaction, which limits the spread of the infection and may lead to a spontaneous cure but may also leave scars.

Sexual reproduction

Dermatophytes reproduce sexually by either of two modes, heterothallism or homothallism. In heterothallic species, interaction of two individuals with compatible mating types are required in order for sexual reproduction to occur. In contrast, homothallic fungi are self-fertile and can complete a sexual cycle without a partner of opposite mating type. Both types of sexual reproduction involve meiosis.

Frequency of species

In North America and Europe, the nine most common dermatophyte species are:

• Trichophyton: rubrum, tonsurans, mentagrophytes, verrucosum, and schoenlenii
• Microsporum: canis, audouinii, and gypseum
• Epidermophyton: floccosum
• About 76% of the dermatophyte species isolated from humans are Trichophyton rubrum.
• 27% are Trichophyton mentagrophytes
• 7% are Trichophyton verrucosum
• 3% are Trichophyton tonsurans
• Infrequently isolated (less than 1%) are Epidermophyton floccosum, Microsporum audouinii, Microsporum canis, Microsporum equinum, Microsporum nanum, Microsporum versicolor, Trichophyton equinum, Trichophyton kanei, Trichophyton raubitschekii, and Trichophyton violaceum.

The mixture of species is quite different in domesticated animals and pets (see ringworm for details).

Epidemiology

Since dermatophytes are found worldwide, infections by these fungi are extremely common.

Infections occur more in males than in females, as the predominantly female hormone, progesterone, inhibits the growth of dermatophyte fungi.

Medications

General medications for dermatophyte infections include topical ointments.

• Topical medications like clotrimazole, butenafine, miconazole, and terbinafine.
• Systemic medications (oral) like fluconazole, griseofulvin, terbinafine, and itraconazole.

For extensive skin lesions, itraconazole and terbinafine can speed up healing. Terbinafine is preferred over itraconazole due to fewer drug interactions.

Treatment

Tinea corpora (body), tinea manus (hands), tinea cruris (groin), tinea pedis (foot) and tinea facie (face) can be treated topically.

Tinea unguium (nails) usually will require oral treatment with terbinafine, itraconazole, or griseofulvin. Griseofulvin is usually not as effective as terbinafine or itraconazole. A lacquer (Penlac) can be used daily, but is ineffective unless combined with aggressive debridement of the affected nail.

Tinea capitis (scalp) must be treated orally, as the medication must be present deep in the hair follicles to eradicate the fungus. Usually griseofulvin is given orally for 2 to 3 months. Clinically dosage up to twice the recommended dose might be used due to relative resistance of some strains of dermatophytes.

Tinea pedis is usually treated with topical medicines, like ketoconazole or terbinafine, and pills, or with medicines that contains miconazole, clotrimazole, or tolnaftate. Antibiotics may be necessary to treat secondary bacterial infections that occur in addition to the fungus (for example, from scratching).

Tinea cruris (groin) should be kept dry as much as possible.