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الانزيمات
Cutaneous mycoses
المؤلف:
Stefan Riedel, Jeffery A. Hobden, Steve Miller, Stephen A. Morse, Timothy A. Mietzner, Barbara Detrick, Thomas G. Mitchell, Judy A. Sakanari, Peter Hotez, Rojelio Mejia
المصدر:
Jawetz, Melnick, & Adelberg’s Medical Microbiology
الجزء والصفحة:
28e , p681-685
2026-02-01
57
Dermatophytosis
Cutaneous mycoses are caused by fungi that infect only the keratinized tissue (skin, hair, and nails). The most important of these are the dermatophytes, a group of about 40 related fungi that belong to three genera: Microsporum, Trichophyton, and Epidermophyton. Dermatophytes are restricted to the nonviable skin because most are unable to grow at 37°C or in the presence of serum. Dermatophytoses are among the most prevalent infections in the world. Although they can be persistent and troublesome, they are rarely debilitating or life threatening—yet billions of dollars are expended annually in their treatment. Being superficial, dermatophyte (ringworm) infections have been recognized since antiquity. In skin, they are diagnosed by the presence of hyaline, septate, branching hyphae, or chains of arthroconidia. In culture, the many species are closely related and often difficult to identify. They are speciated on the basis of subtle differences in the appearance of the colonies and microscopic morphology as well as a few vitamin requirements. Despite their similarities in morphology, nutritional requirements, surface antigens, and other features, many species have particular keratinases, elastases, and other enzymes that enable them to be quite host-specific. The identification of closely related and outbreak strains has been greatly aided by DNA sequence analysis. The several dermatophytic species that are capable of sexual reproduction produce ascospores and belong to the teleomorphic genus Arthroderma.
Dermatophytes are acquired by contact with contaminated soil or with infected animals or humans. The species are classified as geophilic, zoophilic, or anthropophilic depending on whether their usual habitat is soil, animals, or humans. Several dermatophytes that normally reside in soil or are associated with particular animal species are also able to cause human infections. In general, as a species evolves from habitation in soil to a specific animal or human host, it loses the ability to produce asexual conidia and to reproduce sexually. Anthropophilic species cause the greatest number of human infections. They elicit relatively mild and chronic infections, produce few conidia in culture, and may be difficult to eradicate. Conversely, geophilic and zoophilic dermatophytes, being less adapted to human hosts, produce more acute inflammatory infections that tend to resolve more quickly.
Some anthropophilic species are geographically restricted, but others, such as E. floccosum, Trichophyton mentagrophytes var. interdigitale, Trichophyton rubrum, and Trichophyton tonsurans, are globally distributed. The most common geophilic species causing human infections is Microsporum gypseum. Cosmopolitan zoophilic species (and their natural hosts) include Microsporum canis (dogs and cats), Microsporum gallinae (fowl), Microsporum nanum (pigs), Trichophyton equinum (horses), and Trichophyton verrucosum (cattle).
Morphology and Identification
The more common dermatophytes are identified by their colonial appearance and microscopic morphology after growth for 2 weeks at 25°C on SDA. Trichophyton species, which may infect hair, skin, or nails, develop cylindric, smooth-walled macroconidia and characteristic microconidia (Figure 1A). Depending on the variety, colonies of T. mentagrophytes may be cottony to granular; both types display abundant grape-like clusters of spherical micro conidia on terminal branches. Coiled or spiral hyphae are commonly found in primary isolates. The typical colony of T. rubrum has a white, cottony surface and a deep red, nondiffusible pigment when viewed from the reverse side of the colony. The microconidia are small and piriform (pear-shaped). T. tonsurans produces a flat, powdery to velvety colony on the obverse surface that becomes reddish brown on reverse; the microconidia are mostly elongate (see Figure 1A).
Fig1. Examples of the three genera of dermatophytes. A: T. tonsurans is characterized by the production of elongated microcondia attached to a supporting hypha. B: M. gypseum produces individual thin- and rough-walled macroconidia. C: E. floccosum has club-shaped, thin- and smooth-walled macroconidia that typically arise in small clusters.
Microsporum species tend to produce distinctive multicellular macroconidia with echinulate walls (see Figure 1B). Both types of conidia are borne singly in these genera. M. canis forms a colony with a white cottony surface and a deep yellow color on reverse; the thick-walled, 8- to 15-celled macroconidia frequently have curved or hooked tips. M. gypseum produces a tan, powdery colony and abundant thin-walled, four- to six-celled macroconidia. Microsporum species infect only hair and skin.
E. floccosum, which is the only pathogen in this genus, produces only macroconidia, which are smooth-walled, clavate, two- to four-celled, and formed in small clusters (see Figure 1C). The colonies are usually flat and velvety with a tan to olive-green tinge. E. floccosum infects the skin and nails but not the hair.
In addition to gross and microscopic morphology, a few nutritional or other tests, such as growth at 37°C or a test for in vitro hair perforation, are useful in differentiating certain species. Atypical isolates can usually be identified by species specific polymerase chain reaction (PCR) tests.
Epidemiology and Immunity
Dermatophyte infections begin in the skin after trauma and contact. There is evidence that host susceptibility may be enhanced by moisture, warmth, specific skin chemistry, composition of sebum and perspiration, youth, heavy expo sure, and genetic predisposition. The incidence is higher in hot, humid climates and under crowded living conditions. Shoes provide warmth and moisture, a setting for infections of the feet. The source of infection is soil or an infected ani mal in the case of geophilic and zoophilic dermatophytes, respectively. Anthropophilic species may be transmitted by direct contact or through fomites, such as contaminated towels, clothing, shared shower stalls, and similar examples. Unlike other fungal infections, dermatophytes are contagious and frequently transmitted by exposure to shed skin scales, nails, or hair containing hyphae or conidia. These fungal elements can remain viable for long periods on fomites.
Trichophytin is a crude antigen preparation that can be used to detect immediate- or delayed-type hypersensitivity to dermatophytic antigens. Many patients who develop chronic, noninflammatory dermatophyte infections have poor cell mediated immune responses to dermatophyte antigen. These patients often are atopic and have immediate-type hypersensitivity and elevated IgE antibody levels. In the normal host, immunity to dermatophytosis varies in duration and degree depending on the host, the site, and the species of fungus causing the infection.
Clinical Findings
Dermatophyte infections were mistakenly described as ring worm or tinea because of the raised circular lesions, and tradition has maintained this terminology. The clinical forms are based on the site of involvement. A single species is able to cause more than one type of clinical infection. Conversely, a single clinical form, such as tinea corporis, may be caused by more than one dermatophyte species. Table 1 lists the more prevalent etiologies of common clinical forms. Very rarely, immunocompromised patients may develop systemic infection by a dermatophyte.
Table1. Some Clinical Features of Dermatophyte Infection
A. Tinea Pedis (Athlete’s Foot)
Tinea pedis is the most prevalent of all dermatophytoses. It usually occurs as a chronic infection of the toe webs. Other varieties are the vesicular, ulcerative, and moccasin types, with hyperkeratosis of the sole. Initially, there is itching between the toes and the development of small vesicles that rupture and discharge a thin fluid. The skin of the toe webs becomes macerated and peels, whereupon cracks appear that are prone to develop secondary bacterial infection. When the fungal infection becomes chronic, peeling and cracking of the skin are the principal manifestations, accompanied by pain and pruritus.
B. Tinea Unguium (Onychomycosis)
Nail infection may follow prolonged tinea pedis. With hyphal invasion, the nails become yellow, brittle, thickened, and crumbly. One or more nails of the feet or hands may be involved.
C. Tinea Corporis, Tinea Cruris, and Tinea Manus
Dermatophytosis of the glabrous skin commonly gives rise to the annular lesions of ringworm, with a clearing, scaly center surrounded by a red advancing border that may be dry or vesicular. The dermatophyte grows only within dead, keratinized tissue, but fungal metabolites, enzymes, and antigens diffuse through the viable layers of the epidermis to cause erythema, vesicle formation, and pruritus. Infections with geophilic and zoophilic dermatophytes produce more irritants and are more inflammatory than anthropophilic species. As hyphae age, they often form chains of arthroconidia. The lesions expand centrifugally, and active hyphal growth occurs at the periphery, which is the most likely region from which to obtain material for diagnosis. Penetration into the newly forming stratum corneum of the thicker plantar and palmar surfaces accounts for the persistent infections at those sites.
When the infection occurs in the groin area, it is called tinea cruris, or jock itch. Most such infections involve males and present as dry, itchy lesions that often start on the scrotum and spread to the groin. Tinea manus refers to ringworm of the hands or fingers. Dry scaly lesions may involve one or both hands, single fingers, or two or more fingers.
D. Tinea Capitis and Tinea Barbae
Tinea capitis is dermatophytosis or ringworm of the scalp and hair. The infection begins with hyphal invasion of the skin of the scalp, with subsequent spread down the keratinized wall of the hair follicle. Infection of the hair takes place just above the hair root. The hyphae grow downward on the nonliving portion of the hair and at the same rate as the hair grows upward. The infection produces dull gray, circular patches of alopecia, scaling, and itching. As the hair grows out of the follicle, the hyphae of Microsporum species produce a chain of spores that form a sheath around the hair shaft (ectothrix). These spores impart a greenish to silvery fluorescence when the hairs are examined under Wood’s light (365 nm). In contrast, T. tonsurans, the chief cause of “black dot” tinea capitis, produces spores within the hair shaft (endothrix). These hairs do not fluoresce; they are weakened and typically break easily at the follicular opening. In prepubescent children, epidemic tinea capitis is usually self-limiting.
Zoophilic species may induce a severe combined inflammatory and hypersensitivity reaction called a kerion. Another manifestation of tinea capitis is favus, an acute inflammatory infection of the hair follicle caused by Trichophyton schoenleinii, which leads to the formation of scutula (crusts) around the follicle. In favic hairs, the hyphae do not form spores but can be found within the hair shaft. Tinea barbae involves the bearded region. Especially when a zoophilic dermatophyte is involved, a highly inflammatory reaction may be elicited that closely resembles pyogenic infection.
E. Trichophytid Reaction
In the course of dermatophytosis, the patient may become hypersensitive to constituents or products of the fungus and develop allergic manifestations—called dermatophytids (usually vesicles)—elsewhere on the body, most often on the hands. The trichophytin skin test is markedly positive in such persons.
Diagnostic Laboratory Tests
A. Specimens and Microscopic Examination
Specimens consist of scrapings from both the skin and the nails plus hairs plucked from involved areas. In KOH preps of skin or nails, regardless of the infecting species, branching hyphae or chains of arthroconidia (arthrospores) are seen (Figure2). In hairs, most Microsporum species form dense sheaths of spores around the hair (ectothrix). The ectothrix spores of Microsporum-infected hairs fluoresce under Wood’s light in a darkened room. T. tonsurans and Trichophyton violaceum are noted for producing arthroconidia inside the hair shaft (endothrix).
Fig2. Dermatophytosis. Unstained microscopic KOH preparation of scrapings from a ringworm lesion. The epidermal cells are lysed by KOH to reveal hyaline branching septate hyphae. 100×. (Reproduced with permission from Ryan KJ, Ray CG [editors]: Sherris Medical Microbiology, 5th ed. McGraw-Hill, 2010, p. 700. © McGraw-Hill Education.)
B. Culture
The identification of dermatophytic species requires cultures. Specimens are inoculated onto IMA or SDA slants containing cycloheximide and chloramphenicol to suppress mold and bacterial growth, incubated for 1–3 weeks at room temperature, and further examined in slide cultures if necessary.
Species are identified on the basis of colonial morphology (growth rate, surface texture, and any pigmentation), microscopic morphology (macroconidia, microconidia), and, in some cases, nutritional requirements.
Treatment
Therapy consists of thorough removal of infected and dead epithelial structures and application of a topical antifungal drug. To prevent reinfection the area should be kept dry, and sources of infection, such as an infected pet or shared bathing facilities, should be avoided.
Scalp (tinea capitis) infections are treated for several weeks with oral administration of griseofulvin or terbinafine. Frequent shampoos and miconazole cream or other topical antifungal agents may be effective if used for weeks. Alternatively, ketoconazole and itraconazole are quite effective.
For tinea corporis, tinea pedis, and related infections, the most effective drugs are itraconazole and terbinafine. However, a number of topical preparations may be used, such as miconazole nitrate, tolnaftate, and clotrimazole. If applied for at least 2–4 weeks, the cure rates are usually 70–100%. Treatment should be continued for 1–2 weeks after clearing of the lesions. For troublesome cases, a short course of oral griseofulvin can be administered.
Nail infections (tinea unguium) are the most difficult to treat, often requiring months of oral itraconazole or terbinafine as well as surgical removal of the nail. Relapses are common. A new topical imidazole, luliconazole, has been formulated to penetrate the nail plate and demonstrated potent effectiveness against dermatophytes and onychomycosis.
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