Medical Mycology PDF

SECTION V MYCOLOGY 45 C Medical Mycology Mycology is the study of fungi, which are eukaryotic organisms that evolved in tandem with the animal kingdom. However, unlike animals, most fungi are nonmotile and possess a rigid cell wall. Unlike plants, fungi are nonphotosynthetic. Approximately 80,000...

SECTION V MYCOLOGY 45 C Medical Mycology Mycology is the study of fungi, which are eukaryotic organisms that evolved in tandem with the animal kingdom. However, unlike animals, most fungi are nonmotile and possess a rigid cell wall. Unlike plants, fungi are nonphotosynthetic. Approximately 80,000 species of fungi have been described, but fewer than 400 are medically important, and less than 50 species cause more than 90% of the fungal infections of humans and other animals. Rather, most species of fungi are beneficial to humankind. They reside in nature and are essential in breaking down and recycling organic matter. Some fungi greatly enhance our quality of life by contributing to the production of food and spirits, including cheese, bread, and beer. Other fungi have served medicine by providing useful bioactive secondary metabolites such as antibiotics (eg, penicillin) and immunosuppressive drugs (eg, cyclosporine). Fungi have been exploited by geneticists and molecular biologists as model systems for the investigation of a variety of eukaryotic processes, including molecular and cellular biology and development. Overall, fungi exert their greatest economic impact as phytopathogens; the agricultural industry sustains huge crop losses every year as a result of fungal diseases of rice, corn, grains, and other plants. Like all eukaryotes, each fungal cell has at least one nucleus with a nuclear membrane, endoplasmic reticulum, mitochondria, and secretory apparatus. Most fungi are obligate or H A P T E R facultative aerobes. They are chemotrophic, secreting enzymes that degrade a wide variety of organic substrates into soluble nutrients which are then passively absorbed or taken into the cell by active transport. Fungal infections are mycoses. Most pathogenic fungi are exogenous, their natural habitats being water, soil, and organic debris. The mycoses with the highest incidence— candidiasis and dermatophytosis—are caused by fungi that are part of the normal human microbiota and highly adapted to survival on the human host. For convenience, mycoses may be classified as superficial, cutaneous, subcutaneous, or systemic, invading the internal organs (Table 45-1). The systemic mycoses may be caused by endemic fungi, which are usually primary pathogens, or by ubiquitous, often secondary opportunistic pathogens. Grouping mycoses in these categories reflects their most common portal of entry and initial site of involvement. However, there is considerable overlap, since systemic mycoses often exhibit subcutaneous manifestations and vice versa. Most patients who develop opportunistic infections have serious underlying diseases and compromised host defenses. But primary systemic mycoses also occur in such patients, and the opportunists often infect immunocompetent individuals. During infection, most patients develop significant cellular and humoral immune responses to the fungal antigens. 671 www.ketabdownload.com 672 SECTION V Mycology G LOSSARY Conidia: Asexual reproductive structures (mitospores) produced either from the transformation of a vegetative yeast or hyphal cell or from a specialized conidiogenous cell, which may be simple or complex and elaborate. Conidia may be formed on specialized hyphae, termed conidiophores. Microconidia are small, and macroconidia are large or multicellular. Arthroconidia (arthrospores): Conidia that result from the fragmentation of hyphal cells (Figure 45-1). Blastoconidia (blastospores): Conidial formation through a budding process (eg, yeasts). Chlamydospores (chlamydoconidia): Large, thickwalled, usually spherical conidia produced from terminal or intercalary hyphal cells. Phialoconidia: Conidia that are produced by a “vaseshaped” conidiogenous cell termed a phialide (eg, Aspergillus fumigatus, Figure 45-6). Dematiaceous fungi: Fungi whose cell walls contain melanin, which imparts a brown to black pigment. Dimorphic fungi: Fungi that have two growth forms, such as a mold and a yeast, which develop under different growth conditions (eg, Blastomyces dermatitidis forms hyphae in vitro and yeasts in tissue). Hyphae: Tubular, branching filaments (2–10 µm in width) of fungal cells, the mold form of growth. Most hyphal cells are separated by porous cross-walls or septa, but the zygomycetous hyphae are characteristically sparsely septate. Vegetative or substrate hyphae anchor the colony and absorb nutrients. Aerial hyphae project above the colony and bear the reproductive structures. Imperfect fungi: Fungi that lack sexual reproduction; they are represented only by an anamorph, the mitotic As medical advances have significantly prolonged the survival of patients with cancer, AIDS, and hematopoietic stem cell or solid organ transplants, the incidence of opportunistic mycoses has increased dramatically. Pathogenic fungi do not produce potent toxins, and the mechanisms of fungal pathogenicity are complex and polygenic. Most mycoses are difficult to treat. Because fungi are eukaryotes, they share numerous homologous genes, gene products, and pathways with their human hosts. Consequently, there are few unique targets for chemotherapy and effective antibiotics. Fortunately, there is growing interest in medically significant fungi and in the search for virulence factors and potential therapeutic targets. GENERAL PROPERTIES AND CLASSIFICATION OF FUNGI Fungi grow in two basic forms, as yeasts and molds (or moulds). Growth in the mold form occurs by the production or asexual reproductive state. They are identified on the basis of asexual reproductive structures (ie, mitospores). Mold: Hyphal or mycelial colony or form of growth. Mycelium: Mass or mat of hyphae, mold colony. Perfect fungi: Fungi that are capable reproduction, which is the teleomorph. of sexual Pseudohyphae: Chains of elongated buds or blastoconidia. Septum: Hyphal cross-wall, typically perforated. Sporangiospores: Asexual structures characteristic of the Order Mucorales; they are mitotic spores produced within an enclosed sporangium, often supported by one sporangiophore (Figures 45-2 and 45-3). Spore: A specialized propagule with enhanced survival value, such as resistance to adverse conditions or structural features that promote dispersion. Spores may result from asexual (eg, conidia, sporangiospores) or sexual (see below) reproduction. Sexual spores: During sexual reproduction, haploid cells of compatible strains mate through a process of plasmogamy, karyogamy, and meiosis. Ascospores: In the Phylum Ascomycota, following meiosis, four to eight meiospores form within an ascus. Basidiospores: In the Phylum Basidiomycota, following meiosis, four meiospores usually form on the surface of a specialized structure, a club-shaped basidium. Zygospores: In the Order Mucorales, following meiosis, a large, thick-walled zygospore develops. Yeasts: Unicellular, spherical to ellipsoid (3–15 µm) fungal cells that usually reproduce by budding. of multicellular filamentous colonies. These colonies consist of branching cylindric tubules called hyphae, varying in diameter from 2 to 10 µm. The mass of intertwined hyphae that accumulates during active growth is a mycelium. Some hyphae are divided into cells by cross-walls or septa, which typically form at regular intervals during hyphal growth. However, members of the Order Mucorales produce hyphae that are rarely septated. Vegetative or substrate hyphae penetrate the supporting medium, anchor the colony, and absorb nutrients. In contrast, aerial hyphae project above the surface of the mycelium and usually bear the reproductive structures of the mold. When a mold is isolated from a clinical specimen, its growth rate, macroscopic appearance, and microscopic morphology are usually sufficient to determine its genus and species. The most helpful phenotypic features are the ontogeny and morphology of the asexual reproductive spores, or conidia. (See Figures 45-2 through 45-8.) www.ketabdownload.com CHAPTER 45 TABLE 45-1 Medical Mycology 673 The Major Mycoses and Causative Fungi Category Mycosis Causative Fungal Agents Superficial Pityriasis versicolor Tinea nigra White piedra Black piedra Malassezia species Hortaea werneckii Trichosporon species Piedraia hortae Cutaneous Dermatophytosis Candidiasis of skin, mucosa, or nails Microsporum species, Trichophyton species, and Epidermophyton floccosum Candida albicans and other Candida species Subcutaneous Sporotrichosis Chromoblastomycosis Mycetoma Phaeohyphomycosis Sporothrix schenckii Phialophora verrucosa, Fonsecaea pedrosoi, and others Pseudallescheria boydii, Madurella mycetomatis, and others Exophiala, Bipolaris, Exserohilum, and other dematiaceous molds Endemic (primary, systemic) Coccidioidomycosis Histoplasmosis Blastomycosis Paracoccidioidomycosis Coccidioides posadasii and Coccidioides immitis Histoplasma capsulatum Blastomyces dermatitidis Paracoccidioides brasiliensis Opportunistic Systemic candidiasis Cryptococcosis Aspergillosis Hyalohyphomycosis Phaeohyphomycosis Candida albicans and many other Candida species Cryptococcus neoformans and Cryptococcus gattii Aspergillus fumigatus and other Aspergillus species Species of Fusarium, Paecilomyces, Trichosporon, and other hyaline molds Cladophialophora bantiana; species of Alternaria, Cladosporium, Bipolaris, Exserohilum and numerous other dematiaceous molds Species of Rhizopus, Lichtheimia, Cunninghamella, and other zygomycetes Pneumocystis jiroveci Penicillium marneffei Mucormycosis (zygomycosis) Pneumocystis pneumonia Penicilliosis Yeasts are single cells, usually spherical to ellipsoid in shape and varying in diameter from 3 to 15 µm. Most yeasts reproduce by budding. Some species produce buds that characteristically fail to detach and become elongated; continuation of the budding process then produces a chain of elongated yeast cells called pseudohyphae. Yeast colonies FIGURE 45-2 FIGURE 45-1 Arthroconidia formed by the fragmentation of hyphal cells into compact conidia. 400×. Rhizopus. The sporangium of this mold has released its sporangiospores but remains attached to the supporting sporangiophore, and rhizoids are apparent at the base of the sporangiophore. 200×. www.ketabdownload.com 674 SECTION V Mycology FIGURE 45-3 Cunninghamella bertholletiae. The sporangiospores are produced within sporangiola that are attached to a vesicle and supported by a sporangiophore. 400×. are usually soft, opaque, 1–3 mm in size, and cream-colored. Because the colonies and microscopic morphology of many yeasts are quite similar, yeast species are identified on the basis of physiologic tests and a few key morphologic differences. FIGURE 45-4 Penicillium. Chains of conidia are generated by phialides, which are supported by a branched conidiophore. The basal conidium is newest. 400×. FIGURE 45-5 Scopulariopsis. This chain of conidia was produced by an annellide, which is another type of conidiogenous cell. 400×. Some species of fungi are dimorphic and capable of growth as a yeast or mold depending on environmental conditions. Fungi have an essential rigid cell wall that determines their shape and protects them from osmotic and environmental stress. Cell walls are composed largely of carbohydrate layers—long chains of polysaccharides—as well as glycoproteins and lipids. Some sugar polymers are found in the cell walls of many fungi, such as chitin (an unbranched polymer of β-1,4-linked N-acetylglucosamine); glucans, which are glucose polymers (eg, β-1,3-glucan and β-1,6-glucan); and mannans, polymers of mannose (eg, α-1,6-mannose). In addition, other polysaccharides may be unique to specific fungal species. During infection, fungal cell walls exert important pathobiologic properties. The surface components of the cell wall mediate attachment of the fungus to host cells. Specific fungal cell wall moieties bind to pattern recognition receptors on host cell membranes, such as certain toll-like receptors, to stimulate innate immune responses. Cell wall glucans and other polysaccharides may activate the complement cascade and provoke an inflammatory reaction. Most of these polysaccharides are poorly degraded by the host and can be detected with special histologic stains. Cell walls also release immunodominant antigens that may elicit cellular immune responses and diagnostic antibodies. In addition, some yeasts and molds have melanized cell walls, which impart a brown or black www.ketabdownload.com CHAPTER 45 Medical Mycology 675 FIGURE 45-7 FIGURE 45-6 Aspergillus fumigatus. Phialides form on top of a swollen vesicle at the end of a long conidiophore. The basal conidia are the youngest. Mature conidia have rough walls. 400×. pigment to the fungal colony. Such fungi are dematiaceous. Several studies have shown that melanin protects these fungi from host defenses and is associated with virulence. The life cycles of fungi are remarkably versatile. Depending on the fungal species, the predominant nuclear chromosomal count may be haploid or diploid. Some species exist entirely by clonal growth or asexual reproduction, and barring spontaneous mutations, every cell will be a genetic clone. Other species are capable of sexual reproduction, which may or may not require genetically different partners for mating and meiosis. Asexual as well as sexual reproduction can result in the production of spores, which enhance fungal survival. Spores are usually dormant, readily dispersed, more resistant to adverse conditions, and germinate to form vegetative cells when conditions for growth are favorable. Spores derived from asexual or sexual reproduction are termed anamorphic or teleomorphic states, respectively. Like vegetative cells, asexual spores are mitotic progeny (ie, mitospores). The medical fungi produce two major types of asexual spores, conidia, which are produced by most pathogenic fungi, and, in the Order Mucorales, sporangiospores (see below and Glossary). Informative features of spores include their ontogeny (some molds produce complex conidiogenic structures) as well as their morphology (size, shape, texture, color, and unicellularity or multicellularity). Bipolaris. Dematiaceous mold that produces characteristic thick-walled macroconidia. 400×. In some fungi, vegetative cells may transform into conidia (eg, arthroconidia, chlamydospores). In others, conidia are produced by a conidiogenous cell, such as a phialide, which itself may be attached to a specialized hypha called a conidiophore. Sporangiospores result from mitotic replication and spore production within a sac-like structure called a sporangium, which is supported by a sporangiophore. Taxonomy Earlier classifications of fungi into phyla were based largely on phenotypic data, and this approach has been supplanted by molecular systematics, which more accurately reflect phylogenetic relationships, At the basal level, there is some ambiguity about the divergence of fungi and animals and their extant ancesters. The lower fungi were assigned to the Phylum Zygomycota, but this phylum, which was shown to be polyphyletic, has been replaced by the Phylum Glomerulomycota and four subphyla, two of which contain the Orders of zoopathogenic molds, the Mucorales and the Entomophthorales. However, the two largest phyla, Ascomycota and Basidiomycota, are well supported by phylogenetic analyses. Phylum Ascomycota (or ascomycetes) includes more than 60% of the known fungi and about 85% www.ketabdownload.com 676 SECTION V Mycology B. Phylum Ascomycota (Ascomycetes) Sexual reproduction involves a sac or ascus in which karyogamy and meiosis occur, producing ascospores. Asexual reproduction is via conidia. Ascomycetous molds have septate hyphae. Examples: Most pathogenic yeasts (Saccharomyces, Candida) and molds (Coccidioides, Blastomyces, Trichophyton). C. Phylum Basidiomycota (Basidomycetes) Sexual reproduction results in dikaryotic hyphae and four progeny basidiospores supported by a club-shaped basidium. Hyphae have complex septa. Examples: Mushrooms, Cryptococcus. GROWTH AND ISOLATION OF FUNGI FIGURE 45-8 Curvularia. Dematiaceous mold that produces characteristic curved macroconidia with distinctly larger central cells. 400×. of the human pathogens. Most of the other pathogenic fungi are members of the Phylum Basidiomycota (basidiomycetes) or the Order Mucorales of the Phylum Glomerulomycota. In the diagnostic laboratory, the species of a clinical isolate can be identified by molecular or phenotypic methods (eg, signature DNA sequences, morphology of reproductive structures, physiologic properties). Sexual reproduction may be helpful and typically occurs when mating-compatible strains of a species are stimulated by pheromones to undergo plasmogamy, karyogamy (nuclear fusion), and meiosis, resulting in the exchange of genetic information. Since clinical isolates almost always represent infection by a single clone, they reproduce asexually in the laboratory. Consequently, many pathogenic fungi were initially classified according to their asexual reproductive structures. During the evolution to become successful pathogens, some fungi have apparently lost the ability to reproduce sexually. The following classification is highly abridged and only lists taxonomic groups that include major human pathogens A. Phylum Glomerulomycta, Order Mucorales Sexual reproduction results in a zygospore; asexual reproduction occurs via sporangia. Vegetative hyphae are sparsely septate. Examples: Rhizopus, Lichtheimia, Mucor, Cunninghamella. Most fungi occur in nature and grow readily on simple sources of nitrogen and carbohydrate. The traditional mycological medium, Sabouraud’s agar, which contains glucose and modified peptone (pH 7.0), has been used because it does not readily support the growth of bacteria. The morphologic characteristics of fungi used for identification have been described from growth on Sabouraud’s agar. However, other media, such as inhibitory mold agar, have facilitated the recovery of fungi from clinical specimens. To culture medical fungi from non-sterile specimens, antibacterial antibiotics (eg, gentamicin, chloramphenicol) and cycloheximide are added to the media to inhibit bacteria and saprobic molds, respectively. The specimens used for isolation of fungi and other media used to isolate them are discussed in Chapter 47. SUPERFICIAL MYCOSES Pityriasis Versicolor Pityriasis versicolor is a chronic mild superficial infection of the stratum corneum caused by Malassezia globosa, Malassezia restricta, and other members of the Malassezia furfur complex. Invasion of the cornified skin and the host responses are both minimal. Discrete, serpentine, hyper-, or hypopigmented maculae occur on the skin, usually on the chest, upper back, arms, or abdomen. The lesions are chronic and occur as macular patches of discolored skin that may enlarge and coalesce, but scaling, inflammation, and irritation are minimal. Indeed, this common affliction is largely a cosmetic problem. Malassezia species are lipophilic yeasts, and most require lipid in the medium for growth. The diagnosis is confirmed by direct microscopic examination of scrapings of infected skin, treated with 10–20% potassium hydroxide (KOH) or stained with calcofluor white. Short unbranched hyphae and spherical cells are observed. The lesions also fluoresce under Wood’s lamp. Pityriasis versicolor is treated with daily applications of selenium sulfide. Topical or oral azoles are also effective. Rarely, Malassezia may cause an opportunistic fungemia in patients—usually infants—receiving total parenteral nutrition, as a result of contamination of the lipid emulsion. In most cases, the fungemia is transient and corrected by www.ketabdownload.com CHAPTER 45 replacing the fluid and intravenous catheter. Some individuals develop folliculitis due to Malassezia. Species of Malassezia are considered part of the cutaneous microbiota and can be isolated from normal skin and scalp. They have been implicated as a cause of or contributor to seborrheic dermatitis, or dandruff. This hypothesis is supported by the observation that many cases are alleviated by treatment with ketoconazole. Tinea Nigra Tinea nigra (or tinea nigra palmaris) is a superficial chronic and asymptomatic infection of the stratum corneum caused by the dematiaceous fungus Hortaea (Exophiala) werneckii. This condition is more prevalent in warm coastal regions and among young women. The lesions appear as a dark (brown to black) discoloration, often on the palm. Microscopic examination of skin scrapings from the periphery of the lesion will reveal branched, septate hyphae and budding yeast cells with melanized cell walls. Tinea nigra will respond to treatment with keratolytic solutions, salicylic acid, or azole antifungal drugs. Piedra Black piedra is a nodular infection of the hair shaft caused by Piedraia hortae (Figure 45-9B). White piedra, due to infection with Trichosporon species, presents as larger, softer, yellowish nodules on the hairs (Figure 45-9A). Axillary, pubic, beard, and scalp hair may be infected. Treatment for both types consists of removal of the infected hair and application of a topical antifungal agent. Piedra is endemic in tropical countries. Medical Mycology 677 CUTANEOUS MYCOSES 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 probably 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 not debilitating or lifethreatening—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 developed various 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. For some species of dermatophytes, a sexual reproductive state has been discovered, and all dermatophytes with a sexual form produce ascospores and belong to the teleomorphic genus Arthroderma. B FIGURE 45-9 A Piedra. A:White piedra hair with nodule due to growth of Trichosporon. 200×. B:Black piedra hair with a hard, black nodule, caused by growth of the dematiaceous mold, Piedraia hortae. 200×. www.ketabdownload.com 678 SECTION V Mycology A B C FIGURE 45-10 Examples of the three genera of dermatophytes. A:Trichophyton tonsurans is characterized by the production of elongated microcondia attached to a supporting hypha. B:Microsporum gypseum produces individual thin- and rough-walled macroconidia. C:Epidermophyton floccosum has club-shaped, thin- and smooth-walled macroconidia that typically arise in small clusters. Dermatophytes 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 still 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. Dermatophytes are acquired by contact with contaminated soil or with infected animals or humans. Some anthropophilic species are geographically restricted, but others, such as Epidermophyton 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 Sabouraud’s dextrose agar. Trichophyton species, which may infect hair, skin, or nails, develop cylindric, smooth-walled macroconidia and characteristic microconidia (Figure 45-10A). Depending on the variety, colonies of T mentagrophytes may be cottony to granular; both types display abundant grape-like clusters of spherical microconidia 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). Trichophyton tonsurans produces a flat, powdery to velvety colony on the obverse surface that becomes reddish-brown on reverse; the microconidia are mostly elongate (Figure 45-10A). Microsporum species tend to produce distinctive multicellular macroconidia with echinulate walls (Figure 45-10B). Both types of conidia are borne singly in these genera. Microsporum 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. Microsporum gypseum produces a tan, powdery colony and abundant thinwalled, four- to six-celled macroconidia. Microsporum species infect only hair and skin. Epidermophyton 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 (Figure 45-10C). The colonies are usually flat and velvety with a tan to olive-green tinge. Epidermophyton 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 speciesspecific 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 www.ketabdownload.com CHAPTER 45 TABLE 45-2 Medical Mycology 679 Some Clinical Features of Dermatophyte Infection Skin Disease Location of Lesions Clinical Features Fungi Most Frequently Responsible Tinea corporis (ringworm) Nonhairy, smooth skin Circular patches with advancing red, vesiculated border and central scaling. Pruritic Trichophyton rubrum, Epidermophyton floccosum Tinea pedis (athlete’s foot) Interdigital spaces on feet of persons wearing shoes Acute: itching, red vesicular. Chronic: itching, scaling, fissures Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum Tinea cruris (jock itch) Groin Erythematous scaling lesion in intertriginous area. Pruritic Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum Tinea capitis Scalp hair. Endothrix: fungus inside hair shaft. Ectothrix: fungus on surface of hair Circular bald patches with short hair stubs or broken hair within hair follicles. Kerion rare. Microsporum-infected hairs fluoresce Trichophyton mentagrophytes, Microsporum canis, Trichophyton tonsurans Tinea barbae Beard hair Edematous, erythematous lesion Trichophyton mentagrophytes, Trichophyton rubrum, Trichophyton verrucosum Tinea unguium (onychomycosis) Nail Nails thickened or crumbling distally; discolored; lusterless. Usually associated with tinea pedis Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum Dermatophytid (id reaction) Usually sides and flexor aspects of fingers. Palm. Any site on body Pruritic vesicular to bullous lesions. Most commonly associated with tinea pedis No fungi present in lesion. May become secondarily infected with bacteria sebum and perspiration, youth, heavy exposure, 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 animal 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 cellmediated immune responses to dermatophyte antigen. These patients often are atopic and have immediate-type hypersensitivity and elevated IgE concentrations. 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. by more than one dermatophyte species. Table 45-2 lists the more prevalent etiologies of common clinical forms. Very rarely, immunocompromised patients may develop systemic infection by a dermatophyte. 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 Clinical Findings Dermatophyte infections were mistakenly described as ringworm 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 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 www.ketabdownload.com 680 SECTION V Mycology 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 is 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 T 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. spores of Microsporum-infected hairs fluoresce under Wood’s light in a darkened room. B. Microscopic Examination Specimens are placed on a slide in a drop of 10–20% potassium hydroxide, with or without calcofluor white, which is a nonspecific fungal cell wall stain that can be viewed with a fluorescent microscope. A coverslip is added, and the specimen is examined immediately and again after 20 minutes. In skin or nails, regardless of the infecting species, branching hyphae or chains of arthroconidia (arthrospores) are seen (Figure 45-11). In hairs, most Microsporum species form dense sheaths of spores around the hair (ectothrix). Trichophyton tonsurans and T violaceum are noted for producing arthroconidia inside the hair shaft (endothrix). C. Culture The identification of dermatophyte species requires cultures. Specimens are inoculated onto inhibitory mold agar or Sabouraud’s agar 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 chemical or antibiotic. To prevent reinfection the area should 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. FIGURE 45-11 Diagnostic Laboratory Tests A. Specimens Specimens consist of scrapings from both the skin and the nails plus hairs plucked from involved areas. The ectothrix 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, Figure 41-6, p 700. © The McGraw-Hill Companies, Inc.) www.ketabdownload.com CHAPTER 45 be kept dry, and sources of infection, such as an infected pet or shared bathing facilities, should be avoided. A. Tinea Capitis Scalp 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. B. 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. C. Tinea Unguium Nail infections 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. KEY CONCEPTS: SUPERFICIAL AND CUTANEOUS MYCOSES Medical Mycology SPOROTRICHOSIS Sporothrix schenckii is a thermally dimorphic fungus that lives on vegetation. It is associated with a variety of plants—grasses, trees, sphagnum moss, rose bushes, and other horticultural plants. At ambient temperatures, it grows as a mold, producing branching, septate hyphae and conidia, and in tissue or in vitro at 35–37°C as a small budding yeast. Following traumatic introduction into the skin, S schenckii causes sporotrichosis, a chronic granulomatous infection. The initial episode is typically followed by secondary spread with involvement of the draining lymphatics and lymph nodes. Morphology and Identification Sporothrix schenckii grows well on routine agar media, and at room temperature the young colonies are blackish and shiny, becoming wrinkled and fuzzy with age. Strains vary in pigmentation from shades of black and gray to whitish. The organism produces branching, septate hyphae and distinctive small (3–5 µm) conidia, delicately clustered at the ends of tapering conidiophores. Isolates may also form larger conidia directly from the hyphae. Sporothrix schenckii is thermally dimorphic, and at 35°C on a rich medium it converts to growth as small, often multiply budding yeast cells that are variable in shape but often fusiform (about 1–3 × 3–10 µm), as shown in Figure 45-12. 1. Superficial and cutaneous mycoses are among the most common of all communicable diseases. 2. Most superficial and cutaneous fungal infections are caused by species of Malassezia, dermatophytes, or Candida (discussed later). 3. The growth of dermatophytes is inhibited by serum and body temperature, and these fungi rarely become invasive. 4. Geophilic and zoophilic dermatophytes usually cause acute, inflammatory lesions that respond to topical treatment within weeks and rarely recur. 5. Anthropophilic dermatophytes usually cause relatively mild, chronic lesions that may require months or years of treatment and frequently recur. SUBCUTANEOUS MYCOSES The fungi that cause subcutaneous mycoses normally reside in soil or on vegetation. They enter the skin or subcutaneous tissue by traumatic inoculation with contaminated material. For example, a superficial cut or abrasion may introduce an environmental mold with the ability to infect the exposed dermis. In general, the lesions become granulomatous and expand slowly from the area of implantation. Extension via the lymphatics draining the lesion is slow except in sporotrichosis. These mycoses are usually confined to the subcutaneous tissues, but in rare cases they become systemic and produce life-threatening disease. 681 FIGURE 45-12 Sporotrichosis. Cutaneous tissue revealing the small spherical and elongated budding yeast cells (3–5 µm) of Sporothrix schenckii, which are stained black by the Gomori methenamine silver (GMS) stain. 400×. www.ketabdownload.com 682 SECTION V Mycology Antigenic Structure C. Culture Heat-killed saline suspensions of cultures or carbohydrate fractions (sporotrichin) will elicit positive delayed skin tests in infected humans or animals. A variety of serologic tests have been developed, and most patients, as well as some normal individuals, have specific or cross-reactive antibodies. The most reliable method of diagnosis is culture. Specimens are streaked on inhibitory mold agar or Sabouraud’s agar containing antibacterial antibiotics and incubated at 25–30°C. The identification is confirmed by growth at 35°C and conversion to the yeast form. Pathogenesis and Clinical Findings High titers of agglutinating antibodies to yeast cell suspensions or antigen-coated latex particles are often detected in sera of infected patients. However, these tests are generally not useful because elevated titers do not develop early in the course of disease and uninfected or previously exposed patients may give false-positive results. The conidia or hyphal fragments of S schenckii are introduced into the skin by trauma. Patients frequently recall a history of trauma associated with outdoor activities and plants. The initial lesion is usually located on the extremities but can be found anywhere (children often present with facial lesions). About 75% of cases are lymphocutaneous; that is, the initial lesion develops as a granulomatous nodule that may progress to form a necrotic or ulcerative lesion. Meanwhile, the draining lymphatics become thickened and cord-like. Multiple subcutaneous nodules and abscesses occur along the lymphatics. Fixed sporotrichosis is a single nonlymphangitic nodule that is limited and less progressive. The fixed lesion is more common in endemic areas such as Mexico, where there is a high level of exposure and immunity in the population. Immunity limits the local spread of the infection. There is usually little systemic illness associated with these lesions, but dissemination may occur, especially in debilitated patients. Rarely, primary pulmonary sporotrichosis results from inhalation of the conidia. This manifestation mimics chronic cavitary tuberculosis and tends to occur in patients with impaired cell-mediated immunity. Diagnostic Laboratory Tests A. Specimens Specimens include biopsy material or exudate from granulomatous or ulcerative lesions. B. Microscopic Examination Although specimens can be examined directly with KOH or calcofluor white stain, the yeasts are rarely found. Even though they are sparse in tissue, the sensitivity of histopathologic sections is enhanced with routine fungal cell wall stains, such as Gomori methenamine silver, which stains the cell walls black, or the periodic acid-Schiff stain, which imparts a red color to the cell walls. Alternatively, they can be identified by fluorescent antibody staining. The yeasts are 3–5 µm in diameter and spherical to elongated. Another structure termed an asteroid body is often seen in tissue, particularly in endemic areas such as Mexico, South Africa, and Japan. In hematoxylin and eosin-stained tissue, the asteroid body consists of a central basophilic yeast cell surrounded by radiating extensions of eosinophilic material, which are depositions of antigen–antibody complexes and complement. D. Serology Treatment In some cases, the infection is self-limited. Although the oral administration of saturated solution of potassium iodide in milk is quite effective, it is difficult for many patients to tolerate. The treatment of choice is oral itraconazole or another azole. For systemic disease, amphotericin B is given. Epidemiology and Control Sporothrix schenckii occurs worldwide in close association with plants. For example, cases have been linked to contact with sphagnum moss, rose thorns, decaying wood, pine straw, prairie grass, and other vegetation. About 75% of cases occur in males, either because of increased exposure or because of an X-linked difference in susceptibility. The incidence is higher among agricultural workers, and sporotrichosis is considered an occupational risk for forest rangers, horticulturists, and workers in similar occupations. Prevention includes measures to minimize accidental inoculation and the use of fungicides, where appropriate, to treat wood. Animals are also susceptible to sporotrichosis. CHROMOBLASTOMYCOSIS Chromoblastomycosis (chromomycosis) is a subcutaneous mycotic infection that is usually caused by traumatic inoculation of any of the recognized fungal agents, which reside in soil and vegetation. All are dematiaceous fungi, having melanized cell walls: Phialophora verrucosa, Fonsecaea pedrosoi, Fonsecaea compacta, Rhinocladiella aquaspersa, and Cladophialophora carrionii. The infection is chronic and characterized by the slow development of progressive granulomatous lesions that in time induce hyperplasia of the epidermal tissue. Morphology and Identification The dematiaceous fungi are similar in their pigmentation, antigenic structure, morphology, and physiologic properties. www.ketabdownload.com CHAPTER 45 Medical Mycology 683 FIGURE 45-13 Chromomycosis. The diagnostic brownish, melanized sclerotic cells (4–12 µm diameter) are evident in this H&Estained cutaneous biopsy. 400×. The colonies are compact, deep brown to black, and develop a velvety, often wrinkled surface. The agents of chromoblastomycosis are identified by their modes of conidiation. In tissue they appear the same, producing spherical brown cells (4–12 µm in diameter) termed muriform or sclerotic bodies that divide by transverse septation. Septation in different planes with delayed separation may give rise to a cluster of four to eight cells (Figure 45-13). Cells within superficial crusts or exudates may germinate into septate, branching hyphae. A A. Phialophora verrucosa The conidia are produced from flask-shaped phialides with cup-shaped collarettes. Mature, spherical to oval conidia are extruded from the phialide and usually accumulate around it (Figure 45-14A). B. Fonsecaea pedrosoi Fonsecaea is a polymorphic genus. Isolates may exhibit (1) phialides; (2) chains of blastoconidia, similar to Cladosporium species; or (3) sympodial, rhinocladiella-type conidiation. Most strains of F pedrosoi form short branching chains of blastoconidia as well as sympodial conidia (Figure 45-14B). C. Fonsecaea compacta The blastoconidia produced by F compacta are almost spherical, with a broad base connecting the conidia. These structures are smaller and more compact than those of F pedrosoi. D. Rhinocladiella aquaspersa This species produces lateral or terminal conidia from a lengthening conidiogenous cell—a sympodial process. The conidia are elliptical to clavate. B FIGURE 45-14 Identifying conidia produced in culture by the two most common agents of chromomycosis. A:Phialophora verrucosa produces conidia from vase-shaped phialides with collarettes. 1000×. B:Fonsecaea pedrosoi usually displays short branching chains of blastoconidia, as well as other types of conidiogenesis. 1000×. E. Cladophialophora (Cladosporium) carrionii Species of Cladophialophora and Cladosporium produce branching chains of conidia by distal (acropetalous) budding. The terminal conidium of a chain gives rise to the next conidium by a budding process. Species are identified based on differences in the length of the chains and the shape and size of the conidia. Cladophialophora carrionii produces elongated conidiophores with long, branching chains of oval conidia. www.ketabdownload.com 684 SECTION V Mycology Pathogenesis and Clinical Findings The fungi are introduced into the skin by trauma, often of the exposed legs or feet. Over months to years, the primary lesion becomes verrucous and wart-like with extension along the draining lymphatics. Cauliflower-like nodules with crusting abscesses eventually cover the area. Small ulcerations or “black dots” of hemopurulent material are present on the warty surface. Rarely, elephantiasis may result from secondary infection, obstruction, and fibrosis of lymph channels. Dissemination to other parts of the body is very rare, though satellite lesions can occur due either to local lymphatic spread or to autoinoculation. Histologically, the lesions are granulomatous and the dark sclerotic bodies may be seen within leukocytes or giant cells. Diagnostic Laboratory Tests Specimens of scrapings or biopsies from lesions are placed in 10% KOH and examined microscopically for dark, spherical cells. Detection of the sclerotic bodies is diagnostic of chromoblastomycosis regardless of the etiologic agent. Tissue sections reveal granulomas and extensive hyperplasia of the dermal tissue. Specimens should be cultured on inhibitory mold agar or Sabouraud’s agar with antibiotics. The dematiaceous species is identified by its characteristic conidial structures, as described above. There are many similar saprophytic dematiaceous molds, but they differ from the pathogenic species in being unable to grow at 37°C and being able to digest gelatin. FIGURE 45-15 Phaeohyphomycosis. Melanized hyphae are observed in the tissue. 400×. Chromoblastomycosis occurs mainly in the tropics. The fungi are saprophytic in nature, probably occurring on vegetation and in soil. The disease occurs chiefly on the legs of barefoot agrarian workers following traumatic introduction of the fungus. Chromoblastomycosis is not communicable. Wearing shoes and protecting the legs probably would prevent infection. with various types of phaeohyphomycotic infections. They are all exogenous molds that normally exist in nature. Some of the more common causes of subcutaneous phaeohyphomycosis are Exophiala jeanselmei, Phialophora richardsiae, Bipolaris spicifera, and Wangiella dermatitidis. These species and others (eg, Exserohilum rostratum, Alternaria species, and Curvularia species) may be implicated also in systemic phaeohyphomycosis. The incidence of phaeohyphomycosis and the range of pathogens have been increasing in recent years in both immunocompetent and compromised patients. In tissue, the hyphae are large (5–10 µm in diameter), often distorted and may be accompanied by yeast cells, but these structures can be differentiated from other fungi by the melanin in their cell walls (Figure 45-15). Specimens are cultured on routine fungal media to identify the etiologic agent. In general, itraconazole or flucytosine is the drug of choice for subcutaneous phaeohyphomycosis. Brain abscesses are usually fatal, but when recognized they are managed with amphotericin B and surgery. The leading cause of cerebral phaeohyphomycosis is Cladophialophora bantiana. PHAEOHYPHOMYCOSIS MYCETOMA Phaeohyphomycosis is a term applied to infections characterized by the presence of darkly pigmented septate hyphae in tissue. Both cutaneous and systemic infections have been described. The clinical forms vary from solitary encapsulated cysts in the subcutaneous tissue to sinusitis to brain abscesses. Over 100 species of dematiaceous molds have been associated Mycetoma is a chronic subcutaneous infection induced by traumatic inoculation with any of several saprophytic species of fungi or actinomycetous bacteria that are normally found in soil. The clinical features defining mycetoma are local swelling of the infected tissue and interconnecting, often draining, sinuses or fistulae that contain granules, which are Treatment Surgical excision with wide margins is the therapy of choice for small lesions. Chemotherapy with flucytosine or itraconazole may be efficacious for larger lesions. The application of local heat is also beneficial. Relapse is common. Epidemiology www.ketabdownload.com CHAPTER 45 microcolonies of the agent embedded in tissue material. An actinomycetoma is a mycetoma caused by an actinomycete; a eumycetoma (maduromycosis, Madura foot) is a mycetoma caused by a fungus. The natural history and clinical features of both types of mycetoma are similar, but actinomycetomas may be more invasive, spreading from the subcutaneous tissue to the underlying muscle. Of course, the therapy is different. Mycetoma occurs worldwide but more often among impoverished people who reside in tropical areas and wear less protective clothing. Mycetomas occur only sporadically outside the tropics but are particularly prevalent in India, Africa, and Latin America. Actinomycetomas are discussed in Chapter 12. Morphology and Identification The fungal agents of mycetoma include, among others, Pseudallescheria boydii (anamorph, Scedosporium apiospermum), Madurella mycetomatis, Madurella grisea, Exophiala jeanselmei, and Acremonium falciforme. In the United States, the prevalent species is Pseudallescheria boydii, which is selffertile (homothallic) and has the ability to produce ascospores in culture. Exophiala jeanselmei and the Madurella species are dematiaceous molds. These molds are identified primarily by their mode of conidiation. Pseudallescheria boydii may also cause pseudallescheriasis, which is a systemic infection of compromised patients. In tissue, the mycetoma granules may range up to 2 mm in size. The color of the granule may provide information about the agent. For example, the granules of mycetoma caused by Pseudallescheria boydii and Acremonium falciforme are white; those of Madurella grisea and Exophiala jeanselmei are black; and Madurella mycetomatis produces a dark red to black granule. These granules are hard and contain intertwined, septate hyphae (3–5 µm in width). The hyphae are typically distorted and enlarged at the periphery of the granule. Pathogenesis and Clinical Findings Mycetoma develops after traumatic inoculation with soil contaminated with one of the agents. Subcutaneous tissues of the feet, lower extremities, hands, and exposed areas are most often involved. Regardless of the agent, the pathology is characterized by suppuration and abscesses, granulomata, and draining sinuses containing the granules. This process may spread to contiguous muscle and bone. Untreated lesions persist for years and extend deeper and peripherally, causing deformation and loss of function. Very rarely, Pseudallescheria boydii may disseminate in an immunocompromised host or produces infection of a foreign body (eg, a cardiac pacemaker). Diagnostic Laboratory Tests Granules can be dissected out from the pus or biopsy material for examination and culture on appropriate media. The granule color, texture, and size and the presence of hyaline Medical Mycology 685 or pigmented hyphae (or bacteria) are helpful in determining the causative agent. Draining mycetomas are often superinfected with staphylococci and streptococci. Treatment The management of eumycetoma is difficult, involving surgical debridement or excision and chemotherapy. Pseudallescheria boydii is treated with topical nystatin or miconazole. Itraconazole, ketoconazole, and even amphotericin B can be recommended for Madurella infections and flucytosine for Exophiala jeanselmei. Chemotherapeutic agents must be given for long periods to adequately penetrate these lesions. Epidemiology and Control The organisms producing mycetoma occur in soil and on vegetation. Barefoot farm laborers are therefore commonly exposed. Properly cleaning wounds and wearing shoes are reasonable control measures. KEY CONCEPTS: SUBCUTANEOUS MYCOSES 1. Subcutaneous mycoses may be caused by dozens of environmental molds associated with vegetation and soil. 2. These infections are usually acquired when minor cuts or scratches introduce soil or plant debris (eg, splinters, thorns) containing the pathogenic fungus. The ensuing infections are frequently chronic but rarely spread to deeper tissues. 3. Sporothrix schenckii, the cause of sporotrichosis, is a dimorphic fungus that converts from hyphal growth to yeast cells within the host. 4. The diagnostic feature of chromoblastomycosis is the microscopic observation of brownish (melanized), spherical sclerotic bodies within the lesions. 5. The diagnostic feature of phaeohyphomycosis is the presence of brownish (melanized), septate hyphae within the lesions. 6. The hallmark of a mycetoma is localized swelling and the formation of fistulae that contain hard granules composed of hyphae and inflammatory tissue (eg, macrophages, fibrin). ENDEMIC MYCOSES Each of the four primary systemic mycoses—coccidioidomycosis, histoplasmosis, blastomycosis, and paracoccidioidomycosis—is geographically restricted to specific areas of endemicity. The fungi that cause coccidioidomycosis and histoplasmosis exist in nature in dry soil or in soil mixed with guano, respectively. The agents of blastomycosis and paracoccidioidomycosis are presumed to reside in nature, but their habitats have not www.ketabdownload.com 686 SECTION V TABLE 45-3 Mycology Summary of Endemic Mycosesa Mycosis Etiology Ecology Geographic Distribution Tissue Form Histoplasmosis Histoplasma capsulatum Avian and bat habitats (guano); alkaline soil Global; endemic in Ohio, Missouri, and Mississippi River valleys; central Africa (var. duboisii) Oval yeasts, 2 × 4 µm, intracellular in macrophages Coccidioidomycosis Coccidioides posadasii or Coccidioides immitis Soil, rodents Semiarid regions of southwestern United States, Mexico, Central and South America Spherules, 10–80 µm, containing endospores, 2–4 µm Blastomycosis Blastomyces dermatitidis Unknown (riverbanks?) Mississippi, Ohio and St. Lawrence River valleys; southeastern United States Thick-walled yeasts with broad-based, usually single, buds, 8–15 µm Paracoccidioidomycosis Paracoccidioides brasiliensis Unknown (soil?) Central and South America Large, multiply budding yeasts, 15–30 µm a All four endemic mycoses are caused by dimorphic fungi that reside in nature in the mold form producing hyaline septate hyphae and characteristic conidia. Infection is acquired by inhalation of the conidia. With the exception of blastomycosis, the evidence supports a high rate of infection within the endemic areas. Over 90% of infections occur in immunocompetent individuals, 75–90% in males, and 60–95% are asymptomatic and self-limited or latent. Symptomatic disease occurs frequently in immunocompromised patients, including those with HIV/AIDS. been clearly defined. Each of these four mycoses is caused by a thermally dimorphic fungus, and the infections are initiated in the lungs following inhalation of the respective conidia. Most infections are asymptomatic or mild and resolve without treatment. However, a small but significant number of patients develop pulmonary disease, which may involve diss