Chapter 13 13 Common Fungal Infections With respect to the mode of presentation and propa- 13.1.1 gation in tissue there are three categories of fungi: Clinical Appearance 1. Yeast fungi (unicellular fungi) exist only as spores Different parts of the body may be affected. With re- and produce new spores by budding. spect to the location, the eruption may have a more or 2. Filamentous fungi produce filaments (hyphae), but less characteristic appearance. This is the reason why not yeast cells. Some kinds of filamentous fungi the disease is named after the part of the body affected: form septate hyphae (i.e., the hyphae consist of a tinea corporis (includes trunk and limbs), tinea faciei, chain of cells separated by septa); other kinds pro- tinea cruris, tinea manuum, tinea pedis, tinea capitis, duce non-septate hyphae. Filamentous fungi may tinea barbae, and tinea unguium. brake up into spores called arthrospores. A con- For example, tinea circinata is the characteristic glomeration of hyphae is called mycelium. lesion usually seen in tinea corporis. It presents as a 3. Dimorphic fungi are able to form both hyphae and rounded, erythematous, slightly infiltrated, more or yeast spores. They produce new yeast cells by bud- less scaling plaque, which extends gradually at the pe- ding from spores as well as from hyphae. riphery and becomes circinate or annular due to cen- The most common kinds of fungal skin infections are tral healing. The active border is clearly defined and dermatophytosis, Malassezia furfur/pityrosporum in- slightly raised and may contain pustules. fections, candidiasis, and aspergillosis. However, not always do lesions express the pattern described as typical for the location or typical for a fungus lesion in general. They may be mainly papular, 13.1 vesicular, pustular, follicular, or nodular. The intensity Dermatophytosis (Ringworm, Tinea) of the inflammatory reaction depends on several fac- Dermatophytes are species of pathogenic filamentous tors such as the type of fungus, the degree of follicular fungi, which belong to one of three genera: Trichophy- invasion, and the immune state of the patient. Thus, in ton, Microsporum and Epidermophyton (see Table 30.1). contrast to the anthropophilic T. mentagrophytes, the They infect the stratum corneum of the skin and many zoophilic variant gives rise to vesicular and/or pustu- of them also hair and/or nails. According to their nat- lar lesions. Nodular lesions are caused by infection of ural setting they can be categorized as: anthropophilic deep-seated hair follicles. fungi, which primarily infect humans and spread from Tinea capitis, infection of the scalp, may be inflam- one person to another; zoophilic fungi, which primar- matory or non-inflammatory. Usually M. audouinii ily infect animals and can be transmitted to humans; and M. canis give rise to only a slight inflammatory and geophilic fungi, which reside in the soil and oc- reaction. However, M. canis is sometimes the cause casionally infect animals and humans. of kerion celsi, a painful tumefaction due to a puru- Trichophyton rubrum and T. mentagrophytes are lent infection in the dermis and subcutaneous tissue common dermatophytes with a worldwide distribu- that is always combined with cervical lymphadenitis. tion. Trichophyton rubrum, which is anthropophilic, Trichophyton schoenleinii is the most common cause prevails in the western world, where it is the most of a purulent infection of the scalp, called favus, char- common cause of chronic fungal infections. Tricho- acterized by thick yellow crusts consisting of hyphae phyton mentagrophytes exists as an anthropophilic and and cellular debris (Hay et al. 1992; Elewski 1992). a zoophilic variant. Another common and ubiquitous zoophilic dermatophyte is M. canis. Handling an af- fected animal can result in infection. 13.1 Dermatophytosis (Ringworm, Tinea) 87 Fig. 13.1 Dermatophytosis. a Top: segmented hypha in the Bottom: close-up shows the hypha indicated above. The arrows horny layer; PAS. Middle: a string of arthrospores in the horny indicate two septa. PAS. c In this case the horny layer is mark- layer; PAS. Bottom: a row of arthrospores located between the edly thickened. The indicated superficial area of the horny layer hair shaft and the internal root sheath of a hair follicle. H&E (arrowhead) is permeated by thin, black structures, hyphae. (detail from Fig. 13.5b). b Top: there is a single hypha in the d Close-up demonstrates a substantial number of tightly seg- horny layer (arrow). The epidermis is slightly spongiotic and in mented hyphae, one of which is branching (arrow). PAS the papillary dermis there is a sparse infiltrate of lymphocytes. 88 13 Common Fungal Infections 13.1.2 Histopathologic Appearance In sections stained with H&E and vG, hyphae and spores are transparent, and therefore, in most cases, are difficult or impossible to detect. For that reason it is necessary to use special fungal stains, such as PAS or silver stains (Gomori, Grocott). Hyphae and spores are stained red with PAS and black with silver stains. Both types of staining methods give equally good re- sults, but the PAS reaction is faster and the procedure is less complicated than that for silver impregnation. Dermatophytes are filamentous fungi which in tis- sue produce only septate hyphae and arthrospores (Fig. 13.1). These are found in the stratum corneum, Fig. 13.2 Dermatophytosis. There is a bilocular intraepider- hair follicles, hair shafts, and nails. Hyphae are distinct mal vesicle which except for small aggregates of neutrophils is structures which, properly stained, are easily detected empty. The roof of the vesicle consists only of stratum corneum. at low magnification. The length and thickness of the In the subepidermal area there are perivascular infiltrates of in- segments are highly variable. Occasionally one or sev- flammatory cells. One of the few hyphae observed in the horny eral segments are inflated or ballooned. Sometimes layer is shown in Fig. 13.1a. PAS hyphae are branching. Now and then they are broken up into arthrospores, which at first are arranged like strings of pearls and later become dispersed. This phe- frequency of septae are not discriminative. For identi- nomenon can be seen relatively often in hair follicles, fication culture is necessary. In culture the genera and hair shafts and nails, and less often in the stratum cor- species (see Glossary) can be discriminated by means neum. of different forms of spores (conidia) and other char- It is not possible to differentiate one kind of derma- acteristic structures emerging from the hyphae such tophyte from another. Features of the hyphae such as as spirals, nodules, racquets, combs, and antlers (Hay thickness, presence or absence of ballooning, and the et al. 1992; Elewski 1992). Fig. 13.3 Dermatophytosis. a There are arthrospores arrow-( ferent levels. Cross sections may be mistaken for spores which, heads) in the superficial part of the horny layer.b A hair fol- however, are not present. The presence of keratin around the licle in the upper dermis contains hyphae. These are lying in the hair shaft indicates that the follicle is cut above the entrance of keratin that surrounds the hair shaft. The hyphae are cut at dif- the sebaceous ducts. PAS 13.1 Dermatophytosis (Ringworm, Tinea) 89 Fig. 13.4 Dermatophytosis. a Papular and slightly scaling erup- the area indicated in c shows a conglomeration of hyphae which tion on the trunk. b Follicular papules on the buttock. c Biopsy are tightly segmented and focally slightly ballooned. Bottom: specimen from the patient in b. A superficial hair follicle is di- close-up of the abscess demonstrates hyphae breaking up into lated and filled with necrotic material. The orifice is blocked by spores and free-lying spores. PAS (c and d bottom are repro- a keratin plug which contains hyphae (arrow). d Top: close-up of duced from Brehmer-Andersson 1970, with permission) The intensity of the inflammatory tissue reaction (Fig. 13.1b,c). However, usually there are moderate to differs substantially from one case to another and is dense cell infiltrates with dominance of neutrophils in in harmony with the clinical expression. There may be both the dermis and the epidermis and sometimes ve- only small infiltrates of lymphocytes in the papillary siculopustules (Fig. 13.2). dermis and slight or no spongiosis in the epidermis In vellus hair-bearing skin, sometimes also called 90 13 Common Fungal Infections Fig. 13.5 Dermatophytosis. a A hair follicle located deep in the subcutaneous tissue is lying in a large abscess. b Close-up of the follicle shows that the hair shaft is permeated by hyphae and arthrospores. The upper arrow indicates arthrospores arranged like a roll of coins between the shaft and the internal root sheath (also shown in Fig. 13.1a). The lower arrow indicates an area in the hair shaft permeated with hyphae. H&E. c Detail of a sub- cutaneous abscess with a fragment of hair shaft which contains arthrospores and hyphae (right arrow). The left arrow indicates a foreign body giant cell surrounded by neutrophils. PAS the glabrous skin (see Glossary), hair follicle infec- well as histopathologically. He infected children and tions are mostly superficial and thus an integral part adults by inoculating the scalp with spores from these of the infection in the stratum corneum (Fig. 13.3). fungi. He found two types of infection: scalp infection Rarely the infection is confined only to superficial (i.e., infection of the stratum corneum only), and hair follicles (Fig. 13.4). Now and then deep folliculitis infection (i.e., infection of the follicle and hair shaft and perifolliculitis with abscess formation in the sur- only). These two types of infection could exist together rounding tissue are seen (Fig. 13.5a,b). In such cases or each separately.