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ETAS_07 mycology

  1. 1. 7 Medical Mycology Evelyn K. Koestenblatt, MS, MT (ASCP) Jeffrey M. Weinberg, MDC o n t e n t s7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2557.2 Superficial Mycoses . . . . . . . . . . . . . . . . . . . . . . . . . 2567.3 The Dermatophytes . . . . . . . . . . . . . . . . . . . . . . . . . 2587.4 Subcutaneous Mycosis . . . . . . . . . . . . . . . . . . . . . . . 2697.5 Dimorphic Fungi Causing Systemic Disease . . . 2737.6 Opportunistic Organisms . . . . . . . . . . . . . . . . . . . . 2767.7 Miscellaneous Organisms Causing Fungus-like Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2827.8 Random Facts and Summary Table . . . . . . . . . . . 283 Medical Mycology  253
  2. 2. Committed to Your Future For practice exam questions and interactive study tools, visit the Dermatology In-Review Online Practice Exam and Study System at by
  3. 3. 7.1  INTRODUCTION Yeasts: Unicellular oval to round cells, reproduce by budding or fission and form moist colonies. Moulds: Filamentous fungi, characterized by tubular branching cells called hyphae, whichform fuzzy, velvety or smooth colonies. Yeasts and moulds are not mutually exclusive: Dimorphism-mould form in the environment(25° C), yeast or spherule form in tissue (37° C).Microscopic Appearance • Hyphae: Vegetative tube-like structures, mass of hyphae = mycelium – Septate: Transverse cross walls form within the hyphae – Nonseptate: Protoplasm and nuclei run along the length of the hyphael strand uninterrupted • Pseudohyphae: Seen in yeast, resemble true hyphae except: – Constricted at septations – Branching occurs at septations – The terminal cell is smaller than the others • Types of Mycelium: No reproductive capability – Racket forms: Club-shaped cells – Favic chandeliers: Terminal hyphael branches having an antler-like appearance – Pectinate bodies: Hyphae resembling a comb – Spiral hyphae: Hypha forming corkscrew-like turns – Nodular bodies: A knot-like structure of hyphae • Types of reproduction – Sexual reproduction: Fusion of compatible nuclei with meiosis – Asexual reproduction: Mitosis • Arthroconidia: Formed by fragmentation of hyphae, may appear as thick- or thin- walled rectangular cells, example: mould form of Coccidioides immitis • Blastoconidia: Formed by budding, example: yeast • Chlamydoconidia: Thick-walled round cell, resistant to the environment, example: Trichophyton tonsurans • Sporangia: Spores that are produced in a sac, example: Zygomycetes • Conidia: Cells produced on the end or sides of hypha or conidiophore, the size shape and arrangement are generally characteristic of the organism, example: DermatophytesDirect Microscopic Examination • Potassium hydroxide (KOH): Rapid, easy, reliable diagnosis of fungal infections • Swartz Lamkins: Contains a counterstain • KOH with DMSO (dimethyl sulfoxide) • Chlorazol Black E-chitin specific • Calcofluor white-most sensitive, glucan specific immunofluorescent stain • Histology stains: – Gormori Methanamine Silver (GMS) – Periodic Acid Schiff (PAS) – Fontana-Masson – Mayer’s Mucicarmine – Fite stain Medical Mycology  255
  4. 4. Media • Sabouraud Dextrose Agar (SDA) Emmons modification: Gold standard – Nutritionally poor: dextrose, peptones, water, agar, encourages sporulation • SDA with cycloheximide and chloramphenicol (Mycosel or Mycobiotic) – Good for hair skin and nails – Cycloheximide inhibits rapidly growing nonpathogenic moulds and some pathogens (Cryptococcus neoformans, some Candida species, Prototheca, Scytalidium species, yeast forms of Histoplasma and Blastomyces) – Chloramphenicol inhibits bacterial flora • Dermatophyte test media (DTM) – Good for hair, skin, and nails – Contains peptones, dextrose, gentamicin, chlortetracycline, cycloheximide, phenol red – Dermatophytes utilize protein as a carbon source producing alkaline by-products causing the media to turn from amber to red. Nondermatophytes cause the media to turn yellow due to acid by-products7.2 SUPERFICIAL MYCOSES Figure 7-1. Pityriasis versicolor biopsy Pityriasis Versicolor (Tinea Versicolor) • ost current nomenclature: Malassezia furfur, M. pachydermatis, M. dermatis, M. obtuse, M M. restrica, M. sympodialis, M. slooffiae • Lipophilic organisms • Found worldwide, prefer humid, moist, warm environment and ↑ CO2 tension • Appear as round to oval yeast forms on normal skin in sebum rich areas • Conversion to hyphae and spore, “spaghetti and meatballs” • Mild, chronic, sharply demarcated hyper/hypopigmented macules with fine scaling • Lesions most often seen on neck, shoulders, chest, back, upper arms, abdomen • Woods lamp (+) pale yellow fluorescence • Implicated in other diseases: folliculitis (Pityrosporum folliculitis), seborrheic dermatitis, atopic dermatitis, invasive infections, onychomycosis • KOH: Curved septate hyphae with short chains or clusters of budding thick-walled yeast cells, may see only hyphae or only yeast cells • Culture: Organisms difficult to grow, requires olive oil overlay • Topical treatment: Selenium sulfide, ketoconazole shampoo, topical “azoles,” ciclopirox • Systemic treatment: Ketoconazole, itraconazole, fluconazole256   2011/2012 Dermatology In-Review l Committed to Your Future
  5. 5. Tinea Nigra Palmaris (Superficial phaeohyphomycosis) • New Name: Hortaea werneckii Formerly: Phaeoannellomyces werneckii • Asymptomatic, brown to black, macular, nonscaly lesions on palms of hand or soles of feet; deeper pigmentation at advancing border • Warm humid climates: southern U.S., South Africa, Caribbean, Far East, Europe and Australia, Central and South America • Found in decaying vegetation, soil, beach sand, water • KOH: Olive multiple branching, septate hyphae with budding yeast cells • H & E: Dark organisms confined to stratum corneum, variety of shapes • Culture: Shiny black yeast colonies, composed of 2-celled yeast, later colony looses shine as it develops thick-walled dark hyphae with oval, clear to dark 1 or 2-celled conidia • Treatment: Whitfield’s ointment, azole creams • Differential diagnosis: Junctional nevi, melanoma, Addison’s disease, hyperpigmentation of syphilis and pinta, chemicals/dyesPiedras • Limited to hair shaft, characterized by firm, irregular nodules composed of fungal elements Black Piedra • Piedraia hortae • Found in soil and water in humid, tropical areas  Black, firm, adherent concretions 1 mm diameter, most common in scalp, also found in •  pubic area, beard and mustache • KOH: Dark hyphae, ascospores containing asci held together with cement-like substance • Culture: Small, compact black-greenish velvety colony with raised center. Septate dark thick-walled hyphae with intercalary chlamydospores • Treatment: Cut off hair, antifungal shampoo • Differential diagnosis: Nits, hair shaft defects, hair casts White Piedra • New nomenclature: Trichosporon ovoides and T. inkin, formerly Trichosporon beigelii • Keratinophilic soil, water and sewage organism, seen in temperate regions  •  Tan to white soft, nonadherent small concretions ~1mm, seen on scalp, beard, mous- tache, pubic areas. Hairs may fluoresce • KOH: Sleeve of hyphae, blastoconidia, and arthroconidia around hair. Nodules thickest at center and taper on ends • Culture: Cream to yellow colored pasty colony and pseudohyphae with blastoconidia, arthroconidia form in older cultures, inhibited by cycloheximide • Other superficial infections: Onychomycosis, paronychia, post-op wound infections • Treatment: Topical Amp B lotion, benzoic acid, salicylic acid, cut off hair, antifungal shampoo • Differential diagnosis: Lice, nits, hair casts, trichomycosis axillaris • Trichosporanosis – Trichosporon asahii – Disseminated disease seen mainly in immunocompromised patient with severe neutropenia – Cutaneous lesions: Erythematous to violaceous papules that may progress to necrotizing lesions, nodular skin lesions, no concretions on hair – Treatment: Fluconazole, voriconazole, granulocyte infusions Medical Mycology  257
  6. 6. 7.3 THE DERMATOPHYTESIntroduction • Dermatophyte: Group of closely related filamentous fungi, which colonize keratin such as the stratum corneum of the epidermis, hair, nails, feathers of various animals • Dermatophytosis: Cutaneous infections of keratinized tissue by the dermatophyte genera of fungi, Trichophyton, Microsporum, and Epidermophyton • Dermatomycosis: Organisms other than the dermatophytes that may cause deep fungal or systemic infections with cutaneous manifestationsEcology of Dermatophytes • Geophilic: Live in soil; inflammatory infection in humans • Zoophilic: Primarily infects animals; humans become infected through direct indirect contact, infections are generally suppurative. Animals may be asymptomatic carriers • Anthropophilic: Transmitted human to human directly or indirectly through fomites. The response can vary from minimal to markedly inflammatory with pustule or kerion production Table 7-1. Ecology of Common Dermatophytes Geophilic Zoophilic Anthropophilic M. gypseum M. canis E. floccosum M. nanum M. gallinae M. audouinii M. vanbreuseghemii M. nanum M. ferrugineum T. equinum T. concentricum T. mentagrophytes T. megninii T. verrucosum T. mentagrophytes T. rubrum T. schoenleinii T. soudanense T. tonsurans T. violaceumCommon Dermatophyte Infections Factors Favoring Dermatophyte Infection • Large inoculum size • Suitable environment: Hydration, friction, maceration, heat, darkness, occlusion • Growth rate of fungus must be greater than epidermal turnoverTinea Capitis • Dermatophyte infection of the scalp and hair, generally seen in childhood Ectothrix • Arthroconidia coat the outside of the hair, cuticle destroyed • Fluorescent (Woods light, 366 nm, mercury lamp with a nickel chromium oxide filter, fluorescence is due to pteridine production)258   2011/2012 Dermatology In-Review l Committed to Your Future
  7. 7. • Nonfluorescent: T. mentagrophytes, T. rubrum, MNEMONIC T. verrucosum, T. megninii, M. gypseum, M. nanum Fluorescent Ectothrix Fungi • KOH prep: Arthroconidia are visualized on outside of hair Cats And Dogs Fight and Growl shaft Sometimes Endothrix “Black Dot Ringworm” M. canis • Arthroconidia invade interior of the hair shaft M. audouinii • Black dots are remnants of brittle hair broken at the surface M. distortum of the scalp, cuticle intact M. ferrugineum • T. rubrum, T. gourvilli, T. yaounde, T. tonsurans, and sometimes T. soudanense, T. violaceum M. gypseum • KOH prep: Arthroconidia within hair shaft T. schoenleinii Favus • Chronic infection of the scalp - begins in childhood and may extend into adulthood • Scutula: Yellowish cup shaped crusts made up of hyphae and keratinous debris, may have a single hair piercing through the center • Primarily T. schoenleinii, occasionally T. violaceum, M. gypseum • KOH prep: Hyphae and airspaces within hair shaft Treatment • Griseofulvin, itraconazole, terbinafine, and selenium sulfide or ketoconazole or loprox shampoo Kerion u TIP • Boggy, oozing inflammatory reaction to fungus aruritis, fever, pain, regional P • Regional lymphadenopathy lymphadenopathy, scarring alopecia • Scarring alopecia may result aTreatment may include prednisone • Most frequently due to M. canis, T. tonsurans, T. verrucosum, T. mentagrophytes Differential Diagnosis • Seborrheic dermatitis, impetigo, folliculitis, lupus, psoriasis, alopecia areata Table 7-2. Tinea Capitis Fluorescent Endothrix Favus No Hair Involvement Fluorescent Non-Fluorescent M. audouinii M. gypseum* T. gourvilli T. schoenleinii* E. floccosum M. canis M. nanum T. rubrum T. violaceum T. concentricum M. distortum T. megninii T. tonsurans M. gypseum*M. ferrugineum T. mentagrophytes T. soudanense T. rubrum T. yaounde T. verrucosum T. violaceum* May fluoresce Medical Mycology  259
  8. 8. Tinea Corporis • Any of the dermatophytes are capable of causing tinea corporis; the most frequently recovered organisms include: T. rubrum, T. mentagrophytes, M. canis, T. tonsurans • Transmitted directly from individuals, animals or fomites • Organisms invade stratum corneum generally causing an annular lesion with an erythematous raised, scaly advancing border, the center of the lesion may show clearing Tinea Imbricata • T. concentricum; endemic to South Pacific, S. C. America and Far East. Polycyclic scaly noninflammatory lesions Tinea Profunda • Verrucose inflammatory response, patients may have defective cellular immunity Majocchi’s Granuloma • Granulomatous lesion of hair follicle, generally associated with T. rubrum, requires biopsy for dx and oral antifungal Differential Diagnosis • Seborrheic, atopic or contact dermatitis, psoriasis, impetigo, lichen simplex, nummular eczema, tertiary syphilisTinea Barbae • In men, the bearded area of the face and neck, generally inflammatory • Associated with exposure to animals • Inflammatory: T. mentagrophytes, T. verrucosum • Superficial form: T. violaceum, T. rubrum • Abscess: M. canis • Verrucous granulomatosis: E. floccosum • Requires oral antifungalTinea Cruris • Mainly seen in males, involves the groin, perineal and perianal skin • Direct or indirect contact • E. floccosum, T. rubrum, T. mentagrophytesTinea Faciei • Females and children most frequently the upper lip and chin • May be history of animal exposure • T. rubrum, T. mentagrophytes, T. concentricum, M. canisTinea Manuum • Palmar/interdigital areas of the hands, almost always associated with T. pedis • T. rubrum, T. mentagrophytes, E. floccosumTinea Pedis • Moccasin type: E. floccosum, T. rubrum • Interdigital type: E. floccosum, T. mentagrophytes • Vesicular type: T. mentagrophytes • Interweb infections often involve fungi, yeast, gram negative and positive bacteria260   2011/2012 Dermatology In-Review l Committed to Your Future
  9. 9. Tinea Unguium u TIP • Dermatophyte infection of the nails aDistal Lateral Subungual Onychomycosis Onychomycosis •  T. rubrum • Fungal infection of the nails due to dermatophyte, yeast aProximal White Subungual or nondermatophyte Onychomycosis •  AIDS marker Distal Lateral Subungual Onychomycosis •  T. rubum • Infection begins distally and involves the nail bed, nail aWhite Superficial Onychomycosis plate and lateral nail fold; thick nail with debris, loose or •  T. mentagrophytes cracked nail plate • T. rubrum Proximal White Subungual Onychomycosis • Rarest form of onychomycosis • AIDS marker • Organisms enter the cuticle and infect the proximal part of the nail bed causing white islands that slowly invade the nail plate • T. rubrum most frequently recovered • Also T. megninii, T. schoenleinii, T. tonsurans, T. mentagrophytes, E. floccosum White Superficial Onychomycosis • Organism invades the surface of the nail plate of toenails only • Irregular white chalky opaque patches on the nail • Most frequent T. mentagrophytes, also Aspergillus species esp. terreus, Acremonium (formerly Cephalosporium), Fusarium, Scopulariopsis • In HIV population, generally caused by T. rubrumTinea Incognito • The use of corticosteroids can cause an atypical appearing lesionDermatophytids • Eczematous allergic reaction to dermatophyte infection elsewhere on the skin • Lesions are sterile; reaction clears after fungus has been eradicated • Patient will test positive to group-specific trichophyton antigen Table 7-3. Genus DifferentiationEpidermophyton Trichophyton MicrosporumMicroconidia not produced Microconidia diagnostic, numer- Microconidia not distinctive ous with characteristic arrange- ments and shapes (some species do not produce conidia)Macroconidia smooth-walled, Macroconidia not distinctive, Macroconidia diagnostic, rough-club-shaped, 2–6 cells, occurs smooth, thin cell wall, pencil- walled (echinulate), multicellular,singly or in clusters, thin and thick shaped barrel-shaped, thick cell wallcell wallsNo hair involvement Nonfluorescent ecto- and endo- Fluorescent nonfluorescent thrix invasion ectothrix invasion Medical Mycology  261
  10. 10. Epidermophyton Figure 7-2. E. floccosum E. floccosum • Anthropophilic: Worldwide • No hair parasitism, Tinea cruris, T. pedis, occasionally T. corporis, onychomycosis • Colony morphology: Khaki-colored colony, orange-brown reverse, radial grooves, folded center, velvety • Microscopic morphology: Septate hyphae, no microconidia, macroconidia smooth, thin- and thick-walled, club-shaped, two to six cells, occur singly or in characteristic clusters (no other species does this)Microsporum Species Figure 7-3. M. audouinii M. audouinii • Anthropophilic organism: Worldwide • Tinea corporis, formerly the #1 cause of T. capitis in children (fluorescent ectothrix) • Colony morphology: Grey to tan colony, reverse salmon with a reddish brown center, flat surface, “mouse fur appearance” • Microscopic morphology: Septate hyphae with terminal chlamydoconidia often with pointed ends. Pectinate bodies, racquet hyphae and favic chandeliers may occur. Rarely see macroconidia, when present poorly shaped, thick-walled and echinulate. Microconidia occasionally seen • Miscellaneous: Polished Rice (–)262   2011/2012 Dermatology In-Review l Committed to Your Future
  11. 11. Figure 7-4. M. canis M. canis • Zoophilic organism (cats and dogs)  •  Most common cause of T. capitis worldwide (fluorescent ectothrix) • T. corporis, T. faciei, T. unguium, T. pedis (rarely) • Colony morphology: White fluffy, fur-like colony with yellow periphery and feathery border. Reverse deep yellow • Microscopic morphology: Septate hyphae. Macroconidia are numerous, spindle shaped, thick-walled with knoblike ends (“dog’s tail”) having six or more cells. Occasional club- shaped microconidia • Miscellaneous: Polished Rice (+)M. canis var. distortum • Zoophilic organism: Found in Australia and New Zealand • Fluorescent ectothrix tinea capitis • Colony morphology: White to buff velvety, fluffy colony. Reverse yellow • Microscopic morphology: Septate hyphae. Macroconidia resemble distorted M. canis, microconidia present • Miscellaneous: Polished Rice (+)M. ferrugineum • Anthropophilic organism: Found Asia, India and Africa • Fluorescent ectothrix tinea capitis, similar to M. audouinii, Tinea corporis • Colony morphology: Smooth, waxy, heaped, rust colored colony. Reverse cream to yellow orange • Microscopic morphology: Long straight septate hyphae with prominent crosswalls, bamboo-like. Occasional chlamydoconidia. No conidiaM. gallinae • Zoophilic organism: Chicken favus • Rarely causes ectothrix tinea capitis • Colony morphology: Fluffy to felt-like white colony becoming pink with age. Reverse strawberry red diffusible pigment • Microscopic morphology: Septate hyphae. Macroconidia-large echinulate at tip, club- shaped, may be curved, four to ten cells, microconidia present Medical Mycology  263
  12. 12. Figure 7-5. M. gypseumM. gypseum Complex • Geophilic organism human infection results from direct contact from the soil • T. corporis, ectothrix tinea capitis, often inflammatory, may see favus-like crust, and occasionally a dull fluorescence • Colony morphology: Flat, powdery colony, buff to cinnamon with a white periphery. Reverse yellow to orange or purplish in spots • Microscopic morphology: Septate hyphae. Macroconidia numerous, symmetric, up to six cells, microconidia club-shaped • Miscellaneous: Polished Rice (+) Figure 7-6. M. nanumM. nanum • Zoophilic/geophilic organism • Pig ringworm, ectothrix tinea capitis • Colony morphology: Fluffy white colony → powdery beige. Reverse orange to reddish brown • Microscopic morphology: Septate hyphae. Macroconidia echinulate, egg shaped or “pig snout” with a truncated base, one to three cells, microconidia club-shapedM. vanbreuseghemii • Geophilic organism • Rarely infects humans and animals • Colony morphology: Fluffy to powdery colony, cream, tan to pink in color. Reverse colorless to yellow • Microscopic morphology: Septate hyphae, macroconidia long, tapered, echinulate, thick- walled with seven or more cells, microconidia present264   2011/2012 Dermatology In-Review l Committed to Your Future
  13. 13. Trichophyton Species Biochemical Testing 1.) In vitro hair perforation (+) wedge shaped areas in hair shaft → T. mentagrophytes (–) no change in hair shaft → T. rubrum 2.) Pigmentation production on cornmeal agar with 1% dextrose (+) T. rubrum, (–) T. mentagrophytes 3.) Trichophyton agars tests—for growth factor requirements Thiamine T. verrucosum T. concentricum T. violaceum T. tonsurans Niacin T. equinum Histidine T. megninii Inositol and thiamine T. verrucosum 4.) Urease test (+) red - pink T. mentagrophytes (–) amber T. rubrumT. equinum • Zoophilic organism • Frequent cause of infection in horses, rarely infects humans • Colony morphology: Cream to yellow fluffy colony with radial grooves; reverse bright yellow to dark pink or brown • Microscopic morphology: Septate hyphae. Macroconidia rarely seen, fusiform, microconidia tear drop shaped laterally along hyphae • Miscellaneous: Requires niacin (“Horses are nice”)T. megninii • Anthropophilic organism: Seen in Africa and Europe • Primarily causes: T. barbae; ectothrix T. capitis, T. corporis, T. unguium • Colony morphology: White to pink suede like colony flat or with gently folds; reverse red • Microscopic morphology: Septate hyphae. Macroconidia pencil-shaped; microconidia tear drop, resembles T. rubrum • Miscellaneous: Requires histidine Medical Mycology  265
  14. 14. Figure 7-7. T. mentagrophytesT. mentagrophytes • Multiple varieties – Anthropophilic: T. mentagrophytes var. interdigitale (fluffy colony) – Zoophilic: T. mentagrophytes var. mentagrophytes (powdery colony) • Bullous T. pedis, T. corporis, T. barbae, white superficial onychomycosis, ectothrix T. capitis • Colony morphology – Anthropophilic: Fluffy white colony some powdery areas – Zoophilic: Powdery buff colony – Reverse rose brown to red • Microscopic morphology: Septate hyphae, spiral hyphae; macroconidia not always present, cigar-shaped, thin-walled microconidia – Anthropophilic: Fluffy form – few, smaller teardrop shaped, can be confused with T. rubrum – Zoophilic: Powdery form – abundant, round clusters on branched conidiophores – Miscellaneous: Hair perforation (+), pigmentation production CM agar 1% dex (–), urease (+) Figure 7-8. T. rubrumT. rubrum • Anthropophilic organism: Most common dermatophyte worldwide • T. pedis, T. manuum, T. corporis, T. cruris, onychomycosis, Majocchi’s granuloma, rare cause of T. capitis • Colony morphology: Fluffy to granular white to cream colony with a central elevation, some radial folding; reverse nondiffusible red, occasionally yellow-orange266   2011/2012 Dermatology In-Review l Committed to Your Future
  15. 15. • Microscopic morphology: Septate hyphae. Macroconidia rare, thin-walled, pencil-shaped; microconidia delicate teardrop shaped appear laterally on hyphae: “birds on a wire”; arthroconidia form from hyphae and macroconidia • Miscellaneous: Hair perforation (–), pigmentation production CM agar 1% dex (+), urease (–)T. soudanense • Anthropophilic organism: Central and West Africa • Endothrix Tinea capitis similar to T. tonsurans, T. corporis • Colony morphology: Flat to folded suede-like apricot colored colony with a fringed border; reverse deep yellow • Microscopic morphology: Septate hyphae with reflexive branching, arthroconidia, chlamydoconidia; Microconidia teardrop shaped, macroconidia not seen • Miscellaneous: Urease (–) Figure 7-9. T. tonsuransT. tonsurans • Anthropophilic organism •  Most common cause of T. capitis in the U.S. (black dot nonfluorescent endothrix) • Tinea corporis, rarely T. unguium, T. pedis • Colony morphology: Highly variable; powdery to suede-like, often with radial folds. Color varies yellow, brown, white, gray, or rose; reverse reddish brown, which may diffuse into agar • Microscopic morphology: Septate hyphae with spiral coils, chlamydoconidia, arthroconidia; macroconidia rare, irregular, smooth-walled. Microconidia numerous, variable, shape and size; teardrop, balloon forms, matchstick forms • Miscellaneous: Partial requirement for thiamineT. concentricum • Anthropophilic organism: South Pacific Islands, Asia, South America, Mexico • Tinea imbricata (Tokelau), not known to invade hair • Colony morphology: White, waxy colony turns amber or coral red and deeply folded, cerebriform • Microscopic morphology: Tangled septate hyphae without micro or macroconidia • Miscellaneous: Some strains are enhanced with thiamine Medical Mycology  267
  16. 16. Figure 7-10. T. schoenleiniiT. schoenleinii • Anthropophilic: Middle East, Europe, Africa, rare in U.S. • Tinea capitis: favus, dull fluorescence, diffuse, scarring alopecia, hairs remain long, scutula • T. corporis, T. unguium • Colony morphology: Heaped up suede colony usually grows deep into agar, cerebriform; reverse colorless to yellow • Microscopic morphology: Septate hyphae with favic chandeliers and chlamydoconidia, few if any conidiaT. verrucosum • Zoophilic organism: tinea of horses, cattle and dogs • Ectothrix T. capitis, inflammatory T. barbae, T. corporis, T. faciei • Colony morphology: Small folded and heaped, waxy, white colony; reverse colorless to yellow • Microscopic morphology: Best growth at 37˚C: thick irregular branching hyphae with chains of chlamydoconidia • Growth at 37˚ C with thiamine: Microconidia, occasional macroconidia shaped like string beans • Miscellaneous: Grows best at 37˚C, requires thiamine, some strains also require inositolT. violaceum • Anthropophilic organism: Southern Europe, Asia, Africa, Middle East, C. S. America, India • T. capitis, endothrix, black dot, similar to T. tonsurans • May cause favus • T. corporis, T. barbae, occasionally T. unguium • Colony morphology: Waxy, cerebriform, heaped purple colony; reverse deep port wine • Microscopic morphology: Septate tangled, irregular hyphae with intercalary chlamydospores. Few macro and microconidia form with thiamine enrichment • Miscellaneous: Partial requirement for thiamine268   2011/2012 Dermatology In-Review l Committed to Your Future
  17. 17. Dermatophyte-like Infections (Dermatomycosis) Figure 7-11. Scytalidium dimidiatumScytalidium dimidiatum • Dematiaceous (pigmented) organism causing dermatomycoses of the soles and toe webs, paronychia, and onychomycosis • Seen in southeastern U.S., S. America, Caribbean, Africa, India, Far East • Recovered from soil, plant pathogen • KOH: May look similar to dermatophytes, or be contorted with wide and narrow hyphae, don’t always see pigmentation of hyphae • Colony morphology: Initially woolly white colony turning gray to olive brown; reverse gray to black • Microscopic morphology: Hyaline to olive brown pigmented, septate hyphae of variable widths. Forms thin- to thick-walled, round to rectangular, one to two celled arthroconidia • Miscellaneous: Sensitive to cycloheximide, resistant to most antifungals7.4 SUBCUTANEOUS MYCOSIS Figure 7-12. Sporothrix schenckii (culture) Figure 7-13. Sporotrichosis (biopsy) Sporotrichosis • Sporothrix schenckii • Found worldwide, highest rate is in Mexico, Brazil, and South Africa • Risk factors: Gardener, farmer, florist, mason, miners, animal handlers (dog, cat, insects, parrot, horse, rat, armadillos), alcoholism Medical Mycology  269
  18. 18. • Sources: Organisms live in soil, organic material ex. roses, thorns, sphagnum moss, mine timbers, tree bark, straw, grasses • Transmitted by direct inoculation and inhalation • Lymphocutaneous-subcutaneous nodules, ulceration, lymphatic spread • Fixed cutaneous: Lesion without lymphatic spread, due to prior exposure • Disseminated: Mucocutaneous, pulmonary, osteoarticular, u TIP genitourinary, meningitis a ifferential diagnosis: cutaneous D • KOH: Often not helpful, organisms difficult to demonstrate leishmaniasis, cat scratch disease, • Biopsy: Stains poorly with H E, better seen with mycetoma due to Nocardia, PAS, GMS, “cigar bodies” or round yeast cells 4-6m S. apiospermum, TB, M. kansasii, • Asteroid Body: Yeast cell surrounded by eosinophilic M. marinum, deep fungal infection fringe • Direct immunofluorescences, serology, and sporotrichin skin test • 25° C: Cream-colored colony later becomes brown to black, leathery or velvety fold; septate delicate hyphae with conidiophores developing at right angles from the hyphae with conidia developing at the tip in a flowerette arrangement • 37° C: Yeast-like colony; may be gray or cream colored, cigar bodies (1-3 µm x 3-10 µm) and round yeast cells (10 µm), multiple budding yeast cells seen • Lymphocutaneous: Itraconazole, SSKI, terbinafine, fluconazole, heat therapy • Disseminated: Itraconazole and/or amphotericin BMycetoma (Maduromycosis, Madura Foot, Fungus Tumor) • Highest incidence along the Tropic of Cancer—Sudan, u TIP Mexico, India, Central and South America, Africa a aused by true fungi (eumycotic) or C filamentous bacteria (actinomycotic) • Organisms are soil or plant saprophytes • Penetrating wound most commonly foot (70%), lower leg a isease progresses slowly; triad of D tumefaction, draining sinuses, grains or hands, upper back, neck, shoulders granules (aggregates of organism) • Collect grains for KOH, histology and culture causing scarring, swelling, deformity, • Biopsy: Histiologic features of actinomycotic and bone involvement may occur eumycotic are similar. Grain located in the abscess or sinus tract surrounded by neutrophils, multinucleated giant cells, necrotic debris, and pallisading epitheloid cells Eumycotic • Contain hyphae (2-6 µm wide) and chlamydoconidia • Does not stain with gram stain, but stains well with GMS, PAS • Treatment: Debridement, itraconazole, ketoconazole, voriconazole, posaconazole • Relapses common270   2011/2012 Dermatology In-Review l Committed to Your Future
  19. 19. Table 7-4. Eumycotic Mycetoma Etiologic Agent Color of Grain Acremonium spp. white Aspergillus spp. white Curvularia spp. black Exophiala jeanselmei black Fusarium spp. white Leptoshaeria spp. black Madurella grisea black M. mycetomatis black – most common in Africa Pseudalleschella boydii, Scedosporium white-yellow – most common in apiospermum (asexual state) N. America Pyrenochaeta romeroi blackFigure 7-14. Actinomycotic GranuleActinomycotic• Fine branching filaments 0.5–1.5 mm tend to break up into short bacillary and coccoid forms• Stain gram (+); stains well with Giemsa, Brown-Brennen; may not stain well with H E or PAS• Nocardia sp. are gram (+), partially acid fast (fite stain) due to long chain fatty acids in cell wall; Nocardiosis caused by N. asteroides and N. brasiliensis and can manifest as pustules, cellulitis, ulcerations, abscesses and draining sinuses• Treatment of choice: Trimethoprim/sulfamethoxazole, netilmicin, amikacin, erthryomycin, 3rd generation cephalosporins, minocycline Medical Mycology  271
  20. 20. Table 7-5. Actinomycotic Mycetoma Etiologic Agent Color of Grain Actinomadura madurae yellow – white Actinomadura pelletieri red – most common in Africa Nocardia asteroides white – common in Central America Nocardia brasiliensis white – Mexico (most common) N. otitidiscaviarum white Nocardiopsis dassonvillei cream Streptomyces somaliensis yellow – white to brown Figure 7-15. Chromoblastomycosis (biopsy)Chromoblastomycosis (Chromomycosis, Verrucous dermatitis) • Seen mainly in tropics and subtropics, especially C. S. uTIP America, Africa, Cuba, Puerto Rico, Caribbean Islands, a onsecaea pedrosoi (most common), F Fonsecaea compacta, Rhinocladeilla Australia, Japan aquaspersa, Phialophora verrucosa, • Saprophytic organisms found in soil, decaying Exophiala jeanselmei, Cladophialophora vegetation, wood carrionii • Traumatic injury in agricultural workers to foot, leg, occasionally chest, shoulders u TIP • Cauliflower-like tumors may coalesce, irregular a iopsy: pseudoepitheliomatous hyperplasia, B epidermal microabscess, granulomatous verrucose plaques, nodules, annular with a central tissue response, “copper pennies” (sclerotic clearing, transepidermal elimination bodies, medlar bodies, chromobodies) • Complications: Include 2° infection, lymphedema, a opper pennies → brown, round, thick walled C elephantiasis, SCC cells 5-12 µm with septations • May see dematiaceous hyphae in early lesions • KOH: Brown, round thick walled septate cells • Culture: All organisms appear similar—black, velvety to slightly powdery colonies • Treatment: Surgery, itraconazole, +/– flucytosine, terbinafine, amphotericin BLacaziosis (Keloidal Blastomycosis, Lobomycosis, Lobo’s Disease) • Lacazia loboi formerly Loboa loboi • Brazil, Caribbean, associated with bottle-nosed dolphins272   2011/2012 Dermatology In-Review l Committed to Your Future
  21. 21. • Painless keloids, nodules, occasionally ulcers, verrucose lesions on face and upper extremities • No inflammatory reaction around skin • Biopsy: Single or multiple budding thick walled cells 9-10 µm, appear to be attached by a bridge, found free or phagocitized in a granulomatous reaction → “chain of coins” or “brass knuckles,” stains with Fontana Masson stain •  Organism not culturable • Treatment: Surgical excision (antifungals ineffective)7.5 DIMORPHIC FUNGI CAUSING SYSTEMIC DISEASEIntroduction • Virtually all organs are susceptible • Endemic primary pulmonary infections • Often self-limited disease • Seen in immunocompetent and immunocompromised patients • Immunity following disease • Can produce cutaneous manifestations with or without systemic involvement • See increased mortality: don’t have a good way to ID these diseases in a timely fashion • Antibody testing is available for most of the endemic mycoses Figure 7-16. Histoplasma capsulatum (mold form)Histoplasmosis (Cave Disease, Darling’s Disease) • Histoplasma capsulatum var. capsulatum • Soil enriched with bat, bird (especially starling), and chicken droppings • Runs the spectrum from asymptomatic to progressive u TIP dissemination with hematogenous spread to multiple aPrimary pulmonary infection organs andemic to Ohio, Mississippi, Missouri E • Toxic erythema, erythema multiforme, erythema nodosum River Valleys, Caribbean Islands, • Dissemination to bone, GI tract, spleen, liver, lymph nodes, Syracuse NY arthritis seen in AIDS patients • Cutaneous manifestations in AIDS: nonspecific lesions—macules, papules, nodules, ulcers (oral and rectal), impetigo, cellulitis, molluscum-like • Primary cutaneous: Very rare, lab accident, direct inoculation: chancre with lymphadenopathy Medical Mycology  273
  22. 22. • Biopsy: Intracellular organisms may be budding or singular, 2-4 µm, budding cells have a narrow isthmus of attachment; do not have a capsule (shrinkage artifact); look for a halo around the organism • Differential diagnosis: Leishmania, toxoplasmosis, penicilliosis, cryptococcosis, blastomycosis • 25˚C: White cottony colony, turns tan with age, septate hyphae with pear shaped microconidia 2-5 µm and round thick walled tuberculate macroconidia 7-15 µm (Figure 7-16) • 37˚C: Moist yeast colony, small round to oval budding cells 2-5 µm, inhibited by cycloheximide • Treatment will vary depending on clinical manifestation of disease. For disseminated disease: Amphotericin B followed by itraconazole, fluconazole, posaconazole, voriconazole, or ketoconazoleAfrican Histoplasmosis u TIP • Histoplasma capsulatum var. dubosii, endemic to Africa a reatment: Itraconazole drug of T choice for disseminated disease • Affects skin and bone; draining papules, abscesses, ulcers • Yeast phase 10-15 µm with a thick wall, cluster in giant cells Figure 7-17. Blastomyces (biopsy)Blastomycosis (North American Blastomycosis, Gilchrist’s Disease) • Blastomyces dermatitidis u TIP • Asymptomatic or self-limited disease manifesting as a a outheastern U.S.: Ohio and S virus-like respiratory disease, cough, chest pain, low-grade Mississippi River Valley, Great Lakes fever area, Chicago, St. Lawrence Seaway, • Chronic pulmonary: Progressive, involves various organs, Africa, Middle East, India mimics pneumonia, Histoplasmosis, or TB • Gilchrist’s disease: Primary cutaneous blastomycosis; usually an occupational hazard → lab workers, dog handlers (from a dog bite) • Dissemination to skin (80%), bone (25–50%), genitourinary system, CNS • Lesions found most often: face, mucous membranes, u TIP unclothed skin surfaces; first appear as nodules or papules a errucous lesions: sharp borders, V • Differential diagnosis: Coccidioidomycosis, may have a central clearing → indis- Cryptococcosis tiguishable from tuberculosis of skin • 25˚C: White to tan fluffy colony, small round conidia on a lcerative lesions: usually seen in U conidiophores, resemble lollipops mucocutaneous areas274   2011/2012 Dermatology In-Review l Committed to Your Future
  23. 23. • 37˚C: Cream, wrinkled, waxy colony, inhibited by u TIP cycloheximide, yeast cells-broad based, thick walls may a iopsy: granulomatous reaction, B single or broad based budding cells, appear double contoured, “figure 8” in appearance (Figure 8-15 µm; diagnostic; look for thick 7-17) walls • Treatment: Itraconazole drug of choice for non-CNS involvement, ketoconazole, voriconazole • STD treatment for meningeal disease - Amphotericin B Figure 7-18. Coccidioidomycosis (biopsy)Coccidioidomycosis (California Disease, San Joaquin Valley Fever) • Coccidioides immitis •  ndemic area: Southern California, Arizona, New Mexico, Southwest Texas, Northern E Mexico, Guatemala, Honduras, N. Argentina, Paraguay • Organisms become airborne during archeological digs, dust storms, and construction • Asymptomatic and self-limited respiratory tract infection is common • Pulmonary: Flu-like symptoms; erythema nodosum, erythema multiforme, toxic erythema • Cutaneous: Very rare; usually in lab worker → chancre-like lesion, lymphadenitis • Disseminated cocci: Occurs 1% cases; dissemination to subcutaneous tissue, bone, joints, meninges • Lesions appear on face, scalp, and neck as papules, pustules, nodules, verrucous, ulcerative, abscesses •  iopsy: Spherules stain well with PAS, GMS, HE, 10-80 µm containing endospores 2-5 µm B (Figure 7-18) • Differential diagnosis: TB, cryptococcosis, deep fungals • 25˚C or 37˚C: Same morphology—fluffy white or tan colony. Septate hyphae with 90° branching and many thick-walled barrel shaped rectangular arthrocondia alternating with empty cells • Treatment for meningitis: Fluconazole or amphotericin B • Nonmeningitis: Itraconazole or ketoconazole, voriconazoleParacoccioidomycosis (Brazilian Blastomycosis, South American Blastomycosis) • Paracoccidioides brasiliensis • Endemic area: Brazil (80% of reported cases), South and Central America • Primarily in male agricultural workers • Dissemination to GI, CNS, kidneys, liver, skin, lymph nodes, adrenals • Mucocutaneous lesions: Papules, vesicles, crusty granulomatous lesions • Massive lymphadenopathy Medical Mycology  275
  24. 24.  •  Biopsy: “Mariner’s Wheel” - large, thick-walled round cell (5-50 µm) with single and mul- tiple buddings (2-10 µm) attached to the mother cell by narrow connections • Differential diagnosis: TB, leishmaniasis, SCC, BCC, deep fungals, especially Blastomyces dermatitidis • 25˚C: White-brownish folded compact colony, septate hyphae with chlamydoconidia • 37˚C: Waxy cream yeast colony, sensitive to cycloheximide, large thick walled cell 5-50 um with single and multiple buds • Treatment of choice: Itraconazole, also amphotericin B, ketoconazole, or fluconazolePenicilliosis • Penicillium marneffei • Endemic in Southeast Asia, especially Thailand, China, Vietnam • Carried by healthy bamboo rats • Infects immunocompetent and immunocompromised, especially AIDS patients • Disseminated pulmonary infection •  Cutaneous lesions: Molluscum-like, mucocutaneous lesions → papular and ulcerative • Fungemia • Biopsy: Intracellular and extracellular oval to round yeast shaped forms 2-4 µm with cross walls, some sausage-shaped, stains well with PAS, GMS, not HE • Differential diagnosis: Histoplasmosis, cryptococcosis • 25˚C: Downy colony, white with yellowish green areas, reverse red diffusible pigment, phialides bearing oval conidia in chains • 37˚C: White yeast colony- round or oval yeast like cells 3-8 µm, central wall forms as the cells multiply by fission • Treatment: Amphotericin B and/or itraconazole, voriconazole7.6 OPPORTUNISTIC ORGANISMSIntroduction • Predisposing factors: neutropenia, immunocompromised • No particular age, sex, race, or endemic area • Organisms are of minimal virulence • Disease is not contagious • No immunity follows infection • Any fungus can cause invasive disease in the immunocompromised hostAspergillosis • Aspergillus sp. are 2nd only to Candida as the cause of opportunistic infections in patients who are immunocompromised • Organisms are ubiquitous in nature → leaves, grain, soil, decaying vegetation, soft contact lens, refrigerator, walls, dust, air ducts of operation rooms • Predisposing factors for invasive Aspergillosis: Profound neutropenia, bone marrow transplants, tissue injury, burns, long-term steroid use, broad-spectrum antibiotics, chemotherapy, elderly • Not generally seen in patients with cell-mediated immune dysfunction except late stage AIDS • Toxicity due to ingestion of contaminated food: Aflatoxins • Pulmonary: Allergy, asthma, aspergilloma (fungus ball-colonization in lungs, sinuses)276   2011/2012 Dermatology In-Review l Committed to Your Future
  25. 25. • Primary cutaneous: Generally due to trauma (IV and catheter sites) begin as erythematous macules, papules or plaques → hemorrhagic bullous and ulcerations with central necrotic eschar, may resemble cellulitis - Generally due to A. fumigatus and A. flavus • Otitis externa • Onychomycosis • Dissemination from primary pulmonary source to: CNS, kidney, heart, bone, GI, skin •  Necrosis, inflammation, thrombosis, blood vessel invasion • Bx: Best stains—GMS, PAS: dichotomously branching hyphae (3 µm wide) usually at 45o angles, maybe radiating out from a focal point, see conidia with conidiophores (fruiting heads) if fungus is growing in cavity with an air space. Splendore-Hoeppli phenomenon • Organisms evoke a pyogenic reaction accompanied by necrosis due to potent endotoxins • Treatment: Amphotericin B, itraconazole, voriconazole, caspofungin, flucytosine-second line therapy A. flavus • Velvety yellow to green or brown • Septate hyphae, rough conidiophore. Vesicle completely covered with phialides and chains of conidia Figure 7-19. Asperillus fumigatus A. fumigatus • Most common species u TIP • Velvety or powdery, dark green to gray a cute invasive zygomycosis is A • Septate hyphae, phialides on upper 2/3 of vesicle with characterized by: chains of conidia •   ggressive invasion of large blood A A. niger vessels and nerves • Woolly, white turns black with age •  Necrosis of adjacent tissue •  Ischemia, infarction of adjacent • Septate hyphae, phialides cover entire vesicle with chains tissue resulting in black pus of conidia •   isk factors: neutropenia, diabetes R mellitus, metabolic acidosis, trauma,Zygomycosis (Mucormycosis, Phycomycosis) organ transplants, systemic cortico- • Most commonly: Absidia, Rhizopus, Mucor steroids, severe burns, malnutrition, • Others: Cunninghamella, Saksenaeceae, hematologic malignancy Syncephalstrum, Conidiobolus, Rhizomucor, a hinocerebral zygomycosis: associated R Basidiobolus with acidotic diabetes; acute, rapidly progressive and fatal; infection begins • Worldwide distribution: Soil, animal excreta, seeds, in paranasal sinus; dark nasal discharge, fruits, moldy bread, decaying vegetation facial swelling, ulceration - most com- mon form of disease Medical Mycology  277
  26. 26. • Rhinocerebral Zygomycosis: Associated with acidotic diabetes; acute, rapidly progressive and fatal; infection begins in paranasal sinus; dark nasal discharge, facial swelling, ulceration - most common • Pulmonary: Fungoma • Gastrointestinal: Malnourished • Cutaneous: Primary local trauma (contaminated adhesive tape) or disseminated, induration and erythema, necrotic ulcer • Disseminated: Profoundly neutropenic. Starts in lungs hematogenous spread to CNS • Biopsy: Best demonstrated with PAS, GMS, may not stain as well with H E • Wide, ribbon-like hyphae with irregular right angle branching and very infrequent septations, hyphae may be twisted and distorted. Ring-shaped structures represent x-sections of hyphae. No spores are seen • Treatment: Amphotericin B, debridement • Organisms grow rapidly with grey cotton candy-like colonies Figure 7-20. Zygomycosis (biopsy) Figure 7-21. Rhizopus Rhizopus • Most common. Long unbranched sporangiophores, round sporangia, rhizoids directly under sporangiophores (Figure 7-21) Mucor • Long branched sporangiophores, round sporangia, no rhizoids278   2011/2012 Dermatology In-Review l Committed to Your Future
  27. 27. Absidia • Branched sporangiophores, conical swelling just beneath sporangium, pear-shaped sporangia, rhizoids are between sporangiophoresHyalohyphomycosis • Disseminated infection by those organisms having hyaline (nonpigmented) hyphae Figure 7-22. Fusarium Fusarium (Fusariosis) • More frequently seen in air samples than Aspergillus  •  Predisposing factors: Especially in patients with hematologic malignancies, neutropenia, trauma, burns → most common fungus in burn patients (Aspergillus is the second most common), pneumonia, mycotic keratitis, white superficial onychomycosis, disseminated disease • Cutaneous lesions: Target lesions, painful necrotic erythematous nodules, abscess, cellulitis • Bx: Looks similar to Aspergillus • Fluffy pink, violet, yellow, green colony • Septate hyphae with phialides which produce oval-shaped microconidia and banana shaped macroconidia. Chlamydoconidia present (Figure 7-22) • Mortality of patients with profound, prolonged neutropenia ~ 100% • Treatment: Amphotericin B + 5FC, liposomal Amphotericin B, granulocyte infusion may be given with therapy, itraconazole only ~ 50% effective, fluconazole also shows some resistance, voriconazole Penicillium • Ubiquitous in nature, frequent laboratory contaminant • Cutaneous, external ear, mycotic keratitis, bronchopulmonary, dissemination • Blue-green colony with white border • Septate hyphae with brush-like conidiophores and phialides with chains of round conidia Scopulariopis • White superficial onychomycosis • Powdery, brown colony • Septate hyphae with brush like phialides producing chains of round, thick-walled rough conidia Paecilomyces • Immunocompromised patients • Erythematous macules, vesicles, pustules, nodules Medical Mycology  279
  28. 28. • Pinkish, or yellowish-brown colony • Septate hyphae with tapered phialides and elliptical-shaped conidia in chains Figure 7-23. Phaeohyphomycosis Fontana-Masson Stain (biopsy) Phaeohyphomycosis • Represents a broad spectrum of dematiaceous (black or pigmented) fungal infections ranging from superficial to deep organ involvement. Organisms appear in tissue as dark yeast-like cells, pseudohyphae-like elements, variously shaped hyphae, often thick with swollen cell walls or any combination of these forms. All organisms look similar • Fontana-Masson stain reveals the pigment that may be missed with H E • Sclerotic bodies and/or granules are NOT seen • Need culture for identification of organism Figure 7-24. Alternaria Alternaria • Dark, septate hyphae with large, brown conidia in chains. Looks like a hand grenade Curvularia • Dark, septate hyphae with large conidia containing usually 4 cells appear curved due to swelling of the central cell Other Organisms • Exophiala, Bipolaris, Wangiella280   2011/2012 Dermatology In-Review l Committed to Your Future
  29. 29. Figure 7-25. Cryptococcosis Mucicarmine Stain (biopsy)Cryptococcosis • Cryptococcus neoformans and Cryptococcus gatti - seen in immunocompetent patients in tropics and recently in Northwest U.S. and Vancover • Encapsulated yeast, polysaccharide capsule enhances pathogenicity • Ubiquitous, abundant in soil enriched with aged pigeon droppings and roosting areas, moldy fruit, found in small numbers normal skin, vagina, GI tract • Both varieties become airborne • Normal host: Disease asymptomatic or mild pulmonary u TIP infection a IV, immunocompromised patients: H dissemination to CNS, bone, skin. • Primary cutaneous cryp. should be regarded as a sentinel of Cutaneous findings occur 10-15%; disseminated disease disseminated disease may occur • Prevalence in AIDS 3-6% without pulmonary or CNS symptoms. • Biopsy: Encapsulated round, dark walled yeast cell 2-12 µm. Lesions most often found head, neck, May see single or multiple budding within a single capsule mouth, nose and are polymorphous: nodules, papules, ulcers, herpetiform, • Gelatinous pattern: Numerous organisms, minimal cellulitis, molluscum-like, acneiform inflammation • Granulomatous pattern: Fewer organisms, granulomas • The organism stains with PAS, GMS, and Fontana-Masson • The mucopolysaccharide capsule stains with methylene blue, alcian blue, and mucicarmine • India Ink: Good screening method; highlights capsule of organism, use for “touch prep” of lesion • Latex agglutination test: Measures circulating capsular antigen • Culture: Flat to heaped cream-colored colonies may be very mucoid • Treatment: Amphotericin B with/without flucytosine followed by fluconazole for maintenance, itraconazole, fluconazole, voriconazole, posaconazoleCandidiasis • Candida albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, C. dubliniensis, C. kefyr • Most common fungal opportunistic infection, may be difficult to evaluate; yeast are ubiquitous and part of endogenous flora • C. albicans and C. glabrata - most often isolated from patients with invasive candidiasis • Cutaneous and mucocutaneous candidiasis: All ages, most common in very young and elderly, both sexes. Mucosal prevalent in HIV positive individuals Medical Mycology  281
  30. 30. u TIP • Clinical manifestations include: Thrush, perleche, a actors contributing to candida infection: F vulvovaginitis, balanitis, paronychia, onychomycosis, impaired epithelial cellbarrier, systemic ill- intertrigo, folliculitis, congenital and neonatal candidiasis, ness, neutrophil and macrophage systemic dissemination to any organ disorders, immune disorders, therapeutic • Cutaneous lesions: Papulonectrotic eschars, purpura agents, congenital or acquired endo- • Biopsy: Budding yeast, pseudohyphae, some species crine disorders, malignancies, indwelling produce true hyphae catheters, hyperalimentation, heat, humidity and friction • Topical treatment: Topical azoles, nystatin, terbinafine, naftine • Systemic treatment: Amphotericin B, ketoconazole, fluconazole, itraconazole, voriconazole, caspofungin • Culture: Cream colored pasty colony, growth 2-5 days C. albicans • Most common species 50%-60% of candida infections • True and pseudohyphae C. glabrata • 15%-20% of candida infections • Fluconazole resistance C. parapsilosis • Chronic paronychia and systemic infections C. tropicalis • 6-12% • Frequently causes dissemination to skin. Major cause of septicemia and disseminated candidiasis especially in patients with leukemia, lymphoma, and diabetes C. dubliniensis • Implicated in oropharyngeal Candidiasis in HIV infected patients and most frequently implicated in cases of recurrent infection following antifungal drug treatment7.7 MISCELLANEOUS ORGANISMS CAUSING FUNGUS-LIKE INFECTIONSRhinosporidiosis • Rhinosporidium seeberi, an aquatic protozoan previously considered a fungus • Mainly in India, South America, Africa, rarely seen in U.S. • Large polyps, granulomatous, wart-like lesions most frequently in nasal mucosa, eye, mouth •  Biopsy: Spherules or sporangium ~250-350 µm, endospores appear rough like raspberries • Stains red with mucicarmine • The organism is not culturable • Differential diagnosis: Cryptococcus, mucormycosis, paracoccidioidomycosis, Alternaria, Aspergillus • Treatment: Surgical removal, dapsone, local amphotericin B injection282   2011/2012 Dermatology In-Review l Committed to Your Future
  31. 31. Figure 7-26. Protothecosis (biopsy) Protothecosis • Prototheca wickerhamii • Rare cutaneous, subcutaneous, systemic infections cause by achloric algae • Worldwide habitat: Stagnant water • Skin lesions generally seen in immunosuppressed patients after trauma: papules, plaques, vesicles, cellulitis, eczematoid dermatitis, verrucous nodules • Causes olecrenon bursitis 1/3 cases  •  Biopsy: Stains well with PAS or GMS, round to oval nonbudding spherules (sporangia), with prominent cell walls, found free or in giant cells. Mature form contains a symmetrical arrangement of endospores = morula, 8-20 µm (“soccer ball”) (Figure 7-21) • Culture: Creamy white colonies, growth 3 days at 30º C • Round sporangia containing endospores, no budding, and no hyphae • Treatment: Surgical excision, Amphotericin B +/- tetracycline, ketoconazole 7.8 RANDOM FACTS AND SUMMARY TABLE Umbilicated Lesions Seen In • Cryptococcosis • Histoplasmosis • Penicilliosis • Coccidioidomycosis Organisms Found Engulfed by Macrophages → “His Girl Penelope” • Histoplasmosis • Granuloma Inguinale • Rhinoscleroma • Leishmaniasis • Penicilliosis Organisms that are Angiotrophic and Angioinvasive • Aspergillus sp. • Fusarium sp. • Zygomycetes Medical Mycology  283
  32. 32. Table 7-6. Summary of Organism Size and Appearance in Tissue Condition Diameter of Organism (µm) Features Lymphocyte 8-10 Point of Reference Actinomycotic mycetoma 150-290 Granule containing thin filaments Eumycotic mycetoma 500-2000 Granule containing hyphae and chlamydoconidia Aspergillosis 2-4 Septate hyphae Mucormycosis 10-25 Broad Infrequently septate irregular hyphae Blastomycosis 8-15 Broad-based budding yeast Coccidioidomycosis 10-80 Spherule (organisms 2-5 um) Histoplasmosis 3 Yeast, no capsule Paracoccidioidomycosis 60 Mariner’s wheel Penicilliosis 2-4 Oval to round yeast with cross walls Cryptococcosis 4-20 Mucinous encapsulated yeast Protothecosis 6-10 Spherule, Morula (soccer ball) Rhinosporidiosis 250-350 Spherule (organisms 6-10 um) Sporotrichosis 4-6 Round to cigar-shaped yeast Chromoblastomycosis 6-12 Copper pennies, medlar bodies, sclerotic bodies RE F E RE N C E S1. Espinel-Ingroff, A. In vitro activities of the new triazole vorconazole (UK-109,496) against opportunistic fila- mentous and dimorphic fungi and common emerging yeast pathogens. J Clin Microbiol 1998; 36: 198-202.2. Hay RJ. Deep Fungal Infections. In TB Fitzpatrick et al., Eds. Dermatology in General Medicine 5th ed. New York: McGraw Hill, vol II, 2372-2388, 1999.3. Kane, JR, et al. Laboratory Handbook of Dermatophytes. Belmont, CA: Star Publishing, 1997.4. Kwong-Chung, KJ, Bennett, JE. Medical Mycology. Philadephia: Lea and Febiger, 1992.5. Larone, DH. Medically Important Fungi: A Guide to Identification. 4th ed. Washington, DC: ASM Press, 2002.6. Lionakis MS, Kentoyiannis DP. Fusarium Infections in Critically Ill Patients. Semin Respir Crit Med 2004; 25 (2): 159-169.7. McGinnis, MR. Chromoblastomycosis and phaeohyphomycosis: new concepts, diagnosis, and mycology. J Am Acad Dermatol 1983; 1-16.8. Pfaller, MA, et al. In vitro activity of two echinocandin derivatives, LY303366 and MK-0991 (L-743,792), against clincial isolates of Aspergillus, Fusarium, Rhizopus, and other filamentous fungi. Diagn Microbiol Infect Dis 1998; 30:251-255.9. Rippon, JW. Medical Mycology: the Pathogenic Fungi and the Pathogenic Actinomycetes. 3rd ed. Philadelphia: WB Saunders, 1988.10. Sobera JO, Elewski BE. Fungal Disease. In Bolognia JL, Jorizzo JL, Rapini RP Eds. Dermatology 2nd ed. 1135- 1161, 2008.11. Sullivan, D, Coleman D. Candida dubliniensis: characteristics and identification. J Clin Microbiol 1998; 36:329- 334.12. Varkey JB, Perfect JR. Rare and Emerging Fungal Pulmonary Infections. Semin Respir Crit Care Med 29 (2): 121-131, 2008.13. Weitzman, I, Padhye, AA. Dermatophytes, Gross and Microscopic. Derm Clinics 1996; 14:9-22.14. Ellis, David. “Mycology online” 2011. The University of Adelaide, Australia. March 13, 2011 http://www.mycol-   2011/2012 Dermatology In-Review l Committed to Your Future
  33. 33. NOTES Medical Mycology  285
  34. 34. NOTES286   2011/2012 Dermatology In-Review l Committed to Your Future