etas_07 mycology

Medical Mycology 253

7 Medical Mycology

Evelyn K. Koestenblatt, MS, MT (ASCP)

Jeffrey M. Weinberg, MD

C o n t e n t s

7.1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .255

7.2 Superficial Mycoses . . . . . . . . . . . . . . . . . . . . . . . . . .256

7.3 The Dermatophytes . . . . . . . . . . . . . . . . . . . . . . . . . .258

7.4 Subcutaneous Mycosis . . . . . . . . . . . . . . . . . . . . . . .269

7.5 Dimorphic Fungi Causing Systemic Disease . . . . 273

7.6 Opportunistic Organisms . . . . . . . . . . . . . . . . . . . . .276

7.7 Miscellaneous Organisms Causing Fungus-like Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .282

7.8 Random Facts and Summary Table. . . . . . . . . . . .283

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7.1 INTRODUCTIONYeasts: Unicellular oval to round cells, reproduce by budding or fission and form moist colonies.Moulds: Filamentous fungi, characterized by tubular branching cells called hyphae, which

form 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: Dermatophytes

Direct Microscopic Examination• Potassium hydroxide (KOH): Rapid, easy, reliable diagnosis of fungal infections• SwartzLamkins:Containsacounterstain• KOHwithDMSO(dimethylsulfoxide)• ChlorazolBlackE-chitinspecific• Calcofluorwhite-mostsensitive,glucanspecificimmunofluorescentstain• Histologystains:

– Gormori Methanamine Silver (GMS)– Periodic Acid Schiff (PAS)– Fontana-Masson– Mayer’s Mucicarmine – Fite stain

256 2011/2012 Dermatology In-Review l Committed to Your Future

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-products

7.2 SUPERFICIAL MYCOSES

Figure 7-1. Pityriasis versicolor biopsy

Pityriasis Versicolor (Tinea Versicolor)•Mostcurrentnomenclature: Malassezia furfur, M. pachydermatis, M. dermatis, M. obtuse, M. restrica, M. sympodialis, M. slooffiae• Lipophilicorganisms• Foundworldwide,preferhumid,moist,warmenvironmentand↑ CO2 tension• Appearasroundtoovalyeastformsonnormalskininsebumrichareas

• Conversiontohyphaeandspore,“spaghettiandmeatballs”• Mild,chronic,sharplydemarcatedhyper/hypopigmentedmaculeswithfinescaling• Lesionsmostoftenseenonneck,shoulders,chest,back,upperarms,abdomen• Woodslamp(+)paleyellowfluorescence• Implicatedinotherdiseases:folliculitis(Pityrosporumfolliculitis),seborrheicdermatitis,

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: Organismsdifficulttogrow,requiresoliveoiloverlay• Topical treatment: Seleniumsulfide,ketoconazoleshampoo,topical“azoles,”ciclopirox• Systemic treatment: Ketoconazole,itraconazole,fluconazole


Tinea Nigra Palmaris (Superficial phaeohyphomycosis)• NewName:Hortaea werneckii Formerly: Phaeoannellomyces werneckii • Asymptomatic,browntoblack,macular,nonscalylesionsonpalmsofhandorsolesoffeet;

deeper pigmentation at advancing border• Warmhumidclimates:southernU.S.,SouthAfrica,Caribbean,FarEast,Europeand

Australia, Central and South America• Foundindecayingvegetation,soil,beachsand,water• KOH: Olivemultiplebranching,septatehyphaewithbuddingyeastcells• 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’sointment,azolecreams• Differential diagnosis: Junctional nevi, melanoma, Addison’s disease, hyperpigmentation of

syphilis and pinta, chemicals/dyes

Piedras• Limitedtohairshaft,characterizedbyfirm,irregularnodulescomposedoffungalelementsBlack Piedra• Piedraia hortae• Foundinsoilandwaterinhumid,tropicalareas

• 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• Keratinophilicsoil,waterandsewageorganism,seenintemperateregions

• 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-opwoundinfections• Treatment: Topical Amp B lotion, benzoic acid, salicylic acid, cut off hair, antifungal shampoo• Differential diagnosis: Lice,nits,haircasts,trichomycosisaxillaris• Trichosporanosis

– Trichosporon asahii– Disseminated disease seen mainly in immunocompromised patient with severe neutropenia–Cutaneouslesions:Erythematoustoviolaceouspapulesthatmayprogresstonecrotizing

lesions, nodular skin lesions, no concretions on hair– Treatment: Fluconazole, voriconazole, granulocyte infusions


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: Organismsotherthanthedermatophytesthatmaycausedeepfungalorsystemic infections with cutaneous manifestations

Ecology of Dermatophytes• Geophilic: Liveinsoil;inflammatoryinfectioninhumans• Zoophilic: Primarilyinfectsanimals;humansbecomeinfectedthroughdirectindirect

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

Table7-1.EcologyofCommonDermatophytes

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. violaceum

Common Dermatophyte Infections

Factors Favoring Dermatophyte Infection• Largeinoculumsize• Suitable environment: Hydration, friction, maceration, heat, darkness, occlusion• Growthrateoffungusmustbegreaterthanepidermalturnover

Tinea Capitis• Dermatophyteinfectionofthescalpandhair,generallyseeninchildhood

Ectothrix• Arthroconidiacoattheoutsideofthehair,cuticledestroyed• Fluorescent(Woodslight,366nm,mercurylampwithanickelchromiumoxidefilter,

fluorescence is due to pteridine production)


Fluorescent Endothrix Favus No Hair Involvement

• Nonfluorescent: T. mentagrophytes, T. rubrum, T. verrucosum, T. megninii, M. gypseum, M. nanum

• KOH prep: Arthroconidia are visualized on outside of hair shaft

Endothrix “Black Dot Ringworm”• Arthroconidiainvadeinteriorofthehairshaft• Blackdotsareremnantsofbrittlehairbrokenatthesurface

of the scalp, cuticle intact• T. rubrum, T. gourvilli, T. yaounde, T. tonsurans, T. soudanense, T. violaceum• KOH prep: Arthroconidia within hair shaft

Favus• Chronicinfectionofthescalp-beginsinchildhoodandmayextendintoadulthood• Scutula: Yellowish cup shaped crusts made up of hyphae and keratinous debris, may

have a single hair piercing through the center• PrimarilyT. schoenleinii, occasionally T. violaceum, M. gypseum• KOH prep: Hyphae and airspaces within hair shaft

Treatment• Griseofulvin,itraconazole,terbinafine,andseleniumsulfideorketoconazoleorloprox

shampoo

Kerion• Boggy,oozinginflammatoryreactiontofungus• Regionallymphadenopathy• Scarringalopeciamayresult• MostfrequentlyduetoM. canis, T. tonsurans,

T. verrucosum, T. mentagrophytes

Differential Diagnosis• Seborrheicdermatitis,impetigo,folliculitis,lupus,psoriasis,alopeciaareata

Table 7-2. Tinea Capitis

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

uTIPa�Pruritis, fever, pain, regional

lymphadenopathy, scarring alopecia

aTreatment may include prednisone

MNEMONICFluorescent Ectothrix Fungi

Cats And Dogs Fight and Growl

Sometimes

M. canis

M. audouinii

M. distortum

M. ferrugineum

and sometimes

M. gypseum

T. schoenleinii


Tinea Corporis• Anyofthedermatophytesarecapableofcausingtineacorporis;themostfrequently

recovered organisms include: T. rubrum, T. mentagrophytes, M. canis, T. tonsurans• Transmitteddirectlyfromindividuals,animalsorfomites• Organismsinvadestratumcorneumgenerallycausinganannularlesionwithan

erythematous raised, scaly advancing border, the center of the lesion may show clearing

Tinea Imbricata• T. concentricum; endemictoSouthPacific,S.&C.AmericaandFarEast.Polycyclicscaly

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, requiresbiopsy

for dx and oral antifungal

Differential Diagnosis• Seborrheic,atopicorcontactdermatitis,psoriasis,impetigo,lichensimplex,nummular

eczema, tertiary syphilis

Tinea Barbae• Inmen,thebeardedareaofthefaceandneck,generallyinflammatory• Associatedwithexposuretoanimals• Inflammatory: T. mentagrophytes, T. verrucosum• Superficial form: T. violaceum, T. rubrum• Abscess: M. canis• Verrucous granulomatosis: E. floccosum• Requiresoralantifungal

Tinea Cruris• Mainlyseeninmales,involvesthegroin,perinealandperianalskin• Directorindirectcontact• E. floccosum, T. rubrum, T. mentagrophytes

Tinea Faciei• Femalesandchildrenmostfrequentlytheupperlipandchin• Maybehistoryofanimalexposure• T. rubrum, T. mentagrophytes, T. concentricum, M. canis

Tinea Manuum• Palmar/interdigitalareasofthehands,almostalwaysassociatedwithT. pedis• T. rubrum, T. mentagrophytes, E. floccosum

Tinea Pedis• Moccasin type: E. floccosum, T. rubrum• Interdigital type: E. floccosum, T. mentagrophytes• Vesicular type: T. mentagrophytes• Interwebinfectionsofteninvolvefungi,yeast,gramnegativeandpositivebacteria


Tinea Unguium• Dermatophyteinfectionofthenails

Onychomycosis• Fungalinfectionofthenailsduetodermatophyte,yeast

or nondermatophyte

Distal Lateral Subungual Onychomycosis• Infectionbeginsdistallyandinvolvesthenailbed,nailplateandlateralnailfold;thicknailwithdebris,looseorcracked nail plate

•T. rubrum

Proximal White Subungual Onychomycosis•Rarestformofonychomycosis•AIDSmarker•Organismsenterthecuticleandinfecttheproximalpartofthenailbedcausingwhite

islands that slowly invade the nail plate•T. rubrum mostfrequentlyrecovered•AlsoT. megninii, T. schoenleinii, T. tonsurans, T. mentagrophytes, E. floccosum

White Superficial Onychomycosis•Organisminvadesthesurfaceofthenailplateoftoenailsonly•Irregularwhitechalkyopaquepatchesonthenail• MostfrequentT. mentagrophytes, also Aspergillus species esp. terreus, Acremonium

(formerly Cephalosporium), Fusarium, Scopulariopsis• InHIVpopulation,generallycausedbyT. rubrum

Tinea Incognito• Theuseofcorticosteroidscancauseanatypicalappearinglesion

Dermatophytids• Eczematousallergicreactiontodermatophyteinfectionelsewhereontheskin• Lesionsaresterile;reactionclearsafterfungushasbeeneradicated• Patientwilltestpositivetogroup-specifictrichophytonantigen

Table 7-3. Genus Differentiation

Epidermophyton Trichophyton Microsporum

Microconidia not produced Microconidia diagnostic, numer-ous with characteristic arrange-ments and shapes (some species do not produce conidia)

Microconidia not distinctive

Macroconidia smooth-walled, club-shaped, 2–6 cells, occurs singly or in clusters, thin and thick cell walls

Macroconidia not distinctive, smooth, thin cell wall, pencil-shaped

Macroconidia diagnostic, rough-walled (echinulate), multicellular, barrel-shaped, thick cell wall

No hair involvement Nonfluorescent ecto- and endo-thrix invasion

Fluorescent & nonfluorescent ectothrix invasion

uTIPaDistal Lateral Subungual Onychomycosis • T. rubrumaProximal White Subungual Onychomycosis • AIDSmarker • T. rubumaWhite Superficial Onychomycosis

• T. mentagrophytes


Epidermophyton

Figure 7-2. E. floccosum

E. floccosum• Anthropophilic: Worldwide• Nohairparasitism,Tinea cruris, T. pedis, occasionally T. corporis, onychomycosis• Colony morphology: Khaki-coloredcolony,orange-brownreverse,radialgrooves,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• Anthropophilicorganism:Worldwide• Tineacorporis,formerlythe#1causeofT. capitis in children (fluorescent ectothrix)• Colony morphology: Grey to tan colony, reverse salmon with a reddish brown center, flat surface,“mousefurappearance”

• Microscopic morphology: Septate hyphae with terminal chlamydoconidia often with pointedends.Pectinatebodies,racquethyphaeandfavicchandeliersmayoccur.Rarelysee macroconidia, when present poorly shaped, thick-walled and echinulate. Microconidia occasionally seen

• Miscellaneous: Polished Rice (–)


Figure 7-4. M. canis

M. canis• Zoophilicorganism(catsanddogs)

• Most common cause of T. capitisworldwide (fluorescent ectothrix)• T. corporis, T. faciei, T. unguium, T. pedis (rarely)• Colony morphology: Whitefluffy,fur-likecolonywithyellowperipheryandfeathery

border. Reverse deep yellow• Microscopic morphology: Septate hyphae. Macroconidia are numerous, spindle shaped, thick-walledwithknoblikeends(“dog’stail”)havingsixormorecells.Occasionalclub-shaped microconidia

• Miscellaneous: Polished Rice (+)

M. canis var. distortum• Zoophilicorganism:FoundinAustraliaandNewZealand• Fluorescentectothrixtineacapitis• Colony morphology: Whitetobuffvelvety,fluffycolony.Reverseyellow• Microscopic morphology: Septate hyphae. Macroconidia resemble distorted M. canis,

microconidia present• Miscellaneous:PolishedRice(+)

M. ferrugineum• Anthropophilicorganism:FoundAsia,IndiaandAfrica• Fluorescentectothrixtineacapitis,similartoM. audouinii, Tinea corporis• Colony morphology: Smooth, waxy, heaped, rust colored colony. Reverse cream to yellow

orange• Microscopic morphology: Longstraightseptatehyphaewithprominentcrosswalls,bamboo-like.Occasionalchlamydoconidia.Noconidia

M. gallinae• Zoophilic organism: Chicken favus• Rarelycausesectothrixtineacapitis• 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


Figure 7-5. M. gypseum

M. gypseum Complex• Geophilicorganismhumaninfectionresultsfromdirectcontactfromthesoil• 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. nanum

M. nanum • Zoophilic/geophilicorganism• Pigringworm,ectothrixtineacapitis• Colony morphology: Fluffy white colony → powdery beige. Reverse orange to reddish brown• Microscopic morphology: Septatehyphae.Macroconidiaechinulate,eggshapedor“pigsnout”withatruncatedbase,onetothreecells,microconidiaclub-shaped

M. vanbreuseghemii• Geophilicorganism• Rarelyinfectshumansandanimals• 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 present


Trichophyton Species Biochemical Testing 1.) In vitro hair perforation

(+)wedgeshapedareasinhairshaft→ 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 requirementsThiamine 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. rubrum

T. equinum• Zoophilicorganism• Frequentcauseofinfectioninhorses,rarelyinfectshumans• Colony morphology:Creamtoyellowfluffycolonywithradialgrooves;reversebright

yellow to dark pink or brown• Microscopic morphology: Septate hyphae. Macroconidia rarely seen, fusiform,

microconidia tear drop shaped laterally along hyphae• Miscellaneous: Requiresniacin(“Horsesarenice”)

T. megninii• Anthropophilic organism: SeeninAfricaandEurope• Primarily causes: T. barbae; ectothrix T. capitis, T. corporis, T. unguium• Colony morphology: Whitetopinksuedelikecolonyflatorwithgentlyfolds;reversered• Microscopic morphology: Septatehyphae.Macroconidiapencil-shaped;microconidiatear

drop, resembles T. rubrum• Miscellaneous: Requireshistidine


Figure 7-7. T. mentagrophytes

T. mentagrophytes• Multiplevarieties

– Anthropophilic: T. mentagrophytes var. interdigitale (fluffy colony)– Zoophilic: T. mentagrophytes var. mentagrophytes (powdery colony)

• BullousT. 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: Septatehyphae,spiralhyphae;macroconidianotalwayspresent,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:Hairperforation(+),pigmentationproductionCMagar1%dex(–),urease(+)

Figure 7-8. T. rubrum

T. 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, someradialfolding;reversenondiffusiblered,occasionallyyellow-orange


• Microscopic morphology: Septatehyphae.Macroconidiarare,thin-walled,pencil-shaped;microconidiadelicateteardropshapedappearlaterallyonhyphae:“birdsonawire”;arthroconidia form from hyphae and macroconidia

• Miscellaneous: Hairperforation(–),pigmentationproductionCMagar1%dex(+),urease(–)

T. soudanense• Anthropophilic organism:CentralandWestAfrica• EndothrixTineacapitis similar to T. tonsurans, T. corporis• Colony morphology: Flattofoldedsuede-likeapricotcoloredcolonywithafringedborder;

reverse deep yellow• Microscopic morphology: Septate hyphae with reflexive branching, arthroconidia, chlamydoconidia;Microconidiateardropshaped,macroconidianotseen

• Miscellaneous: Urease (–)

Figure 7-9. T. tonsurans

T. tonsurans • Anthropophilicorganism

• Most common cause ofT. capitisin the U.S. (black dot nonfluorescent endothrix)• Tineacorporis,rarelyT. unguium, T. pedis• Colony morphology: Highlyvariable;powderytosuede-like,oftenwithradialfolds.Colorvariesyellow,brown,white,gray,orrose;reversereddishbrown,whichmaydiffuseintoagar

• Microscopic morphology: Septatehyphaewithspiralcoils,chlamydoconidia,arthroconidia;macroconidia rare, irregular, smooth-walled. Microconidia numerous, variable, shape and size;teardrop,balloonforms,matchstickforms

• Miscellaneous:Partialrequirementforthiamine

T. concentricum• Anthropophilic organism: South Pacific Islands, Asia, South America, Mexico• Tineaimbricata(Tokelau),notknowntoinvadehair• Colony morphology: White,waxycolonyturnsamberorcoralredanddeeplyfolded,

cerebriform• Microscopic morphology: Tangled septate hyphae without micro or macroconidia• Miscellaneous: Some strains are enhanced with thiamine


Figure 7-10. T. schoenleinii

T. schoenleinii • Anthropophilic:MiddleEast,Europe,Africa,rareinU.S.• Tineacapitis:favus,dullfluorescence,diffuse,scarringalopecia,hairsremainlong,scutula• T. corporis, T. unguium • Colony morphology: Heapedupsuedecolonyusuallygrowsdeepintoagar,cerebriform;

reverse colorless to yellow• Microscopic morphology: Septate hyphae with favic chandeliers and chlamydoconidia, few

if any conidia

T. verrucosum • Zoophilic organism: tinea of horses, cattle and dogs• EctothrixT. capitis, inflammatory T. barbae, T. corporis, T. faciei• Colony morphology: Smallfoldedandheaped,waxy,whitecolony;reversecolorlessto

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:Growsbestat37˚C,requiresthiamine,somestrainsalsorequireinositol

T. violaceum• Anthropophilic organism: SouthernEurope,Asia,Africa,MiddleEast,C.&S.America,India• T. capitis, endothrix, black dot, similar to T. tonsurans• Maycausefavus• T. corporis, T. barbae, occasionally T. unguium• Colony morphology: Waxy,cerebriform,heapedpurplecolony;reversedeepportwine• Microscopic morphology: Septate tangled, irregular hyphae with intercalary

chlamydospores. Few macro and microconidia form with thiamine enrichment• Miscellaneous: Partialrequirementforthiamine


Dermatophyte-like Infections (Dermatomycosis)

Figure 7-11. Scytalidium dimidiatum

Scytalidium dimidiatum• Dematiaceous(pigmented)organismcausingdermatomycosesofthesolesandtoe

webs, paronychia, and onychomycosis• SeeninsoutheasternU.S.,S.America,Caribbean,Africa,India,FarEast• Recoveredfromsoil,plantpathogen• KOH: May look similar to dermatophytes, or be contorted with wide and narrow hyphae,

don’t always see pigmentation of hyphae• Colony morphology: Initiallywoollywhitecolonyturninggraytoolivebrown;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 antifungals

7.4 SUBCUTANEOUS MYCOSIS

Figure 7-12. Sporothrix schenckii (culture) Figure 7-13. Sporotrichosis (biopsy)

Sporotrichosis • Sporothrix schenckii• Foundworldwide,highestrateisinMexico,Brazil,andSouthAfrica• Risk factors: Gardener, farmer, florist, mason, miners, animal handlers (dog, cat, insects,

parrot, horse, rat, armadillos), alcoholism


• Sources: Organismsliveinsoil,organicmaterialex.roses,thorns,sphagnummoss,minetimbers, tree bark, straw, grasses

• Transmittedbydirectinoculationandinhalation• Lymphocutaneous-subcutaneous nodules, ulceration, lymphatic spread• Fixed cutaneous: Lesionwithoutlymphaticspread,duetopriorexposure• Disseminated: Mucocutaneous, pulmonary, osteoarticular,

genitourinary, meningitis• KOH: Oftennothelpful,organismsdifficulttodemonstrate

•Biopsy:StainspoorlywithH&E,betterseenwith PAS,GMS,“cigarbodies”orroundyeastcells4-6m

• AsteroidBody:Yeastcellsurroundedbyeosinophilicfringe

• Directimmunofluorescences,serology,andsporotrichinskintest• 25°C:Cream-coloredcolonylaterbecomesbrowntoblack,leatheryorvelvety&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-likecolony;maybegrayorcreamcolored,cigarbodies(1-3µm 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 B

Mycetoma (Maduromycosis, Madura Foot, Fungus Tumor)• HighestincidencealongtheTropicofCancer—Sudan,

Mexico, India, Central and South America, Africa• Organismsaresoilorplantsaprophytes• Penetratingwoundmostcommonlyfoot(70%),lowerleg

hands, upper back, neck, shoulders

•CollectgrainsforKOH,histologyandculture• Biopsy: Histiologic features of actinomycotic and

eumycotic are similar. Grain located in the abscess or sinus tract surrounded by neutrophils, multinucleated giant cells, necrotic debris, and pallisading epitheloid cells

Eumycotic •Containhyphae(2-6µm wide) and chlamydoconidia •Doesnotstainwithgramstain,butstainswellwithGMS,PAS •Treatment: Debridement, itraconazole, ketoconazole, voriconazole, posaconazole •Relapsescommon

uTIPa Differential diagnosis: cutaneous

leishmaniasis, cat scratch disease,

mycetoma due to Nocardia,

S. apiospermum, TB, M. kansasii, M. marinum, deep fungal infection

uTIPa�Caused by true fungi (eumycotic) or

filamentous bacteria (actinomycotic)

a�Disease progresses slowly; triad of

tumefaction, draining sinuses, grains or

granules (aggregates of organism)

causing scarring, swelling, deformity,

bone involvement may occur


Table7-4.EumycoticMycetoma

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 apiospermum(asexual state)

white-yellow – most common in N. America

Pyrenochaeta romeroi black

Figure 7-14. Actinomycotic Granule

Actinomycotic• Finebranchingfilaments0.5–1.5mmtendtobreakupintoshortbacillaryandcoccoidforms• Staingram(+);stainswellwithGiemsa,Brown-Brennen;maynotstainwellwithH&EorPAS• Nocardia sp.aregram(+),partiallyacidfast(fitestain)duetolongchainfattyacidsincellwall;NocardiosiscausedbyN. 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


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) • Seenmainlyintropicsandsubtropics,especiallyC.&S.

America, Africa, Cuba, Puerto Rico, Caribbean Islands, Australia, Japan

• Saprophyticorganismsfoundinsoil,decayingvegetation, wood

• Traumaticinjuryinagriculturalworkerstofoot,leg,occasionally chest, shoulders

• Cauliflower-liketumorsmaycoalesce,irregularverrucoseplaques,nodules,annularwithacentralclearing, transepidermal elimination

• Complications: Include 2° infection, lymphedema, elephantiasis, SCC

• Mayseedematiaceoushyphaeinearlylesions• KOH: Brown, round thick walled septate cells• Culture: Allorganismsappearsimilar—black,velvetytoslightlypowderycolonies• Treatment: Surgery,itraconazole,+/–flucytosine,terbinafine,amphotericinB

Lacaziosis (KeloidalBlastomycosis,Lobomycosis,Lobo’sDisease)• Lacazia loboi formerly Loboa loboi• Brazil,Caribbean,associatedwithbottle-noseddolphins

uTIPa Fonsecaea pedrosoi (most common),

Fonsecaea compacta, Rhinocladeilla

aquaspersa, Phialophora verrucosa,

Exophiala jeanselmei, Cladophialophora

carrionii

uTIPa�Biopsy: pseudoepitheliomatous hyperplasia,

epidermal microabscess, granulomatous

tissue response, “copper pennies” (sclerotic

bodies, medlar bodies, chromobodies)

a� Copper pennies → brown, round, thick walled

cells 5-12 µm with septations


• Painlesskeloids,nodules,occasionallyulcers,verrucoselesionsonfaceandupperextremities

• Noinflammatoryreactionaroundskin• 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 →“chainofcoins”or“brassknuckles,”stainswithFontanaMassonstain

• Organismnotculturable• Treatment: Surgical excision (antifungals ineffective)

7.5 DIMORPHIC FUNGI CAUSING SYSTEMIC DISEASE Introduction

• Virtuallyallorgansaresusceptible• Endemicprimarypulmonaryinfections• Oftenself-limiteddisease• Seeninimmunocompetentandimmunocompromisedpatients• Immunityfollowingdisease• Canproducecutaneousmanifestationswithorwithoutsystemicinvolvement• Seeincreasedmortality:don’thaveagoodwaytoIDthesediseasesinatimelyfashion• Antibodytestingisavailableformostoftheendemicmycoses

Figure 7-16. Histoplasma capsulatum (mold form)

Histoplasmosis (Cave Disease, Darling’s Disease) • Histoplasma capsulatum var. capsulatum• Soilenrichedwithbat,bird(especiallystarling),andchickendroppings• Runsthespectrumfromasymptomatictoprogressive

dissemination with hematogenous spread to multiple organs

• Toxicerythema,erythemamultiforme,erythemanodosum• Disseminationtobone,GItract,spleen,liver,lymphnodes,

arthritis seen in AIDS patients• CutaneousmanifestationsinAIDS:nonspecificlesions—macules,papules,nodules,ulcers

(oral and rectal), impetigo, cellulitis, molluscum-like• Primary cutaneous: Very rare, lab accident, direct inoculation: chancre with

lymphadenopathy

uTIPaPrimary pulmonary infection

a�Endemic to Ohio, Mississippi, Missouri

River Valleys, Caribbean Islands,

Syracuse NY


• Biopsy: Intracellular organisms may be budding or singular, 2-4 µm, budding cells have a narrowisthmusofattachment;donothaveacapsule(shrinkageartifact);lookforahaloaround the organism

• Differential diagnosis:Leishmania,toxoplasmosis,penicilliosis,cryptococcosis,blastomycosis• 25˚C: Whitecottonycolony, 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• Treatmentwillvarydependingonclinicalmanifestationofdisease.Fordisseminated

disease: Amphotericin B followed by itraconazole, fluconazole, posaconazole, voriconazole, or ketoconazole

African Histoplasmosis• Histoplasma capsulatum var. dubosii, endemic to Africa• Affectsskinandbone;drainingpapules,abscesses,ulcers• Yeastphase10-15µm with a thick wall, cluster in giant cells

Figure 7-17. Blastomyces (biopsy)

Blastomycosis (North American Blastomycosis, Gilchrist’s Disease) • Blastomyces dermatitidis• Asymptomaticorself-limiteddiseasemanifestingasa

virus-like respiratory disease, cough, chest pain, low-grade fever

• Chronic pulmonary: Progressive, involves various organs, mimics pneumonia, Histoplasmosis, or TB

• Gilchrist’s disease: Primarycutaneousblastomycosis;usuallyanoccupationalhazard→ lab workers, dog handlers (from a dog bite)

• Disseminationtoskin(80%),bone(25–50%),genitourinarysystem,CNS• Lesionsfoundmostoften: face, mucous membranes, unclothedskinsurfaces;firstappearasnodulesorpapules

• Differential diagnosis: Coccidioidomycosis, Cryptococcosis

• 25˚C: Whitetotanfluffycolony,smallroundconidiaonconidiophores, resemble lollipops

uTIPa Southeastern U.S.: Ohio and

Mississippi River Valley, Great Lakes

area, Chicago, St. Lawrence Seaway,

Africa, Middle East, India

uTIPa�Verrucous lesions: sharp borders,

may have a central clearing → indis-

tiguishable from tuberculosis of skin

a Ulcerative lesions: usually seen in

mucocutaneous areas

uTIPa Treatment: Itraconazole drug of

choice for disseminated disease


• 37˚C: Cream, wrinkled, waxy colony, inhibited by cycloheximide, yeast cells-broad based, thick walls may appeardoublecontoured,“figure8”inappearance(Figure7-17)

• Treatment: Itraconazole drug of choice for non-CNS involvement, ketoconazole, voriconazole

• STD treatment for meningeal disease - Amphotericin B

Figure 7-18. Coccidioidomycosis (biopsy)

Coccidioidomycosis (CaliforniaDisease,SanJoaquinValleyFever)• Coccidioides immitis

• Endemicarea:Southern California, Arizona, New Mexico, Southwest Texas, Northern Mexico, Guatemala, Honduras, N. Argentina, Paraguay

• Organismsbecomeairborneduringarcheologicaldigs,duststorms,andconstruction• Asymptomaticandself-limitedrespiratorytractinfectioniscommon• Pulmonary:Flu-likesymptoms;erythemanodosum,erythemamultiforme,toxicerythema• Cutaneous:Veryrare;usuallyinlabworker→ chancre-like lesion, lymphadenitis• Disseminated cocci:Occurs<1%cases;disseminationtosubcutaneoustissue,bone,joints,

meninges• Lesionsappearonface,scalp,andneckaspapules,pustules,nodules,verrucous,ulcerative,

abscesses

• Biopsy: SpherulesstainwellwithPAS,GMS,H&E,10-80µm containing endospores 2-5 µm (Figure 7-18)

• Differential diagnosis: TB, cryptococcosis, deep fungals• 25˚C or 37˚C:Samemorphology—fluffywhiteortancolony.Septatehyphaewith90°

branching and many thick-walled barrel shaped rectangular arthrocondia alternating with empty cells

• Treatment for meningitis: Fluconazole or amphotericin B• Nonmeningitis: Itraconazole or ketoconazole, voriconazole

Paracoccioidomycosis (Brazilian Blastomycosis, South American Blastomycosis)• Paracoccidioides brasiliensis• Endemic area:Brazil(80%ofreportedcases),SouthandCentralAmerica• Primarilyinmaleagriculturalworkers• DisseminationtoGI,CNS,kidneys,liver,skin,lymphnodes,adrenals• Mucocutaneous lesions: Papules, vesicles, crusty granulomatous lesions• Massivelymphadenopathy

uTIPa Biopsy: granulomatous reaction,

single or broad based budding cells,

8-15 µm; diagnostic; look for thick

walls


• Biopsy:“Mariner’sWheel”-large,thick-walledroundcell(5-50µm) with single and multiple 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-brownishfoldedcompactcolony,septatehyphaewithchlamydoconidia• 37˚C:Waxycreamyeastcolony,sensitivetocycloheximide,largethickwalledcell5-50um

with single and multiple buds• Treatment of choice: Itraconazole, also amphotericin B, ketoconazole, or fluconazole

Penicilliosis• Penicillium marneffei• EndemicinSoutheastAsia,especiallyThailand,China,Vietnam• Carriedbyhealthybamboorats• Infectsimmunocompetentandimmunocompromised,especiallyAIDSpatients• Disseminatedpulmonaryinfection

• 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,somesausage-shaped,stainswellwithPAS,GMS,notH&E

• 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:Whiteyeastcolony-roundorovalyeastlikecells3-8µm, central wall forms as the

cells multiply by fission• Treatment: Amphotericin B and/or itraconazole, voriconazole

7.6 OPPORTUNISTIC ORGANISMS Introduction

• Predisposingfactors:neutropenia,immunocompromised• Noparticularage,sex,race,orendemicarea• Organismsareofminimalvirulence• Diseaseisnotcontagious• Noimmunityfollowsinfection• Anyfunguscancauseinvasivediseaseintheimmunocompromisedhost

Aspergillosis• Aspergillussp.are2ndonlytoCandidaasthecauseofopportunisticinfectionsinpatients

who are immunocompromised• Organismsareubiquitousinnature→ 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

• Notgenerallyseeninpatientswithcell-mediatedimmunedysfunctionexceptlatestageAIDS• Toxicity due to ingestion of contaminated food: Aflatoxins• Pulmonary: Allergy, asthma, aspergilloma (fungus ball-colonization in lungs, sinuses)


• Primary cutaneous: Generally due to trauma (IV and catheter sites) begin as erythematous macules,papulesorplaques→ hemorrhagic bullous and ulcerations with central necrotic eschar, may resemble cellulitis - Generally due to A. fumigatus and A. flavus

• Otitisexterna• Onychomycosis• Dissemination from primary pulmonary source to: CNS, kidney, heart, bone, GI, skin

• Necrosis,inflammation,thrombosis,bloodvesselinvasion• Bx: Beststains—GMS,PAS:dichotomouslybranchinghyphae(3µm 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

• Organismsevokeapyogenicreactionaccompaniedbynecrosisduetopotentendotoxins• Treatment: Amphotericin B, itraconazole, voriconazole, caspofungin, flucytosine-second line

therapy

A. flavus• Velvetyyellowtogreenorbrown• Septatehyphae,roughconidiophore.Vesiclecompletelycoveredwithphialidesand

chains of conidia

Figure 7-19. Asperillus fumigatus

A. fumigatus • Mostcommonspecies• Velvetyorpowdery,darkgreentogray• Septatehyphae,phialidesonupper2/3ofvesiclewith

chains of conidia

A. niger• Woolly,whiteturnsblackwithage• Septatehyphae,phialidescoverentirevesiclewithchains

of conidia

Zygomycosis (Mucormycosis, Phycomycosis)• Mostcommonly:Absidia, Rhizopus, Mucor• Others:Cunninghamella, Saksenaeceae,

Syncephalstrum, Conidiobolus, Rhizomucor, Basidiobolus

• Worldwide distribution: Soil, animal excreta, seeds, fruits, moldy bread, decaying vegetation

uTIPa Acute invasive zygomycosis is

characterized by: • �Aggressive�invasion�of�large�blood�

vessels�and�nerves

� • Necrosis�of�adjacent�tissue

� • Ischemia,�infarction�of�adjacent�

� ��tissue�resulting�in�black�pus

� • �Risk�factors:�neutropenia,�diabetes�

mellitus,�metabolic�acidosis,�trauma,�

organ�transplants,�systemic�cortico-

steroids,�severe�burns,�malnutrition,�

hematologic�malignancy

a Rhinocerebral zygomycosis: associated�with�acidotic�diabetes;�acute,�rapidly�

progressive�and�fatal;�infection�begins�

in�paranasal�sinus;�dark�nasal�discharge,�

facial�swelling,�� ulceration�-�most�com-

mon�form�of�disease


• Rhinocerebral Zygomycosis:Associatedwithacidoticdiabetes;acute,rapidlyprogressiveandfatal;infectionbeginsinparanasalsinus;darknasaldischarge,facialswelling,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: BestdemonstratedwithPAS,GMS,maynotstainaswellwithH&E• Wide,ribbon-likehyphaewithirregularrightanglebranchingandveryinfrequent

septations, hyphae may be twisted and distorted. Ring-shaped structures represent x-sections of hyphae. No spores are seen

• Treatment: Amphotericin B, debridement• Organismsgrowrapidlywithgreycottoncandy-likecolonies

Figure 7-20. Zygomycosis (biopsy)

Figure 7-21. Rhizopus

Rhizopus• Mostcommon.Longunbranchedsporangiophores,roundsporangia,rhizoidsdirectly under

sporangiophores (Figure 7-21)

Mucor• Longbranchedsporangiophores,roundsporangia,norhizoids


Absidia• Branchedsporangiophores,conicalswellingjustbeneathsporangium,pear-shaped

sporangia, rhizoids are between sporangiophores

Hyalohyphomycosis• Disseminatedinfectionbythoseorganismshavinghyaline(nonpigmented)hyphae

Figure 7-22. Fusarium

Fusarium (Fusariosis)• MorefrequentlyseeninairsamplesthanAspergillus

• Predisposingfactors:Especiallyinpatientswithhematologicmalignancies,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: LookssimilartoAspergillus• Fluffypink,violet,yellow,greencolony• Septatehyphaewithphialideswhichproduceoval-shapedmicroconidiaandbanana

shaped macroconidia. Chlamydoconidia present (Figure 7-22)• Mortalityofpatientswithprofound,prolongedneutropenia~100%• Treatment: AmphotericinB+5FC,liposomalAmphotericinB,granulocyteinfusionmaybegivenwiththerapy,itraconazoleonly~50%effective,fluconazolealsoshowssomeresistance, voriconazole

Penicillium• Ubiquitousinnature,frequentlaboratorycontaminant• Cutaneous,externalear,mycotickeratitis,bronchopulmonary,dissemination• Blue-greencolonywithwhiteborder• Septatehyphaewithbrush-likeconidiophoresandphialideswithchainsofroundconidia

Scopulariopis• Whitesuperficialonychomycosis• Powdery,browncolony• Septatehyphaewithbrushlikephialidesproducingchainsofround,thick-walledrough

conidia

Paecilomyces• Immunocompromisedpatients• Erythematousmacules,vesicles,pustules,nodules


• Pinkish,oryellowish-browncolony• Septatehyphaewithtaperedphialidesandelliptical-shapedconidiainchains

Figure 7-23. Phaeohyphomycosis Fontana-Masson Stain (biopsy)

Phaeohyphomycosis• Representsabroadspectrumofdematiaceous(blackorpigmented)fungalinfectionsrangingfromsuperficialtodeeporganinvolvement.Organismsappearintissueasdarkyeast-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-MassonstainrevealsthepigmentthatmaybemissedwithH&E• Scleroticbodiesand/orgranulesareNOTseen• Needcultureforidentificationoforganism

Figure 7-24. Alternaria

Alternaria • Dark,septatehyphaewithlarge,brownconidiainchains.Lookslikeahandgrenade

Curvularia• Dark,septatehyphaewithlargeconidiacontainingusually4cellsappearcurveddueto

swelling of the central cell

Other Organisms• Exophiala, Bipolaris, Wangiella


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• Encapsulatedyeast,polysaccharidecapsuleenhancespathogenicity• Ubiquitous,abundantinsoilenrichedwithagedpigeondroppingsandroostingareas,

moldy fruit, found in small numbers normal skin, vagina, GI tract• Bothvarietiesbecomeairborne• Normal host: Disease asymptomatic or mild pulmonary

infection• Primarycutaneouscryp.shouldberegardedasasentinelof

disseminated disease• PrevalenceinAIDS3-6%• Biopsy: Encapsulatedround,darkwalledyeastcell2-12µm.

May see single or multiple budding within a single capsule• Gelatinous pattern: Numerous organisms, minimal

inflammation• Granulomatous pattern: Fewer organisms, granulomas• The organism stains with PAS, GMS, and Fontana-Masson• Themucopolysaccharidecapsulestainswithmethyleneblue,alcianblue,andmucicarmine• India Ink:Goodscreeningmethod;highlightscapsuleoforganism,usefor“touchprep”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, posaconazole

Candidiasis• Candida albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, C. dubliniensis, C. kefyr• Mostcommonfungalopportunisticinfection,maybedifficulttoevaluate;yeastareubiquitousandpartofendogenousflora

• 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

uTIPa HIV, immunocompromised patients:

dissemination to CNS, bone, skin.

Cutaneous findings occur 10-15%;

disseminated disease may occur

without pulmonary or CNS symptoms.

Lesions most often found head, neck,

mouth, nose and are polymorphous:

nodules, papules, ulcers, herpetiform,

cellulitis, molluscum-like, acneiform


• Clinical manifestations include: Thrush, perleche, vulvovaginitis, balanitis, paronychia, onychomycosis, intertrigo, folliculitis, congenital and neonatal candidiasis, systemic dissemination to any organ

• Cutaneous lesions: Papulonectrotic eschars, purpura• Biopsy: Budding yeast, pseudohyphae, some species

produce true hyphae• 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• Mostcommonspecies50%-60%ofcandidainfections• Trueandpseudohyphae

C. glabrata• 15%-20%ofcandidainfections• Fluconazoleresistance

C. parapsilosis• Chronicparonychiaand systemic infections

C. tropicalis • 6-12%• Frequentlycausesdisseminationtoskin.Major cause of septicemia and disseminated

candidiasis especially in patients with leukemia, lymphoma, and diabetes

C. dubliniensis• ImplicatedinoropharyngealCandidiasisinHIVinfectedpatientsandmostfrequently

implicated in cases of recurrent infection following antifungal drug treatment

7.7 MISCELLANEOUS ORGANISMS CAUSING FUNGUS-LIKE INFECTIONSRhinosporidiosis

• Rhinosporidium seeberi, anaquaticprotozoanpreviouslyconsideredafungus• MainlyinIndia,SouthAmerica,Africa,rarelyseeninU.S.• Largepolyps,granulomatous,wart-likelesionsmostfrequentlyinnasalmucosa,eye,mouth

• Biopsy: Spherulesorsporangium~250-350µm, endospores appear rough like raspberries• Stainsredwithmucicarmine• Theorganismisnotculturable• Differential diagnosis: Cryptococcus, mucormycosis, paracoccidioidomycosis, Alternaria,

Aspergillus• Treatment: Surgical removal, dapsone, local amphotericin B injection

uTIPa Factors contributing to candida infection:

impaired epithelial cellbarrier, systemic ill-

ness, neutrophil and macrophage

disorders, immune disorders, therapeutic

agents, congenital or acquired endo-

crine disorders, malignancies, indwelling

catheters, hyperalimentation, heat,

humidity and friction


Figure 7-26. Protothecosis (biopsy)

Protothecosis• Prototheca wickerhamii• Rarecutaneous,subcutaneous,systemicinfectionscausebyachloricalgae• Worldwide habitat: Stagnant water• Skinlesionsgenerallyseeninimmunosuppressedpatientsaftertrauma:papules,plaques,

vesicles, cellulitis, eczematoid dermatitis, verrucous nodules• Causesolecrenonbursitis1/3cases

• 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• Roundsporangiacontainingendospores,nobudding,andnohyphae• Treatment: Surgicalexcision,AmphotericinB+/-tetracycline,ketoconazole

7.8 RANDOM FACTS AND SUMMARY TABLEUmbilicated 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


Table7-6.SummaryofOrganismSizeandAppearanceinTissueCondition Diameter of Organism (µm) Features

Lymphocyte 8-10 Point of Reference

Actinomycotic mycetoma 150-290 Granule containing thin filaments

Eumycoticmycetoma 500-2000 Granule containing hyphae and chlamydoconidia

Aspergillosis 2-4 Septate hyphae

Mucormycosis 10-25 BroadInfrequentlyseptateirregular 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 Ovaltoroundyeastwithcrosswalls

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

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NOTES

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