Lecture 7: Cutaneous & Subcutaneous Fungal Infections

Tinea/Pityriasis Versicolor

Malassezia

Lipid-dependent, dimorphic fungus, of normal skin microbiota

Yeast and pseudohyphae – “spaghetti-meatballs” appearance

Superficial fungal infection

Not contagious

Transforms from yeast cells to pathogenic mycelial form

Macules, patches, and thin plaques can be hypo-, hyperpigmented or erythematous

Fine scale often present

Lesions small but frequently coalesce

Adolescents & adults – upper trunk and proximal upper extremities

Children likely to involve face

UV: fluoresce yellow to yellow-green

Dermatophytosis

Cutaneous mycosis

Filamentous fungi capable of superficial infection

Metabolize & subsist on keratin – skin, hair, & nails

Keratinase - invasion of cytokeratin-containing tissues

Mannan glycoproteins in cell wall = adhesin; inhibit action of macrophages

Produces microconidia and macroconidia on Sabouraud dextrose agar (SDA)

MAIN Infective form/stage – arthrospores – fragmented hyphae

Disseminate from one host to another

Person to person + fomite transmission

Can survive in the environment (fomite)

Arthrospores adhere by fibrils to keratinocytes and germinate

Lactophenol Cotton Blue (LCB) stain

Tinea Corporis

Trichophyton rubrum

Infection of trunk, neck, arms, and legs OR body surfaces other than the feet, groin, face, scalp, or beard hair

Direct skin contact with infected individual, animal, fomites or secondary spread from other dermatophyte infection sites

Begins as pruritic, circular or oval, erythematous or hyperpigmented, scaling patch or plaque

Spreads centrifugally

Center clearing follows, with an active, advancing, raised border remains

Ring-shaped plaque → ringworm

Multiple plaques may coalesce

Pustules occasionally appear

Extensive tinea corporis → underlying immune disorder (e.g. diabetes; HIV)

Tinea Pedis

Athlete’s Foot

Infection of the skin on the foot

Trichophyton rubrum, Trichophyton interdigitale (mentagrophytes), & Epidermophyton floccosum

Direct skin contact with causative microbe, by walking barefoot in locker rooms or swimming pool facilities

Usually occurs – adolescents and adults; rare prior to puberty

Most often medial foot; possible underlying erythema

Can occur in association with onychomycosis, tinea cruris, or tinea manuum – same fungus

Interdigital tinea pedis

Pruritic erosion or scales b/n toes (esp. 3rd or 4th digital spaces)

Associated fissure may cause pain

Possible source for bacterial infection → cellulitis

Hyperkeratotic tinea pedis

Diffuse, hyperkeratotic eruption of souls and medial/lateral surfaces of feet

Variable underlying erythema

Vesiculobullous (inflammatory) tinea pedis

Pruritic, sometimes painful, vesicular/bullous eruption

Tinea Cruris

Jock Itch- Dermatophyte infection crural fold

Trichophyton rubrum, Trichophyton interdigitale (mentagrophytes), & Epidermophyton floccosum

Often spread from concomitant tinea pedis

More common in males than females

Begins w/ erythematous or hyperpigmented patch, proximal medial thigh

Infections spreads centrifugally, w/ partial central clearing & slightly elevated, erythematous or hyperpigmented, sharply demarcated border

Infection may spread to perineum & perianal areas, into gluteal cleft, or onto buttocks

Males - scrotum not or slightly affected

Tinea Capitis

Infection of of the scalp and hair

Pruritic, scaling areas of hair loss

Trichophyton and Microsporum

Trichophyton tonsurans – primary in US

Direct contact of scalp w/ dermatophyte from another infected (carrier) human or animal or fomite

Children, prepubertal – most likely

Adults: Colonization by commensal yeast – Malassezia (Pityrosporum)

Progresses from stratum corneum down into follicle then hair

Endothrix

arthroconidia found w/in hair shaft

Trichophyton tonsurans

Patches of alopecia w/ black dots

black dots due to distal ends of hairs broken at surface

alopecia areas

Ectothrix

arthroconidia primarily surround outside hair shaft

Microsporum canis

Scaly patches with alopecia

Patches few to several cm

enlarge centrifugally wks to months

erythema may be present

Kerion

large, pyogenic abscess w/ thick pus oozing from hair follicles & edema

intense immune response

inflammatory plaque w/ pustules, thick crusting, &/or drainage

tenderness & pain

accompanied by secondary bacterial infection

Favus

hyphae and airspaces are found w/in hair shaft

no arthroconidia

T. schoenleinii

formation of scutula – cup-shaped yellow crusts composed of neutrophils, fungi, dried serum, and epidermal cells

unpleasant odor

possible permanent scarring

Tinea unguium/Onychomycosis

chronic fungal infection of toenails or fingernails

Trichophyton rubrum, T. interdigitale, Epidermophyton floccosum, Microsporum

Toenails - DERMATOPHYTE most common

Fingernails YEAST (Candida) most common

More common adults

Direct contact or spread from affected skin

Nail as site of relative immune privilege; lacks effective CMI

Persistence possibly due to biofilm formation → evade host defenses & antifungal therapy

Nail abnormalities – discoloration, subungual hyperkeratosis, onycholysis (painless separation of nail from nail bed); splitting; nail plate destruction

PAS stain

Distal Lateral Subungual Onychomycosis

Nail discoloration & subungual hyperkeratosis

Proximal Subungual Onychomycosis

Whitish discoloration originating under the surface of the proximal nail plate

Total Dystrophic Onychomycosis

Total destruction of nail w/ ridged hyperkeratotic nail bed

Dermatophytosis Diagnosis

Detection of segmented hyphae

PCR

MALDI-TOF – protein profile – requires pure culture

Dermatophytosis Treatment

Topical - most dermatophytosis limited epidermis

Azoles, allylamines (butenafine), ciclopirox, and tolnaftate

Extensive infections:

Oral -Terbinafine, Itraconazole, Griseofulvin

Hepatotoxicity

Azoles

inhibition ergosterol synthesis

Allylamines

inhibits ergosterol synthesis

Hydroxypyridones - Ciclopirox

chelates polyvalent metal ions

inhibition of enzymes

disrupts DNA repair, cell division signals & structures

Echinocandins

inhibit β-glucan synthesis

Pyrimidine - Flucytosine

inhibits nucleic acid synthesis

Griseofulvin

binds to keratin

Polyenes

aggregate with ergosterol

Selenium sulfide/disulfide

reduction in turnover of epidermal cells

Tolnaftate

inhibits squalene epoxidase, an enzyme in production of ergosterol

Butenafine

inhibits ergosterol synthesis

Dermatophytid Reactions

Dermatophytosis Complications

response to fungal antigens

Occur in patients w/ tinea pedis, manuum, corporis, cruris, or capitis

Autoeczematization reactions– secondary, dermatitic eruptions

Occur in association w/ primary, often inflammatory skin disorders

Pruritic, papulovesicular eruptions

Topical steroids & antipruritic agents

Sporotrichosis

Sporothrix schenkii

Thermal Dimorphic Fungus

Thin, septate, branching hyphae; roseate (bouquet-like) arrangement of conidia in Sabouraud dextrose agar at 25° C

Cigar-shaped budding yeast in human tissue & in vitro

Oval and round yeast as well

In vitro medium – Brain Heart Infusion at 37° C

Subacute to chronic infection

Usually cutaneous & subcutaneous tissue

contact with nature- plants and animals

Sporothrix schenkii Virulence Factors

Thermal dimorphism

Adhesins of cell wall:

GP70 – glycoprotein

PRM – peptidorhamnomannan - also immunogenic

Extracellular proteinases: Digestion of host cells for nutrients

Melanin:

Neutralization of ROS & NO

Resistance to antifungals

Biofilm: Resistance to antifungals

Sporotrichosis Clinical Manifestations

Trauma leading to cutaneous inoculations

Lymphocutaneous sporotrichosis – healthy individual w/ exposure to fungus

Fixed - Local pustule or ulcer

Lymphocutaneous - Nodules along draining lymphatics

Ascending lymphangitis

Disseminated disease - ONLY immunocompromised host

Sporotrichosis Diagnosis and Treatment

Culture – Gold Standard

Sabouraud dextrose agar @ Room Temp

Confirm with growth on Blood Agar at 37° C

MALDI-TOF identify to species level

Localized infection - Itraconazole

Systemic infection - Amphotericin B

Tinea/Pityriasis Versicolor

Sporothrix schenkii

Sporothrix schenkii