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Skin, Blood & Muscle: Fungal

Fungal And Mycobacterial Infections of Skin and Subcutaneous Tissues


Donald Jungkind, Ph.D. Professor, Pathology and Microbiology Director, Clinical Microbiology Lab.
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Diseases Caused by Fungi


Fungal infections (mycoses) are classified by the degree of tissue involvement and mode of entry into the host. These are:
Superficial Localized to the skin, the hair, and the nails.
Relatively common in normal population.

Subcutaneous Systemic Deep infections of the internal organs.


Relatively uncommon in normal population.

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Opportunistic Infection only in the immunocompromised.


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Superficial Mycoses
Development of fungal growth on epithelial tissues such as human hair, skin or nails.
No noticeable invasion of living tissue Dont provoke an immune response by the host.

White Piedra
Caused by several species of Trichosporon
Genus within arthroconidial (spore forming) yeasts. Trichosporon spp. are also known as agents of cutaneous and of systemic infections.
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When keratin is assimilated by dermatophytes, adjacent living tissue can also be affected.
If the fungi live on excreted compounds (lipids etc.), the fungi remain strictly superficial. This is the case with the members of the lipophilic genus Malassezia.
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Trichosporon beigelii - PAS Stain

Clinical Presentation of White Piedra


Asymptomatic growth on outside of hair shaft.
Soft nodules which can easily be pulled off the hair. White, greenish or yellowish.
Composed of compacted fungal elements.

Hairs are not invaded, but they may break if the fungi have been there for long periods. Affects hairs on scalp, p beard, eyelashes, y eyebrows, y axilla, and groin.
Warm, moist conditions predispose.

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White Piedra
The disorder can be controlled by shaving and local application of antifungal agents.
All clinically significant Trichosporon spp. show high in vitro susceptibility to commonly used antifungal agents: Amphotericin B, Clotrimazole, Ketoconazole Itraconazole.

Black Piedra
Black piedra is an asymptomatic but visible colonization of the shaft of scalp hair.
Disorder restricted to humid tropical areas.

The nodules cannot be pulled off the hair shaft. Treatment of black piedra is difficult.
Topical application of azole antifungals has been used with variable degrees of success.

Caused by ascomycete genus Piedraia spp. spp

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Skin, Blood & Muscle: Fungal

Tinea nigra
(Dont Confuse with Black Piedra on Hair)
Superficial infection of SKIN: stratum corneum.
Brown to black lesions. Mainly on the palm, but sometimes on sole of the foot.
Pigmentation is more intense near the border.
Only outer, dead layers of the skin are affected No invasion of living tissue occurs.

Hortae werneckii (Exophiala werneckii)


Colonies are smooth with an oily, glistening, olive-black color.
Aged colonies become velvety as a result of production of aerial hyphae. Hyphae become darker with age.
Hortae werneckii is somewhat halophilic.
Occasionally isolated from beach soil.

Tinea nigra is caused by Hortae werneckii

Skin scraping with KOH stain.


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Colonies on Sab. Dextrose Agar

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Pityriasis Versicolor
Malassezia furfur infects outer layers of stratum corneum.
Usually superficial, chronic, and asymptomatic. Macular rash or fine scaling of the upper trunk and shoulders
Lesions appear lighter or darker than surrounding skin.

Pityriasis versicolor
Laboratory diagnosis is confirmed by microscopy.
Microscopy of skin scrapings. Characteristic morphology of both filaments and yeasts. M. furfur which can be abundant in the scales.
Visual image is of spaghetti and meatballs.

Treatment
Topical antifungals generally clear this superficial infection. Condition C diti frequently f tl recurs.

Lab Dx: Skin scraping with KOH = spaghetti and


Complication: Erythematous follicular DJ papules

meatballs.
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Other Infections with Malassezia spp.


Cause opportunistic systemic infections.
In patients receiving lipid nutrients through central venous catheters. Colonization of the catheter occurs.
Wide spectrum in severity.

Malassezia pachydermatis

Deep-line catheter-associated sepsis in neonates. Involving M. furfur or M. pachydermatis.


In one outbreak of M. pachydermatis, Nurse had multiple dogs, a known carrier.

MAY cause seborrheic dermatitis and dandruff


Old literature name: Pityrosporum ovale

Lab diagnosis.
Isolation of the yeast using lipid-containing media. Can also see yeast in tissues.
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Cutaneous Mycoses: Dermatophytes


Fungi using keratin as nutrient source.
They invade skin, hair and nails. Typical skin lesion Annular (ring), scaly patch with a raised margin. Commonly called ring worm and jock itch. Infection of hair Causes hair loss leaving a dry scaly patch of skin. Nails infections Nails become yellow, thickened, and crack.

Dermatophyte Transmission to Man


Predisposing conditions to chronic infections.
Normal persons with minor immunological blind spots Old age Collagen vascular disease Diabetes mellitus Hematological malignancy

3 sources of infection
Anthropophilic (humans) (humans), Zoophilic (animals), Geophilic (soil).

Transmission
Contact with infected skin scales from humans or animals. Scales can be carried to the next host by way of Dirty moist shower mats Shared nail and hair clippers Shared combs Used shoes
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There can be varying degrees of inflammation of surrounding tissues, but there is no invasion of the fungus itself into the underlying tissues.
Dermatophytes colonize the keratinized tissue of the stratum corneum.
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Microsporum spp.
Members of this genus generally attack skin and hair.
Dont attack nails.

Microsporum canis Top and Reverse

Microscopic exam of cultures:


Distinguishing features Macroconidia are more numerous that microconidia
Macroconidia have rough walls ranging from spiny to warty.
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Microsporum canis

Epidermophyton spp.
Attacks skin and nails
Does not invade hair.

E. floccosum is the only pathogenic species in this genus. E. floccosum spores


Macroconidia Smooth walled large.
Born singly or in banana-like clusters.

Microconidia are absent.


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Epidermophyton floccosum

Trichophyton spp.
Trichophyton spp. attack skin, hair and nails.
Noted for their life life long long nail infections. infections

Microconidia more numerous than macroconidia.


Macroconidia when present are smoothwalled pencil shaped fusiform.
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Trichophyton mentagrophytes Sabouraud agar

T. rubrum
Colony surface typically white, velvety to fluffy,
Colony reverse is wine red.

Urease negative. negative

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Skin, Blood & Muscle: Fungal

Trichophyton rubrum - Potato Dextrose agar. Note Red Color


Top Reverse

T. tonsurans
Major cause of ringworm in skin.

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Clinical Forms of Dermatophyte Infection Special Nomenclature Infections caused by dermatophytes are clinically classified on the basis of the location of the lesions on the body.
Although different body sites may be affected, each focus of infection is simply a local inoculation of a dermatophyte. Name ringworm based on the worm-like appearance of skin lesions with irregular, inflammatory borders.
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Dermatophyte Ringworm

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Tinea corporis
Ringworm of upper parts of covered body
Usually involves trunk, shoulders, axilla, chest and back. Areas with relatively less hair. Lesions are well marginated with raised erythematous, vesicular borders. Infection may be mild to severe. Most serious chronic infection often due to T. rubrum.

Tinea cruris - Jock Itch'


Infection of inguinal area involving groin, perianal, and perineal areas.
Frequently caused in adults by T. rubrum or E. floccosum. Lesions are erythematous, scaly, raised inflamed borders, often with vesicles. Usually bilateral extending down the sides of inner thighs, waist area and buttocks.
Symptoms: Itching and burning.

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Tinea capitis
Infection of scalp, eye brows, eye lashes.
Ectothrix invasion when fungus forms sheath of hyphae and arthroconidia around shafts of hair. Infected hair is lusterless, brittle Infected hair breaks off at scalp. Endothrix invasion when hyphae invade hair follicle and shaft and form many spores within the hair shaft. Infected grayish grayish-white white hairs break off easily at the scalp giving 'black dot' appearance Secondary bacterial infections can result in scarring and other complications.

Tinea capitis

Black Dot

Common agents of tinea capitis:


Ectothrix ringworm of the scalp M. audouinii , M. canis, and M. gypseum. Endothrix ringworm of the scalp in the USA is T. tonsurans.
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Ectothrix and Endothrix Invasions: Dermatophyte Invades Hair Follicle and Shaft
Hair perforation Endothrix Ectothrix Follicular

Tinea pedis - Athlete's Foot'


Ringworm of the feet involves chronic infection of the interdigital webs and soles.
Symptoms: scaling, fissuring, erythema, itching and burning. Less common clinical form is infection of the soles and heels extending up the sides of the foot (moccasin foot )

Acute condition is characterized by vesicles, inflammation, and pustules. Common agents of tinea pedis, which cause infections, are
T. mentagrophytes, T. rubrum, E. floccosum.

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Dermatophyte Infection May Show Vesicles and Sterile Pustules

Tinea barbae
Infection of beard area.
Mild to severe forms occur. More severe form with pustular lesions. Often caused by zoophilic d dermatophytes t h t
T. verrucosum
Cattle

T. mentagrophytes
Mice, Rodents

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Tinea unguium
Invasion of the nail plate by a dermatophyte.
Nail invasion involves the nail bed and skin on the underside of the nail. Causes lifting g of the nail plate p and its detachment from the nail bed.

Tinea unguium

Causes of tinea unguium


Trichophyton rubrum, T. mentagrophytes E. floccosum
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Treatment of Dermatophyte Infections


Decisions regarding the best regimen for therapy must consider
Extent, location and clinical type of infection. Etiological agent Spectrum of activity of the antifungal.

Dermatophyte Infections of the Nails


Most difficult to cure dermatophyte infection.
Agents applied directly to the nail has been disappointing. Unable to penetrate nail plate to nail bed where fungus resides. Nail removal plays a limited role in therapy.

Newer antifungal agents available to treat the dermatophytoses include


Orally active triazoles Allylamines (terbinafine). Orally administered griseofulvin and ketoconazole Topical antifungals thiocarbonates (tolnaftate), and numerous imidazoles.
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Best new treatment is oral systemic antifungal antifungal.


Effective when administered for long periods of time. 3 months or more. Time reach nail bed and incorporate into nail matrix. Partial nail removal and topical therapy may augment systemic therapy.

New antifungals have made systemic therapy possible.


Response rates of up to 90% for fingernails and 70-80% for toenails reported for itraconazole and terbinafine.
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Candidiasis of Skin
Skin infection with Candida usually occurs in moist areas.
Between toes Between folds of skin in obese patients. Diaper rash in infants.

Candida Diaper Rash vs. Generalized Infection

Lesions appear as erythematous papules or as confluent areas of tenderness and redness of skin.
Diagnosis is by stains or skin scrapings or by culture, showing the Candida spp..

Prevention and treatment


Treatment is with topical Nystatin or Clotrimazole Measures to decrease moisture and chronic trauma are useful. Disposable diapers have greatly reduced this problem in babies One family in an area without disposable diapers let their toddler go to the beach and play in the surf and sand without diapers.
Combination of salt water, sunshine, and dry uncovered skin quickly quieted the infection. Double washing and double rinsing cloth diapers, plus the use of fabric softeners will prevent skin irritation and can equal the performance of disposable diapers .
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Candida Skin and Nail Infections

Candida Genital Infection

Groin
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Vaginal
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Hyalohyphomycosis
Pseudo hyphae

Term for non- black mold fungal infections. (Provided there is not already an established older historical name.)
Hyalohyphomycosis was not proposed to serve as a replacement for such wellestablished disease names as aspergillosis. Its intent was to provide the medical community with a name for a group of fungal infections caused by non-melanized septate, filamentous, etiological agents.
Hyalohyphomycosis can cause infection in all parts of the body.

Yeast

Candida albicans Gram Stain 45

Candida albicans Germ tube positive


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Fusarium is one that can infect systemically and show up in blood cultures. It also infects the eye.
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Fungal Eye Infection


Scratches, contact lenses predispose. Caused by various fungi.
Fusarium commonly infects due to its pointed curved shape.

External Otitis
Tissues lining the outer ear have high humidity with surface of waxy secretions.
Several common molds invade this region. They often occur together with mixed populations of bacteria and yeasts, so that establishing their role in otitis can be difficult. The most common molds include various species of Aspergillus. In addition some cases are caused by other molds such as Fusarium spp.

Inflammatory response develops to the infection.


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Subcutaneous Mycoses (Mycetomas)


Chronic subcutaneous infections
Caused by fungi or certain bacteria (actinomycetes) Traumatically implanted into deep tissue from environment.
Puncture wound to the foot.

Phaeohyphomycosis
Term for black mold fungal infections not covered by older historical names
Black molds have melanin containing filamentous hyphae. Colors range from brown to black hyphae

Pathogenesis of subcutaneous infection


A chronic disease which causes deformity and disability. Does not often spread systemically. Infection is seldom fatal. Microbes form large aggregates known as grains. Abscess may discharge to surface through draining sinuses. Abscess may extend to bone, causing chronic osteomyelitis.

Example of preserved historical names:


Pityriasis (tinea) nigra. Chromomycosis

Physician must know whether the mycetoma is caused by bacteria or a fungus.


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Phaeohyphomycosis Alternaria sp. Cutaneous-subcutaneous Lesion

Chromoblastomycosis (Chromomycosis)
Also called "Verrucous dermatitis". Etiologic agents
Genera Phialophora, and Cladosporium. Black pigmented soil fungi.

After traumatic inoculation of the skin, these fungi cause wart-like nodules.
Hard, dry, raised 1-3 mm above skin surface with crusty abscesses. Infection usually remains localized. Spread via bloodstream to other organs is rare. No spread by the lymphatics.

Disease causes a slow, painless infection


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Chromoblastomycosis Painless Lesions

Cladosporium carrionii
Dark Colony and Shield Shaped Conidia

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Sporotrichosis
Infection caused by Sporothrix schenckii.
Fungus of soil, plants, wood and moss. Infection is by splinters, thorns, and cuts of the skin. Typical case history is person who worked in a rose garden and reported numerous pricks to the hands.
More than a week later, , they y noticed a painful p nodular swelling below the skin. Red nodules continued to form, going up the arm in a line following the lymphatics. They seek medical advice, and a culture grows the dimorphic fungus S. schenckii.

Sporotrichosis

Treated with oral potassium iodide (in milk).


Newer medications are oral itraconazole for systemic infections.
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Sporothrix schenckii has a flower like sporulation.


Young colony Old colony Spores

Eumycetoma Madura Foot


Unusual infection associated with trauma to the feet, lower extremities and hands.
Inoculation of etiologic agent causes local swelling with suppuration and abscess formation. Eventually there is formation of granulomas and draining sinuses.

Most common fungal agent in the USA


Pseudoallescheria boydii (Petriellidium boydii).

Treatment
Surgical debridement Long term chemotherapeutic agents Nystatin (topical) or miconazole (systemic).

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Madura Foot (Mycetoma)

Madura Foot
H&E Low and High Power of Granules

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Microscopic Examination of Superficial Fungal Infection


Skin
Scales are taken from the active, advancing border of the lesion

Microscopic Exam of Fungi in Tissue Sections


H & E stain is only a fair stain for fungi. Specific stains are used if H & E is suspicious.
Periodic acid-Schiff (PAS) stain. g The PAS stain is based on the reaction of fungal cell wall polysaccharides with the PAS reagents, PAS gives the fungus a red-violet fuchsin color in the tissue. Silver stain. Stains fungal cell wall black with a blue-green counterstain for non-fungal tissue.

Hair
Collect misshapen stubs of broken hairs from scalp Place on microscope slide. Add 20% potassium hydroxide. Microscopic exam at 100X and 400X Dermatophyte infections
Primarily hyphae are seen.

Tinea versicolor and candidal infections


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Culture for fungi requires special agars with a separate test request for fungal culture.
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Budding yeast and hyphae are seen.

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Wood's Light Examination


Involves viewing the skin in a dark room under ultraviolet light.
Tinea versicolor Fluoresces subtle gold colors. Tinea capitis Caused by Microsporum canis and Microsporum audouinii
Fluoresce a light bright green.

Other Infections: Mycobacterial Infections of the Skin


(Leprosy will be covered in a separate lecture). Mycobacterium marinum
Acid fast photochromogen Colonies on lab media produce yellow pigment when exposed to light. M. marinum requires 28-30 degrees C for optimal growth. The organism does not grow at 37 degrees C.
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Most tinea capitis infections are Trichophyton species,


No fluorescence.

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Mycobacterium marinum Disease


Causes cutaneous infection after traumatic inoculation.
Typical cases report cuts and abrasions of the skin (usually the hands) while working in or around sea water or aquarium water. Clinical suspicion is important to get lab confirmation. Inform the lab to incubate cultures at lower temperatures to check for M. marinum if you see the following: Chronic non-healing lesion on the hands, arms, or feet of a person who works or plays around the sea, boats, aquariums, ponds, marshes, etc. Lesions that did not respond to normal outpatient antibiotics.

Mycobacterium ulcerans
Popularly known as Buruli ulcer Story of this organism is identical to that for M. marinum EXCEPT:
This is a Scotochromogen. In other words, it is non-pigmented. Like M. marinum, it likes 2830C for optimal growth.
AFB Stain Positive

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Mycobacterium ulcerans Buruli ulcer

Mycobacterium chelonae
M. chelonae complex is an acid fast bacillus in the genus Mycobacterium
Causes soft tissue abscesses and chronic cutaneous lesions. Often occurs after traumatic inoculation into the skin.

It can be difficult to treat. Treatment consists of surgical excision plus cefoxitin p culture for mycobacteria. y and amikacin. Special
Early lesion AFB Stain Positive Older lesion

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