Subcutaneous & Systemic Mycoses

TRANSCRIBED GEN CAMATO
SUBCUTANEOUS & SYSTEMIC MYCOSES

M YCOLOGY AND VIROLOGY | LECTURE
Subcutaneous Mycoses
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Involve the deeper layers of the skin, including the cornea,

muscle, and connective tissue
Caused by saprophytic fungi that lives on soil or on
vegetation
Occurs by direct implantation of spores or mycelia fragments
into a puncture wound in the skin
The host immune system recognizes the fungi, resulting in
variable tissue destruction and frequently epitheliomatous
hyperplasia
Tend to remain localized and rarely disseminate systemically
Types of Subcutaneous Mycoses:
c
Sporotrichosis
c
Chromomycosis
c
Mycetoma
c
Rhinosporidiosis
c
Lobomycosis
c
Entomophthoromycosis
SPOROTICHOSIS
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Rose gardeners disease

Thorns of roses would inoculate the spores
Classic infection is associated with traumatic inoculation of
soil or vegetable or organic matter contaminated with the
fungus
Chronic mycotic infection of the cutaneous or subcutaneous
tissues and adjacent lymphatics characterized by nodular
lesions which may suppurate and ulcerate
Occasionally involve the CNS, lungs (Pulmonary
sporothricosis) or genitourinary tract
ETIOLOGIC AGENT:
Sporothrix schenkii
Thrives on vegetation
Dimorphic fungi
Ambient temp= MOLD
In vitro or tissue @ 35C - 37C= small

budding YEAST
Grows in soil and decaying vegetation

PATHOGENESIS & CLINICAL FINDINGS:
Trauma to the skin introduces the conidia or hyphal

fragments
Initial lesion usually on the lower extremities
Can also be anywhere
In children, often with facial lesions

Fixed Sporotrichosis
Single nonlymphangitic nodule
Limited and less progressive
Endemic areas where there is high immunity

level
Lymphocutaneous sporotrichosis
Initial lesion develops as a granulomatous nodule

that may progress to form a necrotic or ulcerative
lesion
Multiple subcutaneous nodules and abscesses
Occur along the lymphatics.
LABORATORY DIAGNOSIS
Specimens
Specimens include biopsy material or

exudate from granulous or ulcerative
lesions.
Microscopic Examination
Sensitivity can be enhanced by

Gomori's and periodic acid-Schiff stain
Mold flowerette or daisy-like conidia
Yeast cigar-shaped yeast cell
Asteroid body
Often seen in tissue
Consists of a central basophilic

yeast cell surrounded by
radiating extensions of
eosinophilic material, which are
depositions of antigen- antibody
complexes and complement
Culture
Most reliable method of diagnosis
Specimens are streaked on inhibitory

mold agar or Sabouraud's agar
containing antibacterial antibiotics and
incubated at 25-30 C
The identification is confirmed by growth

at 35C and conversion to the yeast
form.
Microscopic morphology of the saprophytic or mycelial form of

Sporothrix schenckii when grown on Sabouraud's dextrose agar at
25oC. Note the daisy-like microconidia
Microscopic morphology of the parasitic or yeast form of Sporothrix schenckii when

grown on brain heart infusion agar containing blood and incubated at 370C. Note
budding yeast cells.
439
Sporothrix schenckii on Sabouraud's dextrose agar grown at 25oC colonies are moist
and glabrous, with a wrinkled and folded surface. Pigmentation may vary from white
to cream to black
Lymphocutaneous sporotrichosis
showing more advanced, ulcerating
lesions developing along the lymph
system of the forearm.
Fixed cutaneous verrucous-type

sporotrichosis of the wrist and hand
TREATMENT
Ocassionally self-limiting
Oral administration of saturate solution of

Potassium Iodide in milk
Oral itraconazole or other azoles

CHROMOMYCOSIS/CHROMOBLASTOMYCOSIS
Mycotic infection characterized by the development in tissue

of dematiaceous (brown-pigmented), planate-dividing,
rounded sclerotic bodies (also called Muriform or Medlar
bodies)
Occurs mainly in tropics, usually observed on legs of
barefooted agrarian workers
Skin scrapings from a patient with chromoblastomycosis mounted in

10% KOH and Parker ink solution showing characteristic brown
pigmented, planate-dividing, rounded sclerotic bodies
ETIOLOGIC AGENTS
Phialophora verrucosa
Fonsecaea pedrosoi
Rhiniocladiella aquaspersa
Fonsecaea compacta
Cladosporium carrionii
All dematiaceous
Grow on woody plants and in the soil

PATHOGENESIS & CLINICAL FINDINGS
Agents often gain entry into the human body by

contact with wood splinters or thorns.
Early lesions are small, warty papules and
Usually enlarge only slowly.
Over years lesions become crusted, verrucose,

wart-like with extension along the draining
lymphatics
Cauliflower-like nodules with crusting abscesses

eventually cover the area
Phialophora type
Cladosporium carrionii
Cladosporium
Rhinocladiella aquaspersa
Acrotheca type
Fonsecaea pedrosoi
acrotheca type
Fonsecaea compacta
May exhibit all 3 types of sporulation
Smaller conidia and more compact than

F. pedrosoi
Phialophora type
Flask-shaped or elliptical phialides with flaring

collarettes
Phialospores on top of the phialide
Phialophora)type)
flask-shaped or elliptical
phialides with flaring
phialide
collarettes
phialospores on top of the
phialide
phialospores
Cladosporium type
Cladosporium,carrionii
Cladosporium
type,
Chronic verrucose chromoblastomycosis of the foot due to Phialophora verrucosa.

Note tissue hyperplasia characterized by the formation of verrucoid, warty cutaneous
nodules raised 1 to 3 cm above the skin surface
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clinical presentation histopathologic findings of

chestnut-brown, sclerotic bodies
CULTURE
Slow growing
Suede like
Olive black in color

MICROSCOPIC MORPHOLOGY
Microscopic Morphology
Species can be differentiated by studying the

types of sporulation:
Cladosporium conidia in branching chain

formation
Phialophora - production of vase or flask-shaped

conidiophore
Acrotheca conidia surrounding the swollen,

knotted, club-shaped terminal ends of hyphae
Acrotheca type
Rhinocladiella aquaspersa
Fonseceae pedrosoi
Fonseceae compacta
May exhibit all 3 types of conidiation
TREATMENT
itraconazole and terbinafine
Because of the risk of recurrences developing

within the scar, surgery is not indicated
labmed.ucsf.edu

MYCETOMA
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Human & animal infection characterized by:
Draining sinuses
Granules vary in
-Size
-Color
-Hardness
ETIOLOGIC AGENTS:
r Eumycotic mycetoma
Mycetoma)
Curvularia
Mycetomaa)
subcutaneous
etiologic agents
EUMYCOTIC MYCETOMA
www.mold.ph
Curvularia
Human & animal

infection
characterized by:
www.dehs.umn.edu
draining sinuses
granules vary in
! Size
! color
! hardness
www2.truman.edu
Mycetoma)
Leptosphaeria
subcutaneous
Etiologic agents
caused by traumatic implantation of spores

involves cutaneous & subcutaneous tissues, fascia &
bone of foot or hand
ETIOLOGIC AGENTS:
Actinomycotic mycetoma (caused by bacteria):
Nocardia
Actinomadura
Streptomyces
Eumycotic mycetoma (caused by fungi):
Madurella
Acremonium
Pseudallescheria
Exophiala
Leptosphaeria
Curvularia
Fusarium
Aspergillus
PATHOGENESIS & CLINICAL FINDINGS
The earliest lesion is a small, painless,

subcutaneous nodule or plaque that increases
slowly but progressively in size
As the mycetoma develops,the affected area

gradually enlarges and becomes disfigured as a
result of chronic inflammation and fibrosis.
With time, sinus tracts appear on the skin surface

and drain serosanguineous fluid that often
contains grossly visible granules.
The infection commonly breaches tissue planes

and destroys muscle and bone locally
Key to the diagnosis of eumycotic mycetoma is the

demonstration of grains or granules
Grains can be visualized microscopically by

mounting in 20% KOH.
Grains are easily visualized in tissue stained with

H&E
Culture is usually necessary for definitive

identification of the organism.
EUMYCOTIC MYCETOMA
Leptosphaeria
www.biologie.uni-halle.de
Mycetoma)
Pseudallescheria
subcutaneous
EUMYCOTIC MYCETOMA
Pseudallescheria
Etiologic agents
www.medicine.cmu.ac.th
Grains of Madurella mycetomatis (tissue microcolonies) are brown or black, 0.5 to 1.0
mm in size, round or lobed, hard and brittle, composed of hyphae which are 2 to 5 um in
diameter, with terminal cells expanded to 12 to 15 (30) um in diameter
Aspergillus
TREATMENT
Response to amphotericin B, ketoconazole, or

itraconazole is variable and often poor, although
such therapy may slow the course of infection
Promising treatment responses have recently

been reported for terbinafine, voriconazole, and
posaconazole
Local excision is usually ineffective or not

possible, and amputation is the only definitive
treatment

RHINOSPORIDIOSIS
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ENTOMOPHTHORMYCOSIS
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Is an infection of the mucocutaneous tissue caused by

Rhinosporidium seeberi
Causes a chronic granulomatous disease characterised by
the production of large polyps, tumours, papillomas, or wartlike lesions.
The nose is the most commonly affected site.
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Mature spherule with endospores typical of rhinosporidiosis.
Also known as Subcutaneous zygomycosis

Etiologic agents:
Conidiobolus coronatus (upper part of the body,

face)
Basidiobolus ranarum (lower, legs)

Entomophthoromycosis caused by Basidiobolus
Chronic inflammatory or granulomatous disease generally
restricted to the limbs, chest, back or buttocks
Primarily occurring in children with predominance in males.
Initially, lesions appear as subcutaneous nodules, which
develop into massive, firm, indurated, painless swellings,
which are freely movable over the underlying muscle but are
attached to the skin which is hyperpigmented but not
ulcerated.
Etiologic Agent:
Basidiobolus ranarum (= B. haptosporus)

commonly present in decaying fruit and vegetable
matter, and as a commensal in the intestinal tract
of frogs, toads and lizards.
LOBOMYCOSIS
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Chronic, localised, subepidermal infection

Keloidal, verrucoid, nodular lesions or vegetating crusty
plaques and tumours
Loboa loboi - masses of spheroidal, yeast-like organisms in
lesions
Cauliflower-like and hyper or hypopigmented
Etiologic agent known as "Loboa loboi"
PATHOGENESIS AND CLINICAL FINDINGS
The initial infection is thought to be caused by

traumatic implantation
The lesions begin as small, hard nodules

resembling keloids and may spread slowly in the
dermis and continue to develop over a period of
many years.
Older lesions become verrucoid and may ulcerate.
The disease may be transferred to other areas of

the skin by further trauma or autoinoculation.
90% of cases are men, mostly in farmers and

other high- risk groups exposed to various harsh
conditions as well as aquatic habitats
Haematoxylin and eosin (H&E) stained section of tissue from a lesion

on a child's arm showing broad septate hyphae surrounded by an
eosinophilic sheath (Splenodore-Hoeppli phenomenon) typical of
Entomophthoromycosis
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Lobomycosis
showing extensive
verrucoid lesions
on the legs
Grocotts methenamine silver (GMS) stained tissue section showing numerous darkly pigmented
yeast-like cells, often in chains, 9-12 um in size typical of Loboa loboi.
Microscopic morphology of Basidiobolus ranarum showing numerous round, smooth, thick-walled zygospores
Entomophthoromycosis caused by Conidiobolus

A chronic inflammatory or granulomatous disease that is
typically restricted to the nasal submucosa and
characterized by polyps or palpable restricted
subcutaneous masses.
Human infections occur mainly in adults with a
predominance in males (80% of cases).
Distribution: Worldwide, especially tropical rain forests of
Africa.
Aetiological Agent: Conidiobolus coronatus, commonly
present in soil and decaying leaves.
Laboratory Diagnosis
Both types of subcutaneous zygomycosis require

biopsy for diagnosis
Morphology: Short, poorly stained hyphal

fragments, surrounded by eosinophilic SplendoreHoeppli material
Treatment:
Both types of infection may be treated with

itraconazole.
Facial reconstructive surgery may be necessary
in the case of C. Coronatus infection
CONTROL
Wide surgical excision of the affected area
Clofazimine
Slow and chronic and the although not life

threatening the prognosis is poor.
Entomophthoromycosis caused by Conidiobolus coronatus in a patient seen at the Pasteur Institute in Paris in 1972 from the then French
Camaroons. Note the massive swelling and distortion of the subcutaneous tissue of the nasal and perioral regions, with a large
polypoid protrusion on the inner aspect of the lower lip.
Entomophthoromycosis caused
by Basidiobolus ranarum
showing a subcutaneous lesion
involving the entire thigh and
buttock of an Indonesian boy.
Entomophthoromycosis caused by Basidiobolus ranarum showing an ulcerated

subcutaneous lesions on the abdomen of a young boy from Darwin.
Microscopic morphology of Conidiobolus coronatus showing several mature, spherical sporangiola

(conidia) with hair-like appendages, called villae and prominent papillae, marking the site of former
attachment to the sporangiophore.

Systemic Mycoses
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Deep w/in the body

Caused by fungi that live in the soil
Typically begins in the lungs then spread to other body
tissue
Not contagious
Types of Systemic Mycoses:
Histoplasmosis
Coccidiodomycosis
Blastomycosis
Paracoccidiomycosis
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Tissue section stained with haematoxylin and eosin (H&E) from a biopsy of the mouth lesion
shown in slide 7. Note macrophages containing numerous yeast cells of Histoplasma capsulatum
Microscopic morphology of the parasitic or yeast form of Histoplasma capsulatum

cultured on brain heart infusion agar containing blood incubated at 37oC. Note the small
round to oval budding yeast-like cells.
HISTOPLASMOSIS
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Also known as Cave disease, Darling's disease, Ohio

valley disease, Spelunkers Lung and Caver's disease
Intracellular mycotic infection of the reticuloendothelial
system caused by the inhalation of the fungus
Approximately 95% of cases of histoplasmosis are
inapparent, subclinical or benign.
Five percent of the cases have chronic progressive lung
disease, chronic cutaneous or systemic disease or an acute
fulminating fatal systemic disease
All stages of this disease may mimic tuberculosis.
Distribution: World-wide, especially U.S.A. Sporadic cases
do occur in Australia.
Aetiological Agent: Histoplasma capsulatum, especially
from soil enriched with excreta from chicken, starlings
and bats.
Laboratory Diagnosis:
Specimen: Sputum, bronchoalveolar lavage (BAL)

, blood, bone marrow, tissue
Morphology in Culture
Room Temp (25C); Saprobic phase Mold with tuberculate macroconidia and
small, oval microconidia
Body Temp (37C); parasitic phase

Small budding yeast
Serology
Antibody: complement fixation,

Immunodiffusion
Antigen: serum and urine
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325
Culture of Histoplasma capsulatum on Sabouraud's dextrose agar showing a white suede-like

colony with a pale yellow-brown reverse.
333
332
exoantigen immunodiffusion test kit for the identification of Histoplasma

capsulatum
Exoantigen immunodiffusion plate showing positive identification of Histoplasma capsulatum.

Note H and M bands of identification; EX = culture filtrate; H = Histoplasma antibody and
antigen, C = Coccidioides antibody and antigen; B = Blastomyces antibody and antigen.
COCCIDIOMYCOSIS
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Histoplasmosis of the lower gum showing ulcer around base
of tooth.
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Microscopic morphology of the saprophytic or mycelial form of Histoplasma capsulatum

showing characteristic large, rounded, single-celled, tuberculate (with spike-like
projection) macroconidia formed on short, hyaline, undifferentiated conidiophores.
Culture of Histoplasma capsulatum on Sabouraud's dextrose agar showing a pale yellowbrown reverse.
Commonly known as San Joaquin Valley fever

Initially, a respiratory infection, resulting from the inhalation
of conidia, that typically resolves rapidly leaving the patient
with a strong specific immunity to re-infection
Sometimes the disease may progress to a chronic
pulmonary condition or as a systemic disease involving the
meninges, bones, joints and subcutaneous and cutaneous
tissues.
Distribution: endemic in south-western USA, Northern
Mexico and various centres in South America
Aetiological Agent: Coccidioides immitis, a soil inhabiting
fungus considered as the most virulent of all human mycotic
pathogens; major biohazard to laboratory personnel
Specimen: Sputum, bronchoalveolar lavage (BAL)

, tissue
Room Temp (25C); Saprobic phase Mold with barrel-shaped arthroconidia

Spherul containing endospores
Serology

Immunodiffusion, tube precipitin, latex
particle agglutination

BLASTOMYCOSIS
(continuation Coccidiomycosis)
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Coccidioidomycosis showing
chronic lesions of the face.
Active lesions are seen on the
cheek. An atrophic,
depigmented scar representing a
healed lesion is on the forehead.
Chronic cutaneous coccidioidomycosis

showing granulomatous lesions on
face, neck and chin
Also known as North American Blastomycosis,

Gilchrists disease and Chicago disease
Chronic granulomatous and suppurative disease having a
primary pulmonary stage that is frequently followed by
dissemination to other body sites, chiefly the skin and bone
Distribution: North America, some cases from Africa, Asia
and Europe.
Aetiological Agent: Blastomyxes dermatitidis, a soil
inhabiting fungus.
Laboratory Diagnosis
Specimen: Sputum,BAL, lung, tissue, skin biopsy
Room Temp (25C); Saprobic phase Mold, round to oval or pear-shaped

conidia; lolipop conidia

Broad- based,budding yeast
Serology

Immunodiffusion, enzyme immunoassay
Antigen: serum and urine
106
Extension of pulmonary coccidioidomycosis

showing a large superficial, ulcerated plaque.
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Giemsa stain of Blastomyces dermatitidis showing broad-based

budding yeast
Microscopic morphology of Coccidioides immitis showing typical single-celled, hyaline,
rectangular to barrel-shaped, alternate arthroconidia, separated from each other by a
disjunction cell.
Microscopic morphology of Coccidioides immitis showing typical single-celled,

hyaline, rectangular to barrel-shaped, alternate arthroconidia, separated from each
other by a disjunction cell
107
Direct microscopy of skin scrapings from a cutaneous lesion mounted in 10% KOH
and Parker ink solution showing characteristic endosporulating spherules
(sporangia) of Coccidioides immitis. The presence of spherules with endospores is
diagnostic.
109
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Periodic Acid-Schiff (PAS) stained tissue section of viscera from an experimentally

induced infection in a mouse showing typical endosporulating spherules of Coccidioides
immitis. Young spherules have a clear centre with peripheral cytoplasm and a prominent
thick wall. Endospores (sporangiospores) are later formed within the spherule by
repeated cytoplasmic cleavage. Rupture of the spherule releases endospores into the
surrounding tissue where they re-initiate the cycle of spherule development.
Ulcerated granuloma due to B.

dermatitidis.
Cutaneous blastomycosis of 20 years duration showing loss of skin.
110
Culture of Coccidioides immitis on Sabouraud's dextrose agar showing a suede-like

to downy, greyish white colony
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Cutaneous blastomycosis from

the same patient as in slide 31
showing loss of skin from the
arm and fingers.
Culture of Coccidioides immitis on Sabouraud's dextrose agar showing a tan to brown

reverse.
Blastomyces dermatitidis mold phase.

PARACOCCIDIOIDOMYCOSIS
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**Activities
Also known as South American Blastomycosis

Chronic granulomatous disease that characteristically
produces a primary pulmonary infection, often inapparent,
and then disseminates to form ulcerative granulomata of the
buccal, nasal and occasionally the gastrointestinal mucosa.
Distribution: geographically restricted to areas of South and
Central America
Aetiological agent: Paracoccidioides brasiliensis
Specimen: Sputum, bronchoalveolar lavage (BAL),

tissue
o
Room Temp (25 C); Saprobic phase Mold, round microconidia and
intercalary chlamydospores
o
Body Temp (37 C); parasitic phase multiple, budding yeast; steering
wheel, pilot wheel, mariners
wheel
Serology

Immunodiffusion
FUNGI
DISEASE
MOLD FORM
Blastomyces
dermatitidis
Gilchrists
disease
Lollipop
conidia
Histoplasma
capsulatum
Ohio valley
disease
Tuberculate
macroconidia
Coccidioides
immitis
San Joaquin
valley fever
Barrel shaped
arthroconidia
Paracoccidioides
brasiliensis
South
American
blastomycosis
Round
macroconidia
TISSUE
FORM
Broad base
budding
yeast
Small
budding
yeast
Spherule
with
endospores
Mariners
wheel
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Mucocutaneous paracoccidioidomycosis showing extensive destruction of

facial features.
385
Case%
Mucocutaneous paracoccidioidomycosis showing an ulcerated lesion on

the lips and loss of teeth
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Province%of%South%Africa%presented%with%an%
asymptomatic%growth%at%the%back%for%3%years.%It%
started%as%a%small%papule%which%grew%slowly.%He%
was%diagnosed%type%II%diabetesmellitus%a%year%
ago%and%he%is%on%meAorm%in%500mg%twice%daily%
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also%has%diabetes%mellitus.%He%is%employed%as%a%
security%guard.%
386
Mucocutaneous
paracoccidioidomycosis
showing an ulcerated lesion
on the pharyngeal mucosa.
Grocotts methenamine silver (GMS) stained lung tissue section

showing multiple, narrow base, budding yeast cells "steering wheels" of
P. brasiliensis.
387
REFERENCES: Bailey & Scott's Diagnostic Microbiology 12th Ed

Murray, P eat al. Medical Microbiology 6th Ed.
Before I formed you in the womb, I knew you,

before you were born I set you apart.
Microscopic morphology of Paracoccidioides brasiliensis showing

multiple, narrow base, budding yeast cells "steering wheels" of P.
brasiliensis
Jeremiah 1:5

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