Subcutaneous Mycoses

General Characteristics

▪ Subcutaneous mycoses are fungal diseases that affect subcutaneous tissue

▪ Involve the deeper skin layers, including muscle, connective tissue, and bone
▪ Characteristic clinical features include progressive, non-healing ulcers and the presence of
draining sinus tracts
▪ Usually the result of traumatic implantation of foreign objects into the deep layers of the
skin, permitting the fungus to gain entry into the host
▪ Etiologic agents are commonly found in soil or on decaying vegetation

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 Section 5-2
Agents of Subcutaneous Mycoses

Sporotrichosis

Synonyms
▪ Rose gardener’s disease, rose handler’s disease,
gardener’s disease, alcoholic rose gardener’s
disease
Definition
▪ Sporotrichosis is a chronic, subcutaneous mycosis
with eventual lymphatic involvement
▪ In some advanced, untreated cases, it may become
a generalized infection and involves bones, joints,
and other internal organs
Etiology
▪ Historically, the only known species responsible for sporotrichosis was Sporothrix schenckii
▪ However, molecular studies now demonstrate that
Sporothrix schenckii is a complex of at least six distinct species:

▪ S. schenckii
▪ S. albicans
▪ S. brasiliensis
▪ S. globosa
▪ S. luriei
▪ S. mexicana

▪ Sporothrix species are dimorphic fungi present worldwide, from soil, plants, and decaying
vegetation
▪ Mode of entry is usually traumatic implantation – often a scratch from a rose bush (or other
thorny plants), forcing it into the subcutaneous tissues
▪ Disease produced is usually a localized systemic infection
▪ Incidence of systemic infection is rare

Epidemiology
▪ In temperate countries such as France, Canada, and the US, most cases are associated with
gardening, particularly with exposure to rose thorns (rose handler’s disease) and sphagnum
moss
▪ Frequently encountered in gardeners, forest workers and manual laborer
▪ Only predisposing factor that was identified with any frequency was consumption of alcohol
▪ Stereotype of the patient at risk for sporotrichosis is the “alcoholic rose gardener.”
▪ Conidium is the infective stage of the fungus to man
▪ Through traumatic inoculation with contaminated material
▪ Thorn
▪ Splinter
▪ Brushing against a tree bark
▪ Inhalation of conidia (pulmonary sporotrichosis)

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Clinical Manifestations
1. Lymphocutaneous sporotrichosis
2. Fixed cutaneous sporotrichosis
3. Mucocutaneous sporotrichosis
4. Disseminated sporotrichosis
5. Pulmonary sporotrichosis

▪ Lymphocutaneous sporotrichosis
▪ Most commonly seen presentation
▪ Localized lymphatic variety
▪ Follows the implantation of spores in a wound
▪ Often on the upper and lower extremities
▪ Incubation period is 8 to 30 days
▪ A nodule or pustule forms, which may break down into a small ulcer
▪ When untreated, it usually follows a chronic course, characterized by involvement of
lymphatics from the draining area
▪ Chain of lymphatic nodules develops, called sporotrichoid
▪ New nodules appear at intervals of a few days
▪ Nodules soften and ulcerate, and are connected by tender lymphatic cords
▪ A thin purulent discharge may come from the primary lesion and the earliest
lymphatic nodules
▪ As disease becomes chronic, the regional lymph nodes become swollen and may
break down
▪ Primary lesion may heal spontaneously leaving the lymphatic nodes enlarged

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 ▪ Fixed cutaneous sporotrichosis
▪ Less commonly seen disease state, in which the infection is confined to the site of
inoculation
▪ Lesions may be acneiform, nodular, ulcerated or verrucous; the latter form is
occasionally very extensive
▪ Less commonly, there may be infiltrated plaques or red scaly patches
▪ An ulcer may be gummatous or may simulate an epithelioma

▪ Mucocutaneous sporotrichosis
▪ Relatively rare
▪ Lesions in mouth, pharynx, vocal cords or nose
▪ At first erythematous, ulcerative and suppurative at first
▪ Eventually become granulomatous, vegetative or papilloma-like
▪ Accompanied by pain

▪ Pulmonary sporotrichosis
▪ Less common systemic form probably follows inhalation
▪ Presents either with local pulmonary disease (focal) or widely disseminated lesions
in joints, meninges and skin
▪ Single cavitary lesion of the upper lobe called sporotrichoma (residual fibrocaseous
nodule) is the most distinctive feature
▪ Gradually, chronic pneumonitis with thin-walled cavities with fibrosis and pleural
effusion may develop

Laboratory Diagnosis
▪ Specimen of Choice
▪ Aspirate
▪ Curetting
▪ Biopsy of the skin lesion
▪ Exudates from unopened subcutaneous nodules or from open, draining lesions

▪ Mold Phase of Sporothrix schenckii

▪ Culture Media
▪ Sabouraud dextrose agar with cycloheximide
▪ Also grows well on Mycosel, Mycobiotic, and inhibitory mold agar
▪ Colonies grow in about 5 to 10 days
▪ Culture – Colony Characteristics
▪ Mold colony morphology can be variable
▪ Colonies initially are small, moist, and white to cream colored
▪ On further incubation or as they become mature, colonies become
membranous and coarsely matted, wrinkled, with the color becoming
irregularly dark brown or black, and the colony becoming leathery
▪ Culture – Microscopic Characteristics
▪ Thin-walled hyaline microconidia
▪ Arranged as a rosette around the apex of a conidiophore
▪ Borne on conidiophores that arise at right angles from thin, delicate
hyphae
▪ Arranged sympodially around an expanded vesicle at the tip of the
conidiophore – floret arrangement

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 ▪ Thick-walled, dark, sessile conidia
▪ Produced along the sides of the hyphae (attached directly to the
hyphae)
▪ May be observed more than rosettes in mature cultures
▪ Account for a dematiaceous appearance of the fungus in culture
(melanized fungus)

▪ Conversion of the mold phase to yeast is accomplished by the following:

▪ Inoculation of fungus on BHIA supplemented with sheep’s blood or on
chocolate agar
▪ Incubation at 37°C in an atmosphere of 5% CO2
▪ Formation of yeast colonies may require several subcultures
▪ Complete conversion seldom occurs

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▪ Yeast Phase of Sporothrix schenckii
▪ Direct Microscopic Examination
▪ Histopathological examination of tissue sections stained with Periodic Acid-
Schiff (PAS) or Gomori methenamine silver (GMS) stains
▪ Fluorescent antibody stain
▪ KOH preparation – wet mount
▪ Calcofluor white preparation – wet mount
▪ Histopathology
▪ Yeast cells of Sporothrix are rarely seen in tissue
▪ When present, yeast cells are pleomorphic and round or elongated,
resembling cigars 2 to 6 μm in diameter with narrow-based budding
▪ Histologic responses to Sporothrix include suppurative (including
eosinophils) and granulomatous inflammation
▪ Wet Mount
▪ Wet mounts of material are often unrewarding because of the small
numbers of organisms present
▪ 10-20% KOH or calcofluor white
▪ Colony Characteristics
▪ BHIA supplemented with sheep’s blood or on chocolate agar
▪ Incubation at 37°C in an atmosphere of 5% CO2
▪ Yeast colonies are pasty and grayish

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 ▪ Phenotypic characteristics to distinguish species:
▪ Morphology of conidia
▪ Growth at 30°C, 35°C, and 37°C
▪ Assimilation of sucrose, raffinose, and ribitol

▪ Serology
▪ Especially helpful in the diagnosis of extra-cutaneous or systemic infection
▪ A slide latex agglutination test called yeast cell agglutination test, using peptido-L-
rhamno-D-mannan as antigen is a reliable, sensitive and specific test
▪ Sporotrichin
▪ Molecular studies used to differentiate Sporothrix species:
▪ Calmodulin gene sequence
▪ rRNA internal transcribed spacer sequence data
▪ β-tubulin sequence

Treatment
▪ For cutaneous infection, potassium iodide is given topically or orally
▪ For lymphocutaneous infection, itraconazole is effective
▪ For disseminated infection, amphotericin B is the drug of choice

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 Chromoblastomycosis

Synonyms
▪ Verrucous dermatitidis, chromomycosis
Definition
▪ Chromoblastomycosis is a chronic mycosis of
the skin and subcutaneous tissue that
develops over a period of months or, more
commonly, years
Etiology
▪ Chromomycosis is caused by several
dematiaceous fungi
▪ Fonsecaea pedrosoi – most common species
causing this disease
▪ Phialophora verrucosa – second most common
▪ Less commonly – Cladophialophora carrionii and Rhinocladiella aquaspersa
▪ Although numerous other melanin-producing species may also be involved
Epidemiology
▪ Found most commonly in men who have direct contact with soil
▪ Etiologic agents have also been isolated from wood
▪ Not spread from man to man, and other animals do not contract it
▪ Little is known about predisposing factors, except trauma and contact with soil
▪ Condition is usually found in rural communities
Clinical Manifestations
▪ Characterized by the presence of large, muriform, thick-walled dematiaceous cells called
sclerotic bodies (medlar bodies, fission bodies, or “copper pennies”) within the infected
tissues
▪ Distinguished by the formation of a painless verrucous plaque or nodule at the site of
inoculation following a penetrating trauma, with healing areas of the lesion evident along
with the formation of scar materials
▪ Verrucous nodules may become ulcerated and crusted
▪ Longstanding lesions have a cauliflower-like surface
▪ Mostly asymptomatic in the absence of secondary complications, such as bacterial
infections, carcinomatous degeneration, and elephantiasis
▪ Lesions are usually confined to the extremities, often the feet and lower legs – result of
trauma to these areas
▪ Never involves internal organs

Laboratory Diagnosis
▪ Histopathology
▪ Infected tissue may be sectioned, stained, and viewed microscopically for the
etiologic agents
▪ Brown, round, non-hyphal sclerotic bodies, which are non-budding structures
occurring singly or in clusters, are seen in tissues
▪ Sclerotic bodies (or fission bodies) reproduce by dividing in various planes, resulting
in multicellular forms
▪ Occasionally, short hyphal elements may be seen

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 ▪ Fission bodies are always brown, regardless of what stain is used (not even
necessary to stain for visualization)
▪ Sclerotic bodies are diagnostic for this disease, but do not provide a clue as to
species identification of the mold
▪ An additional characteristic is that chromoblastomycosis infections lead to
excessive proliferation of host tissue
▪ This feature differentiates it from mycetoma and phaeohyphomycosis, which result
in tissue necrosis

▪ Wet Mount
▪ Skin scrapings are removed from a lesion and a KOH preparation made
▪ Fungi are seen as round, thick-walled, dematiaceous cells 5 to 15 μm in diameter –
sclerotic or fission bodies
▪ Sclerotic bodies are usually clumped together, and some may contain a septum;
hyphae are not seen
▪ Fission bodies do not produce buds, thus not considered to be yeast cells
▪ Culture
▪ Culture and recognition of morphologic features of the isolate are needed to identify
the infecting species
▪ Infected skin is cultured into SDA with antibiotics
▪ Incubate at 25°C to 30°C
▪ Most etiologic agents will not grow at temperatures higher than 30°Cs
▪ All organisms grow very slowly, requiring 2 to 3 weeks of incubation
▪ Colonies are always dark brown to black (some have a dark green color) on the
surface, and are dark black on the undersurface
▪ Colonies are usually heavily furrowed and some species produce a very heaped-up
effect
▪ Etiologic agents are identified on the basis of characteristic structures, such as
arrangement of conidia and the manner in which conidia are borne
▪ All these fungi are named according to the dominant form of conidiation

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▪ Phialophora verrucosa
▪ Colonies grow very slowly into a flat, furrowed, brown to black colony
▪ Microscopically, the dominant form of conidiation is the production of vase-like or
flask-shaped phialides with dark collarettes at the apices
▪ Phialides are produced laterally or terminally
▪ Hyphae and phialides are dematiaceous
▪ Hyphae are septate

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▪ Fonsecaea pedrosoi
▪ Strains of this fungus show variation in colony growth rate and type of spore
formation
▪ Colonies are always dark brown to black in color and usually grow relatively slow
▪ Colonies are slightly fuzzy furrowed, and have a heaped-up center

▪ Dominant form of conidiation is sympodial with the conidia confined to the upper
part of the cell
▪ Cladophialophora type – brown single-celled conidia are produced on short
denticles and may in turn produce secondary conidia
▪ Rhinocladiella type – bottle-brush conidia
▪ Phialophora type – flask-shaped phialides
▪ Conidia produced by acropetal budding

▪ Hyphae are dematiaceous and have many well-defined septa

▪ Conidiophores are longer than seen in Fonsecaea compactum, but not as long as
Cladophialophora carrionii
▪ Brown spores are oval and are arranged in chains which are longer than seen in F.
compactum

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 ▪ May occasionally produce phialides (Phialophora type) and conidiophores which are
short, swollen cells

▪ Fonsecaea compactum
▪ Microscopically, very compact dematiaceous hyphae and conidia are observed –
numerous close septa, short conidiophores, and tightly packed conidia
▪ Conidiophores usually contain just a few dark brown, septate cells

▪ Cladophialophora carrionii
▪ Usually requires one month of incubation to produce a colony of 2 to 4 cm in
diameter
▪ Colonies are relatively flat with a slightly raised center
▪ Gray to green to black in color, and composed of short, fuzzy aerial hyphae

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▪ Cladophialophora carrionii
▪ Microscopically, long, slender, branched conidiophores are observed
▪ Conidiophores produce numerous, oval conidia in long chains
▪ Both hyphae and conidia are dematiaceous
▪ Septa in the hyphae are relatively far apart when compared with the other etiologic
agents of this disease

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Treatment
▪ Itraconazole (100-200 mg daily) or terbinafine (250 mg daily) is often successful – responses
to both are thought to be better if the causative organism is C. carrionii
▪ Flucytosine alone or combined with amphotericin B may also be effective, but resistance to
flucytosine may develop if used alone
▪ Cryotherapy
▪ Local application of heat
▪ Surgery
▪ Use of surgery is contentious
▪ In larger plaques, there is a risk in pursuing this approach as satellite lesions may
develop around the excision site
▪ Only indicated in very small lesions combined with chemotherapy

Differential Diagnoses
▪ Blastomycosis – by the absence of a sharp border containing minute abscesses and also the
absence of pulmonary lesions
▪ Cutaneous tuberculosis – Mycobacterium marinum
▪ Leishmaniasis
▪ Syphilis – Treponema pallidum subsp. pallidum
▪ Yaws – Treponema pallidum subsp. pertenue

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 Mycetoma

Synonyms

▪ Madura foot, maduromycosis

Definition
▪ Mycetoma is a tropical disease causing a localized,
chronic granulomatous infection characterized by the
formation of a painless subcutaneous mass of chronic
onset, with multiple sinuses draining pus and grains
(also called granules) with extension to the bone
Etiology
▪ Disease can be caused by bacteria (actinomycotic mycetoma) or by fungi (eumycotic
mycetoma) that are dark pigmented (dematiaceous) or, rarely, non-pigmented (hyaline)
▪ Although clinical manifestations are similar for both types, the etiologic agent must be
determined before appropriate therapy is begun
▪ Actinomycotic mycetoma or actinomycetoma
▪ Nocardia spp.
▪ Actinomadura spp.
▪ Streptomyces spp.
▪ Etiologic agents are bacteria
▪ Granules produced by these bacteria contain very fine, delicate filaments (less than
1 μm in diameter)
▪ Eumycotic mycetoma or eumycetoma
▪ Pseudallescheria boydii
▪ Acremonium falciforme
▪ Madurella mycetomatis
▪ Madurella grisea
▪ Exophiala spp.
▪ Aspergillus spp.
▪ Fusarium spp.
▪ True filamentous fungi
▪ Granules contain large, coarse, septate hyphae (5 to 10 μm in diameter)

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Epidemiology
▪ All mycetoma causing organisms grow in soil as saprophytes
▪ Mycetomas occur in tropical and subtropical areas but are also seen in temperate zones
▪ Most often confined to the hands or feet (also called Madura foot) in immunocompetent
individuals such as farmers, field hands, and others in contact with contaminated soil-laden
materials
Clinical Manifestations
▪ A mycetoma occurs after a traumatic injury with a contaminated object such as a splinter, a
thorn, or any other penetrating item
▪ The foot is the most commonly infected part of the body
▪ As the disease progresses, the foot becomes grossly deformed
▪ Advanced cases have multiple fistulae which drain from the underlying abscesses
▪ Spread occurs through skin facial planes and can involve the bone
▪ Dissemination may occur to muscles and bones
▪ Hematogenous or lymphatic spread is uncommon
▪ Characteristic triad of mycetoma:
▪ Tumefaction – tumor-like swelling
▪ Multiple draining sinuses – pathognomonic of mycetoma
▪ Sclerotia – presence of granules or grains in sinuses

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 ▪ Fungal rhinosinusitis
▪ A noninvasive disease involving the paranasal sinus has been described as a fungal
mycetoma (also called a fungus ball)
▪ Involves the accumulation of dense fungal elements in the sinus cavities, most often
the maxillary sinus
▪ Associated with a variety of molds, including dematiaceous fungi
▪ Although some categorize this infection as a mycetoma, others prefer to describe it
as a fungal rhinosinusitis because this infection does not specifically fit the
description of a mycetoma – absence of granules

Laboratory Diagnosis
▪ Definitive diagnosis of a mycetoma can be achieved by the demonstration of grains (or
granules) in a tissue biopsy, in draining exudates from a sinus tract, or in material aspirated
from an unopened lesion
▪ Granules differ in color, shape, dimension and composition
▪ Black granules are usually fungal in nature
▪ Small red granules – Streptomyces
▪ White or whitish yellow granules – either bacterial or fungal

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▪ Wet Mount
▪ Pus or other exudate from a draining sinus tract are examined for granules
▪ By observing the size, color, and general morphology of the granules, it is possible to
obtain a preliminary identification of the etiologic agent
▪ Exudates are placed on a microscopic slide and one to two drops of 10-20% KOH are
added
▪ Granules are broken up to examine content
▪ Culture
▪ Identification of the etiologic agent requires culture on standard fungal media such
as SDA
▪ May take 4 weeks or longer to grow
▪ Once isolated, the fungus is identified using:
▪ Gross colony morphology and pigmentation
▪ Close observation of the micromorphologic characteristics of reproductive
structures following sporulation
▪ Other Diagnostic Methods
▪ In cases in which sporulation does not occur, biochemical tests such as
carbohydrate and nitrate utilization may aid in identification.
▪ Molecular assays using targets within the rDNA complex have been shown to be
reliable for identification of dematiaceous fungi

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▪ Pseudallescheria boydii
▪ The anamorphic form of P. boydii is the septate filamentous fungus Scedosporium
boydii
▪ Opinions differ regarding this fungus in relation to it being hyaline or phaeoid
▪ Produces oval conidia singly at the tips of conidiogenous cells known as annellides

▪ The teleomorph is noted by the formation of cleistothecia containing ascospores

▪ This phenomenon occurs in fungi that are homothallic (ability of a single organism
to undergo sexual reproduction without a mate)
▪ Isolate grows rapidly and produces white to dark gray colonies on potato dextrose
agar at 22°C and 35°C

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 ▪ Acremonium falciforme
▪ Produces mucoid clusters of single- or two-celled, slightly curved conidia borne
from phialides at the tips of long, unbranched, multiseptate conidiophores
▪ Conidia are held together in mucoid clusters at the apices of the phialides
▪ This isolate is a hyaline, septate, filamentous mold
▪ Colonies grow slowly and are grayish brown, becoming grayish violet
▪ Madurella mycetomatis
▪ Phaeoid, septate fungi
▪ Approximately 50% of the isolates produce conidia from the tips of phialides, but
many remain sterile
▪ Grows very slowly but is initially white, and becomes
▪ Yellow, olivaceous, or brown, with a characteristic diffusible brown pigment with
age
▪ Grows best at 37°C, with slower growth at 40°C

▪ Madurella grisea
▪ Phaeoid, septate fungi
▪ In colonies of M. grisea, only sterile hyphae are observed
▪ Isolate grows slowly, produces olive brown to black colonies, and may produce a
reddish brown pigment
▪ Optimal growth temperature is 30°C
Treatment
▪ Surgery
▪ Surgical excision is recommended for small localized lesions
▪ Debulking of massive lesions
▪ Amputation is rarely done nowadays – done for very advanced lesions with bad
general condition and as a life saving procedure
▪ Eumycetoma – itraconazole, ketoconazole
▪ Actinomycetoma
▪ Amenable to medical treatment with antibiotics and other chemotherapeutic agents

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▪ Combined drug therapy is always preferred over a single drug to avoid drug
resistance and to eradicate residual infection
▪ Amikacin sulphate (15 mg/kg) with Cotrimoxazole (14 mg/kg twice daily) – first line
for actinomycetoma
▪ Streptomycin +/- Dapsone

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 Phaeohyphomycosis

Synonyms
▪ Subcutaneous phaeohyphomycosis
▪ Cerebral chromoblastomycosis
▪ Phaeosporotrichosis
▪ Chromomycetoma
▪ Dematiaceous infections
▪ Cladosporiasis
Definition
▪ Phaeohyphomycosis is a mycotic disease caused by
darkly pigmented fungi or fungi that have melanin
in their cell walls
▪ This term was coined to separate several clinical infections caused by phaeoid fungi from
those distinct clinical entities known as chromoblastomycosis
▪ Tissue morphology of the causative organism is mycelial or mold
▪ Over the years, phaeohyphomycosis has become more recognized as a cause of
subcutaneous and systemic diseases characterized by the formation of brownish to
olivaceous hyphal elements in tissue
▪ Although both chromoblastomycosis and eumycotic mycetoma are caused by
dematiaceous fungi, they are distinguished from phaeohyphomycosis by the appearance in
tissue of sclerotic bodies and mycotic granules, respectively
Etiology
▪ Exophiala dermatitidis – previously Wangiella dermatitidis
▪ Exophiala jeanselmei
▪ Cladosporium spp. – previously Hormodendrum spp.
▪ Alternaria spp.
▪ Ulocladium spp.
▪ Bipolaris spp.
▪ Curvularia spp.
▪ Drechslera spp.
▪ Scedosporium spp.
▪ Exserohilum rostratum
▪ Caused an outbreak of phaeohyphomycosis
▪ Associated with injection of methylprednisolone acetate solution contaminated with
this dematiaceous fungus
▪ E. rostratum had only rarely been reported as a cause of human disease prior to this
outbreak
Epidemiology
▪ Found in nature either growing as soil saprophytes or plant pathogens
▪ Occur worldwide in any type of soil and on almost all forms of vegetation
▪ Major cause of plant rot
▪ Increased exposure to these fungi is most often encountered by people who live or work in
these types of environments
▪ Some of the cases exhibiting subcutaneous cysts may be due to traumatic implantation from
a contaminated source, such as a twig or straw

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Clinical Manifestations
▪ Phaeohyphomycosis can be arbitrarily divided into:
▪ Allergic disease
▪ Includes allergic fungal sinusitis and allergic bronchopulmonary mycosis
▪ Allergic disease that manifests as asthma is linked to exposure to Alternaria
spp. and Cladosporium spp.
▪ Bronchopulmonary form is most frequently due to Bipolaris or Curvularia
▪ Superficial infections
▪ Involve the keratinized tissues such as the fingernails and toenails and the
stratum corneum (e.g., tinea nigra)
▪ These asymptomatic infections are most commonly caused by Hortaea
werneckii, Scopulariopsis brevicaulis, Phoma euphyrena, and Chaetomium
globosum
▪ Deep local infections
▪ Subcutaneous lesions, keratitis, bone and joint infections, and peritonitis
▪ Subcutaneous forms are characterized by the formation of a solitary
asymptomatic subcutaneous nodule or cyst usually in an immunocompetent
individual
▪ Most common dematiaceous fungi associated are
E. jeanselmei, E. dermatitidis and Bipolaris spp.
▪ Subcutaneous phaeohyphomycosis starts as an isolated erythematous
nodule, often on the extremities, and can expand to involve deep tissues,
including bone
▪ The infection can spread locally with the formation of additional nodules
and extension to bone
▪ Immunocompromised persons are at highest risk for this infection
▪ In immunocompromised individuals, the infection can disseminate to other
regions of the body, including the brain

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 ▪ Pulmonary infection
▪ Central nervous system infection
▪ Disseminated infection
▪ Rare complication of immunosuppression
▪ One of the more common species associated with this condition is
Scedosporium prolificans, an aggressive fungus that is generally resistant to
all available antifungal agents

Laboratory Diagnosis
▪ Wet Mount
▪ 10-20% KOH
▪ Strands of dematiaceous septate hyphae, approximately 5-10 μm in diameter
▪ Culture
▪ All etiologic agents grow well on either SDA or Mycosel agar at either room
temperature or 35°C
▪ Fungi require 1 to 4 weeks incubation at either temperature to reach a diameter of 1
cm
▪ Colonies grow as compact and fuzzy, and produce brown to black color especially on
the underside
▪ Colonies look flat and velvety

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Treatment
▪ Surgical debridement is generally necessary for cure
▪ Several antifungal agents are active against these organisms:
▪ Amphotericin B – reserved for life-threatening cases
▪ Itraconazole
▪ Voriconazole
▪ Posaconazole

Rhinosporidiosis

Definition and Etiology

▪ Rhinosporidiosis is a chronic, usually painless
infection of humans and animals that occurs as
mucosal polyps of the nasopharynx and conjunctiva
▪ Formerly thought to be a fungus, the etiologic agent
Rhinosporidium seeberi has never been cultured
▪ Cannot be cultured in cell-free artificial
media
▪ Animal inoculation was also not successful
Epidemiology
▪ Habitat of Rhinosporidium seeberi is unknown but is thought to be freshwater
▪ Swimming in ponds, lakes, and rivers has been linked to disease
▪ Circumstantial evidence indicates that one source of infection may be stagnant water
▪ Mode of infection is not known
▪ However, it is suggested that it is transmitted in dust and water
▪ Fish is believed to be the natural host of this organism
▪ Infection is seen most commonly in persons taking bath in stagnant pools and in individuals
who dive in streams to collect sand from river beds
Clinical Manifestations
▪ Rhinosporidiosis is characterized by development
of large friable polyps or wart-like lesion in the
nose, conjunctiva or eye
▪ Patients can present with nasal obstruction or
nosebleeds
▪ Lesions increase in size over months to years
▪ Rarely, polyps occur in the vagina, urethra, or penis

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Laboratory Diagnosis
▪ Histopathology
▪ Diagnosis is made by biopsy and finding the distinctive appearance of the organisms
on microscopy
▪ Infected tissue, removed from the tumor-like polyp is sectioned and stained with
H&E or PAS
▪ Microscopically, Rhinosporidium seeberi grows as large, spherical sporangia, which
are up to 300 μm in diameter
▪ These structures appear very similar to those seen in coccidioidomycosis but several
times larger
▪ Mature sporangia are filled with spores, which are 10 to 15 μm in diameter
▪ Mature sporangia may be seen as empty due to the release of hundred of spores
into the surrounding tissues
▪ These young spores grow larger, developing into sporangia which eventually are
filled with spores
▪ Yeast cells, hyphae, or other fungal elements are never seen in infected tissue
▪ The round, thick-walled cysts (sporangium) in the submucosa are sometimes visible
in the mucosa as white dots

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Treatment
▪ Treatment of choice is surgery, although recurrences are common
▪ Cauterization
▪ Chemotherapy with dapsone is also useful

Lobomycosis

Definition and Etiology

▪ Lobomycosis is a chronic, localized,
subepidermal infection characterized
by the presence of keloidal,
verrucoid, nodular lesions or
sometimes by vegetating crusty
plaques and tumors
▪ Etiologic agent is Lacazia loboi
▪ Lesions contain masses of
spheroidal, yeast-like organisms
Epidemiology
▪ L. loboi are thought to reside in soil
or vegetation and infect humans via skin trauma
▪ Farmers, hunters, and jungle workers are affected more than others
▪ Dolphins can also be infected, so it is presumed that L. loboi also exists in bodies of water
▪ Affects immunocompetent patients
▪ More common in men (68-92% of cases) than in women

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 ▪ 90% of cases are men
▪ Mostly in farmers and other high-risk groups exposed to various harsh conditions as
well as aquatic habitats
▪ Average age of infected patient is 38 years old
Clinical Manifestations
▪ The disease occurs as slowly forming skin nodules of various sizes that occur on the face,
arms, legs, and feet
▪ Lesions can vary in appearance and can be flat or nodular and warty or ulcerated
▪ Older lesions become verrucoid and may ulcerate
▪ Infection can exist over a period of years, with slow progression of the disease, which is
relatively asymptomatic
▪ Initial infection is thought to be
caused by traumatic implantation,
such as an arthropod sting, snake
bite, sting-ray sting, or wound
acquired while cutting vegetation
▪ May be transferred to other areas of
the skin by further trauma or
autoinoculation; thus, the areas of
involvement may become quite
extensive
▪ Does not become a systemic fungal
infection, but fungal cells can be
found in proximal lymph nodes
▪ Two forms of the disease:
▪ Cutaneous lobomycosis
▪ Subcutaneous lobomycosis
▪ Special staining of lesion biopsy material is required to demonstrate the characteristic
appearance of the fungi
▪ Tissue samples are typically obtained by curettage or surgical biopsy
▪ Stains include GMS, PAS, and Parker Ink
▪ Wet mounts with 10-20% KON may be prepared
▪ L. loboi has never been isolated in culture

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Laboratory Diagnosis
▪ Darkly pigmented fungal cells when GMS is used for staining
▪ Spherical intracellular yeast that are remarkably homogenous
▪ Most likely reproduces through budding
Treatment
▪ Only effective treatment is surgical excision, although clofazimine may be partially
effective
▪ Infection is resistant to therapy with the antifungal medications typically used to treat other
invasive cutaneous mycoses

Entomophthoromycosis
Definition and Etiology
▪ Fungi of the order Entomophthorales are also present in organic debris and can cause a
chronic subcutaneous form of infection, entomophthoromycosis
▪ This is often the result of traumatic implantation of the organisms in the skin
▪ Caused by organisms of two genera, Conidiobolus and Basidiobolus – Conidiobolus
coronatus, Conidiobolus incongruous, and Basidiobolus ranarum (previously known as
Basidiobolus haptosporus)

▪ Basidiobolus ranarum
▪ Causes subcutaneous infection of the proximal limbs in children
▪ Characterized by rubbery masses that can be large and ulcerate
▪ May be found on the shoulders, hips, and thighs
▪ Conidiobolus spp.
▪ Infection is localized to the facial area, predominantly in adults
▪ Occur after inhalation of fungal spores, which subsequently invade the sinuses and
facial soft tissues
▪ May cause painless swelling of the lips and face that can be very deforming
▪ Occasionally, these infections may disseminate to other areas of the body, particularly in
immunocompromised persons
▪ Diagnosis can be made clinically based on the following:
▪ Typical skin and soft tissue findings
▪ Confirmed with biopsy and culture

Laboratory Diagnosis
▪ Histopathology
▪ Tissue sections are stained with either PAS or GMS
▪ Organisms produce very large (10-12 μm in diameter) coenocytic (sparsely septate)
hyphae
▪ No yeast cells are seen
▪ Hallmark of these organisms in tissue are the large, hyaline, non-dichotomously
branching, coenocytic hyphae
▪ Wet Mount
▪ 10-20% KOH
▪ In such preparations, large, hyaline, non-dichotomously branching, coenocytic
hyphae are observed
▪ Culture
▪ Grow well on SDA with or without antibiotics

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 ▪ Room temperature incubation is adequate; however, incubation at 35-37°C results
to a more rapid growth
▪ After 2-3 days of incubation, masses of aerial hyphae are produced which may fill up
the entire Petri dish
▪ Hyphae are so aerial that they may reach up and touch the lid of the Petri dish
▪ Most organisms produce gray mycelia
▪ After 3-5 days incubation, these fungi form spores, which are borne inside sporangia
▪ Sporangia are usually jet black and are seen grossly as minute dark specks on the
aerial hyphae
Treatment
▪ Itraconazole is active against these organisms, although fluconazole, terbinafine, and
amphotericin B have also been effective

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