SUBCUTANEOUS

MYCOSES
PRESENTER: DR PRANAY REDDY
MODERATOR: DR TONITA MN
INTRODUCTION
 Subcutaneous mycoses are fungal infections that remain limited to the skin
and subcutaneous tissues, rarely spreading to internal organs
 The causal agents are saprophytes existing in nature
 The usual mode of infection is through inoculation
 These diseases include :
 Mycetoma
 Chromoblastomycosis
 Phaeohyphomycosis
 Sporotrichosis
 Lobomycosis
 Entomophthormycosis
MYCETOMA
 Chronic, suppurative, granulomatous disease of subcutaneous tissues and
bones
 Presents as localized swellings with multiple sinuses discharging granules that
are the microcolonies of the causative agents
 May be bacterial (actinomycotic) or fungal (eumycotic)
 Actinomycotic mycetoma is caused by aerobic species of actinomycetes
belonging to the genera Nocardia, Streptomyces, and Actinomadura
 Eumycotic mycetoma is caused by fungi, the most common being Madurella
mycetomatis, Pseudallescheria boydii, and Acremonium species
EPIDEMIOLOGY

 More common in tropical and subtropical regions where walking barefoot is

common
 In India, actinomycotic mycetoma is more commonly encountered than
eumycotic mycetoma
 Males > females
 CLINICAL FEATURES
 Begins as a small, painless, subcutaneous nodule at the site of injury
 Multiple nodules develop, ulcerate, and drain through sinus tracts
 The discharge may be serosanguineous, seropurulent, or purulent and contains granules
 The surrounding tissue becomes swollen, indurated, and deformed by fibrous tissue
reaction and sinus formation
 Pain is not a major complaint when only the soft tissue is invaded; the condition becomes
very painful with the involvement of bones or with the secondary bacterial infection
BONE INVOLVEMENT:
 Occurs later in the course of disease
 In eumycotic mycetoma, the lesions are single or multiple punched-out lytic areas
with well-defined walls and little sign of bone reaction
 In actinomycotic mycetoma, both osteolytic and osteosclerotic changes are present
at the same time
 Destruction of the ligaments and articular surfaces results in ankylosis of the joints
DIFFERENTIAL DIAGNOSIS
INVESTIGATIONS

1) MICROSCOPIC EXAMINATION OF GRAINS

 The grains can be collected by saline dressings applied over the swelling for 24
hours
 The color of the grain should be noted. Black grains are almost always eumycotic
whereas red grains are due to Actinomadura pelletierii
 White or pale grains may be either eumycotic or actinomycotic
 The eumycotic organisms producing black grains include Madurella mycetomatis,
Madurella grisea, Leptosphaeria senegalensis, and Curvularia geniculata
 White grains are formed by eumycotic organisms like Pseudallescheria boydii,
Neotestudina rosatii, and actinomycotic organisms like Acremonium spp.,
Fusarium spp., and Nocardia spp
2) KOH MOUNT AND GRAM STAIN OF GRAINS
 Actinomycotic granules are composed of Gram positive filamentous mycelium of
bacterial width and without any chlamydospores
 The eumycotic granules consist of broad septate hyphae with well-defined walls
and chlamydospores
 Acid-Fast Bacilli stains are useful in the identification of Nocardia spp.
3) HPE OF BIOPSY SPECIMEN
 In the initial stages there is an acute suppurate reaction. The infiltrate is composed of
neutrophils, histiocytes, eosinophils, and plasma cells
 Epithelioid cells and Langhans giant cells may be seen as the lesion evolves, giving
rise to a suppurative granuloma
 In the actinomycetoma, fine branching, interlacing filaments are seen
 In eumycetoma, thick-walled septate hyphae are seen
TREATMENT

 1st line- medical management

 2nd line- surgical excision
 Modified Welsh regimen:
• 3-4 cycles of amikacin 15mg/kg IV for 21 days with 15-day intervals
• daily oral cotrimoxazole 35 mg/kg/day
• rifampicin 10 mg/day

 Modified two step regimen:

• gentamicin 80 mg IV 12-hourly
• cotrimoxazole 320/1600 mg BD for 4 weeks followed by a maintenance
phase of cotrimoxazole and doxycycline 100 mg BD to be continued for 6
months after healing
CHROMOBLASTOMYCOSIS
 Chronic granulomatous infection, usually of exposed areas
 Characterized by the development of warty plaques, nodules, or cauliflower-
like lesions, which may ulcerate
 The principal causatve agents are Cladophialophora carrionii and Fonsecaea
pedrosoi
 Less common pathogens include Fonsacea compactum, Phialophora verrucosa,
Rhinocladiella aquaspersa, Exophiala jeanselmei, Exophiala spinifera,
Wangiella dermatitidis, and Ascosubramania
MODE OF TRANSMISSION

 The causative organisms are dematiaceous (brown-pigmented) fungi, which

exist as saprophytes in the soil, decaying vegetation or rotting wood
 Infection occurs following traumatic inoculation into the skin
CLINICAL FEATURES

 The lesion is frequently seen on exposed sites, which are prone to trauma
 It may be:
• localized (commonest presentation)
• multiple where satellite lesions are seen
• sporotrichoid (lymphatic spread)
 Begins as a warty papule and slowly enlarges to form a hypertrophic,
verrucous plaque
 Some lesions may have central atrophy and scarring. Black dots may be seen
on the surface
 Secondary infection and ulceration can occur
 Wide-spread disease with hematogenous spread and bone invasion is rare
 Long-standing cases can result in elephantiasis
 Chronic lesions may show malignant transformation
INVESTIGATIONS

1) KOH MOUNT
 Skin scrapings, crusts, aspirated material, and biopsy tissue
 Characteristic thick-walled, dark brown “sclerotic bodies” or muriform cells
2) HPE OF BIOPSY TISSUE
 In H&E stained tissue sections, the “sclerotic bodies” are easily visible and
no special stain is needed
 Tissue infiltrates may be seen with variably pigmented fungal structures
called muriform cells (medlar bodies/copper pennies/fumagoid bodies)
 These muriform cells are the main diagnostic feature and are defined as
dematiaceous cells dividing in more than one plane, which results in splitting
of cells and formation of multiple-celled clusters
3) FUNGAL CULTURE
 The specimen is inoculated in Sabouraud’s dextrose agar with antibiotics and
cycloheximide
 Incubated at 26°C for at least 6 weeks
 The fungi are slow growing, and species identification is made based on the
morphological, physiological, and biochemical characteristics

4) SEROLOGICAL TESTS
 To identify specific antibodies against Fonsacea pedrosoi antigens
TREATMENT

 Systemic antifungal therapy is the mainstay of treatment

 Good results have been obtained with a combination of itraconazole 200–400 mg/day
and terbinafine 250– 500 mg/day for 6–12 months
 Some cases may take as long as 48 months to improve indicating much variability in
time required to achieve cure
 Iodides and fluconazole have also been reported to be
 Posaconazole can be used for refractory cases
 When the disease is in the early stages, surgical excision or cryosurgery is useful
PHAEOHYPHOMYCOSIS
 Phaeohyphomycosis is the term used for infections other than chromoblastomycosis
and eumycetoma
 It is caused by a variety of dematiaceous (phaeoid or melanized) fungi
 This entity is characterized by septate dark hyphae, pseudohyphae, yeasts, or any
combination of these forms in tissue
ETIOLOGY

 These fungi are commonly found in moist environments like decaying vegetation, bird
nests, wood, and soil; more frequently in subtropical and tropical climates
 The important etiologic agents:
• Exophiala sp.
• Phoma sp.
• Bipolaris sp.
• Phialophora sp.
• Curvularia sp.
• Alternaria sp.
• Wangiella sp.
MODE OF TRANSMISSION

 Penetrating trauma
 Inhalation
 Rarely hematogenous spread of systemic form of disease
PATHOGENESIS

 Dematiaceous fungi contain DHN melanin, localized to the cell wall

 Melanin has been called fungal armor as it is resistant to various agents
including free radicals, toxic metals, desiccation, and ionizing radiation
 Melanin protects the fungus by scavenging free radicals produced by
phagocytic oxidative burst
 It binds to hydrolytic enzymes and prevents their action on the plasma
membrane
 It can also bind to antifungal drugs and prevent their action
 Thermotolerance is an important virulence factor
 Those fungi that fail to grow at 35°C are more likely to be recovered from
superficial sites, while those capable of growth at this temperature have the
potential for more invasive human disease
CLINICAL FEATURES
SUBCUTANEOUS PHAEOHYPHOMYCOSIS
 Classically presents as a subcutaneous cyst
 The lesions begins as a small papule which evolve into a larger asymptomatic
subcutaneous cyst filled with pus
 The most common locations are the feet, fingers, knee, toes, ankles, legs, and
forearms
 In E. spinifera infections, the face has been described as a common site in children
 Other morphologies include: papulonodules, pustules, eschars, verrucous or
ulcerated plaques, nonhealing ulcers, sinuses and scaly hyperkeratotic lesions
 Ulcerated, crusted, and verrucous plaques and sinuses are more common in
immunocompromised patients
 Unusual morphology and dissemination may also be seen in immunocompetent
hosts, especially children. This might be due to the failure of specific immunity
in the pediatric age group to limit the infection
INVESTIGATIONS

1) KOH MOUNT
 KOH examination of aspirated pus or skin scrapings shows pigmented yeasts,
pseudohyphae, and hyphae

2) FNAC
 Good diagnostic modality for phaeohyphomycotic cysts
 Pigmented hyphae, pseudohyphae, and yeasts along with epithelioid cells,
giant cells and inflammatory cells
3) HPE OF SKIN BIOPSY
 Neutrophilic abscess
 Granulomatous inflammation with histiocytes, lymphocytes, and multinucleated
giant cells
 Frequently, a wooden splinter with foreign-body granulomatous reaction is
observed
 Pigmented yeasts, pseudohyphae, and hyphae seen, with or without the
Splendore–Hoeppli phenomenon
 PAS and Gomorri–Grocott stains are helpful to locate the fungi
 Cystic lesions show a fibrous capsule with granulomatous reaction with a necrotic
center
 Fontana–Masson stain for melanin is diagnostic of phaeohyphomycosis
4) CULTURE
 Sabouraud dextrose agar, cornmeal agar, malt extract agar, and potato
dextrose agar
 The colonies are olivaceous to brown or black
 The dark pigmentation is better appreciated in plant-based media
 Grow in temperatures higher than 37°C, unlike saprophytic fungi
TREATMENT

 Localized cystic lesions- surgical excision with or without skin grafting

 Success has been reported with cryotherapy, but multiple cycles are required
 Incision and drainage is usually followed by recurrence
 Pre- and postoperative antifungal therapy is recommended for recurrent
cases and for immunocompromised patients
 Durations of treatment can range from 6 weeks to 24 months
 Flucytosine 150 mg/kg/day
 Itraconazole 200 mg/day
 Ketoconazole 200 mg/day
 IV or intralesional amphotericin B
 Other effective agents: posaconazole and voriconazole
SPOROTRICHOSIS
INTRODUCTION

 Subacute or chronic infection caused by Sporothrix schenkii

 Characterized by nodular and ulcerative lesions of the skin and subcutaneous
tissue, with occasional involvement of the internal organs
 The organism occurs in nature as a saprophyte on dead plant material and soil
 Transmitted through inoculation at sites of trauma
CLINICAL FEATURES
LYMPHOCUTANEOUS SPOROTRICHOSIS

 A small subcutaneous nodule or pustule develops at the site of injury a few days to 3
weeks after trauma. The upper extremity is the most commonly involved
 The nodule breaks down to form a small ulcer
 New nodules develop along the lymphatics at intervals of a few days
 These nodules also ulcerate and are connected by swollen lymphatics, which are felt
like cords
 The regional lymph nodes become enlarged and may suppurate
 The initial lesion tends to heal with scarring after weeks or months and new
nodules/ulcers develop in other areas along the lymphatic channels
 The secondary lesions are more gummatous and persist for months or years.
FIXED CUTANEOUS SPOROTRICHOSIS

 Seen in highly endemic areas, where the population is sensitized and primary infection
is restricted to the site of injury
 The lesions may be ulcerative, verrucous, acneiform, infiltrated erythematous plaques,
or infiltrated scaly plaques that do not involve local lymphatics. Common sites are
upper extremities and face
 May occasionally remit spontaneously
 Mucous membranes can be involved. Primary infection of mucous membrane is
rare but secondary dissemination occurs frequently
 In the mouth, pharynx, vocal cords, or nose, the lesions are erythematous,
ulcerative, suppurative, and later become granulomatous. They heal with
scarring
 Pain is a prominent symptom
PULMONARY SPOROTRICHOSIS

 Infection is due to inhalation of conidia and presents as chronic cavitary

fibronodular disease
 Most common in middle-aged men with underlying risk factors such as alcoholism
and COPD
EXTRACUTANEOUS AND DISSEMINATED
SPOROTRICHOSIS
 May occur from deep implantation of the organism, contiguous spread of
lymphocutaneous disease or hematogenous spread from cutaneous/pulmonary
foci
 Immunocompromised patients are at higher risk
 Common sites include joints, especially the knees, ankles, wrists, and small
joints of the hands and feet, and bones such as tibia
 The CNS may be involved, presenting as chronic meningitis
DIFFERENTIAL DIAGNOSIS OF
LYMPHOCUTANEOUS SPOROTRICHOSIS
 Atypical mycobacterial infection
 Cutaneous tuberculosis
 Cutaneous leishmaniasis
 Neuritic leprosy
 Anthrax
 Gummatous syphilis
 Staphylococcal lymphangitis
 Bromoderma
INVESTIGATIONS

1) HPE OF SKIN BIOPSY

 Suppurative granuloma (combination of granulomatous and pyogenic reactions)
 The granulomatous pattern may be sporotrichotic, tuberculoid, or foreign body
depending on the site of the lesion
 Sporotrichoid pattern: masses of epithelioid histiocytes with a central area
consisting of neutrophils or necrotic materials, surrounded by an infiltrate of
neutrophils
 Tuberculoid pattern: epithelioid cells mixed with fibroblasts, lymphocytes, and
Langhans giant cells. In some, a prominent outer layer of plasma cells may be
present
 Foreign body pattern: only a foreign body granuloma without any pyogenic reaction
is seen
 In chronic lesions pseudoepitheliomatous hyperplasia may occur.
 Demonstration of S. schenckii in tissue sections is difficult and requires the diastase
method or fluorescent antibody techniques
 Asteroid body: round or oval basophilic yeast- like body (3–5 μm), surrounded by radiating
elongated eosinophilic material (7–20 μm)
 This is called the Splendore–Hoeppli phenomenon (demonstration of eosinophilic material
by fungi)
 Asteroid bodies specific for sporotrichosis are demonstrated by staining with anti-
Sporothrix antibody
2) CULTURE
 Sabouraud’s dextrose agar with antibiotics- incubated at 26°C
 Blood agar- incubated at 37°C
 Colonies are white-cream colored that turn brown-black as they grow older. The
mycelium bears the conidia that resembles a flower
 Conversion into the yeast form is important for specific identification of S. schenckii
 Animal inoculation is used for demonstration of the gram positive “cigar bodies” in
the pus from the lesions

3) SPOROTRICHIN SKIN TEST

 Determines exposure to fungus
TREATMENT

1) SATURATED SOLUTION OF POTASSIUM IODIDE (SSKI)

 Initial dose is five drops (1 ml) three times a day after meals
 This is increased by one drop/dose to 40 drops three times a day
 Therapy is continued till the signs of active disease have disappeared, which
may take up to 32 weeks
 The dosage is decreased by one drop/dose until five drops are being given
and then the drug is discontinued
 Care must be taken to reduce the dosage if signs of iodism appear
2) ITRACONAZOLE
 100–200 mg/day
 Better tolerated than potassium iodide (KI) but is more costly
 The treatment should be extended by at least 1–2 weeks after clinical cure has
taken place

3) IV AMPHOTERICIN B- in systemic disease

ENTOMOPHTHORMYCOSIS
 Chronic subcutaneous and mucocutaneous infection typically seen in tropical
areas
 Presents as solid tumor-like subcutaneous swellings with disfiguration
 Progression occurs via direct extension into adjacent tissues
 Angioinvasion is not seen, and dissemination is rare
CLASSIFICATION

 Mucocutaneous
• known as rhinoentomophthoromycosis
• affects mucosa and subcutaneous tissues of the nose
• caused by Conidiobolus spp
 Subcutaneous
• indolent chronic infection of tissues of the thigh, buttock or trunk
• caused by Basidiobolus spp.
• rarely also causes primary visceral involvement
 Primary visceral form
 Entomophthorales has only two genera, Conidiobolus and Basidiobolus
 These produce rhinofacial (conidiobolomycosis) and subcutaneous
(basidiobolomycosis) infections respective
CONIDIOBOLOMYCOSIS

 Rhinofacial form of disease

 Most commonly caused by Conidiobolus coronatus, found in soil and rotting
vegetation
 Seen in tropical areas of Brazil, Africa, Central America, India
 Transmitted by traumatic implantation, trauma to the nasal mucosa or
inhalation of spores
CLINICAL FEATURES
 Disease onset- inflammation of the submucosa of the inferior turbinate of the nose
 Nasal obstruction occurs first, followed by subcutaneous spread with diffuse infiltration and
thickening of the skin on the nose
 Later, there is deformity of the central facial structures
 Affected areas include the cheeks, forehead, and lips, causing a monstrous disfigurement
of the face known as hippopotamus facies
CLINICAL CLASSIFICATION
BASIDIOBOLOMYCOSIS

 Caused by Basidiobolus ranarum

 Infection mainly in children, more common in males
 Proposed modes of transmission:
• Inoculation at sites of minor trauma
• Use of contaminated toilets and using leaves for cleaning skin in rural areas
• Inhalation/ingestion of spores
 CLINICAL FEATURES
 Commonly affects proximal part of the limbs or the girdle
 Painless, woody hard, well- circumscribed subcutaneous swelling, freely
mobile, does not pit on pressure
 The swelling progresses slowly at the margins and can even involve the limb
circumferentially. The boundary of this diffuse swelling is smooth, rounded,
clearly defined, and can be raised up by fingers insinuated beneath the
swelling (doughnut lifting sign)
 The overlying skin may be normal or edematous, desquamating, and
hyperpigmented
 The skin is tethered to the swelling
INVESTIGATIONS

1) KOH MOUNT
 Broad, aseptate or sparsely septate, branching hyphae
 Refractile walls
 Granular inclusions
2) CULTURE
 Tissue biopsy/nasal mucosal biopsy specimen used for culture
 SDA, PDA, cornmeal agar
 Conidiobolus spp.: The colonies are flat, creamy to light grayish color with
radial folds. Waxy colonies turn powdery due to aerial hyphae
 Basidiobolus ranarum: Flat furrowed colonies with a waxy texture; yellowish to
gray colour
3) HPE OF SKIN BIOPSY
 Dermis or subcutis contains granulomas composed of epithelioid histiocytes,
lymphocytes and eosinophils
 large aseptate/sparsely septate hyphae seen as clear spaces surrounded by
eosinophilic smudged hyaline material (Splendore-Hoeppli phenomenon)
 Special stains such as PAS and GMS stain the cell wall of fungal hyphae
TREATMENT

 Potassium iodide, co-trimoxazole, amphotericin B, ketoconazole, itraconazole

have been used with different degrees of success
 Posaconazole oral suspension 800 mg/ day in divided doses in patients
refractory to amphotericin b
LOBOMYCOSIS
 Mainly occurs in tropical climates of Latin America
 Caused by Lacazia loboi, a dimorphic fungus, found in soil, vegetation and water
 Presesnts with polymorphic skin lesions. Keloidal lesions are characteristic
 Zoonotic disease- can affect dolphins
 Infection by traumatic implantation
CLINICAL FEATURES

 Affects predominantly exposed areas (pinna, upper limbs, lower limbs) of adult
males
 The scalp, mucous membranes and internal organs are spared
 initial lesion is a papule, with slow progression over years to a plaque or nodule
 The primary lesion is covered by smooth and shiny intact skin which is flesh
colored/red wine in color with or without telangiectasia. This typical fibrous
appearance resembles a scar or a keloid
 The lesion has sharp lobulated margins, lobulated and indurated surface, not
attached to underlying structures, and a lack of local and systemic symptoms.
 New lesions around the index lesion points to autoinoculation or local lymphatic
dissemination
 Lymph node involvement has been reported in 10% of cases
 Skin overlying chronic lesions may be hyper, hypo or depigmented
 Exophytic lesions are termed as verrucous lobomycosis
CLASSIFICATION

 Based on clinical manifestations:

• infiltrative (papular/nodular)
• keloidal
• gummatous
• verrucoid
• ulcerative
 Based on the distribution of the disease:
• Localized or isolated disease
• multifocal disease but restricted to an anatomical area
• disseminated disease (more than one anatomical segment)

 Based on the immunologic response to the fungus:

• Hyperergic (macules and gumma)
• Hypoergic (keloid-like, verrucous)
COMPLICATIONs

 SCC in chronic cases

 Functional disability due to progressive disease
INVESTIGATIONS

1) KOH MOUNT
 The surface of a lesion is scraped with a scalpel blade onto a glass slide and
examined with KOH solution

2) EXFOLIATIVE CYTOLOGY
 Scrapings from the surface of a lesion are examined under a microscope
3) VINYL ADHESIVE TAPE TECHNIQUE
 Adhesive tape is applied to scaly or scale-crusted areas of the skin, and gentle
pressure is given
 The tape is removed and placed (glue side down) on a glass slide on which KOH
has already been placed
 L. loboi detected through these techniques appears as multiple round and oval
yeast-like bodies with regular size
 6-12 μm in size, with thick walls and a birefringent membrane
 May be connected by small bridges, forming chains with catenular or rosary
beads distribution
3) HPE OF SKIN BIOPSY
 Dense dermal histiocytic infiltrate, with round yeast-like cells (6–12 μm) having a
birefringent membrane and thick wall containing melanin
 Individual fungal cells may be connected by short tubular projections forming 2–10
cell chains
 Silver stain or PAS stains the fungi in the dermis and confirms the diagnosis
TREATMENT

 Localized disease- surgical excision

 Combination therapy: Oral itraconazole and cryosurgery; clofazimine 100 mg/day
and itraconazole 100 mg/day
 Posaconazole in severe cases
 Medical therapy often ineffective
REFERENCES

 IADVL Textbook of Dermatology 5th edition

 Rook’s Textbook of Dermatology 9th edition
THANK YOU