SUBCUTANEOUS AND FUNGAL INFECTIONS

SUBCUTANEOUS MYCOSES
Dr. Ajeet Singh

Basic biology
• Fungi - all the typical eukaryotic features
• Organization of genetic material into chromosomes enclosed
within a membrane‐bound nucleus, mitochondria and
ribosomes.
• Rigid cell wall.
• Absorptive mode of nutrition.
• Within the cell wall, the cytoplasm is bounded by a plasma
membrane in which the predominant sterol is ERGOSTEROL.

Reproduction
• Both sexually and asexually, sometimes simultaneously.
• Sexual phase - Teleomorph
• Asexual phase - Anamorph
• Both are present - Holomorph.
• ‘One Fungus = One Name’ initiative

SUBCUTANEOUS MYCOSES
Sporadically occurring infections caused by fungi directly
inoculated into the dermis or subcutaneous tissue through a
penetrating injury.
• Seldom common even in endemic areas.
• Mainly seen in the tropics
• Long incubation periods.

SUBCUTANEOUS MYCOSES CAUSATIVE AGENT
Sporotrichosis Sporothris complex
Chromoblastomycosis Fonsecaea, Phialophora, Cladosporium
Phaeohyphomycosis Cladosporium, Exophiala, Wangiella,
Bipolaris, Exserohilum, Curvularia
Eumycetoma Genera Madurella, Acremonium,
Scedosporium
Lobomycosis Lacazia loboi
Subcutaneous zygomycosis
(entomophthoromycosis)
Basidiobolus ranarum
Conidiobolus coronatus

SPOROTRICHOSIS
DEFINITION
• Acute or chronic fungal infection caused by Sporothrix
schenckii and closely related species.
• Cutaneous and systemic forms.
• ETIOLOGY :
S. schenckii, S. braziliensis , S. mexicana , S. globosa and
S. lurei.

EPIDEMIOLOGY
Mainly seen in the tropics and subtropics.
Particularly prominent in the mining areas.
High humidity and temperatures between
16 and 22°C

PATHOPHYSIOLOGY
• Fungus enters skin by trauma.
• Not contagious.
• Systemic sporotrichosis – Rare
• Portal of entry - Lungs in these cases.
• Incubation period : 8–30 days
• Presentation & clinical course depends on:
underlying host immunity
size & virulence & thermotolerance of inoculum.

PATHOLOGY
• Sporothrix schenckii - localized in the subcutaneous tissue.
• Spread locally in the subcutaneous lymphatics.
• Widely disseminated in bloodstream after pulmonary infection.
• Mixed granulomatous reaction with neutrophil foci.
• Small (3–5 μm) cigar‐shaped or oval yeasts.
• Surrounded by a thick, radiate, eosinophilic substance that forms the
distinctive asteroid bodies. SPLENDORE HOEPPLI PHENOMENON

ASTEROID BODIESSPLENDORE HOEPPLI
PHENOMENON

CLINICAL FEATURES
Disease starts as a single papule that
appears at site of injury months after
inoculation. It can become ulcerated
with discharge of purulent fluid.
Sporotrichoid pattern – appearance of
several dermal and subcutaneous
nodules & ulcers along lymphatics.
• Enlargement of regional lymph
nodes.
• Most common variety (70 – 80%
cases of cutaneous sporotrichosis).

Fixed pattern – less common
• Disease remains localized at point
of inoculation.
• Lesions may be acneiform,
nodular, ulcerated, verrucous.
Multifacial or disseminated
cutaneous sporotrichosis :
• > 3 lesions involving 2 different
anatomical sites
• Due to multiple traumatic
implantation of fingers.
FIXED SPOROTRICHOSIS

Systemic forms : Less common
Lungs, joints, skin & meninges
Pulmonary disease - cough, fever, weight
loss, cavitation, lymphadenopathy
Immunocompromised patients
Osteoarticular sporotrichosis – Most
common systemic manifestation
Tenosynovitis, joint effusion, & bursitis.

DIFFERENTIAL DIAGNOSIS
• Atypical mycobacterial infections
• Nocardiosis
• Leishmaniasis
• Tuberculosis
• Cat scratch disease
• Tularemia
• Anthrax
• Glanders
• Bacterial infections caused by S. aureus, Strep pyogens.
• Non infectious cause : Lymphoma, Langerhans cell histiocytes.

INVESTIGATIONS
 Direct smear examaination
 FNAC - Epithelioid cells granulomas, asteroid bodies & yeast
cells.
 HPE examination : concentric zones in nodules -
1. Central necrotic zone
2. Middle tuberculoid zone
3. Syphiloid zone
 Culture
 Intradermal tests
 Serology
 Detection by PCR

CULTURE
• Colonies - leathery, moist & whitish with
wrinkled surface.
• Later become brown or black.
• Microscopy : slender (2 μm) hyphae
• Small, oval to pyriform, hyaline conidia in
palmate or flower‐like arrangement.
• Pigmentation se – addition of thiamine.
• Physiological tests: Conversion to yeast
phase, best achieved on BHIA.
• Yeasts - Oval or cigar‐shaped.

TREATMENT
First line
• Itraconazole 100–200 mg/day until clinical recovery (at
least 3 months)
Or
• Terbinafine 250 mg/day until clinical recovery (at least
3 months)
Second line
• Potassium iodide at an initial dose of 5 drops daily of saturated
solution increasing slowly to 4–6 mL daily.
Should be continued for 3 – 4 weeks after clinical cure.

Healed lesions at 12 weeks of treatment

Systemic cases - Intravenous Amphotericin B.
Other treatment options –
Thermotherpy :
• Hyperthermia directly damages pathogens & also enhances
killing capacity of neutrophils.
• Daily application of coal heat (42 - 43ׄc) to lesion.

Mycetoma – Derived from Greek word “fungal tumor”
DEFINITION –
• Localized chronic infection caused by various species of fungi
or actinomycetes.
• Formation of aggregates of the causative organisms (grains)
within abscesses.
• Severe damage to the skin, subcutaneous tissues & bones of
the feet, hands and other parts of the body.
• Grains are discharged to the surface through draining sinuses.

EPIDEMIOLOGY
• Tropical and subtropical climates
• Agricultural workers.
• Actinomycetomas – endemic in central & south america
• Eumycetoma – endemic in Africa
• World wide, M. C. organism - Madurella mycetomatis
• M. C. in central america - Actinomycetomas caused by Nocardia.
• Streptomyces somaliensis - Sudan and Middle East

PATHOPHYSIOLOGY
Critical to the survival - Cell clusters or grains (SCLEROTIA).
Protective mechanisms to evade host immunity :
• Morphology of the grains :
Protective matrix in actinomycetes .
Cell wall thickening in fungi due to intrahyphal
growth.
• Deposition of melanin in the cell wall and as a surrounding
matrix & which also binds to antifungal elements.

Clinical Presentation
The characteristic clinical triad for mycetoma :
1. Swollen tissue
2. Draining sinuses
3. Identification of grains from discharge.
• Initially, feeling of pain or discomfort at the site.
• Inoculation f/b development of a painless subcutaneous nodule.
• Nodule - round and firm, or soft, lobulated or, cystic.
• Nodule increases in size, secondary nodules & papules may develop
with accompanying sinuses that drain serous, serosanguineous, or
purulent discharge.

BLACK GRAINS OF EUMYCETOMA WITH
ULCERATION OVER SOLE
SWELLING OVER DORSUM OF FOOT
WITH MULTIPLE SINUSES

• Overlying skin- shiny with local hyperhidrosis & is usually
hyperpigmented.
• Abscesses occur under the surface of the skin.
• Lesions extend into bony tissue, with disease progression causing
small cavities (2–10mm) to develop.
• If untreated, bony involvement can be extensive and devastating,
leading to complete bone destruction.
• Local lymphadenopathy is common .
• Chronic infection - Disability, distortion and deformity.

Erosive X‐ray changes in a mycetoma

• Soft tissue tumors such as lipoma, fibroma, fibrolipoma,
sarcoma
• Malignant melanoma
• Chronic osteomyelitis
• Tuberculosis
• Kaposi sarcoma
• Other subcutaneous mycoses such as sporotrichosis and
chromoblastomycosis

Investigations
• Microscopic examination of grains
Fungal mycelia – broader filaments (2-6 μm)
Actinomycotic grains – narrow filaments (0.5-1.0 μm)
• Biopsy - Use of a variety of stains, including PAS, or GMS, allows
visualization of grains and fungal and actinomycete filaments.
• Cytology (FNAC)
• Imaging :
Ultrasound
Magnetic resonance imaging
Computed tomography

Management
Combined medical & surgical treatment in Eumycetoma.
Medical treatment : Azoles
• Ketoconazole - 400 mg/day for 9-12 months or longer.
• Posaconazole - 200 mg orally 4 times daily for fungal infections
refractory to other antifungals.
Surgery
• Localized lesions that can be excised without residual disability
are best so treated.
• Amputation of affected limb if there is bony involvement not
responding to continual long-term conservative treatment.

CHROMOBLASTOMYCOSIS
Chronic fungal infection of the skin and subcutaneous
tissues caused by pigmented fungi, which produce thick‐walled
single or multicelled clusters (sclerotic or muriform bodies or
copper penny bodies).
Slow‐growing exophytic lesions, usually on the feet and legs.

Epidemiology
• Found in the tropics.
• Areas with medium to high rainfall.
• Adult male agricultural workers are most often affected.
Causative organisms
Fonsecaea pedrosoi (M. C.)
Phialophora verrucosa
Fonsecaea compacta
Cladophialophora carrionii

Pathophysiology
• Causative fungi - wood and soil
• Trauma, such as puncture from a splinter of wood.
Histopathology
• Foreign‐body granuloma, with isolated areas of microabscess formation.
• Groups of fungal cells seen within giant cells.
• Cells are chestnut or golden brown in colour.
• Characteristically divided in several planes of division by thick septa & are
termed muriform or sclerotic cells.
• Marked pseudoepitheliomatous hyperplasia in the epidermis
• Apparent transepidermal elimination of fungal cells
• Tissue between the granulomatous nodules shows chronic fibrosis.

COPPER PENNY BODIESGIANT CELL CONTAINING MURIFORM CELLS

Clinical features
History
• Lesions usually found on exposed sites,
particularly the feet, legs, arms, face and
neck.
• Disease develops over years rather than
over a shorter period.
Presentation
• Verrucous or hyperkeratotic slow growing
plaques sometimes showing atrophy/
scaling.
• Brown sclerotic bodies visible over surface
of plaques as black dots.
• Hypertrophy with nodules & cauliflower
like growth present in some lesions.

Plaque‐type chromoblastomycosisEarly lesion of chromoblastomycosis

• Secondary ulceration may occur.
• Lesion is usually painless unless the presence of secondary
infection causes itching and pain.
• Satellite lesions - By scratching.
• Secondary infection may lead to lymphatic stasis and
elephantiasis.
• Squamous cell carcinoma - Long standing cases.
Clinical variants
• Psoriasiform lesions in some infections
• Hematogenous spread (rare)
• Brain abscesses

Differential diagnosis
• Blastomycosis (by the absence of a sharp border
containing minute abscesses)
• Cutaneous tuberculosis
• Leishmaniasis
• Syphilis
• Yaws

Investigations
• Skin scrapings from superficial black dots :
Sclerotic bodies.
Hyperpigmented fungi.
• Biopsy – Granulomatous reactions.
• Fungal culture - Colonies of all species are dark grey‐green to black
and velvety or downy, with a black reverse.
Types of conidia on fungal culture :
1. Phialophora verrucosa – flask‐shaped phialides.
2. Fonsecaea pedrosoi – sympodial.
3. Cladophialophora carrionii - acropetal budding.

PHIALOPHORA VERRUCOSA FONSECAEA PEDROSI CLOPHIALOPHORA CARRIONII

Treatment
• Itraconazole 100–200 mg daily until clinical recovery
• Itraconazole pulse therapy – Itraconazole 400 mg daily for
one week per month for total of 7 pulses.
• Terbinafine 250 mg daily until clinical recovery.
• Potassium iodide therapy
• Heat application
• Cryotherapy

PHAEOHYPHOMYCOSIS
DEFINITION
Localized, subcutaneous or intramuscular infection, usually a
cyst or abscess caused by a range of brown‐pigmented
(dematiaceous) fungi.
EPIDEMIOLOGY
Most often in tropical areas.
Immunocompromised patients (on steroid therapy).

CAUSATIVE AGENTS
Exophiala jeanselmei (most common)
Exophiala dermatitidis
Cladophialophora bantiana (m. c. a/w
CNS disease)
Phialophora
Bipolaris
Exserohilum
Alternaria

Pathology
• Fungi found in a subcutaneous
inflammatory cyst.
• Cyst has well‐organized wall with
surrounding fibrosis & a mixed
cellular infiltrate.
• Fungi are usually found in the
inner aspect of the cyst.
• Pigmented in vivo & specific
fungal stains such as PAS are used.
H & E stain showing septate hyphae

CLINICAL FEATURES
• Well‐defined single cystic lesions
on the trunk or limbs.
• Not painful but unsightly
• Can grow large enough to
warrant removal.
• Most Common location – feet,
fingers, knee, toes, ankles,
legs & forearms.

CLASSIFICATION OF PHAEOHYPHOMYCOSIS
• Lipomas
• Epidermal cyst
• Foreign body granulomas
Superficial: Black piedra & tinea nigra
Cutaneous: Dermatophytosis & onychomycosis
Mycotic keratitis
Subcutaneous or phaeohyphomycotic cyst
Invasive, systemic & cerebral type

Investigations
1. KOH Mount – pigmented yeasts, pseudohyphae & hyphae.
2. Histopathological examination
3. Culture
Exophiala jeanselmei - ‘black yeasts’. Colony: initially moist, & black.
Later: filamentous with a grey velvety mycelium.
Microscopy: septate hyphae with elliptical conidia
Bipolaris species - Colony: Pale grey, later becomes olive grey or black.
Microscopy: Sympodial conidiogenous cells.

Exophiala jeanselmei on SDA after incubation for
3 weeks at 30ᵒc. Heaped up, folded appearance.
Microscopy: septate hyphae with typical
accumulation of ellipsoidal annelloconidia
around the top

MANAGEMENT
1. Surgical excision.
2. Oral antifungals –
• Itraconazole 200 mg/day
• Ketoconazole 200 mg/day
• Flucystine 150 mg/kg/day
• Best response – Itraconazole, Voriconazole f/b Amphotericin B.
• Combination therapy – refractory cases
• Synergy between - Amphotericin B & Flucystine
Itraconazole & Flucystine

LOBOMYCOSIS
Definition
• Chronic subcutaneous fungal infection caused by Lacazia
loboi
• Localised keloidal skin lesions.
Pathogenesis
• Causative agent associated with water and gain entry
through a wound.
• Spreads via autoinoculation.

CLINICAL FEATURES
• Keloidal skin lesions on exposed parts
of body i.e. distal extremities, face.
• Plaques enlarge to form multinodular
plaques with smooth or verrucous
surface. Ulceration can occur.
• No lymphadenpathy.
Differential diagnosis
• Chromoblastomycosis
Complications
• Squamous cell carcinoma
Isolated & confluent papules,
plaques & nodules over left leg

Investigations
1. KOH Mount of epidermal crust.
2. HPE -
• Diffuse infiltrate of lymphocytes,
monocytes, & giant cells.
• Fungal cells : 5–10 μm in diameter.
• Characteristic morphology - Aligned in
short chains of 3–8 oval or round cells
all joined by short tubular structures
“BRASS KNUCKLES ”
Treatment
Surgical excision is treatment of choice.
Gomori-Grocott stain highlighting the
bridging connections between the cells

SUBCUTANEOUS MYCOSIS DUE TO
BASIDIOBOLUS AND CONIDIOBOLUS
Definition
• Localized, subcutaneous and predominantly tropical
mycosis characterized by chronic, woody swelling of
subcutaneous tissue.
ETIOLOGY
• Conidiobolus coronatus
• Conidiobolus incongruus
• Basidiobolus ranarum

PATHOGENESIS
Both causative fungi B. ranarum and C. coronatus a/w decaying vegetation
and the gastro‐intestinal tracts of frogs.
BASIDIOBOLOMYCOSIS - Affects LIMB GIRDLE REGION & buttocks in childen.
Portal of entry – skin after insect bites, scratch & minor cuts.
Previous subclinical infection provides immunity.
CONIDIOBOLOMYCOSIS - Affects RHINOFACIAL REGION in adult males
Causes edema & infiltration of centralfacial tissue
Infection occurs by traumatic implantation or inhalation.

CLINICAL FEATURES
BASIDIOBOLOMYCOSIS
• Single, painless, slowly spreading,
subcutaneous swelling.
• Single or multiple satellite lesions.
• Uniform hard consistency & do not
pit on pressure.
• Smooth rounded edge can be
raised up by inserting the fingers
underneath it.
• Overlying skin - Tense, edematous,
bluish or purple colour at active
growing region.
WOODY HARD SWELLING OVER LEFT
GLUTEAL REGION

CONIDIOBOLOMYCOSIS
• Subcutaneous inflammation of
submucosa in central facial
region.
• Starts from inferior turbinates.
• Nasal obstruction f/b infiltration
& thickening of skin over nose.
• Subsequently deformity occurs.
ERYTHEMATOUS SWELLING OVER LOWER HALF
OF FACE

Basidiobolomycosis
• Lymphatic edema
• Subcutaneous malignant lymphoma
Conidiobolomycosis
• Sarcoidosis
• Rhinosporidiosis
• Benign & malignanat tumors of nasal cavity

INVESTIGATIONS
1. KOH mount – hyaline, wide, thin walled aseptate hyphae
2. Histopathological examination
• Granulomatous infiltration mixed cellularity.
• Fungal structures (4-10 μm) surrounded by a thick eosinophilic
sheath called splendore hoeppli phenomenon
3. Culture
B. Ranarum – waxy cream or yellow colonies with radial folds
Microscopy – broad sparsely septate hyphae 8-20 μm diameter.
C. coronatus – waxy white to grey & become powdery.
Microscopy – wide, sparsely septate hyphae.

Broad aseptate hyphae with scanty cytoplasm Multinucleated giant cells with well defined
tubular structures inside them

TREATMENT
1. Itraconazole 300 mg/day.
2. Potassium iodide therapy.
3. Cotrimoxazole shown to be effective in
conidiobolomycosis.

POTASSIUM IODIDE
• “saturated solution of potassium iodide“ – 1 g of KI/ml of sol.
• Each drop of SSKI is assumed to contain about 50 mg iodine
as iodide.
• To prepare SSKI, KI is added to hot purified water, using
sodium thiosulphate as a preservative.
• This process results in a final conc. of KI of about 1 g KI/ml of
saturated KI solution.
• SSKI should be stored in tight, light-resistant containers at a
temperature of 15–30°C.
• Color of KI solution in water is bright yellow.

• Suppresses the ability of the neutrophils to generate the ROIs in vitro.
• Activation of macrophages by iodine responsible for the healing effect.
INDICATIONS
1. Sporothrix
Adults - initially, 250 mg (approx. 5 drops of a 1g/ml solution) thrice a day.
Gradually the dosage is increased to a max. of 2-2.5 g (approx. 40-50
drops) thrice daily for 6-10 weeks.
Children - max. of 1.25-2 g (approximately 25-50 drops) thrice a day.
2. Other varieties of subcutaneous mycosis
3. Panniculitis
4. Neutrophilic dermatoses
5. Wegener’s granulomatosis

SIDE EFFECTS
1. Common side effects - stomach upset, diarrhea, nausea, vomiting,
stomach pain.
2. Iodism:- Iodism may occur following long - term therapy or
with the use of high dosages.
3. Pulmonary edema
4. Hypersensitivity reactions:- Angioedema, cutaneous and mucosal
hemorrhage, signs & symptoms resembling serum sickness.
5. Cutaneous side effects:-
a) Acneiform eruption
b) Iododermas .
c) Aggravation of dermatitis herpetiformis.

CONTRAINDICATIONS
• Known hypersensitivity to KI.
• Hypocomplementemic vasculitis.
• Dermatitis herpetiformis.
• Nodular thyroid diseases (e.g, multinodular goiter)
• Active tuberculosis
DRUG INTERACTIONS
 ACE inhibitors:- Hyperkalemias, cardiac arrhythmias, cardiac arrest.
 Antithyroid drugs:- Potentiation of goitrogenic effects.
 K sparing diuretics:- Hyperkalemia, cardiac arrhythmias.
 Lithium:- Synergistic hypothyroid effects.

Fungal infections - involving deep structures
have propensity to disseminate, usually via the
bloodstream, from original focus of infection.
DIMORPHIC MYCOSES
• Coccidioidomycosis
• Blastomycosis
• Paracoccidioidomycosis
• Histoplasmosis
OPPORTUNISTIC MYCOSES
• Cryptococcosis
• Candidiasis
• Aspergillosis
• Pseudallescheriasis
• Mucormycosis
• Penicilliosis
• Fusariosis

DX APPROACH FOR SYSTEMIC MYCOSES
• Dimorphic fungi - Extremely hazardous to the lab worker.
• Must be handled in CONTAINMENT LEVEL 3 conditions.
• Laboratory must be alerted to the possibility of a dimorphic pathogen
• Serological tests
Valuable in endemic – Immunodiffusion test
Complement fixation test
For opportunistic - Ag & Fungal metabolite detection.

• Direct examination & HPE of samples - sputum, CSF, BAL.
• Culture - Incubation at 30 & 37 degree for 4-6 weeks.
• Isolation of dimorphic fungus - always significant.
• PCR

HISTOPLASMOSIS
• Definition- Highly infectious mycosis caused by Histoplasma
capsulatum and affecting primarily the lungs.
• Endemic in central and eastern states of U.S.
ASEXUAL
SPORES
Tuberculate macroconidia -
Thick walled & fingerlike
projections, important in
laboratory identification
Microconidia - Smaller,
thin, smooth walled spores
transmit infection

Macroconidia Rough-walled
Macroconidia and microconidia
HISTOPLASMA CAPSULATU

ETIOLOGY
• H. capsulatum var. capsulatum – Histoplasmosis (small-form
histoplasmosis) occuring throughout world.
• H. capsulatum var. duboisii – large form or African
Histoplasmosis.
• Grows in soil, heavily contaminated with bird droppings,
especially from starlings.
• Male agricultural workers.

PATHOGENESIS
• Inhaled spores - engulfed by macrophages & develop into yeast
forms.
• H. capsulatum - oval budding yeast inside macrophages.
• Produce alkaline substances, such as bicarbonate and
ammonia, that raise the pH inactivate the degradative
enzyme within the phagolysosome.
• Spread widely throughout the body
• Especially to liver & spleen.

PATHOGENESIS OF HISTOPLASMOSIS

CLINICAL FEATURES
• Skin lesion - H. duboisii > H. capsulatum
• Skin lesions - Papules, ulcers, nodules, granulomas, abscesses, fistulae, scars and
pigmentary changes may be seen.
ACUTE PULMONARY FORM Symptoms of acute infection of lung,
may be a/w EM or EN
Diffuse mottling on X-ray
ACUTE DISSEMINATED FORM Uncommon; seen in AIDS
Lung, cutaneous granuloma, painful
ulcer of mouth, nose , pharynx;
hepatospleenomegaly
CHRONIC PULMONARY Adults; resembles TB
CHRONIC DISSEMINATED FORM Appears after months to yr; oral
ulceration; adrenal insufficiency
PRIMARY CUTANEOUS FORM Very rare ; nodule or indurated ulcer

CUTANEOUS HISTOPLASMOSIS ORAL ULCERATION

• Talaromyces infections.
• Cryptococcosis.
• Molluscum contagiosum.
• Lung involvement can mimic tuberculosis.

INVESTIGATIONS
• Identification of Histoplasma - small intracellular yeast cells
(2–5 μm) in sputum, peripheral blood, bone marrow or in biopsy.
• Culture: At 25°C & 37°C
Growth – 4-6 weeks
Tuberculate microconidia – At 25°C.
White or tan cottony colonies.
• Histoplasmin skin test (epidemiological tool).
• Serology – CFT, IDT.
• PCR

Tiny yeasts, stained black with GMS,
largely intracellular
Typical budding yeasts

TREATMENT
• No therapy in asymptomatic or mild primary infections.
• With progressive lung lesions, oral itraconazole is beneficial.
• In disseminated disease:
1. Amphotericin B (0.5 – 1.0 mg/kg/day) is the
treatment of choice.
2. Maintenance therapy with itraconazole is required.
• In meningitis, fluconazole is often used.

BLASTOMYCOSIS
• Synonyms
• North American Blastomycosis
• Gilchrist’s disease
• DEFINITION - Chronic granulomatous and suppurative
mycosis caused by Blastomyces dermatitidis, affecting primarily
the lungs.
• Mode - inhalation of spores

INCUBATION PERIOD
Pulmonary blastomycosis – 30 to 40 days
Primary cutaneous blastomycosis – 14 days
HISTOLOGY
• Budding yeasts with broad base to the bud in the tissues.
• Marked epidermal hyperplasia.
• Intra & sub - epidermal polymorphonuclear abscesses.
• Granulomatous infiltrate in dermis.
• Giant cells of Langhans’ type - contain organisms with refractile walls.

Tissue sections showing
large, broad-base,
unipolar budding yeast-
like cells

• CLINICAL FEATURES
• Osteomyelitis – 30 % of cases
• Commonest site of infection – spine, ribs & long bones.
• Self limiting genital ulceration reported after venereal transmission in female.
Primary Cutaneous Blastomycosis Very rare ; After inoculation, an
erythematous, indurated area
with a chancre appears in 1–2
weeks with associated
lymphangitis and LAN
Pulmonary Blastomycosis Resembles TB
Disseminated Blastomycosis Commonly skin, bone, CNS
involvement; more in African type

Verrucous lesions of Blastomycosis
Annular hyperkeratotic lesions of
Blastomycosis

• Tuberculosis
• Syphilis
• Leprosy
• Pyoderma gangrenosum
• Drug reaction resulting from bromides and iodides
• Other systemic fungal infections

INVESTIGATIONS
• Direct microscopy – fungus
identification on KOH mount.
• Culture – Gold standard
Brown wrinkled yeast form at 37 ׄc.
Mycelial forms at 25 ׄc.
White fluffy colonies at SDA after
1-3 weeks.
• FNAC – 8-15 μm yeast cell with
refractile cell wall.
• Serological tests
• PCR
Fungal yeast form within giant cell

TREATMENT
Mild to moderate blastomycosis – Oral Itraconazole 10 mg/kg/day
max. upto 400 mg/day × 6 months
ideal serum levels > 500 μg/dl
Severe blastomycosis – AmphotericinB 0.7 - 1 mg/kg/day for 1-2 weeks
or until improvement noted.
Followed by Itraconazole 10 mg/kg/day.
During pregnancy – Azoles should be avoided
Amphotericin B recommended
Newborns – Amphotericin B (1 mg/kg daily) preferred

COCCIDIOIDOMYCOSIS
• Synonyms
• Coccidioidal granuloma
• Valley fever
• San Joaquin valley fever
• Desert rheumatism
• Definition - Respiratory fungal infection caused by Coccidioides
immitis and C. posadasii.
• May become progressive and disseminated, with severe forms.
• Spore inhalation
• Dissemination - Defective in cell-mediated immunity.

• INCUBATION PERIOD – 1-3 weeks for primary pulmonary or cutaneous
coccidioidomycosis.
• HISTOLOGY - In lung tissues, 30 to 80 μm large round spherule containing
endospores without budding.
PAS , silver staining.
• CLINICAL FEATURES -
Asymptomatic form
Primary pulmonary form Mimics influenza; EM/EN may occur in
3-7th week in 3-25%
Gen. macular erythematous rash in
10%
Primary cutaneous form Painless firm nodules, discharging
sinuses with regional LAN
Disseminated form Very uncommon < 0.5%

Discharging sinus in cutaneous
coccidioidomycosis

Microscopy - Characteristic thick-walled
arthroconidia, separated from each other
by alternate empty cells
Spherule containing endospores

TREATMENT
• No treatment is needed in asymptomatic or mild primary infection.
• Amphotericin B / Itraconazole - For persisting lung lesions or
disseminated disease.
• Ketoconazole - effective in lung disease.
• Fluconazole - Drug of choice for meningitis.
• Intrathecal Amphotericin B - induce remission, but long-term results
are often poor.
• New antifungals – Voriconazole & Caspofungin.

PARACOCCIDIOIDOMYCOSIS
• Synonyms
South American Blastomycosis.
Paracoccidioidal granuloma.
• Definition- Chronic granulomatous fungal infection caused by
Paracoccidioides brasiliensis, affecting the skin, mucous membranes,
lymph nodes and internal organs.
• Affects adult male 20-50 yr age.
• Saprophyte on vegetation or in soil.
• Mode - inhalation via the respiratory tract.

• Susceptibility to P. brasiliensis may be related to HLA‐A9.
• Histology - Granuloma and pyogenic inflammation.
Numerous giant cells upto 60 μm.
Multilateral buds in tissue – Diagnostic.
CLINICAL FEATURES -
Pulmonary form Most common
Mucocutaneous form Oral & circumoral lesions, may involve
nose; severe painful ulcerating
stomatitis-> becomes spread ->
mulberry like erosions.
Gum involvement , loosening of teeth.
Lymphatic form Palpable, painful, suppuration

multiple budding yeast
cell
Mucocutaneous lesions of
paracoccidioidomycosis

Multiple, narrow base, budding yeast cells
"steering wheels" of P. brasiliensis

OPPORTUNISTIC MYCOSES
• Candidiasis
• Aspergillosis
• Cryptococcosis
• Mucormycosis
• Penicilliosis

PENICILLIOSIS
• DEFINITION- Disseminated mycosis in both healthy &
immunocompromised patients caused by Penicillium marneffei .
• Strong association with AIDS.
• South east Asia.
CLINICAL FEATURES - Pulmonary symptoms.
Skin lesions in 50% cases.
Small papules, ulcers or molluscum like lesions.
Acneiform lesions widely scattered on face
and trunk.

• D/D - Histoplasmosis
Cryptococcosis
• Dx - forms characteristic cells
divided by septum in tissue.
• Colony – Glucose peptone agar
Green greyish mould with diffusible
pigment.
• Rx - Amphotericin B.

CRYPTOCOCCOSIS
• Definition- Acute, subacute or chronic infection caused by the
encapsulated yeast Cryptococcus neoformans.
• A.k.a Busse-Buschke’s Disease, Torulosis, European Blastomycosis.
• Marked predilection for the brain & meninges.
• Unique feature: Acidic mucopolysaccharide capsule.
• Source – soil, specially bird droppings (Starling).
• Agent - Cryptococcus neoformans var neoformans
Cryptococcus neoformans var gattii

HISTOLOGY - Encapsulated budding cells mixed with a network of
connective tissue.
• Specific capsule stain – Mucicarmine stain.
CLINICAL FEATURES – CNS manifestations; chronic meningitis
• Firm or cystic, slow-growing, subcutaneous, EN like swellings.
• Acneiform papules or pustules - widespread systemic infection, occur
around the nose and mouth.
• Punched out ulcer with rolled up margin.

Single nodular lesion of Cryptococcosis

• Direct microscopy - large (5–15 μm) budding cells with
characteristic capsules seen in CSF or pus in India ink or Nigrosin
mounts.
• Colony - soft, cream to pale brown and usually mucoid.
• TREATMENT- iv Amphotericin B with Flucytosine in non-AIDS
• Clear pigeon excreta
• In AIDS - Amphotericin B + Flucytosine for 7–14 days followed by
long-term oral maintenance with fluconazole 200–400 mg/day

ZYGOMYCOSIS
SYNONYMS
• Mucormycosis
• Phycomycosis
• Infect immunosuppressed people, causing mucormycosis.
CAUSATIVE AGENTS:
1. Mucor
2. Rhizopus
3. Cunninghamella
Mode of transmission : Inhalation

CLINICAL FEATURES –
• Rhino cerebral mucormycosis : Local tissue
necrosis , invade arterial walls &
penetrates the periorbital tissue & cranial
vault  Meningoencephalitis with or
without cerebral infarction.
• Lung involvement : Hemorrhagic
pneumonia
• Cutaneous mucormycosis
• LAB DIAGNOSIS - In Tissue specimen : Non
septate hyphae with branching at 90 ׄ angle
• Culture : SDA @ 37 ׄ C. Dense Hairy Colony.
TREATMENT - Amphotericin B
Woody hard tender swelling wih
ulceration

ASPERGILLOSIS
• Aspergillus fumigatus - Most Common
• Portal of entry – Inhalation of conidia.
• Major Risk factors:
1. Neutropenia.
2. Use of corticosteroids.
• Virulence Factors :
1. Adhesins.
2. Antioxidants (Melanin, Catalase, SOD).
3. Toxins (Aflatoxin -> Ca Liver).

CLINICAL FEATURES
1. Sinusitis, Aspergillus asthma.
2. Colonizing Aspergillosis (Aspergilloma) - Growth of fungus in pre
existing pulmonary cavity -> Fungal ball -> recurrent haemoptysis.
3. Invasive Aspergillosis - Immunosuppressed host, widespread
hematogenous spread involves heart valves, brain.
Necrotizing pneumonia (Target lesion).
DIAGNOSIS - Form fruiting bodies & hyaline septate hyphae ,
branching at acute angle (40 degree).

Septate hyphae branching at
acute angle

TREATMENT
• Allergic forms of aspergillosis:
ABPA & allergic Aspergillus sinusitis – Itraconazole.
• Invasive aspergillosis: Voriconazole.
• Other antifungal medications -
Lipid amphotericin formulations.
Posaconazole, Isavuconazole.
Caspofungin, and Micafungin.
• Surgery - severe cases of aspergillosis.

SUBCUTANEOUS AND FUNGAL INFECTIONS

SUBCUTANEOUS AND FUNGAL INFECTIONS

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