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DEEP CUTANEOUS MYCOSIS
Moderator - Dr. Naushin Aara Ma’am
Presenter - Dr. Monesh Dhakar
Mycosis :
• Divided into :
1. Superficial mycoses
2. Deep mycosis : Subcutaneous mycoses
Systemic mycoses
Subcutaneous mycoses :
• Also called as “Mycoses of implantation”
• Directly inoculated into the dermis or subcutaneous tissue through a penetrating
injury.
• Mainly seen in the tropics.
• The most common of these infections are :
i. Sporotrichosis
ii. Mycetoma
iii. Chromoblastomycosis
• Rarer infections are :
i. Phaeohyphomycosis
ii. Lobomycosis
iii. Rhinosporidiosis
iv. Subcutaneous zygomycosis
1) Sporotrichosis :
• This is an acute or chronic fungal infection caused by Sporothrix
schenckii.
• Dimorphic fungus-S. braziliensis , S. mexicana , S. globosa and S.
lurei
• There are both cutaneous and systemic forms of sporotrichosis.
EPIDEMIOLOGY
• Seen in Tropics and Subtropics.
• Grows on decaying vegetable matter, for example the timber in mines .
Source is probably the soil in the vicinity of the mines
• Occupationally exposed groups include workers using
straw as packing material, forestry workers, florists and
gardeners
• Sporotrichosis can occur at any age. Though rarely seen
in children.
• No gender predilection
• Different clinical variants seen in immunocompromised
patients and those with HIV/AIDS.
clinical presentation
• The disease is classified into :
a. Cutaneous/subcutaneous forms
1. Lymphocutaneous sporotrichosis : mc type
2. Fixed or localised variety
b. Extracutaneous forms
1. Pulmonary sporotrichosis
2. Disseminated sporotrichosis
• Cutaneous sporortichosis is not life threatening. Although it may resolve
spontaneously, chronic and persistent cases lasting for over 5 years are
well known.
• Incubation period = 8 to 30 days.
A) Lymphatic form :
• Common in upper extremity and is known as
lymphangitic sporotrichosis.
• Starts as a Nodule or pustule
small ulcer
• Untreated, follows a chronic course, which is
characterized by involvement of the lymphatics from the
draining area; a chain of lymphatic nodules develops
connected by tender lympahatic cords.
• The primary lesion may heal spontaneously leaving the
lymphatic nodes enlarged. The general health of the
patient may not be affected.
B) The fixed variety, where the pathogen remains more or less
localized at the point of inoculation, is less common.
• In highly endemic areas, the population is sensitized and
primary infection is restricted to the site of injury.
1. acneform,
2. nodular,
3. Ulcerated(An ulcer may be gummatous or may simulate an
epithelioma)
4. verrucous;
5. infiltrated plaques or red scaly patches.
C) Atypical varieties such as mycetoma‐like or cellulitic forms may
occur.
2) Systemic form probably follows inhalation, and presents either with
local pulmonary disease or widely disseminated (joints, meninges and
skin.)
DIAGNOSIS
• In Sporothrix infections there are seldom large numbers of
organisms visible in tissue samples or smears.
• Fluorescent antibody techniques for serological detection .
• Culture : common agar medium
• Microscopy: the slender (2 μm) hyphae bear small, oval to
pyriform, hyaline conidia produced along the sides of the
hyphae.
Histopathology :
• The fungus provokes a mixed granulomatous
reaction with neutrophil foci.
• The fungus is present in the tissue, usually in the
form of small (3–5 μm) cigar‐shaped or oval yeasts,
and these may, on occasion, may be surrounded by
a thick,radiate, eosinophilic substance that forms
the distinctive asteroid bodies ( Splendore Hoeppli
Phenomenon).
• Differential diagnosis
 mycobacterial infection
(marinum-fish tank granuloma)
 leishmaniasis
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
2) Mycetoma :
• Localized chronic infection caused by various species of fungi or
actinomycetes .
• Characterized by the formation of aggregates of the causative
organisms (grains) within abscesses.
• Severe damage to skin, subcutaneous tissues and bones.
• Grains are discharged to the surface through draining sinuses.
Etiology
• Caused by fungi (eumycetoma) and aerobic actinomycetes
(actinomycetoma), saprophytes in soil or on plant
• implanted subcutaneously, usually after a penetrating injury .
• Largely confined to tropical and subtropical climates, usually
among agricultural workers.
• Adult males are most often infected(3:1 male to female ratio) :
20 – 50 yrs
• Presence of different coloured grains, which represent
microcolonies of the organisms.
• Actinomycetomas due to Nocardia sp. are most common in
Central America and Mexico.
• In India, 65% of cases are due to Actinomycetoma and the rest
are mainly due to fungus Madurella mycetomatis.
ETIOLOGICAL AGENTS
Fungi – dark grain Fungi – light grain Actinomycetes
Madurella mycetomatis Scedosporium
apiospermum
Actinomadura madurae
Madurella grisea Neotestudina rosatti Actinomadura pelletieri
Leptosphaeria senegalensis Sarocladium spp Streptomyces somaliensis
Cochliobolus lunata Fusarium spp Nocardia brasiliensis
Nocardia otitidis-caviarium
Nocardia asteroides
clinical features
• Essentially the same no matter which fungus or
actinomycete is concerned
• most lesions are on the foot and lower leg, may occur
anywhere on body.
• Earliest stage is a firm, painless nodule but, with time,
papules, pustules which break down to form draining
sinuses
• Extension to underlying bones and joints gives rise to
periostitis, osteomyelitis and arthritis. In advanced cases,
almost complete destruction of bone and gross deformity
may result.
• Multiple sinus tracts draining pus which may remain open
for months or may close and reopen
• Discharge may be purulent or seropurulent.
Eumycetoma Actinomycetoma
Fungal infection Bacterial infection
On microscopy: Fungal
mycelium with septate
hyphae 2-6 micron in
diameter.
Filamentous ,thin, branching
bacteria 0.5-1 micron in
diameter
PAS positive Gram positive bacteria
Slowly progressive with
delayed involvement of
bone.
Tends to progress more rapidly
with greater inflammation and
tissue destruction and earlier
invasion of bone.
X-ray shows multiple
punched out lytic lesions
Both osteolytic and
osteosclerotic lesions.
Diagnosis :
• A tentative diagnosis made on the basis of grain colour,
texture and direct microscopic appearance.
• Washing of the grain with saline containing antibacterials is
recommended prior to inoculation.
• KOH mount and gram stain should be performed on the
grains.
• HISTOPATHOLOGY :Chronic inflammatory reaction leading to
focal neutrophil abscess formation, with scattered giant cells
and fibrosis.
• Grains in the form of white, yellow, red or black granules are
found in the centre of the inflammatory response
• Slowly extends deeply into the underlying tissues, and invades
muscle and bones.
Distinct hyphal filaments, stained pink with PAS, are clearly visible in a
pale-grained eumycetoma
• Final identification requires the isolation of the causative
agent in culture or molecular diagnostic techniques .
• Differential diagnosis:
 Chronic osteomyelitis of bacterial or tuberculous
aetiology.
 Elephantiasis (there are no sinus tracts).
 Actinomycosis is also similar ( but usually develops
close to certain sites, such as the mouth or the
cecum, where the causative organisms are
sometimes commensals
Treatment :
• EUMYCETOMA : usually responds less well to drug therapy
and therefore combined approach of both medical and
surgical therapy are taken.
• Complete surgical excision followed by antifungals form the
1st line of management.
• Drugs used:
1. Itraconazole ( 400mg/day )
2. Ketoconazole 400-800 mg/day
3. Terbinafine 250-500mg/day)
4. Voriconazole (400mg/day)
5. Posaconazole (200-800mg/day)
• ACTINOMYCETOMA : Dapsone/Cotrimoxazole
+Streptomycin + Rifampicin
• In some patients radical surgery, usually amputation,
remains the only effective means of removing the
infection.
• Localized lesions that can be excised without residual
disability are best so treated.
3) Chromoblastomycosis :
• Synonyms: Chromomycosis , Verrucous dermatitis
• Chronic fungal infection of the skin and subcutaneous tissues
caused by pigmented fungi .
• Produce thick walled single or multicelled clusters (sclerotic or
muriform bodies) in tissue.
• Characterized by the production of slow growing exophytic
lesions, usually on the feet and legs.
• Most common : Phialophora verrucosa, Fonsecaea pedrosoi, F.
compacta and Cladophialophora carrionii
• Adult male agricultural workers are most often affected
Clinical features:
• Lesions are usually found on
exposed sites like feet, legs,
arms, face and neck.
• Warty papule slowly enlarges to
form a hypertrophic plaque
• Plaque is flat and expands slowly
with central scarring.
• Secondary ulceration may occur.
• Lesion is usually painless.
• Satellite lesions are produced by
scratching, and there may be
lymphatic spread to adjacent areas.
• Haematogenous spread is rare .
• Secondary infection after several
years may lead to lymphatic stasis
with the production of elephantiasis.
• Squamous carcinomas may develop in
chronic lesions.
Diagnosis
Histopathology
• In the organized granuloma, mainly
within foreign body giant cells, groups
of fungal cells may be seen.
• Cells are chestnut or golden brown in
colour.
• Cells are divided in several planes of
division by thick septa, termed
muriform or sclerotic cells.
• Marked pseudoepitheliomatous
hyperplasia in the epidermis .
• Transepidermal elimination of fungal
cells, which can be found in the
stratum corneum
• Tissue between the granulomatous
nodules shows chronic fibrosis.
Differential diagnosis:
1. Blastomycosis (by the absence of a sharp border containing
minute abscesses) and also the absence of pulmonary lesions
2. Cutaneous tuberculosis
3. Leishmaniasis
Treatment :
• The main treatment involves use of antifungal
chemotherapy.
• Itraconazole (100–200 mg daily) or terbinafine (250 mg daily)
is often successful
• Flucytosine used on its own or combined with amphotericin B
• Other approaches : cryotherapy or the local application of
heat, ideal for small lesions.
• The use of surgery is debatable; in larger plaques satellite
lesions may develop around the excision site.
• Surgery is really only indicated in very small lesions, and even
in these should be combined with chemotherapy.
4) Pheaohyphomycosis :
• Rare and generally localized, subcutaneous or
intramuscular infection,
• Usually a cyst or abscess caused by a range of
brown-pigmented (dematiaceous) fungi
• Major aetiological agents :
i. Exophiala jeanselmei
ii. Exophiala dermatitidis
iii. Cladophialophora bantiana
iv. Phialophora spp.
v. Bipolaris spp.
vi. Exserohilum spp.
vii. Alterna ria spp.
Clinical features :
• Patients present with well‐defined
single cystic lesions on the trunk or
limbs. These are not painful but are
unsightly and can grow large enough
to warrant removal, at which stage
the diagnosis is made.
• No tendency towards lymphatic spread,
and dissemination is exceedingly
uncommon
Diagnosis
HISTOPATHOLOGY :
• The fungi are found in a subcutaneous inflammatory
cyst. There is usually a well‐organized wall with
surrounding fibrosis and a mixed cellular infiltrate with
multinucleate giant cells, lymphocytes and
macrophages. Neutrophil infiltration also occurs.
• The fungi can be seen in the inflammatory lining of the
cyst wall.
• Haematoxylin and eosin sections - the brown colour
may be obvious
Culture
Treatment :
• Surgical excision is the best treatment .
• Drug of choice – saturated solution of potassium iodide (5drops tds-
gradually increased).
• Usually antifungals are given after excision .
5) Lobomycosis :
• Synonyms:
Keloidal blastomycosis
Lobo’s disease
• Rare disease
• Characterized by keloidal skin lesions
• Remain fairly well localized and apparently do not affect
the general health of the patient
• Causal fungus, which has never been isolated in culture, is
Lacazia loboi .
• It is thought that the agent might be associated with water
and gain entry through a wound.
Clinical features :
• Lesions may be found anywhere on
the body, but are usually on
exposed parts legs, arms and face.
• In most instances , associated with
injuries to the skin.
• Spread by autoinoculation following
injury.
• No marked lymphangitis and no
visceral dissemination.
• Old chronic lesions present as
elevated crusted.
Histopathology :
• There is diffuse infiltrate of lymphocytes, macrophages and giant
cells that contain fungal cells which are 5-10microns in diameter.
• Fungus occurs as chains of globose/oval cells 3-8 cells joined by
short tubular structures. (average 9-10 µm) in diameter
Differential diagnosis: chromoblastomycosis
Treatment:No effective medical therapy, where
possible lesions are excised surgically
6) Rhinosporidiosis :
• Chronic granulomatous mycosis
caused by Rhinosporidium seeberi
• Organism has never been isolated
in vitro.
• Endemic in India and Sri Lanka
• Clinical features :
• Vascular polyps, which may be pedunculated, occur on any
mucosal surface specifically nose, the nasopharynx or the soft
palate is involved in three-quarters of cases(larynx, penis, vagina,
rectum)
• Pink or red surface is lobulated and cauliflower-like .
• Close examination of the surface reveals small white spots,
which represent mature sporangia of the fungus.
• Disease may last for many years. Spontaneous resolution has
been observed rarely.
• Obstruction to breathing is usually the chief complaint
• If the eye is involved there is conjunctivitis and photophobia, and
the weight of the polyps may cause eversion of the lid
diagnosis :
• The causative organisms cannot be cultured
• Diagnosis depends on histopathology and recognition of the
sporangia seen on the surface of the polyp or in tissue sections.
• Depending on maturity, sporangia may attain diameters of 0.5
mm, and can be readily seen by the naked eye as firm white cysts
on or just below the surface.
• Microscopically, these are single, thick-walled and spherical, and
when fully differentiated are packed with numerous rounded
endospores, 6–7 μm in diameter.
Differential diagnosis :
Atypical lesions should be differentiated from warts,
condylomas and haemorrhoids.
Treatment :
Surgical removal resulting in complete eradication of the
disease is the treatment of choice
Subcutaneous zygomycosis
(Entomophthoramycosis)
• Subcutaneous zygomycosis is a chronic subcutaneous
infection characterised by woody swelling of the
subcutaneous tissue.
• The class Zygomycetes includes two fungal orders:
Mucorales and Entomophthorales.
• When the term zygomycosis alone is used, it usually
refers to mucormycosis, whereas the term subcutaneous
zygomycosis usually refers to infections by
Entomophthorales.
• Entomophthorales contains the
genera Basidiobolus and Conidiobolus.
Entomophthorales Mucorales
Host Usually infects
immunocompetent
hosts.
Predominantly infect
immunocompromised
hosts.
Distribution Tropical and subtropical
climates.
Throughout the world.
Mode of transmission Traumatic implantation Inhalation of spores
Systems involved Subcutaneous mycosis
and sinusitis
Pulmonary,
rhinocerebral,cutaneous
/subcutaneous,gastric
involvement
Histopathology Chronic inflammatory
response
Angioinvasion,
thrombosis, and tissue
necrosis
Splendore-Hoeppli
Phenomenon
Characteristic Rarely seen
Septation More common Less common
Dissemination Extremely uncommon Commonly seen and
fatal
• Infection due to Basidiobolus occurs mainly in
children (80% younger than 20 years.) with
male:female ratio of 3: 1.
• In Conidiobolomycosis, male: female ratio is 10:1 and
the disease is predominantly seen in young adults,
rare among children.
• Both types of entomophtharomycosis are seen most
commonly in Africa and to a lesser extent in India.
• In South India, subcutaneous zygomycosis is the 2nd
most common deep mysosis after mycetoma.
• Mode of transmission of Basidiobolus species is
mostly via minor trauma and insect bites.
• Mode of transmission of Conidiobolus is via inhalation
of fungal spores that get implanted in the nasal
mucosa or through minor trauma.
BASIDIOBOLOMYCOSIS CONIDIOBOLOMYCOSIS
Important species include
B.haptosporus and B.ranarum.
C.coronatus, C.incongruous.
Site: usually involves the limb
girdles. Most common site is on the
thighs and buttocks in a bathing suit
distribution.
Characteristically manifests as
painless, well-circumscribed, firm to
hard subcutaneous masses that
grow slowly at the periphery and
may envelop parts or whole limb.
Border is smooth,rounded, clearly
defined and can be raised by
inserting fingers underneath it which
is thought to be almost a diagnostic
feature.
Satellite lesions may develop..
Significant non pitting edema of the
limb can occur
Site: Usually begins as swelling of
the inferior nasal turbinates and
extents nearly to all nearby tissues.
Clinical classification includes 3
phases:
Phase 1 : Infection limited to the
nasal fossae, paranasal sinuses and
the pharynx.
Phase 2 : Infection spreads to frontal
region and the lips.
Phase 3 : Infection involves muscles,
bones and viscera.
Rarely involves gastrointestinal tract.
Histopathology :
• Eosinophilic granuloma lying deep in the subcutaneous tissue
and largely replacing fat.
• Wide, sparsely septate hyphae, branching at right angles, are
scattered throughout the granuloma
• The diagnosis is usually established histologically by biopsy
and culture.
Differential diagnosis :Lymphatic oedema, which lacks the
distinctive edge
 Subcutaneous malignant lymphoma, which grows more
rapidly
• Treatment :Itraconazole is useful in this condition.
• Lesions also usually respond to oral treatment with potassium
iodide
• Co-trimoxazole can be used in addition in conidiobolomycosis.
Systemic mycosis :
• Systemic mycoses are fungal infections that involve deep
structures, and that have the propensity to disseminate,
usually via the bloodstream, from the original focus of
infection.
• Two main groups of disease:
1. Endemic mycoses: eg- histoplasmosis (classic and African
types), blastomycosis, coccidioidomycosis,
paracoccidioidomycosis and infection caused by Talaromyces
(previously Penicillium) marneffei.
2. Opportunistic systemic mycoses: systemic infections that
only occur in patients with some underlying predisposition-
Cryptococcosis, systemic candidiasis, aspergillosis,
zygomycosis,and pneumocystosis.
 Cryptococcosis shares features of both
1) Histoplasmosis :
• Also called : Darling disease
• Highly infectious mycosis caused by Histoplasma
capsulatum affecting primarily the lungs, where it is
generally asymptomatic.
• The fungus is intracellular, parasitizing the
reticuloendothelial system and involving the spleen, liver,
kidney, central nervous system and other organs.
• Rarely, the disease may become chronic, progressive and
fatal.
• The disease caused by H. capsulatum var. capsulatum , referred to
here as histoplasmosis (small‐form histoplasmosis), is widely
distributed throughout the world, occurring in some 60 temperate
and tropical countries in the Americas, Africa and Australia.
• Infections with the H.duboisii form, known as African histoplasmosis
or large‐form histoplasmosis, have been reported only from
Africa.(skin lesions
• Infants and children are frequently infected.
• Infection rate in adults is highest in male agricultural workers.
• Lymphoma appears to favour the development of the infection . In
addition, histoplasmosis is an important complicating infection in
patients with AIDS.
• The fungus has been demonstrated in the soil of caves inhabited by
bats, and in endemic areas histoplasmosis is recognized as a hazard
to cave explorers.
Clinical features :
The four main clinical varieties of histoplasmosis are
• Acute pulmonary : has symptoms of acute infection of lungs
(erythema multiforme or erythema nodosum have been observed )
• Acute disseminated histoplasmosis: lung involvement is prominent.
there is widespread dissemination to other organs such as the
liver and spleen, lymphoreticular system, and bone marrow.
Patients present with progressive weight loss. This form is most
likely to occur in untreated AIDS patients.Indurated
granulomatous ulcers of the mouth, nose and larynx are present and
are distinctive.
• Chronic pulmonary : Resembles Pulmonary TB.
• Chronic disseminated endemic area: presents with oral ulceration
and Addison disease caused by adrenal infiltration.
• Primary cutaneous histoplasmosis: Rare.The primary lesion is a
nodule or indurated ulcer and there is often local lymphadenopathy)
Diagnosis :
• The diagnosis of histoplasmosis is established by identifying the
small intracellular yeast cells (2–5 μm) of Histoplasma in sputum,
peripheral blood, bone marrow or biopsy specimens.
• Histoplasma is predominantly an intracellular parasite, growing
within the cells of the reticuloendothelial system as an oval yeast
Differential diagnosis: 1)Talaromyces infections
2)cyrptococcosis
3)molluscum contagiosum
• All phagocytic cells of the reticuloendothelial system are
involved, including those in the liver, spleen, lymph nodes
and bone marrow, so that the cytoplasm is swollen with
masses of fungal cells.
• There is at first little tissue reaction; later, necrosis takes
place to be followed by granulomatous changes and
fibrosis.
• It often elicits an inflammatory response in which giant
cells predominate
• intracellular yeasts are clearly seen with specific fungal
stains such as methenamine silver and PAS.
• First line
• Itraconazole 100 mg daily until clinical remission
• For patients who are severely ill, amphoterocin B 0.5–1
mg/kg daily (or liposomal amphotericin B 3 mg/kg daily)
for 2 weeks. Itraconazole 200 mg once or twice daily may
then be used for a further period depending on clinical
response
• For mild disease, patients can be started straight on
itraconazole 200 mg daily for a period determined by
clinical response
• Second line
• Fluconazole 800 mg daily for 3 months and then 400 mg
daily until clinical remission is achieved
• There is insufficient evidence to recommend posaconazole
at present
2) Blastomycosis :
• Called as North American blastomycosis/ Gilchrist disease.
• Blastomycosis is a chronic granulomatous and suppurative mycosis
caused by Blastomyces dermatitidis .
• It affects primarily the lungs but disseminating forms also affect the
skin, bones, central nervous system and other sites.
• Adult males most commonly affected,majority being between the
ages of 30 and 50 years.
:
Clinical features
• There are three forms of blastomycosis:
1. Primary cutaneous: very rare and follows trauma to the
skin and introduction of the fungus.
• The condition has been seen mainly in laboratory
workers (e.g. pathologists carrying out autopsy
examinations) .
• After inoculation, an erythematous, indurated area with
a chancre appears in 1–2 weeks with associated
lymphangitis and lymphadenopathy
2. Pulmonary : This is very similar to pulmonary
tuberculosis.
• There may be no symptoms, or there may be low‐
grade fever, chest pain, cough and haemoptysis.
Occasionally, erythema nodosum develops.
• The disease, if untreated, may frequently disseminate
and often progresses to death.
3. Disseminated: symmetrical and usually on the trunk .
Each consists of a papule or nodule that may ulcerate
and discharge pus. The lesions enlarge at the
periphery, and tend to show central scarring.
• Eventually, after a relentless progress for months, the
lesion is serpiginous in outline, the borders are raised
and warty and have a violaceous margin studded
with miliary abscesses containing the organisms.
Diagnosis :
• Tissue sections must be scanned carefully to identify organisms
Blastomyces dermatitidis produces budding yeasts with a
characteristic broad base to the bud in the tissues.
• Intra and subepidermal polymorphonuclear abscesses and a
granulomatous infiltrate are found in the dermis. These include
giant cells of the Langhans type, which contain the round or
oval organisms with thick, refractile walls.
• Culture
• Microscopy: small, rounded or pear‐shaped conidia (2–5 μm)
are produced on short stalks arising at right angles from the
hyphae.
Treatment
• Itraconazole 200‐400 mg daily until clinical remission.
• For patients who are severely ill, amphoterocin B 0.5–1 mg/kg daily
for 2 weeks followed by itraconazole for a further period depending
on clinical response
3) Coccidioidomycosis :
• This is a (primary) respiratory fungal infection caused by
Coccidioides immitis and C. posadasii , which may become
progressive and disseminated, with severe or fatal forms.
• Also known as Coccidioidal granuloma/Valley fever/Desert
rheumatism
• Coccidioidomycosis is endemic in desert areas of the southwestern
states of the USA, and in parts of Central and South America
Clinical features:
• There is a higher risk of dissemination in pregnant women.
1. Primary Pulmonary form: most common form, can be
asymptomatic or may simulate influenza or occasionally
Pulmonary TB.Erythema multiforme and Erythema nodosum
seen in 3-25% of patients particularly females.
2. Disseminated coccidioidomycosis is very uncommon and
develops in fewer than 0.5% of infected individuals, usually in
black, Filipino or immunosuppressed patients.
• Disseminated lesions may occur in the skin, subcutaneous
tissues, bones, joints and all organs.
• The skin lesions may appear as abscesses, granulomas, ulcers or
discharging sinuses, particularly if there is underlying bone or
joint disease
• Diagnosis :
• The large (usually 30–80 μm, occasionally larger) globular spherules
with endospores may be seen in potassium hydroxide mounts of
sputum, cerebrospinal fluid or pus.
• Confirmation depends on the isolation of the fungus in culture.
• Colony: cultures of C. immitis and C. posadasii are mycelial, fast
growing, initially waxy then cottony, and white to tan .
• Microscopy: characteristic thick‐walled arthroconidia, separated
from each other by alternate empty cells, are observed.
Treatment :
• Oral itraconazole (200–400 mg daily) and fl uconazole (400–800 mg
daily) are effective in some forms of localized infection such as
solitary disseminated skin lesions- duration depends on clinical
response.
• Intravenous amphotericin B (0.5–1 mg/kg daily) or liposomal
amphotericin (3 mg/kg daily) is used for many of the other clinical
forms of coccidioidomycosis, including severe disease for periods of
between 2 and 4 weeks
4) Paracoccidioidomycosis :
• This is a chronic granulomatous fungal infection caused
by Paracoccidioides brasiliensis , affecting the
skin,mucous membranes,lymph nodes and internal
organs.
• Also called as South American blastomycosis
• It has been reported from most Latin American
countries, but the infection is most commonly found in
Brazil.
• Adult males between the ages of 20 and 50 years are most
frequently infected, although exposure rates are equal
across the two sexes.
Clinical features :
• The most common site of infection is the lung (pulmonary
form), although skin and mucous membranes
(mucocutaneous form) or lymph nodes (lymphatic form)
are also often involved.
• Patients with pulmonary lesions present with weight loss
and chronic cough.
• Mucocutaneous lesions may be present in patients with lung
disease, or can occur on their own. Oral and circumoral
lesions are common although may also occur in the nose,
conjunctiva and anus.
• Haematogenous or lymphatic spread results in
subcutaneous abscesses
Diagnosis :
• KOH mount from exudates and scrapings show rounded refractile
cells with the characteristic multiple budding seen.
• Culture
• Microscopy:
the hyaline, unicellular, pear shaped conidia (3–4 μm) are
borne directly on the hyphae or on short stalks.
• In histological sections
the reaction resembles that seen in blastomycosis,
namely granulomas with pyogenic inflammation. Giant cells are
conspicuous and these frequently contain the rounded budding cells.
Treatment :
• All forms require antifungal therapy.
• The treatment of choice in most cases is itraconazole 200–400 mg
daily, which can produce remission in 3–6 months.
• Some patients, particularly those with more rapidly progressive and
extensive infections, may require amphotericin B 0.5–1 mg/kg for 2
weeks followed by oral itraconazole 200 mg daily
5) Cryptococcosis :
• Cryptococcosis is an acute, subacute or chronic infection
caused by the encapsulated yeast Cryptococcus
neoformans .
• There is a marked predilection for the brain and
meninges, although the lungs and occasionally the skin
and other parts of the body may be involved.
• Associated with AIDS , lymphomas, malignancies,
collagen disease, systemic sterod therapy,
immunosuppression in patients after renal
transplant.
• Cryptococcosis is caused by C. neoformans and C.
gattii .
Clinical features
• Most common clinical manifestation of
disease is meningoencephalitis.
• Pulmonary infection can be found in about
10% of those with meningitis.
• Cutaneous lesions may develop in about 10%
of cases but are seldom pathognomonic.
diagnosis :
• The large (5–15 μm) budding cells with their characteristic
capsules are best observed by direct microscopy of
cerebrospinal fluid or pus in India ink or nigrosin mounts.
Treatment :
First line
• Amphotericin B 0.5–1 mg/kg daily for 4–6 weeks or
• Amphortericin B 0.2–1 mg daily (or liposmal amphotericinB
3 mg/kg daily) for 2 weeks
• Followed by fluconazoloe 400 mg daily for 4 weeks or until
remission
Second line
• Fluconazole 800 mg daily for 6–8 weeks
DEEP FUNGAL MYCOSIS_100307.pptx

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DEEP FUNGAL MYCOSIS_100307.pptx

  • 1. DEEP CUTANEOUS MYCOSIS Moderator - Dr. Naushin Aara Ma’am Presenter - Dr. Monesh Dhakar
  • 2. Mycosis : • Divided into : 1. Superficial mycoses 2. Deep mycosis : Subcutaneous mycoses Systemic mycoses
  • 3. Subcutaneous mycoses : • Also called as “Mycoses of implantation” • Directly inoculated into the dermis or subcutaneous tissue through a penetrating injury. • Mainly seen in the tropics. • The most common of these infections are : i. Sporotrichosis ii. Mycetoma iii. Chromoblastomycosis • Rarer infections are : i. Phaeohyphomycosis ii. Lobomycosis iii. Rhinosporidiosis iv. Subcutaneous zygomycosis
  • 4. 1) Sporotrichosis : • This is an acute or chronic fungal infection caused by Sporothrix schenckii. • Dimorphic fungus-S. braziliensis , S. mexicana , S. globosa and S. lurei • There are both cutaneous and systemic forms of sporotrichosis. EPIDEMIOLOGY • Seen in Tropics and Subtropics. • Grows on decaying vegetable matter, for example the timber in mines . Source is probably the soil in the vicinity of the mines
  • 5. • Occupationally exposed groups include workers using straw as packing material, forestry workers, florists and gardeners • Sporotrichosis can occur at any age. Though rarely seen in children. • No gender predilection • Different clinical variants seen in immunocompromised patients and those with HIV/AIDS.
  • 6. clinical presentation • The disease is classified into : a. Cutaneous/subcutaneous forms 1. Lymphocutaneous sporotrichosis : mc type 2. Fixed or localised variety b. Extracutaneous forms 1. Pulmonary sporotrichosis 2. Disseminated sporotrichosis • Cutaneous sporortichosis is not life threatening. Although it may resolve spontaneously, chronic and persistent cases lasting for over 5 years are well known. • Incubation period = 8 to 30 days.
  • 7. A) Lymphatic form : • Common in upper extremity and is known as lymphangitic sporotrichosis. • Starts as a Nodule or pustule small ulcer • Untreated, follows a chronic course, which is characterized by involvement of the lymphatics from the draining area; a chain of lymphatic nodules develops connected by tender lympahatic cords. • The primary lesion may heal spontaneously leaving the lymphatic nodes enlarged. The general health of the patient may not be affected.
  • 8. B) The fixed variety, where the pathogen remains more or less localized at the point of inoculation, is less common. • In highly endemic areas, the population is sensitized and primary infection is restricted to the site of injury. 1. acneform, 2. nodular, 3. Ulcerated(An ulcer may be gummatous or may simulate an epithelioma) 4. verrucous; 5. infiltrated plaques or red scaly patches. C) Atypical varieties such as mycetoma‐like or cellulitic forms may occur. 2) Systemic form probably follows inhalation, and presents either with local pulmonary disease or widely disseminated (joints, meninges and skin.)
  • 9. DIAGNOSIS • In Sporothrix infections there are seldom large numbers of organisms visible in tissue samples or smears. • Fluorescent antibody techniques for serological detection . • Culture : common agar medium • Microscopy: the slender (2 μm) hyphae bear small, oval to pyriform, hyaline conidia produced along the sides of the hyphae.
  • 10. Histopathology : • The fungus provokes a mixed granulomatous reaction with neutrophil foci. • The fungus is present in the tissue, usually in the form of small (3–5 μm) cigar‐shaped or oval yeasts, and these may, on occasion, may be surrounded by a thick,radiate, eosinophilic substance that forms the distinctive asteroid bodies ( Splendore Hoeppli Phenomenon). • Differential diagnosis  mycobacterial infection (marinum-fish tank granuloma)  leishmaniasis
  • 11. 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
  • 12. 2) Mycetoma : • Localized chronic infection caused by various species of fungi or actinomycetes . • Characterized by the formation of aggregates of the causative organisms (grains) within abscesses. • Severe damage to skin, subcutaneous tissues and bones. • Grains are discharged to the surface through draining sinuses. Etiology • Caused by fungi (eumycetoma) and aerobic actinomycetes (actinomycetoma), saprophytes in soil or on plant • implanted subcutaneously, usually after a penetrating injury .
  • 13. • Largely confined to tropical and subtropical climates, usually among agricultural workers. • Adult males are most often infected(3:1 male to female ratio) : 20 – 50 yrs • Presence of different coloured grains, which represent microcolonies of the organisms. • Actinomycetomas due to Nocardia sp. are most common in Central America and Mexico. • In India, 65% of cases are due to Actinomycetoma and the rest are mainly due to fungus Madurella mycetomatis.
  • 14. ETIOLOGICAL AGENTS Fungi – dark grain Fungi – light grain Actinomycetes Madurella mycetomatis Scedosporium apiospermum Actinomadura madurae Madurella grisea Neotestudina rosatti Actinomadura pelletieri Leptosphaeria senegalensis Sarocladium spp Streptomyces somaliensis Cochliobolus lunata Fusarium spp Nocardia brasiliensis Nocardia otitidis-caviarium Nocardia asteroides
  • 15. clinical features • Essentially the same no matter which fungus or actinomycete is concerned • most lesions are on the foot and lower leg, may occur anywhere on body. • Earliest stage is a firm, painless nodule but, with time, papules, pustules which break down to form draining sinuses • Extension to underlying bones and joints gives rise to periostitis, osteomyelitis and arthritis. In advanced cases, almost complete destruction of bone and gross deformity may result. • Multiple sinus tracts draining pus which may remain open for months or may close and reopen • Discharge may be purulent or seropurulent.
  • 16.
  • 17. Eumycetoma Actinomycetoma Fungal infection Bacterial infection On microscopy: Fungal mycelium with septate hyphae 2-6 micron in diameter. Filamentous ,thin, branching bacteria 0.5-1 micron in diameter PAS positive Gram positive bacteria Slowly progressive with delayed involvement of bone. Tends to progress more rapidly with greater inflammation and tissue destruction and earlier invasion of bone. X-ray shows multiple punched out lytic lesions Both osteolytic and osteosclerotic lesions.
  • 18. Diagnosis : • A tentative diagnosis made on the basis of grain colour, texture and direct microscopic appearance. • Washing of the grain with saline containing antibacterials is recommended prior to inoculation. • KOH mount and gram stain should be performed on the grains. • HISTOPATHOLOGY :Chronic inflammatory reaction leading to focal neutrophil abscess formation, with scattered giant cells and fibrosis. • Grains in the form of white, yellow, red or black granules are found in the centre of the inflammatory response • Slowly extends deeply into the underlying tissues, and invades muscle and bones.
  • 19. Distinct hyphal filaments, stained pink with PAS, are clearly visible in a pale-grained eumycetoma
  • 20. • Final identification requires the isolation of the causative agent in culture or molecular diagnostic techniques . • Differential diagnosis:  Chronic osteomyelitis of bacterial or tuberculous aetiology.  Elephantiasis (there are no sinus tracts).  Actinomycosis is also similar ( but usually develops close to certain sites, such as the mouth or the cecum, where the causative organisms are sometimes commensals
  • 21. Treatment : • EUMYCETOMA : usually responds less well to drug therapy and therefore combined approach of both medical and surgical therapy are taken. • Complete surgical excision followed by antifungals form the 1st line of management. • Drugs used: 1. Itraconazole ( 400mg/day ) 2. Ketoconazole 400-800 mg/day 3. Terbinafine 250-500mg/day) 4. Voriconazole (400mg/day) 5. Posaconazole (200-800mg/day)
  • 22. • ACTINOMYCETOMA : Dapsone/Cotrimoxazole +Streptomycin + Rifampicin • In some patients radical surgery, usually amputation, remains the only effective means of removing the infection. • Localized lesions that can be excised without residual disability are best so treated.
  • 23. 3) Chromoblastomycosis : • Synonyms: Chromomycosis , Verrucous dermatitis • Chronic fungal infection of the skin and subcutaneous tissues caused by pigmented fungi . • Produce thick walled single or multicelled clusters (sclerotic or muriform bodies) in tissue. • Characterized by the production of slow growing exophytic lesions, usually on the feet and legs. • Most common : Phialophora verrucosa, Fonsecaea pedrosoi, F. compacta and Cladophialophora carrionii • Adult male agricultural workers are most often affected
  • 24. Clinical features: • Lesions are usually found on exposed sites like feet, legs, arms, face and neck. • Warty papule slowly enlarges to form a hypertrophic plaque • Plaque is flat and expands slowly with central scarring. • Secondary ulceration may occur. • Lesion is usually painless.
  • 25. • Satellite lesions are produced by scratching, and there may be lymphatic spread to adjacent areas. • Haematogenous spread is rare . • Secondary infection after several years may lead to lymphatic stasis with the production of elephantiasis. • Squamous carcinomas may develop in chronic lesions.
  • 26. Diagnosis Histopathology • In the organized granuloma, mainly within foreign body giant cells, groups of fungal cells may be seen. • Cells are chestnut or golden brown in colour. • Cells are divided in several planes of division by thick septa, termed muriform or sclerotic cells. • Marked pseudoepitheliomatous hyperplasia in the epidermis . • Transepidermal elimination of fungal cells, which can be found in the stratum corneum • Tissue between the granulomatous nodules shows chronic fibrosis.
  • 27. Differential diagnosis: 1. Blastomycosis (by the absence of a sharp border containing minute abscesses) and also the absence of pulmonary lesions 2. Cutaneous tuberculosis 3. Leishmaniasis
  • 28. Treatment : • The main treatment involves use of antifungal chemotherapy. • Itraconazole (100–200 mg daily) or terbinafine (250 mg daily) is often successful • Flucytosine used on its own or combined with amphotericin B • Other approaches : cryotherapy or the local application of heat, ideal for small lesions. • The use of surgery is debatable; in larger plaques satellite lesions may develop around the excision site. • Surgery is really only indicated in very small lesions, and even in these should be combined with chemotherapy.
  • 29. 4) Pheaohyphomycosis : • Rare and generally localized, subcutaneous or intramuscular infection, • Usually a cyst or abscess caused by a range of brown-pigmented (dematiaceous) fungi • Major aetiological agents : i. Exophiala jeanselmei ii. Exophiala dermatitidis iii. Cladophialophora bantiana iv. Phialophora spp. v. Bipolaris spp. vi. Exserohilum spp. vii. Alterna ria spp.
  • 30. Clinical features : • Patients present with well‐defined single cystic lesions on the trunk or limbs. These are not painful but are unsightly and can grow large enough to warrant removal, at which stage the diagnosis is made. • No tendency towards lymphatic spread, and dissemination is exceedingly uncommon
  • 31. Diagnosis HISTOPATHOLOGY : • The fungi are found in a subcutaneous inflammatory cyst. There is usually a well‐organized wall with surrounding fibrosis and a mixed cellular infiltrate with multinucleate giant cells, lymphocytes and macrophages. Neutrophil infiltration also occurs. • The fungi can be seen in the inflammatory lining of the cyst wall. • Haematoxylin and eosin sections - the brown colour may be obvious Culture
  • 32. Treatment : • Surgical excision is the best treatment . • Drug of choice – saturated solution of potassium iodide (5drops tds- gradually increased). • Usually antifungals are given after excision .
  • 33. 5) Lobomycosis : • Synonyms: Keloidal blastomycosis Lobo’s disease • Rare disease • Characterized by keloidal skin lesions • Remain fairly well localized and apparently do not affect the general health of the patient • Causal fungus, which has never been isolated in culture, is Lacazia loboi . • It is thought that the agent might be associated with water and gain entry through a wound.
  • 34. Clinical features : • Lesions may be found anywhere on the body, but are usually on exposed parts legs, arms and face. • In most instances , associated with injuries to the skin. • Spread by autoinoculation following injury. • No marked lymphangitis and no visceral dissemination. • Old chronic lesions present as elevated crusted.
  • 35. Histopathology : • There is diffuse infiltrate of lymphocytes, macrophages and giant cells that contain fungal cells which are 5-10microns in diameter. • Fungus occurs as chains of globose/oval cells 3-8 cells joined by short tubular structures. (average 9-10 µm) in diameter Differential diagnosis: chromoblastomycosis Treatment:No effective medical therapy, where possible lesions are excised surgically
  • 36. 6) Rhinosporidiosis : • Chronic granulomatous mycosis caused by Rhinosporidium seeberi • Organism has never been isolated in vitro. • Endemic in India and Sri Lanka
  • 37. • Clinical features : • Vascular polyps, which may be pedunculated, occur on any mucosal surface specifically nose, the nasopharynx or the soft palate is involved in three-quarters of cases(larynx, penis, vagina, rectum) • Pink or red surface is lobulated and cauliflower-like . • Close examination of the surface reveals small white spots, which represent mature sporangia of the fungus. • Disease may last for many years. Spontaneous resolution has been observed rarely. • Obstruction to breathing is usually the chief complaint • If the eye is involved there is conjunctivitis and photophobia, and the weight of the polyps may cause eversion of the lid
  • 38. diagnosis : • The causative organisms cannot be cultured • Diagnosis depends on histopathology and recognition of the sporangia seen on the surface of the polyp or in tissue sections. • Depending on maturity, sporangia may attain diameters of 0.5 mm, and can be readily seen by the naked eye as firm white cysts on or just below the surface. • Microscopically, these are single, thick-walled and spherical, and when fully differentiated are packed with numerous rounded endospores, 6–7 μm in diameter.
  • 39. Differential diagnosis : Atypical lesions should be differentiated from warts, condylomas and haemorrhoids. Treatment : Surgical removal resulting in complete eradication of the disease is the treatment of choice
  • 40. Subcutaneous zygomycosis (Entomophthoramycosis) • Subcutaneous zygomycosis is a chronic subcutaneous infection characterised by woody swelling of the subcutaneous tissue. • The class Zygomycetes includes two fungal orders: Mucorales and Entomophthorales. • When the term zygomycosis alone is used, it usually refers to mucormycosis, whereas the term subcutaneous zygomycosis usually refers to infections by Entomophthorales. • Entomophthorales contains the genera Basidiobolus and Conidiobolus.
  • 41. Entomophthorales Mucorales Host Usually infects immunocompetent hosts. Predominantly infect immunocompromised hosts. Distribution Tropical and subtropical climates. Throughout the world. Mode of transmission Traumatic implantation Inhalation of spores Systems involved Subcutaneous mycosis and sinusitis Pulmonary, rhinocerebral,cutaneous /subcutaneous,gastric involvement Histopathology Chronic inflammatory response Angioinvasion, thrombosis, and tissue necrosis Splendore-Hoeppli Phenomenon Characteristic Rarely seen Septation More common Less common Dissemination Extremely uncommon Commonly seen and fatal
  • 42. • Infection due to Basidiobolus occurs mainly in children (80% younger than 20 years.) with male:female ratio of 3: 1. • In Conidiobolomycosis, male: female ratio is 10:1 and the disease is predominantly seen in young adults, rare among children. • Both types of entomophtharomycosis are seen most commonly in Africa and to a lesser extent in India. • In South India, subcutaneous zygomycosis is the 2nd most common deep mysosis after mycetoma. • Mode of transmission of Basidiobolus species is mostly via minor trauma and insect bites. • Mode of transmission of Conidiobolus is via inhalation of fungal spores that get implanted in the nasal mucosa or through minor trauma.
  • 43. BASIDIOBOLOMYCOSIS CONIDIOBOLOMYCOSIS Important species include B.haptosporus and B.ranarum. C.coronatus, C.incongruous. Site: usually involves the limb girdles. Most common site is on the thighs and buttocks in a bathing suit distribution. Characteristically manifests as painless, well-circumscribed, firm to hard subcutaneous masses that grow slowly at the periphery and may envelop parts or whole limb. Border is smooth,rounded, clearly defined and can be raised by inserting fingers underneath it which is thought to be almost a diagnostic feature. Satellite lesions may develop.. Significant non pitting edema of the limb can occur Site: Usually begins as swelling of the inferior nasal turbinates and extents nearly to all nearby tissues. Clinical classification includes 3 phases: Phase 1 : Infection limited to the nasal fossae, paranasal sinuses and the pharynx. Phase 2 : Infection spreads to frontal region and the lips. Phase 3 : Infection involves muscles, bones and viscera. Rarely involves gastrointestinal tract.
  • 44. Histopathology : • Eosinophilic granuloma lying deep in the subcutaneous tissue and largely replacing fat. • Wide, sparsely septate hyphae, branching at right angles, are scattered throughout the granuloma • The diagnosis is usually established histologically by biopsy and culture. Differential diagnosis :Lymphatic oedema, which lacks the distinctive edge  Subcutaneous malignant lymphoma, which grows more rapidly • Treatment :Itraconazole is useful in this condition. • Lesions also usually respond to oral treatment with potassium iodide • Co-trimoxazole can be used in addition in conidiobolomycosis.
  • 45. Systemic mycosis : • Systemic mycoses are fungal infections that involve deep structures, and that have the propensity to disseminate, usually via the bloodstream, from the original focus of infection. • Two main groups of disease: 1. Endemic mycoses: eg- histoplasmosis (classic and African types), blastomycosis, coccidioidomycosis, paracoccidioidomycosis and infection caused by Talaromyces (previously Penicillium) marneffei. 2. Opportunistic systemic mycoses: systemic infections that only occur in patients with some underlying predisposition- Cryptococcosis, systemic candidiasis, aspergillosis, zygomycosis,and pneumocystosis.  Cryptococcosis shares features of both
  • 46. 1) Histoplasmosis : • Also called : Darling disease • Highly infectious mycosis caused by Histoplasma capsulatum affecting primarily the lungs, where it is generally asymptomatic. • The fungus is intracellular, parasitizing the reticuloendothelial system and involving the spleen, liver, kidney, central nervous system and other organs. • Rarely, the disease may become chronic, progressive and fatal.
  • 47. • The disease caused by H. capsulatum var. capsulatum , referred to here as histoplasmosis (small‐form histoplasmosis), is widely distributed throughout the world, occurring in some 60 temperate and tropical countries in the Americas, Africa and Australia. • Infections with the H.duboisii form, known as African histoplasmosis or large‐form histoplasmosis, have been reported only from Africa.(skin lesions • Infants and children are frequently infected. • Infection rate in adults is highest in male agricultural workers.
  • 48. • Lymphoma appears to favour the development of the infection . In addition, histoplasmosis is an important complicating infection in patients with AIDS. • The fungus has been demonstrated in the soil of caves inhabited by bats, and in endemic areas histoplasmosis is recognized as a hazard to cave explorers. Clinical features : The four main clinical varieties of histoplasmosis are • Acute pulmonary : has symptoms of acute infection of lungs (erythema multiforme or erythema nodosum have been observed )
  • 49. • Acute disseminated histoplasmosis: lung involvement is prominent. there is widespread dissemination to other organs such as the liver and spleen, lymphoreticular system, and bone marrow. Patients present with progressive weight loss. This form is most likely to occur in untreated AIDS patients.Indurated granulomatous ulcers of the mouth, nose and larynx are present and are distinctive. • Chronic pulmonary : Resembles Pulmonary TB. • Chronic disseminated endemic area: presents with oral ulceration and Addison disease caused by adrenal infiltration. • Primary cutaneous histoplasmosis: Rare.The primary lesion is a nodule or indurated ulcer and there is often local lymphadenopathy)
  • 50. Diagnosis : • The diagnosis of histoplasmosis is established by identifying the small intracellular yeast cells (2–5 μm) of Histoplasma in sputum, peripheral blood, bone marrow or biopsy specimens. • Histoplasma is predominantly an intracellular parasite, growing within the cells of the reticuloendothelial system as an oval yeast Differential diagnosis: 1)Talaromyces infections 2)cyrptococcosis 3)molluscum contagiosum
  • 51. • All phagocytic cells of the reticuloendothelial system are involved, including those in the liver, spleen, lymph nodes and bone marrow, so that the cytoplasm is swollen with masses of fungal cells. • There is at first little tissue reaction; later, necrosis takes place to be followed by granulomatous changes and fibrosis. • It often elicits an inflammatory response in which giant cells predominate • intracellular yeasts are clearly seen with specific fungal stains such as methenamine silver and PAS.
  • 52. • First line • Itraconazole 100 mg daily until clinical remission • For patients who are severely ill, amphoterocin B 0.5–1 mg/kg daily (or liposomal amphotericin B 3 mg/kg daily) for 2 weeks. Itraconazole 200 mg once or twice daily may then be used for a further period depending on clinical response • For mild disease, patients can be started straight on itraconazole 200 mg daily for a period determined by clinical response • Second line • Fluconazole 800 mg daily for 3 months and then 400 mg daily until clinical remission is achieved • There is insufficient evidence to recommend posaconazole at present
  • 53. 2) Blastomycosis : • Called as North American blastomycosis/ Gilchrist disease. • Blastomycosis is a chronic granulomatous and suppurative mycosis caused by Blastomyces dermatitidis . • It affects primarily the lungs but disseminating forms also affect the skin, bones, central nervous system and other sites. • Adult males most commonly affected,majority being between the ages of 30 and 50 years.
  • 54. : Clinical features • There are three forms of blastomycosis: 1. Primary cutaneous: very rare and follows trauma to the skin and introduction of the fungus. • The condition has been seen mainly in laboratory workers (e.g. pathologists carrying out autopsy examinations) . • After inoculation, an erythematous, indurated area with a chancre appears in 1–2 weeks with associated lymphangitis and lymphadenopathy
  • 55. 2. Pulmonary : This is very similar to pulmonary tuberculosis. • There may be no symptoms, or there may be low‐ grade fever, chest pain, cough and haemoptysis. Occasionally, erythema nodosum develops. • The disease, if untreated, may frequently disseminate and often progresses to death. 3. Disseminated: symmetrical and usually on the trunk . Each consists of a papule or nodule that may ulcerate and discharge pus. The lesions enlarge at the periphery, and tend to show central scarring. • Eventually, after a relentless progress for months, the lesion is serpiginous in outline, the borders are raised and warty and have a violaceous margin studded with miliary abscesses containing the organisms.
  • 56. Diagnosis : • Tissue sections must be scanned carefully to identify organisms Blastomyces dermatitidis produces budding yeasts with a characteristic broad base to the bud in the tissues. • Intra and subepidermal polymorphonuclear abscesses and a granulomatous infiltrate are found in the dermis. These include giant cells of the Langhans type, which contain the round or oval organisms with thick, refractile walls. • Culture • Microscopy: small, rounded or pear‐shaped conidia (2–5 μm) are produced on short stalks arising at right angles from the hyphae.
  • 57. Treatment • Itraconazole 200‐400 mg daily until clinical remission. • For patients who are severely ill, amphoterocin B 0.5–1 mg/kg daily for 2 weeks followed by itraconazole for a further period depending on clinical response
  • 58. 3) Coccidioidomycosis : • This is a (primary) respiratory fungal infection caused by Coccidioides immitis and C. posadasii , which may become progressive and disseminated, with severe or fatal forms. • Also known as Coccidioidal granuloma/Valley fever/Desert rheumatism • Coccidioidomycosis is endemic in desert areas of the southwestern states of the USA, and in parts of Central and South America
  • 59. Clinical features: • There is a higher risk of dissemination in pregnant women. 1. Primary Pulmonary form: most common form, can be asymptomatic or may simulate influenza or occasionally Pulmonary TB.Erythema multiforme and Erythema nodosum seen in 3-25% of patients particularly females. 2. Disseminated coccidioidomycosis is very uncommon and develops in fewer than 0.5% of infected individuals, usually in black, Filipino or immunosuppressed patients. • Disseminated lesions may occur in the skin, subcutaneous tissues, bones, joints and all organs. • The skin lesions may appear as abscesses, granulomas, ulcers or discharging sinuses, particularly if there is underlying bone or joint disease
  • 60. • Diagnosis : • The large (usually 30–80 μm, occasionally larger) globular spherules with endospores may be seen in potassium hydroxide mounts of sputum, cerebrospinal fluid or pus. • Confirmation depends on the isolation of the fungus in culture. • Colony: cultures of C. immitis and C. posadasii are mycelial, fast growing, initially waxy then cottony, and white to tan . • Microscopy: characteristic thick‐walled arthroconidia, separated from each other by alternate empty cells, are observed.
  • 61. Treatment : • Oral itraconazole (200–400 mg daily) and fl uconazole (400–800 mg daily) are effective in some forms of localized infection such as solitary disseminated skin lesions- duration depends on clinical response. • Intravenous amphotericin B (0.5–1 mg/kg daily) or liposomal amphotericin (3 mg/kg daily) is used for many of the other clinical forms of coccidioidomycosis, including severe disease for periods of between 2 and 4 weeks
  • 62. 4) Paracoccidioidomycosis : • This is a chronic granulomatous fungal infection caused by Paracoccidioides brasiliensis , affecting the skin,mucous membranes,lymph nodes and internal organs. • Also called as South American blastomycosis • It has been reported from most Latin American countries, but the infection is most commonly found in Brazil. • Adult males between the ages of 20 and 50 years are most frequently infected, although exposure rates are equal across the two sexes.
  • 63. Clinical features : • The most common site of infection is the lung (pulmonary form), although skin and mucous membranes (mucocutaneous form) or lymph nodes (lymphatic form) are also often involved. • Patients with pulmonary lesions present with weight loss and chronic cough. • Mucocutaneous lesions may be present in patients with lung disease, or can occur on their own. Oral and circumoral lesions are common although may also occur in the nose, conjunctiva and anus. • Haematogenous or lymphatic spread results in subcutaneous abscesses
  • 64. Diagnosis : • KOH mount from exudates and scrapings show rounded refractile cells with the characteristic multiple budding seen. • Culture • Microscopy: the hyaline, unicellular, pear shaped conidia (3–4 μm) are borne directly on the hyphae or on short stalks. • In histological sections the reaction resembles that seen in blastomycosis, namely granulomas with pyogenic inflammation. Giant cells are conspicuous and these frequently contain the rounded budding cells.
  • 65. Treatment : • All forms require antifungal therapy. • The treatment of choice in most cases is itraconazole 200–400 mg daily, which can produce remission in 3–6 months. • Some patients, particularly those with more rapidly progressive and extensive infections, may require amphotericin B 0.5–1 mg/kg for 2 weeks followed by oral itraconazole 200 mg daily
  • 66. 5) Cryptococcosis : • Cryptococcosis is an acute, subacute or chronic infection caused by the encapsulated yeast Cryptococcus neoformans . • There is a marked predilection for the brain and meninges, although the lungs and occasionally the skin and other parts of the body may be involved. • Associated with AIDS , lymphomas, malignancies, collagen disease, systemic sterod therapy, immunosuppression in patients after renal transplant. • Cryptococcosis is caused by C. neoformans and C. gattii .
  • 67. Clinical features • Most common clinical manifestation of disease is meningoencephalitis. • Pulmonary infection can be found in about 10% of those with meningitis. • Cutaneous lesions may develop in about 10% of cases but are seldom pathognomonic.
  • 68. diagnosis : • The large (5–15 μm) budding cells with their characteristic capsules are best observed by direct microscopy of cerebrospinal fluid or pus in India ink or nigrosin mounts. Treatment : First line • Amphotericin B 0.5–1 mg/kg daily for 4–6 weeks or • Amphortericin B 0.2–1 mg daily (or liposmal amphotericinB 3 mg/kg daily) for 2 weeks • Followed by fluconazoloe 400 mg daily for 4 weeks or until remission Second line • Fluconazole 800 mg daily for 6–8 weeks

Editor's Notes

  1. Most common form –n lymphatic
  2. Mri for depth of bony involvement
  3. although chemotherapy of mycetomas caused by fungi has, so far, been found to be quite unsatisfactory in most cases, despite the fact that certain fungi have been found to be relatively sensitive in vitro to therapeutic agents such as amphotericin B . Infection by species of actinomycetes may be susceptible to chemotherapeutic agents.
  4. Endemic mycoses: inhalation of the causative organisms. They are usually asymptomatic and the primary infection can only be detected in retrospect by a positive skin test, as in tuberculosis.(eg-histoplasmosis (classic and African types), blastomycosis, coccidioidomycosis, paracoccidioidomycosis and infection caused by Talaromyces (previously Penicillium) marneffei.) opportunistic systemic mycoses: systemic infections that only occur in patients with some underlying predisposition. Cryptococcosis shares features of both