This document discusses various subcutaneous and systemic fungal infections. It describes subcutaneous mycoses, which are fungal infections that remain limited to the skin and subcutaneous tissues. Key subcutaneous mycoses discussed include mycetoma, chromoblastomycosis, phaeohyphomycosis, sporotrichosis, and lobomycosis. It provides details on the causative agents, epidemiology, clinical presentation, diagnosis and management of these infections. Specifically, it focuses on describing the characteristics of mycetoma including its clinical features, grain morphology, and treatment approach.

1. DR.NIVETHA

2. INTRODUCTION
 Two groups:
 subcutaneous fungal infections (subcutaneous
mycoses)
 systemic fungal infections (systemic mycoses).

3. SUBCUTANEOUS MYCOSIS
 infections that usually remain limited to the skin and
subcutaneous tissues,
 rarely spreading to the internal organs.
 The causal agents have a saprophytic existence in
nature.
 The usual mode of infection is through inoculation.

4.  They include
 mycetoma,
 chromoblastomycosis,
 phaeohyphomycosis,
 sporotrichosis,
 lobomycosis,
 rhinosporidiosis
 subcutaneous zygomycosis

5. MYCETOMA (SYN. MADURA FOOT,
MADUROMYCOSIS)
 Mycetoma – Derived from Greek word “fungal
tumor”
 Mycetoma is a chronic, suppurative, granulomatous
disease of the subcutaneous tissues and bones,
 characterized by localized swellings
 with multiple sinuses discharging granules that are the
micro-colonies of the causative agents

6. • Localized chronic infection caused by various species of fungi
or actinomycetes.
• Formation of aggregates of the causative organisms (grains)
within abscesses.
• Tropical and subtropical climates
• Agricultural workers.
• World wide, M. C. organism - Madurella mycetomatis

7. ❖ Reported by Gill from Madurai, S.India.
❖ Maduramycosis or Madura foot.
❖ Fungi associated with fungal mycetoma are
opportunistic.
❖ Mycotic mycetoma - usually more common in men
(3:1 to 5:1) than in women
❖ Usually results from trauma or puncture wounds to
feet, legs, arms and hands (usually on the feet)

8. Mycetoma
Eumycetoma
Actinomycetom
a

13. Clinical features
❖ Site: foot and lower leg
❖ The earliest stage is a firm, painless nodule but, with time, papules, pustules
which break down to form draining sinuses, appear on the skin surface.
❖ The whole area becomes hard and swollen, often without significant pain.
❖ Extension to underlying bones and joints gives rise to periostitis, osteomyelitis
and arthritis
❖ There are usually multiple sinus tracts draining pus
❖ The discharge may be purulent or seropurulent.
❖ The condition is painless and usually develops slowly
❖ Lymph node involvement is rare
❖ Madurella mycetomatis causes the majority of the cases with the black grains.

14. ❖ Characterized by a clinical triad
of:
1. Tumefaction – tumor like
swelling
2. Multiple draining sinuses
3. Presence of grains or
granules in sinuses.

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

16. • 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.

17. Xray
❖ Soft tissue swellings
❖ Irregular destruction from without or
around the periphery of the affected
bones: osteolysis
❖ A periosteal reaction
❖ Sclerosis of the affected bones and the
absence of true sequestra
❖ The shaggy periostitis, reactive
sclerosis and resorption of bone gives
a melting snow appearance

18. Erosive X‐ray changes in a mycetoma

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

21. Lab diagnosis
❖ Specimen: pus, fluids, scrapings of sinuses, grains, biopsy
specimen.
❖ Color of grain: Black grains are always eumycotic whereas red
grains are due to Actinomadura pelletierri.
❖ KOH : eumycotic cells consists of broad septet hyphae with well
defined walls and chlamydospores.
❖ Gram stain
❖ AFB to identify Nocardia.
❖ Culture on SDA media to identify the species.

22. FNAC smear showing PAS positive fungal hyphae
Actinomycetoma-neutrophilic infiltrate surrounding the
actinomycotic colony with occasional giant cell (H and E, ×250)
Histology
The causal organisms produce a chronic infammatory reaction leading to
focal neutrophil abscess formation, with scattered giant cells and fibrosis.

27. 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.

30. 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).
(SYN. CHROMOMYCOSIS, VERRUCOUS DERMATITIS,
PHAEOSPOROTRICHOSIS)
Slow‐growing exophytic lesions, usually on the feet and legs.

31. 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

32. 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.

33. COPPER PENNY BODIES
GIANT CELL CONTAINING MURIFORM CELLS

34. 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.

35. Plaque‐type chromoblastomycosis
Early lesion of chromoblastomycosis

36. • 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.
• Warty cutaneous nodules which resembles flouts of
cauliflower.

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

38. 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.

39. PHIALOPHORA VERRUCOSA FONSECAEA PEDROSI CLOPHIALOPHORA CARRIONII

40. ❖ Specimen: scraping, crust,
aspirated material, biopsy
tissue.
❖ KOH: thick walled dark brown
sclerotic bodies or muriform
cells.
❖ H/E: variably pigmented fungal
cells called
muriform/sclerotic/copper
penny bodies.
sclerotic/medlar bodies in
KOH
shows mononuclear cell infiltrate and a dark-brown, round
sclerotic body resembling a “copper penny” (arrow), consistent
with chromoblastomycosis

41. ❖ Culture: SDA medium at 26 C for 6 weeks.
❖ Typical velvety brown colored colony
❖ Multiplication in vivo is by fission rather than budding, and this results in the production of single, two-
or multiple-celled clusters giving a chest-nut appearance
❖ Fonsecaea pedrosoi – conidia is confined to the upper part of the cell, produced by acropetal budding
❖ Phialophora verrucosa - flowers in the vase conidiation)
phialophora
Fonsecae
a

42. 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

43. PHAEOHYPHOMYCOSIS
DEFINITION
Localized, subcutaneous or intramuscular infection, usually a
cyst or abscess caused by a range of brown‐pigmented
(dematiaceous) fungi.
❖ A mycotic infection of humans and lower animals
caused by a number of dematiaceous (brown-
pigmented) fungi where the tissue morphology of
the causative organism is mycelial.
❖ This separates it from other clinical types of disease
involving brown- pigmented fungi where the tissue
morphology of the organism is a grain (mycotic
mycetoma) or sclerotic body (chromoblastomycosis).

44.  EPIDEMIOLOGY
 Most often in tropical areas.
 Immunocompromised patients (on steroid
therapy).

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

46. 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

47. 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.

48. ❖ Subcutaneous or intramuscular lesions with abscess or cysts - single
circumscribed lesion with a central cavity filled with pus and surrounded
by a fibrous wall.
❖ Apart from classical forms, papulonodules, pustules, eschars, verrucous
lesions have also been described.
❖ Unlike in chromoblastomycosis, these organisms form short, irregular,
pigmented hyphae in tissue.
❖ Brain abscess is caused by Cladosporium
❖ Cystic lesions caused by non-pigmented fungi are also found called
hyalohyphomycotic cysts

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

51. 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.

52. ❖ KOH: septet hyphae seen
❖ SDA: olivaceous to brown
or black colony
Dematiaceous septate
fungi

53. Intra and extracellular, round to oval, thick walled
brown cells with septate hyphae (H and E, ×40
(H and E, ×10) Granuloma in the dermis composed of
epithelioid cells, lymphocytes, and fibroblasts. (b) (H and E,
×100) closer view

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

55. SPOROTRICHOSIS
❖ Chronic infection involving cutaneous, subcutaneous
and lymphatic tissue.
❖ Frequently encountered in gardeners, forest workers and
manual labourers, urban alcoholics ,particularly homeless.
❖ Rose gardener’s disease
❖ Caused by the thermally dimorphic fungus Sporothrix schenckii
❖ 25˚C – mold, 37°C – yeast.
❖ Saprophytic fungus – grows on decaying vegetation, soil,
thorns.

56. 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

57. SPOROTRICHOSIS
Cutaneous Extra cutaneous
Fixed/localised
Lymphocutaneous Pulmonar
y
Disseminated

58. Clinical presentation
❖ Spore is the infective stage of the
fungus.
❖ It causes infection primarily on the
hand or the forearm through direct
contact of the skin by spores.
❖ Typically, infection is introduced in skin
through a penetration of thorn.
❖ At the site of thorn injury, it causes a
local pustule or a nodules that
breaks down to form a ulcer.
❖ Frequently , the regional lymph
nodes draining the ulcer enlarge,
suppurate and may ulcerate.
(lymphocutaneous form)

59. 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).

60. 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

61. 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.

62. HISTOLOGY
❖ 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
❖ These may be surrounded by a
thick,radiate,eosinophilic substance,
which forms the distinctive asteroid
bodies (a rounded oval, basophilic,
yeast-likebody, with an eosinophilic
substance radiating from the yeast
cell).
❖ This is called “ Splendore-Hoeppli”
phenomenon due to immune
complex deposition around the
organism

63. ASTEROID BODIES
SPLENDORE HOEPPLI
PHENOMENON

64. ❖ 3 granulomatous patterns:
❖ Sporotrichoid type-concentric zones with necrotic
material in the centre surrounded by epitheloid
histiocytes, neutrophils, plasma cells.
❖ Tuberculoid type- merges into the area of epitheloid
cells
❖ Foreign body type without pyogenic reaction may be
seen.

66. Lab investigations
❖ Specimens – pus, exudate &
aspirate from nodules,
curettage or swabs from open
lesions.
❖ Direct microscopy usually
negative or few organisms may
be seen.
❖ Others : serology/sporotrichnin
test.
❖ Culture on SDA media

67. 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.

68. Microscopic morphology of the saprophytic or mycelial
form of Sporothrix schenckii when grown on Sabouraud's
dextrose agar at 25oC. Note clusters of ovoid conidia
produced sympodially on short conidiophores arising at
right angles from the thin septate hyphae.
The arrangement of the conidia at the apex of the
conidiogenous cell is often described as palmate or flower-
like, with each conidium attached by a denticle to the small
vesicle
Yeast phase of sporothrix

69. 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.

70. 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.

71. Lobomycosis
❖ Also called Keloidal blastomycosis or Lobo’s
disease
❖ Caused by Lacazia loboi (Hydrophilic fungus)
: exists only as yeast cells.
❖ May occur anywhere but mainly involves
exposed parts- legs, arms and face, ear.
❖ Chronic, localized, subepidermal infection
characterized by the presence of keloidal,
verrucoid, nodular lesions or sometimes by
vegetating crusty plaques and tumors.
❖ The lesions contain masses of spheroidal,
yeast- like organisms tentatively referred to
as Loboa loboi.
❖ Painless, occasionally pruritic, dysesthetic or
anesthetic.
❖ No systemic spread.

72. 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

73. LAB DIAGNOSIS
❖ KOH -spheroid, yeast - like cells, 5 -12µ thick - walled &
multinucleate. Form chain with cells joined by bridges.
❖ HPE –dense granulomatous infiltrate with epithelia
cells and multinucleate giant cells. May show ‘asteroid
bodies’.
❖ Culture- cannot be cultured
❖ Fungal elements can be stained with PAS, Gomori,
Grocott stains.

74. 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 ”
Gomori-Grocott stain highlighting the
bridging connections between the cells

75. Diagnosis is made by skin biopsy and there is a characteristic
appearance of the fungal spores which line up like “chains of lemons
Multiple, confluent, keloid-like, hyperchromic nodules with at shiny surfaces involving the entire free border, posterior aspect, and
lobule of the left ear of a sherman, Venezuela. B) Numerous Lacazia loboi tissue-phase organisms within the stroma. Note the typical
chain pattern showing simple gemation budding (Gomori-Grocott stain, magni cation ×100). C) Yeast cells showing typical double
refraction of the membrane and protoplasmic bodies within cells (periodic acid–Schiff stain, magni cation ×600)

76. Treatment
❖ No effective medical treatment
❖ Complete excision
❖ Cryosurgery.
❖ Clofazimine at the dose of 300mg/day can be used with
maintenance dose of 100 mg for unto 2 years.
❖ Clofazimine can be combined with itraconazole or
posaconazole.

77. Rhinosporidiosis
❖ Caused by a hydrophilic protist, Rhinosporidium
seeberi
❖ It has high incidence among people who frequently
bath along with domestic animals in ponds, tanks,
lakes.
❖ A chronic granulomatous disease characterized the
development of friable polyps, usually confined to
nose, mouth or eye but rarely seen on the genitalia or
other mucous membranes.

78. Rhinosporidiosis
Mucosa
Friable, vascular polyp
Cutaneous
Friable wart like growth with crenated
surfaces
Disseminated
(livers,lungs,spleen, brain)

80. ❖ Nasal polyp : Obstruction to breathing is usually the
chief complaint.
❖ Eye: If the eye is involved there is conjunctivitis and
photophobia
❖ Miscellaneous forms: Buccal cavity, vagina, vulva,
penis, urethra or rectum

82. Large (100 - 450 microns), thick walled sporangia with 1000+ endospores, each 6 - 10 microns, accompanied by a mixed inflammatory
infiltrate (h/e), GMS stain
Lab diagnosis
Direct microscopy can be done with KOH to demonstrate sporangia,H/E & PAS/GMS are
diag

83. Treatment
❖ Radical Surgery:- Excision/ Electrocautery
❖ Dapsone (widely used)
❖ Recurrence common

84. SUBCUTANEOUS MYCOSIS
 Subcutaneous zygomycosis is a chronic, subcutaneous
infection characterized by woody swelling of the
subcutaneous tissue.
 The disease is caused by organisms belonging to the class
Zygomycetes, order Entomophthorales and genera
Basidiobolus and Conidiobolus.
 They exist as saprophytes in soil, decaying vegetation, and
the gastrointestinal tracts of frogs, causing infection in
normal persons.
 The infection occurs in tropical and subtropical climates.

85. Entomophthorales
❖ Name is derived from Greek word (‘ Entomon ’ = insect; phthoro = destroyer)
❖ slow -growing tumoral -like masses in infected tissues
❖ SITES AFFECTED: Conidiobolus spp - Face ( generally around nose )
Basidiobolus -
limbs, intestinal tract, and rarely other body areas.
❖ A typical feature of these pathogens: Splendore – Hoeppli phenomenon
Basidiobolomycosis Conidiobolomycosis
B. ranarum
B.haptospores
C. coronatus
C. incongrus
C. lampragues

86. • Mainly afflicts children
• PORTAL OF ENTRY: Insect bite,
ingestion, and inhalation
• Frequently in tropical Africa and
Southeast Asia and
occasionally in India, Costa
Rica, and Brazil
• Usually adults
• Inhalation or through trauma
to nasal mucosa
• Rainforests of tropical Africa ,
South or Central America and
Southeast Asia and India
Basidiobolomycosis Conidiobolomycosis

87. Basidiobolomycosis
 The lesion usually involves the limbs or
limb-girdle areas.
 Children are mostly affected.
 It starts as a subcutaneous nodule, and
gradually increases in size
❖ Patients present with a
single painless, unilateral, well-
circumscribed subcutaneous mass on
the buttock or thigh.
❖ Initial single nodule is hard and woody
and progressively grows into contiguous
subcutaneous tissues.
❖ It may be single, or there may be
multiple satellite lesions.

88. ❖The disc shaped masses have a uniform hard
consistency,and they do not pit.
❖Hematogenous spread typically does not occur.
❖Characteristically, the examiner’s fingers can be
insinuated under the edge and the swelling lifted
off the underlying tissues

89. ❖The subcutaneous nodule is anchored to underlying muscle
fascia and is not attached to the overlying skin
❖The smooth rounded edge, which may be lobulated, can be
raised up by inserting the fingers underneath it.
❖Pain and tenderness may be absent.
❖The overlying skin may be tense,oedematous, desquamating,
hyperpigmented or normal.Ulceration does not occur.

90. Conidiobolomycosis
❖ Over an extended period of time, infection
undermines the mucosa of the nasal cavity.
❖ Expansion of the nasal mass produces
painless swelling of overlying tissue of
forehead , upper lip, and about the eye
with intact dermal layer without ulceration.
❖ Signs of nasal obstruction may be present.
❖ Long standing cases hippopotamus look
may be present.
❖ Does not usually disseminate, may involve
lymph nodes

91.  the lesion starts as a nasal swelling in the inferior
turbinates and slowly or at times rapidly extends to the
submucosal structures.
 Bilateral and disfiguring .
 Painless and does not ulcerate or become verrucous.
 The mass is anchored to the underlining structures but not
to the overlying dermis.
 Edema may develop.
 X-ray examination shows an opaque antrum, obliteration
of the nasal air space and mucosal thickening.
 The patient is otherwise normal and healthy

92. Lab diagnosis
❖ Specimen : scrapings ,biopsy tissue.
❖ KOH: Ribbon-like broad, aseptate or sparsely septate
hypha ( 3.5 to 10μm ) with right or wide-angle branching
and covered by a hyaline material. Presumptive infection
by members of the Entomophthoromycota.
❖ CULTURE: SDA media at 30 C & 37 C: yellowish to grey
colonies in case of basidiomycosis and white colonies in
coniobolus

93. HPE
 The lesion is an eosinophilic granuloma in the
subcutaneous tissue.
 Wide, sparsely septate hyphae, branching at right
angles, course through the tissue and are surrounded
by an eosinophilic sleeve or halo (Splendore–Hoeppli
phenomenon).
 The vessel wells and lumen are not invaded. Often
there is dense fibrosis.

94. ft tissue shows dense infiltrate of eosinophils and fibrosis (a) (H and E, ×100). High power photomicrograph shows a few transverse septae (black arrows) in these fungal profiles (b

95. Treatment
❖ Treatment for entomophthoramycosis : both medical and surgical.
❖ Systemic prolonged antifungal therapy coupled with surgical
debridement is the cornerstone treatment.
❖ SSKI( Supersaturated solution of Potassium iodide) used to treat. Oral
dosage for adults: Therapy is usually initiated at 600 mg (roughly 12
drops of SSKI) PO three times daily. This dosage is often gradually
increased up to 4—6 g/day (127 drops/day of SSKI) if tolerated. The
duration of therapy is often 6—10 weeks.
❖ Amphotericin B , dapsone, and ketoconazole, itraconazole, or
fluconazole for 6 months have been used.

96. SYSTEMIC MYCOSES
 The systemic mycoses can be considered under two
subgroups:
 Endemic mycoses
 Opportunistic mycoses

97. ENDEMIC MYCOSIS
 Previously known as pathogenic fungus infections,
 The causal agents exist as soil saprophytes and the usual
mode of infection is through inhalation.
 In many cases, the infection is asymptomatic and in others,
mild and self-limited.
 In the progressive form of the disease, dissemination
occurs to internal organs with a fatal outcome unless
antifungal therapy is instituted.

98.  They include
 Histoplasmosis,
 Blastomycosis,
 Coccidioidomycosis
 Paracoccidioidomycosis.

99. OPPORTUNISTIC MYCOSES
 The opportunistic fungus infections occur in a setting
of immunosuppression.
 Any fungus may be considered as a potential pathogen
when the normal defence mechanisms are impaired.

100.  The most common of these infections are
 Cryptococcosis,
 Systemic candidiasis,
 Aspergillosis,
 Zygomycosis,
 Penicilliosis,
 Pneumocystosis

101. HISTOPLASMOSIS
• Histoplasma capsulatum causes histoplasmosis.
• (SYN. DARLING’S DISEASE, CAVE DISEASE,
OHIO VALLEY DISEASE)
• H. capsulatum is a dimorphic fungus that exists as a
mold in soil and as a yeast in tissue.
• It forms two types of asexual spores
(1)Tuberculate macroconidia, with typical thick walls
and fingerlike projections that are important in
laboratory identification,
(2)Microconidia, which are smaller, thin, smoothwalled
spores that, if inhaled, transmit the infection.

102. TRANSMISSION & EPIDEMIOLOGY OF
HISTOPLASMA
• This fungus occurs in many parts of the world.
• It grows in soil, particularly if the soil is heavily
contaminated with bird droppings, especially from
starlings.
• Although the birds are not infected, bats can be infected
and can excrete the organism in their feces.

103. TRANSMISSION & EPIDEMIOLOGY OF
HISTOPLASMA
• In areas of endemic infection, excavation of the soil
during construction or exploration of bat-infested
caves has resulted in a significant number of infected
individuals.
• In several tropical African countries, histoplasmosis is
caused by Histoplasrna duboisii.
• The clinical picture is different from that
caused by H. capsulatum.

104. PATHOGENESIS & CLINICAL FINDINGS
OF HISTOPLASMA
• Inhaled spores are engulfed by macrophages and
develop into yeast forms.
• In tissues, H. capsulatum occurs as an oval budding
yeast inside macrophages

105. PATHOGENESIS & CLINICAL FINDINGS
OF HISTOPLASMA
• The yeasts survive within the phagolysosome of the
macrophage by producing alkaline substances, such
as bicarbonate and ammonia, that raise the pH and
thereby inactivate the degradative enzymes of the
phagolysosome .
• The organisms spread widely throughout the body;
especially to the liver and spleen, but most infections
remain asymptomatic, and the small granulomatous
foci heal by calcification.

106. PATHOGENESIS & CLINICAL FINDINGS
OF HISTOPLASMA
• With intense exposure (eg, in a chicken house or
batinfested cave), pneumonia may become clinically
manifest.
• Severe disseminated histoplasmosis develops in a small
minority of infected persons, especially infants and
individuals with reduced cell-mediated immunity, such as
AIDS patients.
• In AIDS patients, ulcerated lesions on the tongue are typical
of disseminated histoplasmosis. In immunocompetent
people, EN can occur.

107. PATHOGENESIS & CLINICAL FINDINGS
OF HISTOPLASMA
• EN is a sign that cell-mediated immunity is active and
the organism will probably be contained.
• A skin test using histoplasmin (a mycelial extract)
becomes positive, ie, shows at least 5 mm of
induration, within 2-3 weeks after infection and
remains positive for many years.
• However, because there are many false-positive
reactions (due to cross-reactivity) and many false-
negative reactions (in disseminated disease), the skin
test is not useful for diagnosis.

108. PATHOGENESIS & CLINICAL FINDINGS
OF HISTOPLASMA
• Furthermore, the skin test can stimulate an antibody
response and confuse the serologic tests.
• The skin test is useful for epidemiologic studies, and
up to 90% of individuals have positive results in areas
of endemic infection.

109. CUTANEOUS HISTOPLASMOSIS ORAL ULCERATION

110. LABORATORY DIAGNOSIS OF
HISTOPLASMA
• In tissue biopsy specimens or bone marrow
aspirates, oval yeast cells within macrophages are
seen microscopically.
• Cultures on Sabouraud's agar show hyphae with
tuberculate macroconidia when grown at low
temperature, eg, 25°C and yeasts when grown at
37°C.
• Tests that detect Histoplasma antigens by
radioimmunoassay and Histoplasma RNA with DNA
probes are also useful.

111. LABORATORY DIAGNOSIS OF
HISTOPLASMA
• An antibody titer of 1:32 in the CF(complement
fixation) test with yeast phase antigens is
considered to be diagnostic.
• However, cross-reactions with other fungi, especially
Blastomyces, occur.
• CF titers fall when the disease becomes inactive and
rise in disseminated disease.
• The ID(immunodiffusion) test detects precipitating
antibodies (precipitins) by forming two bands, M
and H, in an agar-gel diffusion assay.
• The ID test is more specific but less sensitive than the
CF test.

112. PAS stain showing Histoplasma
capsulatum yeast cells in liver specimen

113. Rough-walled macroconidia
Macroconidia and microconidia
HISTOPLASMA CAPSULATUM

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

115. TREATMENT & PREVENTION OF
HISTOPLASMA
• No therapy is needed in asymptomatic or mild primary
infections.
• With progressive lung lesions, oral itraconazole is
beneficial.
• In disseminated disease, arnphotericin B is the treatment
of choice.
• In meningitis, fluconazole is often used because it
penetrates the spinal fluid well.

116. Budding yeast cell
inside macrophages

117. TREATMENT & PREVENTION OF
HISTOPLASMA
• Oral itraconazole is used to treat pulmonary or
disseminated disease, as well as for chronic
suppression in patients with AIDS.
• There are no means of prevention except avoiding
exposure in areas of endemic infection.

118. 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

119. 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.

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

121. • 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

122. Verrucous lesions of Blastomycosis
Annular hyperkeratotic lesions of
Blastomycosis

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

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

125. 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.

126.  During pregnancy-
 Azoles should be avoided
 Amphotericin B recommended
 Newborns – Amphotericin B (1 mg/kg daily) preferred

127. 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.

128. PATHOGENESIS
 Arthrospores inhaled to the lungs  forms
spherules filled with endospore  rupture 
endospore release  forms new spherules 
disseminate throughout the body

129. • 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%

130. Discharging sinus in cutaneous
coccidioidomycosis

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

132. Septate
hyphae
Arthroconidia
Septate hyphae

133. COCCIDIOIDES IMMITIS SHOWING TYPICAL
SINGLE-CELLED, HYALINE, RECTANGULAR TO BARREL-
SHAPED, ALTERNATE
ARTHROCONIDIA

134. 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.

135. 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.

136. • 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

137. multiple budding yeast
cell
Mucocutaneous lesions of
paracoccidioidomycosis

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

139. OPPORTUNISTIC MYCOSES

140. 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.

142. • 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.

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

144. 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

145. 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).

146. 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).

147. Septate hyphae branching at
acute angle

149. 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.

150. 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

151. 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.

152. Single nodular lesion of Cryptococcosis

153. • 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

155. NOCARDIOSIS
 Nocardiosis is an acute or chronic, suppurative,
granulomatous disease caused by members of the
genus Nocardia.
 Nocardia species are aerobic actinomycetes living free
in nature
 Nocardia form extensively branched hyphae
fragmenting into bacillary and coccoid elements

156. C/F
 The lesion develops after a
history of local trauma and
contact with soil as cellulitis,
pustules, pyoderma,
ulcerations and a
lymphocutaneous syndrome
mimicking sporotrichosis.
 N. brasiliensis is usually
associated with this.
 In normal hosts, the disease
is benign and often resolves
spontaneously or with
iodides or sulfonamides

157.  Nocardiosis is primarily a pulmonary disease.
 The organism has a predilection for the central nervous
system.
 The clinical manifestations include malaise, weight loss,
fever, night sweats, and cough.
 The lesion may be a solitary lung abscess, an acute
necrotizing pneumonia or a progressive fibrosis with
extension to the pleura and chest wall with penetration

158. INVESTIGATIONS
 Samples of sputum, bronchial
aspirate, pleural fluid,
cerebrospinal fluid, and biopsy
material should be examined
 the presence of gram positive,
partially acid-fast, branching
filaments of bacterial width and
cocco-bacillary forms
 Tissue sections should be
stained by Brown and Brenn
modification of gram and
Kinyoun’s acid-fast stain or
methenamine silver stain in
order to visualize the organism.

159.  In addition to routine culture on Sabouraud’s dextrose
agar paraffin, bait technique should be used for
isolation of Nocardia
 Because of their ability and the inability of most
commensal microflora to utilize paraffin as the sole
source of carbon and grow on it.

160. TREATMENT
 Sulfa-containing antimicrobials are the drugs of choice
either alone or in combination with other
antimicrobials.
 The most widely used therapy is cotrimoxazole for 6–
12 months or sulfadiazine and sodium bicarbonate for
4–6 weeks followed by sulfisoxazole for 12–18 months

161. ACTINOMYCOSIS
 Actinomycosis is a chronic, suppurative, granulomatous
disease .
 characterized by the presence of multiple draining sinuses
discharging “sulfur granules” which are the microcolonies
of the etiologic agent.
 The organisms are anaerobic or microaerophilic, gram-
positive, nonacid-fast filaments which fragment into
bacillary and coccoid forms without any spores.
 Actinomyces israelii is the predominant pathogen in
human infection.

162. C/F
 Cervicofacial Actinomycosis –
 The organism enters through trauma to the mucous
membrane of the mouth or pharynx.
 The condition starts with pain and swelling along the
alveolar ridge and associated areas.
 The swelling becomes firm, nodular and “wooden” or
“lumpy”, softens and breaks down to form multiple
sinuses discharging pus containing sulfur granules.

163.  Thoracic Actinomycosis –
 The hilar region and the basal parenchymal areas are the
most common sites.
 Fever and cough with production of purulent sputum
develop
 when the infection spreads to involve the pleura and
thoracic wall, multiple draining, sinuses often containing
the “sulfur granules” are seen.

164.  Abdominal Actinomycosis
 This may result from
perforation of the intestinal
wall by fish or bones, gunshot
wounds or surgery.
 Often the primary source is
the appendix.
 The symptoms are insidious
and related to the involved
organ.
 With extensive spread and
penetration of the abdominal
wall, draining sinuses develop

165. INVESTIGATIONS
 The pus, scrapings from
sinuses, biopsy material or
sputum should be examined
for the presence of the
diagnostic “sulfur granules”
 Gram staining reveals gram
positive filaments breaking
up into bacillary and coccoid
forms.
 They are not acid-fast.
 Histologic sections should be
examined for the presence of
characteristic granules.

166. TREATMENT
 Penicillin is the drug of choice
 In patients with penicillin allergy, erythromycin,
doxycycline or clindamycin may be used.
 Amoxicillin 500 mg 4 times per day has been used in
cases with extensive diseases.
 A four week course of imipenem has effected a cure in
a relapse of abdominothoracic actinomycosis.19

167. THANK YOU