subcutaneous fungal infections in brief

1. Presenter: Dr Rohini
Soni
Moderator: Dr Sundeep
Chowdhry
Subcutaneous
mycosis

2. Introduction
❖ Subcutaneous mycoses, or mycoses of implantation,
are sporadically occurring infections caused by fungi
present in the natural environment, which are directly
inoculated into the dermis or subcutaneous tissue
through a penetrating injury.

3. ❖ Eumycetoma
❖ Sporotrichosis
❖ Chromoblastomycosis
❖ Rhinosporodosis
❖ Phaeohyphomycosis
❖ Lobomycosis
❖ Subcutaneous zygomycosis

4. Mycetoma
(madura foot)
❖ Chronic, slowly progressive granulomatous infection of skin & subcutaneous
tissues with the involvement of underlying fasciae & bones commonly
affecting the extremities.
❖ Reported by Gill from Madurai, S.India.
❖ Maduramycosis or Madura foot.
❖ Tropical & subtropical countries of Asia , Africa, Central & S.America
❖ 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)

5. Mycetoma
EumycetomaActinomycetoma

7. 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.

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

9. Differences between eumycetoma and actinomycetom

10. 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.

11. 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.

12. 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

14. Treatment of eumycetoma
❖ Oral Ketoconazole (200- 400 mg) daily for several months
❖ A trial of therapy with terbinafine , itraconazole,
Voriconazole, Posaconazole is worth attempting.
❖ AMB (1mg/kg) for Madurella & Fusarium species.
❖ Protracted case – Surgery (debridement with skin graft)

15. 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.

16. SPOROTRICHOSIS
Cutaneous Extra cutaneous
Fixed/localisedLymphocutaneous Pulmonary Disseminated

17. 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)

18. ❖ The primary lesion may remain localized (fixed
sporotrichosis) or in the immunocompromised
individuals may disseminate to involve the bones, joints,
lungs and rarely the central -nervous system
(meningitis).
❖ Pulmonary forms results from inhalation of conidiaand
presents as chronic cavitary fibronodular disease.
Patient presents with the features of pneumonitis or
bronchitis.

19. 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-
like body, with of an eosinophilic substance radiating
from the yeast cell).
❖ This is called “ Splendore-Hoeppli” phenomenon :
due to immune complex deposition around the
organism
❖ The characteristic formation of the perifungal
Splendore-Hoeppli reaction probably prevents
phagocytosis and intracellular killing of the insulting
agent leading to chronicity of infection

20. ❖ 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.

22. 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

23. 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

25. Treatment
❖ Treatment ladder
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
❖ AMB – disseminated & CNS disease.
❖ Thermotherapy

26. 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.
❖ The disease has been found in humans and dolphins
and is restricted to the Amazon Valley in Brazil.

27. LAB DIAGNOSIS
❖ KOH spheroid, yeast - like cells, 5 -12µ thick - walled &
multinucleate. Form chain with cells joined by bridges.
❖ HE –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.

28. 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)

29. 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.

30. Rhinosporidiosis
❖ Caused by a hydrophilic protist, Rhinosporidium seeberi
❖ 1st identified in Argentina, but majority of cases occur in
India and Sri lanka.
❖ 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.

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

33. ❖ 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

35. 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

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

37. CHROMOBLASTOMYCOSIS
❖ A chronic granulomatous fungal infection of the
dematiaceous (pigmented fungi), which produce
thick walled single- or multicelled clusters
(sclerotic or muriform bodies)
❖ Commonest fungi -
1. Fonsecaea Species
2. Phialophora verrucosa
3. Cladosporium carrionii
4. Fonsecaea compacta
5. Rhinocladiella aquaspersa- rare
❖ Also called as Verrucous dermatitis
❖ Fungi is isolated from wood and soil
❖ Adult male agricultural workers are most often
affected

38. Presentation
❖ Enter the skin by traumatic implantation and lesions
develop slowly around the site of implantation
❖ Warty cutaneous nodules which resembles flouts of
cauliflower.
❖ Frequently ulcerate
❖ Confined to the subcutaneous tissue of the feet and
lower legs
❖ Satellite lesions are produced by scratching.
❖ Presence of secondary infection causes itching and
pain.
❖ Haematogenous spread has occurred but is rare,
and brain abscesses have reported.
❖ Complications of chromoblastomycosis include local
lymphedema, leading to elephantiasis and
squamous carcinomas

39. Lab investigations
❖ 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

40. ❖ 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)
phialophoraFonsecaea

41. Treatment
❖ Itraconazole (100–200 mg daily) or terbinafine (250 mg daily) is often
successful, although responses to both are thought to be better if the
causative organism is C. carrionii .
❖ Flucytosine used on its own or combined with amphotericin B may also be
effective, but resistance to flucytosine may develop if used alone.
❖ Other approaches to treatment: cryotherapy or the local application of heat
❖ The use of surgery is contentious; in larger plaques there is a risk in
pursuing this approach as satellite lesions may develop around the excision
site.
❖ Surgery is really only indicated in very small lesions combined with
chemotherapy.

42. Subcutaneous zygomycosis
Zygomycota
Zygomycetes
MucoralesEntomophthorales
phylum
Subcutaneous
zygomycosis
Usually infect immunocompetent
Traumatic implantation
s/c mycosis and sinusitis
Dissemination rare

43. 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.haptosporus
C. coronatus
C. incongrus
C. lampragues

44. ❖ Pathogens .. plant detritus, where they could associate
with insects or mammals by producing forcibly ejected
sticky conidia
❖ Both Conidiobolus spp. and Basidiobolus spp. are
thermophilic fungi .
❖ Affected patients are apparently healthy without
predisposing factors.
Fungal spores on
Bristles of insect
Eaten up by reptiles Faeces of reptiles in soil
People using toilet
leaves

45. • 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

46. Basidiobolomycosis
❖ 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.
❖ The disc shaped masses have a uniform hard consistency,
and they do not pit.
❖ Hematogenous spread typically does not occur.
❖ 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.

47. 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

48. 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

49. 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

50. 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 (0.5 mg/d) for 2 weeks or 1 month, dapsone , (1-2
mg/kg of body weight daily), and ketoconazole (400 mg/d), itraconazole
(300 mg/d), or fluconazole (300 mg/d) for 6 months have been used.

51. PHAEOHYPHOMYCOSIS
❖ 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).
❖ Etiological agents:
1. Wangiella dermatitidis
2. Exophiala jeanselmei
3. Cladophilophora bantiana
4. Nattrassia mangiferae
5. Alternaria species
6. Ulocladium species
7. Bipolaris species
8. Chaetomium species
9. Curvularia species
10.Exserohilum species etc

52. Phaeohy
phomyco
sis
Superfici
al
Piedra
Cutaneous
Deramato
mycosis
Invasive
Systemic
Cerebral
Subcutan
eous
Keratiti
s

53. ❖ 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

55. Lab investigations
❖ Specimen
Aspirates from cysts
Curreting from plaques, nodules
and drained abscess
❖ KOH: septet hyphae seen
❖ SDA: olivaceous to brown or
black colony
Dematiaceous septate fungi

56. 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

57. Treatment
❖ Local excision for subcutaneous forms
❖ Invasive infections – I.V. AMB + Oral Flucytosine.

58. Thank you

59. Case scenario 1
❖ A 29 year-old man (forest ranger) who was a
native of the Peruvian jungle noticed a painless
but pruriginous papular lesion on his left earlobe at
the age of 12 years.
❖ He did not recall previous trauma. At the age of
23, he was given a misdiagnosis of cutaneous
leishmaniasis on the basis of clinical findings and
was treated with meglumine antimoniate
(Glucantime™) for five days with no improvement
❖ After 17 years of slow disease progression, the
patient came to the hospital for clinical evaluation.
❖ At physical examination, the entire left earlobe
was involved, presenting diffuse infiltration, as well
as multiple nodules and ulcers.
❖ At that time, direct examination and pathologic
findings of a skin biopsy specimen showed
multiple, round yeast-like cells in chains of 3–4
elements.

60. LOBOMYCOSIS

61. CASE SCENARIO 2
❖ A 30-year-old gentleman was referred for a
nonresolving cellulitis of the right hand and
forearm for a 6-week duration.
❖ The patient gave a history of a motorbike accident
before the onset of his problem.
❖ The patient did not sustain any other injury apart
from a minor superficial wound over the dorsum of
his right hand.
❖ After 3 days, he developed pain and redness over
the dorsum of his right hand.
❖ In addition, he claimed that there was an on-off
serous discharge from his wound associated with
the swelling.
❖ After the injury, he denied contact with soils,
untreated water source, or any other dirty
environment. He does not have pets in his house.

62. ❖ Examination of the patient's right hand revealed a 1 cm × 3 cm
healing wound over the dorsal region.
❖ There was no active discharge noted.
❖ His right hand, as well as his forearm was erythematous almost up
to the elbow level.
❖ The erythema over the forearm followed a distinctive pattern.
❖ It spread along the lymphatic channels of the forearm.
❖ There was no other skin lesion or ulcer noted.
❖ There was tenderness over the erythematous area associated with
multiple discrete swellings with sizes ranging from 2 mm to 5 mm

63. Sporotrichosis
Mature blackish fungal colony growth noted on the Sabouraud agar media

64. THANK YOU