SUBCUTANEOUS MYCOSES

OUTLINE
•Introduction
•Etiological agents
•Epidemiology
•Pathogenesis
•Clinical features
•Laboratory Diagnosis
•Management
•References
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SUBCUTANEOUS MYCOSES

• Are saprophytic fungi of soil or decaying

vegetation involving the deeper skin layers,
including muscle, connective tissue, and bone.

• They produce a progressive local disease with

tissue destruction and sinus formation.

• Except in certain patient populations,

dissemination through the blood to major organs
does not occur.
Commonly Occuring Subcutaneous
Mycosis
1. Mycetoma
2. Chromoblastomycosis
3. Phaeohyphomycosis
4. Sporotrichosis
5. Lobomycosis
6. Subcutneous zygomycosis
7. Rhinosporidiosis
1. MYCETOMA (Madura foot)
• A chronic, slowly progressive granulomatous infection
of the skin and subcutaneous tissues with the
involvement of underlying fasciae and bones.

• Types include: Eumycetoma (fungi), Actinomycetoma

(bacteria)

• It is characterized by tumefaction, an eruption of sinus

tracts through the skin, and the presence of sulfur
granules; mainly affecting the legs. Other parts can be
affected too.
Madura Foot ......
Types of Mycetoma based on
Causative Agent
Actinomycetoma Eumycetoma
• Actinomycetes • Madurella mycetomatis

• Streptomyces • Pseudallescheria boydii

somaliensis
• Acremonium
• Nocardia brasilienses
• Aspergillus
• Actinomadurae madurae
Epidemiology

• 1st reported in the mid-19th century in Madurai,

India.

• Distributed worldwide but endemic in tropic and

subtropic areas named as ‘Mycetoma belt’.
i.e. Bolivia Republic of Venezuela, Chad,
Ethiopia, India, Mauritania, Mexico, Senegal,
Somalia, Sudan, Thailand and Yemen.

• Global burden is not known; commonly affects

young adults aged between 15 – 30years.
 Pathogenesis
• The causative organism (Saprotrophs/Heterotrophs)
enters through sites of local penetrative trauma
commonly thorn pricks.
• Common agents: Nocardia brasiliensis and Madurella
mycetomatis

• A neutrophillic response initially occurs which may be

followed by granulomatous reaction. Spread then occurs
through the skin’s fascial planes, therefore invading the
blood, can eventually involve the bone.

• Incubation period: usually months. No person to person

transmission.
Signs and Symptoms
• Mycetoma is characterized by a triad of painless
subcutaneous mass, multiple sinuses and discharge
containing grains.

• It usually spreads to involve the skin, deep structures

and bone resulting in destruction, deformity and loss
of function which may be fatal.

• Mycetoma commonly involves the extremities, back

and gluteal region.
Features Eu-mycetoma Actinomycetoma

causes fungi Bacteria like

actinomycetes
Grains contain Fungal hyphae Filamentous bacteria
Tumour Single well defined margin Multiple tumor masses
with ill defined margin
Sinus Appear late, few Appear early, numerous
with raised inflamed
opening

Discharge Serous Purulent

Bone Osteoscelerotic lesion Osteolytic lesion
Granules Black if caused madurella White to yellow granules
mycetomatis,white if if caused Actinomadura
caused by Pseudali madurae ,Norcadia spp
escheria boydii Pink to red granules if
caused by Actinomadura
pelletieri
Clinical presentations of
Mycetoma
Laboratory Diagnosis

1. Direct examination (Microscopy)

- Specimen collection: After cleaning with antiseptic, using sterile gauze, press
the sinuses from periphery.
- Wash the grains in the sterile saline and keep between slides
- KOH preparation for microscopic analysis

• If positive KOH
• Eumycetoma :2-6µm wide interwoven hyphae with large swollen cells
(chlamydospores). Staining of granules – cement like substances, palisade arrangement
of hyphae
• Actinomycetoma: filaments with a diameter of 0.5-1µm, as well as coccoid bacillary
forms. If hyphae are seen on KOH mount use special stains ( e.g. Acid fast staining for
Norcardia)
2. Culture

Actinomycetoma: Lowenstein Jensen medium then sub-cultured on

Sabouraud Dextrose Agar.

Eumycetoma: Blood agar and sub-cultured on Sabouraud agar.

 Incubation period for fungal growth is 2-3 weeks

3. Biopsy for histopathology:

sample collected around the path of the sinus will show vesicular or
filamentous elements in fungal granule (Gomoric-Grocott stain).

• Histopathological examination is conclusive in determining the

causative fungus or bacteria.
TREATMENT
• Pharmacological:

1. Eumycetoma
Drug of choice is ketoconazole.
Other drugs: -Itraconazole, Terbinafine, and Amphotericin B

2. Actinomycetoma
Modified Welsh regimen = Gentamicin + Cotrimoxazole
Prolonged term of treatment ~ 2 years
Surgical
Excision of the mycetoma lesions that can be excised
completely without residual disability

Role of surgery:
Exploration and drainage of sinus tracts.
Debridement of deceased tissue.
Removal of bone cysts.
They help healing faster.
Amputation is rarely done, except for advanced lesions as a
life saving procedure.
 2. CHROMOBLASTOMYCOSIS
• It is a long term fungal infection of the skin and
subcutaneous tissue found in damp soil and plants.

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Clinical presentation
Clinical presentation
Cont…

• This disease is caused by Fonsecaea pedrosoi and

Phialophora verrucosa; both of which are
dematiaceous fungi (darkly brown pigmented)

• It’s characterized by the formation of verrucose

(rough), irregular, warty-cutaneous nodules, which
may be raised 1-3 cm above the skin
surface resembles the florets of cauliflower.

• Most commonly in tropical or subtropical climates,

often in rural areas.
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 Clinical presentations
• Red or violet color on skin
may resemble a ringworm
lesion

• Develops into a verrucous

lesion over years.

• Pruritus (itchiness) and

papules may develop

• Fungus gets under the skin

(produces bumps) bumps
may block lymphatic system 21
Lab Diagnosis
• Microscopic: Scrapping in 10% KOH (dark, round fungus
cells = sclerotic bodies diagnostic)

• Tissue biopsy - look at the skin for fungus

• Haematoxylin stain - look for fungal cells scattered among skin
cells
• Confirmatory diagnostic test

• Culture (media-Sabouraud’s and digests gelatin) of the fungus

from biopsy tissue - colonies of fungi are dark or blackish
• Incubation period 2-3weeks

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 Treatment
• Surgical excision with wide margins for small
lesions.

• Thiabendazole shows promise; given orally and

on skin mixed with Dimethyl sulfoxide (DMSO)
to deliver drug– experimental drug.

• Chemotherapy with Itraconazole (

200-400mg/day) for 6-12 months plus Terbinafine
250-500mg/day for larger lesions.
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Cont…

• Heat therapy may be beneficial by inhibiting

the growth of fungi

• Relapse is common.

• Late complications include lymphedema,

elephantiasis, and exceptionally squamous
carcinoma

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 3. PHAEOHYPHOMYCOSIS

• Refers to infections caused by many kinds of dark,

melanin-pigmented dermatiaceous fungi.

• A subcutaneous or brain abscess caused by dermatiaceous

fungi.

• It is distinguished from Chromoblastomycosis and

mycetoma by the absence of specific histopathologic
findings.

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Cont
• These infection can be caused by a wide range of
fungi, all of which exist in nature as saprophytes of
soil, wood and decaying vegetation

• Includes Bipolaris spp, Cladophialophora,

Cladosporium, Rhinocladiella and Wangiella
dermatitidis.

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 Diagnosis
• Specimens: pus, tissue biopsy

• Direct microscopic
examination: KOH and smear
brown/dark septate hyphae

• Culture on Sabouraud(very
slow growing black or grey
colonies).

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Treatment

• Surgical excision

• Plaque like lesion can be treated with oral antifungal.

• Antifungal used: Flucytosine 150mg/kg/day

- Itraconazole 200mg/day or Ketoconazole 200mg/day
or IV/ILS Amphotericin B

• Triple antifungal combinations give best results for

refractory cases Amphotericin B, flucytosine and
Itraconazole.
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 4. SPOROTRICHOSIS (rose –
thorn/rose – gardeners’ disease)
• Sporotrichosis is a disease caused by the infection of
the fungus Sporothrix schenckii.

• This fungal disease usually affects the skin, although

other rare forms can affect the lungs, joints, bones,
and even the brain.

• Because roses can spread the disease, it is one of a

few diseases referred to as rose-thorn or rose-
gardeners' disease.
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30
Clinical presentation
Sporothrix Schenckii

• Exhibits Thermal Dimorphism: it produces hyphae

in the environment at temperatures lower than
human body and exists as yeast at 37⁰C in vitro
and vivo.

• Antigenic structure: cell wall contains chitin,

glucans and mannans.

• In addition to glucose and mannose its cell wall

contains L-rhamnose(5 carbon Sugar) which
makes it unique.
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Clinical presentation

• A papule develops at the site of inoculation. Lesion

may ulcerate but usually remain nodular with
overlying erythema.

• Discharge from the wound is odourless and not

grossly purulent. Pain usually minimal and systemic
symptoms are typically absent

• Similar lesions subsequently occur along lymphatic

channels proximal to the original lesion, a finding
called nodular lymphangitis.
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Cont..

• Lesion: Lymphocutaenouse and subcutaneous

granulomatous lesion – suppurate, ulcerate (nodules
or ulcers in local lymphatic).

• Affected sites: extremities, joints.

• Most common in agricultural communities,

dimorphic imperfect fungus in trees, sharps and
decaying vegetations.

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Virulence Factors

• Glycoprotein GP70 in the cell wall mediates

adhesion to extracellular matrix.

• Endothelial cell surface proteins to initiate invasion.

• Extracellular Proteinases: for hydrolyzing collagen

and elastin.

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Laboratory diagnosis

• Sample specimen: Pus, blood and serum sample

• Laboratory examinations
• Direct microscopic examination of stained pus smear to detect cigar shape, gram
positive spores.
• PAS stain to demonstrate organism: Oval, round or cigar shape.

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Cont..
Isolation of the organism on SDA containing
Chloramphenicol and cycloheximide
• smooth white colony will appear, thin septate
hyphae with microconidia under microscope.
• Incubation period of S.schenckii is 4days in SDA
media

Differential diagnosis:
• Epizootic lymphangitis ,
• Ulcerative lymphangitis.

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Treatment

• Treatment of Sporotrichosis varies with the type of

disease.
• vitro susceptibility studies show good activity for
amphotericin B, Itraconazole, and terbinafine.
• Surgical removal, cryotherapy and thermotherapy,
either alone or in conjunction with antifungal drugs.

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 5. LOBOMYCOSIS
• Lobomycosis, also known as keloidal blastomycosis or
Lobo disease, is an uncommon and chronic
subcutaneous mycosis.

• Lesion: keloidal-verrucoid-nodular

• Site: face, ear, legs

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Etiology

• Obligately parasitic fungus commonly seen in

farmers, fishermen and hunters.

• Dolphin to human transmission is reported.

• Caused by Lacazia loboi previously known as

Loboa loboi.

• Does not grow in culture like SDA media or

tissue culture.

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41
 Clinical features
•Nodular keloid like lesion is the most
common arising from traumatized areas of
the skin, face, extremities and ears.

•The disease does not involve the mucous

membranes or internal organs

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Cont..

• Patients are asymptomatic

• Lacaziosis is characterised by slowly
developing cutaneous nodule of varying size
and shape.
• The dermal lesion are polymorphic ranging
from macule , papule, keloid nodule and
plaques to verrucous and ulcerated lesion, all
of which may be present in a single patient

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Investigation

Direct microscopy
• KOH shows round yeast-
like organisms, singly or in
chains connected by short
tubular projections.

• They have bifringement

membrane with central
granules.
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Treatment

• Surgical excision is a treatment of choice.

• Pharmacological:
i. Clofazimine 300mg/day initial dose with
maintenance dose of 100mg/day for 2
years.
• Ketoconazole, Itraconazole, Posaconazole.
• Electrocautery
• Cryosurgery

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6.SUBCUTNEOUS ZYGOMYCOSIS

• Is a chronic subcutaneous infection characterized by

woody swelling of subcutaneous tissue caused by
Conidiobolus and Basidiobolus.

• Mucorales is a rare but very serious form of

subcutaneous zygomycosis.

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 Mucorales Basidiobolus

Conidiobolus

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48
 Conidiobolus Basidiobolus

Commonly in young adults Commonly seen in young adults

Transmitted by inhalation of fungal Transmitted by minor trauma/insect
spores/frequent nose pricking bit/contaminated toilets/vegetation
habits. containing animal faeces.

Produces elastase, esterase, Produces extracellular proteinase

collagenase and lipase. and lipases.

Thermophilic (grows readily at Thermo tolerant (grows poorly at

37℃). 37℃).

Monstrous disfigurement of Bathing suit distribution with a

face(stuffiness, discharge, epistaxis
and nasal obstruction are
symptoms)
painless well circumcised, firm to
hard, smooth rounded SC masses
that can be raised by inserting
fingers underneath it(freely
mobile). 49
• Microscopy
• KOH from scrapings show broad, septate branching
hyphae
• Culture
Conidiobolus-white surface, becomes beige to brown ,
no odour. Incubation of 2-3 days in SDA at 28 0C -300C.
Basidiobolus- flat and furrowed, yellowish grey colour
with musty odour. Incubation of 3 days at 30 0C on
SDA.
Mucorales-Grows faster, incubation period of 3-7days
in SDA

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Treatment

Itraconazole /SSKI – 1st line choices

Treated continuously for 1-2 months after clinical
cure

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7. RHINOSPORIDIOSIS

• ETIOLOGY AND EPIDEMIOLOGY

Caused by Rhinosporidium seeberi-protistan
parasite of class Mesomycetozoea.
Common pond bathing with buffalos is a risk
factors.
Associated with mucosal disease.

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Cont…

Begin as tiny papules and enlarge to become warts

like/tumorous growth.

They are friable and have crenated surface, often

ulcerated and painless.

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54
 Clinical manifestation

Symptoms (Nasal):
• Unilateral nasal obstruction
• Epistaxis
• Local pruritis
• Rhinorrhoea
• Post nasal discharge with cough
• Foreign body sensation
• History of exposure to contaminant water.

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Cont…

• On examination: Pink to deep red polyps,

Strawberry like appearance, Bleeds easily upon
manipulation.

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• Diagnosis
• KOH for sporangia with endospores.

• Definitive Dx of rhinosporidiosis depends on

histological examination with immunochemistry.

• Culture and serologic test are unsuccessful

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Treatment

• Anti-rhinosporidial Dapsone (4,4- diaminodiphenyl

sulphone) 100mg once daily for 6 months to several
years.( check LFT and blood counts every 2 weeks).

• Surgical excision.

• Electrocoagulation.
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REFERENCES

• Medical Microbiology,4th edition edited by Samuel Baron,1996.

• Slideshare; Classification of mycoses by Dr. Rakesh Prasad Sah published
on Sept 26,2018.
• Slideshare: A presentation on Subcutaneous Mycosis by Dermatology
resident, Dr. Jerriton published on Sept 10,2018.

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Cont…

• Slideshare: Deep mycoses by Saikat Mandal, published on May

26,2015.
• Medical Microbiology, 24th Edition. By Jawetz, Melnick, & Adelberg's.
• Textbook of Microbiology and Immunology, 2nd Edition, Parija.
• http://scmhabra.org/eresources/Microbiology-General_sem-
4_mycoses.pdf

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