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General mycology Last updated: January 7, 2021

Summary

Mycoses are infections caused by fungi. They may be caused by dermatophytes (e.g.,
Trichophyton), yeast (e.g., Candida), or molds (e.g., Aspergillus). In immunocompetent
individuals, mycoses usually result in local infection, which can be treated with local
antifungals. Fungal infections may cause systemic infection in immunocompromised
individuals (e.g., HIV-positive individuals, bone marrow transplant recipients), potentially
leading to meningitis or severe sepsis.

Basics of mycology
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Structure and characteristics of fungi

Fungi are eukaryotes.


Possess a cell wall and a cell membrane that contains ergosterol (analogous to cholesterol
in humans)
Basic morphological elements

Particularly in dermatophytes and molds


Hyphae: multicellular compartments, which are connected by porous septa
Mycelium: a network of hyphae, which are formed by asexual reproduction

Particularly in yeasts
Budding cells (blastospores): in unicellular fungi, formed by budding of daughter cells

Pseudomycelium (pseudohyphae): chains of budding cells, which are stretched in a


hyphen-like manner but are divided by septa

Fungi are not considered plants and are nonphotosynthetic. They extract
energy (e.g., sugar and proteins) from living or dead organic matter.

Azoles target the synthesis of ergosterol, the principal sterol in fungal


cell membranes. They inhibit the synthesis of ergosterol from lanosterol by
interfering with 14α-demethylase (cytochrome P-450 enzyme).

Substances synthesized by fungi

Penicillin by Penicillium chrysogenum

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Toxins
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A atoxins by molds (e.g., Aspergillus avus) on nuts, seeds, and grains; : poisonous
carcinogen associated with hepatocellular carcinoma
Amanitin (see “Amanita phalloides”)

Ergot alkaloids such as ergotamine produced by the ergot fungus Claviceps purpurea,
which grows on rye: causes vasoconstriction by binding to 5-HT1D serotonin receptors
and alpha-adrenergic receptors

Detection of fungal infections

Clinical features and microscopy for evaluation of fungal morphology


Additional characterization via:

Culture, e.g., Sabouraud agar (a growth medium that contains dextrose and peptones)

Staining, e.g.:

Silver stain
India ink stain: a type of negative stain with carbon that is most commonly used to
identify organisms with a polysaccharide capsule such as Cryptococcus neoformans (the
capsule is not penetrated by the ink and appears as a halo around the organism against a
dark background)
Mucicarmine: a staining method used to identify the thick polysaccharide capsule of
some organisms (e.g., Cryptococcus neoformans) and mucin (e.g., in gastric tumors)

Antigen detection, e.g., capsule components in serum

Antibody detection plays a minor role.


Wood lamp examination: a diagnostic test to examine skin lesions with a lamp that emits
ultraviolet light

Used to evaluate super cial fungal infections of the skin (e.g., tinea versicolor) which
appear characteristically yellow-green uorescent under ultraviolet light

Can also be used to evaluate hypopigmented or depigmented lesions (e.g., vitiligo) which
appear blue-white uorescent

Latex agglutination test

Fungi overview

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Dermatophytes: lamentous fungi (mainly affect skin and nails)


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Trichophyton

Microsporum

Epidermophyton species
Yeasts: budding fungi (may affect skin, mucous membranes, and internal organs)

Candida species (particularly Candida albicans) cause candidiasis

Cryptococcus neoformans causes cryptococcosis

Malassezia furfur causes tinea versicolor

Molds: Aspergillus fumigatus causes aspergillosis (may affect internal organs)

Dimorphic fungi: exist as molds (hyphal form) at colder temperatures (∼ 20oC) and as yeasts
at warmer temperatures (∼ 37oC)
Blastomyces dermatitidis

Candida albicans

Histoplasma capsulatum

Sporothrix schenckii

See “Systemic fungal infections” below.

To remember the temperatures at which the different forms of


dimorphic fungi exist, think of “Mold in the cold, yeast in the beast!”.
Dimorphic fungi exist as molds at cooler temperatures (cold) and as yeasts at
warmer temperatures (beastly heat).

Opportunistic fungal infections

Overview of the most common opportunistic fungal infections

Pathogen Risk factors Clinical features Diagno

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Overview of the most common opportunistic fungal infections


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Pathogen Risk factors Clinical features Diagno

Aspergillosis Aspergillus Immunocompromise ABPA ABP


fumigatus Associated with E
Chronic
asthma and
Aspergillus granulomatous E
cystic brosis
avus infection le
Causes P
bronchiectasis i
and eosinophilia c
Pulmonary
Pulm
aspergilloma:
asp
chronic cough,
X
hemoptysis
m
Invasive
S
aspergillosis
p
: fever, cough,
A
respiratory distress
Inva
Endocarditis : tis
sho
bra
hyp
bod

Candidiasis Candida Immunosuppression Oral thrush Bes


albicans (e.g., HIV, sho
Candida esophagitis
diabetes mellitus) yea
Vaginal yeast pse
Medications infection 20°
(antibiotics, steroids
, cytostatic agents, Candidiasis of the Con
immunosuppressive skin: erythematous cult
therapy patches with small tiss
) satellite lesions in
AID
intertriginous areas
↑ Estrogen levels and digital web
con
during pregnancy if es
spaces
trac
Hematologic
Diaper dermatitis lung
malignancies (e.g.,
Disseminated: sepsis invo
acute myeloid
leukemia , meningitis, multiple
, multiple myeloma) abscesses,
endocarditis
Compromised skin
(excessive moisture,
local lesions from
dentures or burns)

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Overview of the most common opportunistic fungal infections


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Pathogen Risk factors Clinical features Diagno

Cryptococcosis Cryptococcus AIDS Cryptococcal Late


neoformans meningoencephalitis test
Exposure to pigeon
or brain abscess : po
droppings/soil
Hematogenous cryp
Transmission via spread of fungi to poly
inhalation meninges cap
H
Headache, fever,
a
signs of increased
intracranial S
pressure o
, confusion, CSF
absent I
meningeal signs c
Isolated pneumonia
M
is possible
s
i
p
c

F
S
s

MR
lesi
cryp
enc
AID
con
if ex

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Overview of the most common opportunistic fungal infections


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Pathogen Risk factors Clinical features Diagno

Pneumocystis P. jirovecii Immunosuppression Fever, CT:


(previously (especially if CD4 exertional dyspnea, gro
pneumonia
P. carinii) count < 200/μL) nonproductive opa
cough, weight loss,
impaired
X-ra
oxygenation
opa
Bro
lava
or lu
spu
silve
imm
sho
yea
AID
con

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Overview of the most common opportunistic fungal infections


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Pathogen Risk factors Clinical features Diagno

Zygomycetes Diabetes, Invasive Ima


Mucormycosis Mucor and particularly with chronic sinusitis and A
Rhizopus ketoacidosis orbital cellulitis o
(e.g., a
Immunosuppression May lead to tissue
Rhizopus i
Chronic sinusitis (> necrosis and and
oryzae)
3 months) contiguous spread H
to the orbit, brain, w
Iron overload or and palate i
treatment with Headache, facial i
deferoxamine pain Tiss
Black necrotic (con
eschar on face ang
and/or palate irre
bro
Possible cranial
hyp
nerve
involvement
Rhinocerebral,
frontal lobe abscess
Cavernous sinus
thrombosis
Pulmonary
mucormycosis:
aggressive infection
of the bronchioli and
alveoli, manifesting
with fever and
hemoptysis
Cerebritis,
mediastinitis,
cardiac involvement
in severe cases

Candida, Aspergillus, and Cryptococcus are opportunistic fungal pathogens


with low inherent virulence. They commonly cause systemic mycoses in
immunocompromised hosts but do not normally affect healthy hosts.

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Cutaneous fungal infections

Overview of the most common cutaneous fungal infections

Pathogen Risk factors Clinical features Diagnostic

Dermatophytes Trichophyton Profuse sweating, Tinea capitis Best ini


obesity, diabetes, (head): scaling KOH sh
Microsporum
immunosuppression and hair loss hyphae
Epidermophyton
Tinea corporis Con rm
(body): ring- fungal c
shaped, pruritic Wood l
lesions with test for
central clearing tinea ca
and elevated
borders on an
erythematous
base
Tinea cruris
(groin): usually
spares the
scrotum
Tinea manuum
(hand),
tinea pedis
(foot): pruritic
lesions in
interdigital
spaces, on the
soles of the feet
or as vesicles
Onychomycosis
(nails): thick,
opaque nails

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Overview of the most common cutaneous fungal infections


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Pathogen Risk factors Clinical features Diagnostic

Tinea Malassezia Hot or humid Small, Best ini


furfur weather conditions hyperpigmented KOH sh
versicolor
or short hy
( hypopigmented and spo
pityriasis macules on that hav
versicolor chest and back “spaghe
and
)
meatba
May coalesce to
appeara
form patches

Systemic fungal infections


Etiology

Pathogen: dimorphic fungi

No interpersonal transmission
Clinical features: pneumonia, disseminated systemic infection

Overview of the most common systemic fungal infections

Pathogen Risk factors Clinical features

Histoplasmosis Histoplasma Endemic areas: Often asymptomatic


capsulatum Mississippi and the
Flulike illness: fever
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Flulike illness: fever,
Ohio river valley
Overview of the most common systemic fungal infections weight loss,
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Exposure to bird or erythema nodosum,
bat droppings in hepatosplenomegaly,
Pathogen Risk factors Clinical features
endemic areas lymphadenopathy,
through activities nonproductive cough
such as spelunking Ulcerative oral lesion
(cave exploration) (palatal, tongue ulcer
Immunosuppression
(e.g., AIDS)

Coccidioidomycosis ( Coccidioides Travel to Flu-like illness or


immitis Southwestern pneumonia: fever,
valley fever)
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valley fever)
United States, cough, night sweats,
Overview of the most common systemic fungal infections
California REGISTER / LOG
anorexia, chest pain,IN
and dyspnea
Soil/dust exposure
Pathogen Risk factors Clinical features
in endemic areas Extrapulmonary
(e.g., during ndings
windstorms, CNS: meningitis
earthquakes, Skin:
archeological erythema nodosum
explorations) [2] (desert bumps)
Joints: arthralgia
(desert rheumatism
Bone: multiple
osteolytic lesions [

Paracoccidioidomycosis Paracoccidioides Travel to South and Infected patients ofte


species Central America asymptomatic
Paracoccidioides
brasiliensis
♂>♀ [4] Painful nasal,
pharyngeal, and
Paracoccidioides laryngeal mucosal
lutzii ulcerations
Lymphadenopathy
(usually cervical)
Can disseminate →
extrapulmonary
manifestations (e.g.,
verrucous skin lesion
similar to those of
cutaneous
blastomycosis)

Blastomyces Travel to Pneumonia


Blastomycosis dermatitidis Southeastern,
Extrapulmonary
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Extrapulmonary
Central, Eastern,
Overview of the most common systemic fungal infections ndings
and the Great Lakes REGISTER / LOG IN
Skin: verrucous
region of the United
lesions and
Pathogen Risk factors
States Clinical features
granulomatous
nodules (lesions
resemble
squamous cell
cancer
)
Bone:
osteolytic lesions
(most commonly in
the ribs, vertebrae
and long bones) [5]
Genitourinary
involvement:
prostatitis, orchitis
epididymitis
CNS lesions:
meningitis,
epidural/intracran
abscesses

“History of the hidden Ohio and Mississippi river valleys:” Histoplasma is


hidden within macrophages and Ohio and Mississippi river valleys are the
endemic regions of histoplasma.

“Paracoccidiomycosis steers the ship to South and Central America at the


captain's wheel: ”Paracoccidiomycosis is endemic in South and Central
America and its budding yeast has a captain's wheel appearance.

The yeast form of Blastomycosis forms broad-based buds.

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Unlike most other dimorphic fungi, Blastomyces can cause disseminated


disease even in immunocompetent hosts.

Other fungal infections

Sporotrichosis (Rose gardener disease)

Etiology
Pathogen: Sporothrix schenckii (a dimorphic fungus that feeds on vegetation)

Risk factor: traumatic injury to the skin while gardening (e.g., thorn prick)
Clinical features

Pustules and ulcers with ascending lymphangitis


Nodules along draining lymphatics

Disseminated disease (in immunocompromised patients): pneumonia, meningitis


Diagnostics

Fungal culture; (sputum, pus, biopsy tissue) showing dimorphic, cigar-shaped yeast (this
form exists in humans)

Septate hyphae, rosette-like clusters of conidia at the tips of the conidiophores (this form
exists in soil/vegetation)

Treatment
Cutaneous or lymphocutaneous: oral itraconazole OR potassium iodide
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Disseminated: IV amphotericin B
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“A rose gardener plants roses in a pot while smoking a cigar:” sporotrichosis is


associated with traumatic gardening injuries, treatment includes potassium
iodide, and Sporothrix appears as a cigar-shaped yeast in culture.

Dermatophytes
Pathogenicity

Dermatophytes produce keratinase, which allows them to infect the skin, hair, and nails.
Many dermatophytes are obligate pathogens.

Morphology
Form hyphae and mycelium

After penetration into the skin, concentric propagation may occur around the entry site.

Overview of the most important dermatophytes

Characteristics Diseases Treatment

Occurs worldwide Tinea corporis Local: terbina ne PLUS


Trichophyton (ringworm) azoles
Partial yellow-green
species
uorescence under Tinea capitis Systemic: terbina ne,
Wood lamp itraconazole, uconazole,
Tinea or griseofulvin
Occurs worldwide unguinum (
Epidermophyton
No typical onychomycosis
species )
uorescence under
Wood lamp Tinea cruris (
jock itch)

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Tinea pedis (
Overview of the most important dermatophytes
athlete's foot) REGISTER / LOG IN

Characteristics Diseases Treatment

Occurs worldwide
Microsporum
Partial blue-green
species
uorescence under
Wood lamp

Yeasts
Pathogenicity
Usually an opportunistic pathogen

Can infect the skin, mucous membranes, or internal organs


Morphology

Demonstrate budding cells and pseudomycelium


Single yeast cells are 5–8 μm in size.
Gram positive staining

Overview of the most important yeasts

Characteristics Diseases Treatment

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Overview of the most important yeasts


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Characteristics Diseases Treatment

Candida albicans is the most Vaginal yeast Local: ciclopirox,


Candida common Candida species infection nystatin,
species worldwide and is almost , balanitis clotrimazole,
exclusively found in miconazole,
Erosio
humans. ketoconazole
interdigitalis
blastomycetica Systemic
IV caspofungin OR
Oral thrush micafungin (
echinocandins)
Candida
Alternatively:
esophagitis
uconazole
OR
Candidal amphotericin B
intertrigo
Invasive
candidiasis

Humans are infected via Cryptococcal Amphotericin B


Cryptococcus contaminated dust meningitis PLUS ucytosine,
neoformans particles. followed by
uconazole
Possesses a capsule, which Cryptococcosis
maintenance therapy
can be visualized using
for at least 12
India ink
months

Yellow-orange uorescence Tinea Local: selenium


Malassezia under Wood lamp versicolor sul de lotion or
furfur shampoo, miconazole
Particularly present in the
, ketoconazole, OR
infundibulum of the hair Involved in the
terbina ne
follicle pathogenesis
of Systemic:
seborrheic uconazole OR
eczema itraconazole

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Molds
Pathogenicity
Usually an opportunistic pathogen

Mold antigens are one of the most frequent causes of allergies.


Molds produce various toxins. Infection is caused by either aerogenic uptake or is
foodborne (e.g., a atoxins).
Morphology

Formation of monomorphic septate hyphae that branch at 45° and mycelium


Mold can infest food products and acquire a fuzzy appearance that is macroscopically
visible.
Pathogen: Aspergillus fumigatus

Ubiquitous occurrence
Some species produce a atoxins

Diseases
Aspergillosis

Allergic bronchopulmonary aspergillosis (ABPA)


Aspergilloma

Invasive pulmonary aspergillosis


Endocarditis
Treatment

ABPA
Oral prednisone if severe
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Itraconazole if recurrent
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Pulmonary aspergilloma: lobectomy
Invasive aspergillosis: IV voriconazole, caspofungin, amphotericin

References
1. Zhang P, Lian L, Wang F. Magnetic resonance imaging features of gelatinous pseudocysts in
cryptococcal meningoencephalitis. Acta Neurol Belg. 2018; 119 (2): p.265-267. doi:
10.1007/s13760-018-1033-6 . | Open in Read by QxMD

2. Thompson G, Brown J, Benedict K, Park B. Coccidioidomycosis: epidemiology. Clinical


Epidemiology. 2013 : p.185. doi: 10.2147/clep.s34434 . | Open in Read by QxMD
3. Arora NP, Taneja V, ReyesSacin C, Bhanot R, Natesan SK. Coccidioidomycosis masquerading
as malignancy.. BMJ case reports. 2012; 2012 . doi: 10.1136/bcr.12.2011.5357 . | Open in
Read by QxMD
4. Paracoccidioidomycosis. https://rarediseases.org/rare-diseases/paracoccidioidomycosis/ .
Updated: January 1, 2009. Accessed: April 22, 2020.

5. Blastomycosis. https://rarediseases.org/rare-diseases/blastomycosis/ . Updated: January 1,


2009. Accessed: May 2, 2020.

6. Kumar V, Abbas AK, Aster JC. Robbins & Cotran Pathologic Basis of Disease. Elsevier
Saunders ; 2014

7. Le T, Bhushan V, Sochat M, Chavda Y, Zureick A. First Aid for the USMLE Step 1 2018.
McGraw-Hill Medical ; 2017

8. Brooks G, Carroll KC, Butel J, Morse S, Mietzner TA. Jawetz Melnick & Adelbergs Medical
Microbiology. McGraw Hill Professional ; 2012

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