1
Q

Which primary Fungal infections from inhalation

A

Cryptococcus
Histoplasmosis - dimorphic
Paracoccidioidomycosis - dimorphic
Talaromyces - dimorphic
Coccidioides - dimorphic
Blastomyces - dimorphic

[no human-human]

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2
Q

Which fungal infection has a tendency to migrate from lungs -> target Joints/bones/skin/CNS?
What is the skin disease?
Geography?
Found where?
Rx mild?CNS? Disseminated?

A

coccidioides immitis - califonia ‘Valley fever’
C. Posadasii - everywhere else

Skin rash, either diffuse pruritic erythematous rash or erythema multiforme or erythema nodosum

Western US central/south America

Itraconazole for mild
Amphotericin B for severe / disseminated

dimorphic fungus
[coccyx is a bone]

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3
Q

Generally when would you use fluconazole vs itraconazole for fungal infetions

A

Fluconazole -> CNS / joints
-Azole of choice for candida, crypto, and CNS cocci

Itra -> skin / abdo
-blasto , histo , sporo , and non CNS cocci.

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4
Q

Which primary fungal infection Lung - > (lymph nodes) skin and mucus eg oral nasal
Geography?
Found where?
Rx if mild?

A

paracoccidioides brasiliensis (lutzii)
Jungle soil brazil/peru/columbia
itraconazole

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5
Q

Which fungal infection if infection in HIV starts in lung -> CNS?
Found where?
2 strains - which one causes meningitis in immunocompetent?

A

Cryptococcus. neoformans - Bird poo [new poo to fall on the mans]

Cryptococcus. Gatti - Eucalyptus trees
-Can cause cryptococcus meningitis even in immunocompetent [Gatt out of my head]

Any extrapulm/CNS manifestations are always in immunocompromised

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6
Q

Which primary fungal infection Lung - > liver/spleen + nodes + (skin/adrenal)
Found where?
Geography?
Rx if mild?
Which -azole is the only one that doesn’t really work?

A

histoplasma capsulatum
bird poo and soil
Worldwide - mostly in the Americas

Particularly cavitating in lungs

[-capsule in the lungs
-spleen protects from capsulated bacteria. liver capsule pain]

Itraconazole - mild/mod disease
Liposomal Amphotericin B if severe /disseminated disease

[Fluconazole sucks for histo]

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7
Q

Which fungal infection mostly lungs -> Skin pustules, papules, warts or ulcers. They are usually painless?
Found where
Rx if mild?

A

blastomyces dermatitidis
North America
-(little bit in Africa / middle east)

Itraconazole
Ampho if disseminated / CNS

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8
Q

Histoplasmosis bug

A

Histoplasma capsulatum - dimorphic fungus

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9
Q

Histoplasmosis infection from? clincial features acute vs chronic pulm sx?

A

Bat / bird poo
-Get from inhalation eg from caves

May be asymptomatic

Acute pulm histoplasmosis
-acute broncopulm illness with generalised shadowing on CXR

Chronic pulm histoplasmosis
-Causes pulm nodules which can be seen on CXR. may cause focal consolidation / cavitation

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10
Q

Who gets acute disseminated histoplasmosis? Differentiate from cryptococcus?

A

Immunocompromised - often AIDS

Much more oral ulceration in histoplasmosis

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11
Q

Histoplasmosis dx? rx?

A

Blood / sputum culture
intradermal histoplasmin skin test
From any other biopsy / sample

Often self limiting
Best is 200mg daily itraconazole [can use fluconazole]
-may require either term secondary prophylaxis

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12
Q

Cause of African histoplasmosis? often called? how is it different?

A

Histoplasma capsulatum duboisii
‘Progressive disseminated histoplasmosis’
Usually presents with skin nodules / ulcers

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13
Q

2 key stains for fungi

A

Periodic acid-schiff (PAS)
methenanine silver
KOH

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14
Q

Pustule / nodule usually on hand followed by spread along lymphatics causing nodular ulcerating lesions most commonly? rx?

A

Sporothrix schenckii
itraconazole for 3 months

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15
Q

sporotrichosis diangnosis

A

smear microscopy and culture in Sabouraud’s medium

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16
Q

Common age and gender paracocci? Geography

A

Males aged 30-50
-Oestrogen prevents transformation of mould to yeast

Humid rain forest around 1000-1500m
South America only

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17
Q

Acute vs chronic paracocci
Usual age
Skin test
Which organ common

A

Acute
- young ~20s
- Skin test negative (Don’t mount a TH1 response)
- Fever + lymph nodes + liver/spleen + skin

Chronic
- Older ~45
- skin test positive
- Lung + oral mucosa (some lymph nodes)

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18
Q

Which paracocci - Lymphadenopathy, oral ulcers and bilat pulm infiltrates

A

Chronic adult (multifocal)

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19
Q

Which paracocci with hepatosplenomegally and these facial lesions

A

Acute-juvenile

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20
Q

Pulm paracocci differentiate from TB

A

Apex of lung look normal
-cavitary lesions and pleural effusions are
less common
[Similar to histoplasmosis]

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21
Q

Paracocci vs mucosal leish oral lesions

A

Para - haemorrhagic dots, gum/teeth/lips involvement common
Painful

Leish - nasal collapse, granuloma

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22
Q

Paracocci chronic vs acute biopsy

A

Acute - more extensive necrosis, more yeast

Chronic - granulomas, and fibrosis

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23
Q

2 main culture mediums for fungi

A

Sabouraud Dextrose Agar (SDA)
Mycosel Agar (Chloramphenicol + Cycloheximide)

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24
Q

Name 3 fungi that can cause primary subcut disease

A

Sporothrix schenckii/ brasiliensis
Fonsecaea pedrosoi
Lacazia loboi
Madurella mycetomatis

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25
Q

Most likely Dx?

A

Sporotricosis

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26
Q

Most likely?

A

Sporotrichosis

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27
Q

Most likely

A

Sporotricosis

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28
Q

What temp do I grow best at?

A

sporotrichosis 25-30 degrees

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29
Q

Sporothrix . schenckii diagnosis

A

Culture -> microscopy

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30
Q
A

Chromoblastomycosis

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31
Q
A

Chromoblastomycosis

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32
Q

Chromoblastomycosis diagnosis

A

Sclerotic bodies on KOH stain

[culture several forms - Phialophora verrucosa, Fonsecaea pedrosoi, Fonsecaea compact, Cladophialophora carrionii]

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33
Q
A

Mycetoma

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34
Q

Mycetoma with these grains?

A

Fungal - eumycetoma

KOH stain - can see hyphae on grain

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35
Q

Swelling of foot - which stain best to see hyphae on grain?

A

PAS - eumycetoma

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36
Q

Dx eumycetoma?

A

Direct examination: Hyphae within the grains

Black grains

Culture: Madurella mycetomatis
[Madurella grisea, Pseudoallesheria boydii]

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37
Q

Spot dx?

A

Lobomycosis

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38
Q
A

Lacazia loboi blastospores, KOH (x400)

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39
Q
A

Lacazia loboi blastospores, Histopatology, Grocott x 400

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40
Q

Lobomycosis dx?

A

Direct examination: Round to lemon shaped-cells
- either singly or in short chains.

[Culture: Never isolated]

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41
Q
A

Paracocci
Gums affected

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42
Q
A

Paracoccidiodes brasiliensis blastospores, KOH (x 400)

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43
Q
A

Paracoccidiodes brasiliensis blastospores, Grocott (x 400)

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44
Q

Paracoccidiodes brasiliensis dx?

A

Direct examination: Characteristic budding yeasts. (85%)

Culture: Paracoccidioides brasiliensis and Paracoccidioides lutzii.
Histopathology: Characteristic budding cells
Serology: Immunodiffusion test* easy

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45
Q
A

Histoplasmosis

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46
Q
A

Histoplasma capsulatum blastospores (Giemsa stain, 1000x)

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47
Q
A

Histoplasma capsulatum, Culture and KOH preparation (x400)

48
Q

Histomplasmosis Dx?

A

Lots of options …

Urine Antigen
Culture - Histoplasma capsulatum complex (Sepedonium chrysospermum)
Serology - immunodiffusion
Histopathology - Giemsa stain: *very small Small yeast cells

49
Q
A

C. neoformans blastospore (India ink)

50
Q
A

Yeast cells of C.neoformans, Mayer’s mucicarmine stain ( X1000 )
Mayers - stains cryptococcus capsule red

51
Q

Cryptococcus diagnosis

A

India Ink: Encapsulated yeasts
Culture: Cryptococcus neoformans, Cryptococcus
gattii
Histopathology: Encapsulated yeasts
Serology: Latex agglutination test,
Crypto Antigen LFA test (CRAG)

52
Q
A

Aspergillus hyphae (KOH)

53
Q
A

Aspergillus hyphae (KOH)

54
Q
A

Dichotomous branching hyphae of Aspergillus, PAS (X1000)

55
Q
A

Aspergillus fumigatus (KOH X400)

56
Q
A

Aspergillus flavus (KOH X400)

57
Q
A

Aspergillus niger (KOH X400)

58
Q

Aspergillous diagnosis

A

Direct examination: Branching hyphae
Culture: Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Aspergillus oryzae, etc.
Histopathology: Branching hyphae
Serology:
-Antibodies: Immunodiffusion
-Antigen: Platelia, Aspergillus Antigen Immunoassay.

59
Q

What is this?

A

Immunodiffusion - negative sample is one at the bottom

60
Q
A

Histoplasma
NOT amatigotes

61
Q
A

Histoplasma

62
Q
A

Histoplasma

63
Q
A

Morphology of macro-colony of:
(A) Aspergillus flavus;
(B) Aspergillus fumigatus;
(C) Aspergillus niger

on Sabouraud Dextrose agar (top images),
micro-colonies on slide agar (bottom images).

64
Q
A

Aspergillus fumigatus (culture)

65
Q
A

Aspergillus niger (Culture)

66
Q

What carries the virulence for cryptococcus

A

Capsule - acapsular forms cause almost no disease

[Capsule is:
-Antiphagocytic
-Depletes complement
-Produces antibody unresponsiveness
-Dysregulates cytokine secretion
-Produces brain oedema]

67
Q

Common finding in phenotypically normal patients who get cryptococcal CNS? usually how long to diagnosis from start of symptoms?

A

antibodies to IFN γ receptors

Diagnosis takes:
-3 months for normal people
-1 month for immunocompromised

68
Q

Who gets cryptococcus cellulitis

A

Mostly organ transplant
[HIV + other immunocompromised]

Note capsule on biopsy

69
Q

Along with drug rx what is the key aspect of cryptococcal meningitis Rx

A

Therapeutic LP

70
Q

Why is this not a bacterial pneumonia? 3 key DDx

A

Nodular - especially if multinodular
Bilateral

[fungal / TB / nocardia]

71
Q

Cause of central African histoplasmosis

A

Histoplasma duboisii

72
Q

35 yo man with advanced HIV; CD4=13
He presents with 2 week h/o progressive diffuse papular rash, fever (40C), hypotension (90/50) and dyspnea (RR= 36).
Alveolar biopsy show image + bone marrow all demonstrate

A

Histoplasma capsulatum

73
Q
A

blood with intracellular
H. capsulatum

74
Q
A

KOH prep from sputum with narrow
based budding yeasts
H capsulatum

75
Q
A

KOH prep from sputum with narrow
based budding yeasts
H capsulatum

76
Q

41 YOM with rheumatoid arthritis related interstitial lung
disease on immunosuppressive medications who presented with syncope and acute gastrointestinal bleeding. Duodenal perf
Had incidentally discovered cavitary nodules on CT chest
lesion on tongue

A

Histoplasma capsulatum
Silver stain (GMS)

77
Q

lymphadenopathy, hepatosplenomegaly, and skin and mucous membrane lesions (papules, pustules, ulcers, and nodules).

Adrenal insufficiency and hypercalcemia should raise suspicion of?

A

Disseminated histoplasmosis

78
Q

Histoplasmosis Ix?

A

Urine / serum antigen
Culture
Serology - immunodiffusion
Histopathology

79
Q
A

Histoplasma capsulatum

80
Q

Visited desert in califonia 4 weeks ago. Now arthralgia and erythema nodosum

A

Coccidioides immitis

81
Q

18yo male college student from south Alabama with a 6 months h/o scant sputum production with streaky hemoptysis. Aching in joints.
Insulin dependent DM (age 3),
SH: He visited Laredo, TX, and Northern Mexico on a
hunting trip approx 2 years ago (2 weeks prior to initial
episode of CAP). No tobacco or drugs. He drinks alcohol

A

Coccidiodes spp .

82
Q

Most common site affected in Disseminate Coccidioidomycosis

A

skin
[bones and joints especially knee / vertebrae]

83
Q

bar causes of immunosuppression, name 2 at-risk groups for disseminated Coccidioidomycosis?

A

, African American and Filipino men >60 years.
Pregnant women 2-3rd trimester

84
Q

Coccidioidomycosis ix?

A

Lateral flow device best

Culture - grows in 3-7 days

histopathology. Identification of spherules

85
Q

Coccidioidomycosis CNS infection and cant toleerate fluconazole / AmphoB

A

Voriconazole for those who cannot tolerate fluconazole

86
Q

Name 2 causes of sporotrichosis? which in China&India?

A

Sporothrix schenckii
(S. mexicana, S. globosa, S. brasiliensis, S. luriei)

87
Q

Sporotrichosis Rx

A

Itraconazole
-Treatment of choice in most settings

Fluconazole
-Not as effective as itra , but available and well tolerated

Terbinafine 500 mg bid
-Effective but expensive

88
Q

Sporotrichosis local therapy

A

Heat - thermotherapy
Saturated solution of Potassium Iodide (SSKI)

89
Q

Which inhaled fungi is most commonly dissemninated at presentsiton?

A

Blastomycosis
-pulmonary (60-80%),
-skin (40-60%),
-osseous (20-30%),
-genitourinary (10%)
-CNS (<5%)

90
Q
A

Classic broad based budding yeast with doubly refractile cell wall of B. dermatitidis

91
Q

Broad based budding yeast =

A

PAS stain of B. dermatitidis

92
Q

Diagnosis blastomycosis

A

-characteristic broad based budding yeasts in clinical specimens.
-Culture hard
-Serologic test (urine assay, MiraVista Diagnostics) is sensitive but non specific, cross reacts with Histo/Cocci antigens

93
Q

Main difference with fungal and mammal cells?

A

Fungal has a rigid cell wall
- we just have a cell membrane

94
Q

Flucytosine mechanism

A

DNA synthesis
[only antifungal with this mechanism]

Azoles work on cell membrane

95
Q

Toxicity with amphotericin 2 parts?

A

During infusion -> fever / rigors / hypotension

Renal toxicity + HypoK/Mg

96
Q

Amphotericin mechanism

A

Binds to cell membrane (not wall) to ergosterol and makes a pore
-> leaks K/Mg = fungicidal

97
Q

2 Key fungi resistant to ampho B

A

Aspergillus terreus
Candida auris

98
Q

How do the -azoles work?

A

Azoles inhibit the synthesis of ergosterol by blocking demethylation of lanosterol

99
Q

Why ketoconazole rarely used

A

Very hepatotoxic
Oral only

100
Q

Which has more interactions intra or fluconazole

A

Itra

101
Q

Key side issue with itraconazole bar drug interactions

A

Fluid retention + increased BP
->heart failure in susceptible people

[liver disease too]

102
Q

Which candida does fluconazole not work on

A

Candida krusei

[Kruseis past]

103
Q

Which of the -azoles does not work on aspergillus?

A

fluconazole

104
Q

Which -azoles work against the zygomycetes - eg mucormycosis

A

Posaconazole
Isavuconazole

105
Q

voriconazole side effects

A

Temporary visual disturbance
Rash and link to skin Ca
Mild hepatotoxicity

[v - visual]

106
Q

Which of the -azoles has the broadest spectrum? Key issue?

A

Posaconazole (analogue of itraconazole)
-Has same issue with fluid retention/cardiac as itra too

107
Q

Which 2 azoles get into the CNS best

A

Fluconazole
Voriconazole

108
Q

Aspergillosis first choice azole

A

Voriconazole

109
Q

What class is Caspofungin? Mechanism? Admisinisteration? side effects?

A

Echinocandins
-Inhibit B-D glucan synthase

only IV

Very few side effects and interactions

110
Q

What are the only organisms sensitive to Echinocandins (-fungins)?

A

Candida
Aspergillus
[PCP]

111
Q

1st line Rx invasive candida? When would they not be?

A

-Fungins Eg Caspofungin

CNS
[also low data for opthal/urine candida]

112
Q

Flucytosine (5-FC) key side effects

A

Pancytopenia (think its almost 5-FU chemo)
-Mild hepatic/GI

113
Q

5-FC works on which 2 bugs? which sneaky resistant one?

A

Cryptococcus
Candida - but NOT C. krusei

(it kreuseis past)

114
Q

SSKI
supersaturated potassium iodide only real use

A

Sporotrichosis

115
Q
A

Coccidioides immitis spherules

116
Q

Name the dimorphic fungi

A

Body Heat Temperature Probably Changes Shape

Blastomyces dermatitidis.
Histoplasma capsulatum
Talaromyces marneffei
Paracoccidioides brasiliensis.
Coccidioides immitis.
Sporothrix schenckii.

117
Q

Nasal stuffiness, facial pain and oedema with necrotic black nasal turbinates. Dx? Looks like on microscopy? Rx?

A

Mucor ssp
Amphotericin B and Posiconazole

wide ribbon-like, non-septated hyphae that are right angle branching.