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
Most likely Dx?
Sporotricosis
26
Most likely?
Sporotrichosis
27
Most likely
Sporotricosis
28
What temp do I grow best at?
sporotrichosis 25-30 degrees
29
Sporothrix . schenckii diagnosis
Culture -> microscopy
30
Chromoblastomycosis
31
Chromoblastomycosis
32
Chromoblastomycosis diagnosis
Sclerotic bodies on KOH stain [culture several forms - Phialophora verrucosa, Fonsecaea pedrosoi, Fonsecaea compact, Cladophialophora carrionii]
33
Mycetoma
34
Mycetoma with these grains?
Fungal - eumycetoma KOH stain - can see hyphae on grain
35
Swelling of foot - which stain best to see hyphae on grain?
PAS - eumycetoma
36
Dx eumycetoma?
Direct examination: Hyphae within the grains Black grains Culture: Madurella mycetomatis [Madurella grisea, Pseudoallesheria boydii]
37
Spot dx?
Lobomycosis
38
Lacazia loboi blastospores, KOH (x400)
39
Lacazia loboi blastospores, Histopatology, Grocott x 400
40
Lobomycosis dx?
Direct examination: Round to lemon shaped-cells - either singly or in short chains. [Culture: Never isolated]
41
Paracocci Gums affected
42
Paracoccidiodes brasiliensis blastospores, KOH (x 400)
43
Paracoccidiodes brasiliensis blastospores, Grocott (x 400)
44
Paracoccidiodes brasiliensis dx?
Direct examination: Characteristic budding yeasts. (85%) Culture: Paracoccidioides brasiliensis and Paracoccidioides lutzii. Histopathology: Characteristic budding cells Serology: Immunodiffusion test* easy
45
Histoplasmosis
46
Histoplasma capsulatum blastospores (Giemsa stain, 1000x)
47
Histoplasma capsulatum, Culture and KOH preparation (x400)
48
Histomplasmosis Dx?
Lots of options ... Urine Antigen Culture - Histoplasma capsulatum complex (Sepedonium chrysospermum) Serology - immunodiffusion Histopathology - Giemsa stain: *very small Small yeast cells
49
C. neoformans blastospore (India ink)
50
Yeast cells of C.neoformans, Mayer’s mucicarmine stain ( X1000 ) Mayers - stains cryptococcus capsule red
51
Cryptococcus diagnosis
India Ink: Encapsulated yeasts Culture: Cryptococcus neoformans, Cryptococcus gattii Histopathology: Encapsulated yeasts Serology: Latex agglutination test, Crypto Antigen LFA test (CRAG)
52
Aspergillus hyphae (KOH)
53
Aspergillus hyphae (KOH)
54
Dichotomous branching hyphae of Aspergillus, PAS (X1000)
55
Aspergillus fumigatus (KOH X400)
56
Aspergillus flavus (KOH X400)
57
Aspergillus niger (KOH X400)
58
Aspergillous diagnosis
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
What is this?
Immunodiffusion - negative sample is one at the bottom
60
Histoplasma NOT amatigotes
61
Histoplasma
62
Histoplasma
63
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
Aspergillus fumigatus (culture)
65
Aspergillus niger (Culture)
66
What carries the virulence for cryptococcus
Capsule - acapsular forms cause almost no disease [Capsule is: -Antiphagocytic -Depletes complement -Produces antibody unresponsiveness -Dysregulates cytokine secretion -Produces brain oedema]
67
Common finding in phenotypically normal patients who get cryptococcal CNS? usually how long to diagnosis from start of symptoms?
antibodies to IFN γ receptors Diagnosis takes: -3 months for normal people -1 month for immunocompromised
68
Who gets cryptococcus cellulitis
Mostly organ transplant [HIV + other immunocompromised] Note capsule on biopsy
69
Along with drug rx what is the key aspect of cryptococcal meningitis Rx
Therapeutic LP
70
Why is this not a bacterial pneumonia? 3 key DDx
Nodular - especially if multinodular Bilateral [fungal / TB / nocardia]
71
Cause of central African histoplasmosis
Histoplasma duboisii
72
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
Histoplasma capsulatum
73
blood with intracellular H. capsulatum
74
KOH prep from sputum with narrow based budding yeasts H capsulatum
75
KOH prep from sputum with narrow based budding yeasts H capsulatum
76
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
Histoplasma capsulatum Silver stain (GMS)
77
lymphadenopathy, hepatosplenomegaly, and skin and mucous membrane lesions (papules, pustules, ulcers, and nodules). Adrenal insufficiency and hypercalcemia should raise suspicion of?
Disseminated histoplasmosis
78
Histoplasmosis Ix?
Urine / serum antigen Culture Serology - immunodiffusion Histopathology
79
Histoplasma capsulatum
80
Visited desert in califonia 4 weeks ago. Now arthralgia and erythema nodosum
Coccidioides immitis
81
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
Coccidiodes spp .
82
Most common site affected in Disseminate Coccidioidomycosis
skin [bones and joints especially knee / vertebrae]
83
bar causes of immunosuppression, name 2 at-risk groups for disseminated Coccidioidomycosis?
, African American and Filipino men >60 years. Pregnant women 2-3rd trimester
84
Coccidioidomycosis ix?
Lateral flow device best Culture - grows in 3-7 days histopathology. Identification of spherules
85
Coccidioidomycosis CNS infection and cant toleerate fluconazole / AmphoB
Voriconazole for those who cannot tolerate fluconazole
86
Name 2 causes of sporotrichosis? which in China&India?
Sporothrix schenckii (S. mexicana, S. globosa, S. brasiliensis, S. luriei)
87
Sporotrichosis Rx
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
Sporotrichosis local therapy
Heat - thermotherapy Saturated solution of Potassium Iodide (SSKI)
89
Which inhaled fungi is most commonly dissemninated at presentsiton?
Blastomycosis -pulmonary (60-80%), -skin (40-60%), -osseous (20-30%), -genitourinary (10%) -CNS (<5%)
90
Classic broad based budding yeast with doubly refractile cell wall of B. dermatitidis
91
Broad based budding yeast =
PAS stain of B. dermatitidis
92
Diagnosis blastomycosis
-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
Main difference with fungal and mammal cells?
Fungal has a rigid cell wall - we just have a cell membrane
94
Flucytosine mechanism
DNA synthesis [only antifungal with this mechanism] Azoles work on cell membrane
95
Toxicity with amphotericin 2 parts?
During infusion -> fever / rigors / hypotension Renal toxicity + HypoK/Mg
96
Amphotericin mechanism
Binds to cell membrane (not wall) to ergosterol and makes a pore -> leaks K/Mg = fungicidal
97
2 Key fungi resistant to ampho B
Aspergillus terreus Candida auris
98
How do the -azoles work?
Azoles inhibit the synthesis of ergosterol by blocking demethylation of lanosterol
99
Why ketoconazole rarely used
Very hepatotoxic Oral only
100
Which has more interactions intra or fluconazole
Itra
101
Key side issue with itraconazole bar drug interactions
Fluid retention + increased BP ->heart failure in susceptible people [liver disease too]
102
Which candida does fluconazole not work on
Candida krusei [Kruseis past]
103
Which of the -azoles does not work on aspergillus?
fluconazole
104
Which -azoles work against the zygomycetes - eg mucormycosis
Posaconazole Isavuconazole
105
voriconazole side effects
Temporary visual disturbance Rash and link to skin Ca Mild hepatotoxicity [v - visual]
106
Which of the -azoles has the broadest spectrum? Key issue?
Posaconazole (analogue of itraconazole) -Has same issue with fluid retention/cardiac as itra too
107
Which 2 azoles get into the CNS best
Fluconazole Voriconazole
108
Aspergillosis first choice azole
Voriconazole
109
What class is Caspofungin? Mechanism? Admisinisteration? side effects?
Echinocandins -Inhibit B-D glucan synthase only IV Very few side effects and interactions
110
What are the only organisms sensitive to Echinocandins (-fungins)?
Candida Aspergillus [PCP]
111
1st line Rx invasive candida? When would they not be?
-Fungins Eg Caspofungin CNS [also low data for opthal/urine candida]
112
Flucytosine (5-FC) key side effects
Pancytopenia (think its almost 5-FU chemo) -Mild hepatic/GI
113
5-FC works on which 2 bugs? which sneaky resistant one?
Cryptococcus Candida - but NOT C. krusei (it kreuseis past)
114
SSKI supersaturated potassium iodide only real use
Sporotrichosis
115
Coccidioides immitis spherules
116
Name the dimorphic fungi
Body Heat Temperature Probably Changes Shape Blastomyces dermatitidis. Histoplasma capsulatum Talaromyces marneffei Paracoccidioides brasiliensis. Coccidioides immitis. Sporothrix schenckii.
117
Nasal stuffiness, facial pain and oedema with necrotic black nasal turbinates. Dx? Looks like on microscopy? Rx?
Mucor ssp Amphotericin B and Posiconazole wide ribbon-like, non-septated hyphae that are right angle branching.