Systemic Mycoses Flashcards
1
Q
the big 4 mycoses in the US?
A
- coccidioides
- histoplasma
- blastomyces
- paracoccidioides
2
Q
major themes
A
- environmental- spores/ fungi in soil
- inhaled into lungs
- thermal dimorphism
- wide range of severity: asymptomatic clearance to death
- NOT person to person
- coccidio, histoplasma, blastomyces may mimic TB, source is American dirt, not foreign crowds
- drug resistance is low
3
Q
coccidio
A
- coccidiodes immitis (most common)
- C. posadasii
- dimorphic- mold in soil, spherule in tissue
- grow in the rainy season as mycelia (noninfectious)
- in dry summer, forms hyphae with alternating athrospores and empty cells
- when disturbed by wind or excavation, readily release arthroconidia (infectious)
- spores are carried by the wind and inhaled by humans
- can have asymptomatic seroconversion in a healthy person
4
Q
coccidio 2
A
- endemic in southwest US and Latin America, may travel home in returning patient or arrive in contaminated shipped material
- caseload has increased as endemic areas have become population areas (old people go southwest!!)
- symptomatic disease can keep a previously healthy person out of school or work for a month
- was considered rare and uniformly fatal until 1929 when some med student named Harold Chope inhaled it and got lung illness accompanied by erythema nodosum
5
Q
pathogenesis of coccidio
A
- athrospores (arthroconidia) are inhaled
- infectious dose can be as low as a single IU, though high dosage more likely to cause symptoms
- within terminal bronchiole they change form
- spherules are highly resistant to eradication by immune system
- 30 micrometer in diameter
- thick, double refractive wall
- filled with endospores
- wall ruptures to release endospores develop into new spherules
- spherules and endospores aren’t infectious
- *endospores can make new spherules in lung but not new arthrospores
6
Q
what can happen with low dose and healthy innate immunity?
coccidio
A
-asymptomatic clearing
7
Q
what happens with a moderate dose and healthy CMI?
Coccidio
A
- asymptomatic containment
- nonspecific flulike illness, containment
- mild, pneumonia, erythema, nodosum, containment
8
Q
what happens with a high dose and immunosuppressed?
Coccidio
A
- serious pneumonia
- dangerous dissemniation
9
Q
acute phase of coccidio pathogenesis?
A
-innate immunity (macrophage response) attempts to clear infection and is often successful
10
Q
chronic phase of coccidio pathogensis?
A
- innate immunity inadequate for clearance
- lymphocytes and histiocytes initiate granuloma and giant cell formation (containment)
- if CMI is healthy, infection is contained in granulomas in the lung, many eventually cleared asymptomatically
- many patients who become ill have nonspecific flulike symptoms that resolve at home
- 60% exposures= asymptomatic +flulike
11
Q
symptomatic disease of coccidio?
A
- symptomatic disease may appear as valley fever or desert rheumatism
- fever
- arthralgias
- erythema nodosum- immunogenic, painful tender rash esp on shins
- erythema multiforme
- chest pain
12
Q
coccidio pathogenesis 2?
A
- if immunosuppressed, disseminated infection both by intracellular travel in macrophages and hematogenous spread
- risk factors- advanced age, immunocompromise, late stage pregnancy, occupational high level exposure (farmers, construction), black or Fillipino race
- may affect any organ, primarily seen in bones and meninges
- induces immune anergy, may be rapidly fatal
- localized extrapulmonary infection may also result from contaminated injury, usually resolves without treatment
13
Q
coccidio Dx on exam
A
- usually summer or autumn, incubates 7-30 days
- obtain history of travel to or residence in endemic area
- PPD with coccidio or pherulin
- if exposed with cleared or contained infection
- neg is unexposed or disseminated infection
14
Q
what does contained infection look like on exam?
Coccidio
A
\+PPD -often asymptomatic -may have flu like illness 50% have lung changes on xray -infiltrates -adenopathy -effusions -nodules resembling malignancy -bronchoscopy may be useful -10% develop erythema nodosum in adults, erythema multiform in peds or arthralgias
15
Q
erythema nodosum
A
- desert bumps, hypersensitivity reaction
- red, tender nodules on exterior surfaces like lower legs
- delayed cell mediated hypersensitivity to final antogens
- immunogenic complication of granulomatous diseases
- hypersensitivity may also manifest in eye as conjunctivitis
- EN means risk of dissemination is low
16
Q
what does disseminated infection look like on exam?
Coccidio
A
- may affect any organ most common:
- meninges, classic sx but insidious onset
- bone (osteomyelitis)
- skin or lymph node (soft tissue abscess, hematogenously seeded)
- disseminates in 1% of general population, 10% of African American, Fillipino, late pregnancy patients, diabetes, pre-existing cardiopulmonary
- dramatic sweats, dyspnea, fever, weight loss
- erythema nodosum is a good sign
- may arise after prolonged incubation or reactivated after treatment
- night sweats, dyspnea, fever, weight loss, and chronic cough may also appear in smokers from chronic lung infection
17
Q
coccidio dx on lab
A
- take biopsies of relevant tissues, CSF, blood, urine, stain with H&E or fungal stains, look for spherules
- cultures on sabourauds agar at 25C: cottony white mold composed of hyphae with arthrospores (cultures are infectious!) biosafety level 3
- serology for exposure, titers (IgG from blood and/or CSF), titer spikes if disseminating
- positives are very reliable, but some false negatives occur
- PCR available
18
Q
CSF of coccidio?
A
-lymphocytic pleocytosis, elevated protein, hypoglycorrgachia, eosinophilia, CF IgG
19
Q
treatment for coccidio?
A
- high morbidity but low mortality
- no treatment required for mild disease
- oral azoles may be used, no data indicate faster or better resolution
- must treat if predisposed to complications- severe immunosuppression, diabetes, Black/Fillipino, cardiopulmonary disease (oral azoles), pregnancy (amphotericin B)
- persisting lung or disseminated: Amph B and long term itraconazole
- meningitis: fluconazole, intrathecal Amph B if severe (steroids to prevent immunogenic sx)
- min of 6 mo of therapy, followup for a year
20
Q
Organism of Histoplasma?
A
- Histoplasma capsulatum
- most common systemic mycosis
- thermally dimorphic, mold in soil, yeast in tissue
- forms two types of asexual spores- tuberculate macroconidia and microconidia
- endemic in patches worldwide
- in the US: Ohio, Missouri, Mississippi
- river valleys- acidic damp soil with high organic content
- 80% of people exposed in this area have asymptomatic seroconverstion
- environmental- soil, bird droppings, esp from starlings or bat guano
- excavation from contaminated soil for construction can set off an outbreak
- african histoplasmosis by H duboisii is different
21
Q
tuberculate macroconidia
A
- asexual spore of histoplasmosis
- thick walls
- fingerlike projections
22
Q
microconidia
A
- asexual spore of histoplasma
- smaller, thin, smooth walled
- infectious
23
Q
pathogenesis of histoplasma?
A
- healthy CMI, once raised, activates macrophages to kill most intracellular histoplasma, form granulomas around remainder, eventually calcify, contain infection
- may see EN during IF response
- high dose exposure may cause pneumonia with cavitary lung lesions on primary infection
- very young, very old, immunosuppressed may progress to more severe dissemination
- pancytopenia
- ulcerated lesions on tongue
24
Q
Histoplasma dx on exam?
A
- 95% resolve at home
- acute febrile respiratory illness 3-14 days after exposure
- history- residence in or travel to an endemic river valley, occupational exposure from soil, birds, bats, immune predisposition
- mild cases are non-specific flulike, disease is usually self limited, findings minimal, may include EN or EM
- if spreading in lungs, cough, chest pain, hemoptysis, ARDS, cavitary lesions
25
Histoplasma diagnosis of disseminated disease?
- tongue lesions
- granulomas in liver and spleen
- weight loss
- cardiac-endocarditis and dysrhythmia
- GI-lesions, mass
- ocular- scars in back
- CNS- mass lesions, meningismus, cranial nerve deficits
26
histoplasma diagnosis on lab
- culture from sputum, blood, bronchoalveolar, lavage, CSF
- tissue biopsy or bone marrow aspirate for histology, oval yeast cells within macrophages
- bloodwork-pancytopenia in disseminated
- two cultures on Sabouraud's agar (thermally dimorphic)
- 25C- tuberculate macroconidia
- 37C yeasts
- ELISA for histoplasma polysaccharide antigen
- DNA probes for histoplasma RNA
- serologic tests for antibody titers can be useful but may cross react with other fungal infections or turn negative in immunosuppressed
27
treatment for lung fungal infections
-oral itraconazole 6-12 weeks
28
treatment for disseminated disease
- ampho B
- liposomal if any kidney probs
- follow with 1 year of itraconazole
29
treatment for fungal meningitis
- fluconazole
| - amph B if severe
30
blastomyces organism
- Blastomyces dermatitidis
- dimporhic fungus
- mold form is hyphae with small pear shaped conidia, conidia infections by inhalation
- yeast form is round with doubly refractive wall and a single broad based bud
- endemic in eastern North America and great lakes region, most common in US
- wet, rich, soil
31
pathogenesis of blastomyces
- infection by inhalation of conidia
- monocytes, macrophages, neutrophils readily kill conidia by once yeast conversion takes places begin to slow down
- ~50% asymptomatic infection, successful clearance
- most of remainder contain infection with granulomatous response, may develop pulmonary symptoms in process
- immunosuppression or preexisiting pulmonary disease predispose to disseminatoin
- hematogeneous seeding or many possible sites
- untreated symptomatic cases have significant mortality
32
virulence factor of blastomyces?
-yeast, not mold, produces immune modulator BAD1 on cell surface
33
blastomyces mild form on exam
- non-specific flulike illness
| - resolves spontaneously
34
blastomyces pneumonia on exam
- high fever
- chills
- cough with mucopurulent sputum
- pleutitic chest pain
- occasionally EN
35
blastomyces chronic illness
- looks like TB
| - pulmonary symptoms with weight loss, night sweats, hemoptysis
36
fast severe form of blastomycea
-ARDS with fever
37
common factors of blastomyces on exam
- include slow development of skin lesions
- bone joint pain
- CXR is abnormal but variable
- bronchoscopy with needle biopsy may be useful
38
blastomyces diagnosis on lab
- sputum microscopy (KOH mount)- 75% diagnostic in patients with pneumonia
- tissue biopsy in skin or lung, stain with periodic acid Schiff or silver, not H&E
- thick walled yeast cells with single, broad based buds, microabscesses, suppurating granulomatous reaction, not caseating
- may need a careful check to differentiate from sq cell carcinoma
- culture from sputum or biopsy: hyphae with small pear shaped conidia
- exoantigen testing and DNA probe tests are available for cultures
- PPD and serology are inadequately specific
39
treatment for blastomyces
- symptomatic but not severe- itraconazole
- severe including CNS- ampho B, may switch it itraconazole after improvement
- fluconazole also appropriate for meningitis
- surgical excision of loci
40
paracoccidioides organism
- Paracoccidioidomycosis, south american blastomycosis, lutz splendore, almedia disease
- paracoccidioides brasiliensis
- dimorphic fungus
- mold form has thin, separate hyphae
- yeast form is thick walled with multiple buds
- endemic to rural Latin America
41
pathogenesis of paracoccidio
- spores are inhaled
- early lesions occur in lungs
- asymptomatic infection common
- more severe infection includes oral mucous membrane lesions, lymph node enlargement
- dissemination is possible if immunosuppressed (CMI) or untreated for years
- cutaneous infection is possible from minor injuries with spore coated wood
- total untreated mortality is 16-25%
42
paracoccidio dx on exam
- most common in adult men
| - history of ag work, malnutrition, smoking, alcoholism, immunocompromise
43
chronic adult form of paracoccidio on exam
- less severe
- very long latency period (up to 30 year) followed by endogenous reactivation
- pulmonary symptoms- cough, dyspnea, malaise, fever
- weight loss
- oral lesions
- skin lesions
- LAD, may include draining fistulas
- nonspecific immunogenic sx
- less common: adrenal glands, long bones, CNS
44
juvenile/acute paracoccidio
- peds or immunosuppressed
- more severe
- skin lesions
- fever, malaise, weight loss
- LAD and HSM
- lung imaging more abnormal than breath sounds
- right sided heart failure
- Xray often shows interstitial infiltrates or mixed lesions, usually bilateral and symmetric, usually central and basal portions of lungs
45
paracoccidio diagnosis on lab
- pus or tissue samples: KOH mount for yeast cells with multiple buds
- stain biopsies with silver for yeast cells, adult form also granulomas
- culture on sabouraud takes 2-4 weeks
- serologic testing not available outside endemic area
- skin test not helpful
- CSF smear is seldom helpful
**LOOK AT PICTURE ON SLIDE REBECCA SAID IT WAS IMPORTANT
46
trt for paracoccidio
- oral itraconazole for 6 mo
- IV Amph B initially if presentation is severe, switch to oral azole after improvement
- in combination with correction of anemia, improved diet, rest, cessation of smoking and alcohol
- paracoccidio is more opportunistic than others- risk reduction
