Unit 4 - Pulmonary Fungal Infections; Systemic Mycoses Flashcards

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1
Q

what are major themes of systemic mycoses?

A
  • environmental: in spores/fungi in soil
  • -not likely to be drug resistant, but likely unable to eradicate
  • inhaled into lungs
  • thermal dimorphism
  • range of severity: asymptomatic clearance to death
  • not person-person transmissible (not contagious)
  • differential will include TB, but source is American dirt, not foreign crowds
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2
Q

explain what the coccidioides organism is

  • how it is transmitted
  • which seasons
A

Coccidioides immitis and posadasii

  • dimorphic: mold in soil, spherule in tissue
  • -grow in rainy season as noninfectious mycelia mold
  • endemic in SW US and Latin America
  • -dry areas; in travel and shipped material
  • in dry summer soil, forms hyphae with alternating arthrospores and empty cells
  • arthrospores are carried on wind
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3
Q

explain the pathogenesis of coccidioides

A

arthrospores are inhaled; infectious dose as low as 1 IU, but if higher have more symptoms

  • within terminal bronchiole, changes form:
  • -30 um spherules highly resistant to eradication by immune system
  • -thick, doubly-refractive wall willed with endospores
  • -wall ruptures to releases endospores w/in lung that develop into new spherules
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4
Q

which form of coccidioides is infectious? how does it spread?

A

arthrospores only, not spherules or endospores (which disseminate in lung)
-spreads by direct extension

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5
Q

what does coccidioides endospore/spherule growth lead to?

A

granulomatous lesions

  • CMI delayed hypersensitivity response
  • if CMI is healthy, infection is contained in granulomas in lungs (like TB, except it resolves)
  • if immunosuppressed, disseminated infectious by hematogenous spread via MP seen in bones and meninges
  • -induces immune anergy and may be fatal
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6
Q

what are risk factors of coccidioides?

A
  • age
  • immunocompromised
  • late-stage pregnancy
  • occupational
  • Black/Filipino (rare fact of exception)
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7
Q

what is the difference between acute and chronic coccidioides?

A

acute: innate immunity (MP) may spread it
chronnic: lymphocytes and histiocytes initiate granuloma and giant cell formation (containment)

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8
Q

what does the PPD exam show for coccidioides?

A

PPD with coccidioidin or spherulin
+ if exposed w/ cleared or contained infection
- if unexposed or immunosuppressed (disseminated infection)

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9
Q

what does physical exam of contained coccidioides show?

A

often asymptomatic, but +PPD; if symptoms, called “valley fever” or “desert rheumatism” and subsides spontaneously

  • may have influenza-like illness (fever, cough)
  • 50% have lung changes on X-ray
  • 10% may develop erythema nodosum (adults) or multiforme (peds), or arthralgias
  • -this ironically means that the risk of dissemination is low (due to positive immune response)
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10
Q

what does X-ray show in coccidioides?

A
  • infiltrates
  • adenopathy
  • effusions
  • nodules resembling malignancy (biopsy)
  • bronchoscopy is useful
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11
Q

what does erythema nodosum in coccidioides look like?

A

“desert bumps”

  • red, tender nodules on exterior surfaces like lower legs
  • delayed cell-mediated hypersensitivity to fungal Ag
  • immunogenic complication of granulomatous diseases
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12
Q

what does disseminated coccoidioides look like?

A

may affect any organ (mostly meningitis, osteomyelitis, and skin or lymph nodes –> soft tissue abscess, hematogenously seeded)

  • disseminates in 1% of general population, 10% of Africans, Filipino, or late-pregnancy, DM, cardiopulmonary
  • associated with sweat, dyspnea, fever, wt loss; may reactivate after treatment
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13
Q

what is a good sign of coccidioides immunity?

A

erythema nodosum (adults) or multiforme (peds)

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14
Q

what do labs say about coccidioides?

A
  • tissue specimens are spherules microscopically
  • Sabouraud’s agar at 25 C shows cottony white mold; hyphae with arthrospores –> thus they are infectious
  • serology for exposure and titers; they spike if disseminating
  • -very specific, not sensitive
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15
Q

what is treatment for coccidioides?

A
  • none for mild disease (high morbidity, low mortality)
  • persisting lung lesions or disseminated: amphotericin B or itraconazole (need years of therapy)
  • meningitis: fluconazole, continue as long-term suppressive, may add intrathecal amphotericin B
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16
Q

how to prevent coccidioides?

A

immunosuppressed people should avoid travel to endemic areas

17
Q

explain the organism that causes Histoplasma

A

Histoplasma capsulatum (most common systemic mycoses)

  • thermally dimorphic (mold in soil, yeast in tissue)
  • two types of asexual spores; tuberculate macroconida and microconida
  • endemic in patches of acidic, damp soil (Ohio and Mississippi river valley), or bird droppings (esp. starlings or bat guano)
  • excavation of contaminated soil for construction can set off an outbreak
18
Q

how is histoplasma different from African histoplasmosis?

A

Histoplasma = Histoplasma capsulatum (most common systemic mycosis)
African histoplasmosis = Histoplasma duboisii (different disease)

19
Q

what are the differences between tuberculate macroconida and microconida of histoplasma?

A

both are forms of asexual spores

  • macro: grows in culture, with thick walls and finger-like projections
  • micro: infectious form from environment, with smaller, thin, smooth walls
20
Q

explain the pathogenesis of histoplasma

A
  • spores are inhaled, then engulfed by alveolar MP
  • can survive endocytosis and lysosomal fusion by producing bicarbonate and ammonia (raise pH to inactivate hydrolytic enzymes)
  • replicate as yeasts in MP (convert), then spread throughout body
  • healthy CMI will be asymptomatic and clear at low dose (form granulomas that calcify and contain infection)
  • -may see erythema nodosum during initial inflammatory response
  • high dose exposure may cause pneumonia with cavitary lung lesions on primary infection
  • immunosuppression (or very young/old) leads to more sever dissemination
21
Q

what is clinically seen in immunosuppressed histoplasma patients?

A
  1. pancytopenia

2. ulcerated lesions on tongue

22
Q

how do you diagnose histoplasma?

A
  • PPD not useful; too many false +/-
  • mild cases are nonspecific-flulike; self-limited, minimal findings, EN/EM
  • cough, chest pain, hemoptysis if spreading in lungs
  • -cavitary lung lesions
  • granulomas in the liver and spleen
  • may see weight loss in geriatric
23
Q

what do labs look like in histoplasma

A
  • tissue biopsy or bone marrow aspirate for oval yeast cells within MP
  • bloodwork shows pancytopenia if disseminated
  • Sabouraud’s agar shows tuberculate macroconida at 25 C, yeasts at 37 C
  • ELISA for histoplasma polysaccharide Ag
  • DNA probes for histoplasma RNA
  • urine Ag test
  • serologic tests can be useful, but may X-react w/ other fungal infectious, or turn negative in immunosuppressed
24
Q

what is treatment for histoplasma?

A
  • no treatment for mild cases
  • if spreading in lung, oral itraconazole (6-12 weeks)
  • if disseminated, amphotericin B; must use liposomal if kidney problems
  • if meningitis, fluconazole (penetrates spinal fluid well)
25
Q

explain the organism of blastomyces?

A

Blastomyces dermatitidis (NA blastomycosis)

  • dimorphic fungus
  • -mold form is hyphae w/ small, pear-shaped conidia is diagnostic
  • -yeast form is round w/ doubly refractive wall and single broad-based bud
  • endemic in eastern NA and Great lakes
  • grows in wet, rich soil
26
Q

explain the pathogenesis of blastomyces

A

infection by inhalation of conidia

  • 50% asymptomatic infection (once yeast conversion b/c has immune-modulation BAD1)
  • immunosuppression or preexisting pulmonary disease predisopose to dissemination
  • -hematogenous seeding of many sites
27
Q

explain the diagnostic exam of blastomyces?

A
  • mild form: nonspecific flulike illness, resolves spontaneously
  • pneumonia: high fever, chills, cough w/ mucopurulent sputum, pleuritic chest pain; rarely get EN
  • chronic illness: looks like TB (pulmonary symptoms w/ weight loss, night sweats, hemoptysis
  • fast, severe form: ARDS w/ fever
  • all may include skin lesions, slow development (if mo-yrs old), bone/joint pain
  • CXR is variable, nonspecific
28
Q

what does blastomyces show on lab?

A
  • tissue biopsy - thick-walled yeast cells with single, broad-based buds (non-caseating)
  • culture - hyphae w/ small pear-shaped conidia
  • PPD and serology are inadequately specific
  • sputum microscopy (KOH mount) is 75% diagnostic
29
Q

what is treatment for blastomyces?

A
  • most people: itraconazole
  • severe: amphotericin B
  • surgical excision of loci
  • meningitis: fluconazole
30
Q

what does disseminated histoplasma look like?

A
  • cardiac or CNS symptoms in addition to tongue lesions
  • granulomas in liver/spleen (sonogram)
  • mass lesions, meningismus, cranial nerve deficits
  • GI lesions or masses
  • ocular scars in the back
31
Q

what are other names for paracoccidioides?

A

S. American blastomycosis (PCM, Lutz-Splendore-Almedia disease)

32
Q

what is the organism involved in paracoccidioides?

A

Paracoccidioides brasiliensis

  • dimorphic fungus
  • -mold form has thin, septate hyphae
  • -yeast form is thick-walled with multiple buds (diagnostic)
  • endemic to rural Latin America (travelers or immigrants)
33
Q

explain the pathogenesis for paracoccidioides?

A
  • spores are inhaled
  • early lesions occur in lungs
  • asymptomatic infectiou common
  • more severe infection includes oral mucous membrane lesions and LN enlargement (immunosuppressed = malnourished)
  • dissemination is possible if immunosuppressed or treated for years
  • cutaneous infection if minor injuries w/ spore-coated wood
34
Q

what is the diagnostic exam for juvenile type paracoccidioides?

A

acute form (rare, but much more severe)

  • in pediatrics or immunosuppressed
  • skin lesions, fever, malaise, weight loss
  • lymphadenopathy and hepatosplenomegaly
  • history of agricultural work, malnutrition, smoking, alcoholism
  • lung imaging more abnormal than breath sounds
  • R-sided heart failure
  • X-ray shows interstitial infiltrates or mixed lesions, usually bilateral and symmetric, in central and basal parts of lung
35
Q

what is the diagnostic exam for adult type paracoccidioides?

A

chronic and much more common (less severe)

  • very long latency period (up to 30 yrs)
  • pulmonary symptoms
  • oral and skin lesions
  • nonspecific immunogenic symptoms
36
Q

what do labs look like for paracoccidioides?

A
  • pus or tissue samples: yeast cells with multiple buds (diagnostic; stain siler)
  • culture takes 2-4 weeks
  • serologic testing: significant Ab titers correlate with active disease
  • skin test not helpful, non-CSF
37
Q

what is treatment for paracoccidioides?

A
  • oral itraconazole for 6 mo and IV amphotericin B if severe, then switch
  • improvements in general health, as PC is more opportunistic than other systemic mycoses (correct diet, rest, smoke alcohol)