Unit 4 - Pulmonary Fungal Infections; Systemic Mycoses

Question 1

what are major themes of systemic mycoses?

Answer 1

• 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

Question 2

explain what the coccidioides organism is

• how it is transmitted
• which seasons

Answer 2

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

Question 3

explain the pathogenesis of coccidioides

Answer 3

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

Question 4

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

Answer 4

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

Question 5

what does coccidioides endospore/spherule growth lead to?

Answer 5

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

Question 6

what are risk factors of coccidioides?

Answer 6

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

Question 7

what is the difference between acute and chronic coccidioides?

Answer 7

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

Question 8

what does the PPD exam show for coccidioides?

Answer 8

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

Question 9

what does physical exam of contained coccidioides show?

Answer 9

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)

Question 10

what does X-ray show in coccidioides?

Answer 10

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

Question 11

what does erythema nodosum in coccidioides look like?

Answer 11

“desert bumps”

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

Question 12

what does disseminated coccoidioides look like?

Answer 12

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

Question 13

what is a good sign of coccidioides immunity?

Answer 13

erythema nodosum (adults) or multiforme (peds)

Question 14

what do labs say about coccidioides?

Answer 14

• 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

Question 15

what is treatment for coccidioides?

Answer 15

• 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

Question 16

how to prevent coccidioides?

Answer 16

immunosuppressed people should avoid travel to endemic areas

Question 17

explain the organism that causes Histoplasma

Answer 17

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

Question 18

how is histoplasma different from African histoplasmosis?

Answer 18

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

Question 19

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

Answer 19

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

Question 20

explain the pathogenesis of histoplasma

Answer 20

• 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

Question 21

what is clinically seen in immunosuppressed histoplasma patients?

Answer 21

1. pancytopenia

2. ulcerated lesions on tongue

Question 22

how do you diagnose histoplasma?

Answer 22

• 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

Question 23

what do labs look like in histoplasma

Answer 23

• 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

Question 24

what is treatment for histoplasma?

Answer 24

• 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)

Question 25

explain the organism of blastomyces?

Answer 25

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

Question 26

explain the pathogenesis of blastomyces

Answer 26

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

Question 27

explain the diagnostic exam of blastomyces?

Answer 27

- 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

Question 28

what does blastomyces show on lab?

Answer 28

- 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

Question 29

what is treatment for blastomyces?

Answer 29

- most people: itraconazole - severe: amphotericin B - surgical excision of loci - meningitis: fluconazole

Question 30

what does disseminated histoplasma look like?

Answer 30

- 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

Question 31

what are other names for paracoccidioides?

Answer 31

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

Question 32

what is the organism involved in paracoccidioides?

Answer 32

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)

Question 33

explain the pathogenesis for paracoccidioides?

Answer 33

- 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

Question 34

what is the diagnostic exam for juvenile type paracoccidioides?

Answer 34

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

Question 35

what is the diagnostic exam for adult type paracoccidioides?

Answer 35

chronic and much more common (less severe) - very long latency period (up to 30 yrs) - pulmonary symptoms - oral and skin lesions - nonspecific immunogenic symptoms

Question 36

what do labs look like for paracoccidioides?

Answer 36

- 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

Question 37

what is treatment for paracoccidioides?

Answer 37

- 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)