Fungal Pneumonia

Question 1

endemic fungal pneumonia

Answer 1

histoplasmosis

blastomycosis

coccidioidomycosis

Question 2

fungal pneumonia associated with immunosuppression

Answer 2

aspergillosis

pneumocystosis

Question 3

What are some of the major characteristics of endemic mycoses?

Answer 3

thermally dimorphic fungi that exist in nature, soil

hyphal form in the environment, yeast form in tissue

inhalation leads to pulmonary infection and dissemination

no evidence of transmission among humans or animals

otherwise healthy individuals are infected

Question 4

general characteristics of Histoplasma capsulatum

Answer 4

soil-based fungus associated with river valleyes and bird and bat guano

in the US, mostly endemic to Ohio and Mississippi river valleys

acquisition associated with disruption of the soil by excavation or construction, inhilation and pulmonary infection

dimorphic - mycelial (37 degrees C or higher) and yeast phase

hallmark of tissure response is caseating or noncaseating granulomas

Question 5

clinical manifestations of H. capsulatum

Answer 5

> 90% go unrecognized, asymptomatic or mild influenza-like illness

Ghon complex and pulmonary calcifications are common in healed pulmonary histoplasmosis

Question 6

complications of H. capsulatum infection

Answer 6

mediastinal lymphadenitis

mediastinal fibrosis

cavitary pulmonary histoplasmosis

progressive disseminated histoplasmosis (PDH)

Question 7

diagnosis of Histoplasmosis

Answer 7

culture in brain heart infusion agar with blood, antibiotics, and cyclohexamide

cultures incubated for 30 degrees C for up to 6 weeks

majority cultures show grwoth within 7 days

sputum culture

histopathology

rapid diagnosis by polysaccharide antigen detection in urin, serum, BAL fluid

Question 8

histopathology of Histoplasmosis

Answer 8

yeast visualized poorly by H and E stain

better seen with periodic acid-Schiff (PAS) and Gomorimethenamine silver (GMS) stains

Question 9

treatnebt if Histoplasmosis

Answer 9

acute pulmonary disease

if symptoms less than 4 weeks no treatment

if symptoms greater than 4 weeks itraconazole for 6-12 weeks

chronic pulmonary disease, disseminated disease, granulomatous mediastinitis - Amphotericin B then Itraconazole for 6-24 months

Question 10

general characteristics of Blastomyces dermatitidis

Answer 10

organism found in warm, moist soil of wooded areas rich in organic debris, such as decaying vegetation

dimorphic funcgus, mycelial form at room temeprature and yeast form at 37 degrees C

endemic to North America, including southeasterna nd south central states, especially those bordering the Mississippi and Ohio River basins and the Great Lakes

usualt portal of entry in humans is through the inhalation of conidia, which convert to the yeast phase in the lung

the typical inflammatory response consists of clusters of neutrophils and noncaseating granulomas with epithelioid and giant cells

Broad Based Budding yeast

Question 11

clinical manifestation of Blastomycosis

Answer 11

pulmonary blastomycosis - acute or chronic, mimics infection with pyogenic bacteria, TB, other fungal infections, and malignancy

extrapulmonary manifestations - cutaneous disease and bone infection

Question 12

diagnosis of Blastomycosis

Answer 12

definitive diagnosis requires recovery in culture

can also examine secretions

histopathological examination - pyogranuloma, GMS stain

antigen assay

serologic testing - complement fixation, immunodiffusion, radioimmunoassay, ezyme immunoassay

Question 13

treatment of Blastomycosis

Answer 13

asymptomatic disease limited to the lungs - follow the patient closely for disease progression or dissemination

in immunocompromized, progressive pulmonary disease, or extrapulmonary disease - amphotericin B and itraconazole

Question 14

What are the two species of Coccidioides?

Answer 14

• Coccidioides immitis* (CA)
• Coccidioides Posadasii* (other states and countries outside the US)

Question 15

Where is Coccidioidomycosis endemic to?

Answer 15

southwestern US, especially in New Mexico, Arizona, and the San Joaquin Valley of California

Question 16

general characteristics of Coccidioides spp.

Answer 16

dimorphic fungi that exists as either a mycelium or a spherule

found in the soil, grows by apical extension, true septa form along course

alternating mycelial cells undergo autolysis

remaining cells (arthroconidida) develop a hydrophobic outer layer and can remain viable for long periods

fragile attachments of arthroconidia to adjacent cell remnants make them prone to separation by physical disruption or mild air turbulence

arthroconidia become airborne and can be inhaled and deposited in the lungs

Question 17

Coccidioides spp. development in the lungs

Answer 17

arthroconidia remodel into spherical cells, shedding outer wall

cell multiplication -> spherule divide into endospores

in tissue, spherules can develop to a size of 75 microns in diameter, containing 100 endospores

spherule matures, outer wall thins and ruptures

endospores are released to propagate in tissue or revert to mycelial growth if removed from tissue

Question 18

clinical manifestations of Coccidioidomycosis

Answer 18

asymptomatic or subclinical

non-specific respiratory infection

pulmonary nodule - hard to distinguish form malignancy

chronic fibrotic pneumonia

disseminated disease - skin, bone and joints, meningitis (fatal if untreated)

Question 19

diagnosis of Coccidioidomycosis

Answer 19

not detected by Gram staining

spherules visualized in tissue by H and E stains, silver or periodic acid-Schiff stains

grow well on most media after 5-7 days of incubation - highly infectious cultures

serologic testing - most frequent means of diagnosing primary infection, highly specific for active infection

urine antigen testing

Question 20

treatment of Coccidioidomycosis

Answer 20

vast majority of early infections resolve without specific antifungal therapy

solitary pulmonary nodule - no treatment

cavitary disease - no treatment if asymptomatic

severe pneumonia and chronic progressive fibrocavitary pulmonary or disseminated disease - treat with amphotericin B, fluconazole, or itraconazole for 3-6 months

diffuse pneumonia needs one year or more of treatment

meningitis or ongoing immunosuppression is life-long

Question 21

general characteristics of Aspergillus spp.

Answer 21

ubiquitous, found in soil, water, food, air, decaying vegetation

normal pulmonary host defenses - rarely develop disease

prolonged and profound neutropenia result in high risk for invasive aspergillosis

usually infect through inhaled conidia

infection progresses across tissue planes invades blood vessels leading to infarction of distal tissue

Question 22

clinical manifestations of Aspergillosis

Answer 22

fever, chest pain, shortness of breath, cough, and/or hemoptysis

patients with severe neutropenia frequently present with fever and no localizing pulmonary symptoms

Question 23

diagnosis of Aspergillosis

Answer 23

chest CT more sensitive than x-ray for detecting earliest stages of disease

• single or multiple nodules with or without caviation
• patchy consolidation or peribronchial infiltrates

“Halo sign”

infection may involve sinuses, CNS, heart, and skin

histopathology - septate hyphae with acute angle branching

antigen assays in serum or BAL - galactomannan and beta-d-glucan

Question 24

Halo sign

Answer 24

in CXR for aspergillosis, nodule with surrounding ground glass infiltrate - hemorrhage into area surrounding fungal infection

Question 25

treatment of Aspergillosis

Answer 25

voriconazole is the treatment of choice

alternatives include amphotericin B, the echinocandins, posaconazole, and itraconazole

recovery of neutrophils in patients with neutropenia is critical to recovery

Question 26

general characteristics of Pneumocystic jiroveci

Answer 26

fungus, morphologic forms include cysts, sporozites, and trophozoites

worldwide distribution - mostly healthy children exposed by 3-4

airborne and person-to-person transmission

disease associated with defects in cellular and humoral immunity

Pneumocystis does not appear unless CD4 count is less than 200

Question 27

clinical presentation of Pneumocystis

Answer 27

progressive exertional dyspnea, fever, non-productive cough, chest discomfort, worsens over days-weeks

Question 28

diagnosis of Pneumocystis

Answer 28

laboratory findings include hypoxemia and elevated LDH

CXR findings include diffuse bilateral symmetrical intersittial infiltrates

chest CT shows patchy ground glass attenuation

diagnosis confirmed by identification of the organism by immunofluorescent antibody staining of induced sputum or BAL fluid with excellent sensitivity and specificity

Question 29

treatment of Pneumocystis

Answer 29

trimethoprim-sulfamethoxazole or trimethroprim plus dapsone, clindamycin plus primaquine, atovaquone, and pentamidine

corticosteroids for severe disease, decreases inflammation with dying organisms