Fungal Pneumonia And Pneumonia In The Immunocompromised (8/18)

Front 1

4 major types of fungal infections?

Back 1

–Superficialand cutaneous mycoses: common; limited to skin, hair, nails

–Subcutaneousmycoses: involve skin, subcutaneous tissue, lymphatics

–Endemicmycoses: caused by dimorphic fungi; can cause serious disease in both healthy andimmunocompromisedpatients

–Opportunisticmycosis: Can cause life-threatening disease in immunosuppressedpatients

Front 2

Most common etiologic agents of pulmonaryinfection by fungi in healthy hosts, causing over 1 million infections/year inthe U.S.?

Back 2

Dimorphic fungi

Front 3

How do dimorphic fungi grow?

Back 3

•Grow as yeast in human tissue and as moldunder some laboratory conditions (typically room temperature)

Front 4

How does infection by dimorphic fungi occur?

Back 4

•Infection results from inhalation ofspores that have mold forms in soil.

Front 5

What happens once dimorphic fungi settle in the lungs?

Back 5

•Within the lungs the spores differentiateinto yeasts or spherules.

–Mostlung infections are self-limited and even asymptomatic, however..

–Allcan cause pneumonia and disseminate.

Front 6

4 types of dimorphic fungi?

Back 6

•Blastomyces dermatitidis•Histoplasma capsulatum•Coccidioides immitis•Paracoccidioides brasiliensis

Front 7

Where is Histoplasma capsulatum endemic to?

Back 7

•Endemic in Mississippi and Ohio RiverValleys.

Front 8

In what conditions does Histoplasma capsulatum grow?

Back 8

•Grows in soil; bird droppings

Front 9

Most common disseminated infection in AIDS patient?

Back 9

Histoplasma capsulatum

Front 10

Clinical manifestations of Histoplasma capsulatum?

Back 10

–Asymptomaticpulmonary infection

–Respiratoryinfection characterized by fever, chills, cough, chest pain (usually withintense exposure)

–Insetting of AIDS: severe disseminateddisease can develop•Pancytopenia (due to bone marrow infiltration) •Mouth/GI ulcers•Skin rash (pustules, nodules)•Mortality up to 10%

Front 11

Dx for Histoplasma capsulatum?

Back 11

–Tissuebiopsy will show oval yeast cells within macrophages

–Serology

–Urinaryantigen

–CXR:infiltrates, mediastinalLAD, cavitarylesions

Front 12

Treatment for Histoplasma capsulatum?

Back 12

•Treatment: Amphotericin for severe disease; Itraconazole otherwise

Front 13

Erythema nodosum (EN) manifests how?

Back 13

Erythema nodosum (EN) manifests as red, tender nodules(“desert bumps”) on extensor surfaces such as the skin over the tibia and ulna.

Front 14

What kind of hypersensitivity reaction is EN?

Back 14

It is a delayed (cell-mediated) hypersensitivity response to fungal antigens

Front 15

What kind of prognosis does EN indicate?

Back 15

Its an indicator of a good prognosis. Indicates that cell-mediatedimmunity is active.

Front 16

Where is Blastomycesdermatitidis endemic?

Back 16

•Endemic in Ohio/Mississippi River Valley, Missouriand Arkansas River basins

Front 17

In what conditions does Blastomycesdermatitidis grow?

Back 17

Grows in moist soil

Front 18

Clinical manifestations of Blastomycesdermatitidis?

Back 18

–Asymptomaticrespiratory illness

•50% will have cough, chest pain,sputum production, fever/night sweats which most often resolves spontaneously

-Disseminated disease results inulcerated granulomatous lesions of the skin (70%), bone(33%), GU tract (25%) and CNS (10%). Mostcommonly a verrucous lesion. Can also be ulcerated. Gray to violet colored.

•Seen in both immunocompetent and immunocompromised

Front 19

Diagnosis of Blastomyces?

Back 19

–CXR: lobar consolidation, multilobarinfiltrates, multiple nodules, etc.

–Tissuebiopsy: thick-walled yeast cells with singlebroad-based bud

–Serology

Front 20

Treatment for Blasto?

Back 20

–Itraconazole

–Amphotericinused for severe disease

Front 21

Where is Coccidioidesimmitis endemic?

Back 21

•Endemic in Southwestern U.S. and LatinAmerica

Front 22

Pathogenesis of Cocci?

Back 22

In the lungs, large spherules form and arefilled with endospores–Uponrupture of spherule wall, endosporesare released and differentiate to form new spherules

Front 23

Clinical manifestations of Cocci?

Back 23

Mildinfluenza-like illness with fever and cough (“valley fever”) in 10%•Erythema nodosum seen

Front 24

Dissemination rate? In what population? Where does it go?

Back 24

Dissemination occurs in 1% (AfricanAmericans, Filipinos and women in 3rd trimester of pregnancy atincreased risk)

»Bone, meninges and skin

Front 25

Dx for Cocci?

Back 25

–Serology

–Spherulesseen microscopically

–Eosinophiliais common

–Skintest reactivity to diagnose exposure

Front 26

Treatment for Cocci?

Back 26

–Amphotericinfor persistent lung lesions or disseminated disease

–Fluconazolefor meningitis

•Long term suppression to preventrecurrence

Front 27

How common of the dimorphic fungi is Paracoccidioidesbrasiliensis?

Back 27

Least common

Front 28

Paracoccidioidesbrasiliensis is endemic where?

Back 28

•Rural Latin America, especially Brazil

Front 29

Clinical manifestations of Paracocci?

Back 29

–Mildrespiratoryinfection which can progress with dissemination and development of oral, nasal,and facial nodular ulcerated lesions and submandibular lymphadenopathy.

Front 30

Diagnosis for Paracocci?

Back 30

–Tissuebiopsy shows yeast cells with multiple buds

-Serology

Front 31

Treatment for Paracocci?

Back 31

–Severalmonths of Itraconazole

–Amphotericinfor severe disease

Front 32

Configuration of multiple budding Paracocci?

Back 32

Pilot wheel configuration

Front 33

True or false: facial nodules result from Paracocci?

Back 33

True

Front 34

Where do you find Aspergillusfumigatus?

Back 34

Worldwide

Front 35

What is Aspergillus fumigatus? Where does it grow?

Back 35

Mold with septate hyphae

Front 36

On what does Aspergillus fumigatus grow and in what configuration?

Back 36

Growthon decaying vegetationproducing chains of conidia

Front 37

Main features of Aspergillus infection?

Back 37

–Fungusball formed within cavities of the lungs; can produce hemoptysis

–Allergicinfection of the bronchi that produces asthmatic symptoms and high IgEtiter; causes expectoration of brownish bronchial plugs containing hyphae

–InvasivePNA producing hemorrhage, infarction and necrosis, esp. in those withhematologic malignancies and neutropenia (common cause of death)

Front 38

Diagnosis of Aspergillusfumigatus?

Back 38

Biopsy: septate,acute-angle branching hyphae;radiating chains of conidia

Front 39

Aspergillus CT scan shows what?

Back 39

Singleor Multiple nodules with or without cavitation, halo sign (areas of focal hemorrhagearound the lesion)

Front 40

Aspergillus treatment? Goal of treatment if it forms a fungus ball? For allergic bronchopulmonary apergillosis (ABPA)?

Back 40

–1stline treatment: Voriconazole (Amphotericinor echinocandinsare alternative if patients don’t tolerate Vori)

–Removethe fungus balls

–ForABPA: steroids and antifungalagents

Front 41

What is Mucormycosis?

Back 41

•Opportunistic infection caused bybread mold fungi (Mucor, Rhizopus, Cunninghamella, Lichtheimia) belonging to the family Mucormycetes

Front 42

Risk factors for mucormycosis infection?

Back 42

•Risk factors for infection: Diabetes, neutropenia, iron overload, burns/surgicalwounds, corticosteroid use

Front 43

How is mucormycosis spread?

Back 43

•Transmitted by airborne spores,invades tissues (also angioinvasive) of patients with reduced hostdefenses

Front 44

Clinical manifestations of mucormycosis?

Back 44

–Invasiverhinocerebralsinusitis, frontal lobe abscesses

•Originates in the paranasal sinuses and spreads to the orbit,hard palate and brain and carries high mortality rate.

•Headache, facial pain

–Pneumonia

–Cutaneousinfections

Front 45

How is the configuration of mucormucosis characterized?

Back 45

Mucor is characterized by nonseptatebroad hyphae withfrequent right angle branching

Front 46

Orbital infections in mucormycosis are caused by what? Prognosis?

Back 46

Invasive rhinosinusitis. Not good.

Front 47

Diagnosis of mucormycosis?

Back 47

Biopsywith nonseptatebroad hyphae withfrequent right angle branching; spores in a sporangium

Front 48

Treatment of mucormycosis?

Back 48

–Treatthe underlying disorder plus Amphotericinand surgical removal of necrotic infected tissue

•Posaconazole can also be used

Front 49

What is Pneumocystisjiroveci(carinii)?

Back 49

Yeast

Front 50

Symptoms of Pneumocystisjiroveci(carinii) infection?

Back 50

•Most infections asymptomatic; 70% of thepopulation has been infected worldwide

•Important cause of pneumonia in immunosuppressed (PCP)

Front 51

What population is Pneumocystisjiroveci very common in, often causing death?

Back 51

•Common opportunistic infection andone of the leading causes of death in AIDS patients

Front 52

Reservoir of Pneumocystisjiroveci transmission?

Back 52

Unknown

Front 53

Describe the pathogenesis of Pneumocystisjiroveci infection?

Back 53

•Cysts in alveoli produceinflammatory response, resulting in frothy exudate that blocks oxygen exchange.

•Organism does not invade lungtissue.

Front 54

Why is Pneumocystis jiroveci (PCP) so common in AIDS patients?

Back 54

•CD4+ T cells recruit monocytes and macrophages which areresponsible for clearance of the organism

–CD4count <200 main risk factor

Front 55

Clinical manifestations of PCP?

Back 55

–Drycough–Dyspneathat is progressive–Fever–Tachypnea–Hypoxemia

Front 56

Mostcommon CXR findings of PCP?

Back 56

Diffuse, bilateral,interstitial, or alveolar infiltratesCXR normal in up to 1/4

Front 57

Can Pneumothoraces occur in PCP infection?

Back 57

Yes Pneumothoracescan occur

Front 58

Diagnosis of PCP?

Back 58

–Findingcysts by microscopic exam of lung tissue or fluids obtained by bronchoscopy orlung biopsy

–Visualizationof cysts by methenaminesilver, Giemsastain or other stains

–Flourescentantibody staining

–PCRon respiratory tract specimens

Front 59

PCP treatment?

Back 59

•1st line: Trimethoprim-sulfamethoxazole

•Other options (2nd line): –Clindamycin/Primaquine–Atovaquone–Pentamidine

Front 60

What do you give AIDS patients with CD4 count below 200 for prophylaxis against PCP?

Back 60

•Prophylaxis for AIDS patients withCD4 count below 200: Bactrim, Dapsone or Atovaquone.

Front 61

What is Cryptococcus neoformans and where is it found?

Back 61

•Yeast present in soil and bird (pigeon) droppings

Front 62

Describe configuration of Cryptococcus.

Back 62

–Ovalbudding yeast with wide polysaccharide capsule; forms narrow-based bud

Front 63

What does Cryptococcus do in immunocompromised patients? How serious of a problem is it for AIDS patients?

Back 63

Causes meningitis inimmunocompromised patients (AIDS especially) and is the most commonlife-threatening disease in AIDS patients. It also causes pneumonia inimmunosuppressed as well as immunocompetent persons.

Front 64

Crypto symptoms in immunocompetent patients? Immunosuppressed patients?

Back 64

–Vastmajority of immunocompetentpatients will be asymptomatic or have only mild respiratory symptoms.

–Inimmunocompromised populations symptoms include fever, chest pain, dyspnea, cough, andhemoptysis

Front 65

Describe CMV (Cytomegalovirus).

Back 65

•DNA enveloped virus similar inmorphology and structure to other Herpes viruses.

Front 66

Where does CMV infection occur?

Back 66

Worldwide

Front 67

How many infected people have antibodies against CMV?

Back 67

80%

Front 68

Symptoms for CMV infection

Back 68

Usually asymptomatic unless immunocompromised

Front 69

Pathogenesis of CMV?

Back 69

•Enters latent state primarily in monocytes and can be reactivated whencell-mediated immunity is decreased

Front 70

What does CMV do if you are immunosuppressed?

Back 70

•In immunosuppressed population (esp. renal and stemcell transplant recipients), pneumonitis commonly develops

–AIDSpatients: colitis and retinitis (typically NOT pneumonitis)

Front 71

What causes Nocardiosis?

Back 71

•Caused by the bacterium Nocardia asteroides

Front 72

What kind of metabolism does Nocardia asteroides have and where is it found?

Back 72

–Aerobes. Found in the soil.

Front 73

Describe histology of Nocardia.

Back 73

–Thinbranching filaments, gram-positive on Gram stain. Many isolates are weakly acid-fast.

Front 74

What does Nocardia do in the immunocompromised?

Back 74

–Inimmunocompromised,produce lung infection and may disseminate – have predilection for brain tissue

•Can cause pneumonia, lung abscesswith cavity formation, lung nodules or empyema

•Spreads to brain where it causesbrain abscesses

Front 75

Diagnosis for Nocardia?

Back 75

–Diagnosis: gram stain/acid-fast stain; culture

Front 76

Tx for Nocardia?

Back 76

–Treatment: Trimethoprim-sulfamethoxazole

•Sometimes combination therapy isneeded

•Resistance can occur. Sensitivities should be performed.