Fungal Respiratory infections

Question 1

What are some opprotunistic molds by their category?

Answer 1

• Hyaline Molds – Aspergillus Sp. – Fusarium – Zygomycetes
• Dermatiaceous Molds – Pseudoallescheria boydii – Scedosporium inflatum – Bipolaris spicifera
• Yeasts – Cryptococcus neoformans – Candida Spp. – Trichosporon beigelii

Question 2

What are some pathogenic dimorphic fungi?

Answer 2

• Histoplasma capsulatum • Coccidioides immitis • Blastomyces dermatitidis • Penicillum marneffei • Sporothrix schencki

Question 3

What are the classes of aspergillosus disease in the lungs?

Answer 3

• Allergic – Extrinsic allergic alveolitis – Extrinsic asthma – Allergic bronchopulmonary aspergillosis – Allergic aspergillus sinusitis
• Saprophytic – Pulmonary aspergilloma
• Invasive – Bronchopneumonia – Necrotizing tracheobronchitis – Invasive sinusitis – Chronic necrotizing aspergillosis – Disseminated aspergillosis

Question 4

Who is at higher risk and lower risk of getting Aspergillosis?

Answer 4

– Highest Risk • Allogeneic HSCT • Hematologic malignancies and neutropenia

– Lower risk • Autologous HSCT • Solid organ transplant • HIV • Prolonged steroids

Question 5

What are the clinical manifestations of invasive sinopulmonary aspergillosis?

Answer 5

Clinical Manifestation – Invasive sinus disease • Headache, stuffiness, fever, epistaxis • Proptosis, cranial nerve palsies – Invasive pulmonary disease • Fever, cough, pleuritic pain, hemoptysis

Question 6

Diagnosis of aspergillosis?

Answer 6

• Radiology – CT scan (ground-glass attenuation surrounding a pulmonary nodule “Halo sign”) – Other features (multiple nodules, lobar infiltrates to pleura)
• Cultures – Positive culture interpreted with risk factors – Significant in hematologic malignancies, neutropenia, HSCT
• Histology – Dichotomous acute-angle branching hyphae
• Serology – Galactomannan assay

Question 7

Therapy for Aspergillosis?

Answer 7

Therapy

– Amphotericin B

– Azoles • Itraconazole • Voriconazole • Posaconazole

– Echinocandins • Caspofungin • Anidulofungin

– Combination Therapy

– Immunomodulating agents • G-CSF

Question 8

General features of Cryptococcus? Immunity?

Answer 8

General – World wide – usually in excreta of birds (pigeons) – Species • Cryptococcus neoformans var. grubii (immunosuppressed) • Cryptococcus var. gatti (immunocompetent)

– Immunity • Cell mediated • Th1 response – Production of TNF, IFN, IL2

Question 9

Predisposing factors to a Cryptococcus infection?

Answer 9

– HIV infection

– Corticosteroids

– Solid organ transplant

– Hematologic malignancies

– CD4 T-cell lymphopenia

– Connective tissue diseases • Sarcoid, SLE, RA – Monoclonal antibodies • Etanercept, infliximab, alemtuzumab

– Cirrhosis

– Pregnancy

Question 10

Clinical manifestations of Cryptococcus?

Answer 10

Most often • CNS • Respiratory

– Less often • Prostate • Skin • Bone • Urinary tract • Blood

Question 11

What is most important about Cryptococcus? Clinical manifestations?

Answer 11

• Most important portal of entry
• Clinical manifestations – Asymptomatic – Fever, nonproductive cough, chest pain, weight loss – Acute respiratory failure – Immunocompromised have associated CNS involvement

Question 12

Radiology of Cryptococcus?

Answer 12

• Radiology – Most often – Well defined single nodules – Multiple pulmonary nodules • Cavitation in compromised
• Less often – Pleural effusion – Hilar adenopathy – Diffuse reticulonodular infiltrates

Question 13

Serology of Cryptococcus?

Answer 13

Serology – Cryptococcal antigen is negative in immunocompetent

Question 14

Lab diagnosis of Cryptococcus?

Answer 14

– Direct exam of specimens • Round encapsulated yeast cells (5 – 20 mm)

– Histopathology • Pulmonary nodules, BAL, lung tissue • Gomoris methenamine silver stain, PAS stain, FontanaMasson silver stain

– Serology • Cryptococcal antigen – Not helpful in diagnosing and deciding therapy – Usually negative in competent patients with localized respiratory infection

• Cryptococcal antibody – False positive with blastomycosis, histoplasmosis

– Culture • Nohyphae or pseudohyphae • Urease positive

Question 15

Management of Cryptococcus?

Answer 15

– Asymptomatic with positive respiratory secretions • Observe vs. therapy

– Immunocompromised or symptomatic • Fluconazole • Itraconazole • Amphotericin B

– Severe immunocompromised with symptoms • Amphotericin B plus flucytosine for 2 weeks, then fluconazole for 10 weeks

Question 16

Epidimiology of Histoplasmosis?

Answer 16

– Endemic in Mississippi and Ohio River Valley • Very high in Indianapolis

– Large flocks of birds • Landscaping, cleaning in attics, and barns • Tearing down structures where birds nest

– Cave explorers (spelunking) • Bats

Question 17

Pathogenesis of Histoplasmosis?

Answer 17

– Microcondia is infectious form • To alveoli and engulfed by neutrophils and macrophages

– Yeast phase • Exists intracellular in macrophages • Spreads to hilar and mediastinal nodes and hematogenous to RES

– Cell mediated immunity • Internally controls the disease • Severe disease in CMI deficient

– Exists in latent infection • Reactivates in immunocompromised

Question 18

Explain the clinical manifestations of histoplasmosis pulmonary infection?

Answer 18

Pulmonary Infection

– Acute pulmonary histoplasmosis • Fever, chills, fatigue, myalgia, dyspnea, non-productive cough • Chest x-ray – Patchy infiltrates – Multilobar, nodular infiltrates with hilar and mediastinal nodes

– Granulomatous mediastinitus • Large mediastinal, hilar nodes, necrotic • Impinge on adjacent structures • Dysphagia, chest pain, cough • Tracheoesophageal fistula

– Chronic cavitary pulmonary histoplasmosis • Fever, fatigue, anorexia, weight loss, productive cough, hemoptysis • Chest x-ray • Mimmics tuberculosis • Cavitary upper lobe infiltrate

– Fibrosing mediastinitus • Young women • Excessive fibrotic response in mediastinum • Entrapment of great vessels and bronchus • Dyspnea, cough, wheezing, hemoptysis • Superior vena cava syndrome, heart failure, pulmonary emboli

Question 19

Diagnosis of Histoplasmosis?

Answer 19

– Growth on tissue or fluid samples definitive for diagnosis • Uniform appearing 2 – 4 mm oval budding yeast

– Stains • Methenamine silver or Periodic Acid-Schiff (PAS) • Bone marrow, liver, lymph nodes, ulcers

– Urine antigen • Useful for disseminated infection

– Antibody tests • Immunodiffusion (H or M antibodies) • Complement fixation • Useful for chronic disseminated or chronic pulmonary histoplasmosis

Question 20

Explain a disseminated infection in histoplasmosis? Seen in? Symptoms? Labs?

Answer 20

– Seen mostly in immunocompromised patients • AIDS, transplants, TNF inhibitor, steroids

– Symptoms • Chills, fever, malaise, anorexia, weight loss, dyspnea • Hypotension, ARDS, sepsis syndrome, DIC

– Lab • Pancytopenia, elevated alkaline phosphatase

Question 21

Treatment of histoplasmosis?

Answer 21

– Severe • Amphotericin B

– Mild to Moderate • Azoles (Itraconazole, Fluconazole, Voriconazole)

– Echinocardins • Inactive

Question 22

Blastomycosis epidimiology?

Answer 22

– Endemic in South Central and North Central USA • Wisconsin, Minnesota, Southern Ontario, Manitoba, Alberta

– Natural habitat • Soil, decaying wood • Large outbreak in beaver pond

– Seen in outdoorsmen • African Americans • Aboriginal population of Manitoba

Question 23

Pathogenesis of blastomycosis?

Answer 23

– Acquired through inhalation of mold form into alveoli

– Change to yeast form in lungs and multiply • Dissemination hematogenously before immunity develops

– Immunity • Neutrophils • CMI with T cells, macrophages • More severe disease in immunocompromised

Question 24

Pulmonary manifestations of Blastomycosis? Chest x-ray?

Answer 24

– Asymptomatic

– Overwhelming severe infection • ARDS

– Acute pneumonia • Atypical presentation without response to antibiotics

– Sub acute, chronic pneumonia • Fever, night sweats, fatigue, productive cough, dyspnea

– Chest x-ray • Often mass-like lesions • Multiple nodular lesions • Lobar infiltrates • Cavitary lesions • Hilar, mediastinal nodes rarely seen

Question 25

Cutaneous lesions of Blastomycosis?

Answer 25

Cutaneous lesions • Well circumscribed, nonpainful papules, nodules, plaques • May be verrucous with microabscess • May ulcerate • May be confused with squamous cell cancer, atypical pyoderma gangrenosum or nontuberculous mycobacterial lesions

Question 26

Commonly seen other clinical manifestations of Blastomycosis without skin or pulmonary?

Answer 26

– Genitourinary • Prostate

– Septic arthritis

– Osteomyelitis

Question 27

Diagnosis of Blastomycosis? Serology?

Answer 27

– Growth of organism from tissue biopsy, sputum, or body fluid is definitive – Histopathology from tissue biopsy • Early diagnosis • Yeasts are large, thick-walled, and buds single and broad based • Stain with methenamine silver or PAS

– Serology • Antibody tests not sensitive nor specific • Urine antigen is available

Question 28

Therapy for Blastomycosis?

Answer 28

– Severe disseminated disease • Amphotericin B

– Mild to moderate disease • Azoles – Itraconazole preferred – Fluconazole higher dose 800 mg q.d. – Voriconazole – no data – Posaconazole – no data

Question 29

Describe the epidiomolgy of coccidiomycosis?

Answer 29

• Dimorphic Fungus – Arthroconidia (spores) – Spherule with endospores (tissue)
• Region – Southwestern USA – San Joaquin Valley – Arizona – Mexico
• Ecology – Soil organism (arthroconidia) – Dispersed in air
• Persons at risk – Occupation with soil exposure – Immunocompromised patients • AIDS • Transplants • TNF antagonists • Pregnancy – Persons of Filipino or African-American descent

Question 30

Pathogenesis of coccidiomycosis?

Answer 30

– Arthroconidia are inhaled – Ingested by pulmonary macrophages • Convert to spherule with hundreds of asexual endospores

– Spherule ruptures • Endospores disseminate hematogenously to other organs

– Host control is through cell-mediated immunity

Question 31

Clinical presentation of Coccidiomycosis?

Answer 31

– Primary pulmonary infection • Asymptomatic • Resembles CAP or influenza

– Fever, cough, pulmonary infiltrates • Most resolve spontaneously • Special conditions

– Rheumatologic syndromes » Erythema nodosum, erythema multiforme

– Pleural effusion

– Immunosuppression » Develops into progressive disease and dissemination – Pregnancy »3 rd trimester with complications – Race » Filipinos, African-Americans with progression

Question 32

Outcomes of the primary coccidiomycosis infection?

Answer 32

– Uneventful healing

– Coccidioidoma • Benign mass-like lesion

– Progressive or persistent pneumonia • In immunocompromised • Usually infiltrates are present over 2 months and progress with cavitation

– Chronic pulmonary coccidiomycosis • 5% of patients • Smoldering over years • Nodules may cavitate and fibrose • Destroy lungs progressively • May need resection

– Disseminated disease • All regions of body except GI • Mortality high – CNS • Life long therapy

Question 33

Diagnosis of Coccidiomycosis?

Answer 33

– Culture • Most definitive for diagnosis

– Histopathologic findings • Methenamine silver, PAS • Spherules with endospores

– Immunologic • Complement fixation – 1:16 or > worsening disease • Immunodiffusion • ELISA, IgG, IgM (sensitive and specific)

Question 34

Therapy for Coccidiomycosis?

Answer 34

– Amphotericin B • Primary disease • CNS

– Azoles • Ketoconazole (not used) • Itraconazole • Fluconazole

– Primary disease • Voriconazole • Posaconazole

– Echinocandins • New agents