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L22 Fungal lung disease

  1. Fungi
    overview
    • Yeasts: round fungi that reproduce by budding with smooth colonies on agar
    • -Candida
    • -Cryptococcus (cryptococcus neoformans - endemic)

    • Mold: filamentous fungi consisting of tubular structures called hyphae that grows by branching or longitudinal extension with fuzzy colonies on agar
    • -Aspergillus
    • -Mucorales

    • Dimorphic: grwo in the host as yeast; grow outside the host as molds (aka "endemic" fungi; regionally endemic)
    • -Histoplasma capsulatum
    • -Coccidioides immitis
    • -Blastomyces dermatitidis
    • -Paracoccidioides brasiliensis
    • (Cryptococcus neoformans is an endemic yeast)

    Opportunistic fungi: generally only cause significant disease in those who are immunocompromised

    • Dx: identification of organism
    • -Yeasts: biochemical tests
    • -Molds: appearance
  2. Histoplasma capsulatum
    • Endemic to:
    • -Soil based fungus, river valleys
    • -mean temperature 22-29 degrees C; annual precipitation 35 to 50 inches
    • -bird and bat guano, and soil

    Image Upload 2

    • Histology:
    • Image Upload 4
    • -Culture/soil: tuberculate macroconidia and microconidia (micro is infectious form)


    • Pathophysiology:
    • -Microconidia are inhaled and lodge in the terminal bronchioles and alveoli
    • -body temp (37C) --> yeast form; change in form occurs within macrophages
    • Image Upload 6

    • Host response:
    • -Macrophages and T cells required for restriction of growth
    • -dormant forms persist

    • Presentation:
    • -most primary infection goes unrecognized
    • -Sx depend on inoculum size and virulence
    • -Incubation: 7-14 days
    • -Sx: fever, headache, nonproductive cough and substernal chest pain
    • -Less common sx: erythema multiforme, erythema nodosum, arthralgia in 6%
    • -Resolution in ~10days
    • PE: usually normal; few rales, occasionally HSM
    • CxR: patchy pneumonia and hilar adenopathy
    • Image Upload 8
    • -Calcified lesions indicate old disease

    • Epidemiology:
    • -Male>female (for symptoms) 4:1; equal skin test reactivity

    • Pathology:
    • -Caseating and noncaseating granulomas develop and calcify
    • Image Upload 10
  3. Histoplasmosis
    Complications, Dx, treatment
    • Complications:
    • -Pericarditis (6%)
    • -mass-like lesion
    • -mediastinal fibrosis
    • -chronic cavitary disease
    • -disseminated disease (especially immunocompromised)
    • -Liver and splenic calcifications common in healed acute histoplasmosis

    • Dx:
    • -Culture on brain heart infusion agar (positive in 10% of acute cases, 60% with cavitary disease, 90% in AIDS pts with progressive disseminated disease)
    • -Antigen detection in urine (positive in 20% of acute cases, 40% with cavitary disease, 90% with progressive disseminated)
    • -Serology (can follow titers to monitor progression; if it becomes disseminated)

    • Tx:
    • -Many recover spontaneously and don't need treatment
    • -Itraconazole if symptomatic, hypoxemic
    • -Liposomal Amphotericin B if severely ill
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    • Histoplasma capsulatum
    • Wright-Giemsa stain
  5. Image Upload 14
    • H. capsulatum
    • PAS stain
  6. Image Upload 16
    • H. capsulatum
    • Silver Stain
  7. Coccidioides immitis
    • Pathogen:
    • -soil based dimorphic fungus
    • -little rain, hot summers, mild winters, alkaline soil

    • Species:
    • -Coccidioides immitis (California)
    • -Coccidioides posadasii

    • Culture, soil: Arthroconidia
    • Image Upload 18

    • Tissue: Spherule
    • Image Upload 20

    • Endemic: southwest (Arizona>California)
    • -"Valley Fever"
    • Image Upload 22
  8. Valley Fever
    Coccidioides immitis
    • -San Joaquin Valley (Imperial Valley)
    • -Outbreak where soil disturbed

    • Coccidioides immitis:
    • -Infectious form: arthroconidia (inhaled, land in terminal bronchioles)
    • -Change into spherules and cause local inflammation
    • -Acute infection involves neutrophils and eosinophils
    • -later: granulomatous inflammation
    • -Dissemination occurs --> endospores within macrophages

    • Immune response:
    • -Control requires T lymphocytes
    • -those w/disseminated infection don't make interferon gamma in response to cocci antigens
    • -Disseminated infection is more common in African Americans, Latinos, Filipinos

    • Illness:
    • -endemic areas, may be responsible for up to 1/3 CAP
    • -incubation 7-21 days
    • -Sx: cough, chest pain, SOB, fever, fatigue, weight loss

    • Complications:
    • -Erythema multiforme
    • -Erythema nodosum
    • -Migratory arthralgias
    • -Hilar adenopathy may persist
    • -Nodules may develop
    • -Initial lesions may cavitate

    • CxR:
    • Acute
    • Image Upload 24

    • Chronic 
    • Image Upload 26
  9. Disseminated Cocci
    • CxR often normal
    • Skin disease
    • meningitis
    • Joint and bone involvement
  10. Coccidioides
    diagnosis and treatment
    • Dx:
    • -Demonstration of fungus in tissue
    • -growth from culture
    • -Serology: Precipitin, Complement fixation, immunodiffusion, ELISA
    • -Skin testing used to be available (not done now)

    • Tx:
    • -Depends on extent of disease
    • -Amphotericin
    • -Fluconazole
    • -Dissemination generally requires lifelong suppression
  11. Blastomyces dermatitidis
    • -Dimorphic soil fungus
    • -Infectious form = conidia -->aerosolized when the mycelia are disturbed
    • Image Upload 28

    • -Body temp --> converted to yeast forms: thick, refractile wall, 8-15 micromilliter
    • -reproduce by broad based bud
    • Image Upload 30
    • Image Upload 32
    • Epidemiology:
    • -Sporadic cases in humans and dogs
    • -River basins, predominantly Ohio and Mississippi 
    • Image Upload 34
    • -Warm, moist soil with decaying wood or vegetation
  12. Blasto
    Pathogenesis and pathology
    • -Lung is the portal of entry
    • -most cutaneous disease is from hematogenous spread

    • Path: similar to cocci: polys f/b noncaseating granulomas
    • -cutaneous disease has pseudoepitheliomatous hyperplasia and microabscesses - may mimic squamous cell carcinoma

    • Immunity:
    • -Polys and macrophages can control conidia, but not yeast
    • -T cells needed to control infection once yeast forms present

    • Clinical presentation:
    • -Many/most infections asymptomatic
    • -Pulmonary infection may be acute or chronic
    • -Skin, bone, GU tract are the most common extrapulmonary sites
    • -Incubation period: 30-45 days
    • -Sx: cough, myalgias, arthralgia, chills, fever
    • -Pleuritic pain may be prominent but transient

    • Imaging:
    • -Lobar or segmental consolidation of CxR
    • -Pleural fluid uncommon
    • -Hilar adenopathy uncommon
    • Image Upload 36

    • Chronic: present almost like lung cancer
    • -weight loss
    • -cough
    • -anorexia
    • -hemoptysis
    • -pleuritic chest pain

    • Dx:
    • -cytology, wet mount
    • -culture positive in 75% (92% in bronchoscopy)
    • -PAS or GMS stains of tissue
    • -Serology not very sensitive nor specific
    • -Antigen detection in urine +93%

    • Tx:
    • -Acute disease: treat (not the wait and watch)
    • -Azoles for mild-moderate
    • -Amphtericin B f/b itraconazole for severe infection
  13. Paracoccidioides brasiliensis
    • -Dimorphic fungus found in South America
    • -Yeast form 4-40 micromillimeters, double cell wall, intracytoplasmic lipid globules, multiple daughter cells mimicing a "pilot wheel"
    • Image Upload 38
    • Image Upload 40

    • Presentation:
    • -Disease of male agricultural workers (15:1 M:F)
    • 2 Forms:
    • -Chronic progressive pulmonary and extrapulmonary infection in adults
    • -Juvenile form with more severe acute disease
    • -Skin presentations:
    • Image Upload 42

    • Dx:
    • -Direct examination of specimens
    • -Histology
    • -Culture
    • -Serology
    • Image Upload 44

    • Tx:
    • -Sulfadiazine (for 3-5 years)
    • -TMP/Sulfa (12-24months)
    • -Amphotericin
    • -Itraconazole
Author
jknell
ID
200847
Card Set
L22 Fungal lung disease
Description
Fungal lung diseases
Updated

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