Systemic Mycoses

Snapshot

• A 35-year-old woman presents to her primary care physician for a 2-week history of dry cough and worsening shortness of breath. She reports that she also has joint pains in her knees and ankles, as well as a rash on her legs. She recently traveled to southern California on a business trip, where she hiked with the team in the desert. A small earthquake occurred on the 2^nd day of her business trip. On physical exam, she has multiple nodules on her anterior shins. A chest radiograph shows a consolidation in the right lower lung field. (Coccidioidomycosis)

Introduction

• Introduction
  • dimorphic yeasts
    • mold form in the soil, outside the body
      • grows on Sabouraud agar
    • yeast form in tissues, inside the body
      • grows on blood agar
    • Coccidioides immitis is an exception
      • spherule form, not yeast, in tissue
  • demographics
    • depends on geographic location 
  • transmission
    • inhalation of spores
    • cannot be transmitted between people
  • pathogenesis
    • inhalation causes a pulmonary infection
    • fungi can then disseminate to other organs, particularly the skin
    • causes granulomas
      • composed of epithelioid cells and multinucleated giant cells
      • Th1 mediated
  • clinical syndromes
    • pneumonia
    • chronic inflammatory lung disease
• systemic dissemination

Overview of Systemic Mycoses
Clinical Syndrome	Histoplasmosis	Coccidioidomycosis	Blastomycosis	Paracoccidioidomycosis
Organism	Histoplasma capsulatum	Coccidioides immitisCoccidioides posadasii	Blastomyces dermatitidis	Paracoccidioides brasiliensisParacoccidioides lutzii
Demographics	MississippiOhio River Valley	Southwestern USCalifornia	Eastern USCentral US	Latin America
Skin manifestations	Ulcers on oral mucosa	Erythema nodosumErythema multiforme	Verrucous skin lesions	Verrucous skin lesions
Histology	Macrophages filled with fungus cells	Spherules (larger than red blood cells (RBCs)) filled with endospores	Broad-based budding yeast (same size as RBCs)	Budding yeast larger than RBCs

• Differential
  • tuberculosis 
    • also affects the pulmonary system
    • causes granulomas, cavitations, and calcifications
    • unlike these systemic mycoses, tuberculosis can be transmitted person to person
• Treatment
  • amphotericin B
    • systemic infections
  • itraconazole or fluconazole
• localized infections

Histoplasmosis

• Histoplasma capsulatum
  • demographics
    • Mississippi
    • Ohio River Valley (Ohio and Tennessee)
  • risk factors
    • bird or bat excretions
    • chicken farms
    • exploring caves or spelunking 
    • HIV infection
• Presentation
  • pneumonia
    • usually self-limiting
  • chronic cavitary lung disease
  • hilar lymphadenopathy
  • gastrointestinal symptoms
  • splenomegaly
  • oral mucosal ulcers on tongue or palate
• Imaging
  • chest radiograph
    • normal or with patchy infiltrates with hilar/mediastinal lymphadenopathy
• Studies
  • detection of antigen in serum or urine
  • tissue biopsy
• methenamine silver or periodic acid-Schiff stains show oval yeasts within macrophages   

Coccidioidomycosis

• Coccidioides immitis or Coccidioides posadasii
  • demographics
    • southwestern US
      • Arizona, New Mexico, and southern California
    • Central and South America
  • risk factors
    • earthquakes release spherules from soil
• Presentation  
  • pneumonia
  • dissemination to skin in 50% of patients
    • erythema nodosum
      • “desert bumps”
    • erythema multiforme
  • arthralgias
    • “desert rheumatism”
  • meningitis
• Imaging
  • chest radiograph
    • consolidations, hilar/mediastinal lymphadenopathy, or pleural effusions
  • chest computed tomography (CT)
    • multifocal ground glass opacities
• Studies
  • detection of immunoglobulin M (IgM) in serum
  • detection of antigen in serum
  • tissue biopsy  
• spherules (larger than RBCs) filled with endospores  

Blastomycosis

• Blastomyces dermatitidis
  • demographics 
    • eastern US
    • central US
  • risk factors
    • HIV infection
• Presentation
  • majority are asymptomatic
  • pneumonia
  • severe chronic inflammatory lung disease
  • dissemination to skin, often on the face
    • verrucous skin lesions
    • granulomatous nodules
    • ulcers
• Imaging
  • chest CT
    • infiltrates without hilar lymphadenopathy
    • cavitary lesions in chronic disease
• Studies
  • tissue biopsy   
    • fungal stain shows broad-based budding yeast
• same size as red blood cells (RBCs)

Paracoccidioidomycosis

• Paracoccidioides brasiliensis or Paracoccidioides lutzii
  • also known as “South American blastomycosis”
  • demographics
    • Latin America
    • male > female
  • risk factors
    • contact with soil
• Presentation 
  • severe chronic inflammatory lung disease
  • pneumonia
  • lymphadenopathy
  • dissemination to skin, often on the face but can also affect mucous membranes
    • verrucous skin lesions
    • granulomatous nodules
• Imaging
  • chest radiograph
    • bilateral iniltrates without cavitation
• Studies
  • tissue biopsy 
    • budding yeast
    • “captain’s wheel” formation
    • granulomas