L22 Fungal lung disease

• 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

• 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

• Histology:
• -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

• 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
• -Calcified lesions indicate old disease

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

• Pathology:
• -Caseating and noncaseating granulomas develop and calcify

• 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

• Histoplasma capsulatum
• Wright-Giemsa stain

• H. capsulatum
• PAS stain

• H. capsulatum
• Silver Stain

• Pathogen:
• -soil based dimorphic fungus
• -little rain, hot summers, mild winters, alkaline soil

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

• Culture, soil: Arthroconidia

• Tissue: Spherule

• Endemic: southwest (Arizona>California)
• -"Valley Fever"

• -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

• Chronic 

• CxR often normal
• Skin disease
• meningitis
• Joint and bone involvement

• 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

• -Dimorphic soil fungus
• -Infectious form = conidia -->aerosolized when the mycelia are disturbed

• -Body temp --> converted to yeast forms: thick, refractile wall, 8-15 micromilliter
• -reproduce by broad based bud
• Epidemiology:
• -Sporadic cases in humans and dogs
• -River basins, predominantly Ohio and Mississippi 
• -Warm, moist soil with decaying wood or vegetation

• -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

• 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

• -Dimorphic fungus found in South America
• -Yeast form 4-40 micromillimeters, double cell wall, intracytoplasmic lipid globules, multiple daughter cells mimicing a "pilot wheel"

• 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:

• Dx:
• -Direct examination of specimens
• -Histology
• -Culture
• -Serology

• Tx:
• -Sulfadiazine (for 3-5 years)
• -TMP/Sulfa (12-24months)
• -Amphotericin
• -Itraconazole