Introduction Systemic mycoses consist of 4 dieases histoplasmosis (Histoplasma capsulatum) coccidiomycosis (Coccidioides immitis) blastomycosis (Blastomyces dermatitidis) paracoccidioidomycosis (Paracoccidioides brasiliensis) Characteristics of systemic mycoses dimorphic mold in soil (↓ temperature, "mold in the cold") yeast in Tissue (↑ Temperature) C. immitis is an exception spherule (not yeast) in tissue endemic to a specific area Pathogenesis fungi inhaled in spore form lungs are locally infected infection disseminates hematogenously Presentation Symptoms asymptomatic majority of cases most people never visit the doctor pneumonia fever cough may be acute or chronic clinical presentation is similar to TB disseminated disease fever and malaise seen in immunocompromised Evaluation Radiographs CXR will show lesion Biopsy Delayed hypersensitivity reaction can be used to diagnose (similar to PPD) coccidioidin histoplasmin note: many people have been exposed and will show seroconversion Differential Diagnosis Tuberculosis similarities with TB inhaled lung infection wide range of severity (asymptomatic to chronic) granulomas, cavitations, and calcifications hematogenous dissemination diagnosis with PPD-like hypersensitivity reaction fungal infections do NOT transmit via person-to-person unlike TB Treatment Fluconazole or ketoconazole (local infection) indications used to treat all types of local systemic mycoses Amphotericin B (systemic infection) indications used to treat all types of local systemic mycoses Snapshot A 45-year-old woman presents to the infectious disease clinic with a five-week history of a dry cough, shortness of breath, fever, and weight loss. She has been HIV positive for 10 years, has lost her insurance six months ago, and has been non-compliant with her HAART regimen. She recently moved from Cinncinnati and has lived there for the past 5 years. Her temperature is 102°F(38°C), pulse 90/min, and respirations are/min. Physical exam reveals diffuse crackles in both lung fields, hepatosplenomegaly, and generalized lymphadenopathy. Her CD4 count is 100/mm^3. Chest radiograph shows reticulonodular infiltrates, calcified granulomas, and hilar lymphadenopathy. Histoplasma capsulatum Diseases histoplasmosis (pneumonia) hilar lymphadenopathy ulcerated tongue lesions Pathogenesis invades macrophages oval yeast cells seen within macrophages the only systemic fungus with yeasts phagocytosed by macrophages Transmission cave exploring/spelunking endemic to Mississippi and Ohio River valleys Ohio and Tennessee found in bird and bat droppings Laboratory NOT encapsulated despite name Snapshot A 75-year-old male presents to the hospital with chest pain, shortness of breath, arthralgia of knees and ankles, and mild fever. He lives in a retirement community in Arizona. He was being treated for community-acquired pneumonia when he developed painful red bumps on his shins. A chest radiograph reveals multiple pulmonary nodules. Direct sputum microscopy reveals spherules. Coccidioides immitis Diseases coccidioidomycosis mild pneumonia opportunistic infection in AIDS patients in Arizona meningitis disseminated disease to skin and bone in immunocompromised Transmission endemic to southwest U.S. AZ, NM, and southern CA San Joaquin Valley incidence ↑ after earthquakes spherules released from soil Laboratory spherule (not yeast) in tissue spherules contain endospores seen on biopsy Snapshot A 24-year-old-man presents to the hospital with a three-month history of dry cough, fatigue, fever, and weight loss and is HIV-negative. There is a poor response to an anti-TB regimen. Physical exam is notable for disseminated scaling papulonodular lesions. Chest radiograph reveals a right pleural effusion. Cultures of a pleural tap are pending, but skin biopsy revealed broad-based budding of spores on a background of lymphocytes and scanty neutrophils. Blastomyces dermatitidis Diseases blastomycosis (most severe disease of the group) chronic inflammatory lung disease granulomatous nodules dissemination to skin and bone rarest of the group Transmission endemic to Mississippi River valley and Central America Laboratory round, broad-based budding yeast thick, double refractive walls Snapshot A 50-year-old-man presents to a hospital in Brazil with a one-year history of a 30 pound weight loss, progressive shortness of breath, and dry cough. He denies fever and night sweats, is a migrant farm worker, and is HIV negative. He started an anti-TB regimen, but stopped when his sputum proved to be negative for AAFB. There is no lymphadenopathy, hepatosplenomegaly, or skin lesions on physical exam. Chest radiograph reveals bilateral diffusion and infiltration of the lungs. Culture of a core needle biopsy specimen revealed budding yeast with a captain's wheel appearance. Paracoccidioides brasiliensis Diseases paracoccidioidomycosis (pneumonia) Transmission endemic to Latin America Laboratory "captain's wheel" appearance budding yeast