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Disseminated Blastomycosis 59-year-old white male Presents in Pensacola, FL with a 3 month history of fatigue, weakness, intermittent fever, chills, shortness of breath Development of ulcerative lesions on his right thigh and left forearm Purulent discharge

59-year-old white male Presents in Pensacola, FL with a 3 month history of fatigue, weakness, intermittent fever, chills, shortness of breath Development

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59-year-old white male Presents in Pensacola, FL with a 3 month history of fatigue, weakness, intermittent fever, chills, shortness of breath Development of ulcerative lesions on his right thigh and left forearm Purulent discharge Slide 2 Previous oral antibiotics have failed Past medical history: Hypertension, arthritis and gout Patient is an avid gardener Travel history over past year: Minnesota, Wisconsin and Ohio Spelunking trip to Indiana Slide 3 Physical exam Mildly tachypenic Dyspnea upon exertion Chest x-ray: single, large patchy density in the upper left lung Vital signs: Temp = 102.5F HR = 131 BP = 115/70 R = 20 Slide 4 Skin: Right thigh scattered erythematous 3-4 cm ulcers Left forearm single, 1 cm subcutaneous nodule Slide 5 Initial laboratory data: WBC: 17,100 /L (4,000-11,000) with 83% PMNs Hgb: 10 g/dL (13-16.7)ALP: 385 U/L (32-148) Hct: 30% (38-50)AST: 65 U/L (15-37) BUN: 23 mg/dL (6-20)ALT: 160 U/L (30-65) Creat: 0.9 mg/dL (0.4-1.3) GGT: 887 U/L (11-49) Total Bili: 3.8 mg/dL (0.4-1.2) Disseminated Blastomycosis Slide 6 An aspirate of the subcutaneous lesion was submitted for C&S and fungal culture. Direct Gram stain report: Large budding yeast seen Acid fast stain report: Large broad-based budding yeast seen 20 u Gram stain Acid fast stain Disseminated Blastomycosis Slide 7 Based on these findings, a presumptive diagnosis of Blastomycosis was made Slide 8 Epidemiology: Endemic around the midwest (MO, MS & OH U.S. river valleys ) Ecologic niche is unclear - moist soil w/ high organic content Rarely isolated from soil; microconidia believed to be infective Infection initiated by inhalation of infectious propagules Virulence factors & pathogenesis: Inhaled microconidia evolve to form yeast phase Yeast escape recognition by macrophages, and disseminate via bloodstream Defects in CMI predispose to systemic disease Biggest threat to immunocompromised Slide 9 Clinical Manifestations: Respiratory infection mild, may resolve spontaneously Chronic granulomatous disease affecting lungs, skin, and mucous membranes Chronic cutaneous blastomycosis: Ulcerated lesions Exposed or mucocutaneous tissues Systemic Blastomycosis Dissemination to subcutaneous tissues is common May become chronic Involves any organ bone lesions and osteomyelitis are often encountered Slide 10 Blastomycosis Clinical Manifestations Slide 11 Blastomyces dermatitidis: Thermally dimorphic fungus Specimen: Sputum, BAL, BM or skin lesions In tissue: thick-walled, large yeast (8-15 um) with single budding cells w/ wide junction between the cells Not intracellular! In 25C culture: SDA and SDA-CC positive, 2-4 weeks; SABHI positive, 1-2 weeks Hyaline, septate hyphae with single laterally-borne oval to round conidia (3-4 m) At 37C: Large single budding yeast cells (broad-based bud) Slide 12 No skin test is available for Blastomycosis Serologic tests: Cross reactions with histoplasmin and coccidioidin Lack sensitivity and specificity Slide 13 Blastomycosis Slide 14 Blastomycosis Slide 15 Blastomycosis Slide 16 - May take 4 weeks Blastomycosis Slide 17 Blastomycosis Slide 18 Blastomycosis Slide 19 May take 4 wks to grow! Definitive Identification of Blastomyces dermatitidis Slide 20 Exoantigen test allows definitive ID without temperature regulated-phase conversion Definitive Identification of Blastomyces dermatitidis Slide 21 Treatment: Treatment: Mild cases = bed rest Amphotericin B for severe, life threatening pulmonary, disseminated or CNS disease Itraconazole for less severe cases Relapses may occur long-term oral itraconazole may be needed Success rates range from 70-95% AIDS & immunocompromised: Long-term itraconazole survival rates range from 35-50% in this later group Slide 22 For our patient: Hospitalized for 10 days Treated with Amphotericin B, followed by long term azole therapy Our case highlighted common features of disseminated Blastomycosis Seemingly previously healthy patient Chronic cutaneous involvement