Systemic mycoses Notes

NOTES NOTES SYSTEMIC MYCOSES GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES DIAGNOSIS ▪ Fungal infections in internal organs (esp. lungs) DIAGNOSTIC IMAGING CAUSES LAB RESULTS ▪ Dimorphic species of fungi ▪ Transmitted by spore inhalation; lymphohematogenous dissemination SIGNS & SYMPTOMS ▪ X-ray, CT scan, MRI ▪ Culture-based observation, direct microscopy, serologic tests, lab tests (e.g. abnormal blood exams) TREATMENT MEDICATIONS ▪ Cough, chest pain, fever ▪ Antifungal agents BLASTOMYCES SPP. osms.it/blastomyces PATHOLOGY & CAUSES ▪ Blastomycosis ▫ Systemic fungal infection caused by Blastomyces dermatitidis, B. gilchristii; usually manifests as chronic pneumonia ▪ Incubation period: 3–6 weeks ▪ Spore inhalation → conversion to yeast in lungs → phagocytosis by macrophages → acute suppurative inflammation ▪ Immune response: mainly cellular, mediated by T-lymphocytes, macrophages ▪ Common sites of infection: primarily lungs (90%); skin, bones, genitourinary tract, central nervous system (CNS) 558 OSMOSIS.ORG Blastomyces spp. ▪ Size: 8–15μm ▪ Broad-based budding (wide connection between two cells before splitting apart during reproduction) ▪ Thermal dimorphism ▫ Mold form (< 37°C/98.6°F): produces spores ▫ Yeast form (37°C/98.6°F): multinucleate; antiphagocytic (e.g. thick cell wall) ▪ Virulence ▫ Thick cell wall: resistance to phagocytosis ▫ BAD-1: cell surface glycoprotein; adhesin ▫ Binds yeast to extracellular matrix, macrophages

Chapter 100 Systemic Mycoses ▫ Blocks production of tumor necrosis factor (TNF) alpha (proinflammatory cytokine) Clinical syndromes ▪ Pulmonary blastomycosis ▫ Pneumonia, mostly chronic ▫ Frequently affects upper lobes ▪ Primary cutaneous blastomycosis ▫ Ulcerative/verrucous skin lesions ▪ Disseminated blastomycosis ▫ Osteomyelitis; prostatitis, epididymoorchitis (inflammation of epididymis/ testicles); meningitis; intracranial abscesses RISK FACTORS Outdoor occupations (e.g. farming) Recreational exposure to soil Immunosuppression High prevalence in North America Recent travel to endemic areas (e.g. Ohio, Mississippi river valleys) ▪ Comorbid conditions ▪ ▪ ▪ ▪ ▪ COMPLICATIONS LAB RESULTS Culture-based observation ▪ tissue, sputum, body fluids ▫ Sabouraud dextrose agar without cycloheximide ▫ Confirmation requires conversion (mold → yeast) at 37°C/98.6°F Direct microscopic examination ▪ Periodic acid–Schiff stain ▪ Differentiation: size, yeast morphology Lab tests ▪ Anemia, leukocytosis, ↑ erythrocyte sedimentation rate Tissue biopsy ▪ Pyogranulomatous response ▪ Skin ▫ Epithelial hyperplasia, intraepidermal abscesses, multinucleated cells ▪ Fungus observation Serologic tests ▪ Polymerase chain reaction (PCR) ▫ Antigen detection assays ▪ Acute respiratory distress, multiorgan disease, chronicity SIGNS & SYMPTOMS ▪ Cough, fever, weight loss, sputum production, dyspnea, night sweats, chills, hemoptysis, arthralgia, soft tissue swelling ▪ Verrucous skin lesions with irregular borders, ulcerative skin lesions DIAGNOSIS TREATMENT MEDICATIONS ▪ Antifungal treatment ▪ Amphotericin B; followed by azole ▫ Liposomal amphotericin B: CNS infections SURGERY ▪ Resection of abscesses, devitalized bone, empyemas, pericardial effusion DIAGNOSTIC IMAGING X-ray ▪ Pneumonia ▫ Lobar consolidation, alveolar infiltrates, fibronodular infiltrates, cavitation, nodules, pleural effusion ▪ Osteomyelitis ▫ Well-defined, osteolytic bone lesions OSMOSIS.ORG 559

COCCIDIOIDES SPP. osms.it/coccidioides ▫ Metalloproteinase: inhibits phagocytosis ▫ Alteration of pulmonary surfactant proteins PATHOLOGY & CAUSES ▪ Coccidioidomycosis ▫ Systemic fungal infection caused by Coccidioides immitis, C. posadasii; usually manifests as acute pneumonia ▪ AKA San Joaquin Valley Fever/“desert rheumatism” (associated with arthralgia) ▪ Arthroconidium inhalation → conversion to spherules → activation of T-lymphocytes → production of cytokines → inflammation → acute pneumonia ▫ In infected tissue, spherules grow, septate → release endospores → infection spreads ▪ Immune response ▫ Mainly mediated by Th1 cells ▫ Interleukin 17, TNF alpha, interferongamma ▪ Incubation period: 1–4 weeks ▪ Common sites of infection: lungs, skin, bones, CNS ▪ High prevalence areas: arid, dry regions in U.S. (e.g. California, Southwest), Mexico, Central America, South America Coccidioides spp. ▪ Size: 20–70μm ▪ Dimorphism ▫ Mold form: found in soil ▫ Yeast form: parasitic ▪ Produces arthroconidia (barrel-shaped, multinucleated spores) ▫ Production stimulated by human sex hormones ▫ Arthroconidia convert to spherules (2–5μm; in infected tissues) ▪ Infectious particles: arthroconidia ▪ Virulence ▫ Enzyme with elastase activity: ↑ infection, inflammation ▫ Cell surface glycoprotein with adhesin activity 560 OSMOSIS.ORG Clinical syndromes ▪ Acute pneumonia ▪ Dermatologic lesions ▫ Wart-like lesions on face ▫ Erythema nodosum/multiforme ▪ Osteomyelitis ▪ Meningitis RISK FACTORS ▪ Outdoor occupations; recreational exposure to soil (e.g. gardening, camping); immunosuppression; recent travel to endemic areas; comorbid conditions COMPLICATIONS ▪ Adult respiratory distress syndrome; fatal multilobar pneumonia; pyopneumothorax; meningitis; chronicity SIGNS & SYMPTOMS ▪ ▪ ▪ ▪ ▪ Mostly mild/asymptomatic Non-specific: fever, malaise Cough, pleuritic pain, hemoptysis, arthralgia Erythema nodosum/multiforme Wart-like lesions on face (e.g. nasolabial folds) DIAGNOSIS DIAGNOSTIC IMAGING X-ray ▪ Pneumonia ▫ Parenchymal infiltrates, thin-walled cavities ▪ Osteomyelitis ▫ Osteolytic bone lesions

Chapter 100 Systemic Mycoses LAB RESULTS TREATMENT ▪ Culture-based observation Serologic tests ▪ IgM, IgG antibody detection (e.g. enzyme immunoassays) ▪ Antigen detection Direct microscopic observation ▪ Spherules in sputum, blood, body fluid samples Lab tests ▪ ↑ erythrocyte sedimentation rate ▪ Eosinophilia (mostly with dissemination) MEDICATIONS High risk of dissemination ▪ E.g. immunosuppression, pregnancy ▫ azoles Severe ▪ Amphotericin B SURGERY ▪ Debridement of abscesses, devitalized bone, pyopneumothorax Extrathoracic tissue biopsy ▪ Essential for diagnosis of Coccidioides dissemination ▪ Pyogranulomatous inflammation ▪ Presence of spherules Spherulin skin test ▪ Positive after resolution; not available in U.S. Figure 100.1 Numerous spores in the lungs of an individual with coccidioidomycosis. OSMOSIS.ORG 561

HISTOPLASMA CAPSULATUM osms.it/histoplasma-capsulatum PATHOLOGY & CAUSES ▪ Histoplasmosis ▫ Systemic fungal infection caused by Histoplasma capsulatum; usually manifests as acute pneumonia ▪ Most frequent systemic mycoses in U.S. ▪ Microconidia inhalation → conversion to yeast form → macrophage phagocytosis → inflammation → pneumonia ▪ Immune response: mainly cellular, mediated by T-lymphocytes, macrophages, TNF alpha, interferon-gamma ▪ Infection sites: primarily lungs; may disseminate to other organs Histoplasma capsulatum ▪ Size: 2–3μm x 3–4μm ▪ Thermal dimorphism ▫ Mold form (< 35°C/95°F); produces microconidia (spores, 2–5μm) ▫ Yeast form (37°C/98.6°F) ▪ Infectious particles: microconidia ▪ Bird, bat fecal material promotes growth Pulmonary histoplasmosis clinical syndromes ▪ Pneumonia: acute (diffuse/localized); chronic ▪ Broncholithiasis Disseminated histoplasmosis clinical syndromes ▪ Progressive disseminated histoplasmosis: excessive reticuloendothelial infection ▪ Adrenal perivasculitis (common) ▪ Endocarditis ▪ Mediastinal granuloma ▪ Mediastinitis ▪ Meningitis ▪ Ocular histoplasmosis (e.g. retinal lesions) ▪ Lesions: intestinal (e.g. ulcers, polyps), skin (e.g. dermatitis, papules) 562 OSMOSIS.ORG RISK FACTORS ▪ Outdoor occupations (e.g. construction, excavation) ▪ Outdoor activities (e.g. camping) ▪ Immunosuppression ▪ High prevalence regions: U.S. (Ohio, Mississippi river valleys), Mexico, Central America, South America ▪ Recent travel to endemic areas ▪ Comorbid conditions ▪ Extremes of age COMPLICATIONS ▪ Fatal acute diffuse pneumonia, mediastinal granuloma, mediastinitis, chylothorax, pleural effusion SIGNS & SYMPTOMS ▪ Mostly asymptomatic Acute pulmonary histoplasmosis ▪ Systemic ▫ Fever, headaches, fatigue ▪ Chest pain (pleuritic/substernal), dry cough, myalgia, arthralgia, erythema nodosum/ multiforme Chronic pulmonary histoplasmosis ▪ Systemic ▫ Fever, fatigue, night sweats, weight loss ▪ Productive cough, hemoptysis, dyspnea ▪ Consolidation: dullness to percussion, crackles DIAGNOSIS DIAGNOSTIC IMAGING Chest X-ray ▪ Hilar/mediastinal lymphadenopathy, patchy/ nodular pulmonary infiltrates, occasional cavitation

Chapter 100 Systemic Mycoses LAB RESULTS ▪ Culture-based observation ▪ Direct microscopic observation Serologic tests ▪ Antibody detection (e.g. immunodiffusion, complement fixation assays) ▪ Antigen detection in urine, sputum, body fluids (e.g. enzyme immunoassays) Lab tests ▪ Anemia, ↑ erythrocyte sedimentation rate, progressive disseminated histoplasmosis (e.g. pancytopenia) Tissue biopsy ▪ Granulomas, lymphohistiocytic aggregates, mononuclear cell infiltrates, fungi visualization TREATMENT Figure 100.2 Grocott methenamine silver stain highlights spores in the lung tissue of an immunocompromised individual with histoplasmosis. MEDICATIONS ▪ Progressive disseminated/prolonged/severe pulmonary histoplasmosis ▫ Corticosteroids: ↓ inflammation ▫ Antifungal treatment: amphotericin B, azoles PARACOCCIDIOIDES BRASILIENSIS osms.it/paracoccidioides-brasilienses PATHOLOGY & CAUSES ▪ Paracoccidioidomycosis ▫ Systemic fungal infection caused by Paracoccidioides brasiliensis, P. lutzii; usually manifests as chronic lung disease ▪ AKA South American blastomycosis ▪ Spore inhalation → conversion to yeast form in lungs → phagocytosis by macrophages → inflammation → pneumonia ▪ Immune response: mostly cell-mediated ▪ Common sites of infection: mainly lungs; oral mucosa, skin, adrenal glands, CNS Paracoccidioides spp. ▪ Size: 4–40μm ▪ Thermal dimorphism ▫ Mold form (22–26°C/71.6–78.8°F): present in soil ▫ Yeast form (37°C/98.6°F): “pilot’s wheel” appearance ▪ Stimulated by sex hormones Clinical syndromes ▪ Acute/subacute paracoccidioidomycosis ( juvenile) ▫ Hepatosplenomegaly, OSMOSIS.ORG 563

lymphadenopathy, skin lesions, pulmonary manifestations (rare) ▪ Chronic paracoccidioidomycosis (adult) ▫ Progressive pulmonary fibrosis (esp. lower lobes), ulcers (mouth, larynx); adrenal involvement RISK FACTORS ▪ High prevalence regions: Central, South America (80% in Brazil) ▪ Outdoor occupations ▪ Outdoor activities: contact with soil ▪ More common in individuals who are biologically male ▪ Immunosuppression COMPLICATIONS ▪ Bone marrow, adrenal dysfunction; chronic respiratory failure SIGNS & SYMPTOMS ▪ Generally asymptomatic (95%) ▪ Non-specific symptoms: fever, weight loss ▪ Cough, dyspnea, hepatosplenomegaly, lymphadenopathies, odynophagia, sialorrhea, skin lesions (ulcers, nodules) ▪ Compressive manifestations: jaundice (bile duct obstruction) DIAGNOSIS DIAGNOSTIC IMAGING X-ray/CT scan ▪ Acute/subacute paracoccidioidomycosis ▫ Lymph node enlargement ▪ Chronic paracoccidioidomycosis ▫ Pulmonary disease: alveolar/interstitial infiltrates, consolidation, masses/ nodules, cavitation ▫ CNS disease: ring enhancing lesions ▫ Articular disease: effusion, erosions, space narrowing LAB RESULTS ▪ Direct microscopic observation ▪ Culture-based observation 564 OSMOSIS.ORG Figure 100.3 A child with numerous lesions on the face caused by Coccidioidomycosis brasiliensis. Serologic tests ▪ Detection of antibodies through immunodiffusion TREATMENT MEDICATIONS ▪ Antifungal treatment: azoles ▪ Trimethoprim-sulfamethoxazole