Updated: 1/9/2019

Systemic Mycoses

Review Topic
6 6
6 6
  • 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 2nd 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
    • 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
Blastomycosis Paracoccidioidomycosis
  • Histoplasma capsulatum
  • Coccidioides immitis
  • Coccidioides posadasii
  • Blastomyces dermatitidis
  • Paracoccidioides brasiliensis
  • Paracoccidioides lutzii
  • Mississippi
  • Ohio River Valley
  • Southwestern US
  • California
  • Eastern US
  • Central US
  • Latin America
Skin manifestations
  • Ulcers on oral mucosa
  • Erythema nodosum
  • Erythema multiforme
  • Verrucous skin lesions
  • Verrucous skin lesions
  • 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
  • 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
  • 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
  • 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)
  • 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

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Questions (6)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2

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(M1.MC.14.14) A 59-year-old man with no significant past medical history presents to the emergency room with the ulcerative skin lesion shown in Figure A. He had a bad pneumonia several weeks ago. His vital signs are stable, and the remainder of his physical examination is benign. The lesion is swabbed and cultured revealing the organism shown in Figure B. Which of the following is most likely true regarding this disease? Review Topic | Tested Concept

QID: 104899

The patient received the illness from bat droppings and may be treated with PO itraconazole




The patient received the illness in the Southwest and may be treated with PO fluconazole or itraconazole




The patient received the illness in the Eastern USA and may be treated with PO itraconazole




The patient received the illness in Latin America and the organism may form a captain's wheel formation




The patient received the illness from plant material and may be treated with potassium iodide



L 2 D

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(M1.MC.13.12) A 43-year-old man presents to the emergency department with cough and fever. On a sputum sample he is found to have spherules containing endospores, as shown in Figure A. How is he most likely to have contracted his disease? Review Topic | Tested Concept

QID: 101471

Hunting in the woods of Connecticut




Swimming in a freshwater pond in Louisiana




Hiking in the deserts of Arizona




Walking in caves in the Mississippi River Valley




Cleaning out pigeon coops in Ohio



L 1 E

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