Blastomyces/Blastomycosis

Blastomycosis is an infection caused by inhalation of the spores of the fungus, Blastomyces. Blastomyces species thrive in moist soil and decaying material and are common in the Ohio and Mississippi River valleys and the Great Lakes regions of the United States and Canada. Although most patients are asymptomatic, some can develop pneumonia. Extrapulmonary disease, such as skin lesions, osteomyelitis, genitourinary infections, and meningitis can occur. The diagnosis is made by identifying the organism in sputum or tissue samples using culture, PCR, or antigen testing. Antifungals are used for treatment.

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General Characteristics and Epidemiology

Basic features of Blastomyces

  • Taxonomy:
    • Order: Onygenales
    • Family: Ajellomycetaceae
  • Dimorphic microfungus:
    • Mycelial phase:
      • Present at room temperature
      • White mold → trunks that are light brown
      • Branching hyphae
      • Right angle conidiophores with single conidium
      • Form conidia (spores)
    • Yeast phase:
      • Occurs at 37°C (98.6°F)
      • Cream or tan color
      • Thick cell wall
      • Multinucleate
      • Asexual reproduction: budding
Blastomyces dermatitidis yeast form

Blastomyces dermatitidis yeast form at 37°C

Image: “Blastomyces dermatitidis yeast form” by Medmyco. License: CC0 1.0

Clinically relevant species

Blastomycosis is caused by Blastomyces dermatitidis.

Epidemiology

  • Endemic in the soils of:
    • Ohio and Mississippi River valleys
    • Great Lakes region
    • Southeastern United States
  • Annual incidence rates in endemic regions: < 1 case per 100,000 people

Pathogenesis

Reservoir

  • Moist soil
  • Decomposing material

Transmission

The conidia form of B. dermatitidis can be aerosolized by disturbing the fungal colony followed by inhalation.

Host risk factors

Blastomycosis is more common in individuals who are immunocompromised, but can occur in immunocompetent individuals too.

Virulence factors

  • Thick cell walls provide resistance to phagocytosis. 
  • Blastomyces adhesin (BAD)-1: 
    • Glycoprotein adhesin
    • Allows attachment to host cells
    • Impairs proinflammatory response
  • DPP-IVA:
    • Serine protease
    • Blunts cytokine release

Pathophysiology

  • Conidia are inhaled → phagocytosed by neutrophils and macrophages in alveoli → infection cleared
  • Some fungi evade phagocytosis → rapidly move into the yeast phase → resistant to phagocytosis
  • Yeast multiplies in lung tissues → spreads through blood or lymphatics to other tissues: 
    • Skin
    • Bone
    • Genitourinary tract
    • Brain 

Clinical Presentation

Severity of the infection depends on a person’s immune system.

Pulmonary disease

  • Acute pneumonia:
    • Fever
    • Cough:
      • Initially nonproductive
      • Often becomes productive (purulent sputum)
    • Chest pain
    • Dyspnea
    • Hemoptysis
    • Myalgia
  • Chronic pneumonia:
    • Presents similar to TB
    • Low-grade fever
    • Cough
    • Night sweats
    • Weight loss
  • ARDS:
    • Rare
    • Diffuse pneumonitis
    • Rapidly progressive
    • High mortality

Extrapulmonary disease

  • Cutaneous:
    • Verrucous (wart-like)
    • Ulcerated with small pustules at the margins
  • Bone and joint:
    • Osteomyelitis:
      • Lytic lesions can cause bone or joint pain.
      • Soft tissue swelling
      • Draining sinus tract
    • Arthritis
  • Genital:
    • Asymptomatic pyuria
    • Prostatitis
    • Epididymo-orchitis
    • Endometritis
    • Tubo-ovarian abscess
  • Nervous system:
    • Meningitis
    • Intracranial abscess
    • Epidural abscess

Diagnosis and Management

Diagnosis

  • Confirmed by the identification of organisms in sputum or tissues using:
    • KOH prep
    • Histology (tissue biopsy) 
  • PCR for B. dermatitidis DNA
  • Urine antigen testing
  • Culture of the organism

Management

Spontaneous remission can occur, but patients should be indicated antifungal therapy to reduce the chances of dissemination or recurrence.

  • Itraconazole (treatment of choice for most forms of the disease)
  • Amphotericin B:
    • More toxic alternative
    • Reserved for critically ill patients and those with CNS infections
  • Azoles:
    • Used as step-down therapy for patients with CNS disease
    • Good CNS penetration
    • Options:
      • Itraconazole
      • Voriconazole
      • Fluconazole

Prognosis

  • Recurrence is rare.
  • 80%–95% of immunocompetent individuals are successfully treated.
  • Prognosis is poor in patients who are immunocompromised.

Differential Diagnosis

  • Tuberculosis: an infectious disease caused by Mycobacterium tuberculosis complex bacteria. Pulmonary disease presents with fever, night sweats, cough, hemoptysis, fatigue, and weight loss. Extrapulmonary manifestations can include pleurisy, meningitis, Pott’s disease, pericarditis, and miliary disease. The diagnosis is established using a tuberculin skin test, sputum culture, and lung imaging. The mainstay of management is antimycobacterial drugs.
  • Atypical pneumonia: a form of pulmonary infection that typically has a slow onset and progression and presents with a nonproductive, dry cough and extrapulmonary symptoms such as fatigue, malaise, and headaches. Diagnosis is made based on history, physical exam, and chest imaging. Atypical pneumonia is usually treated with antibiotics.
  • Lung cancer: the malignant transformation of lung tissue and the leading cause of cancer-related deaths. Lung cancer is generally classified histologically as either small cell lung cancer or non-small cell lung cancer. Symptoms include cough, dyspnea, weight loss, and chest discomfort. Definitive diagnosis and staging are made by biopsy, genetic mutation with biomarker testing, and imaging. Management is guided by the cancer stage and associated molecular profile.
  • Tularemia: a rare infection caused by Francisella tularensis, acquired by contact with animal tissue, ticks, or biting flies. The infection manifests as a papule, followed by fever, headache, and suppurative lymphadenopathy. Tularemia may have multiorgan involvement. Diagnosis is based on the culture of blood and infected tissues. Treatment is with antibiotics.
  • Squamous cell carcinoma (SCC): the malignant proliferation of atypical keratinocytes. The cancer presents as a firm, erythematous, keratotic plaque or papule. Histopathologic examination should be performed for all suspected cases, as many lesions, such as actinic keratosis, mimic the appearance of SCC. Surgical excision is the mainstay of treatment. 
  • Pyoderma gangrenosum: a chronic, progressive, neutrophilic skin necrosis. The etiology of pyoderma gangrenosum is unknown but often associated with systemic illnesses. Patients can have varying presentations, with skin lesions progressing from a papule or nodule to ulcers with a necrotic base and violaceous border. Fever and malaise may accompany these presentations. The diagnosis is clinical. Management includes wound care, and treatment with anti-inflammatory medications and immunosuppressants.

References

  1. Centers for Disease Control and Prevention (2020). Fungal Diseases: Blastomycosis. Retrieved June 10, 2021, from https://www.cdc.gov/fungal/diseases/blastomycosis/index.html
  2. Castillo, C.G., Kauffman, C.A., Miceli, M.H. (2016). Blastomycosis. Infectious Disease Clinics of North America. https://pubmed.ncbi.nlm.nih.gov/26739607
  3. Cano, M.V., Ponce-de-Leon, G.F.; Tippen, S., Lindsley, M.D.; Warwick, M., Hajjeh, R.A. (2003). Blastomycosis in Missouri: Epidemiology and Risk Factors for Endemic Disease. Epidemiology and Infection. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2870035
  4. Smith, J.A., Riddell, J., Kauffman, C.A. (2013). Cutaneous manifestations of endemic mycoses. Curr Infect Dis Rep. https://www.ncbi.nlm.nih.gov/pubmed/23917880
  5. Gray, N.A., Baddour, L.M. (2002). Cutaneous inoculation blastomycosis. Clin Infect Dis. https://www.ncbi.nlm.nih.gov/pubmed/11981746
  6. Saccente, M., Woods, G.L. (2010). Clinical and laboratory update on blastomycosis. Clin Microbiol Rev. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2863359/
  7. Lohrenz, S., Minion, J., Pandey, M., Karunakaran, K. (2018). Blastomycosis in Southern Saskatchewan 2000-2015: Unique presentations and disease characteristics. https://www.ncbi.nlm.nih.gov/pubmed/29924358
  8. Patel, A.J., Gattuso, P., Reddy, V.B. (2010). Diagnosis of blastomycosis in surgical pathology and cytopathology: Correlation with microbiologic culture. Am J Surg Pathol. https://www.ncbi.nlm.nih.gov/pubmed/20090507
  9. Goughenour, K.D., Rappleye, C.A. (2017). Antifungal therapeutics for dimorphic fungal pathogens. Virulence. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354166/
  10. Lestner, J., Hope, W.W. (2013). Itraconazole: An update on pharmacology and clinical use for the treatment of invasive and allergic fungal infections. Expert Opin Drug Metab Toxicol. https://www.ncbi.nlm.nih.gov/pubmed/23641752
  11. Baker, T., Patel, A., Halteh, P., Toussi, S.S., DeLaMora, P., Lipner, S., Schuetz, A.N., Hartman, B. (2017). Blastomycosis during pregnancy: A case report and review of the literature. Diagn Microbiol Infect Dis. https://www.ncbi.nlm.nih.gov/pubmed/28291633
  12. Schwartz, I.S., Embil, J.M., Sharma, A., Goulet, S., Light, R.B. (2016). Management and Outcomes of Acute Respiratory Distress Syndrome Caused by Blastomycosis: A Retrospective Case Series. Medicine (Baltimore). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4863776/
  13. Bradsher, Jr., R.W. (2020). Mycology, pathogenesis, and epidemiology of blastomycosis. In Mitty, J. (Ed.), UpToDate. Retrieved June 10, 2021, from https://www.uptodate.com/contents/mycology-pathogenesis-and-epidemiology-of-blastomycosis
  14. Bradsher, Jr., R.W. (2020). Clinical manifestations and diagnosis of blastomycosis. In Mitty, J. (Ed.), UpToDate. Retrieved June 10, 2021, from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-blastomycosis
  15. Bradsher, Jr., R.W. (2020). Treatment of blastomycosis. In Mitty, J. (Ed.), UpToDate. Retrieved June 10, 2021, from https://www.uptodate.com/contents/treatment-of-blastomycosis
  16. Miceli, A., and Krishnamurthy, K. (2020). Blastomycosis. [online] StatPearls. Retrieved June 10, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK441987/

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