Overview 

Blastomycosis is a fungal infection caused by the Blastomyces dermatitidis pathogen. Though the disease is rare with an annual incidence of less than 2 cases per 100,000 people it can affect individuals across all demographics, with the potential to cause serious complications if left untreated.¹ The disease occurs when humans inhale microscopic fungal spores called conidia that have become airborne after contaminated soil is disturbed. The lungs are the primary site of blastomycosis infection, though the disease can also affect other body parts such as the skin, bones and central nervous system (CNS).²

Risk Factors 

Living in or visiting certain locations can increase an individual's risk of contracting blastomycosis. The disease is more prevalent in specific regions, particularly within the United States. The Ohio and Mississippi River Valleys, the Great Lakes region, and the Southeastern US experience a higher incidence of the disease.² While cases have been reported in other parts of the country and outside the US, the risk is significantly lower in these areas. 

Individuals working in industries such as forestry, construction and landscaping are at increased risk of exposure due to their close contact with the fungus's natural soil habitat. Similarly, outdoor enthusiasts who hunt, camp or hike are at higher risk of contracting the disease due to an increased chance of exposure to the spores in the soil.³

People with weakened immune systems, such as those with HIV/AIDS, organ transplant recipients or individuals on immunosuppressive medications are also particularly vulnerable to blastomycosis. Their compromised immune systems are less effective at fighting off the infection, resulting in a higher risk of developing severe symptoms and a lower initial number of spores able to cause disease.³

Clinical Presentation

Blastomycosis can take many different forms. Of these forms, the two main categories are pulmonary (lungs) and extrapulmonary (non-lungs). Each category of this disease has its unique symptoms, clinical features, and severity levels.⁴

Pulmonary Blastomycosis

Pulmonary blastomycosis is the most common form of the disease affecting up to 80% of patients.⁵ This form of the disease primarily exhibits respiratory symptoms including:

• Cough 
• Fever
• Chest Pain
• Shortness of Breath
• Fatigue

In severe cases, pulmonary blastomycosis can lead to life-threatening complications,⁶ such as:

• Acute Respiratory Distress Syndrome (ARDS): A severe lung condition causing widespread inflammation and rapidly progressing respiratory failure
• Respiratory Failure: Lungs may become unable to supply sufficient oxygen to the body or remove carbon dioxide

Extrapulmonary Blastomycosis

Extrapulmonary (disseminated) blastomycosis is a more concerning form of the disease. It occurs when the infection spreads from the lungs to other organs and tissues in the body.⁵ Common sites of this disseminated infection include:

• The Skin (Cutaneous): Disease can present as:  
  • Small, painless pink or red spots that may resemble pimples or insect bites
  • Spots can grow larger and become wart-like with irregular borders and a crusty surface
  • Lesions typically affect exposed areas like the face, hands, and legs but can occur anywhere on the body

• Bones and Joints (Osteoarticular): Disease can present as:
  • Osteomyelitis (Infection and inflammation of the bone) 
  • Arthritis (Joint inflammation) 
  • Bone weakening
  • Symptoms:
    • Localised pain and tenderness
    • Swelling and warmth over affected areas
    • Joint stiffness and reduced range of motion

• Central Nervous System (CNS): CNS involvement in blastomycosis, though rare, can be severe and life-threatening. It can present as:
  • Meningitis (Inflammation of the protective membranes covering the brain and spinal cord)
  • Brain abscesses  (Localised collections of pus within the brain tissue)
  • Epidural abscesses (Infections in the space between the skull/vertebrae and the dura mater)
  • Symptoms:
    • Persistent headaches
    • Fever and neck stiffness
    • Altered mental status or confusion
    • Seizures

• Urinary and Reproductive Organs (Genitourinary): The disease can present as: 
  • Prostatitis (Inflammation of the prostate)
  • Orchitis (Inflammation of the testicles)
  • Epididymitis (Inflammation of the epididymis)
  • Symptoms:
    • Pelvic pain or discomfort
    • Testicular pain and swelling
    • Difficulty urinating / painful urination 
    • Increased frequency or urgency of urination

While the symptoms of blastomycosis are often mild, severe cases can lead to serious complications emphasising why the early diagnosis and appropriate treatment of the disease are crucial for patients. 

Disease Progression 

The course of blastomycosis varies depending on several factors, such as the person's immune system, how much and how long they were exposed to the fungus and the specific strain of the fungus that caused their infection in the first place. People with weakened immune systems often experience faster progression and worse outcomes with the disease than those with healthy immune systems.²
Longer and more intense exposure to high concentrations of spores raises the risk of severe disease.⁷ Different strains of the fungus can also have varying levels of virulence, which refers to how severe or aggressive the disease is. Some strains may cause milder infections, while others can lead to severe and potentially life-threatening illness.⁸

Recurrence

Recurrence of blastomycosis after treatment is relatively rare, occurring in only about 5-10% of cases.¹ However, as mentioned above, certain factors can increase the risk of relapse, including inadequate initial treatment, underlying immunosuppression in the patient, and extensive disease at the time of presentation.

Mortality

In mild to moderate cases of lung infection, mortality rates are typically low, ranging from 5-10% with appropriate treatment. However, in severe cases of lung infection mortality rates can rise to 50%, despite appropriate treatment. Disseminated blastomycosis, especially when it involves the CNS is also associated with high mortality rates, ranging from 30 to 40%, even with optimal medical therapy.¹

Diagnostic Challenges 

Diagnosing blastomycosis based solely on clinical presentation is a formidable challenge for healthcare providers. The symptoms of the disease often mimic those of other respiratory infections, particularly bacterial pneumonia, leading to potential misdiagnosis.⁹ Complicating matters further, the initial manifestation of blastomycosis can be subtle or even asymptomatic, allowing the infection to progress undetected. Since the disease can affect multiple organ systems, it presents a wide array of symptoms depending on the site of infection, creating a diagnostic problem for medical professionals. The disease does not follow a predictable pattern, further complicating accurate diagnosis.

Summary

Blastomycosis, though rare, presents a significant health threat with the potential for severe complications. Its diverse clinical manifestations pose a diagnostic challenge. Pulmonary blastomycosis, the most common form, often mimics other respiratory infections, making accurate diagnosis difficult. Extrapulmonary manifestations, affecting the skin, bones, joints, and central nervous system, further complicate the diagnostic process. By raising awareness of the diverse clinical presentations of the disease we can improve early detection and management of this fungal infection. This will ultimately improve patient outcomes and reduce mortality rates associated with blastomycosis.