Differential Diagnosis for Suspected Systemic Fungal Infection

The differential diagnosis for a suspected systemic fungal infection is broad and can be categorized based on the likelihood and potential impact of missing the diagnosis.

• Single Most Likely Diagnosis
  • Candidiasis: This is often the most likely diagnosis, especially in patients with risk factors such as immunosuppression, recent antibiotic use, or indwelling catheters. Candida species are common commensals on human skin and mucous membranes and can become pathogenic under certain conditions.
• Other Likely Diagnoses
  • Aspergillosis: Common in immunocompromised patients, especially those with neutropenia or on corticosteroid therapy. Aspergillus species are ubiquitous in the environment, and infection typically occurs through inhalation of spores.
  • Cryptococcosis: Particularly likely in patients with HIV/AIDS or other forms of immunosuppression. Cryptococcus neoformans can cause severe meningitis and disseminated disease.
  • Histoplasmosis: Should be considered in patients who have been exposed to bird or bat droppings, or who have lived in or visited endemic areas. Histoplasma capsulatum can cause a range of diseases from mild respiratory illness to severe disseminated infection.
• Do Not Miss Diagnoses
  • Mucormycosis: Although rare, mucormycosis (previously known as zygomycosis) is highly lethal, especially in diabetic or immunocompromised patients. It requires prompt diagnosis and treatment.
  • Pneumocystis jirovecii Pneumonia (PCP): While not a fungal infection in the traditional sense (P. jirovecii is now classified as a fungus), PCP is a critical diagnosis to consider in immunocompromised patients, particularly those with HIV/AIDS, due to its high mortality if untreated.
• Rare Diagnoses
  • Blastomycosis: Caused by Blastomyces dermatitidis, this infection is rare but can be severe, particularly in immunocompromised individuals. It is endemic to certain regions of North America.
  • Coccidioidomycosis: Also known as Valley fever, this infection is caused by Coccidioides immitis/posadasii and is primarily found in the southwestern United States and northern Mexico. It can cause severe pulmonary and disseminated disease.
  • Paracoccidioidomycosis: A rare fungal infection caused by Paracoccidioides brasiliensis, primarily affecting rural workers in Latin America. It can cause chronic and severe disease if not treated.

Workup for Suspected Systemic Fungal Infection

The workup should include:

• Clinical Evaluation: Detailed history and physical examination to identify risk factors and signs of infection.
• Laboratory Tests: Blood cultures, fungal antigen tests (e.g., galactomannan for aspergillosis, beta-D-glucan for various fungal infections), and PCR for specific fungal DNA.
• Imaging Studies: Chest X-rays, CT scans of the chest, abdomen, and other affected areas to identify signs of infection such as nodules, cavitations, or infiltrates.
• Biopsy and Histopathology: When possible, to obtain a definitive diagnosis through direct visualization of the fungus and its effects on tissue.
• Serologic Tests: For certain infections, such as histoplasmosis and coccidioidomycosis, where antibody tests can aid in diagnosis.

Each patient's workup should be tailored based on their specific risk factors, clinical presentation, and suspected pathogens.