What are the symptoms of cryptococcosis?

Symptoms of Cryptococcosis

Cryptococcosis most commonly presents as a subacute meningitis or meningoencephalitis with fever, malaise, and headache, though symptoms can vary widely depending on the site of infection. 1

Central Nervous System Manifestations

The most common clinical presentation of cryptococcosis is meningoencephalitis, particularly in immunocompromised patients. Key symptoms include:

• Fever
• Headache (often persistent)
• Malaise
• Altered mental status, including:
  • Lethargy
  • Personality changes
  • Memory loss
  • Confusion

Notably, classic meningeal symptoms such as neck stiffness and photophobia occur in only 25-33% of patients. 1 Encephalopathic symptoms typically result from elevated intracranial pressure, which occurs in up to 75% of patients. 1

Pulmonary Manifestations

Pulmonary cryptococcosis is the second most common manifestation and may present with:

• Cough (often with scant sputum)
• Dyspnea
• Fever (may be recurrent)
• Chest pain
• Abnormal chest radiographs
• Intrathoracic lymphadenopathy 1, 2

Some patients with pulmonary cryptococcosis may be asymptomatic, with pulmonary nodules found incidentally on routine chest radiographs. 1

Disseminated Disease

When cryptococcosis occurs in immunocompromised patients (especially HIV-infected individuals), disseminated disease is common. Symptoms may include:

• Skin lesions that often mimic molluscum contagiosum 1
• Generalized lymphadenopathy 3
• Multiple organ involvement
• Cryptococcemia (positive blood cultures in up to 75% of HIV-associated cryptococcal meningitis) 1

Special Considerations in Children

In children, cryptococcosis is less common but can present differently:

• In the United States, meningismus, photophobia, and focal neurological signs are uncommon presenting symptoms 1
• In contrast, studies from Zimbabwe show more acute presentations with:
  • Nuchal rigidity (70%)
  • Seizure activity (40%)
  • Focal neurologic signs (20%) 1

Diagnostic Clues

Several laboratory findings can help confirm cryptococcosis:

• CSF analysis typically shows:

  • Mildly elevated protein
  • Normal to low glucose
  • Lymphocytic pleocytosis (though some patients have no cells)
  • Positive India ink stain for yeasts
  • Elevated opening pressure (>20 cm H₂O in up to 75% of patients) 1

• Cryptococcal antigen is almost always detected in CSF at high titers in meningitis cases and in serum for disseminated disease 1

Clinical Pitfalls

1. The absence of classic meningeal signs does not rule out cryptococcal meningitis, as they are present in only a minority of patients.

2. Pulmonary cryptococcosis may be misdiagnosed as other respiratory conditions due to nonspecific symptoms. 2

3. Cryptococcal skin lesions can be mistaken for other conditions, particularly molluscum contagiosum in HIV-infected patients. 1

4. In immunocompetent patients, symptoms may be more subtle and insidious, leading to delayed diagnosis. 4

5. CSF eosinophilia can occur in cryptococcal meningitis, which might lead to consideration of other diagnoses. 5

Always consider cryptococcosis in immunocompromised patients presenting with headache, fever, and altered mental status, even in the absence of classic meningeal signs. Early diagnosis is crucial for reducing morbidity and mortality.