Background
Epidemiology
- The majority of cases occur in patients with advanced HIV or other severely immunocompromising conditions
Pathophysiology
- Initially acquired by inhalation, followed by hematogenous dissemination with strong neurotropism
Clinical Manifestations
- Infects CNS, lung, and bloodstream
- Cryptococcal meningitis is the most common clinical manifestation
- Pulmonary infection more common with Cryptococcus gattii while CNS infection and fungemia were more common with Cryptococcus neoformans
Cryptococcal Meningitis
- Typically subacute presentation over 1-2 weeks (in HIV) or 6 to 12 weeks (non-HIV)
- Headache (most common sign, near-universal), altered cognition (50%), lethargy, fever (50-70%), nuchal rigidity, nausea/vomiting (in about 70%), seizure (15%)
- Visual symptoms include diplopia and photophobia, followed by decreased visual acuity
- Can also develop ataxia, aphasia, seizures, and chorea
- Symptoms in advanced HIV can be subtle or absent
Differential Diagnosis
- Other causes of meningoencephalitis and CNS mass lesions in immunocompromised patients
Investigations
- Lumbar puncture for CSF
- High opening pressure >18 (in around 80%)
- >25 cm H2O is a poor prognostic sign
- Low glucose (can be undetectably low) and elevated protein
- WBC count can be normal; when elevated (usually in the tens to hundreds), typically lymphocytic pleocytosis
- Cryptococcal antigen (CRAg); or India ink staining if CrAg unavailable
- Cryptococcal antigen (CRAg) can also be sent serum
- CT chest for pulmonary infection
- Most commonly shows clustered nodular pattern
- May also show solitary pulmonary nodule/mass with or without cavitation, scattered nodules, or peribronchovascular consolidation
Diagnosis
- Made with cryptococcal antigen from CSF or blood, India ink staining, or fungal culture
Management
Patients with HIV
CNS Disease
- Induction (first 2+ weeks): liposomal amphotericin B (3-4 mg/kg IV daily) plus flucytosine (100 mg/kg per day orally in 4 divided doses)
- IV formulations may be used in severe cases and in those without oral intake where the preparation is available) for at least 2 weeks
- Consolidation: fluconazole (400 mg [6 mg/kg] per day orally) for a minimum of 8 weeks
- Maintenance:
- Fluconazole (200 mg per day orally) or itraconazole (200 mg twice per day orally; drug-level monitoring strongly advised)
- Start HAART 2–10 weeks after starting antifungals
- Consider stopping antifungals once CD4 >= 100 for 3 months
Fungemia
- First, rule out meningitis with an LP
- If no meningitis, can treat with fluconazole 400 mg po daily until immune reconstitution
Organ Transplant Patients
- Always consider decreasing immunosuppression if able to
CNS, Severe, or Disseminated Disease
- Induction (first 2+ weeks): liposomal amphotericin B (3–4 mg/kg per day IV) plus flucytosine (100 mg/kg per day in 4 divided doses)
- If not including flucytosine, then extend induction to 4-6 weeks
- Consolidation: fluconazole (400–800 mg [6–12 mg/kg] per day orally) for 8 weeks, then by fluconazole (200–400 mg per day orally) for 6–12 months (B-II)
Mild-to-Moderate Non-CNS Disease
- Includes mild-to-moderate pulmonary disease
- Fluconazole (400 mg [6 mg/kg] per day) for 6–12 months
Patients Without HIV or Organ Transplant
- Induction (first 4+ weeks): amphotericin B deoxycholate (0.7–1.0 mg/kg per day IV) plus flucytosine (100 mg/kg per day orally in 4 divided doses)
- If neurological complications or positive CSF cultures after 2 weeks of treatment, consider extending to 6 weeks total
- If not including flucytosine, then extend induction by 2 weeks
- If there is amphotericin B deoxycholate toxicity, liposomal amphotericin B may be substituted in the second 2 weeks
- Consolidation: fluconazole (400 mg per day) for 8 weeks
- Maintenance: fluconazole (200 mg [3 mg/kg] per day orally) for 6–12 months
Pregnant Patients
Further Reading
