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 H2 O 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 monthsPatients 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
