Infectious Disease · Fungal Infections
The facts most likely to be tested
Cryptococcal meningitis is caused by the encapsulated yeast *Cryptococcus neoformans*, typically acquired via inhalation of aerosolized spores from pigeon droppings.
The classic patient presentation involves an immunocompromised host, most commonly those with HIV/AIDS and a CD4 count < 100 cells/µL.
Clinical manifestations include a subacute onset of headache, fever, neck stiffness, and altered mental status.
The diagnostic test of choice for cerebrospinal fluid (CSF) is the cryptococcal antigen (CrAg) test, which has high sensitivity and specificity.
CSF analysis typically reveals elevated opening pressure, low glucose, elevated protein, and a lymphocytic pleocytosis.
The gold standard for visualization of the organism in CSF is the India ink stain, which demonstrates the characteristic thick polysaccharide capsule as a clear halo.
Initial induction therapy consists of intravenous amphotericin B plus flucytosine, followed by fluconazole for consolidation and maintenance therapy.
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A 34-year-old male with a history of untreated HIV presents to the emergency department with a 2-week history of worsening headache, nausea, and lethargy. On physical exam, he is febrile and exhibits nuchal rigidity, though focal neurologic deficits are absent. His most recent CD4 count was 45 cells/µL. A lumbar puncture is performed, revealing an opening pressure of 28 cm H2O, low glucose, and elevated protein. An India ink stain of the CSF is ordered.
What is the most likely diagnosis?
Cryptococcal meningitis
The patient's severe immunosuppression (CD4 < 100), subacute presentation, and elevated opening pressure are classic for cryptococcal meningitis, which is confirmed by the presence of the encapsulated yeast on India ink stain.
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High yield triage
Etiology / Epidemiology
Opportunistic infection in HIV/AIDS patients with CD4 < 100 cells/µL; caused by Cryptococcus neoformans.
Clinical Manifestations
Subacute onset of headache, fever, and meningeal signs; soap bubble lesions on MRI.
Diagnosis
Lumbar puncture showing Cryptococcal antigen (CrAg); India ink stain is classic.
Treatment
Amphotericin B plus flucytosine for induction; do not start ART immediately.
Prognosis
High mortality if untreated; elevated intracranial pressure is the primary cause of death.
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Epidemiology & Etiology
Primarily affects immunocompromised hosts, specifically those with advanced HIV/AIDS. The pathogen is an encapsulated yeast found in pigeon droppings and soil. It is the most common cause of fungal meningitis in the world.
Pertinent Anatomy
The infection targets the leptomeninges and brain parenchyma. It frequently causes basilar meningitis, which can obstruct cerebrospinal fluid flow and lead to hydrocephalus.
Pathophysiology
Inhalation of spores leads to pulmonary infection, followed by hematogenous dissemination to the central nervous system. The thick polysaccharide capsule inhibits phagocytosis and allows the yeast to evade the host immune response. Proliferation in the subarachnoid space causes inflammation and increased intracranial pressure.
Clinical Manifestations
Patients present with a subacute course of headache, malaise, and confusion. Meningeal signs like nuchal rigidity are often absent in severely immunocompromised patients. Red flags include cranial nerve palsies, visual disturbances, and altered mental status indicating elevated intracranial pressure.
Diagnosis
The gold standard is the CSF Cryptococcal antigen (CrAg) test, which has high sensitivity and specificity. India ink stain of CSF reveals encapsulated yeast. CSF analysis typically shows low glucose, elevated protein, and lymphocytic pleocytosis.
Treatment
Induction therapy consists of Amphotericin B plus flucytosine for at least 2 weeks. Avoid immediate ART initiation to prevent IRIS (Immune Reconstitution Inflammatory Syndrome). Follow with fluconazole consolidation and maintenance therapy.
Prognosis
Management of elevated intracranial pressure via serial lumbar punctures is critical to prevent permanent neurological damage. IRIS is a major complication occurring after ART initiation, characterized by worsening symptoms despite fungal clearance.
Differential Diagnosis
Bacterial meningitis: acute onset with neutrophilic pleocytosis
Tuberculous meningitis: associated with basilar enhancement and cranial nerve deficits
Viral meningitis: typically self-limiting with normal glucose
Neurosyphilis: positive VDRL/RPR in CSF
Primary CNS lymphoma: ring-enhancing lesions on MRI