Cryptococcosis differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Serge Korjian M.D.; Yazan Daaboul, M.D.


Cryptococcosis is more common among immunocompromised patients who are at high risk for other fungal, bacterial and viral infections. Cryptococcal meningitis can be indistinguishable from bacterial or viral meningitis. Cryptococcosis must be differentiated from diseases that cause symptoms of lower respiratory tract infection (fever, dyspnea, cough) and meningitis (fever, headache, neck stiffness, focal neurological deficits) such as coccidioidomycosis, histoplasmosis, tuberculosis, and community/hospital-acquired pneumonia. Cutaneous cryptococcosis in HIV/AIDS patients must be differentiated from molluscum contagiosum and Kaposi's sarcoma.

Differentiating Cryptococcosis from other Diseases

Cryptococcosis is more common among immunocompromised patients who are at high risk for other fungal, bacterial, and viral infections. It should be differentiated from the following diseases which all may cause neurological dysfuntion in an immunocompromised patient:

Disease Differentiating signs and symptoms Differentiating tests
CNS lymphoma[1]
Disseminated tuberculosis[2]
Chagas disease[4]
CMV infection[5]
HSV infection[6]
Varicella Zoster infection[7]
Brain abscess[8][9]
Progressive multifocal leukoencephalopathy[10]
  • Symptoms are often more insidious in onset and progress over months. Symptoms include progressive weakness, poor coordination, with gradual slowing of mental function. Only seen in the immunosuppressed. Rarely associated with fever or other systemic symptoms

Cutaneous Cryptococcosis must be differentiated from the following diseases:

Differentiating cryptococcal meningitis from other causes of meningitis

Cryptococcal meningitis may be differentiated from other causes of meningitis by cerebrospinal fluid examination as shown below:[15][16][17][18][19]

Cerebrospinal fluid level Normal level Bacterial meningitis[18] Viral meningitis[18] Cryptococcal meningitis Tuberculous meningitis[20] Malignant meningitis[15]
Cells/ul < 5 >300 10-1000 10-500 50-500 >4
Cells Lymphocyte:Monocyte 7:3 Granulocyte > Lymphocyte Lymphocyte > Granulocyte Lympho.>Granulocyte Lymphocytes Lymphocytes
Total protein (mg/dl) 45-60 Typically 100-500 Normal or slightly high High Typically 100-200 >50
Glucose ratio (CSF/plasma)[16] > 0.5 < 0.3 > 0.6 <0.3 < 0.5 <0.5
Lactate (mmols/l)[17] < 2.1 > 2.1 < 2.1 >3.2 > 2.1 >2.1
Others ICP:6-12 (cm H2O) CSF gram stain, CSF culture, CSF bacterial antigen PCR of HSV-DNA, VZV CSF gram stain, CSF india ink PCR of TBC-DNA CSF tumor markers such as alpha fetoproteins, CEA


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