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.
Overview
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 disease:
- Bacterial/Viral Meningitis
- May be indistinguishable before antigen testing and CSF stain and culture, although onset of fungal meningitis is classically less acute than bacterial meningitis.
- Bacterial coverage is recommended for all meningitides, even if cryptococcal meningitis is highly suspected.
- Bacterial/Viral Pneumonia[1]
- May be indistinguishable before antigen testing.
- May be equally as common as cryptococcal pneumonia in immunocompromised patients, more common in immunocompetent patients.
- Pneumocystis jirovecii Pneumonia[1]
- Also a very common cause of pneumonia among HIV/AIDS patients with low CD4 counts.
- Cryptococcal pneumonia may present with ground glass opacities on chest X-ray.
- P. jirovecii is not usually associated with CNS disease.
- Tuberculosis[1]
- May present similarly given that immunocompromised status may prevent granuloma formation.
- Molluscum contagiosum[2]
- Is very similar in appearance to disseminated cryptococcosis manifesting on the skin (umbilicated lesions).
- Patients are usually less sick, as molluscum is restricted to the skin.
- Kaposi's Sarcoma[3][4]
- Coccidioidomycosis[5]
- Usually disease course is more protracted, except with severe immunocompromise.
- Not ubiquitous, more common is endemic areas in the Southwest United States.
- Histoplasmosis[5]
- Also related to contaminated with bird or bat droppings.
- Not ubiquitous. Common in the Central and Eastern United States.
- Blastomycosis[5]
- CNS involvement is much less common with blastomyces.
- Cutaneous manifestations may resemble cutaneous cryptococcosis
- Not ubiquitous, more common is endemic areas in North America.
Fungal meningitis may be differentiated from other causes of meningitis by cerebrospinal fluid examination as shown below:[6][7][8][9][10]
| Cerebrospinal fluid level | Normal level | Bacterial meningitis[9] | Viral meningitis[9] | Fungal meningitis | Tuberculous meningitis[11] | Malignant meningitis[6] |
|---|---|---|---|---|---|---|
| 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)[7] | > 0.5 | < 0.3 | > 0.6 | <0.3 | < 0.5 | <0.5 |
| Lactate (mmols/l)[8] | < 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 |
References
- ↑ 1.0 1.1 1.2 Friedman EP, Miller RF, Severn A, Williams IG, Shaw PJ (1995). "Cryptococcal pneumonia in patients with the acquired immunodeficiency syndrome". Clin Radiol. 50 (11): 756–60. PMID 7489624.
- ↑ Penneys NS, Hicks B (1985). "Unusual cutaneous lesions associated with acquired immunodeficiency syndrome". J Am Acad Dermatol. 13 (5 Pt 1): 845–52. PMID 3001157.
- ↑ Jones C, Orengo I, Rosen T, Ellner K (1990). "Cutaneous cryptococcosis simulating Kaposi's sarcoma in the acquired immunodeficiency syndrome". Cutis. 45 (3): 163–7. PMID 2311432.
- ↑ Blauvelt A, Kerdel FA (1992). "Cutaneous cryptococcosis mimicking Kaposi's sarcoma as the initial manifestation of disseminated disease". Int J Dermatol. 31 (4): 279–80. PMID 1634295.
- ↑ 5.0 5.1 5.2 Boyars MC, Zwischenberger JB, Cox Jr CS. Clinical manifestations of pulmonary fungal infections. Journal of thoracic imaging. 1992 Sep 1;7(4):12-22.
- ↑ 6.0 6.1 Le Rhun E, Taillibert S, Chamberlain MC (2013). "Carcinomatous meningitis: Leptomeningeal metastases in solid tumors". Surg Neurol Int. 4 (Suppl 4): S265–88. doi:10.4103/2152-7806.111304. PMC 3656567. PMID 23717798.
- ↑ 7.0 7.1 Chow E, Troy SB (2014). "The differential diagnosis of hypoglycorrhachia in adult patients". Am J Med Sci. 348 (3): 186–90. doi:10.1097/MAJ.0000000000000217. PMC 4065645. PMID 24326618.
- ↑ 8.0 8.1 Leen WG, Willemsen MA, Wevers RA, Verbeek MM (2012). "Cerebrospinal fluid glucose and lactate: age-specific reference values and implications for clinical practice". PLoS One. 7 (8): e42745. doi:10.1371/journal.pone.0042745. PMC 3412827. PMID 22880096.
- ↑ 9.0 9.1 9.2 Negrini B, Kelleher KJ, Wald ER (2000). "Cerebrospinal fluid findings in aseptic versus bacterial meningitis". Pediatrics. 105 (2): 316–9. PMID 10654948.
- ↑ Brouwer MC, Tunkel AR, van de Beek D (2010). "Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis". Clin Microbiol Rev. 23 (3): 467–92. doi:10.1128/CMR.00070-09. PMC 2901656. PMID 20610819.
- ↑ Caudie C, Tholance Y, Quadrio I, Peysson S (2010). "[Contribution of CSF analysis to diagnosis and follow-up of tuberculous meningitis]". Ann Biol Clin (Paris). 68 (1): 107–11. doi:10.1684/abc.2010.0407. PMID 20146981.