Cryptococcosis differential diagnosis: Difference between revisions

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{{CMG}} {{AE}} {{SSK}}; {{YD}}
{{CMG}} {{AE}} {{SSK}}; {{YD}}
==Overview==
==Overview==
Cryptococcosis is more common among [[Immunocompromised|immunocompromised patients]] who are at high risk for other [[fungal]], [[bacterial]], and [[viral infections]]. Cryptococcal [[meningitis]] can be indistinguishable from [[Bacterial meningitis|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 neurologic signs|focal neurological deficits]]) such as [[coccidioidomycosis]], [[histoplasmosis]], [[tuberculosis]], and [[Community-acquired pneumonia|community]]/[[hospital-acquired pneumonia]]. Cutaneous cryptococcosis in [[HIV AIDS|HIV/AIDS patients]] must be differentiated from [[molluscum contagiosum]] and [[Kaposi's sarcoma]].
[[Cryptococcosis]] is more common among [[Immunocompromised|immunocompromised patients]] who are at high risk for other [[fungal]], [[bacterial]], and [[viral infections]]. Cryptococcal [[meningitis]] can be indistinguishable from [[Bacterial meningitis|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 neurologic signs|focal neurological deficits]]) such as [[coccidioidomycosis]], [[histoplasmosis]], [[tuberculosis]], and [[Community-acquired pneumonia|community]]/[[hospital-acquired pneumonia]]. Cutaneous [[cryptococcosis]] in [[HIV AIDS|HIV/AIDS patients]] must be differentiated from [[molluscum contagiosum]] and [[Kaposi's sarcoma]].


==Differentiating Cryptococcosis from other Diseases==
==Differentiating Cryptococcosis from other Diseases==
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* '''[[Meningitis|Bacterial/Viral Meningitis]]'''
**
**May be indistinguishable before antigen testing and [[CSF analysis|CSF]] stain and culture, although onset of fungal meningitis is classically less acute than bacterial meningitis.
**Bacterial coverage is recommended for all [[Meningitis|meningitides]], even if cryptococcal meningitis is highly suspected.
*'''[[Pneumonia|Bacterial/Viral Pneumonia]]'''<ref name="pmid7489624">{{cite journal| author=Friedman EP, Miller RF, Severn A, Williams IG, Shaw PJ| title=Cryptococcal pneumonia in patients with the acquired immunodeficiency syndrome. | journal=Clin Radiol | year= 1995 | volume= 50 | issue= 11 | pages= 756-60 | pmid=7489624 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7489624  }} </ref>
**May be indistinguishable before antigen testing.
**May be equally as common as cryptococcal pneumonia in [[Immunocompromised|immunocompromised patients]], more common in immunocompetent patients.
*'''[[Pneumocystis jirovecii pneumonia|''Pneumocystis jirovecii'' Pneumonia]]'''<ref name="pmid7489624">{{cite journal| author=Friedman EP, Miller RF, Severn A, Williams IG, Shaw PJ| title=Cryptococcal pneumonia in patients with the acquired immunodeficiency syndrome. | journal=Clin Radiol | year= 1995 | volume= 50 | issue= 11 | pages= 756-60 | pmid=7489624 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7489624  }} </ref>
**Also a very common cause of pneumonia among [[HIV AIDS|HIV/AIDS]] patients with low [[CD4]] counts.
**Cryptococcal [[pneumonia]] may present with ground glass opacities on chest X-ray.
**[[Pneumocystis jirovecii|P. jirovecii]] is not usually associated with [[CNS disease]].
*'''[[Tuberculosis]]'''<ref name="pmid7489624">{{cite journal| author=Friedman EP, Miller RF, Severn A, Williams IG, Shaw PJ| title=Cryptococcal pneumonia in patients with the acquired immunodeficiency syndrome. | journal=Clin Radiol | year= 1995 | volume= 50 | issue= 11 | pages= 756-60 | pmid=7489624 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7489624  }} </ref>
**May present similarly given that immunocompromised status may prevent [[granuloma]] formation.
*'''[[Molluscum contagiosum]]'''<ref name="pmid3001157">{{cite journal| author=Penneys NS, Hicks B| title=Unusual cutaneous lesions associated with acquired immunodeficiency syndrome. | journal=J Am Acad Dermatol | year= 1985 | volume= 13 | issue= 5 Pt 1 | pages= 845-52 | pmid=3001157 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3001157  }} </ref>
*'''[[Molluscum contagiosum]]'''<ref name="pmid3001157">{{cite journal| author=Penneys NS, Hicks B| title=Unusual cutaneous lesions associated with acquired immunodeficiency syndrome. | journal=J Am Acad Dermatol | year= 1985 | volume= 13 | issue= 5 Pt 1 | pages= 845-52 | pmid=3001157 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3001157  }} </ref>
** Is very similar in appearance to disseminated cryptococcosis manifesting on the skin ([[umbilicated lesions]]).
** Is very similar in appearance to disseminated cryptococcosis manifesting on the skin ([[umbilicated lesions]]).
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**Cutaneous cryptococcosis may also present with violaceous [[papules]].
**Cutaneous cryptococcosis may also present with violaceous [[papules]].
**It can only be differentiated by [[Skin biopsy|biopsy]].
**It can only be differentiated by [[Skin biopsy|biopsy]].
*'''[[Coccidioidomycosis]]'''<ref name="pmid1404541">Boyars MC, Zwischenberger JB, Cox Jr CS. Clinical manifestations of pulmonary fungal infections. Journal of thoracic imaging. 1992 Sep 1;7(4):12-22.</ref>
**
**Usually disease course is more protracted, except with severe immunocompromise.
**Not ubiquitous, more common is [[endemic]] areas in the Southwest United States.
*'''[[Histoplasmosis]]'''<ref name="pmid1404541">Boyars MC, Zwischenberger JB, Cox Jr CS. Clinical manifestations of pulmonary fungal infections. Journal of thoracic imaging. 1992 Sep 1;7(4):12-22.</ref>
**Also related to contaminated with bird or bat droppings.
**Not ubiquitous. Common in the Central and Eastern United States.
*'''[[Blastomycosis]]'''<ref name="pmid1404541">Boyars MC, Zwischenberger JB, Cox Jr CS. Clinical manifestations of pulmonary fungal infections. Journal of thoracic imaging. 1992 Sep 1;7(4):12-22.</ref>
*'''[[Blastomycosis]]'''<ref name="pmid1404541">Boyars MC, Zwischenberger JB, Cox Jr CS. Clinical manifestations of pulmonary fungal infections. Journal of thoracic imaging. 1992 Sep 1;7(4):12-22.</ref>
**CNS involvement is much less common with [[blastomyces]].
**CNS involvement is much less common with [[blastomyces]].
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===Differentiating cryptococcal meningitis from other causes of meningitis===
===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:<ref name="pmid23717798">{{cite journal| author=Le Rhun E, Taillibert S, Chamberlain MC| title=Carcinomatous meningitis: Leptomeningeal metastases in solid tumors. | journal=Surg Neurol Int | year= 2013 | volume= 4 | issue= Suppl 4 | pages= S265-88 | pmid=23717798 | doi=10.4103/2152-7806.111304 | pmc=3656567 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23717798  }} </ref><ref name="pmid24326618">{{cite journal| author=Chow E, Troy SB| title=The differential diagnosis of hypoglycorrhachia in adult patients. | journal=Am J Med Sci | year= 2014 | volume= 348 | issue= 3 | pages= 186-90 | pmid=24326618 | doi=10.1097/MAJ.0000000000000217 | pmc=4065645 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24326618  }} </ref><ref name="pmid22880096">{{cite journal| author=Leen WG, Willemsen MA, Wevers RA, Verbeek MM| title=Cerebrospinal fluid glucose and lactate: age-specific reference values and implications for clinical practice. | journal=PLoS One | year= 2012 | volume= 7 | issue= 8 | pages= e42745 | pmid=22880096 | doi=10.1371/journal.pone.0042745 | pmc=3412827 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22880096  }} </ref><ref name="pmid10654948">{{cite journal| author=Negrini B, Kelleher KJ, Wald ER| title=Cerebrospinal fluid findings in aseptic versus bacterial meningitis. | journal=Pediatrics | year= 2000 | volume= 105 | issue= 2 | pages= 316-9 | pmid=10654948 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10654948  }} </ref><ref name="pmid20610819">{{cite journal| author=Brouwer MC, Tunkel AR, van de Beek D| title=Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. | journal=Clin Microbiol Rev | year= 2010 | volume= 23 | issue= 3 | pages= 467-92 | pmid=20610819 | doi=10.1128/CMR.00070-09 | pmc=2901656 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20610819  }} </ref>
Cryptococcal meningitis may be differentiated from other causes of [[meningitis]] by [[cerebrospinal fluid]] examination as shown below:<ref name="pmid23717798">{{cite journal| author=Le Rhun E, Taillibert S, Chamberlain MC| title=Carcinomatous meningitis: Leptomeningeal metastases in solid tumors. | journal=Surg Neurol Int | year= 2013 | volume= 4 | issue= Suppl 4 | pages= S265-88 | pmid=23717798 | doi=10.4103/2152-7806.111304 | pmc=3656567 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23717798  }} </ref><ref name="pmid24326618">{{cite journal| author=Chow E, Troy SB| title=The differential diagnosis of hypoglycorrhachia in adult patients. | journal=Am J Med Sci | year= 2014 | volume= 348 | issue= 3 | pages= 186-90 | pmid=24326618 | doi=10.1097/MAJ.0000000000000217 | pmc=4065645 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24326618  }} </ref><ref name="pmid22880096">{{cite journal| author=Leen WG, Willemsen MA, Wevers RA, Verbeek MM| title=Cerebrospinal fluid glucose and lactate: age-specific reference values and implications for clinical practice. | journal=PLoS One | year= 2012 | volume= 7 | issue= 8 | pages= e42745 | pmid=22880096 | doi=10.1371/journal.pone.0042745 | pmc=3412827 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22880096  }} </ref><ref name="pmid10654948">{{cite journal| author=Negrini B, Kelleher KJ, Wald ER| title=Cerebrospinal fluid findings in aseptic versus bacterial meningitis. | journal=Pediatrics | year= 2000 | volume= 105 | issue= 2 | pages= 316-9 | pmid=10654948 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10654948  }} </ref><ref name="pmid20610819">{{cite journal| author=Brouwer MC, Tunkel AR, van de Beek D| title=Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. | journal=Clin Microbiol Rev | year= 2010 | volume= 23 | issue= 3 | pages= 467-92 | pmid=20610819 | doi=10.1128/CMR.00070-09 | pmc=2901656 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20610819  }} </ref>
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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:

Disease Differentiating signs and symptoms Differentiating tests
CNS lymphoma
  • Single solitary ring enhacning lesion on CT or MRI
Disseminated Tuberculosis
Aspergillosis
  • CSF fungal culture, galactomannan.
Cryptococcosis
Chagas disease
  • History of residence in Central and South America
  • Acute infection is rarely symptomatic,
  • Encephalitis or focal brain lesions
  • Myocarditis
  • Chronic infections in immunocompromised patients develops into encephalitis with necrotic brain lesions causing mass effect.
  • Trypanosoma cruzi in blood, tissue or CSF, PCR of tissue or body fluids, serologic tests.
CMV infection
  • Brain CT/MRI/biopsy: location of lesions are usually near the brain stem or periventricular areas.
  • PCR of CSF with detectable virus is diagnostic.
  • Brain biopsy with + staining for CMV or evidence of owl's eyes is also diagnostic, but it is rarely performed, because of the location of brain lesions.
HSV infection
  • Seizures, headache, confusion and/or urinary retention can be seen in disseminated disease, which usually affects only immunocompromised or acute infections
  • In pregnant women it may be associated with concurrent genital/oral lesions; can be spread to the neonate during acute infection in the mother, or via viral shedding in the birth canal.
  • Neonatal HSV can range from localized skin infections to encephalitis, pneumonitis, and disseminated disease.
  • Brain CT/MRI/biopsy: location of lesions is usually the medial temporal lobe or the orbital surface of the frontal lobe.
  • PCR of CSF with detectable virus is diagnostic.
Varicella Zoster infection
  • Multifocal involvement has subacute course, usually only in immunosuppressed, with headache, fever, focal deficits, and seizures.
  • Unifocal involvement is more typically seen in immunocompetent hosts, occurring after contralateral cranial nerve herpes zoster, with mental status changes, TIAs, and stroke.
  • Disseminated varicella zoster virus can occur in adults during primary infection, presenting with pneumonitis and/or hepatitis.
  • Disease is a vasculopathy, with hemorrhage and stroke.
  • PCR of CSF with detectable virus is diagnostic.
Brain abscess
  • Associated with sinusitis (abutting the sinuses) or with bacteremia.
  • Signs and symptoms includes fever and necrotizing brain lesions with mass effect
  • CSF culture or culture of brain abscess.
Progressive multifocal leukoencephalopathy
  • 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.
  • PCR of CSF for JC virus.
  • Biopsy reveals white matter lesions and not well-circumscribed lesions.

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:[5][6][7][8][9]

Cerebrospinal fluid level Normal level Bacterial meningitis[8] Viral meningitis[8] Cryptococcal meningitis Tuberculous meningitis[10] Malignant meningitis[5]
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)[6] > 0.5 < 0.3 > 0.6 <0.3 < 0.5 <0.5
Lactate (mmols/l)[7] < 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. ↑ 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.
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ Boyars MC, Zwischenberger JB, Cox Jr CS. Clinical manifestations of pulmonary fungal infections. Journal of thoracic imaging. 1992 Sep 1;7(4):12-22.
  5. ↑ 5.0 5.1 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.
  6. ↑ 6.0 6.1 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.
  7. ↑ 7.0 7.1 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.
  8. ↑ 8.0 8.1 8.2 Negrini B, Kelleher KJ, Wald ER (2000). "Cerebrospinal fluid findings in aseptic versus bacterial meningitis". Pediatrics. 105 (2): 316–9. PMID 10654948.
  9. ↑ 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.
  10. ↑ 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.
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