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Cryptococcosis - ClinicalKey
Cryptococcosis - ClinicalKey
Cryptococcosis - ClinicalKey
CLINICAL OVERVIEW
Cryptococcosis
Copyright © 2023 by Elsevier, Inc. All rights reserved.
Bouton, Tara C., MD, MPH, TM; Chan, Philip A., MD, MS
Publicado January 1, 2023.
Basic Information
Definition
Cryptococcosis is an infection caused by the encapsulated yeast Cryptococcus spp .
Synonyms
C. neoformans infection
C. gattii infection
C. albidus infection
C. laurentii infection
ICD-10CM CODES
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Predominant Sex
Equal sex distribution when adjusted for HIV status
Predominant Age
Less than 2 yr of age; 20 to 40 yr of age
Peak Incidence
20 to 40 yr (parallel to HIV/AIDS epidemic)
Neonatal Infection
Very uncommon
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1. In the lungs (fever, cough, dyspnea, and typically with lobar consolidation)
Etiology
• There are four Cryptococcus spp. that cause disease in humans, although most laboratories are not able to
differentiate between species. C. neoformans (Table E1
(https://clinicalkey.unicartagenaproxy.elogim.com/#!/content/derived_clinical_overview/76-s2.0-B9780323755733002444#t0015)) is the
cause of a majority of global disease burden, primarily in immunocompromised patients. C. gattii infections
are much less common and occur more often in normal hosts, with recent outbreaks in the Pacific
Northwest. C. albidus and C. laurentii are even rarer causes of disease.
• Infection originates by inhalation into the respiratory tract followed by dissemination to the CNS in most
cases, usually without recognizable lung involvement.
• Almost always in the setting of AIDS (most with CD4 counts <100) or other disorders of cellular immune
function, such as organ transplantation.
TABLE E1
Summary of Characteristics of Cryptococcus gattii and Cryptococcus neoformans
From Cherry JD et al: Feigin and Cherry’s pediatric infectious diseases, ed 8, Philadelphia, 2019, Elsevier.
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AIDS, Acquired immunodeficiency syndrome; ART, antiretroviral therapy; CGB, l-canavanine, glycine, and bromothymol blue; CNS, central nervous
system; MALDI-MS, matrix-assisted laser desorption/ionization time of flight.
Diagnosis
Differential Diagnosis
• Subacute meningitis (caused by Listeria monocytogenes, Mycobacterium tuberculosis, Histoplasma
capsulatum, viruses)
• Pulmonary involvement confused with Pneumocystis jiroveci pneumonia when diffuse or confused with TB
or bacterial pneumonia when focal or involving the pleura
• Skin lesions can take many forms and may be confused with bacterial cellulitis or molluscum contagiosum
Workup
• Lumbar puncture to exclude cryptococcal meningitis, with measurement of opening pressure because CSF
opening pressure is elevated in 60% to 80% of HIV patients and may require drainage. In cryptococcal
meningitis, CSF reveals lymphocytic pleocytosis (although a paucity of WBCs may be found in CSF of HIV
patients)
• CT scan of the head when focal lesion or increased intracranial pressure is suspected
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Laboratory Tests
• Culture and India ink stain (60% to 80% sensitive in culture-proven cases [Fig. E1
(https://clinicalkey.unicartagenaproxy.elogim.com/#!/content/derived_clinical_overview/76-s2.0-B9780323755733002444#f0010)]);
examination of the CSF in all cases when CNS involvement is suspected
• Cryptococcal antigen detection in the CSF of symptomatic adults living with HIV undergoing workup of
their first episode of cryptococcal meningitis is both highly sensitive and specific
• Blood and serum cryptococcal antigen assay (>90% sensitivity and specificity in immunocompromised
patients; lower sensitivity in immunocompetent patients)
FIG. E1
A, India ink staining of cerebrospinal fluid demonstrates Cryptococcus neoformans and capsule, which
excludes the stain and results in a halo around the organism. B, Computed tomography scan of a child with
rhabdomyosarcoma reveals nodule (white arrow) secondary to C. neoformans. C, Mucicarmine staining of a
lung from a rat with experimentally induced pulmonary cryptococcosis shows granulomas containing C.
neoformans (black arrows). D, Immunostaining for cryptococcal polysaccharide reveals extensive shedding of
polysaccharide within the brain parenchyma and around cryptococcomas of a rat with experimentally induced
cryptococcal meningoencephalitis.
From Cherry JD et al: Feigin and Cherry’s pediatric infectious diseases, ed 8, Philadelphia, 2019, Elsevier.
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Imaging Studies
• CT scan or MRI of the head if focal neurologic involvement or cryptococcoma is suspected.
Treatment
Acute General Rx
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• Treatment of cryptococcosis consists of three stages: Induction, consolidation, and maintenance. Induction
therapy for CNS disease (meningitis) was historically initiated with IV amphotericin B deoxycholate (0.7 to
1.0 mg/kg/day) with flucytosine 100 mg/kg/day PO in four divided doses; however, there is growing clinical
evidence for liposomal amphotericin B (3 to 6 mg/kg/day) plus flucytosine, especially in HIV-infected
patients and in those with renal dysfunction. Induction therapy is generally recommended for 2 to 4 wk and
until repeat CSF cultures are negative; it is then recommended to transition to consolidation therapy with
fluconazole 400 mg PO q24h for 8 wk, followed by ongoing fluconazole 200 mg PO q24h maintenance
therapy (up to 2 yr) to reduce relapse rate. Maintenance therapy is indicated in patients with AIDS until
these patients have been receiving antifungal therapy for at least 1 yr and they have responded to
antiretroviral therapy (CD4 cell count ≥100/microliter for ≥3 mo). In patients without HIV, the duration of
maintenance therapy is generally 6 to 12 mo. Lifelong antifungal therapy is needed in organ transplant
patients.
• Alternative: IV fluconazole combined with flucytosine for initial therapy in patients unable to tolerate
amphotericin B.
• Data support increased mortality with early initiation of antiretroviral therapy in the setting of cryptococcal
meningitis due to immune reconstitution syndrome; therefore it is generally recommended to wait 2 to 10
wk after starting cryptococcal therapy prior to starting antiretroviral therapy.
• CSF removal with daily lumbar puncture or insertion of a shunt is beneficial in patients with elevated
intracranial pressure.
Chronic Rx
• Fluconazole (200 to 400 mg PO qd) is highly effective in preventing a relapse in HIV-infected patients;
development of resistance may occur. Itraconazole is an alternative agent, along with growing evidence for
voriconazole and posaconazole use.
Disposition
Without maintenance therapy, relapse rate is >50% among AIDS patients.
Referral
• For consultation with infectious diseases specialist in all cases
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Suggested Readings
Boulware D., et al.: Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis. N Engl J Med 2014; 370: pp.
2487-2498.
Maziarz E.K., Perfect J.R.: Cryptococcosis. Infect Dis Clin North Am 2016; 30: pp. 179-206.
Perfect J.R., et al.: Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the Infectious
Diseases Society of America. Clin Infect Dis 2010; 50: pp. 291-322.
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