cryptococcosis
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Etiology
- risk factors
- pre-existing lung disease
- immunosuppression
- 33-50% of patients with cryptococcosis are immunosuppressed
- reported in 7-9% of patients with AIDS
- solid organ transplantation
- glucocorticoids
- advanced malignancies
- sarcoidosis
- type 2 diabetes mellitus
- idiopathic (not identified risk factors) 20%[10]
Epidemiology
- see Cryptococcus & Cryptococcus neoformans
- cryptococcal meningitis is the most common form of meningitis in patients with AIDS (most with CD4 count < 100/uL)[1]
- incidence in immunosuppressed pateitns is declining, probably secondary to use of fluconazole for treatment of oral thrush
Pathology
- lung is the portal of entry
- CNS is most common site of dissmenintated cryptococcosis[1]
- subacute & chronic meningoencephalitis in immunocompromised patients[10]
- increased intracranial pressure may result in blindness or death[1]
- may affect lung, bone marrow, skin, prostate[1]
* remal cruptococcosis (images)[14]
Clinical manifestations
- subacute or chronic meningitis or meningoencephalitis
- may occur as a result of immune reconstitution inflammatory syndrome (IRIS)
- insidious onset of symptoms may develop over weeks
- fever (50-90%)[1][10]
- headache (80-90%)[1]
- altered mental status: personality changes, memory loss 920-30%)[1]
- neurologic deficits, cranial nerve palsy
- nausea/vomiting (50%)[1]
- anorexia
- cough with scant sputum 15%
- chest pain (45%)
- dyspnea (25%)
- hemoptysis (7%)
- night sweats (25%)
Laboratory
- cryptococcal serum antibody titers
- screening tool
- serum titer has no prognostic significance
- Cryptococcus neoformans polysaccharide antigen
- Cryptococcus neoformans antigen in serum
- titer has no prognostic value
- Cryptococcus neoformans antigen in CSF
- positive in 90-95% of CNS infections[1]
- titer > 1:1024
- associated with poor prognosis
- suggests relapse or treatment failure
- indicated even in the absence of CNS symptoms*[1]
- urine
- Cryptococcus neoformans antigen in serum
- CSF analysis[9]
- opening pressure may be elevated[9]
- opportunity to lower intracranial pressure by draining CSF
- increased cell count, predominantly lymphocytes
- gram stain & india ink stain of CSF[9] (images)
- opening pressure may be elevated[9]
- culture
- sputum (35%)
- bronchoscopic specimen (35%)
- open lung biopsy (100%)
- CSF culture[1]
* lumbar puncture indicated to rule out CNS infection[1]
Radiology
- chest X-ray
- nodular infiltrates with cavitation
- hilar adenopathy (occasional)
- solitary mass (occasional)
- computed tomography (CT) or magnetic resonance imaging (MRI) of the brain to assess obstructive hydrocephalus
- cerebral atrophy, enhancement of gyri, nodules (cryptococcomas)
- normal in 50% of cases[10]
Complications
- poor prognostic indicators
- altered mental status
- visual impairment
- CSF WBC < 20/uL
- CSF cryptococcal antigen > 1:10,000
- HIV1 infection without prior antiretroviral therapy[1]
Differential diagnosis
Management
- pharmacologic agents (cryptococcal meningitis)
- induction
- amphotericin B 1 mg/kg IV QD, plus flucytosine 25 mg/kg PO every 6 hours for 14 days (AIDS)[1]
- use liposomal amphotericin B for transplant patients & other immunocompromised patients
- induction period is >= 4 weeks for immunocompetent patients
- consolidation: fluconazole 400 mg PO QD for 8 weeks[1][4]
- maintenance:
- fluconazole 200 mg PO QD for >= 1 years (AIDS), 6-12 months (transplant, immunocompetent)
- continue maintenance until CD4 count >= 100/uL for >= 3 months & HIV1 viral load is suppressed[1]
- induction
- non-meningeal cryptococcosis
- fluconazole
- itraconazole is a 2nd line agent
- suspected intracranial hypertension
- CT or MRI to assess obstructive hydrocephalus
- ventriculostomy if present
- correction of elevated CSF pressure
- most important determinant of short-term survival
- may be accomplished by daily lumbar puncture
- goal is stable CSF pressure of < 25 cm of H2O in < 1 week
- lumbar drain infrequently required
- ventriculoperitoneal shunt
- CT or MRI to assess obstructive hydrocephalus
- HIV1 coinfection
- delaying initiation of antiretroviral therapy for 5 weeks after diagnosis of meningitis is associated with improved survival[6]
- relapses
- non-compliance
- resistance to fluconazole
- prophylaxis
- fluconazole 100 mg QD
- dollar cost of prophylaxis may exceed benefit
- discontinue prophylaxis in HIV patients who have achieved immune reconstitution[3]
More general terms
Additional terms
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2009, 2012, 2015, 2018, 2021.
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 808
- ↑ 3.0 3.1 Lortholary O et al, Long-term outcome of AIDS-associatate cryptococcus in the era of combination antiretroviral therapy AIDS 2006 20:2183 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17086058
- ↑ 4.0 4.1 Day JN et al. Combination antifungal therapy for cryptococcal meningitis. N Engl J Med 2013 Apr 4; 368:1291. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23550668 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1110404
- ↑ Perfect JR, Dismukes WE, Dromer F et al Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2010 Feb 1;50(3):291-322. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20047480 corresponding NGC guideline withdrawn Feb 2016
- ↑ 6.0 6.1 Boulware DR et al. Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis. N Engl J Med 2014 Jun 26; 370:2487 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24963568
- ↑ La Hoz RM, Pappas PG. Cryptococcal infections: changing epidemiology and implications for therapy. Drugs. 2013 May;73(6):495-504. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23575940
- ↑ Brizendine KD, Baddley JW, Pappas PG. Pulmonary cryptococcosis. Semin Respir Crit Care Med. 2011 Dec;32(6):727-34. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22167400
- ↑ 9.0 9.1 9.2 9.3 Recio R, Perez-Ayala A. Cryptococcus neoformans Meningoencephalitis. N Engl J Med 2018; 379:281. July 19, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30021095 https://www.nejm.org/doi/full/10.1056/NEJMicm1801051
- ↑ 10.0 10.1 10.2 10.3 10.4 NEJM Knowledge+ Question of the Week. Nove 20, 2018 https://knowledgeplus.nejm.org/question-of-week/540/
- ↑ Pappas PG, Perfect JR, Cloud GA et al. Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy. Clin Infect Dis 2001 Jul 31; 33:690 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11477526
- ↑ Abassi M, Boulware DR, Rhein J. Cryptococcal meningitis: diagnosis and management update. Curr Trop Med Rep 2015 Jun 1; 2:90. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26279970 Free PMC Article
- ↑ Maziarz EK, Perfect JR. Cryptococcosis. Infect Dis Clin North Am. 2016 Mar;30(1):179-206. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26897067 Free PMC Article
- ↑ 14.0 14.1 Saltaren LE, Perez RA. Images in Clinical Medicine. Renal Cryptococcosis. N Engl J Med 2020; 383:2371. Dec 10 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33296563 https://www.nejm.org/doi/full/10.1056/NEJMicm2007464