Post on 30-Jun-2020
Too Competent for Cryptococcus
Starr Steinhilber, MD Victoria Johnson, MD
SGIM Clinical Vignettes Session F
May 12, 2012
48 yo healthy AAM
Fevers Chills Headache Back pain Vomiting
Headache Back pain Vomiting
Blurry vision
Increased headache
ED visit Doxycycline
ED visit Unknown antibiotic
Admission in August
Sx
Tx
- 4 weeks
- 1 week - 3 days Current
23 lb weight loss
Histories
l PMH : Rocky Mountain Spotted Fever w/ rash post tick bite in ~1992
l Family History : +sarcoidosis, DM, gout
Social History
l Lives in north Alabama- hunter, outdoorsman l Veteran- served internationally in the 1980s l No travel x 30 years
l Prior heavy ETOH/cocaine/marijuana in military l Multiple female sexual partners, uses condoms
Physical Exam
T 99.4 P 99 BP 122/64 R 21 98% on RA BMI 19.6 l Gen: good muscle tone
mild distress, diaphoretic, warm to touch neck stiffness with meningismus
l Neuro: Alert and oriented x 4, CN 2-12 intact persistent bilateral horizontal nystagmus with left lateral gaze
l Skin: no inoculation escar, target lesions, or other rashes
Laboratory Data
135 99 17 3.3 30 1.0
Ca 8.6 Mag 1.9 Phos 2.4
Hepatic Function normal
UDS neg CT head normal CXR normal
Normal differential
94 11 13
40 259
Laboratory Data
135 99 17 3.3 30 1.0
Ca 8.6 Mag 1.9 Phos 2.4
Hepatic Function normal
94 11 13
40 259
Fever + Headache +
meningismus = meningitis
Next Step: Lumbar
Puncture
Cerebrospinal Fluid
Opening pressure 46 mmHg Nucleated Cells 538 mg/dl N 19%
L 71%
Protein 141 mg/dl Glucose 23 mg/dl Gram stain – few
neutrophils, moderate mononuclear cells
VDRL negative India Ink positive Cryptococcal Antigen
1: 512
Further evaluation of immune status
l HIV nonreactive CD4, CD8 % and absolute wnl
l IgA, IgG, IgM, IgD, IgE wnl l C3, C4, CH50 wnl
l Negative malignancy w/u
Serum cryptococcus Ag 1:2048
Cryptococcus
l Affects 1 million annually l 600,000 deaths/year worldwide l Incidence 2-7/1000 HIV patients l Of cryptococcus cases, up to 20% will be normal
hosts
Healthy Male
Intact Immune System
Cryptococcus
Not improving with treatment
Cryptococcus gattii !!
C. neoformas vs C. gattii
neoformans l Immunocompromised l Acute l Mortality l Proven treatment
regimen
gattii l Immunocompetent l Subacute l Morbidity l Longer and more
complex treatment
Capsule
gattii neoformans
Treatment?
A. Amphotericin lipid complex B. Flucytosine C. Fluconazole D. Interferon gamma E. Steroids
Treatment
Amphotericin Flycytocine
VP Shunt
Interferon gamma
Discharged on Fluconazole + Steroid taper
Day 1 75 20 14
Headaches High opening pressure CSF Crytpto Ag 1:2048
CSF Cryptococcal Ag still positive
CSF negative
Now
Stable On Fluc/Steroids
Take Home points
l Cryptococcus can be found in normal hosts l C. gattii is harder to treat l Speciating cryptococcus early in a normal host
could lead to faster escalations of treatment l Scan for cryptococcomas in C. gattii patients
Questions?
References l Pappas PG , et al. “Recombinant interferon- gamma 1b as adjunctive therapy for AIDS-related
acute cryptococcal meningitis.” J Infect Dis. 2004 Jun 15;189(12):2185-91. l Jarvis JN, et al. “Adjunctive interferon-γ immunotherapy for the treatment of HIV-associated
cryptococcal meningitis: a randomized controlled trial.” AIDS. 2012 Mar 20. l (3) Desalermos A, et al. “Update on the epidemiology and management of cryptococcal
meningitis.” Expert Opin Pharmacother. 2012 Apr;13(6):783-9. l ( 4) Harris JR, et al. “Cryptococcus gattii in the United States: clinical aspects of infection with
an emerging pathogen.” Clin Infect Dis. 2011 Dec;53(12):1188-95. l Springer DJ, et al. “Projecting Global Occurrence of Cryptococcus gattii.” Emerging Infectious
Diseases • www.cdc.gov/eid • Vol. 16, No. 1, January 2010 l CDC. “Emergence of Cryptococcus gattii-- Pacific Northwest, 2004-2010.” MMWR Morb Mortal
Wkly Rep. 2010 Jul 23;59(28):865-8 l Lester SJ, et al. “Cryptococcosis: update and emergence of Cryptococcus gattii.” Vet Clin
Pathol. 2011 Mar;40(1):4-17 l * Chaturvedi V, et al. “Cryptococcus gattii: a resurgent fungal pathogen.” Trends Microbiol.
2011 Nov;19(11):564-71 l Datta, K et al. "Spread of Cryptococcus gattii into Pacific Northwest region of the United
States". Emerging infectious diseases (1080-6040), 15 (8), p. 1185. l Phillips P et al, “Dexamethasone in Cryptococcus gattii Central Nervous System Infection.”
Clinical Infectious Diseases2009;49:591–5.
Extra Slides
l Things to read about : l Australia history l Why immunocompetent l CSF profile
Latent vs Primary Infection?
1980s 1990s 2000s 2010s current
Marines Hawaii, Philippines, Thailand, Australia, Okinawa, Hong Kong
National Guard Missouri, Mississippi
Worked in a scrapping yard with pigeons, in a North AL chicken house, and construction
Hunts/east/skins rabbits, squirrels, deer, groundhogs, turtles, wild hogs
The Capsule
l Negatively charged protects from phagocytosis l Causes adherence and inhibition of neutrophil migration l Capsule increases by: l Decreased iron l Increased CO2 concentration l Increased age of organisms l Increase in duration of infection
l Increased capsule = resistance to drugs and phagocytosis
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Cryptococcus
Serotype B & C C. neoformans
var gattii
Serotype A C. neoformans
var grubii
Serotype D
C. neoformans var neoformans
C. gattii
Risk Factors
l Steroid use
l Underlying pulmonary disease.
l > 50 yo
l Current smokers
l Immunosuppression due to HIV or invasive malignancy.
l Exposure
l Negative workup :
Urine Histoplasma
Chlamydia
Gonorrhoea
Aspergillus
CMV Ag
RMSF Ag Hepatitis A, B, C
Why immunocompetent?
l Was it just lack of disease awareness and reporting? No.
Too competent for Cryptococcus
Starr Steinhilber, MD Victoria Johnson, MD
University of Alabama at Birmingham
SGIM Clinical Vignettes Session F
May 12, 2012
Too competent for Cryptococcus
Starr Steinhilber, MD Victoria Johnson, MD
SGIM Clinical Vignettes Session F
May 12, 2012