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