Too Competent for Cryptococcus Starr Steinhilber, MD Victoria Johnson, MD

Transcription

1 SGIM Clinical Vignettes Session F May 12, 2012 Too Competent for Cryptococcus Starr Steinhilber, MD Victoria Johnson, MD

2 48 yo healthy AAM Sx Fevers Chills Headache Back pain Vomiting Headache Back pain Vomiting Blurry vision Increased headache - 4 weeks - 1 week - 3 days Current Tx ED visit Doxycycline ED visit Unknown antibiotic Admission in August 23 lb weight loss

3 Histories PMH : Rocky Mountain Spotted Fever w/ rash post tick bite in ~1992 Family History : +sarcoidosis, DM, gout

4 Social History Lives in north Alabama- hunter, outdoorsman Veteran- served internationally in the 1980s No travel x 30 years Prior heavy ETOH/cocaine/marijuana in military Multiple female sexual partners, uses condoms

5 Physical Exam T 99.4 P 99 BP 122/64 R 21 98% on RA BMI 19.6 Gen: good muscle tone mild distress, diaphoretic, warm to touch neck stiffness with meningismus Neuro: Alert and oriented x 4, CN 2-12 intact persistent bilateral horizontal nystagmus with left lateral gaze Skin: no inoculation escar, target lesions, or other rashes

6 Laboratory Data Ca 8.6 Mag 1.9 Phos 2.4 Hepatic Function normal UDS neg CT head normal CXR normal Normal differential

7 Laboratory Data Ca 8.6 Mag 1.9 Phos 2.4 Hepatic Function normal Fever + Headache + meningismus = meningitis Next Step: Lumbar Puncture

8 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

9 Further evaluation of immune status HIV nonreactive CD4, CD8 % and absolute wnl IgA, IgG, IgM, IgD, IgE wnl C3, C4, CH50 wnl Negative malignancy w/u Serum cryptococcus Ag 1:2048

10 Cryptococcus Affects 1 million annually 600,000 deaths/year worldwide Incidence 2-7/1000 HIV patients Of cryptococcus cases, up to 20% will be normal hosts

11 Healthy Male Intact Immune System Cryptococcus Not improving with treatment

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13 Cryptococcus gattii!!

14 C. neoformas vs C. gattii neoformans Immunocompromised Acute Mortality Proven treatment regimen gattii Immunocompetent Subacute Morbidity Longer and more complex treatment

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16 Capsule gattii neoformans

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18 Treatment? A. Amphotericin lipid complex B. Flucytosine C. Fluconazole D. Interferon gamma E. Steroids

19 Treatment Amphotericin Flycytocine VP Shunt Interferon gamma Discharged on Fluconazole + Steroid taper Stable On Fluc/Steroids Day Now Headaches High opening pressure CSF Crytpto Ag 1:2048 CSF Cryptococcal Ag still positive CSF negative

20 Take Home points Cryptococcus can be found in normal hosts C. gattii is harder to treat Speciating cryptococcus early in a normal host could lead to faster escalations of treatment Scan for cryptococcomas in C. gattii patients

21 Questions?

22 References Pappas PG, et al. Recombinant interferon- gamma 1b as adjunctive therapy for AIDS-related acute cryptococcal meningitis. J Infect Dis Jun 15;189(12): Jarvis JN, et al. Adjunctive interferon-γ immunotherapy for the treatment of HIV-associated cryptococcal meningitis: a randomized controlled trial. AIDS Mar 20. (3) Desalermos A, et al. Update on the epidemiology and management of cryptococcal meningitis. Expert Opin Pharmacother Apr;13(6): ( 4) Harris JR, et al. Cryptococcus gattii in the United States: clinical aspects of infection with an emerging pathogen. Clin Infect Dis Dec;53(12): Springer DJ, et al. Projecting Global Occurrence of Cryptococcus gattii. Emerging Infectious Diseases Vol. 16, No. 1, January 2010 CDC. Emergence of Cryptococcus gattii-- Pacific Northwest, MMWR Morb Mortal Wkly Rep Jul 23;59(28):865-8 Lester SJ, et al. Cryptococcosis: update and emergence of Cryptococcus gattii. Vet Clin Pathol Mar;40(1):4-17 * Chaturvedi V, et al. Cryptococcus gattii: a resurgent fungal pathogen. Trends Microbiol Nov;19(11): Datta, K et al. "Spread of Cryptococcus gattii into Pacific Northwest region of the United States". Emerging infectious diseases ( ), 15 (8), p Phillips P et al, Dexamethasone in Cryptococcus gattii Central Nervous System Infection. Clinical Infectious Diseases2009;49:591 5.

23 Extra Slides Things to read about : Australia history Why immunocompetent CSF profile

24 Latent vs Primary Infection? Marines Hawaii, Philippines, Thailand, Australia, Okinawa, Hong Kong Worked in a scrapping yard with pigeons, in a North AL chicken house, and construction 1980s 1990s 2000s 2010s current National Guard Missouri, Mississippi Hunts/east/skins rabbits, squirrels, deer, groundhogs, turtles, wild hogs

25 The Capsule Negatively charged protects from phagocytosis Causes adherence and inhibition of neutrophil migration Capsule increases by: Decreased iron Increased CO2 concentration Increased age of organisms Increase in duration of infection Increased capsule = resistance to drugs and phagocytosis

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27 Byrnes III EJ, et al. Emergence and Pathogenicity of Highly Virulent Cryptococcus gattii Genotypes in the Northwest United States. PLoS Pathog April; 6(4)

28 Cryptococcus Serotype A Serotype B & C Serotype D C. neoformans var grubii C. neoformans var gattii C. neoformans var neoformans C. gattii

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31 Risk Factors Steroid use Underlying pulmonary disease. > 50 yo Current smokers Immunosuppression due to HIV or invasive malignancy. Exposure

32 Negative workup : Urine Histoplasma Chlamydia Gonorrhoea Aspergillus CMV Ag RMSF Ag Hepatitis A, B, C

33 Why immunocompetent? Was it just lack of disease awareness and reporting? No.

34 SGIM Clinical Vignettes Session F May 12, 2012 Too competent for Cryptococcus Starr Steinhilber, MD Victoria Johnson, MD University of Alabama at Birmingham

35 SGIM Clinical Vignettes Session F May 12, 2012 Too competent for Cryptococcus Starr Steinhilber, MD Victoria Johnson, MD