Histoplasmosis L. Joseph Wheat

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Histoplasmosis L. Joseph Wheat

• Request CD
• Notes in normal view

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Endemic in US
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Endemic Impact for 2002
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Microconidia Infectious
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Yeast Pathogenic

• Mold?Yeast lt24 hr
• Disseminates in pre-immune phase
• Splenic granuloma
• Bone marrow abnormalities
• Hepatic enzymes
• Cellular defense prevents progression

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Heavy Inoculum?Acute Diffuse

• Moderate-severe
• Retic-nod or miliary
• Dissemination 37
• Prolonged recovery

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Light Inoculum?Subacute Focal

• Asympt or mild illness
• Focal or patchy infiltrates
• Hilar or mediastinal adenopathy
• Spontaneous recovery in 1 month

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Rheumatologic Syndrome Mistaken as Sarcoidosis
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Histoplasma Pericarditis
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COPD?Chronic Pulmonary

• Underlying COPD
• Cavitary infiltrates
• Resembles TB
• Slowly progressive

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Histo on Etanercept
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Reactivation Latent Histo Rare

• Group /total Incidence
• BMT 0/147 0
• SOT 0/449 0
• --Sero 0/48 0
• --CXR 0/23 0
• Literature
• AIDS 1
• Infliximab lt0.1
• Etanercept lt0.01

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Smoldering or New Exposure

• Rationale
• lt0.1 too low for reactivation
• Why not 50-80?
• Rate endemic rate
• lt 60 d after start infliximab
• Too early to reactivate

• Implications
• RO active infection at initiation
• CXR and/or CT
• Antigen antibody?
• Workup new illness
• Pulmonary symptoms
• Fever weight loss
• Screen during high risk?
• Infliximab first 6 mo
• Etanercept first year

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Mucocutaneous Dissemination
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Gastrointestinal Dissemination
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Adrenal Dissemination

• lt10 of cases
• Adrenal mass
• Adrenal insufficiency if extensive necrosis
• Think histo
• Think Addisons

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CNS Dissemination
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Clinical Manifestations
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Rapid Diagnosis
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Histopathology
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3rd Gen Histo Antigen Assay
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Reproducibility 3rd Gen Histo Antigen Assay
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Interpretation Guideline
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Antigen Detection in BAL
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Antigenemia Clears First
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Summary Diagnosis

• Battery of test recommended
• Antigen, cytology/histopath, culture, serology
• Only culture 100 specific, but insensitive
• Antigen not perfect
• Sensitivity not 100 negative not exclude
• Specificity not 100 positive not prove
• Should validated antigen!
• Repeat positive antigen
• Do other tests
• Seek advice if uncertain
• 317-856-2681 ext 452
• jwheat_at_miravistalabs.com

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Indications for Treatment

• Indicated and effective
• Progressive disseminated
• Chronic pulmonary
• Acute diffuse pulmonary
• Indication and effectiveness uncertain
• Subacute localized pulmonary
• Mediastinal granuloma

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Response of PDH in AIDS to Ampho B
Severe Non-Severe
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L-AmB vs. D-AmB Study Design

• AIDS with moderate or severe PDH
• Randomized, double blind
• 21 randomization AmB for 7-14 d
• Liposomal AmB 3 mg/kg/d
• Deoxycholate-AmB .7 mg/kg/d
• Itra 200 mg bid for 10 weeks

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L-AmB vs D-AmB Outcome
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Response to Itraconazole or Fluconazole in PDH in
AIDS
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Causes Itraconazole Failure

• Inadequate drug exposure
• Adherence/tolerance
• Drug-interactions
• Absorption
• Resistance
• Not reported or observed
• Measure random drug levels, gt2 µg/ml

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Cause for Fluconazole Failure
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Activity Newer Triazoles
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Emergence of Resistance
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CYP51 Tyr?Phenylalanine at Y136F
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Voriconazole MIC vs Blood Concentration
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IDSA Histo Guideline 2007

• Liposomal Ampho B 3 mg/kg/d
• Moderate to severe
• Initial therapy
• Itraconazole 200 mg bid
• Milder cases
• Continued therapy
• Monitor levels
• Posaconazolegtgtfluconazole voriconazole?
• Alternative to itraconazole
• Monitor levels voriconazole posaconazole
• Seek advise if uncertain!

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New in 2007

• Quantitative 3rd generation antigen assay
• Cross reaction in coccidioidomycosis
• Monitor clearance antigenemia then antigenuria
• BAL 92 sensitive
• Posaconazole preferred alternative to itra
• Therapeutic drug monitoring