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Information about Histoplasmosis2007

Published on October 4, 2007

Author: Joshua

Source: authorstream.com

Histoplasmosis L. Joseph Wheat :  Histoplasmosis L. Joseph Wheat Request CD Notes in normal view Endemic in US :  Endemic in US Endemic Impact for 2002 :  Endemic Impact for 2002 Microconidia Infectious :  Microconidia Infectious Yeast Pathogenic:  Yeast Pathogenic Mold→Yeast <24 hr Disseminates in pre-immune phase Splenic granuloma Bone marrow abnormalities Hepatic enzymes Cellular defense prevents progression Heavy Inoculum→Acute Diffuse:  Heavy Inoculum→Acute Diffuse Moderate-severe Retic-nod or miliary Dissemination 37% Prolonged recovery Light Inoculum→Subacute Focal:  Light Inoculum→Subacute Focal Asympt or mild illness Focal or patchy infiltrates Hilar or mediastinal adenopathy Spontaneous recovery in 1 month Rheumatologic Syndrome Mistaken as Sarcoidosis:  Rheumatologic Syndrome Mistaken as Sarcoidosis Histoplasma Pericarditis:  Histoplasma Pericarditis COPD→Chronic Pulmonary:  COPD→Chronic Pulmonary Underlying COPD Cavitary infiltrates Resembles TB Slowly progressive Histo on Etanercept:  Histo on Etanercept Reactivation “Latent Histo” Rare :  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 <0.1 Etanercept <0.01 Smoldering or New Exposure:  Smoldering or New Exposure Rationale <0.1% too low for reactivation Why not 50-80%? Rate ~ endemic rate < 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 Mucocutaneous Dissemination:  Mucocutaneous Dissemination Gastrointestinal Dissemination:  Gastrointestinal Dissemination Adrenal Dissemination:  Adrenal Dissemination <10% of cases Adrenal mass Adrenal insufficiency if extensive necrosis Think histo Think Addisons CNS Dissemination:  CNS Dissemination Clinical Manifestations:  Clinical Manifestations Rapid Diagnosis :  Rapid Diagnosis Histopathology :  Histopathology 3rd Gen Histo Antigen Assay:  3rd Gen Histo Antigen Assay Reproducibility 3rd Gen Histo Antigen Assay:  Reproducibility 3rd Gen Histo Antigen Assay Interpretation Guideline:  Interpretation Guideline Antigen Detection in BAL:  Antigen Detection in BAL Antigenemia Clears First:  Antigenemia Clears First Summary Diagnosis :  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@miravistalabs.com Indications for Treatment:  Indications for Treatment Indicated and effective Progressive disseminated Chronic pulmonary Acute diffuse pulmonary Indication and effectiveness uncertain Subacute localized pulmonary Mediastinal granuloma Slide28:  Severe Non-Severe Response of PDH in AIDS to Ampho B L-AmB vs. D-AmB Study Design:  L-AmB vs. D-AmB Study Design AIDS with moderate or severe PDH Randomized, double blind 2:1 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 L-AmB vs D-AmB Outcome:  L-AmB vs D-AmB Outcome Response to Itraconazole or Fluconazole in PDH in AIDS:  Response to Itraconazole or Fluconazole in PDH in AIDS Causes Itraconazole Failure:  Causes Itraconazole Failure Inadequate drug exposure Adherence/tolerance Drug-interactions Absorption Resistance Not reported or observed Measure random drug levels, >2 μg/ml Cause for Fluconazole Failure:  Cause for Fluconazole Failure Activity Newer Triazoles :  Activity Newer Triazoles Emergence of Resistance :  Emergence of Resistance CYP51 Tyr→Phenylalanine at Y136F:  CYP51 Tyr→Phenylalanine at Y136F Voriconazole MIC vs Blood Concentration:  Voriconazole MIC vs Blood Concentration IDSA Histo Guideline 2007 :  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 Posaconazole>>fluconazole ~voriconazole? Alternative to itraconazole Monitor levels voriconazole & posaconazole Seek advise if uncertain! New in 2007:  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

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