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ID Subspeciality Rounds

ID Subspeciality Rounds. 12/9/08 Dr.Akshra Verma Dr.Janet Jokela. Case. 74y/o WM with lethargy and confusion x 1 day Hemoptysis : 2-3 months No fever but chills present Lost 40lb of weight – 1yr ROS: Dyspepsia, malena x2, hematuria – 2 days

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ID Subspeciality Rounds

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  1. ID Subspeciality Rounds 12/9/08 Dr.Akshra Verma Dr.JanetJokela

  2. Case 74y/o WM with lethargy and confusion x 1 day Hemoptysis : 2-3 months No fever but chills present Lost 40lb of weight – 1yr ROS: Dyspepsia, malena x2, hematuria – 2 days 2 months back- noted to have a left upper lobe cavitary lesion

  3. Case  6.    Prilosec 7.    Flomax 8.   .Mometasone  9.    Niacin  10.  Lovastatin PAST MEDICAL HISTORY: COPD, Spondylolisthesis, GERD, BPH, Hypertension, Diabetes with Nephropahty, CKD stage III Allergies: Iodine (loss of consciousness) Medications:   1.    Actos2.    Byetta3.    Valsartan4.    Vicodin 5.    Diclofenac SOCIAL HISTORY:  Smoker 1PPD since age 14, quit 3 weeks ago. No alcohol.

  4. 7.9 130.53 117 24.8 115 55 139 113 4.0 2.9 17 Exam: T:97.6 °F P:119 BP: 97/58 RR: 23  O2 sat 98 % on 6L NC Chest: Coarse breath sounds, Breath sounds diminished b/l

  5. What is your differential? What tests do you want next?

  6. Chest x-ray

  7. CT scan

  8. Lab work up Pneumococcal andLegionella urine antigen- negative.  RSV negative.  Mycoplasma antibodynegative LAP: 280

  9. Previous work up •  FNAC x 2  • Cytology revealed organisms consistent with histoplasmosis • Culture was negative • Cultures for AFB and fungus were negative on both studies. • No malignancy • istoplasmascreen was positive - M band was noted on histoplasmaimmunodiffusion • Histoplasma urine antigen negative at that time • Results not available for current admission • Work up for Wegener’s negative

  10. Pulmonary Histoplasmosis Causative agent: Histoplasmacapsulatum Found worldwide United States- midwestern states located in the Ohio and Mississippi River valleys Reservoir : soil contaminated with bird or bat droppings Portal of entry- lungs Low-inoculum exposure in a healthy individuals- asymptomatic Large inoculum or immunosuppressed- severe and potentially fatal, acute diffuse pulmonary infection

  11. Clinical Presentation • Asymptomatic pulmonary histoplasmosis • Symptomatic pulmonary histoplasmosis - Acute • Subacute pulmonary infection weeks to months following exposure • Fever, chills, headache, myalgia, anorexia, cough, and pleuritic chest pain (2-4 weeks following exposure) • Coryza and sore throat are not typical - alternative diagnoses • Radiographs- focal infiltrates and mediastinal or hilar lymphadenopathy • Diffuse reticulonodular/ miliary pulmonary infiltrates • Chronic pulmonary histoplasmosis • Xray- fibrotic apical infiltrates with cavitation

  12. Does pulmonary histoplasmosis always need treatment?

  13. Indications for antifungal therapy

  14. Antifungals • Lipid/Liposomal formulation of amphotericin B • 3.0–5.0 mg/kg daily IV • Deoxycholate formulation of amphotericin B • 0.7–1.0 mg/kg daily IV • Itraconazole • 200 mg 3 times PO daily for 3 days and then 200 mg once or twice PO daily • Other azoles-second line: Fluconazole, ketoconazole, posaconazole, voriconazole • No role of echinocandins

  15. Monitoring response to therapy • Histoplasmaantigenuria and/or antigenemia, levels decrease during therapy • Levels increase in 90% of those who relapse • Measure antigen levels • before treatment is initiated, at 2 weeks, at 1 month, and then approximately every 3 months during therapy and for at least 6 months after treatment is stopped

  16. Acute Pulmonary Histoplasmosis Mild-to-Moderate Moderately Severe to Severe • Lipid formulation of amphotericin B for 1–2 weeks followed by itraconazole • 2. The deoxycholate formulation of amphotericin B • 3. Methylprednisolone during the first 1–2 weeks for patients who develop respiratory complications 1.Treatment is usually unnecessary 2. Itraconazole for 6–12 weeks is recommended for patients who continue to have symptoms for >1 month

  17. Chronic Cavitary Pulmonary Histoplasmosis Itraconazole for at least 1 year is recommended Montior Blood levels of itraconazole at 2 weeks to ensure adequate drug exposure

  18. Complications for Pulmonary Histoplasmosis Pericarditis Arthritis/ ErythemaNodosum Mediastinal lymphadenitis MediastinalGranuloma Mediastinal Fibrosis Broncholithiasis Pulmonary Nodule

  19. Disseminated histoplasmosis Clinical illness that does not improve after at least 3 weeks of observation and that is associated with physical or radio-graphicfindings and/or laboratory evidence of involvement of extrapulmonary tissues. Hepatosplenomegaly, mucosal ulcers, skin lesions, gastrointestinal involvement Pancytopenia, progressive elevation of hepatic enzyme levels, increased lactate dehydrogenase level, and increased serum ferritin level. Laboratory evidence : demonstration of granulomas with yeasts re-sembling H. capsulatum in extrapulmonary tissues, growth in culture of H. capsulatum, and persistent antigenuria and/or antigenemia.

  20. Progressive Disseminated Histoplasmosis Mild-to-Moderate Moderately Severe to Severe Liposomal amphotericin B (3.0 mg/kg daily) is recommended for 1–2 weeks, followed by oral itraconazole for a total of at least 12 months Substitution of another lipid formulation at a dosage of 5.0 mg/kg daily The deoxycholate formulation of amphotericin B (0.7–1.0 mg/kg daily) is an alternative Itraconazole for at least 12 months is recommended Lifelong suppressive therapy with itraconazole (200mg daily) may be required in immunosuppressed patients if immunosuppression cannot be reversed and in patients who relapse despite receipt of appropriate therapy

  21. Role of Prophylaxis in immunosuppressed patients • Prophylaxis with itraconazole (200 mg daily) is recommended in patients with HIV infection with CD4 cell counts <150 cells/mm3 in specific areas of endemicity where the incidence of histoplasmosis is 110 cases per 100 patient-years • Prophylaxis with itraconazole (200 mg daily) may be appropriate in specific circumstances in other immunosuppressed patients • Active histoplasmosis during the past 2 years • History of pulmonary infection, with radiographic findings showing infiltrates, nodules, or lymphadenopathy without a clear etiology; • Histoplasmaantigenuria; or anti-Histoplasma complement fixationantibodytiters >=1:32.

  22. CNS Histoplasmosis Liposomal amphotericin B (5.0 mg/kg daily for a total of 175 mg/kg given over 4–6 weeks) followed by itraconazole 200 mg 2 or 3 times daily) for at least 1 year and until resolution of CSF abnormalities, including Histoplasma antigen levels, is recommended Measure blood levels of itraconazole

  23. Take home points • Itraconazole is the preferred azole for initial therapy for patients with mild-to-moderate histoplasmosis and as step-down therapy after receipt of amphotericin B • Severe or moderately severe histoplasmosis -amphotericin B formulation initially • Monitor electrolytes, renal function, blood cell count • Measure Itraconazole drug levels during the first month • Hisoplasma urine or serum antigen to document response to therapy

  24. Questions?

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