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ID Subspeciality Rounds 12/9/08 Dr.Akshra Verma Dr.Janet Jokela.

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Presentation on theme: "ID Subspeciality Rounds 12/9/08 Dr.Akshra Verma Dr.Janet Jokela."— Presentation transcript:

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

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

3 Case PAST MEDICAL HISTORY: COPD, Spondylolisthesis, GERD, BPH, Hypertension, Diabetes with Nephropahty, CKD stage III PAST MEDICAL HISTORY: COPD, Spondylolisthesis, GERD, BPH, Hypertension, Diabetes with Nephropahty, CKD stage III Allergies: Iodine (loss of consciousness) Allergies: Iodine (loss of consciousness) Medications: Medications: 1. Actos 2. Byetta 3. Valsartan 4. Vicodin 1. Actos 2. Byetta 3. Valsartan 4. Vicodin 5. Diclofenac 5. Diclofenac SOCIAL HISTORY: Smoker 1PPD since age 14, quit 3 weeks ago. No alcohol. SOCIAL HISTORY: Smoker 1PPD since age 14, quit 3 weeks ago. No alcohol. 6. Prilosec 7. Flomax 8..Mometasone 9. Niacin 10. Lovastatin

4 Exam: T:97.6 °F P:119 BP: 97/58 RR: 23 O2 sat 98 % on 6L NC 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 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 and Legionella urine antigen- negative. Pneumococcal and Legionella urine antigen- negative. RSV negative. RSV negative. Mycoplasma antibody negative Mycoplasma antibody negative LAP: 280 LAP: 280

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

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

11 Clinical Presentation Asymptomatic pulmonary histoplasmosis Asymptomatic pulmonary histoplasmosis Symptomatic pulmonary histoplasmosis - Acute Symptomatic pulmonary histoplasmosis - Acute Subacute pulmonary infection weeks to months following exposure Subacute pulmonary infection weeks to months following exposure Fever, chills, headache, myalgia, anorexia, cough, and pleuritic chest pain (2-4 weeks 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 Coryza and sore throat are not typical - alternative diagnoses Radiographs- focal infiltrates and mediastinal or hilar lymphadenopathy Radiographs- focal infiltrates and mediastinal or hilar lymphadenopathy Diffuse reticulonodular/ miliary pulmonary infiltrates Diffuse reticulonodular/ miliary pulmonary infiltrates Chronic pulmonary histoplasmosis Chronic pulmonary histoplasmosis Xray- fibrotic apical infiltrates with cavitation 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 Lipid/Liposomal formulation of amphotericin B 3.0–5.0 mg/kg daily IV 3.0–5.0 mg/kg daily IV Deoxycholate formulation of amphotericin B Deoxycholate formulation of amphotericin B 0.7–1.0 mg/kg daily IV 0.7–1.0 mg/kg daily IV Itraconazole Itraconazole 200 mg 3 times PO daily for 3 days and then 200 mg once or twice PO daily 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 Other azoles-second line: Fluconazole, ketoconazole, posaconazole, voriconazole No role of echinocandins No role of echinocandins

15 Monitoring response to therapy Histoplasma antigenuria and/or antigenemia, levels decrease during therapy Histoplasma antigenuria and/or antigenemia, levels decrease during therapy Levels increase in 90% of those who relapse Levels increase in 90% of those who relapse Measure antigen levels 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 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-ModerateModerately Severe to Severe 1.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 Itraconazole for at least 1 year is recommended Montior Blood levels of itraconazole at 2 weeks to ensure adequate drug exposure Montior Blood levels of itraconazole at 2 weeks to ensure adequate drug exposure

18 Complications for Pulmonary Histoplasmosis Pericarditis Pericarditis Arthritis/ Erythema Nodosum Arthritis/ Erythema Nodosum Mediastinal lymphadenitis Mediastinal lymphadenitis Mediastinal Granuloma Mediastinal Granuloma Mediastinal Fibrosis Mediastinal Fibrosis Broncholithiasis Broncholithiasis Pulmonary Nodule 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-graphic findings and/or laboratory evidence of involvement of extrapulmonary tissues. Clinical illness that does not improve after at least 3 weeks of observation and that is associated with physical or radio-graphic findings and/or laboratory evidence of involvement of extrapulmonary tissues. Hepatosplenomegaly, mucosal ulcers, skin lesions, gastrointestinal involvement Hepatosplenomegaly, mucosal ulcers, skin lesions, gastrointestinal involvement Pancytopenia, progressive elevation of hepatic enzyme levels, increased lactate dehydrogenase level, and increased serum ferritin level. 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. 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-ModerateModerately Severe to Severe 1.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 2.Substitution of another lipid formulation at a dosage of 5.0 mg/kg daily 3.The deoxycholate formulation of amphotericin B (0.7–1.0 mg/kg daily) is an alternative 1.Itraconazole for at least 12 months is recommended 2.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) 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 Prophylaxis with itraconazole (200 mg daily) may be appropriate in specific circumstances in other immunosuppressed patients Active histoplasmosis during the past 2 years Active histoplasmosis during the past 2 years History of pulmonary infection, with radiographic findings showing infiltrates, nodules, or lymphadenopathy without a clear etiology; History of pulmonary infection, with radiographic findings showing infiltrates, nodules, or lymphadenopathy without a clear etiology; Histoplasma antigenuria; or anti-Histoplasma complement fixation antibodytiters >=1:32. Histoplasma antigenuria; or anti-Histoplasma complement fixation antibodytiters >=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 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 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 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 Severe or moderately severe histoplasmosis - amphotericin B formulation initially Monitor electrolytes, renal function, blood cell count Monitor electrolytes, renal function, blood cell count Measure Itraconazole drug levels during the first month Measure Itraconazole drug levels during the first month Hisoplasma urine or serum antigen to document response to therapy Hisoplasma urine or serum antigen to document response to therapy

24 Questions?


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