TB Intensive Tyler, Texas December 2-4, 2008

Transcription

1 TB Intensive Tyler, Texas December 2-4, 2008 TB Case Presentations Douglas B. Hornick, MD December 3, 2008 Pulmonary Fascinomas with a Tuberculous Attitude Douglas B. Hornick, MD Professor University of Iowa College of Medicine Iowa City, Iowa 1

2 Ponder These Cases Proactive vs. Passive TB diagnosis University TB Speechless in Waterloo Gee whiz Granulomas Galore! Paradox Gee whiz too It s back Screening Early TB Detection 21 yo University student just arrived from India Screening program for new foreign students: + TST Asymptomatic, no exposure to active TB, +BCG hx, no HIV risk factors Chest x-ray (RUL small round cavitary infiltrate Made A Alim, referred by Fritzsche 2

3 More Data Unable to produce sputum in clinic, no AM sputum Bronchocopy: Transbronchial Bx negative, BAL AFB smears negative Two weeks elapses; Still asymptomatic; Balky What would you do now? Chest x-ray shows same RUL findings & evidence for new process LUL More Data Rx: INH, rifampin, pyrazinamide, & ethambutol, daily DOT (from date of abnormal chest x-ray) Four weeks: BAL cultures: Mycobacterium tuberculosis Six weeks: Susceptibilities show INH resistance Chest x-ray slightly improved What now? Add quinolone? Do you add 2 drugs? Do you stop INH & continue other meds? 3

4 Recall Basic Principles TB Rx Start Rx immediately upon suspicion for active TB Principles that underlie initiation of 4 drugs for active TB Use drugs to which the bugs are sensitive The more bugs, the more drugs Ensure adherence to Rx (DOT) Never add a single drug to a failing regimen INH Resistant TB Rx No reference studies Daily supervised Rx (not 2 or 3x/week) Consider extending Rx to 9 or 12 months Treatment options, stop INH and If pyrazinamide during 1 st 2 mos, continue rifampin & ethambutol x 9 mos. If PZA not used initially, use rifampin & ethambutol x12 mos If extensive disease: rifampin, pyrazinamide, & ethambutol plus quinolone (levo- or moxifloxacin) If responding, adding quinolone doesn t violate do not add single drug rule 4

5 INH Resistant TB Rx No reference studies Daily supervised Rx (not 2 or 3x/week) Consider extending Rx to 9 or 12 months Treatment options, stop INH and Rifampin, pyrazinamide, & ethambutol x 6 months If extensive disease: rifampin, pyrazinamide, & ethambutol plus quinolone (levo- or moxifloxacin) If responding, adding quinolone doesn t violate do not add single drug rule ATS, CDC, IDSA Guidelines 2003 Rest of the story Rifampin, ethambutol, pyrazinamide (daily DOT) continued x 9 months Chest x-ray complete resolution at end of Rx 5

6 Examples of Early TB Cases Detected Through Screening TST +, asymptomatic, CXR abnormal, sputum often AFB smear negative (culture positive) General: Less severe disease, easier to cure Seattle-King County: 11% of TB cases identified via screening Yield of screening varies (case detection/screened): Immigrants/refugees B1, B2 classification: 2-14% Homeless shelter (outbreak): 3.1, 4.3 % Contact investigations: 1-3% Inner City residents seeking SS: 0.5% Homeless Shelter (routine): 0.18, 0.36% Correctional facility intake: 0.07, 0.17% University intake foreign born students:???? CDC: MMWR Rec & Reports 54(RR12) 2005 Screening Early TB Detection +TST, BCG hx, Subtle CXR infilt., Smear-, Culture+ Comprehensive TB screening of foreign-born students Active cases occasionally surface: +TST, asymptomatic, BCG, Balky Subtle, non-cavitary chest x-ray infiltrate Smear negative, culture positive (AM sputum x3) Bronchoscopy in many but not all Note: Smear negative, culture negative uncommon Often faster response to treatment (small organism burden) Successful management: Teamwork Vigilant/Supportive Student Health Service University Administration ($ for testing, QFT-G) Department of Public Health Unique TB Presentation Proactive instead of Passive Process 6

7 R Upper Lobe Bronchus Intermedius Viet Nam Korea Philippines Screening Early TB Argentina Malaysia Smear-, Culture- India Case 41 yo WF, rural Iowa, NH aid, HIV-, no IVDA, no travel 1995 PPD+, CXR normal, INH x6 mos 1999, 2000 Chest X-ray: bilateral UL infiltrates First Episode 12/01 Hemoptysis, smear/culture positive, CXR bilateral UL infiltrates No contact conversions outside of immediate family (no NH contacts) Rx (?DOT) x 6 months: INH 300, Rif 600, PZA 500 daily x 4 weeks INH 750, Rif 600, PZA 3000 twice/week x4 weeks 12 weeks smear & cultures negative INH 750, Rif 600 twice/week x16 weeks Relapse 8/02 Smear/culture positive Pansusceptible TB, No new cases in contacts & NH CXR bilateral UL infiltrates 7

8 Received standard ATS/IDSA/CDC Rx DOT x9 months Smear & Culture - by 4mos Asymptomatic 6 months after Rx completion Sputum smear/culture negative It s Back 12/05 (~3 years later) Relapse 2 Pan susceptible TB; DNA fingerprinting: all isolates identical No new cases in contacts & NH CXR bilateral UL infiltrates, RUL more dense & cavitary Analogous case: 31 yo Bosnian male, relapse 2 Well documented DOT for prior 2 Rx courses From a county w/ experience & good track record for DOT Complete immunodeficiency w/u nothing useful DNA fingerprinting: all isolates identical Do you see this? What would you do in these cases? Both patients received daily DOT x 12 mos (+PZA) 8

9 (After r/o drug resistant TB) Suggestions Add PZA to regimen for increased intracellular therapeutic activity Check serum drug levels increased doses required Peloquin lab, National Jewish Check isolates against database strains which are prone to relapse (not d/t drug resistance, not necessarily related to virulence/contagion) Steve Holland lab, NIAID Patrick Moonan lab, CDC Case 41 yo WF, rural Iowa, NH aid, HIV-, no IVDA, no travel 1995 PPD+, CXR nor mal, INH x6 mos 1999, 2000 Chest X-ray: bi lateral UL infiltrates First Episode 12/01 Hemoptysis, smear/culture positive, CXR bilateral UL infiltrates No contact co nversions outside of immediate family (no NH contacts) Rx (?DOT) x 6 months: INH 300, Rif 600, PZA 500 daily x 4 weeks INH 750, Rif 600, PZA 3000 twice/week x4 weeks 12 weeks sme ar & cultures negative INH 750, Rif 600 twice/week x16 weeks Relapse 8/02 Smear/culture po sitive Pansusceptib le TB, No new DOT cases x9 in months contacts & NH Smear & Culture- by 4mos CXR bilateral UL infiltrates Sputum smear/culture negative Received standard ATS/IDSA/CDC Rx Asymptomatic 6 months after Rx completion 9

10 It s Back 12/05 (~3 years later) Relapse 2 Pan susceptible TB; DNA fingerprinting: all isolates identical No new cases in contacts & NH CXR bilateral UL infiltrates, RUL more dense & cavitary Analogous case: 31 yo Bosnian male, relapse 2 Well documented DOT for prior 2 Rx courses From a county w/ experience & good track record for DOT Complete immunodeficiency w/u nothing useful DNA fingerprinting: all isolates identical Do you see this? What would you do in these cases? Both patients received daily DOT x 12 mos (+PZA) (After r/o drug resistant TB) Suggestions Add PZA to regimen for increased intracellular therapeutic activity Check serum drug levels increased doses required Peloquin lab, National Jewish Check isolates against database strains which are prone to relapse (not d/t drug resistance, not necessarily related to virulence/contagion) Steve Holland lab, NIAID Patrick Moonan lab, CDC 10

11 JP: 4 mos Rx, 2 nd Relapse JP: 7 mos Rx, 2 nd Relapse OA: 9/05 Relapse 2 OA: DOT daily x 4 drugs 3/06 11

12 Unusual Extrapulm TB Case(s) 66 yo mildly mentally retarded male who lives alone Presented with rectal pain & biopsy showed inflammation c/w Crohns disease Rectal/GI symptoms worsened despite Prednisone Referred UIHC evaluation starting Inflixamab Chest x-ray abnormalities raised concerns Unable to produce sputum, TST negative Thoracentesis: yellow fluid, exudate, ph 7.25, WBC 14K (12K PMNs, 0.1K L) Gram stain: Many WBCs, no organisms; AFB negative What next? Pleural biopsy: No granulomas Acute Inflammation w/ many AFB Subsequent sputum AFB smear positive Rest of the story: Retrospective AFB stain of rectal biopsy: sheets of AFB (No Granulomas!) W/u for immune deficiency: HIV, INF & other immune deficiency negative Organisms pan susceptible DOT (daily) Treatment: 4 drugs x 2 months, then INH/Rif x 9 months Cured; no relapse or other infections (f/u 2 yrs after finishing Rx) 12

13 Gee Whiz Pleural/Pulmonary/Rectal TB Dangerous TB Case: Unsuspected plus steroid Rx AFB positive, no granulomas! (?immunodeficiency) Pleural TB Small number of organisms cause extensive reaction (hypersensitivity) Pleural fluid: lymphocyte predominant, low ph, AFB smear & culture positive ~20%, elevated adenosine deaminase Pleural biopsy w/ culture: positive ~75% (x2, to 90%) Check out the far end of the pleural infection spectrum 18-year-old man w/ no clinically significant medical history, six-month history of an increasing mass on the left side of his back (Panel A) 3 days before seen Serous drainage from L chest CT: Pleural nodules, empyema fluid encasing L lung & leaking out Pleural fluid & bx negative AFB, but granulomas & culture positive Empyema Necessitatis Chaiyasate, K. et al. N Engl J Med 2005;352:e8 13

14 TB Laryngitis Case 31 yo Bosnian female w/ hoarseness, neck swelling, pain & dyspnea worsening over 5 months. ENT: ulcerated lesions on epiglottis & VC Biopsy: granulomas, but no AFB, culture negative Neck LN needle: lymphocytes, no AFB, not cultured Neck CT: bilateral adenopathy Radiologist noted infiltrates could be seen in few cuts that showed upper lung fields! Past Hx: TST positive 1 yr previous, CXR showed upper lobe infiltrates, sputum smears x3 negative, Rx stopped after ~14days (pt refused/disappeared) 14

15 Any cavitation? How would you treat? Culture showed pan-susceptible TB Isoniazid, Rifampin, Pyrazinamide, & Ethambutol (all x 2 months, then INH/Rif) twice weekly DOT. 15

16 Outcome Public Health: Although sputum 3+ smear positive, Oto MD/staff already TST+ didn t become re-infected. Patient: Hoarseness, neck pain/swelling & dyspnea resolved quickl y on Rx Standard DOT x9 months (no relapse >2 y rs f/u) Midpoint 6 mos post Rx Speechless in Waterloo Laryngeal TB Symptoms by frequency: hoarseness, dys-, odynophagia Presentation varies w/ TB epidemiology: High rate untreated TB: Manifestation a/w extensive cavitary TB in lung Ulcerative lesions VC, posterior larynx d/t supine & pooling infectious secretions Effective Rx & HIV era still common a/w cavitary lung ds but Can be initial TB manifestation d/t lymphohematogenous spread: HIV: Sentinel opportunistic infection Non-HIV: Reactivation Anterior laryngeal lesions (hypertrophic & ulcerative less often) Biopsy recommended: TB lesions mimic Squamous Cell Ca biopsy those w/ RF for laryngeal Ca overlap w/ typical TB population. TB Rx results in resolution within weeks VC fibrosis & permanent hoarseness rare complication 16

17 Disseminated TB Case 32 yo female Grad student (Chemistry) from India w/ cough, DOE, & fever x2 wks 8 months previous: Arrived in US, TST negative x2 (1 st 6 mos in Texas, roommate Rx for TB), HIV neg, CXR normal CXR abnormal Pleural fluid: bloody, exudate, ph 7.44, Gm stain: many WBC, No organisms; AFB negative Dx: CAP w/ uncomplicated parapneumonic effusion All bacterial cultures negative, sputum AFB neg, TST neg, HIV neg D/C home (azithromycin/cefpodoxime) after 4 days in hospital Note: fever on da y of discharge (Na 130) 17

18 She s Back 2 weeks post d/c, friends bring SJ to ER: couple days of weird behavior, then confused, aphasic Na 128 Head CT: L frontal lobe hemorrhage & edema; at least 5 <1 cm ring enhancing lesions Brain MRI: L frontal lobe edema; many <1 cm ring enhancing lesions (at least 11 in both lobes of cerebellum!) 18

19 Now What? DDx: Bacterial cerebritis, Toxoplasmosis, disseminated Histo or TB Rx: ceftriaxone, flagyl, pyrimethamine, amphotericin B, Isoniazid, Rifampin, Pyrazinamide, & Ethambutol!! Work-up continues: Unable to produce sputum for AFB smears Chest CT: nonspecific diffuse, bilateral nodular infiltrate, pleural Massive Grand Mal seizure ICU, respiratory failure, mechanical ventilation effusion improved Bone marrow: multiple granulomas, fungus/afb stains neg Liver biopsy: necrotizing granulomas, fungus/afb stains neg Trach aspirate: fungus/afb stains negative VATS lung & pleural biopsy: necrotizing granulomas, fungus/afb stains negative Stool & small bowel aspirate: fungus/afb stains negative Repeat trach aspirates x3: on one, a single AFB seen! 3 weeks later: Liver, pleural, lung biopsies, & trach aspirates all grow pan-susceptible M. tuberculosis Granulomas Galore! Outcome: DOT x9 mos (no recurrence), L frontal encephalomalacia, residual seizures (less frequent w/ time), minimal R hemiplegia & cognitive defects (improved w/ time) Disseminated TB (non HIV) CNS TB (non HIV) Very young children; patients >60 Primary or reactivation; granulomas in multiple organs TST negative 25-40% Sputum for AFB negative in most cases Lung radiographs: multiple sm. nodules (1-2 mm) miliary For diagnosis: Biopsy organ most involved (symptoms) & send culture Rx: no different than pulmonary TB Notoriously difficult diagnosis Many have no lung disease, nonspecific symptoms (HA, low grade fever) initially, then progress to confusion, CN palsy, hemiplegia CSF: high protein, lymphocytosis, AFB smear & culture low yield (PCR disappointing tuberculostearic acid by GLC very sensitive, where available) Steroids recommended (CN palsy, cerebral edema, CSF protein) High index of suspicion for TB required! 19