Extrapulmonary Tuberculosis

Transcription

1 Extrapulmonary Tuberculosis Timothy H. Dellit, MD Professor, UW Allergy & Infectious Diseases Associate Medical Director Harborview Medical Center No financial conflicts

2 Tuberculosis in King County : 100 cases, 5.0 per 100, : 87% Foreign-born PHSKC Seattle & King County Annual Tuberculosis Report 2014

3 Incidence of Pulmonary vs. Extrapulmonary TB Nationally: Pulmonary 69%, EXPTB 21%, Both 10% King County 2011: Pulmonary 40%, EXPTB 49%, Both 11% Harborview 2014: Pulmonary 62%, EXPTB, 29%, Both 10% Clin Infect Dis 2009;49: CDC Reported Tuberculosis in the United States 2014

4 Risk Factors for Extrapulmonary TB TB reference center in Portugal 1/2008-1/ (67.4%) pulmonary 126 (32.6%) extrapulmonary Rev Port Pneumol 2015;21:90-93

5 Extrapulmonary TB and Vitamin D Deficiency? Birmingham UK US CDC Extrapulmonary disease associated with: Female gender Non-white ethnicity Foreign-born Vitamin D deficiency Doubling serum 25(OH)D reduced risk (OR 0.55 CI 0.41 to 0.73) Thorax 2015;70:

6 Mycobacterium bovis Part of MTB complex 1-2% of human tuberculosis in US due to M. bovis Unpasteurized dairy Mono-resistance to PZA Emerg Infect Dis 2015;21: Clin Infect Dis 2008;47:

7 Sites of Extrapulmonary TB United States 2014 Other 20% Necrotizing granulomas Laryngeal 0% Lymphatic 38% Meningeal 5% Peritoneal 6% Genitourinary 5% Bone and Joint 10% Pleural 16% CDC Reported Tuberculosis in the United States 2014

8 Masquerading Extrapulmonary TB No initial airborne precautions in 10/14 (71%) Shizuoka Cancer Center Hospital Am J Infect Control 2014;42:

9 35 year old Vietnamese man presents to emergency department with three week history of worsening nonproductive cough, fever, night sweats, and right-sided chest pain. Thoracentesis is performed 1200 WBC 88% lymphocytes Total protein 5.4 LDH 358

10 Which of the following is MOST correct regarding Pleural TB? A. Pleural TB is a form of extra-pulmonary TB and hence, this patient is non-infectious B. Pleural fluid PCR is the most sensitive test for diagnosing pleural TB C. A negative TST rules out pleural TB D. Pleural biopsy should be performed, sending to both micro and pathology

11 Diagnosis of Pleural TB Diagnostic Approach Sensitivity Pleural fluid culture 10-40% Pleural biopsy culture 55-85% Pleural biopsy histology 50-80% Combined pleural biopsy culture and histology 80-95% Other tests: PCR Pleural fluid -Sensitivity 62%, specificity 98% -More sensitive in cases of culture-positive pleural fluid Pleural biopsy sensitivity 90%, specificity 100% Adenosine deaminase (ADA) Sensitivity 92%, specificity 90% Respir Med 2008;102: BMC Infect Dis 2004;4:6 Chest 2003;124:

12 Sputum and Pleural TB Sputum culture positive 10-30% Thought to be dependent on presence of infiltrate Are patients without concomitant pulmonary infiltrates non-infectious? 84 Patients with Pleural TB Pleural biopsy histology 66 (78%) Pleural biopsy culture 52 (62%) Pleural fluid culture 10 (12%) Induced sputum culture 44 (52%) No infiltrate on CXR: AFB smear (7/64) 11%, culture 35/64 (54%) Am J Resir Crit Care Med 2003;167:723-5

13 43 y o woman from Eritrea with 3 week h/o non-productive cough, fever, and night sweats

14 Now What? AFB smear neg x 5 (3 sputum, 2 BAL) Sputum PCR neg

15 Which of the following is the BEST approach? A. Remove from airborne isolation as a negative PCR test rules out infectious TB B. Begin 4 drug therapy and remove patient from airborne isolation due to multiple negative AFB smears C. Begin 4 drug therapy and keep in airborne isolation D. Obtain interferon-gamma releasing assay (IGRA) as a negative result would rule out TB

16 Miliary Tuberculosis Lymphohematogenous dissemination Millet seeds in lungs Impaired diffusion Sputum smear positive in only 1/3 High blood flow organs Spleen, liver, bone marrow, kidneys, adrenals Meningitis in 10-30% Increased TST anergy Lancet Infect dis 2005;5:415-30

17 26 y o woman from Ethiopia with left neck swelling

18 What is your initial diagnostic strategy? A. Surgical excision of all involved lymph nodes B. TST and empiric TB therapy C. FNA for histopathology and culture D. Treat with azithromycin for cat scratch

19 Symptoms % Cervical Tuberculous Lymphadenopathy Postgrad Med J 2001;77:185-7 Clin Infect Dis 2011; Importance of epidemiology Often multiple-matted lymphnodes FNA sensitivity > 90% Medical therapy for 6 months Paradoxical reaction in 20%

20 19 y o man from Guatamala with fainting spell 2 weeks PTA, then progressive frontal headaches with nausea and emesis. PE: T 39.6, left VI nerve palsy MRI with leptomeningeal enhancement in left temporal lobe CSF WBC 338 L60, protein 136, glucose 32 CSF HSV negative CSF TB PCR negative

21 How good are nucleic amplification tests for TB meningitis? A. Sensitivity 98%, specificity 56% B. Sensitivity 56%, specificity 98% C. Sensitivity 98%, sensitivity 98% D. Sensitivity 56%, specificity 56% Lancet Infect Dis 2003;3:633-43

22 CSF Characteristics California Encephalitis Project Characteristic CNS TB HSV-1 Enterovirus No. Cases CSF leukocytes per ml, median CSF protein, mg/dl, median CSF glucose, mg/dl, median CNS TB cases all culture positive 4/17 (24%) CSF TB PCR positive Emerg Infect Dis 2008;14:1473-5

23 In this patient Sputum AFB smear 1/3 positive Sputum AFB culture 3/3 positive CSF AFB culture positive

24 20 y o woman from Peru with 3 week history of fever, headache, nausea, and altered mental status. No respiratory symptoms. CSF: WBC 195 N70 prot 144, gluc 39 MRI: leptomeningeal enhancement along skull base involving cerebellar sulci and cranial nerves r/o TB check quantiferon

25 What is the role of Interferon-Gamma Release Assays (IGRAs) in diagnosing active TB? A. IGRAs are preferred to TST for the diagnosis of active TB due to increased sensitivity and specificity. B. A negative IGRA rules out activetb. C. A positive IGRA obviates the need for tissue biopsy. D. IGRAs may be useful adjunctive tests, but are not sufficient alone to diagnose active TB.

26 IGRAs and Extrapulmonary TB Sensitivity Specificity QFT-G a 69% 82% QFT-2G b 86% 84% TST b 57% 49% a Diagn Microbiol Infect Dis. 2009;63:182-7 b Respirology 2009;14:276-81

27 Pulmonary Involvement in Extrapulmonary TB 72 patients with XPTB 36 lymph nodes 12 pleura 6 CNS 6 GI 57 had sputum collection Weight loss associated with positive sputum cx OR 4.3 ( ) 25% 20% 15% 10% 5% 0% Chest 2008;134: % had abnormal CXR

28 Percent of Cases Sputum AFB Smear Smear+ Culture + Smear - Culture + Smear positive 5,000-10,000 organisms per ml of sputum must be present Smear negative, culturepositive TB Responsible for roughly 17% of TB transmission in San Francisco and Vancouver Smear - Culture % of pulmonary TB cases in King County are smear negative Am Rev Respir Dis 1966;95:998 Lancet 1999;353;444, Thorax 2004;59:286

29 Rapid Molecular Detection of Pulmonary TB and Rifampin Resistance Multi-center study of 1462 patients with suspected pulmonary TB (38.8%) smear and culture positive (11.9%) smear-negative, culture positive Sensitivity Smear positive, culture positive 98.2% Smear negative, culture positive (first sample) 72.5% Second sample 85.1% Third sample 90.2% Rifampin-resistance c/w phenotypic testing 97.6% N Engl J Med 2010;363:

30 Xpert MTB/RIF for Extrapulmonary TB Meta-analysis of 18 studies and 4461 samples WHO 2013 Xpert MTB/RIF should be used in preference to conventional microscopy and culture as the initial diagnostic test for CSF specimens from patients suspected of having TB meningitis (alternative for lymph nodes and other tissues) Eur Respir J 2014;44: Ann Intern Med 2015;162:JC11

31 19 y o man from Philipines presented with 8 weeks of HA and progressive LE weakness CSF WBC 120, 90L Protein 1500 Glucose 40 MRI with extensive basal leptomeningeal enhancement Role of intrathecal therapy? Role of CSF drug levels?

32 TB Drugs and CNS Isoniazid and pyrazinamide bactericidal and penetrate inflamed and uninflamed meninges Rifampin, streptomycin, and ethambutol levels roughly around MIC and do not penetrate uninflamed meninges as well After induction phase with 4 drugs, some may consider continuing INH, Rifampin, and Pyrazinamide Fluoroquinolones?

33 Intensified Therapy in TB Meningitis Randomized, double-blind, placebo controlled study in Vietnam Standard Therapy 3 months INH Rifampin (10 mg /kg) PZA Ethambutol Intensified 8 weeks Rifampin 15 mg/kg Levo 20 mg/kg Followed by 6 months INH and rifampin All received dexamethasone for 6-8 weeks N Engl J Med 2016;374:

34 CNS TB and Paradoxical Response Balance between host immunologic response and direct effects of mycobacterial products Neurological decline Increase in size, number, or appearance of tuberculomas Typically occur within 3 months of therapy In setting of tapering or discontinuing steroids Does not represent failure of therapy Do not need to change regimen TB meningitis May be associated with neutrophilic predominance More frequent development of tuberculomas Clin Infect Dis 1994;19: Infection 2003;31:387-91

35 29 y o man from Somali presents with seizures, chronic back pain, and difficulty urinating

36 Pott s Disease with Paravertebral Abscess Classically begins with anterior vertebral body and disk Progressive collapse, anterior wedging, and gibbus formation Posterior involvement of vertebral arch and spinous process N Am J Med Sci 2013; 5:

37 Spinal Tuberculosis Accounts for 50% of skeletal tuberculosis Hip 15%, knee 10% Hematogenously spread Batson s plexus Paucibacillary disease, slow growing months of therapy Medical therapy alone curative > 90% Surgery limited to neurologic compromise, spinal stability, tissue diagnosis MRI may initially demonstrate increase in bony destruction and size of abscess despite clinical improvement Clinical Orthopaedics and Related Research 2007;460:29-38 Clinical Orthopaedics and Related Research 2002;398:11-19

38 44 y o Vietnamese man with 6 month h/o pain and swelling of left medial thigh associated with fevers and night sweats

39 27 y o man from Ethiopia with 2 day h/o severe abdominal pain, nausea and emesis Also 2 month h/o fever, night sweats, 15 lb wt loss, and dry cough

40 Could he have pulmonary involvement?

41 Tuberculosis of Small Bowel Pathogenesis Swallowing infected sputum Ingestion of contaminated milk Hematogenous spread Direct extension Ileocecal and jejuno-ileum most common sites Patterns Ulceroconstrictive lesions, with perforation and fistulae in 5% Obstruction in 20% Right lower quadrant abdominal mass 25% Doughy abdomen classic, but less common Mimics Periappendiceal abscess, Crohn s disease, Yersinia, Amebiasis

42 Symptom % Peritoneal Tuberculosis Ascitic Fluid Exudative Lymphocytic pleocytosis Protein > g/dl SAG < 1.1 g/dl Diagnositics AFB smear < 3% AFB culture 20-83% ADA % Laparoscopy with biopsy 85-95% Am J Gastroenterol 1993;88: Colorectal Dis 2007;9:773-83

43 25 y o man from Mexico with 2 month history of fever, chills, night sweats, cough, and 30 lb wt loss Also dysuria with 3+ WBC and RBC Sputum 4+ AFB

44 Urogenital Tuberculosis May present with dysuria, hematuria, or flank pain Asymptomatic patients with classic sterile pyuria Men Kidney, prostate, seminal vesicles, epididymis, testes Oligospermia Women Endosalpinx with spread to peritoneum, endometrium, ovaries, cervix, vagina Pelvic pain, infertility, vaginal bleeding Mycobacterial culture of early morning urine specimens Am Fam Physician 2005;72:1761-8

45 For which of the following would you use adjunctive steroids? A. Tuberculous peritonitis B. Tuberculous pleurisy C. Tuberculous pericarditis D. Tuberculous meningitis E. C and D F. B, C, and D

46 Tuberculous Meningitis and Steroids Seven Randomized Studies RR CI Death Stage 1 (mild) Stage 2 (moderate) Stage 3 (severe) Death or disabling neurologic deficit Death stratified by HIV status Cochrane Database Syst Rev Jan 23;(1):CD002244

47 Tuberculous Meningitis and Steroids 545 patients randomized to double-blind placebo controlled study of adjunctive dexamethasone with 5 year follow up (9.2% lost) Two-year survival: 0.63 vs (p=0.07) Five-year survival: 0.54 vs (p=0.51) PLoS One 2011;6:e27821

48 TB Pericarditis and Steroids: Changing recommendations Multicenter randomized study comparing prednisolone vs. placebo in 1400 adults with TB pericarditis NEJM 2014;371:

49 Summary Tuberculosis can occur anywhere within the body Diagnosis can be extremely challenging Microbiology Pathology Nucleic amplification TST vs. interferon-gamma release assays? Evaluate for pulmonary disease Coordinated management with public health