Extrapulmonary Tuberculosis

Transcription

1 Extrapulmonary Tuberculosis Randall Reves, MD, Colorado University Denver, volunteer TB Clinician Denver Metro TB Control Program Slides adapted from originals by Timothy H. Dellit, MD, Harborview Medical Center No financial conflicts US Reported TB Cases by Site (14 yrs) Total US reported cases 253,299 EPTB only 47,293 (19%) Both EPTB & PTB 14,910 (6%) Disseminated TB 4,478 (2%) PTB only 186,540 (74%) Unknown - < 1% Peto, et. al CID 2009;49: Peto. CLIN INFECT DIS 49(9): Extrapulmonary TB, U.S (n=47,293, 19% of cases)) 1

2 Incidence of Pulmonary vs. Extrapulmonary TB Nationally: Pulmonary 69%, EXPTB 21%, Both 10% Clin Infect Dis 2009;49: CDC Reported Tuberculosis in the United States 2014 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: Mycobacterium bovis: more likely extrapulm. but most still pulmonary Part of MTB complex 1-2% of human tuberculosis in US due to M. bovis Unpasteurized dairy Mono-resistance to PZA 62.5% pulm. Emerg Infect Dis 2015;21: Clin Infect Dis 2008;47:

3 35 year old Vietnamese man in ED: 3 weeks of worsening non-productive cough, fever, night sweats, and right-sided chest pain. Thoracentesis: 1200 WBC 88% lymphs Total protein 5.4 LDH y.o. homeless woman with TST conversion but no symptoms April 09 April y.o. homeless woman: pleural bx nondiagnostic, sputum sm (-)/cult + April 09 July 09 3

4 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 80-95% culture and histology 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: y o woman from Eritrea with 3 week h/o non-productive cough, fever, and night sweats Now What? AFB smear neg x 5 (3 sputum, 2 BAL) Sputum PCR neg 4

5 Miliary Tuberculosis Lymphohematogenous dissemination Millet seeds in lungs* Impaired diffusion Sputum smear positive in 1/3 High blood flow organs Spleen, liver*, bone marrow*, kidneys*, adrenals Meningitis* in 10-30% Increased TST anergy *Potential positive specimens: sputum, BAL, urine, stool, CSF, tissue biopsies, rarely blood Lancet Infect dis 2005;5: y.o. man with chronic renal failure Chronic hemodialysis for polycystic disease Hepatitis C due to IDU Hospitalized from prison for fever and hemoptysis Left pleural effusion developed Fever persistent despite ceftriaxone & azithro Worsening anemia, mild pancytopenia, rising alkaline phosphatase 42 y.o. man with chronic renal failure Sputum AFB smear & culture negative PPD 8 mm Transudative pleural fluid not cultured for TB Bone marrow biopsy neg for granuloma no AFB culture done! Discharged after response to levofloxacin 5

6 42 y.o. man with CRF: clues for TB Right apical scar Rising alk phos? granulomatous hepatitis Liver biopsy recommended 43 y.o. with CRF: readmitted 2 wks later liver biopsy done transjugular: granulomas, AFB stain & culture-negative 43 y.o. man with CRF treated empirically for TB Symptoms resolved Anemia improved Alkaline phos returned to normal All cultures remained negative Reported as a clinical case of TB 6

7 47 yr old woman Swollen cervical lymph node x 1 month Denies other symptoms Born in Vietnam and previously treated for TB 20 years ago 47 yr old female: sputum negative Node biopsy is smear (+) and confirms INH resistant TB HIV (-) 6 weeks into therapy, the inflammation is worse 47 yr old female: needle drainage 7

8 Cervical Tuberculous Lymphadenopathy Symptoms % 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% 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 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:

9 75 y.o. Peruvian-born woman with erythema induratum for 6 years May 09 Nov y.o. woman: cultures negative, response to IRE for 2 mo., IR for 4 Nov 09 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:

10 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 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 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? 10

11 TB Drugs and CNS INH & PZA - bactericidal and penetrate inflamed and uninflamed meninges RIF, streptomycin & EMB - do not penetrate uninflamed meninges as well Fluoroquinolones penetrate CSF Is there a role for treatment intensification Higher dose RIF, adding FLQ? Continuing PZA and/or adding cycloserine or ethionamide throughout 9 months of therapy? Intensified Initial Therapy in TB Meningitis: No Benefit Randomized, double-blind, placebo controlled study in Vietnam, n=817, 43% HIV+ Standard Therapy 3 months INH Rifampin (10 mg /kg) PZA Ethambutol Intensified 8 weeks Rifampin 15 mg/kg Levo 20 mg/kg Followed by 7 months INH and rifampin All received dexamethasone for 6-8 weeks Mortality 28% in STD and Intensive Note: INH-res.: 39% (16/41) vs 24% (11/45), p=0.06 N Engl J Med 2016;374: 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:

12 33 y.o. man with LTBI & DM TST 16 mm 7 yrs ago Developed diabetes mellitus Started on INH with 25 mg pyridoxine Had a seizure at home after 2 weeks PCP thought cause was hypoglycemia Repeat seizure 3 weeks later 33 y.o. with 2 nd seizure 33 y.o. on INH with brain mass Seizures controlled with phenytoin Tuberculoma removed at craniotomy AFB stains negative IRZE started post-op Are there drug interactions to consider? 12

13 29 y o man from Somali presents with seizures, chronic back pain, and difficulty urinating 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: 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:

14 44 y o Vietnamese man with 6 month h/o pain and swelling of left medial thigh associated with fevers and night sweats 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 Could he have pulmonary involvement? 14

15 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 Peritoneal Tuberculosis Ascitic Fluid Exudative Lymphocytic pleocytosis Protein > g/dl SAG < 1.1 g/dl Symptom % Diagnositics AFB smear < 3% AFB culture 20-83% ADA % Laparoscopy with biopsy 85-95% 0 Am J Gastroenterol 1993;88: Colorectal Dis 2007;9: y.o. woman: nursing home pneumonia BAL culture: K. pneumonia Living independently till admission 3 mo. earlier for failure to thrive pancreatic mass, no biopsy Imipenem/cilastin + gentamicin 15

16 96 y.o. woman: nursing home pneumonia Improved over 1 wk Expired on 9 th day BAL culture grew M. tuberculosis, drugsusceptible No known TB exposure Visited twin sister in IL one month prior to health deterioration 96 y.o. woman: presumptive pancreatic TB Complex mass/fluid extending into LUQ,? infection Mass contained calcifications, consistent with pancreatic TB Assessment: death due to pancreatic TB with dissemination; probably infected in childhood 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 16

17 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: 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):CD 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:e

18 TB Pericarditis and Steroids: Changing recommendations Multicenter randomized study comparing prednisolone vs. placebo in 1400 adults with TB pericarditis NEJM 2014;371: y.o. Cambodian-born woman in US 30 yrs 4 months s/p 2 nd CABG & Mitral Valve Repl. High-pressure fluid collection in pacemaker pouch Epicardial wires removed M.tb on culture Presumed origin: pericardial TB Kestler, Int J Tuberc Lung Dis 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 18