Tanya Van, M.D. has the following disclosures to make:

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1 Imaging of Pulmonary Mycobacterial TB Infection Tanya Van, M.D. April6, 2016 TB Intensive April 5 8, 2016 San Antonio, TX EXCELLENCE EXPERTISE INNOVATION Tanya Van, M.D. has the following disclosures to make: No conflict of interests No relevant financial relationships with any commercial companies pertaining to this educational activity 1

2 Imaging of Pulmonary Mycobacterial TB Infection Tanya Van, M.D. Assistant Clinical Professor Department of Radiology University of Texas Health Science Center San Antonio A Note Appreciation and Thanks For the invitation to address you today For much of the material you will view today Dr. Michael McCarthy, Retired UTHSCSA Dr. Santiago Restrepo, UTHSCSA Dr. Amy Mumbower, UTHSCSA Dr. Ken Kist, UTHSCSA 2

3 Radiologist, TCID Disclosures Does TB still matter? The world seems full of tragedies. Wars, poverty and repression are daily headlines. Newspapers report new infectious diseases in every edition. 3

4 TB is still one of the most dangerous diseases in the world Plague (in the US): ~1 life MERS: ~ 200 lives Flu (in US): ~2300 lives Ebola: ~20,000 lives Malaria: ~600,000 lives HIV: ~1,500,000 lives TB: ~1,500,000 lives TB is significant in the US In 2013, a total of 9,588 new tuberculosis (TB) cases were reported in the United States, with an incidence rate of 3.0 cases per 100,000 population The proportion of TB cases occurring in foreign-born persons continues to increase, reaching 64.6% in

5 TB is significant in Texas Four states (California, Texas, New York, and Florida), home to approximately one third of the U.S. population, accounted for approximately half the TB cases reported in The proportion of TB cases occurring in these four states increased from 49.9% in 2012 to 51.3% in In 2014, 1,269 cases of tuberculosis (TB) were reported in Texas, a rate of 4.7 per 100,000 (DSHS). Goals Review common imaging (XR and CT) appearance of: Primary TB Post-Primary (reactivation) TB TB in Immune compromised/hiv-infected adults Complications including Extrapulmonary TB Role of imaging in dx and management of these patients 5

6 Commonly Encountered Patterns/Findings in Thoracic Imaging Lung disease Air space opacity / Consolidation Interstitial opacity Atelecasis Nodules and masses Cysts and cavities Lymphadenopathy Pleural abnormalities General Information Imaging has a valuable role in diagnosis of TB, however. Definitive diagnosis via detection/culture of AFB in sputum, bronchiolar lavage sample and/or pleural fluid specimen 6

7 General Information Once infection occurs, disease course depends on interaction between host response and virulence of organism If organism overpowers host defenses, disease progresses either locally or in other parts of the lung or body after spread via airways, lymphatic vessels, or bloodstream Tendency toward more fulminant disease in immunocompromised hosts If host factors prevail, gradual healing occurs and sometimes parenchymal scars that may calcify are left behind which can be seen on CXR (although frequently chest XR is normal) Years after initial infection, if immune status is weakened, disease may manifest / reactivate. Most typically classified imaging wise as Primary vs. Post-primary Disease Pulmonary Tuberculosis Primary TB No prior exposure to disease with exposure occurring via air-borne route Frequently asymptomatic or sub-clinical; thus not typically detected clinically or radiographically and often heals without treatment When clinically detectable disease does occur, typically in infancy/childhood (<5), elderly, immunosuppressed Post-primary TB Prior exposure to disease (previous sensitization) Disease of adulthood (and adolescence) Usually symptomatic and progressive without treatment 7

8 Goals Review common imaging appearance of Primary TB (including in children) Post-Primary or reactivation TB TB in Immunocompromised/HIV-infected adults Complications including Extrapulmonary TB Role of imaging in dx and management of these patients Primary TB Infection After inhalation of infected droplets, alveolar macrophages ingest and kill organism with variable success, depending on host resistance and organism virulence Macrophages may be overwhelmed and burst with released bacilli spreading via lymphatics and bloodstream In patients with intact immune systems, growth usually arrested by development of cell-mediated immunity and delayed hypersensitivity and patients remain asymptomatic Most lesions (2/3) heal without further manifestations, sometimes taking up to 2 years to resolve CXR is usually normal In the remaining 1/3, a scar forms in the region which calcifies in up to 15% of cases Some of the bacilli within these healed lesion remain dormant and viable for many years.. 8

9 Primary TB Infection Referred to as latent TB infection May be detected by positive PPD tuberculin skin test, whole-blood interferon-γ assay (e.g. QuantiFERON or T-SPOT) or bacterial DNA analysis Radiologically identifiable calcification at site of primary lung infection and/or in regional lymph nodes Ghon focus = calcified pulmonary nodule Ranke/Ghon Complex = calcified mediastinal/hilar node(s) with the calcified pulmonary nodule Ghon Focus Courtesy: Dr. Santiago Restrepo 9

10 Ghon Focus and Ghon/Ranke Complex Courtesy: Dr. Santiago Restrepo Imaging in PMTB If immune status is compromised at time of initial exposure (such as in extremes of age, alcoholics, HIV etc), the infection manifests as DISEASE. Imaging findings including: Lymphadenopathy Lung parenchymal disease Consolidation and/or atelectasis Pleural effusion Miliary disease 10

11 Lymphadenopathy Hallmark of primary dz 95% of children and 45% of adults Right hilar/ paratracheal 2/3 Bilateral 1/3 Courtesy: Dr. Santiago Restrepo Lymphadenopathy Hallmark of primary dz 95% of children and 45% of adults Right hilar/ paratracheal 2/3 Bilateral 1/3 CT more sensitive Nodes often have lowattenuation center Highly suggestive of active disease Courtesy: Dr. Santiago Restrepo 11

12 LAD immunosupressed young male Courtesy: Dr. Santiago Restrepo Lymphadenopathy DDX Atypical mycobacterial or other atypical infections Lymphoma Metastases 12

13 Consolidation may involve entire lobe Right>Left with slight basal predominance Cavitation uncommon Parenchymal Disease DDX Often indistinguishable from other bacterial pneumonias aside from adenopathy Malignancy and vasculitides are also in ddx Courtesy Dr. Santiago Restrepo 3 y.o. Atelectasis Enlarged lymph nodes cause extrinsic airway compression/collapse Results in volume loss and abnormal parenchymal opacity More often seen in children Courtesy: Dr. Santiago Restrepo 13

14 Atelectasis Often better appreciated on CT.. CT will also better characterize the extent of associated adenopathy and degree of airway compromise Courtesy: Dr. Santiago Restrepo Pleural Effusion Usually small and unilateral May be sole manifestation of the disease Usually 3 7 months after initial exposure Empyema and bronchopleural fistulas may occur as complication Residual pleural thickening and calcification may also later be seen 14

15 Take Home --- Primary Disease Clinical infection may or mayn t follow first exposure CXR often normal Ghon focus: local infection may be calcified Ranke complex: local infection with lymph node spread also may be calcified (latent TB infection) If DISEASE develops Adenopathy is hallmark!! Common in children, less common in adults Air-space consolidation, may be lobar, often slow to clear Atelectasis in kids secondary to airway compression Pleural effusion may be seen with/without lung disease Cavitation and miliary spread uncommon Goals Review common imaging appearance of Primary TB (including in children) Post-Primary or reactivation TB TB in Immunocompromised/HIV-infected adults Complications including Extrapulmonary TB Role of imaging in dx and management of these patients 15

16 Post Primary Disease Endogenous reactivation of latent dz Years after initial infection Typically in setting of decreased immune status On imaging most often see: Consolidation/Cavitation ***** Less often Pleural effusion and rarely LAD Miliary disease Consolidation and cavitation are most common Lung disease Typically seen in the posterior segments of upper and superior segments of lower lobes Relative high oxygen tension and decreased lymphatic drainage in these segments 16

17 Lung disease Cavities evident on CXR in about 50% of cases (better visualized on CT) These patients expel higher # of aerosolized organisms Walls may be thin and smooth or thick and nodular air-fluid levels may be seen Lung Disease May manifest as solitary pulmonary nodule (tuberculoma) usualy circumscribed but can be spiculated Endobronchial spread encountered as 2-4 mm nodules distributed in a segmental or lobar distribution with/without branching linear opacities (tree-in bud) when necrotic focus of dz communicates with bronchial tree ~20% of cases typically lower (dependent) lung zones These are all signs of ACTIVE DISEASE!!!! 17

18 Tuberculoma Courtesy: Dr. Santiago Restrepo Lung Disease May manifest as solitary pulmonary nodule (tuberculoma) usualy circumscribed but can be spiculated Endobronchial spread encountered as 2-4 mm nodules distributed in a segmental or lobar distribution with/without branching linear opacities (tree-in bud) when necrotic focus of dz communicates with bronchial tree ~20% of cases typically lower (dependent) lung zones These are all signs of ACTIVE DISEASE!!!! 18

19 Tree in Bud Courtesy: Dr. Santiago Restre 19

20 Multi-drug Resistant TB Courtesy: Dr. Santiago Restrepo 20

21 Courtesy: Dr. Santiago Restrepo Courtesy: Dr. Santiago Restrepo 21

22 DDX Cavitary Consolidation Other infections Histoplasmosis, Coccidiodomycosis, Blastomycosis, Nocardia, Staph, etc. Malignancy Vasculitides Pleural Disease Usually effusions are small and associated with parenchymal disease Typically septated/loculated and can remain stable in size for many years Pleura may become thickened, which can result in a tuberculous empyema and bronchopleural fistulas 22

23 Courtesy of Dr. Michael McCarthy Adenopathy only about 5% of patients with postprimary disease 23

24 Take Home Points Post Primary DZ From reactivation of latent infection, occurs in approximately 5% of pts with LTBI adult patients, generally during time of relative immune incompetence Associated with progressive disease without treatment Imaging findings: Poorly defined consolidation upper lobe/sup seg LL Cavitation Endobronchial spread of disease LAD and effusions less common vs primary dz Miliary disease Goals Review common imaging appearance of Primary TB (including in children) Post-Primary or reactivation TB TB in Immunocompromised/HIV-infected adults Complications including Extrapulmonary TB Role of imaging in dx and management of these patients 24

25 Immunocompromised patients Significantly higher prevalence vs. general population May have pulmonary involvement, extrapulmonary disease or both, and compared to other populations, prevalence of extrapulmonary involvement is significantly higher Also more likely to be infected with multidrug resistant TB organism HIV and TB Imaging manifestations in HIV patients depends on CD4 count Relatively preserved immunity (CD4 above 200) usually post-primary pattern of disease Upper lobe consolidation, cavitation and nodules usually without pleural effusion or LAD If CD4 200 below usually disease resembling primary MTB Adenopathy, consolidation, pleural effusion and miliary disease Often LAD is dominant or only finding, often necrotic 25

26 Findings: RLL consolidation Right paratracheal adenopathy DDx: Community acq. pnm Malignancy Courtesy of Dr. Michael McCarthy Findings: Right Hilar Adenopathy DDx: Malignant mets vs. lymphoma Other infectious agents Courtesy of Dr. Michael McCarthy 26

27 Lymphadenopathy in AIDS Courtesy of Dr. Michael McCarthy Lymphadenopathy in AIDS pt on CT Courtesy of Dr. Michael McCarthy 27

28 Miliary Disease Affects ~10% of ALL patients with TB but more common with post-primary dz Occurs as result of viable bacilli being discharged into blood stream or lymphatics and embolized to multiple organs Lung most commonly involved organ Sputum often negative and transbronchial biopsy may necessary for diagnosis Innumerable randomly distributed 1 3-mm non-calcified nodules, mild basilar predominance Normal x-rays early typical miliary lesions often not visible for 3 6 weeks after dissemination CT much more sensitive Nodules usually resolve within 2 6 months with appropriate treatment Miliary Disease 28

29 Miliary Disease Miliary Disease 29

30 Courtesy: Dr. Santiago Restrepo DDX miliary disease Dusts pneumoconiosis/inhalational EG (Langerhan s) Sarcoidosis Fungal -- histo, cocci, blasto Viral Exanthem -- varicella Metastatic disease (thyroid, melanoma, choriocarcinoma, renal cell etc.) 30

31 Goals Review common imaging appearance of Primary TB (including in children) Post-Primary or reactivation TB TB in Immunocompromised/HIV-infected adults Complications including Extrapulmonary TB Role of imaging in dx and management of these patients Complications/Sequelae Intrapulmonary Extrapulmonary. Rasmussen aneurysm Empyema and empyema Aspergillus necessitans mycetoma formation Bronchopleural fistula Airway dz Extrathoracic lymph nodal Broncholith spread Bronchiectasis CNS Abscess and basal meningitis Strictures Osteomyelitis/ spondylodiskitis Others abdomen, etc. 31

32 Rasmussen Aneurysm Pseudoaneurysm of pulmonary or bronchial artery caused by erosion from an adjacent cavity Uncommon and may develop months to years after formation of the cavity Present with hemoptysis which may be life threatening Seen on post-contrast enhanced CT in area of necrotizing cavitary consolidation Arterial embolization effective method to achieve primary control of bleeding TB & Hemoptysis 32

33 Rasmussen aneurysm Rasmussen aneurysm 33

34 Pulmonary Complications/Sequelae Intrapulmonary Rasmussen aneurysm Extrapulmonary. Empyema and empyema necessitans Bronchopleural fistula CNS Abscess and basal meningitis Osteomyelitis/ spondylodiskitis Empyema DDX Other infectious processes Malignancy Courtesy: Dr. Santiago Restrepo 34

35 Empyema Necessitans Complication of tuberculous empyema Extension of disease through the parietal pleura with dissection of contents into the subcutaneous tissues of the chest wall Courtesy: Dr. Santiago Restrepo xxxxxx DDx: Malignancy Mets, lung primary or lymphoma Infections Actinomycosis, blasto, aspergillus, mucormycosis 35

36 Bronchopleural Fistula Occur when cavitary lesions extend to/through visceral pleura and rupture into the pleural space Bronchopleural Fistula Occur when cavitary lesions extend to/through visceral pleura and rupture into the pleural space 36

37 Bronchopleural Fistula Extrapulmonary TB 85% Pulmonary 15% Extrapulmonary Lymphatic (27.5%) * Pleural (23.4%) Genitourinary (12.8%) Miliary (9.5%) Bone and joint (9.4%) Other (8.6%) Meningeal/CNS (5%)* Peritoneal (3.8%) CDC:

38 Distant Extrapulmonary Sites CNS Lymph nodes Musculoskeletal System CNS Meningitis most common manifestation of CNS tuberculosis across all age groups Parenchymal Abscesses may be solitary, multiple, or miliary Courtesy: Dr. Santiago Restrepo 38

39 Extrathoracic Lymph Nodes Where are the nodes?? 18 y.o with AIDS bilateral painless cervical lymphadenitis AKA scrofula initially homogeneous but later undergo central necrosis Courtesy: Dr. Santiago Restrepo Tuberculous Spondylitis Musculoskeletal involvement occurs in up to 10% of cases of TB and may have severe consequences 50% of these cases manifests as tuberculous spondylitis Result of hematogenous disemination through the paravertebral plexus Usually in the lower thoracic /upper lumbar region Infection usually starts adjacent to the endplate and then spreads into the disc After disc infection the disease spreads into the adjacent paraspinal soft tissues Pott s disease/pott s abscess 39

40 Tuberculous Spondylitis Courtesy: Dr. Santiago Restrepo Tuberculous Diskitis/Osteomyelitis Courtesy: Dr. Santiago Restre 40

41 Goals Review common imaging appearance of Primary TB (including in children) Post-Primary or reactivation TB Immune compromised/tb in HIV-infected adults Complications including Extrapulmonary TB Role of imaging in dx and management of these patients Imaging in TB Chest radiographs play a major role in screening, diagnosis, and monitoring of response to treatment of patients with TB CXR may be normal (up to 15%of cases) or show only mild or nonspecific findings in patients with active disease Diagnosis of TB may be missed on x-ray failure to recognize adenopathy in primary disease overlooked mild parenchymal abnormalities or nodule or mass obscured by overlapping structures in upper lobes in patients with reactivation disease 41

42 Imaging in TB CT more sensitive than CXR in detection and characterization of dz Parenchymal disease (cavitation, endobronchial spread of disease) Airway disease stenosis, bronchiectasis, compromise Nodal disease extent and necrosis Effusions empyema, BPF Miliary disease Other complications such as Rasmussen an. So When Should We Order CT? Symptoms in face of negative CXR Further analysis of abnormal CXR or concerning sx e.g. hemoptysis give IV contrast!! Surgical planning Lack of response to standard therapy (patient management issues) Disadvantage Expensive and more radiation dose 42

43 Role of PET/CT Very Limited Utility - in assessing malignancy vs. infection (false +) More rapid identification of response to therapy than CXR or CT in patients with extensive parenchymal disease in whom therapy decisions may need to be made for example if toxic effects to therapy encountered and need to assess response PET may show overall decreased avidity of 18F-FDG or 11C-choline when the morphologic changes in the region are grossly stable/don t show improvement on CT Much More Expensive Imaging in TB Radiographic evidence of original primary infection in form of calcified lymph nodes and nodules and/or upper lobe fibrotic changes are found in approximately 20% 40% of individuals with active, postprimary disease Thus..radiographic determination of disease activity based on their presence is unreliable 43

44 Active Dz Patterns suggesting active disease CONSOLIDATION/CAVITIES ENDOBRONCHIAL DZ PATTERN MILIARY PATTTERN NECROTIC/ENHANCING LYMPH NODES Imaging in TB Response to Treatment Evaluation of response to antibiotic treatment best assessed by repeated sputum examinations in patients with positive bacteriology although interval x-rays during treatment are often obtained for various reasons Baseline chest radiograph often obtained completion of treatment which may be useful for future comparison purposes In persons with negative pretreatment sputum, radiographic and clinical evaluation become major indicators of response to therapy and are the most common methods used in children (as bacteriologic confirmation is often possible in only about 1/3 of cases) 44

45 Imaging in TB Response to Treatment Regression of radiographic abnormalities in pulmonary TB is a slow process In children, may see extension of parenchymal dz and development or enlargement of nodes during first 3 months even when receiving appropriate therapy In majority of patients, parenchymal and nodal abnormalities usually regress in parallel Imaging in TB Response to Treatment In adults, failure of radiographic findings to improve after 3 months of appropriate therapy suggests drug-resistant organisms or a superimposed process Regression of parenchymal abnormalities may require from 6 months to 2 years on radiographs and up to 15 months on CT scans Lymphadenopathy may persist for several years after treatment When assessing temporal evolution, lack of radiographic change over 4-6 month allows radiologist to say that disease is STABLE rather that INACTIVE 45

46 TB: Summary Who develops TB: Anyone. At Greatest Risk, HIV+, immune compromised; young and very old Most infected individuals: Latent TB, normal CXR & never develop the disease Imaging reflects immune status, not the time course: so search for cause of immune compromise needs to be performed if not already known There is a DDX for Imaging Findings: not always conclusive of TB (Atypical mycobacterial disease); Cancer; Granulomatous infections) Additional Take Home Extrathoracic dz/complications may occur in both forms of dz Extrapulmonary disease is more common in most severely immune compromised patients In HIV patients, pattern of disease related to CD 4 level Order further imaging with CT as indicated (monitor therapy response, assess for complications, surgical planning) may need IV contrast, especially in the setting of hemoptysis And finally.imaging findings can confirm stability but not inactivity 46

47 Thank You 47