Differential diagnosis of tuberculosis, other ... ... Differential diagnosis of tuberculosis, other

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  • Differential diagnosis of tuberculosis, other granulomatous diseases and oncology

    Professor Dr. Graham Bothamley

    EACCTB, Rotterdam 2019

    1

  • Disclosure of speaker’s interests

    (Potential) conflict of interest None

    Potentially relevant company relationships in connection with event 1

    NA

    ▪ Sponsorship or research funding2

    ▪ Fee or other (financial) payment3

    ▪ Shareholder4

    ▪ Other relationship, i.e. …5

    None

  • Plan of talk

    • Symptomatology

    • Physical examination

    • Radiology

    • Histopathology

    • Laboratory tests

    • Summary

    3

  • Symptoms Epidemiology; sensitivity and specificity

    4

  • Presenting symptoms Common

    • Cough

    • Sputum

    • Fever

    • Malaise

    • Loss of appetite

    Uncommon

    • Haemoptysis

    • Night sweats

    • Weight loss

    • Lymphadenopathy

    5

  • Hackney Borough Council: active screening

    • Survey attached to payslip

    • Symptoms of TB

    • TB risk: previous TB, contact with TB

    • Date of screening at place of work

    6

  • Hackney Borough Council Symptoms Non-smokers (n = 785) Smokers (n = 173) Total (%)

    None 486 (62) 108 (63) 594 (62)

    Cough > 3 week 52 (6.6) 19 (11) 71 (7.4)

    Sputum >3 week 50 (6.4) 22 (13) 72 (7.5)

    Night sweats >3 weeks; fever >3 weeks 16 (2.0); 3 (0.4) 5 (2.9); 1 (0.6) 21 (2.2); 4 (0.4)

    Unexpected weight loss > 5% 15 (1.9) 4 (2.3) 19 (2.0)

    New lumps/swellings 15 (1.9) 3 (1.7) 18 (1.9)

    Loss of appetite 11 (1.4) 4 (2.3) 15 (1.6)

    Haemoptysis 6 (0.8) 4 (2.3) 10 (1.0)

    Previous TB 7 (0.9) 3 (1.7) 10 (1.0)

    Contact TB 2 (0.3) 0 2 (0.2)

    3 symptoms or more 10 (1.3) 0 10 (1.0)

    7

    Incomplete forms: 16 TB cases: 0 Rate of smoking: 24%

  • Hackney Borough Council Symptoms Non-smokers (n = 785) Smokers (n = 173) Total (%)

    None 486 (62) 108 (63) 594 (62)

    Cough > 3 week 52 (6.6) 19 (11) 71 (7.4)

    Sputum >3 week 50 (6.4) 22 (13) 72 (7.5)

    Night sweats >3 weeks; fever >3 weeks 16 (2.0); 3 (0.4) 5 (2.9); 1 (0.6) 21 (2.2); 4 (0.4)

    Unexpected weight loss > 5% 15 (1.9) 4 (2.3) 19 (2.0)

    New lumps/swellings 15 (1.9) 3 (1.7) 18 (1.9)

    Loss of appetite 11 (1.4) 4 (2.3) 15 (1.6)

    Haemoptysis 6 (0.8) 4 (2.3) 10 (1.0)

    Previous TB 7 (0.9) 3 (1.7) 10 (1.0)

    Contact TB 2 (0.3) 0 2 (0.2)

    3 symptoms or more 10 (1.3) 0 10 (1.0)

    8

    Incomplete forms: 16 TB cases: 0 Rate of smoking: 24%

  • Cough clinic • Part of cancer program

    • Cough > 3 weeks

    • Primary care action • Check medication (ACE-inhibitors)

    • Antibiotics if indicated (check TB risk)

    • Smoking cessation advice

    • Assess for asthma

    • Trial of anti-reflux (PPI 1st m; PPI + metoclopramide 2nd if no response)

    • CXR Turner & Bothamley. npj Primary Care Resp Med 2016; 26: 15081

    9

  • Outcomes of cough clinic Diagnosis Number (%) Asthma 75 (29)

    Gastro-oesophageal reflux 56 (22)

    ACE-inhibitor use 37 (14)

    Post-infective 30 (12)

    Smoking 23 (8.8)

    Upper airway pathology (e.g. rhinosinusitis) 17 (6.5)

    COPD 5 (1.9)

    Lower respiratory tract infection 4 (1.5)

    Voluntary coughing/throat clearing 3 (1.1)

    Malignancy 2 (0.8)

    Bronchiectasis 1 (0.4)

    Pulmonary fibrosis 1 (0.4)

    Other (half resolved with time) 31 (11.8)

    10

    Turner & Bothamley. npj Primary Care Resp Med 2016; 26: 15081

  • Unexpected weight loss • 5-10% over 6 months

    • Cancer diagnosis in >60 year olds (systematic review; GP coding)

    • 3-7% women; 11-14% men • acute and chronic leukaemia and non-metastatic colorectal cancer

    • 2nd most powerful predictor of cancer (Swedish registry) after • rectal bleeding in colorectal cancer • haemoptysis in lung cancer • rib pain in myeloma • jaundice in pancreatic cancer • haematuria in renal tract cancer

    Nicholson BD et al. BMJ; 5 October 2019: 31-33.

    11

  • Haemoptysis

    • When did it start?

    • What time of day?

    • How much?

    • Bright or dark red?

    • Streak or blob?

    12

  • Differential diagnosis of haemoptysis Diagnosis Cough Purulent

    sputum

    Fever Chest

    pain

    Quantity

    Nose bleed   - - +

    Pulmonary embolus  - - + dark

    Lung cancer + - -  streak

    Tuberculosis + + +   to +++

    Bronchiectasis + +  -  to +++

    Aspergilloma + + - - +++

    Foreign body + + + - +

    Anticoagulation + - - -  to +++

    Rare:

    Polyangiitis syndromes

    Goodpasture’s

    Hereditary telangiectasia

    +

    -

    -

    -

    -

    -

    -

    -

    -

    +

    13

  • Low specificity symptoms for TB

    Common

    • Cough

    • Sputum

    • Fever

    • Malaise

    • Loss of appetite

    Uncommon

    • Haemoptysis

    • Night sweats

    • Weight loss

    • Lymphadenopathy

    14

  • TB, sarcoidosis or lymphoma TB Sarcoidosis Lymphoma

    None (7%) None (80%) None (40%)

    Cough with phlegm Dry cough Breathlessness

    Haemoptysis Breathlessness Fever (B)

    Fever Red eyes Night sweats (B)

    Night sweats Skin lesions Weight loss (B)

    Weight loss Thirst, polyuria (Ca2+) Malaise

    Malaise Arthritis Itching

    Lymph node Neurological Lymph node

    15

  • Likelihood of diagnoses (Europe)

    Lung cancer Tuberculosis Sarcoidosis Lymphoma Polyangiitis

    Non-Hodgkin’s Hodgkin’s

    Age (yr) > 50 20-35; >70 25-45 (also F, 50-70)

    >60 15-35; 70-90 40-60

    Incidence 23.1 10.7 (2 – 40) 7 (5 – 40) 6 - 12 2.7 0.3 - 1.4

    Most common symptom

    Smoker High incidence (Night sweats)

    Dry cough Lymph node; liver, spleen

    LN (CXR); spleen

    Haematuria

    16

  • Physical examination The cold lymph node

    17

  • Primary TB Post-primary TB

    18

  • Skin sarcoid

    19

  • Uveitis

    20

  • Radiology

    21

  • Lung cancer screening

    • Dutch-Belgian Randomised Lung Cancer Screening (NELSON): • > 50 years • Smoking: >15/d for >25 yr or 10-15/d for 30 yr; current or M; upper lobe; larger (older, FH, emphysema, part-solid, fewer)

    • S Korea: 313 nodules in 53,036; 179/186 transient; 2/7 TB

    • S Korea: 118/1587 nodules; 4 lung cancers; false-positives 96.6%

    • Mumbai: 191 PET scans: 144 cancer, 16 TB (overlap in uptake)

    Han S, et al. IJTLD 2019; 23(6): 698-706

    Kim HJ et al. ERJ 2016; 47(5): 1510-7. Ju SM et al. Thorac Canc 2013; 4: 405-9

    Purandare MC et al. Indian J Cancer 2017; 54: 271-5

    22

  • PET-CT

    23

  • BHL

    24

  • 25

  • Pulmonary infiltrates

    26

  • Gallium scan

    Lacrimal glands

    Parotid glands

    Bilateral hilar lymphadenopathy

    27

  • PET scanning and sarcoidosis

    28

  • Case detection Sputum smear Sputum culture

    29

  • Mtb DNA amplification

    Genotype MDRTBPlus

    Xpert MTB/RIF

    30

  • Common tests Sarcoidosis Lymphoma TB

    Symptoms Rare EtOH and sweats NS, WL

    Examination Eye, skin Other LN; liver, spleen Thin

    Fbc Normal Normal or lymphocytes+ Normal

    Calcium Raised Normal raised

    CRP Normal Normal 10-70 mg/L

    SACE > 52 IU/mL Normal Normal

    CXR BHL Mid zones

    BHL BHL Upper zones

    Tuberculin response Negative (BCG+) Negative Positive (75%)

    IGRA 5% +ve Negative 80% +ve

    31

  • Granulomas Inflammation; collection of immune cells (macrophages always present)

    Wall off foreign material that can’t be eliminated

    32

  • Some common causes of granulomas

    Infections - lung Infections – usually outside lung

    Immune Other

    Tuberculosis Sarcoidosis Aspergillosis Non-tuberculous mycobacteria Nocardia Histoplasmosis Coccidiomycosis Blastomycosis Aspiration pneumonia Pneumocystis pneumonia

    Cat scratch disease Toxoplasmosis Cryptococcus Rheumatic fever Schistosomiasis Leishmaniasis Listeria Leprosy Plague Tularaemia

    Rheumatoid arthritis Crohn’s Polyangiitis (WG, CS) Behçet’s

    Foreign body Keratin Necrobiosis lipoidica Berylliosis Chronic granulomatous disease

    33

    Shah KK, et al. J Clin Tub Other Mycobact Dis 2017; 7:1-12

  • Granulomas

    34

  • Granulomas in Taiwan

    Treated (n=40) Number (%)

    Untreated (n=67) Number (%)

    Age yr: mean (SD) 55.5 (12.4) 56.8 (14)

    Female 14 (35) 29 (43)

    PMH TB 2 (5) 10 (15)

    Caseation 31 (78) 24 (36)