Resp - TB (II) Flashcards
Tuberculosis:
Route of transmission?
Airborne - Inhale mycobacteria into lungs
Other routes:
- Inoculation
- Oral route
- Organ transplant
Difference between infection and disease?
Difference in TB infection and active disease?
Infection:
- Invasion and multiplication of micro-organism not normally present in the body
Disease:
Condition of abnormal vital function involving any structure, part, or system of an organism
Set of signs and symptoms
only 10% of TB infections become active disease
4 outcomes in MTB infection
Inhalation of MTB
a) Immediate killing
b) Host-TB interaction: Primary complex
i) Localized disease (Primary TB)
ii) Dissemination of TB (Active disease)
iii) Containment (Latency)
Lifestyle risk factors for TB
Smoking and Alcohol
Socioeconomic: Stress, poverty, malnutrition
Drug addiction
Immunosuppression risk factors for TB
DM HIV Cancer and chemotherapy Hematological malignancies Bone marrow transplant Solid organ transplant Drugs: Steroids, immunosuppressants, biologics
General host risk factors for TB
Genetics
Young or Old
Pregnant
Symptoms and signs of Pulmonary TB
TB infection = symptomatic?
Prolonged cough Sputum Hemoptysis Fever Night sweat Weight loss Shortness of breath
** TB can be asymptomatic ***
3 different presentations of Pulmonary TB infection?
- Acute presentation, pneumonia-like
- Classic pulmonary and systemic symptoms and signs over time
- Asymptomatic
Proportion of pulmonary vs extrapulmonary TB in HK?
Pulmonary = 75%
Extra pulmonary = 20%
Both = 5-10%
3 prong method to diagnose extrapulmonary TB
High index of clinical suspicion
Microbiological examination of fluids, biopsies
Pathohistological exam: granulomatous inflammation, ZN stain
2 reasons why extrapulmonary TB is difficult to Dx early?
TST/ IGRA not sensitive for specific enough for Dx
Specimen for microbiological studies (pleural fluid, CSF…etc) may be hard to obtain
Most common form of extra-pulmonary TB?
Pathogenesis?
Pleural TB
Breakdown of sub-pleural TB foci into pleural space»_space; inflammatory response»_space; pleural effusion develops
List 4 tests on pleural fluid for Dx of Pleural TB
- Microscopy: high lymphocyte
- AFB staining: High failure, mostly negative
- AFB culture: High failure, Positive in < 1/3
- Adenosine deaminase ** Gold Standard for pleuritis **
2 methods of pleural biopsy
closed pleural biopsy - Abraham needle
Pleuroscopy
TB Lymphadenitis.
- Clinical presentation
Gradual, painless enlargement of cervical LN over weeks
Overlying skin becomes shiny and thin, erythematous, fluctuant from abscess formation
Empirical TB treatment started upon FNA Dx of TB Lymphadenitis, but the cervical LN grows even more fluctuant and pustular.
Explain
Intense inflammation and abscess formation because of disrupted mycobacterial antigens released from dead bacilli
Normal, does not signify treatment failure
Methods to obtain cervical and mediastinal LN specimen
Cervical: FNAC
Mediastinal: Transbronchial needle aspirate
Definite Dx of TB Lymphadenitis
D/dx?
- Demonstrate MTB in LN aspirate: +ve AFB stain
- Pathohistological: Granuloma with caseous necrosis +/- AFB
- Positive TST
D/dx:
- Metastatic LN (e.g. NPC)
- Lymphoma
Most common form for CNS TB infection?
TB meningitis
Common cause of neurological deficit in pediatric patients before
Presentation of CNS TB infection.
Headache, Poor sleep Fever Convulsion Focal neurological deficit Impaired conscious state
CSF tap:
- High protein, low glucose
- PCR +ve
- AFB culture
- High opening pressure
MRC Staging for CNS TB infection?
1: Non-specific symptoms without changes in consciousness levels (apathy, fever, nausea, vomiting…etc)
2: Disturbed consciousness +/- focal neurological signs, Not comatose or delirious
3. Stupors (almost unconscious) or coma +/- focal neurological signs
2 methods to Dx CNS TB Infection
- CT/ MRI brain
CSF tap:
- High protein, low glucose
- Lymphocytic pelocytosis (PMN at early stage)
- TB- PCR ***
- AFB culture
- High opening pressure
Management of CNS TB infection (3)
- Anti-TB drugs
- Adjunctive steroids: anti-inflammatory to decrease ICP, prevent meninges scarring
- Surgical drainage of obstructive hydrocephalus. excision of tuberculoma, Biopsy for Dx
Cause of Miliary TB?
Presentation?
Confirmation of Dx?
Haematogenous spread of TB to any organ
Presentation: Non-specific fever, lethargy, weight loss, cough
X-ray shows tiny millet-like shadowing
Dx: Biopsy and histology of organs involved
Genital TB- Female
- Typical presentation
- D/dx?
Abdominal pain Irregular menses Pelvic mass Ascites Infertility (3/4 normal CXR)
GREAT MIMIC OF GYNAE MALIGNANCY
Explain why genital TB is a great mimicker of Gynaecological malignancies.
How to differentiate?
PET-CT shows abnormal signals compatible with CA
CA125 marker for CA ovary also elevated in TB
Endometrial aspirate for AFB culture/ biopsy by laparoscopy
Genital TB- male
- Typical presentation
- Dx method?
Scrotal swelling Sterile pyuria Hematuria Dysuria Infertility
Dx:
- Early morning urine for AFB culture and TB- PCR
- Semen for AFB culture and TB- PCR
- Biopsy
5 forms of cutaneous TB
TB verrucosa cutis
Lupus vulgaris
Scrofuloderma
Miliary TB abscessus
Tuberculid
Feature of TB Verrucosa cutis? Location?
Direct inoculation of TB into skin
Purple/ brown warty growth
Knees, elbows, hands, feet, buttock
Feature of Lupus vulgaris
Persistent and progressive cutaneous TB
Face
Feature of scrofulderma
Extension of underlying TB LN, bone, joint
Feature of Miliary TB abscessus
Micro TB abscess
From blood spread of TB
Tuberculid features
Strong positive TST
Erythema induratum
Papulonecrotic tuberculid
No identifiable focus of active TB in skin
Which form of TB is associated with high incidence and high mortality in the elderly?
Extensive pulmonary TB
Risk factors of extensive pulmonary TB in elderly?
Comorbidities: malnutrition, immunosuppressive states
Smokers
Aging - decline in cell mediated immunity
Socio-economically deprived = late presentation and Dx
Effect of TB on under 65 and over 65 years old? (presentation, CXR differences?)
Over 65:
- Lower body weight
- Less hemoptysis
- Lower serum albumin
- Less upper lobe infiltration on CXR
- More extensive infiltration of both lungs / lower zone involvement
Why is Cryptic miliary TB so hard to Dx?
think presentation, investigations
Insidious onset with non-specific symptoms
Symptoms presumed due to chronic disease or tumours
CXR: miliary shadows not obvious
Sputum: AFB negative
TST: negative
> > > Dx often very late or missed
Definitive Dx of Cryptic Miliary TB?
When to suspect Cryptic TB?
Bone marrow and liver biopsy
50% Dx post-mortem
Suspect in all cases of PYREXIA OF UNKNOWN ORIGIN
> > start treatment even without definitive evidence
5 risk factors for missed TB diagnosis.
- Female
- Ongoing malignancies (except lung cancer)
- Old-age home rest
- Drug abuse
- CXR not done when alive
Challenges in Dx of TB in young patients under 5?
- Extra-pulmonary involvement common
- Symptoms and signs not specific
- Hard to get good quality specimen for exam
Presenting features of TB in the very young?
Failure to thrive
TB contact
Persistent cough and fever
Extra-pulmonary TB symptoms
Common forms of TB in children?
TB lymphadenopathy
Miliary TB
TB meningitis
Pleural TB
Abdominal TB (peritoneal)
Osteoarticular TB
Pericardial TB
3 iatrogenic causes of immunosuppression
Systemic steroids
Immunosuppresion by drugs: transplant, auto-immune diseases, chemotherapy, biologics
Gastrectomy
4 challenges in management of TB in immunosuppressed?
- Lots of medication
- Potential drug interactions: Rifampicin = potent CYP450 inducer
- Additive drug toxicity to liver, kidneys, bone
- Change in primary disease management, need isolation
How to manage SLE patient intolerant to TB treatment?
High dose prednisolone to control SLE and allow TB drugs to work
Describe the bi-directional interaction between HIV and TB
HIV cause immunosuppression = TB reactivation and progress
TB lesions release pro-inflammatory cytokines to increase HIV viraemia
> > > High mortality with co-infection
Classical presentation of HIV + TB infection
Early stage: Haemoptysis + Upper zone lesions with cavitation, Positive TST
Severe stage: Less* hemoptysis, No zonal lesions, no cavitation, more extrapulmonary disease (LN, abdomen, CNS…etc)
Negative TST
Which biologics is associated with high risk TB infection? Explain.
Example of diseases treated by this drug?
Anti-TNF Biologics (Infliximab, Etanercept)
TNF = mediator for granuloma maintenance to contain TB infection
E.g. RA, Inflammatory bowel diseases, Ankylosing spondylitis
Procedure for TB prevention before starting biologics treatment
- Screen for active and latent TB
- Active TB = treat with standard regimen before starting biologics
- Latent TB = Isoniazid for 9 months
NTM:
- Source
- Transmission
- Environment: Animal, Soil, Food, Water
- Transmission: environment acquired
Virulence of NTM?
- Are all NTM infectious?
- Host factors that predispose NTM infection?
Only some NTM species cause infection, different strains within species have different virulence
Host factors
- Host immunity
- Lung disease
- Esophageal motility disorders
- Body morphotype
Definitive Dx of NTM?
Molecular Dx:
- Negative TB - PCR to rule out TB
- Gene sequencing for NTM
< cards about NTM causing resp. skin/ soft tissue, LN, Disseminated infection >
< TBC >
4 major clinical manifestations of NTM lung diseases?
- Infection in previously damaged lungs
- Primary lung disease (middle aged or elderly)
- Hypersensitivity like disease
- Lung infection in immunocompromised patient: primary lung or disseminated
Clinical presentation of NTM infection in previously damaged lungs?
CXR feature progression
Non-specific respiratory and constitutional symptoms
Progression of diseased and scarred lungs
Worsening radiological features
Clinical presentation of NTM infection as primary lung disease in middle aged or elderly
CXR, CT features
Chronic cough and sputum
CXR: nodular shadowing at Mid and lower zones (unlike typical TB at apical regions)
CT thorax: Small airway inflammation as centrilobular nodules + bronchiectasis
Clinical presentation of NTM infection as hypersensitivity like disease in lungs
Source of infection
Hypersensitivity pneumonitis with allergic type host response to NTM
- Subacute cough, SOB, fever, respiratory failure
- Nonspecific infiltrate and nodules
Hot Tub Lung: inhale mycobacteria in indoor spa bath, pool or shower
Hypersensitivity like disease by NTM infection of lungs.
- CT features
- CXR features
Nonspecific infiltrate and nodule in CXR
CT thorax: GGO and mosaic pattern + nodules and consolidations
Clinical presentation of NTM infection in immunocompromised?
Radiographic features?
Culture?
- Variable, non-specific respiratory symptoms
- Rapidly deteriorating if severely immunosuppressed
- Non-specific radiographic features: consolidation, nodules, cavities, GGO
- Mycobacteraemia (blood culture +ve)
