Tuberculosis - Clinical manifestations (II) Flashcards by Max Kam

Tuberculosis:

Route of transmission?

Airborne - Inhale mycobacteria into lungs

Other routes:

Inoculation
Oral route
Organ transplant

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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

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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)

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Lifestyle risk factors for TB

Smoking and Alcohol
Socioeconomic: Stress, poverty, malnutrition
Drug addiction

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Immunosuppression risk factors for TB

DM 
HIV 
Cancer and chemotherapy 
Hematological malignancies 
Bone marrow transplant 
Solid organ transplant 
Drugs: Steroids, immunosuppressants, biologics

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General host risk factors for TB

Genetics
Young or Old
Pregnant

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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 ***

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3 different presentations of Pulmonary TB infection?

Acute presentation, pneumonia-like
Classic pulmonary and systemic symptoms and signs over time
Asymptomatic

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Proportion of pulmonary vs extrapulmonary TB in HK?

Pulmonary = 75%

Extra pulmonary = 20%

Both = 5-10%

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3 prong method to diagnose extrapulmonary TB

High index of clinical suspicion

Microbiological examination of fluids, biopsies

Pathohistological exam: granulomatous inflammation, ZN stain

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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

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Most common form of extra-pulmonary TB?

Pathogenesis?

Pleural TB

Breakdown of sub-pleural TB foci into pleural space&raquo_space; inflammatory response&raquo_space; pleural effusion develops

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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 **

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2 methods of pleural biopsy

closed pleural biopsy - Abraham needle

Pleuroscopy

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TB Lymphadenitis.

- Clinical presentation

Gradual, painless enlargement of cervical LN over weeks

Overlying skin becomes shiny and thin, erythematous, fluctuant from abscess formation

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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

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Methods to obtain cervical and mediastinal LN specimen

Cervical: FNAC

Mediastinal: Transbronchial needle aspirate

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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

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Most common form for CNS TB infection?

TB meningitis

Common cause of neurological deficit in pediatric patients before

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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

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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

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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

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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

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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?

1. Infection in previously damaged lungs 2. Primary lung disease (middle aged or elderly) 3. Hypersensitivity like disease 4. 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)