Tuberculosis

Question 1

What is tuberculosis?

Answer 1

• An infectious, chronic granulomatous disease caused by Mycobacterium tuberculosis
• Typically affects lungs (esp. upper lobes) however infection may spread haematologically to any organ, causing extrapulmonary TB
• In many patients, M tuberculosis is dormant before it progresses to active TB (primary TB = asymptomatic)

Question 2

What are the 2 types of TB a patient could have?

Answer 2

1. Primary TB ⇒ non-immune host who is exposed to m.tuberculosis. In immunocompetent individuals, this will usually heal.
2. Secondary TB ⇒ If the host becomes immunocompromised the initial infection may become reactivated.

Question 3

What are the risk factors for TB?

Answer 3

• exposure to infection
• immunosuppression (diabetes, cushings, steroid use)
• silicosis (form of lung fibrosis)
• malignancy
• birth in an endemic country (India/Bangladesh/Sub Saharan Africa)
• HIV
• overcrowded areas
  ◦ Low CD4
  ◦ High ESR
  ◦ Co-infections
  ◦ Poor nutrition
  ◦ High viraemia

Question 4

Describe the pathophysiology of tuberculosis

Answer 4

● Mycobacterium tuberculosis is an intracellular organism
● It survives after being phagocytosed by macrophages
● When TB is first taken in via air droplets in to lungs, it leads to primary TB which is when you get signs of infection after exposure, although this does not always cause major symptoms.
● 3 weeks after this, there is cell-mediated immunity which leads to granuloma formation around the infected area of the alveoli. Inside the granuloma, there is cell necrosis called caseous necrosis. This usually occurs in the sub-pleural, lower lobe area.
● In some cases, although some scarring occurs, the TB is killed off by the immune system. But, in other cases, the TB may remain viable but latent.
● In these cases, when the person’s immune system is weakened i.e. due to HIV or age, the TB is reactivated and spreads to the upper lobes where oxygenation is optimal (TB = aerobe).
● Here, there are more caseous regions formed and then cavities. This leads to dissemination throughout the lungs and via the vascular system leading to miliary TB
● Military TB involves spread to multi-organs

Question 5

Summarise the epidemiology of tuberculosis

Answer 5

● Annual mortality = 2 million (95% in developing countries)
● Annual UK incidence = 8200
● Asian immigrants are the highest risk group in the UK

Question 6

What are the presenting symptoms/ signs of TB?

Answer 6

Mostly ASYMPTOMATIC
1. Cough → productive (may have haemoptysis), doesn’t respond to conventional antibiotic therapy
2. Fever
3. Weight Loss
4. Night Sweats
5. SOB (shortness of breath)
6. Anorexia
7. Malaise
8. Pleuritic Chest Pain
9. Cervical Lymphadenopathy + Hilar Lymphadenopathy
10. Pott’s Disease → spread to bones (Similar presentation to lung cancer → look at age of patient and presence of fever
10. wheeze
11. Erythema nodosum ( tender, red bumps, usually found symmetrically on the shins)
12. Phlyctenular conjunctivitis (a nodular inflammation of the cornea or conjunctiva)

Question 7

What investigations are used to diagnose/ monitor TB?

Answer 7

1. CXR → 1st line test. May show consolidation and bi-hilar lymphadenopathy. May see cavitating lesion in upper lobe (caseating granulomas).
2. Sputum Culture → most sensitive and specific test. Gold Standard diagnostic test.
   - Sputum acid-fast bacilli smear → uses a Ziehl-Neelson stain, AFB positive
3. Mantoux Test → screens for latent TB (usually offered for contacts of infected patients)
   - Immunosuppression may cause false negative (sarcoidosis, steroid use, lymphoma, AIDS)
4. FBC- anaemia and increased WBC (leucocytosis without left shift) 
5. Interferon Gamma Tests (IGRA) 
   - Useful in latent TB 
   - Exposure of host T cells to TB antigens leads to release of interferon 

Question 8

How is TB managed?

Answer 8

1. Latent TB → isoniazid + rifampicin
2. Active TB → Rifampicin, Isoniazid, Pyrazinamide, Ethambutol (RIPE)
   - Start all 4 at same time
   - Rifampicin and Isoniazid → 6 months RIS
   - Pyrazinamide and Ethambutol → 2 months PET

Question 9

What are the side effects of Rifampicin in the treatment of TB?

Answer 9

(action= inhibits bacterial RNA polymerase)
- red/orange secretions, hepatitis.
- P450 inducer hence increases metabolism of warfarin and decreases INR.

Question 10

What are the side effects of Isoniazid?

Answer 10

(action= inhibits mycolic acid synthesis)
- hepatitis
- drug-induced lupus
- peripheral neuropathy (pyridoxine (vit B6) to prevent this)

Question 11

What are the side effects of Pyrazinamide?

Answer 11

(action= inhibits fatty acid synthase)
hepatitis or gout (hyperuricaemia)

Question 12

What are the side effects of Ethambutol?

Answer 12

(action= inhibits arabinosyl transferase)
- optic neuritis, avoid in CKD

Question 13

What should be done for a patient with TB before starting treatment?

Answer 13

Before commencing treatment ⇒ U&E’s, LFTs, Vision Testing, FBC

Question 14

What signs of TB can be found on a chest X-Ray?

Answer 14

1. Primary Infection
   ▪ Peripheral consolidation
   ▪ Hilar lymphadenopathy
2. Miliary Infection
   ▪ Fine shadowing
3. Post-Primary
   ▪ Upper lobe shadowing
   ▪ Streaky fibrosis and cavitation
   ▪ Calcification
   ▪ Pleural effusion
   ▪ Hilar lymphadenopathy

Question 15

What pneumonic is used to remember the adverse drug effects of TB drugs?

Answer 15

“RIPE ONGON”
Rifampicin = Orange secretions
Isoniazid = Neuropathy (drug induced lupus)
Pyrazinamide = Gout (hyperuricaemia)
Ethambutol = Optic Neuritis