Tuberculosis 2: Different Faces Of TB Flashcards
Route of transmission
Airborne: inhalation of mycobacteria into lungs
Others (very rare):
- Inoculation
- Oral
- Organ transplant
Infection vs Disease
- Only 10% TB infected people will develop disease
- Half develop disease within first 2 years of infection
- Depends on balance between host defence and virulence / quantity of mycobacteria
Progression:
Inhalation of MTB
—> Immediate killing of MTB / **Host-TB interaction: Primary complex
——> **Localised disease (Primary TB)
——> Dissemination of TB —> **Active disease / Containment (Latency) —> Reactivation
——> Containment (Latency) —> **Reactivation
Life cycle of TB
Entry
—> Multiplication in unique niche
—> **Infection of macrophages
—> Expansion in **innate granuloma
—> Granuloma maturation with **lymphocytes
—> Granuloma necrosis with **extracellular replication
***Type 4 Delayed type hypersensitivity
Delayed type: 1-2 days after antigen exposure
Mediator: T helper cell (Th1): IFNγ, IL-12 (Major effector mechanism against facultative intracellular pathogens)
Effector: Cell-mediated inflammatory response + macrophage + CD8 T cell
- Sensitisation phase:
APC (dendritic cells / Langerhans cells) —> CD4 T helper —> Th1 - Effector phase:
Sensitised Th1 —> IFNγ, IL-12
—> activate macrophage + CD8 T cell
—> ↑ Class II MHC, TNF receptor, oxygen radicals, Nitric oxide
Example:
1. Allergic contact dermatitis (poison ivy, latex)
Re-exposure —> rapid recruitment of macrophage + CD8
—> inflammatory infiltration + local oedema + erythema
- Granulomatous hypersensitivity (Tuberculosis)
- Granuloma: Caseous necrosis (with persistent pathogen) surrounded by Epitheloid macrophage, Langhans giant cells, T Lymphocytes (Th1), Fibroblast
- Dendritic cell carry Mtb antigen + IL-12 production —> activate Th1 —> IFNγ
—> activate macrophage —> cannot kill mycobacteria and contain the infection
—> Infected macrophage continue to present Mtb antigen to Th1 —> IFNγ
—> activate macrophage —> infected macrophage
—> chronic inflammation (vicious cycle)
—> granuloma formation
—> Chronic localised delayed-type hypersensitivity / Cell-mediated inflammation
Other example: Leprosy, Sarcoidosis , Crohn’s disease
Host risk factors
- Genetic
- Extremes of age
- Pregnancy
- Smoking
- Alcohol
- Malnutrition
- Socioeconomic
- stress
- poverty
- drug addicts - ***Concurrent diseases
- DM
- Renal
- Silicosis
- Post gastrectomy
- HIV
- Cancer and chemotherapy
- Haemic malignancy
- Bone marrow / Solid organ transplant - ***Immunosuppression
- Steroid
- Post organ transplant
- Treatment of autoimmune disease
- Biologics
- Chemotherapy for malignancy
- Pulmonary TB
Common symptoms
1. **Prolonged cough
2. **Sputum
3. **Haemoptysis
4. **Fever
5. ***Nightsweat
6. Weight loss
7. SOB
8. Asymptomatic —> only found during health check
9. ARDS-like (rare)
***2. Extrapulmonary TB
- LN
- Pleura
- Abdomen
- Others
Diagnosis is difficult:
- Usual presentation: Fever + Abnormal radiological / physical findings
- TST / IGRA: not sensitive / specific for diagnosis
- specimens usually hard to obtain (e.g. pleural fluid, ascitic fluid, CSF)
Diagnosis:
1. High index of suspicion
2. **Microbiology examination (e.g. urine, pleural fluid, CSF)
3. **Histological (+/- Microbiological) examination —> Granulomatous inflammation +/- Positive ZN stain
- Pleural TB
Breakdown of sub-pleural TB foci into pleural space
—> Inflammatory response
—> ***Pleural effusion
Associated with pulmonary TB
Diagnosis:
1. Pleural fluid
- **Exudation (Protein >0.5, LDH >0.6), **Lymphocyte predominant
- AFB D/S: negative
- AFB culture: positive <1/3
- Adenosine deaminase (ADA)
- Pleural biopsy
- closed pleural biopsy (Abraham needle)
- pleuroscopy + biopsy
- TB Lymphadenitis
- mainly in ***Cervical region
- children / young adult
- gradual ***painless enlargement of cervical LN over weeks to months
- overlying skin intact in early stage —> shiny + thin —> pink / red + warm
- initially firm —> ***fluctuant (abscess formation) —> drain out via breakage of overlying skin
- no systemic symptoms usually
- abscess formation while on treatment does ***not imply treatment failure —> TB LN are usually pauci-bacillary —> abscess formation is due to heightened inflammatory response to disrupted mycobacterial antigens released from dead bacilli during treatment
DDx:
- Metastatic LN (e.g. NPC)
- Lymphoma
Diagnosis:
1. ***Demonstration of MTB in LN aspirate (Definitive)
2. +ve TST
3. +ve AFB smear in 20-60%, culture +ve 36-70%
4. Histology: Granuloma with caseous necrosis +/- stainable AFB
- TB meningitis
- potential mortality + morbidity
- permanent neurological deficits for paediatric patients in old days
Symptoms:
1. Headache
2. Impaired conscious state
3. Fever
4. Focal neurological deficit
5. Convulsion
MRC Stages:
- Stage 1: non-specific symptoms without changes in consciousness
- Stage 2: **disturbed consciousness but not yet comatose / delirious, focal neurological signs
- Stage 3: **stupors / coma with / without focal neurological signs
Diagnosis:
1. Imaging CT / MRI
2. LP: High opening pressure
3. **CSF
- **high protein
- **low glucose
- **lymphocytic pleocytosis (PMN in early stage)
- AFB D/S
- AFB culture
- TB-PCR
Management:
1. Anti-TB treatment
- Steroid (adjunct)
- ***prevent ICP ↑
- ↓ late sequalae from scarring of meninges
- for stage 2 and 3 - Surgical intervention
- drainage of **obstructive hydrocephalus (early / late)
- excision + debulking of **tuberculoma
- biopsy for diagnosis
- Miliary TB
- Widespread of TB by ***haematogenous route —> all organs involved
- Tiny ***millet-like shadowing on CXR (classical radiological feature) (DDx: Lymphangitis carcinomatosis (SpC Medicine))
Symptoms:
1. Non-specific
2. Fever, lethargy, weight loss
3. Cough
Diagnosis:
1. Sputum for AFB D/S usually **negative
2. Early morning urine (EMU) for urinary involvement
3. **Biopsy / Histology of involved organs (Definitive)
Management:
- Start treatment based on clinical and radiological features
- watch out for other organ involvement (e.g. CNS)
- Female Genital TB
Insidious and mild
- Pain
- Menstrual irregularities
- Pelvic mass
- Ascites
- CXR normal
- Infertility common
- Great mimic of ***gynae malignancy
- ***CA 125 (tumour marker for CA ovary) also ↑
- High index of suspicion
Diagnosis:
1. **Endometrial aspirate for AFB culture
2. **Biopsy
- Male Genital TB
Insidious and mild
- Scrotal swelling
- Dysuria
- Sterile pyuria
- ***Haematuria (Haemospermia)
- Subfertility / Infertility (Presentation / Complication)
High index of suspicion
Diagnosis:
1. **EMU for AFB culture + TB-PCR
2. **Semen for AFB culture + TB-PCR
3. ***Biopsy
- Cutaneous TB
- TB verrucosa cutis
- direct inoculation of TB into skin
- ***purplish / brownish-red warty growth
- knees, elbows, hands, feet, buttocks - Lupus vulgaris
- persistent and progressive
- face - Scrofuloderma
- extension of underlying TB LN, bone / joint (pointing abscess) - Miliary TB abscessus
- micro TB abscessus from haematogenous spread - Tuberculid
- strongly positive tuberculin skin tests
- erythema induratum (Bazin disease)
- papulonecrotic tuberculid
- Other extra-pulmonary TB
- Kidneys, bladder
- Gut
- Bone and joints
- Spine
- Larynx
- Nasopharynx
