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HEPATO-BILLIARY
TB
Clinical syndromes of hepato-biliary TB
 Congenital TB – jaundice and failure to thrive (newborn)
 Primary hepatic TB
 Disseminated / miliary TB
 Tuberculoma
 TB of biliary tract
 Granulomatous hepatitis
 TB pylephlebitis
 ATT induced hepatitis
Hepatobiliary TB
 Rt. Hypochondrial pain and swelling
 Hepatomegaly – Mildly tender
Nodular or granular
 Miliary hepatic TB
Sometimes, liver abscess
- Tender hepatomegaly
 Jaundice
Biliary duct obstruction – obstructive jaundice
 TB of GB
Hepato-biliary TB – D/D
 Other hepatic lesions (Hepato-megaly)
 Viral hepatitis – chronic
 Fatty liver, alcoholism
 Connective tissue diseases (SLE, Rh. arthritis)
 Hemosiderosis
 Amyloidosis
 Sarcoidosis
 Drug induced hepatitis
 Primary biliary cirrhosis
 Lymphomas
 Metastases
Genito-urinary TB: Renal
Involves kidneys, ureters, urinary bladder
Symptoms:
 Irritation and pain while voiding urine
 Hematuria
 Sterile pyuria
 Flank pain, renal mass
 Recurrent urinary tract infection
 Urinary calculi
Genital TB - Males
TB of testes, epididymis, prostate,
penis, urethra
S/S: Hemospermia
Scrotal pain and swelling
Nodularity of epididymis, vas
deferens, prostate
Sometimes, sinus formation; perineal fistula
Genital TB - Females
 Fallopian tubes – common
 Endometrial
 Ovarian
 Cervix, vagina, vulva
S & S: Ch. lower abd. pain
abnormal discharge
Altered menses
Infertility
Tubo-ovarian masses, ascites, adhesions etc.
Skeletal TB
 Most ancient form – pre-historic
 Hematogenous spread
 Involves spine and other bones – hip joint, knee, ankle, foot bones etc.
 Types:
 Osseus granular (Metaphysis or epiphysis)
 Osseus caseus
 Synovial granular
 Synovial caseus
Spinal TB
 Lower thoracic and lumbar vertebrae
 Infection begins in cancellous area of vertebral body – destruction –
collapse of vertebra
 Exudation – cold abscess
 Symptoms of local compression from cold abscess
 Spinal: paraparesis – plegia
 Mediastinal structures
 Psoas abscess
Pott’s paraplegia - Mechanism
i. Extrinsic or mechanical causes
 Cold abscess
 Granulation tissue
 Sequestrated bone and disc
 Fibrous tissue
 Gliosis of spinal cord
ii. Intrinsic or non-mechanical causes
 TB inflammation (spinal meningitis)
 Thrombosis of ant. spinal artery
Pott’s Spine (Spinal Kyphosis -TB)
D/D of spinal TB
 Developmental defects – hemivertebrae
 Infections – pyogenic, mycotic
 Benign neoplasms – hemangioma, aneurysm, bone cyst
 Primary malignant tumours (Ewing’s sarcoma, chordoma, lymphoma)
 Secondary deposits
 Langerhan’s cell histiocytosis
 Paget’s disease
 Trauma
Spinal Cold abscess
Joint TB
 Synovial membrane involvement – inflammation and fibrosis
 Insidious onset
 Local warmth
 Joint pain, tenderness
 Immobility – restriction of movements
 Joint effusion – doughy swelling
Synovial fluid – thin and opalescent; contains cells and fibrin flakes
 Sinus formation
 Ankylosis; bone destruction
Bone and Joint TB (Knee, Scapula)
Neurological TB
 Tuberculous meningitis
 TB arachnoiditis
Basal
Opticochiasmatic
Spinal
 Tuberculoma
Intracranial
Spinal
 TB abscess
S/S of Neurological TB
Symptoms: Fever, Altered sensorium, Seizures, Behavioural
changes
Signs: Neck rigidity, Papilloedema, Abducens nerve palsy,
Hemiplegia. Facial nerve palsy, Optic atrophy, decerebration,
abnormal movements, oculo-motor palsy, choroidal tubercles.
D/D of TB-meningitis
 Partially treated bac. meningitis
 Cryptococcal
 Viral meningo-encephalitis
 Carcinomatosus
 Parameningeal infections
 Neurosarcoidosis
 Neurosyphilis
Complications of TB meningitis
 Cerebral oedema, stupor
 Cranial nerve palsy
 Focal neurological deficits
 Hydrocephalus
 Tuberculoma
 TB abscess
 Visual loss
 TB arteritis – stroke
 Endocrine disturbances
 Diabetes inspidus
Cerebral TB (Miliary, Abscesses)
Miscellaneous organs in TB
i. Skin: TB chancre
Lupus vulgaris
Scrofuloderma
Tuberculides
ii. ENT: Laryngeal TB
Ear, nose, pharynx
iii. Adrenal gland: Addison’s disease
iv. Ocular TB: Choroiditis
Retinitis, iritis
v. Muscles, breasts, spleen
Cutaneous TB
Diagnosis of Pulmonary TB
 Clinical Features
 Sputum Examination
 Chest Radiology
 Bronchoscopy
 Mantoux test
 Indirect laboratory tests
Radiological Characteristics
I. Chest: Upper Lobes/Diffuse miliary
Infiltrates/Exudates/Fibrosis
Multiple, thin walled cavities
Lymphadenopathy, Pl.effusion
II. Others: Enlargement of organs
Erosions/Effusions
Caseations/collections
Role of Chest X-ray
 No chest X-ray pattern is absolutely typical of TB
 10-15% of culture-positive TB patients not diagnosed by X-ray
 40% of patients diagnosed as having TB on the basis of x-ray alone do
not have active TB
X-ray is unreliable for diagnosing and monitoring treatment of
tuberculosis

Role of bronchoscopy
 Valuable in early diagnosis of strongly suspected sputum-
negative TB.
 Diagnosis of endobronchial TB/miliary TB
 TBLB yield is greater (82%) than BAL (26%)
 TBNA has a role in mediastinal lymph nodal tuberculosis
with negative sputum smears
NO ROLE IN DIAGNOSIS
ESR?
Tuberculin (Mantoux) Test
 Infection with mycobacterium tuberculosis leads delayed
hypersensitivity reaction which can be detected by Mantoux test
 About 2 to 4 weeks after infection, intracutaneous injection of
purified protein derivative (PPD) of M.tuberculosis induces a
visible and palpable induration that peaks in 48 to 72 hours
How to do the test?
 Sub cutaneous
 Weal formation
 Itching – no scratch.
 Read after 72 hours.
 Induration size.
 5-10-15mm
Mx Interpretation
(i) Induration less than 5 mm – no exposure to tubercular bacilli.
(ii) Induration between 5-9 mm – this can be due to atypical
mycobacteria or BCG vaccination. It may suggest infection in
immunocompromised children such as HIV infection or other
immunosupression;
(iii) Induation 10 mm or more – an induration of 10 mm or more at
48-72 hours in a child with symptoms of tuberculosis should be
interpreted as tubercular disease
Positive test
Clinical significance
 Denotes infection
 Does not differentiate infection from active disease
 A strongly positive Mantoux can support a clinical diagnosis
 Better negative than positive predictive value
 Cut-off for a positive test?
Tests for mycobac aetiology
i. Smear examination
ii. Culture for mycobacteria
LJ medium
Rapid culture methods
iv. Nucleic acid amplification tests
Polymerase chain reaction
Mycobacterial demonstration
Samples to be tests
Sputum, induced sputum
Fiberoptic bronchoscopy – BAL
Bronchial or transbronchial
lung biopsy
Gastric lavage (Children)
Pleural fluid
Mycobacterial Demonstration
1. Smear: - Easiest, quickest
- Requires > 10000 AFB/ml
- Sensitivity 50-60%; Specificity: High
2. Culture: - More sensitive; 10 AFB/ml
- Traditional 6-8 wks
- Septi Chek: Biphasic; High yield
- Radiometric: BACTEC
3. Others: - Animal pathogenicity
- Antimicrobial sensitivity
Drug Susceptibility Methods
1. Conventional
 Absolute concentration
 Resistant Ratio
 Proportion Method
2. Rapid Methods
 Radiometric (BACTEC)
 Mycobac. Growth Indicator Tube
 PCR Based
 RFLP (DNA Finger printing)
Indirect Tests: Markers
1. Biochemical: LDH, Proteins
Adenosine Deaminase
Bromide Partition Test
Gas Chromatography – Fatty acids, alcohols etc.
2. Immuno-diagnosis
Skin test (Mantoux)
Detection of Antibodies (Tests banned)
Serological Tests
 Low turn around time.
 Limitation: low sensitivity in:
smear negative patients, HIV positive cases,
in disease -endemic countries with a high infection rate.
Poor standardization.
Banned in 2012.
Newer Tests
 Gamma Interferon Assay Test
(Gold – IGRA)
 Genetic/Molecular techniques
Gene X-pert TB
Detection of DNA specific base sequences
DNA amplification and detection
 RNA: Presence of multiplying bacteria
 An alternative to the TST in the form of a new type of in-vitro T-cell-
based assay
(Test-tube TST)
Gold IGRA
Elispot T test
 T cells of individuals sensitized with tuberculosis antigens produce
interferon-γ when they re-encounter mycobacterial antigens
 High level of interferon-γ production - presumptive of tuberculosis
infection
 In the absence of a gold standard for diagnosis of Latent TBI,
the sensitivity and specificity cannot be directly estimated
 IGRA have higher specificity than TST
 Better correlation with surrogate markers of exposure to M
tuberculosis
(in low-incidence setting countries)
 Less cross reactivity as a result of BCG vaccination than TST
Gene X-pert Test
 Detection and identification of mycobacteria
directly from clinical samples
 Cartridge based, PCR test for detection of mycobacteria and
Rifampicin resistance
 Rapid test. Results within hours.
 Costly
 Continuous electric supply and temperature maintenance
 ? Field feasibility, sensitivity and specificity
in India.
Confirmation of diagnosis of Pulm TB
 Clinical features are not confirmatory.
 Zeil Nielson Stain
 Culture most sensitive and specific test.
 Conventional Lowenstein Jensen media 3-6 wks.
 Automated techniques within 9-16 days
 PCR is available, but should only be performed by experienced
laboratories
 Mantoux test
Diagnosis of Extra Pulmonary TB
Sputum or other smears are often Negative. These are difficult to use for
 Diagnosis and start of treatment
 Follow up
 Monitoring
 End point
 Recurrence / Relapse
Mostly clinico-radio-histo/cytological
Invasive procedures frequently required to obtain tissue, fluids, etc. to
look for T.b. and/or histo-cytological criteria.
Difficulties of Extra-pulmonary Tuberculosis
 Largely clinical and radiological.
 Supported by laboratory parameters and other TB markers.
 Invasive procedures frequently required to obtain tissue, fluids,
etc. to look for T.b. and/or histo-cytological criteria.
 Therapeutic trial as a diagnostic modality should not be used.
THANK YOU

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Presentation on Hepato-Billiary TB | Jindal Chest Clinic

  • 2. Clinical syndromes of hepato-biliary TB  Congenital TB – jaundice and failure to thrive (newborn)  Primary hepatic TB  Disseminated / miliary TB  Tuberculoma  TB of biliary tract  Granulomatous hepatitis  TB pylephlebitis  ATT induced hepatitis
  • 3. Hepatobiliary TB  Rt. Hypochondrial pain and swelling  Hepatomegaly – Mildly tender Nodular or granular  Miliary hepatic TB Sometimes, liver abscess - Tender hepatomegaly  Jaundice Biliary duct obstruction – obstructive jaundice  TB of GB
  • 4. Hepato-biliary TB – D/D  Other hepatic lesions (Hepato-megaly)  Viral hepatitis – chronic  Fatty liver, alcoholism  Connective tissue diseases (SLE, Rh. arthritis)  Hemosiderosis  Amyloidosis  Sarcoidosis  Drug induced hepatitis  Primary biliary cirrhosis  Lymphomas  Metastases
  • 5. Genito-urinary TB: Renal Involves kidneys, ureters, urinary bladder Symptoms:  Irritation and pain while voiding urine  Hematuria  Sterile pyuria  Flank pain, renal mass  Recurrent urinary tract infection  Urinary calculi
  • 6. Genital TB - Males TB of testes, epididymis, prostate, penis, urethra S/S: Hemospermia Scrotal pain and swelling Nodularity of epididymis, vas deferens, prostate Sometimes, sinus formation; perineal fistula
  • 7. Genital TB - Females  Fallopian tubes – common  Endometrial  Ovarian  Cervix, vagina, vulva S & S: Ch. lower abd. pain abnormal discharge Altered menses Infertility Tubo-ovarian masses, ascites, adhesions etc.
  • 8. Skeletal TB  Most ancient form – pre-historic  Hematogenous spread  Involves spine and other bones – hip joint, knee, ankle, foot bones etc.  Types:  Osseus granular (Metaphysis or epiphysis)  Osseus caseus  Synovial granular  Synovial caseus
  • 9. Spinal TB  Lower thoracic and lumbar vertebrae  Infection begins in cancellous area of vertebral body – destruction – collapse of vertebra  Exudation – cold abscess  Symptoms of local compression from cold abscess  Spinal: paraparesis – plegia  Mediastinal structures  Psoas abscess
  • 10. Pott’s paraplegia - Mechanism i. Extrinsic or mechanical causes  Cold abscess  Granulation tissue  Sequestrated bone and disc  Fibrous tissue  Gliosis of spinal cord ii. Intrinsic or non-mechanical causes  TB inflammation (spinal meningitis)  Thrombosis of ant. spinal artery
  • 11. Pott’s Spine (Spinal Kyphosis -TB)
  • 12. D/D of spinal TB  Developmental defects – hemivertebrae  Infections – pyogenic, mycotic  Benign neoplasms – hemangioma, aneurysm, bone cyst  Primary malignant tumours (Ewing’s sarcoma, chordoma, lymphoma)  Secondary deposits  Langerhan’s cell histiocytosis  Paget’s disease  Trauma
  • 14. Joint TB  Synovial membrane involvement – inflammation and fibrosis  Insidious onset  Local warmth  Joint pain, tenderness  Immobility – restriction of movements  Joint effusion – doughy swelling Synovial fluid – thin and opalescent; contains cells and fibrin flakes  Sinus formation  Ankylosis; bone destruction
  • 15. Bone and Joint TB (Knee, Scapula)
  • 16. Neurological TB  Tuberculous meningitis  TB arachnoiditis Basal Opticochiasmatic Spinal  Tuberculoma Intracranial Spinal  TB abscess
  • 17. S/S of Neurological TB Symptoms: Fever, Altered sensorium, Seizures, Behavioural changes Signs: Neck rigidity, Papilloedema, Abducens nerve palsy, Hemiplegia. Facial nerve palsy, Optic atrophy, decerebration, abnormal movements, oculo-motor palsy, choroidal tubercles.
  • 18. D/D of TB-meningitis  Partially treated bac. meningitis  Cryptococcal  Viral meningo-encephalitis  Carcinomatosus  Parameningeal infections  Neurosarcoidosis  Neurosyphilis
  • 19. Complications of TB meningitis  Cerebral oedema, stupor  Cranial nerve palsy  Focal neurological deficits  Hydrocephalus  Tuberculoma  TB abscess  Visual loss  TB arteritis – stroke  Endocrine disturbances  Diabetes inspidus
  • 20. Cerebral TB (Miliary, Abscesses)
  • 21. Miscellaneous organs in TB i. Skin: TB chancre Lupus vulgaris Scrofuloderma Tuberculides ii. ENT: Laryngeal TB Ear, nose, pharynx iii. Adrenal gland: Addison’s disease iv. Ocular TB: Choroiditis Retinitis, iritis v. Muscles, breasts, spleen
  • 23. Diagnosis of Pulmonary TB  Clinical Features  Sputum Examination  Chest Radiology  Bronchoscopy  Mantoux test  Indirect laboratory tests
  • 24. Radiological Characteristics I. Chest: Upper Lobes/Diffuse miliary Infiltrates/Exudates/Fibrosis Multiple, thin walled cavities Lymphadenopathy, Pl.effusion II. Others: Enlargement of organs Erosions/Effusions Caseations/collections
  • 25.
  • 26.
  • 27.
  • 28. Role of Chest X-ray  No chest X-ray pattern is absolutely typical of TB  10-15% of culture-positive TB patients not diagnosed by X-ray  40% of patients diagnosed as having TB on the basis of x-ray alone do not have active TB X-ray is unreliable for diagnosing and monitoring treatment of tuberculosis 
  • 29. Role of bronchoscopy  Valuable in early diagnosis of strongly suspected sputum- negative TB.  Diagnosis of endobronchial TB/miliary TB  TBLB yield is greater (82%) than BAL (26%)  TBNA has a role in mediastinal lymph nodal tuberculosis with negative sputum smears
  • 30. NO ROLE IN DIAGNOSIS ESR?
  • 31. Tuberculin (Mantoux) Test  Infection with mycobacterium tuberculosis leads delayed hypersensitivity reaction which can be detected by Mantoux test  About 2 to 4 weeks after infection, intracutaneous injection of purified protein derivative (PPD) of M.tuberculosis induces a visible and palpable induration that peaks in 48 to 72 hours
  • 32. How to do the test?  Sub cutaneous  Weal formation  Itching – no scratch.  Read after 72 hours.  Induration size.  5-10-15mm
  • 33. Mx Interpretation (i) Induration less than 5 mm – no exposure to tubercular bacilli. (ii) Induration between 5-9 mm – this can be due to atypical mycobacteria or BCG vaccination. It may suggest infection in immunocompromised children such as HIV infection or other immunosupression; (iii) Induation 10 mm or more – an induration of 10 mm or more at 48-72 hours in a child with symptoms of tuberculosis should be interpreted as tubercular disease
  • 35. Clinical significance  Denotes infection  Does not differentiate infection from active disease  A strongly positive Mantoux can support a clinical diagnosis  Better negative than positive predictive value  Cut-off for a positive test?
  • 36. Tests for mycobac aetiology i. Smear examination ii. Culture for mycobacteria LJ medium Rapid culture methods iv. Nucleic acid amplification tests Polymerase chain reaction
  • 37. Mycobacterial demonstration Samples to be tests Sputum, induced sputum Fiberoptic bronchoscopy – BAL Bronchial or transbronchial lung biopsy Gastric lavage (Children) Pleural fluid
  • 38. Mycobacterial Demonstration 1. Smear: - Easiest, quickest - Requires > 10000 AFB/ml - Sensitivity 50-60%; Specificity: High 2. Culture: - More sensitive; 10 AFB/ml - Traditional 6-8 wks - Septi Chek: Biphasic; High yield - Radiometric: BACTEC 3. Others: - Animal pathogenicity - Antimicrobial sensitivity
  • 39. Drug Susceptibility Methods 1. Conventional  Absolute concentration  Resistant Ratio  Proportion Method 2. Rapid Methods  Radiometric (BACTEC)  Mycobac. Growth Indicator Tube  PCR Based  RFLP (DNA Finger printing)
  • 40. Indirect Tests: Markers 1. Biochemical: LDH, Proteins Adenosine Deaminase Bromide Partition Test Gas Chromatography – Fatty acids, alcohols etc. 2. Immuno-diagnosis Skin test (Mantoux) Detection of Antibodies (Tests banned)
  • 41. Serological Tests  Low turn around time.  Limitation: low sensitivity in: smear negative patients, HIV positive cases, in disease -endemic countries with a high infection rate. Poor standardization. Banned in 2012.
  • 42. Newer Tests  Gamma Interferon Assay Test (Gold – IGRA)  Genetic/Molecular techniques Gene X-pert TB Detection of DNA specific base sequences DNA amplification and detection  RNA: Presence of multiplying bacteria
  • 43.  An alternative to the TST in the form of a new type of in-vitro T-cell- based assay (Test-tube TST) Gold IGRA Elispot T test  T cells of individuals sensitized with tuberculosis antigens produce interferon-γ when they re-encounter mycobacterial antigens  High level of interferon-γ production - presumptive of tuberculosis infection
  • 44.  In the absence of a gold standard for diagnosis of Latent TBI, the sensitivity and specificity cannot be directly estimated  IGRA have higher specificity than TST  Better correlation with surrogate markers of exposure to M tuberculosis (in low-incidence setting countries)  Less cross reactivity as a result of BCG vaccination than TST
  • 45. Gene X-pert Test  Detection and identification of mycobacteria directly from clinical samples  Cartridge based, PCR test for detection of mycobacteria and Rifampicin resistance  Rapid test. Results within hours.  Costly  Continuous electric supply and temperature maintenance  ? Field feasibility, sensitivity and specificity in India.
  • 46. Confirmation of diagnosis of Pulm TB  Clinical features are not confirmatory.  Zeil Nielson Stain  Culture most sensitive and specific test.  Conventional Lowenstein Jensen media 3-6 wks.  Automated techniques within 9-16 days  PCR is available, but should only be performed by experienced laboratories  Mantoux test
  • 47. Diagnosis of Extra Pulmonary TB Sputum or other smears are often Negative. These are difficult to use for  Diagnosis and start of treatment  Follow up  Monitoring  End point  Recurrence / Relapse Mostly clinico-radio-histo/cytological Invasive procedures frequently required to obtain tissue, fluids, etc. to look for T.b. and/or histo-cytological criteria.
  • 48. Difficulties of Extra-pulmonary Tuberculosis  Largely clinical and radiological.  Supported by laboratory parameters and other TB markers.  Invasive procedures frequently required to obtain tissue, fluids, etc. to look for T.b. and/or histo-cytological criteria.  Therapeutic trial as a diagnostic modality should not be used.