TUBERCULOSIS

DR .. MAGDI ELBALOOLA AHMED

PHYSCIAN & GASTROHEPATOLOGIST
 Tuberculosis is a chronic infection caused by
mycobacterium tuberculosis and occasionally by M. bovis
M. africana .

Pulmonary TB is a common form of tuberculosis but it

can affect many other organs and tissues.
Pathology
Primary TB;

It is the first infection with M. tuberculosis , after inhalation it

reaches subpleural area & drain by lymphatics to the hilar LNs
(Ghon focus),some organisms gain access to the blood stream from
where it spread to different organs.

 The immediate reaction of immune system is ingestion of bacilli by

macrophages, inside macrophages it proliferate, now again
macrophages respond by secretion of cytokines that attract
neutrophils & monocytes. On the other hand it present the antigen to
T. lymphocyte . By this it develop cellular immunity to bacilli in 3-8
weeks that can be expressed as +ve tuberculin test .
 granuloma developed which is composed of central
caseation surrounded by epithelioid & Langhans cells
(macrophages). Latter a delayed hypersensitivity reaction
developed leading to tissue necrosis (main pathological feature) .
lymphocytes causes caseating areas and fibrosis, eventually
. become calcified
it is believed that; 20% of this calcified lesions contains a dormant
bacilli that reactivated when immunity declines causing (Latent
.TB)
 Post primary TB ;
Is the all forms of TB that occur after the first few weeks
after the primary infection when the immunity to
mycobacterium has developed .
Clinical Features
 Symptoms are typically gradual
- malaise , tiredness , anorexia
- fever , night sweating & loss of weight
- cough , sputum (mucoid , purulent or blood stained)
O/E;
- Low body built , Clubbing, pallor.
 Crackles
 P.effusion
 tracheal deviation, ↓ air entry.
 features of upper lobe fibrosis.
 Radiological findings
Ghon focus Rt. U.Lobe fibrosis
 Radiological findings
P. effusion Rt. U. lobe Cavity
Lung fibrosis
Diagnosis
CBC & ESR
 Imaging; CXR _ CT scan
 Sputum ZN stain for AAFB
 sputum for C / S
 Fibreoptic bronchoscopy with wash replaces gastric washes
in dry cough.
 biopsy ; from LN , pleura , lung.
Management
 Notification of health  Balanced nutrition .
authorities.

Bed rest , admission &  Contact tracing .

isolation ⇒ for very ill
patients & smear  Vaccination for Mantoux
positive patients. –ve contacts
& clinical assessment for
 Well aerated room. +ve contacts.
 Management
DOT (directly observed therapy)
 A program that is adopted by health systems in different
countries .

 It deal with the problem of compliance (the leading cause

of drug resistance).

 Incentives like money & meals are encouraging .

 Management
Six-month regimen Longer regimens

 For pulmonary TB & TB of the

lymph nodes .
 Rifampicin (450mg,600mg)
Isoniazid (300mg)
pyrazinamide(1.5mg,2mg)
ethambutol (15mg)
pyridoxine (10 mg)
 Nine (9) month regimen for
bone TB.
+
+  Twelve (12) month regimen
+ for Tuberculous meningitis.
+

These for the first 2 months then

rifampicin+INH (Refinah) for the
next 4 months.
Side effects of Anti-tuberculous
Rifampicin INH

 Transient AST elevation Polyneuropathy

(discontinued when >3ULN)  Allergy, skin rash & fever .
 Hepatitis  hepatitis (<1%)
 thrombocytopenia
 Pink discoloration of the
urine and body fluid .
Side effects of Anti-tuberculous
Pyrazinamide Ethambutol

 Gout (↓urate excretion) .  Optic neuritis

 Hepatitis (rare). ↓ Visual acuity
Central scotoma

Streptomycin

Sensory neural deafness

Tuberculin tests
Tests that when positive indicate previous exposure to
mycobacteria or BCG .Used as screening test & for contacts.
When positive with no previous exposure and no BCG it
indicates the high probability of active TB

1- Mantoux test ; intradermal injection of 0.1 ml of purified

protein derivative (PPD) with the result read in 72 hours.
>10mm induration (+ve in thoes who have previous infection
without BCG vaccination)
>15mm induration (+ve in thoes who have previous infection
with previous BCG vaccination)
2- Heaf test;
intradermal injection of PPD with a gun of six puncture
needles. The result read after 3-7 days; this classified into 4
grades
Grade 1: 4-6 indurated papules
Grade 2 : confluent ring of papules
Grade 3 : solid induration of 5-10 mm
Grade 4 : solid induration of > 10 mm
The result read as follows;
Grade 2-3 : is considered as a +ve test in thoes with
previous infection without BCG vaccination.
Grade 3-4 : is considered as a +ve test in thoes with
previous infection with BCG vaccination.
 Interferon gamma test ;
Is an expensive blood test used after strongly
positive tuberculin test in thoes with previous
BCG . It indicate that the positive tuberculin
test is related to active tuberculosis .
Drug Resistance
 Primary drug resistance ⇒initial failure to respond
to ttt (exposure to others infected with resistant
organisms )

 Secondary drug resistance ⇒ initial response

followed by resistance (non- compliant
patients)
Types o drug resistance (WHO)

1- Multidrug resistance (MDR)⇒ resistance to

rifampicin & INH

2- Extensive drug resistance (XDR)⇒ resistance to

rifampicin,INH,quinolone & at least one of
the following second line drugs; kanamycin,
capreomycin, amikacin
 ttt of drug resistance;
1-in resistance to one drug continue with other
three
2- in MDR use at least three drugs to which
organism is sensitive.
3- therapy continued for up to 2 years
4- HIV patients continue therapy for 12 months after –ve
culture.
 Second line anti-tuberculous
capreomycin , amikacin , kanamycin ,
ciprofloxacin , ofloxacin , mofloxacin ,
clarithromycin , azithromycin , cycloserine ,
ethionamide & rifabutin
 Miliary TB
 It´s an acute dissemination of tubercle bacilli by blood stream
(haematogenous spread).
This form of TB usually occur in elderly with the original site
being primary infection or reactivation of latent focus.
untreated miliary TB is almost universally fatal .
 features ;
 Vague ill health
 wt loss
 fever (late)
 hepatosplenomegaly
 choroidal tubercle
Choroidal tubercle
 DisseminatedTB
Disseminated tuberculosis (DTB) refers to involvement of
two or more non-contiguous sites.

Dissemination can occur during primary infection or

after reactivation of a latent focus/re-infection. small
numbers of tubercle bacilli gain access to the circulation
through the lymphatics and disseminate to visceral sites
which have rich vascular supply and good oxygenation
such as the liver, spleen, bone marrow and the brain.
These foci heal by calcification in a majority of the
patients
 Extrapulmonary TB (EPTB)
 EPTB constitutes about 15 to 20 % of all cases of
tuberculosis in immunocompetent patients and
accounts for more than 50 % of the cases in HIV-
positive individuals. Lymph nodes are the most
common site of involvement followed by pleural
effusion and virtually every site of the body can be
affected.
 Due to atypical presentation of EPTB & difficulty in
tissue samples the diagnosis is often delayed.
 Tuberculous lymphadenitis (Scrofula)
 It is the most common form of EPTB.
 As a cause , Tuberculous mycobacteria is more
common in underdeveloped countries. while non
Tuberculous mycobacteria is more common in
developed countries.
 In adults tuberculous mycobacteria is more common
while in children non tuberculous mycobacteria is
more common.
Pathogenesis
 LNTB caused by MTB is considered as a local
manifestation of a systemic disease where NTM causes a
pure localized disease in LNs.
 Infection may start in hilar LNs and then spread to other
LNs or from the tonsils.
 the infection causes matting & fixation of the LNs with
caseous and pus formation
 overlying skin showed induration, ulceration & sinus
formation.
 common LN affected are cervical then axillary then
inguinal
Pleural effusion and empyema
 Tuberculous pleural effusion is categorised as
extrapulmonary despite an intimate anatomic
relationship between pleura and the lungs.

P.effusion in TB considered as type IV (delayed)

hypersensitivity reaction and empyema may result from
rupture of a cavity into the pleural space . Less commonly
from paratracheal LNs , paravertebral absces or from
osteomyelitis of the ribs .
Abdominal tuberculosis
Abdominal tuberculosis include TB of the
gastrointestinal tract, peritoneum, omentum,
mesentery and its nodes and other solid intra-
abdominal organs such as liver, spleen and pancreas.

The organism gain access to these areas through

haematogenous spread from primary infection ,
reactivated latent infection or by ingestion of
contaminated food eg. Mycobacterium bovis in raw
milk .
Neurological tuberculosis
Neurological involvement is five times more
frequent in HIV-positive compared to HIV-negative
patients.

Neurological tuberculosis may be classified into three

clinico-pathological categories:
- tuberculous meningitis (TBM)
- tuberculoma
- arachnoiditis
Tuberculous meningitis (TBM)
accounts for 70-80% of neurological tuberculosis.
Neurological tuberculosis is invariably secondary to
tuberculosis elsewhere in the body.
In the bacteraemic phase of primary lung infection,
metastatic foci can be passed to any organ, which
may become active after a variable periods of clinical
latency.
The critical event in the development of meningitis is the
rupture of a subependymal tubercle (Rich focus) resulting in
the release of infectious material into the subarachnoid
space.
pathological features
pathological features of TBM:
(i) inflammatory meningeal exudate
(ii) ependymitis
(iii) vasculitis
(iv) encephalitis
(v) disturbance of cerebrospinal fluid (CSF)
circulation and absorption.
Clinical features
Onset usually evolves gradually over two to six weeks.
Acute onset has also been described.
vague ill-health,
apathy, irritability, anorexia and behavioural changes
Headache, vomiting and fever.
 Focal neurological deficits
 pyramidal signs may develop due to increasing hydrocephalus and tentorial
herniation.
 Complete or partial loss of vision is a major complication of TBM
 features of raised intracranial tension
Focal or generalised seizures
Cranial nerve palsies (sixth nerve involvement being the most common)
 coma and decerebrate or decorticate posturing.
Intracranial tuberculomas
tuberculomas still constitute about 5 to 10 per cent of
intracranial space occupying lesions in the developing
world.
Tuberculoma is a mass of granulation tissue made up of a
conglomeration of microscopic small tubercles.
 The size of cerebral tuberculomas is highly variable. In
most cases their diameter range from a few millimetres
(mm) to four centimeters.
 under the age of 20 yr are usually infratentorial, but
supratentorial lesions predominate in adults.
-Tuberculoma (MRI⇒single enhancing lesion surrounded by
edema)
Pericardial tuberculosis

Pericardial involvement in tuberculosis may result

in acute pericarditis, chronic pericardial effusion, cardiac
tamponade or pericardial constriction.
TB has been reported to be the cause of acute
pericarditis in 4% of patients in the developed world and
60 - 80 %of the patients in the developing world.
TB pericarditis has been estimated to occur in 1- 8 % of
patients with pulmonary tuberculosis.
In industrialised countries TB pericarditis is not so
common except in patients with HIV infection and AIDS.
Pathological stages of
Tuberculous pericarditis

(i) dry stage

(ii) effusive stage
 (iii) absorptive stage; and
 (iv) constrictive stage
Clinical features:
insidious onset
 Acute onset has been reported in 20 % of patients and some patients can
present with cardiac tamponade.
fever, malaise, weakness and vague chest pain
 Dyspnoea, cough, and weight loss
 Chest pain, orthopnoea and ankle oedema occur in nearly 40 to 70 % of
patients.
Tachycardia, raised JVP with a prominent y descent
 The JVP may rise further on inspiration (Kussmaul’s sign).
 Pulsus paradoxus is seen in less than 1/3 of cases and signifies presence of
some fluid or a relatively elastic pericardium .
O/E… pericardial rub.
Cardiomegaly on a chest radiograph.
 TB Pericarditis (imaging)
Pericardial effusion Pericardial effusion (echo)
(globular heart)
 Bone TB , joint TB
and (Pott´s disease)
Skeletal tuberculosis is a haematogenous infection that can affects
almost all bones.
 Spinal tuberculosis (TB spine) is the most common form of skeletal
tuberculosis
Lower thoracic and lumbar vertebrae are the most common sites of
spinal tuberculosis.
 The infection begins in the cancellous area of vertebral body
commonly in epiphyseal location and less commonly in the central or
anterior area of vertebral body. The infection spreads and destroys the
epiphyseal cortex, the intervertebral disc and the adjacent vertebrae,
leading to vertebral collapse and acute angulation (gibbus).
 cold absces is formed tracking along tissue planes and discharge at a
point far from the affected vertebrae.
Constitutional symptoms such as loss of appetite and
weight, evening rise of temperature and night sweats
generally occur before the symptoms related to the
spine manifest.
 local back pain and lately swelling over the affected
vertebrae.
 neurological symptoms and signs that constitute LL
weakness ( UMN signs associated with sensory level).
 treatment is as same as Pulmonary .TB but extended
to 9 months (bone TB) with initial immobilization.
Pott´s disease X-ray Pott´s disease MRI
 Genitourinary tuberculosis
Genitourinary tuberculosis (GUTB) complicates 3-4% of
patients with pulmonary tuberculosis. Haematogenous
dissemination from an active site of infection results in GUTB.
Initially metastatic lesions (tubercles) are formed in the
kidneys with macroscopic progression of the disease is often
unilateral. Usually, these lesions heal spontaneously or as a
result of treatment. However, they may enlarge even after
years of inactivity and rupture into the nephrons producing
bacilluria.
 There is descending spread of infection, inflammation and
scarring.
GUTB – Clinical features & complications
 Active GUTB usually develops 5 to 25 yr after
the primary pulmonary infection.
 - dysuria, haematuria which may be painless
 - flank pain, renal mass, sterile pyuria
 - recurrent urinary tract infection.
 - pyelonephritis
 - Other uncommon presentations : non healing
wounds, sinuses or fistulae, haemospermia
 - Female genital tuberculosis is an important cause
of infertility
Cutaneous tuberculosis

 0.11 -2.5 % of all patients with skin diseases.

1-not previously exposed to M. tuberculosis
- miliary tuberculosis of the skin
- tuberculosis chancre.
2- Previously sensitised
- lupus vulgaris
- scrofuloderma
- tuberculosis verrucosa cutis
- Other lesions seen are lichen scrofulosorum, papulonecrotic
tuberculid ,erythema induratum, erythema nodosum.
- Lupus vulgaris is the most common variety followed by
tuberculosis verrucosa cutis and scrofuloderma
HIV infection and AIDS
In patients with HIV infection and AIDS, the lesions
may not fit into the above described categories and
usually present as papules, nodules, vesicles or
induration.
Ulceration and discharge from the surface
of the lesions may occur.
The diagnosis is usually not suspected clinically and it
has been suggested that all atypical cutaneous lesions
developing in immunosuppressed individuals should
be biopsied and subjected to mycobacterial culture
Scrofula Scrofuloderma
Other EPTB
 Tuberculosis of the pharynx, oral cavity, larynx and
salivary glands
Tuberculosis of the ear
 Tuberculosis of paranasal sinuses and nasopharynx
 Ocular TB
 Breast TB
Complications and sequale of EPTB
Lymph node tuberculosis Pleural effusion
 Scars, sinuses
 Tracheo-oesophageal fistula  Pleural thickening & fibrosis
 Oesophageo-mediastinal fistula  Empyema thoracis
 Chylothorax  Empyema
 Chylous ascites
 Chyluria
Complications and
Neurological tuberculosis
sequale of EPTB
 Raised intracranial tension,
cerebral oedema, stupor
 Basal meningitis with cranial
nerve palsies
 Focal neurological deficits
 Hydrocephalus
 Tuberculoma
 Cerebral abscess
 Visual loss
 Arteritis leading to stroke
 Endocrine disturbances
 Hypothalamic disorders
 Diabetes insipidus
 Syndrome of inappropriate
antidiuretic hormone
secretion of (SIADH)
 Internuclear ophthalmoplegia
 Hemichorea
 Spinal block
 Spinal arachnoiditis
Complications and sequale of EPTB
Abdominal tuberculosis Pericardial tuberculosis
 Subacute intestinal obstruction  Cardiac tamponade
 Perforation and peritonitis  Chronic constructive pericarditis
 Haemorrhage
 Fistula, sinus formation
Complications and sequale of EPTB
Bone and joint
Genitourinary tuberculosis
tuberculosis
 Compressive myelopathy  Infertility
 paraplegia  Hydronephrosis
 Pyonephrosis
 Ureteric stricture & stenosis
Ocular tuberculosis  Urinary bladder related
 Visual Loss abnormalities
 Secondary glaucoma
 Optic atrophy
∆ of EPTB
 Definitive diagnosis of EPTB involves demonstration of M. tuberculosis
by microbiological, cytopathological or histopathological methods
 suspicion is the first step in the way of diagnosis
 CBC⇒ normocytic anaemia & lymphocytosis/↑ ESR
 Tuberculin skin test; In countries where tuberculosis is highly endemic,
tuberculin skin test alone is not sufficient evidence to diagnose EPTB
 non-invasive; ultrasound scan / CT scan / MRI
 invasive ; OGD, colonoscopy, laparoscopy, cystoscopy ē biopsy &
FNAC.
 Immunodiagnostic methods like (ELISA) can detect mycobacterial
antigens or antibodies in the blood and body fluids.
Clinical problem
A 32 years gentleman who work as a shop keeper presented to
the refer clinic with vague ill health, cough, loss of wt, low mood
& insomnia .
His PMH include; allergic rhinitis, recurrent chest infection.
O/E; looks ill, wasted, pale with multiple painful erythematous
Nodular swellings over his both shins.
Chest; stony dull percussion over Rt lower zone,↓air entry & end
Inspiratory crackles.

Investigations; CBC ⇒ anaemia, ↑TWBC ē lymphocytosis.

CXR; trachea shifted to the Rt side, fibrosis & p.effusion.
Clinical problem
Concerning this young man condition, please answer the
the following questions ;

(1) Mention other three clinical signs ?

(2) Mention three differential diagnosis ?
(3) Describe three helpful investigations ?
(4) What is your treatment plan ?
BOF
A 22 years old, non smoker lady who has 4 weeks history of cough &
copious, rusty, mucopurulent, blood stained sputum. undergone
general health survey came back with the following tests;
- neutrophilia - anaemia - normal PLT.
- CXR; diffuse mottling, fibrosis & hyperventilation.
What is first diagnosis that would cross your mind ?
(a) Idiopathic pulmonary fibrosis.
(b) Pulmonary TB
(c) Pneumonia
(d) Bronchiectasis
(e) Ca lung
‫اللهم صلي وسلم علي سيدنا محمد‬
‫وعلي اله وصحبه‬

‫‪THANK YOU‬‬