TB from A to Z

1. Tuberculosis and
Sarcoidosis
Dr . Samia Hussein Mustafa

2. 2
It is a communicable systemic chronic
granulomatous disease caused by
Mycobacterium Tuberculosis .

3. 3

4. 4
ETIOLOGY
• M. tb complex (MTBC) includes other mycobacteria that
can cause TB: M. bovis, M. africanum, M. canettii, M.
microti
• M.Tuberculosis.
The tubercle bacilli are :
• An aerobic.
• Non-spore forming.
• Non-motile.
• Grow best at(37-41)ْc.
• Acid alcohol fast bacilli i,e.(is difficult to stained due to
high lipid contents of the cell wall and once stained they
resist decolorization with acid-alcohol).
• Ziehl-Neelsen staining methods for identification.

5. 5

6. Global Problem
- WHO declared TB a global emergency 1993
- 9.6 million new cases/yr of which 37% are
unreported /undiagnosed.
- Leading cause of death worldwide,1.5 million
death/year.
- Co-infection with HIV in 12% of new cases
- Major problem with affordable therapy in some
countries

7. Tuberculosis
• 1882 – Robert Koch – “one seventh of all
human beings die of tuberculosis and… if one
considers only the productive middle-age
groups, tuberculosis carries away one-third
and often more of these…”

8. M tuberculosis as causative
agent for tuberculosis
1886
Robert Koch

9. 9

10. How Are TB Germs Spread?
• TB germs are passed through the air when a person
who is sick with TB disease coughs, sings, sneezes, or
laughs
• To become infected with TB germs, a person usually
needs to share air space with someone sick with TB
disease (e.g., live, work, or play together)
• The infectivity depends on the number of bacilli
present in droplets.
• These number is greatest in secretion from individual
with +ve culture sputum

11. TB: Airborne Transmission

12. Risk Factors for TB Infection
• Sharing air space with someone sick with TB
disease (e.g., live, work, or play together)
• Crowded living conditions
• Residency or travel in a country with a high
incidence of TB disease
• High risk occupations including laboratory and
health care jobs

13. Risk Factors for TB Disease
• Low socioeconomic status
• Homelessness
• Diseases, conditions or drugs that weaken the immune
system – Cancer – Transplantation – Malnutrition –
Diabetes – Alcoholism – HIV infection
• TB is the leading cause of death worldwide in HIV
infected individuals • 10% lifetime risk for developing
active TB among HIV uninfected
• Major surgical procedures may occasionally trigger
dissemination

14. How Are TB Germs NOT Spread?
• Through quick, casual contact, like passing
someone on the street
• By sharing utensils or food
• By sharing cigarettes or drinking containers
• By exchanging saliva or other body fluids
• By shaking hands
• Using public telephones

15. TB Infection vs. TB Disease
• There is a difference between TB “infection”
and TB “disease”
• TB infection: TB germs stay in your lungs, but
they do not multiply or make you sick
– You cannot pass TB germs to others
• TB disease: TB germs stay in your lungs or
move to other parts of your body, multiply,
and make you sick
– You can pass the TB germs to other people

16. Latent TB vs. Active TB
Latent TB (LTBI) (Goal = prevent future active disease)
= TB Infection
= No Disease
= NOT SICK
= NOT INFECTIOUS
Active TB (Goal = treat to cure, prevent transmission)
= TB Infection which has
progressed to TB Disease
= SICK (usually)
= INFECTIOUS if PULMONARY (usually)
= NOT INFECTIOUS if not PULMONARY (usually)

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Pulmonary TB
1. Primary pulmonary TB.
2. Progressive primary TB.
3. Post-primary(reactivated)(secondary)TB.

19. Primary Tuberculosis
- Primary complex = lesion + draining gland
- usually asymptomatic (75%)or have flu-like
symptoms along with fever and chest pain
• Around 3 weeks after infection, they become PPD+
(skin test)
• For most, the lesions eventually heal with fibrosis and
calcification
• Dormant lesions that still contain bugs may reactivate
to yield secondary TB

20. 20
Primary pulmonary tuberculosis:
• Usually asymptomatic.
• Non productive cough ,mild dyspnea ,Weakness or fatigue
,loss of appetite and difficulty gaining wt ,fever with night
sweats , anorexia with decreased activity.
• Diagnosis by +ve Mantoux test.
• Usually have a normal chest x-ray.
• Sometimes after 6 wks pt. develop Hypersenesitivity
manifestations which include:
1. Erythema nodosum.
2. phlyctenular keratoconjuctivitis.
3. fever & malaise.
4. pleural effusion.
• haemoptysis is rare .

21. Progressive Primary TB
• Some individuals (5-15%) don’t contain the primary
infection and develop a progressive disease that
resembles a necrotizing bacterial pneumonia
• This presents with fever, productive cough, and
chest pain
• Coughing aerosolizes secretions and distributes
them throughout the lung
• There are expanding areas of caseating necrosis
with irregular cavity formation along with erosion
of blood vessels resulting in hemoptysis
• Lesions will usually heal by fibrosis with adequate
treatment
• may have consolidation , cavitations and
lymphadenopathy in the chest -x ray

22. Post primary pulmonary tuberculoses
- Local spread – Pneumonia
- Haematogenous spread – Milliary
- Spread to bones and joints
- Spread to kidneys
- Reactivation
- Exogenous re-infection

23. • The lesions typically localize to the apex of the upper
lobes
• There is rapid tissue response (Th1) because of
previous sensitization
• Cavity formation is very likely
• Symptoms include low grade fever, night sweats, and
weight loss
• Without therapy, miliary TB may develop

24. Milliary Tuberculosis
- Uncontrolled haematogenous dissemination
- Progressive primary or reactivation
- Requires impaired immunity thus 50% in infants, elderly
and HIV+
- Clinical course variable; fumlinant to subacute
- Non specific presentation; failure to thrive ,night sweats,
pyrexia, ARDS
- Difficult to diagnose, 20% post mortem
- Hepatomegaly , ascites, deranged liver function
- Meningeal disease in 15 – 20%

25. • Multiorgan failure, septic shock, and
respiratory distress, followed by death, may
occur

26. Pathogenesis

27. TB Invades/Infects the Lung
Effective immune
response
Infection limited
to small area of lung
Immune response
insufficient

28. TB – A Multi-system Infection

29. Primary
Disease

30. Lobar
Pneumonia

31. Upper lobe
cavitatory
disease

32. Pleural Disease

33. Miliary Disease

34. Other Sites
- Lymph node
- Skin
- Meninges
- Renal tract
- Pericardial
-Hepatic and GI
-Bone
-Reproductive system
-Eye

35. Common Symptoms of TB Disease
• Cough (2-3 weeks or more)
• Coughing up blood
• Chest pains
• Fever
• Night sweats
• Feeling weak and tired
• Losing weight without trying
• Decreased or no appetite
• If you have TB outside the lungs, you may have
other symptoms

36. Diagnosis

37. 37

38. Diagnosis
Non-bacteriological
• screen HIV status
• Symptoms of disease
• History of TB exposure, infection, or disease
• Past TB treatment
• Demographic risk factors for TB
• Other medical conditions that increase risk for TB disease
(diabetes , immunosuppresion ,ESRD ,HIV , alcoholism
,silicosis )….

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Investigations:
•Full Blood Count:
•Hb  anemia.
•TWBC & Differential  leukocytosis
lymphocytosis.
•ESR  +++ >100 mm/hr.
•PBP  Type of anemia.
•Chest x-ray  severity of the disease. (usually
normal in primary T.B).

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*These chest X-rays show advanced pulmonary
tuberculosis. There are multiple light areas (opacities) of
varying size that run together (coalesce). Arrows indicate
the location of cavities within these light areas. The X-ray
on the left clearly shows that the opacities are located in
the upper area of the lungs toward the back. The
appearance is typical for chronic pulmonary tuberculosis.

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*Secondary
tuberculosis.
Some consolidation
in the right upper
lobe with a cavity
(arrowed), typical of
secondary
tuberculosis.

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Mantoux test:
•An intradermal injection.
•Usually in the volar surface of the
forearm.
stabilized purified tuberculus
Antigen.(PPD).
•0.1ml volume slowly injected.
•Is the standard for screening high-risk
populations and for diagnosis in all ill
Pt. or contacts.

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•10 mm induration reaction after 3 days
traditionally indicated infection.
• 5-10 mm induration indicates infection in a
high-risk populations(e.g , strong clinical
suspicion of TB , close contacts & HIV).
• 15 mm induration may be positive for low-
risk Pts.

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•Microscopic examination of sputum smears
•Sputum smear:
•defined as +ve < if at least 5 AFB are seen in 100 oil immersion fields of
the smear.
• sputum specimens must be collected and examined in 2-3 consecutive
days.
•Smear +ve pulm TB is confirmed when there are at least 2 AFB+ve
smear results or when one sputum specimen is +ve + radiographic
abnormalities consistent with active pulm TB.
sputum culture:
It is a complex and sophisticated tool which takes several weeks to
yeiled results (6 wks).

49. AFB smear-microscopy
Acid-fast bacilli (AFB) (shown in red) are tubercle bacilli

50. 50
TB suspect
Sputum examination
2 samples +ve or one positive
treat as + ve
2samples -ve
Give
antibiotics
No
improvment
Repeat sputum
At least 1+ve
2 -ve
Do other inv.
diagnostic
Treat as -ve
No TB
No TB
improved

51. 51
•Histo-pathological examination
Biopsies can play a role in the
confirmation of the diagnosis of extra
pulmonary TB , such as Tuberculus
lymphadenitis
Others
Automated test - Radiometric culture C14
PCR and other nucleic acid amplification
tests
Nucleic acid probes for various
mycobacteria

54. •
AIMS OF TREATMENT
1. To cure the Pt. of TB.
2. To prevent death from active TB.
3. To prevent complications.
4. To prevent relapse of TB.
5. To decrease transmission to others.
6. To prevent drug-resistance.
54

55. Notification
- TB is a notifiable disease
- Contact tracing
-Who was the source?
- Has the current patient been a source?
- Outcomes
- Not infected………….discharge
- Seroconversion but no clinical disease ……..chemo-
prophylaxis
- Active disease………..treatment

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*The requirements for adequate
chemotherapy are:
1. An appropriate combination of at least three to four drugs.
2. Prescribed in the correct dosage.
3. Taken regularly by the Pt.
4. For a sufficient period of time.
*The Pt. should be classified according to the following
criteria:
• Site of disease(pulm or extra-pulm).
• Severity of disease.
• bacteriological status(assessed by sputum microscopy).
• Hx of anti-TB treatment.

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Notes:
• Don’t start TB treatment until a firm diagnosis has
been made.
• Once diagnosis is made , and before beginning
treatment , every Pt. must be questioned carefully
as to whether or not they have ever taken anti- TB
drug before.
• Measuring baseline liver enzyme levels before the
initiation of isoniazid therapy is recommended only
in patients with a condition that puts them at risk
for hepatotoxicity, such as pregnancy or
postpartum status, human immunodeficiency virus
infection, alcoholism or chronic hepatitis.

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Antituberculus drugs:
*Rifampicin:
Is bacteriocidal ,excreted in bile but some times dose Not appear in
urine.
It found in form of tabs, capsules(300,150 mg)
Dosage:
10 mg/kg (<50kg ____ 450mg)
(>50kg ____ 600mg)
Adverse effect:
Hepatitis, hypersensetivity reactions, induction of Liver enzymes
Risk group of jaundice:
elderly women, alcoholic, pt with history of liver or Billiary disease.

59. 59
*Isoniazid:
Dose:
5mg/kg in chemotherapy
12mg/kg in miliary
Adverse effect:
Hepatits, hypersensetivity
*Pyrazinamide:
Given oraly, found in form of tabs 500mg, it execreted
By billiary system.
Dosage:
35mg/kg (<50kg ____ 1,5g)
(50-74 ___ 2g)
(>75kg ____ 2,5g)
Advese effect:
Arthralgia, hepatitis
.

60. 60
*Streptomycin:
Given in I.M inj, it excreted by glomerular filtration.
Dosage:
20mg/kg (<50kg _____ 750mg)
(>50kg _____ 1g)
(750mg given if pt >40years old)
Adverse effect:
Affect the 8th C.N, the vestibular effect is more than the
Auditary effect.
Pt presented with: unsteadiness of gait & nystagmus.
it’s ototoxic to fetus.

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*Ethambutol:
Given orally, excreted in the urine.
Dosage:
15mg/kg
Adverse effect:
Retrobulbar neuritis, pt presented with blurred vesion,
Disturbance of red.green vision.
(Best to be avoided in young children)

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?
?
?

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DIRECTLY OBSERVED TREATMENT , SHORT
COURSE
•
Is in practice a public health programme , implemented
by the general health services , which when applied
widely and continuously can avert the suffering , death
and disability from TB.
•
It means that a TB Pt. who is eligible for short course treatment
has to be given his drugs under the direct supervision of a health
worker whenever taking a combination of medication which
include rifampicin.

64. 64
*Each of the standardised chemotherapeutic regimens for the smear +ve cases consist of 2
phses:
.1
The initial intensive phase:
• For 2 months  new case.
• For 3 months  re-treatment cases
*Aim: To reduce rapidly and if possible eliminate the actively multiplying mycobacteria
without allowing the development of acquired resistance to the applied drugs .
This is a vital stage of the treatment and it should be absolutely certain that the Pt.
completes it correctly.
2.The continuation phase:
•
2-3 drugs  for 5 -6 months (Refina).
*Regimen
Pulmonary  6 , 8 moths
Extrapulm meningitis,miliary , bone/jont dis12 mo.

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Advantages of combinedtherapy:
-
INH is effective against rapidly metabolized bacilli.
-
pyrazinamide is effective in low PH & in prsistant
Bacilli (dormant).
-Rifampicicn is active against sporadically active bacilli.
There for combined therapy will attack the bacilli in all
Stages & will prevent the emergance of resistance to one
Drug.

66. • Follow-up of Treatment
1. History.
2. Examination.
3. Investigation
66

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68. 68
Complications of TB
•Haemoptysis.
•Pleural effusion.
•Spontaneous pneumothorax.
•Bronchiactisis
•Fibrosis.
•According to the site e.g;
•TB spine paraplegia.
•Constrictive pericarditis.
•Death.

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Prevention
•BCG vaccination.
•Health education.
•Good ventilation & reduce crowding.
•Keep hospitalized Pt. in a separate ward for the 1st.
2wks of T.
•Good nutrition.
•Pasteurisation or sterilisation of milk.
•INH chemoprophylaxis (daily dose of 5 mg/kg for 6
mo) for high risk Pt.

70. Vaccines
–
BCG (the Calmette-Guérin bacillus), a live attenuated
vaccine derived from M. bovis, is the most established
TB vaccine. It is administered by intradermal injection
and is highly immunogenic. BCG appears to be
effective in preventing disseminated disease, including
tuberculous meningitis, in children, but its efficacy in
adults is inconsistent and new vaccines are urgently
needed. Current vaccination policies usually target
children and other high-risk individuals. BCG is very
safe with the occasional complication of local abscess
formation. It should not be administered to those who
are immunocompromised (e.g. by HIV) or pregnant.

71. HIV and TB
- Nearly 40 million HIV+ 70% in sub-Saharan Africa
- 23/24 countries with prevalence of >5%. are in
sub-Saharan Africa
- 12-13 million have HIV + TB
- Annual risk of clinical TB if HIV+ is about 10%
(compared to 10% lifetime risk if HIV-)
- Both diseases worsen each others outcome
- Presentations can be similar
(Weight loss, Lymphadenopathy, Fevers sweats)

72. Take home messages
- Primary tuberculosis is usually asymptomatic
- High degree of suspicion required to diagnose
pulmonary tuberculosis
- Radiology helpful but diagnosis ultimately rests on
cultured samples, Newer diagnostic methods are
being developed
- Mortality appreciable despite drug treatment
which is lengthy and requires skilled supervision
- Notification, contact tracing and follow up
essential

73. Sarcoidosis

74. Objectives
• Definition
• Pathogenesis
• Clinical presentation
• Organ systems involved
• Diagnostic evaluation
• Current evidence on treatment

75. Sarcoidosis (Morbus Boeck)
• It is clinically well defined, systemic,
granulomatous disease of unknown origin.
•
Histology
•
Altered immune
response
75 75

76. Etiology and Pathogenesis
• Cause is unknown, although both genetic and
environmental factors suspected.
• Theory that disease develops in genetically
predetermined hosts who are exposed to
certain environmental agents that trigger an
exaggerated inflammatory immune response
leading to granuloma formation.

77. Etiology and Pathogenesis
• Hallmark is noncaseating granulomas, composed of a
central core of epithelioid histocytes and
multinucleated giant cells.
• Activated T cells and macrophages accumulate at site
of inflammation.
• Release chemoattractants and GF’s lead to cellular
proliferation and granuloma formation.
• Progressive granulomatous inflammation leads to
injury, dysfunction, and destruction of the affected
organs.

78. T cells, Macrophages
Chemoattractants
Growth Factors
Cellular proliferation
Granuloma
Fibrosis
Pathogenesis

79. Clinical features
The peak incidence is in the third and fourth decade.
- Females are more affected than males
- The most common presentation is with respiratory symptoms
or abnormal X-ray (50%)
- Fatigue or weight loss (5%)
- Peripheral lymphadenopathy (5%)
- Fever (4%)
- Neurological presentations are rare

80. Clinical Presentation
• Onset of sarcoidosis in white patients is
usually asymptomatic.
• African Americans tend to present with an
earlier onset and a more aggressive and
severe clinical course.
• Chronic pulmonary sarcoidosis and the
disfiguring cutaneous lesions of lupus pernio
are also more common in African Americans.

81. Clinical Presentation
• Spontaneous remission in two-thirds of
patients within 2 years of presentation
• 10%-30% experience chronic disease causing
progressive organ damage
• Leads to death in 4% of patients, usually those
with pulmonary, cardiac, or CNS involvement

82. Systems affected by Sarcoidosis
Cardiac
30%
Palpitations, syncope, dizziness, chest pain,
arrhythmia, sudden death
Cutaneous
25%
Erythema nodosum, lupus pernio, plaques,
subcutaneous nodules, maculopapular eruption,
alopecia, hyper/hypopigmentation
Endocrine Hypo/hyperthyroidism, adrenal insufficiency
Exocrine Painless swelling of parotid gland, keratocon-
junctivis sicca
Hepatic
50-80%
Asymptomatic or abdominal pain, abnormal LFT’s,
hepatomegaly
Lymphatic Extrapulmonary lymphadenopathy, splenomegaly
Signs and symptoms

83. Erythema Nodosum

84. Lupus Pernio

85. Systems affected by Sarcoidosis
Neurologic
5%
Cranial nerve palsy, seizures, basal granulomatous
meningitis, hypothalamic or pituitary lesions,
hydrocephalus, peripheral neuropathy, psychiatric
Ocular
20%
Uveitis, chorioretinitis, keratoconjunctivitis,
glaucoma, cataracts, blindness, Heerfordt
syndrome
Pulmonary
90%
Asymptomatic or dyspnea, nonproductive cough,
wheezing, radiographic findings from hilar
adenopathy to fibrosis
Renal Hypercalcemia, hypercalciuria, renal insufficiency
Signs and symptoms

86. Clinical Presentation
• A progressive course is more likely in:
– Age of onset > 40 yrs
– Black race
– Cardiac or renal involvement
– Lupus pernio
– Chronic uveitis
– Hypercalcemia
– Nasal mucosal involvement
– Cystic bone lesions
– Neurosarcoidosis
– Pulmonary fibrosis

87. Clinical features of sarcoidosis
87 87

88. Clinical Presentation
• Most patients have the pulmonary
manifestations, most commonly presenting
with incidental findings on CXR.
• Interstitial disease
• Symptoms include dry cough, dyspnea, and
chest discomfort
• Unpredictable course

89. 4 Stages of Pulmonary Sarcoidosis
I Bilateral hilar lymphadenopathy
and paratracheal adenopathy
55-90%
remission
II Mediastinal adenopathy with
pulmonary parenchymal
involvements
40-70%
III Pulmonary parenchymal without
adenopathy
10-20%
IV Pulmonary fibrosis with
honeycombing
0-5%

90. Stages

91. 91 91

92. Approach to Suspected Sarcoid
• History (occupational and environmental)
• PE (lungs, skin, eyes, liver, and heart)
• CXR, PFT’s and ECG
• CBC, ACE level, Calcium level
• HRCT CHEST
• BAL
• TBB: Biopsy for histological confirmation of
noncaseating granulomas and culture and/or special
staining to R/O fungal or TB (Tuberculin test:
negative)
• Ophthalmologic evaluation

93. • Gallium scan
• Mediastinoscopy
93 93

94. Differential Diagnosis of BHL
• Granulomatous infections
• TB
• Histoplasmosis
• Coccidiomycosis
• Autoimmune disorders
• Malignancy (Lymphoma)

95. Differential Diagnosis of Noncaseating
Granulomas
• TB
• Fungal infections
• Lymphoma
• Epithelioid tumors of the breast
• Lung cancer

96. Treatment
• Observation
• Initiating corticosteroid therapy when
appropriate
• Monitoring response to therapy

97. Treatment
• Systemic corticosteroids for patients with
unresponsive ophthalmic manifestations,
cardiac, neurologic and progressive pulmonary
involvement.
• Systemic therapy for patients with
hypercalcemia.

98. Treatment
• Prednisone, 20 to 40 mg/d in divided doses or
alternate-day dosing is used for organ
involvement that is not life threatening.
• Higher dosage is used off-label for potentially
life threatening disease.

99. Treatment
Clinical improvement should be assessed after 3
months of corticosteroids.
Other immunosuppressive or anti inflammatory
if corticosteriods uncontrolling the disease or
there is side effects.
Long term adverse affects of therapy include
weight gain, mood swings, cataracts, GERD,
osteoporosis

100. Alternatives
Drug, dosage Use in sarcoidosis Comment
Methotrexate, 10-25
mg once weekly to
max of 1 g or 2 yrs
Chronic or worsening
disease, common second
line drug
Effect may take 6 mo,
Nausea, neutropenia,
and liver toxicity
Azathioprine
(Imuran), 50-200 mg
QD
Chronic or worsening
disease, advanced fibrotic
sarcoidosis
Nausea, neutropenia
Cyclophosphamide
(Cytoxan) 50-150 mg
QD or 500-2,000 mg
q 2wk IV
Refractory cases only Toxicity limits use,
Nausea, neutropenia
Requires intense
monitoring and F/U
Hydroxychloroquine
(Plaquenil), 200-400
mg QD
Cutaneous manifestations,
hypercalcemia, chronic
pulmonary fibrotic disease
Corneal deposits,
retinopathy. Ophtho
exam prior to treat-
ment and q 6 mo

101. Thank You!