Tuberculosis

Thurgaashini
Amanina Athirah
Liew John
Types of tuberculosis &
managements
Types of tuberculosis

1. Pulmonary tuberculosis (mainly involves in

lungs and pleura)
a. Primary tuberculosis
b. Secondary tuberculosis
2. Extrapulmonary tuberculosis
a. Lymph node tb
b. Genito-urinary
c. disseminated /miliary tb
d. Skeletal tb
e. Meningeal tb
f. Pericardial tb
Pulmonary tuberculosis

● The major pathology in tuberculosis is necrotizing granulomatous inflammation with the lungs
being the primary organs of involvement
○ Main pathological feature: granuloma formation (a rounded collection of macrophages
surrounded by lymphocytes with unique feature - “caseation” or central necrosis)
● Risk factors:
○ It commonly affects people living in crowded conditions
■ Institutionalized patients
■ immigrants from countries with a high prevalence of tuberculosis
○ immunocompromised such as patients with HIV or diabetes, chronic corticosteroid used
○ Health care workers
● Transmission: via aerosolized microdroplets
○ From coughing patients with active tuberculosis
○ Sneezing
○ Prolonged exposure towards active tuberculosis patients
Primary infection of PTB

● Majority patients will remains asymptomatic where most of them able to clear off the
infection
● However, some patients may enters ‘latent’ phase where patients have risk for reactivation
in the future
● Clinical signs and symptoms
○ Prolonged fever with diurnal pattern
○ Prolonged cough: progressively worsening and may produce greenish or blood-tingew sputum
○ Shortness of breath
○ Night sweats
○ Nonpulmonary symptoms such as lymphadenopathy, fatigue, pharyngitis, anorexia, weight loss and
loss of muscle mass
Secondary TB/latent TB

● Majority of infected individuals who get infected do not actually develop symptoms
until months to years after their initial exposure.
● Reactivation of tuberculosis is a prolonged process that take years to progress and
usually occurred after immunosuppression in the host
● Symptoms are not very different from primary disease
● Classical signs and symptoms
○ fever, cough, shortness of breath, and weight loss
● The lesions of secondary tuberculosis are usually seen in the lung apices
○ presence of cavitation (differences with primary progressive tuberculosis)
Extrapulmonary TB

● Clinical signs that highly suspicious for EPTB

○ Ascites with lymphocyte predominance and negative bacterial cultures
○ Chronic lymphadenopathy (especially cervical) *most commonly occurring form of EPTB
○ CSF lymphocytic pleocytosis with elevated protein and low glucose
○ Differential diagnosis of Crohn’s disease and amebiasis
○ Exudative pleural effusion with lymphocyte predominance, negative bacterial cultures, and pleural
thickening
○ HIV infection
○ Joint inflammation (monoarticular) with negative bacterial cultures
○ Persistent sterile pyuria
○ Unexplained pericardial effusion, constrictive pericarditis, or pericardial calcification
○ Vertebral osteomyelitis involving the thoracic spine
 Lymphadenitis Tb

● Most commonly occurring form of extrapulmonary

tuberculosis.
● Cervical adenopathy is most common, but inguinal,
axillary, mesenteric, mediastinal, and intramammary
involvement
● Patients without HIV infection typically present with
chronic, nontender lymphadenopathy
● Patients with HIV infection usually present with fever,
night sweats, and weight loss
● The nodes are discrete, firm, and nontender; with time,
a firm mass of matted nodes becomes visible.
● If untreated, the nodes become fluctuant and drain
spontaneously with sinus tract formation.
Miliary tuberculosis
● Any progressive, disseminated form of tuberculosis
○ the disease can occur during primary dissemination or after years of untreated tuberculosis.
● Presenting symptoms include fever, chills, night sweats, weight loss, and anorexia.
○ Clinical manifestations depend on the organs involved.
○ Fulminant disease including septic shock, acute respiratory distress syndrome, and
multiorgan failure
● A chest radiograph or CT scan reveals numerous 2- to 3-mm nodules scattered throughout the
lung
● Laboratory investigations may reveals normochromic anemia, leukopenia or leukocytosis,
elevated sedimentation rate, and hyponatremia.
● Examination of the sputum, bronchoalveolar lavage, gastric washings, CSF, blood culture, or
biopsies of liver and bone marrow may be necessary for diagnosis
Central Nervous System TB
● Central nervous system tuberculosis includes tuberculous meningitis (the most common presentation)
intracranial tuberculomas and spinal tuberculous arachnoiditis
● Meningitis results from intense inflammation following rupture of a subependymal tubercle into the
subarachnoid space which can spread to cranial nerves and vessels leading to cranial nerve palsies and
communicating hydrocephalus
● Clinical signs and symptoms
○ Loss of consciousness, seizures, and raised intracranial pressure
○ An initial phase of malaise, headache, fever, or personality change is followed in two to three
weeks by protracted headache, meningismus, vomiting, confusion, and focal neurologic
findings.
○ If untreated, mental status deteriorates into stupor or coma.
○ Atypical presentations include a rapid progression simulating pyogenic meningitis, subtle
cognitive decline mimicking dementia and a predominant syndrome of encephalitis.
Cont.

● A high index of suspicion is necessary for timely diagnosis and prompt initiation of therapy.
● CSF typically reveals
○ moderate lymphocytic pleocytosis (100 to 500 cells per μL [0.10 to 0.50×109 per L])
○ Neutrophilic predominance can be seen
○ CSF protein levels range from 100 to 500 mg per dL (1,000 to 5,000 mg per L) and can be extremely high (2 to
6 g per dL [20 to 60 g per L])
○ Xanthochromia in the presence of subarachnoid block
○ CSF glucose concentration usually is less than 45 mg per dL (2.50 mmol per L).
○ AFB smears on CSF may reveals positive results
○ CSF culture for M. tuberculosis will shows positive results but takes four to six week
● A CT scan of the head with contrast may reveal basilar arachnoiditis, infarction, hydrocephalus, or tuberculomas
Management

1. Newly diagnosed pulmonary Tb

○ Standard anti-TB treatment (6 month regimen which consist of daily 2 month of EHRZ and followed by daily 4
month of HR)
 Duration of treatment

● May be prolonged if
○ Persistently AFB smear
positive after 2 months
○ Extensive cavitation on
CXR
TB in HIV co-infection

● Active TB should be ruled out in all HIV-positive patients.

● Isoniazid prophylaxis therapy for 6 months
● Initiation of HAART during TB: reduces mortality and results in earlier culture clearance
○ Efavirenz - preferred Non-Nucleoside Rwverse Transcriptase Inhibitor (NNRTI) with combination of 2
Nucleoside Reverse Transcriptase Inhibitors
Extrapulmonary TB

● A six- to nine-month regimen

○ two months of isoniazid [INH], rifampin [Rifadin], pyrazinamide, and ethambutol [Myambutol]
○ followed by four to seven months of isoniazid and rifampin
● For patients with central nervous system tuberculosis, including meningitis
○ at least nine to 12 months of therapy
● Extended therapy also may be required for patients with bone and joint tuberculosis, delayed treatment
response, or drug resistance.
● Adjunctive corticosteroids may be useful in patients who have tuberculous meningitis, tuberculous
pericarditis, or miliary tuberculosis with refractory hypoxemia
Precautions

● Patients with suspected active tuberculosis should be isolated with airborne precaution
○ requiring negative pressure room either through a high-efficiency particulate air filter
or by exhausting the air outside
○ Any person entering the room should be wearing high-efficiency airborne masks (Eg
N-95) to filter the tubercle bacillus
● Isolation should continue until collected sputum smears are negative for three consecutive
determinations, usually after approximately 2 to 4 weeks of treatment
 Referral criteria to Tb expertise

● Unsure of TB diagnosis
● Retreatment of TB
● Adverse events following antiTB drugs
● MDR-TB & extensively drug-resistant
TB
● EPTB except for tuberculous
lymphadenitis
● Renal &/or liver impairment with TB
● HIV-TB co-infection
● Smear negative TB
● Smear positive after 2 months of treatment
● All children diagnosed with TB
● Maternal TB
● Complex TB cases requiring surgical
intervention
Adverse Drug Reaction of Anti
Tuberculosis Drugs
Common Adverse Effects of Anti-tuberculosis Drugs

Isoniazid -Skin rash, jaundice, hepatitis, anorexia, nausea, abdominal pain, burning/numbness/ tingling
sensation in hands or feet

Rifampicin - Skin rash, jaundice, hepatitis, anorexia, nausea, abdominal pain, orange/red urine, flu syndrome
(fever, chills, malaise, headache, bone pain)

Ethambutol - Visual impairment

Pyrazinamide - Skin rash, jaundice, hepatitis, anorexia, nausea, abdominal pain, joint pain
• Anti-tuberculosis cutaneous adverse drug reactions

Range in severity from mild to severe

Severe cutaneous adverse reaction (SCAR) is a term specifically used to describe drug induced

-Stevens Johnson Syndrome,

-Toxic Epidermal Necrolysis,

-Drug Reaction with Eosinophilia and Systemic Symptoms,

-Acute Generalised Exanthematous Pustulosis.

SCARs are potentially life-threatening and hence patients with suspected SCAR should be referred to dermatologists for
co-management.
Anti-tuberculosis drug-induced liver injury

Anti-TB drugs may cause an elevation of ALT either through liver adaptation or liver injury.

Liver adaptation to drugs is a benign process that is associated with transient, mild ALT elevation that resolves
despite continuation of treatment

Drug induced liver injury leads to serious complications if treatment is continued

 How to diagnose anti-TB drug-induced liver injury
The American Thoracic Society criteria:

i. In patients with symptomatic hepatitis, an ALT ≥3 times the upper limit of normal (ULN)

ii. In patients without any symptoms, an ALT ≥5 times the ULN

2. The international drug-induced liver injury expert consensus criteria uses any of the following, regardless of symptoms.

i. an ALT ≥5 times ULN

ii. an ALP ≥2 times ULN

iii. an ALT ≥3 times and total bilirubin 2 times ULN

Other causes of abnormal liver function should be ruled out.

Drug challenge

Drug challenge is the gold standard for diagnosing anti-TB ADR including drug hypersensitivity reaction.

Drug challenge is used when multiple drugs may be responsible for the suspected ADR.

It is done with the least likely offending drug first or in the order of the drug’s importance. In severe or serious
ADR, drug challenge should be done in a graded manner when the patient has recovered.
Recurrence of ADR during drug challenge identifies the offending drug(s). Recurrence of ADR during
drug challenge identifies the offending drug(s).
Treatment of adverse drug reactions in active tuberculosis

•Symptomatic management and reassurance should be offered to all patients with ADR

• In cases of mild to moderate ADR, addition of symptomatic treatment may be sufficient

• In cases of severe ADR, all anti-TB treatment should be interrupted unless the offending drug is known
Drug desensitisation
Drug desensitisation may be attempted in cutaneous ADR except for SCARs

Drug desensitisation may be started at 1:100 of the full dose of the offending drug

2 drug desensitisation techniques are used.

• In rapid desensitisation, the drug is given in escalating doses at hourly interval or less. The daily cumulative
dose should not exceed the maximum daily dose for the drug.

• Slow desensitisation is done at a slower rate than rapid desensitisation. It is typically done daily or twice a day.
It may also be attempted in patients who have failed rapid desensitisation
Human Immunodeficiency Virus-Tuberculosis (HIV-TB) Co-infection

TB is one of the most important opportunistic infections and causes of death amongst people living with HIV

PTB may show atypical features especially in advanced HIV infection. PLHIV with TB may not CXR.

TB-HIV coinfected patients, antiretroviral treatment (ART) should be initiated regardless of their CD4 cell count.

However, TB treatment should be initiated first in ART-naïve patients.

In HIV with TB meningitis, initiation of ART may need to be delayed until two months post-TB treatment as
immediate ART is associated with more severe ADR
 Immune reconstitution Inflammatory Syndrome
Immune Reconstitution Inflammatory Syndrome (IRIS) is an augmented inflammatory response in patients commenced on
ART and anti-TB.

Usually occurs within three months of TB treatment, typically within two to twelve weeks after the initiation of ART.

Major symptoms include fever and lymphadenitis

Risk factors for IRIS:

-EPTB

-Hb < 10g/dL

-Baseline CD4 < 50 cell/µL

Tuberculosis in pregnancy and lactation

Standard anti-TB regimen (2EHRZ/4HR) can safely be administered

RIF may cause yellow or orange coloured-milk which is harmless, Breastfeeding should be continued in lactating
mothers

Drugs in breast milk should not be considered to serve as an effective treatment for TB or for LTBI in a nursing infant

Surgical mask should be used if the mother is infectious

Tuberculosis with renal impairment

All four anti-TB drugs may be administered after hemodialysis to facilitate DOT as well as to avoid premature
drug removal

There is significant renal excretion of EMB and metabolites of PZA, and doses should therefore be adjusted

Dose in renal impairment: CrCl <30 ml/min or HD

Ethambutol :20 - 25 mg/kg/dose 3 times/week
Pyrazinamide : 25 - 35 mg/kg/dose 3 times/week