Miliary Tuberculosis After Pneumonia Infection

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Presented by:Arif Fakhrudin

February 22nd 2011

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AFB : Acid Fast Bacilli

BCG : Bacill Calmete Guerin

BMI : Body Mass Index

BW : Body Weight IBW : Ideal Body Weight

TB : Tuberculosis

TST : Tuberculin Skin Test

WHO : World Health Organization

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Introduction

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Miliary TB

a form of progressive tuberculosis resultingfrom massive lymphohematogenous

dissemination of Mycobacterium tuberculosis

from a pulmonary or extrapulmonary focus tovarious organs.

Chest radiography: Millet like (range 1-5 mm)seeding of TB Bacilli

4Baker SK, Glassroth J. Milliary tuberculosis. In: Rom WN, Garay SM, editors. Tuberculosis. 2 ed.Philadelphia: Lippincott William&Wilkins, 2003:427-44.


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Miliary TB must be considered in the differential

diagnosis when antibiotic therapy for commonorganisms fails to treat pneumonia.

About 50-90% of patients present the miliary

pattern with disseminated tuberculosis

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Fernandes SR, Homa MN, Igarashi A, Salles AL, Jaloretto AP, Freitas MS, et al. Miliary tuberculosis with

positive acid-fast bacilli in a pediatric patient. Sao Paulo Med J2003;121(3):125-7.


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The risk of TB infection ~ duration and proximity of

exposure to an infectious case

Initial primary exposure plays significant role

in the development of a latent TB infection

Predisposing factors of miliary TB:

immunodeficiency, malnutrition, corticosteroids and

immunosuppressive therapy

6Golden MP, Vikram HR. Extrapulmonary tuberculosis: an overview. Am Fam Physician 2005;72(9):1761-8.

Sablan B. An update on primary care management for tuberculosis in children. Curr Opin Pediatr

2009;21(6):801-4.


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The characteristic feature of post primary TB:

- Extensive lung destruction with cavitation,

- Positif sputum smear,

- Upper lobe involvement- Usually no intrathoracic lymphadenopathy.

A first episode of TB may be primary orpost primary (reactivation of the dormant tubercle)

7

Maher D. The natural history of Mycobacterium tuberculosis infection in adults. In: Schaaf HS, Zumla A,

editors. Tuberculosis a comprehensive clinical reference. London: Saunders Elsevier, 2009.129-32


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OBJECTIVE

Present a case of miliary tuberculosis after

pneumonia infection in a chlid.

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Case Report

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Case Report

A, 3 years old girl

Main complaint:

Shortness of breath since 3 days before admission.Preceded by a productive cough 10 days prior

admission.

High grade fever 3 days prior admission.

No other people around her has same sign and

symptom.

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Previous and family history

No history of chronic cough and dyspneu.No complaint of vomiting, lost of appetite or weight lost.

Her weight one month before was 20 kg.

TB contact:Her mother had been treated with anti tuberculosis

drug when she was 1 years old.

Her uncle wich is her neighbour has been treating

antituberculosis drug since 3 months ago.

Immunization: complete

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Physical examination

An alert, irritable girl

BP: 90/60 mmHg, Pulse: 126 x/min, RR: 60 x/min t :

38,9 C.

Dyspneu (+), nasal flare (+)

Chest symetric, retraction intercostal spaces,epigastric and clavicula region

The breath sound: vesiculer/vesiculer, coarse rales

+/+, wheezing -/-

Heart : normal Abdominal : normal

Extremities : normal

Enlargement of lymph nodes -12


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BW=19 kg

BH=95cm

BMI 21kg/m2

> 3SD

Nutritional status


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Hb :11.1 g/dlWBC : 21.5 K/uL

Platelet : 465 K/uL

Hct : 30.9%

pH : 7.47pCO2 : 27

pO2 : 48

HCO3 : 19.7

BE : -4.0SaO2 : 86%

Potassium : 4.6meq/l Sodium : 144 meq/l

Chloride : 106 mmol/l

Calsium : 7.9 meq/l

AST : 42 U/I ALT : 34 U/I

CRP : 87,5

Laboratory examination

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Chest X-ray

The heart was normal in shape and size.

The diffuse spread of infiltrat was found in both of the lung

field. There were no lung cavity, pneumatocele and pleural

efusion 15


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History

Clinical manifestations

Laboratory findings

Radiology findings

Severe Pneumoniawith Obesity

Initial treatments:

- Oxygenation

- Ampicilin sulbactam- Amikacin

- Antipyretic

- Adequate fluid and nutrition

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On the 7th day of admission

-Weak condition, no fever, dyspnue, chest retraction

-Tuberculin skin test + (induration 15 mm)-Acid Fast Bacilli +

Chest x-ray: Miliary spot in both of the lung fields without pleural effusion,

cavity and pneumatocele

Dx: severe pneumonia, miliary tuberculosis and

obesity.

Antibiotic was continued, antiTB drug was

administered

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On the 13th day of admission,

six days of antitubercolosis treatment

No any complaint. There were no fever, dyspneu, chest retractionand rales. The blood culture was no bacterial overgrowt.

The chest radiograph still revealed miliary spot in the both of lung

field.

The patient was discharged with a good conditionand was planned to routinely going to Pediatric

Pulmonary Outpatient Clinic of DR Soetomo

General Hospital.

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Discussion

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On admission 7th days of

admission13th days of

admission

The progression of chest x-ray

The diffuse spread

of infiltrat

Miliary spot in both

of the lung

still revealed

miliary spot


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On the admission Dx: severe pneumonia although there was TB contact

The WHO has defined pneumonia solely on the basis

of clinical findings obtained by visual inspection and

timing of the respiratory rate. Pneumonia isrespiratory disease which shown evidence of cough,

dyspnoe, fever, moist rales and infiltrate in

radiographic features of the chest

- Cough- Dyspnea

- Fever

- Moist rales

-Infiltrat in xray

Pneumonia

21McIntosh K. Community-acquired pneumonia in children.N Engl J Med2002;346(6):42937.


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-3 years old,

-dyspnea,

- high fever,-leucocytosis,

-diffuse infiltrate on chest

x-ray

Bacterial infections such as Streptoccocus Pneumoniae

< 5years.

Bacterial pneumonia usually presence suddenly,The patient seen toxic, high fever with trembling and

dyspneu getting worse in short time.

Bacterial infection

Tx: B lactame and

aminoglicoside

22McIntosh K. Community-acquired pneumonia in children.Engl J Med2002;346(6):42937.Ostachuck M, Robert DM, Haddy R. Community-aquired pneumonia in infant and children. Am Fam Physician-


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After 7 days of treatment:

The sign and symptom were improved.

- Tuberculin skin test +

- Acid Fast Bacilli +

- Chest x-ray: suggesting

TB (miliary spot)

TB score:6

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Dx: Miliary TB


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The onset of miliary TB is insidious: weight loss, fever,

cough.Usually chest sign are not present at the onset but later

fine crackles may be heard over the whole of the chest.

The fever runs a irregular course with spikes up to 400C.

Wasting may be extreme.

In this patient we found high fever, cough and no

weight loss

24Robinson MJ, Lee EL. Tuberculosis in childhood. In: Robinson MJ, Lee EL, editors.Paediatric problem in tropical countrie. 2 ed. Singapura: PG Publishin, 1991:193-8.


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A positive or reactive TST indicates TB infection.

Defined as > 10 mm diameter of induration when

read 48-72 hours after administration in any childirrespective of BCG immunization.

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On this patient, had BCG immunization, and TST

result + (15 mm of induration)

Graham SM, Marais BJ, Gie RP. clinical features and index of suspicion of tuberculosis in children. In: Schaaf HS,

Zumla A, editors. Tuberculosis a comprehensive clinical reference. London: Saunder Elsevier, 2009:154-63.

Colditz GA, Brewer TF, Berkey CS, Wilson ME, Burdick E, Fineberg HV, et al. Efficacy of BCG vaccine in theprevention of tuberculosis. Meta-analysis of the published literature.JAMA 1994;271(9):698-702.

False positive reaction can be caused by cross

sensitization to antigens of nontuberculousmycobacteria (


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The mother got antiTB drugs for 3 years ago, and

now already improved.

Unfortunately she still have a tuberculosis contact

from her uncle.

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The mother and uncle had obviously infected this

patient


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The chest X-ray shows a miliary pattern at

presentation in more than half of the patients.

It is important to note that even if not present

initially, miliary patterns often become apparentdays to weeks later.

The chest x-ray showed wide spread miliary TB

but in the first time of chest x-ray revealed difuseinfiltrate.

27Baker SK, Glassroth J. Milliary tuberculosis. In: Rom WN, Garay SM, editors. Tuberculosis. 2 ed. Philadelphia: LippincottWilliam&Wilkins, 2003:427-44.

This patient


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AFB was gold standar for TB diagnosis in adult but

no for children.

AFB (+) indicated the infection of the endobroncial

due to post primary TB.

28Fernandes SR, Homa MN, Igarashi A, Salles AL, Jaloretto AP, Freitas MS, et al. Miliary tuberculosiswith positive acid-fast bacilli in a pediatric patient. Sao Paulo Med J2003;121(3):125-7.

On this patient: had positive AFB from gastric

aspirates


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Miliary tuberculosis is due to spread through the

blood stream of large number of TB which the

patients defences are to week to kill off.

Reactivation of an old tuberculous lession (primary or

post primary) with erosions of a blood vessel.Reactivation may occur if the patients defences are

lowered

The immunosupresion was caused by severe

pneumonia and also caused by obesity

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Many cases of primary TB infection in children are

asymptomatic, self-healing and remain completelyunnoticed or accidentally discovered at a later stage.

Factors :host genetics, microbial virulence andunderlying conditions that impair immune

competence determine the outcome of infection.

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a reflection on the immaturity of the immune response.

Newton SM, Brent AJ, Anderson S, Whittaker E, Kampmann B. Paediatric tuberculosis.Lancet Infect Dis 2008;8(8):498-510.


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This child was a three years old

Age is an important aspect of the epidemiology of

childhood tuberculosis. About 60% of tuberculosiscases in children in the United States occur in

infants and children


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Risk of disease following primary infection (%)Age at infection

(years)Disseminated TB Pulmonary TB No disease Comments


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This patient has obese of nutrition status

Nutritional status is significantly lower in

patients with active pulmonary TBcompared

with healthy controls in different studies inIndonesia, England, India, and Japan.

In Indian study, tuberculosis patients were

respectively 11 and 7 times more likely to have a

BMI < 18.5

Gupta KB, Gupta R, Atreja A, Verma M, Vishvkarma S. Tuberculosis and nutrition.Lung India 2009;26(1):9-16.

Lamas O, Marti A, Martinez JA. Obesity and immunocompetence.Eur J Clin Nutr2002;56 Suppl 3:S42-5.


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Positing that cytokines from adipocytes cannot be

important in this arena because they are restricted toareas near their secretion site and do not reach the

site of the infection, the lung

M. TB spread promptly from the primary site of

infection via lymphatics and the bloodstream to

hilar lymph nodes, apices of both lungs, and sitesthroughout the body, where they can remain

dormant but viable, capable of reactivating disease

at any time.

Lamas O, Marti A, Martinez JA. Obesity and immunocompetence.Eur J Clin Nutr2002;56 Suppl 3:S42-5.


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Summary


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A case of miliary tuberculosis afterpneumonia infection has been presented.

Post primary TB occured after a latent

period of 3 years after primary infection,

with tuberculosis contact, tuberculin skin

test, acid fast bacilli from gastric aspirates

and chest x-ray was supported


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Thankyou

Parameter 0 1 2 3

Table Scoring system for diagnosis tb in children


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TbcontactNotclear

Family report, AFBor not clear

Cavity +,AFBnot clear

AFB +

Tuberculin test negPositive ( 10 mm

or 5mm inimmunocom-

promised condition)

Bodyweight ornutritional status

BW/H< 90 % orBW/age < 80 %,BW not >> in2 mo

Severe mal-nutrition orBW/ H


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In our case

PULMONARY

TUBERCULOSIS

History ofcontact withadult activetuberculosispatient

FeverCough

Chest Ro :miliary TB

Tuberculin test

positive 15 mm AFB positive

Environment:Poor ventilation

room

BMI > 3SD


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Anti TB Drugs

Mechanism of Action Side Effect

Isoniazid Bactericidal & bacteriostatic

Inhibition of biosintesis mycolic acid

especially organism that actively developedpenetrates rapidly into all tissues & lesions,its activity is not influenced by the pH of theenvironment

Hepatotoksic

Neuritis

Rifampisin Strong bactericidal & bacteriostatic

DNA-dependent RNA polymerase (rantaisintesis RNA) inhibition

Hepatotoksic

Ethambutol Bacteriostatic (inhibition of biosintesis ofarabinogalactan, main polisacarid

Mycobacterium membrane)

Effective for INH/RIF resisten

Neuritis

Retrobulbar

Uric acid


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Mechanism of Action Side EffectPyrazinamid Bacterisidal, sterilizing effect inside

macrophages where organisms growslowly because of the acid pH of theenvironment

Hepatotoksic

Streptomisin Bacterisidal & bacteriostatic

(supression, not eradication)

Disturb protein synthesis (ribosomsubunit 30S)

Can get into cavity, but cantpenetrates into intracelluler fluid

Ototoksic

Nefrotoksic


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Improvement of M.tbinfection

Th1

IFNIL12 IL-2

Th2

Th

IL-4

IgE

+


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Genetic as well as acquired defects in host immune

response pathways greatly increase the risk of

progressive disease.

TB disease susceptibility is highly likely to bepolygenic, with contributions from many minor

loci. A large number of TB susceptibility markers

have been identified from candidate gene studies

as disease-causing genes including TIRAP, HLA

DQB1, VDR, IL-12,IL12R1, IFN-, SLC11A1

andMCP-1.

This patient suffer from TB so does her mother

and uncle

Levin M, Newport M. Understanding the genetic basis of susceptibility to mycobacterial infection.Proc Assoc Am Physicians 1999;111(4):308-12.

N t iti l t t


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BW=19 kg

BH=95cm

IBW 14.5 kg

130% IBW

Mild obese.

Nutritional status

N t iti l t t


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BW=19 kg

BH=95cm

BMI =21 kg/m2

> P 95

Nutritional status

Miliary Tuberculosis After Pneumonia Infection

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