Case Conference

De Vera, Dela Cruz, Dela Cruz, Dela Cruz, Dela Rosa, Dimalala

General Data

J.T.6 years and 2 months old, Female416 Hernandez 2nd St. Sampaloc ManilaRoman CatholicFilipino

Informant: Mother Reliability: Good

CHIEF COMPLAINT:

Right lateral cervical mass

History of Present Illness

9 days PTC: patient had productive cough with whitish phlegm, no fever, no colds

-no medications and consultations done-resolved after 2 days

7 days PTC: appearance of mass on the left lateral part of the neck.

-progressed in size and became tender-sought consult = MUMPS no

medications given-progression in size

REVIEW OF SYSTEMSNo weight loss, no weight gainNo rashes, no jaundice, no pruritus, alopeciaNo dizziness, no lacrimation, no hearing difficulties, no aural discharge,

no toothache, no sore throatNo chest pain, no difficulty of breathingNo cyanosis, no easy fatigabilityNo abdominal pain, change in bowel movements, melena,

hematocheziaNo hematuria, no frequency, no discharge, no edema, anuria, oliguria,

dysuriaNo tremors, no convulsions, no behavioral changesNo polyuria, polydipsia, polyphagia, no heat/cold intoleranceNo weakness, no joint swellings, no limitation of motionNo pallor, no bleeding, no easy bruisability

Family History

(+) Hypertension – maternal and paternal grandparents

(+) Diabetes – maternal aunt(+) Bronchial asthma – cousins(+) allergy – mother (fish)(-) tuberculosis, cancer, seizure, blood dyscrasia,

renal, congenital anomalies

Past Medical History

2 years old: German measlesNo previous hospitalizations and operations

Family members Age Occupation Condition

Father 30 years old Employee Healthy

Mother 29 years old Housewife Healthy

Sibling (Justine Richie) 7 years old Grade 1 Healthy

Sibling (Jama Lian) 3 years old

Sibling (Jermaine) 2 years old

Environmental History

• The patient lives with both parents and siblings in a concrete house, well-lit, and well ventilated. No factories are nearby.

• Pets: none• Garbage is collected everyday by a garbage

truck, not properly segregated

Physical Examination

Conscious, coherent, alert, ambulatory, well looking, well hydrated, not in cardio-respiratory distress

BP: 90/60 CR: 96, regular RR: 18, regularTemp: 36.5 C Ht: 115cm z = 0Wt: 21.2 kg z = 0 BMI: 16.03 z = 0

Physical ExaminationSkin: warm, moist skin, no lesionsHead: normocephalic, thick shinny hair, no hair nits, no

hair lice, no tenderness, no palpable massesEyes: no swelling, lids not matted, pink palpebral

conjunctiva, anicteric sclera, pupils 2-3 mm ERTLEars: no swelling, no tragal tenderness, nonhyperemic

EAC, impacted cerumen AUNose: no discharge, turbinates not congested, midline

septum Mouth/ Throat: moist buccal mucosa, nonhyperemic

posterior pharyngeal wall, tonsils not enlarged, no dental caries, no oral ulcers

Neck: supple neck, (+) 5cm x 3cm non movable, tender mass on the left retroauricular extending up to the angle of the mandible

Lung/ Chest: no intercostal and supraclavicular retractions, symmetrical chest expansion, clear breath sounds, equal vocal fremiti

Heart: adynamic precordium, apex beat at 4th Left ICS MCL, S1>S2 apex, S2>S1 base, no heaves, thrills, murmurs

Abdomen: flat abdomen, normoactive bowel sounds, soft, nontender, no palpable masses

Extremities/ Pulses: pulses full and equal, no deformities, no cyanosis, no edema

Neurologic examination: unremarkable

Salient Features:

6 years oldFilipino Sampaloc, Manila(+) non productive cough(+) 5cm x 3cm non movable, tender mass on the

left retroauricular extending up to the angle of the mandible

(-) TB exposure

RIGHT LATERAL CERVICAL MASSPresenting Manifestation

Cervical Lymphadenopathy in children

Infectious• Bacterial• Viral

Non-infectious• Connective tissue disorders• Leukemia• Lymphoma• Kawasaki disease• Periodic fever, aphthous

stomatitis, pharyngitis, adenitis (PFAPA)

• Medications

Approach to Diagnosis

• History– Duration and laterality of adenopathy and change in size

over time– Associated symptoms– Ill contacts– Ingestion of unpasteurized animal milk or undercooked

meats– Dental problems or mouth sores– Skin lesions or trauma– Animal exposures– Immunization status– Medications– Geographic location and travel

Approach to Diagnosis• Physical examination

– Examination of the lymphatic system, including assessment of the liver, spleen, cervical lymph nodes, and noncervical lymph nodes should be performed.

• Hepatosplenomegaly with generalized adenitis indicates a possible infection with EBV, CMV, HIV, histoplasmosis, TB, or syphilis.

• These findings also may be signs of neoplastic disease, collagen vascular disease, or other noninfectious etiology

Approach to Diagnosis• Physical examination

– The lymph node number, location, size, shape, consistency, tenderness, mobility, and color should be recorded.

• "Reactive" lymph nodes are usually discrete, mobile, feel rubbery, and are minimally tender.

• Infected lymph nodes are usually isolated, asymmetric, tender, warm, and erythematous; they may be fluctuant; they are less mobile and discrete than reactive lymph nodes.

• Malignant lymph nodes often are hard, fixed or matted to the underlying structures; they are usually nontender.

– Oral cavity —periodontal disease, herpangina, gingivostomatitis, or pharyngitis

– Eyes — Conjunctival injection– Skin — generalized rash, pustular or papular lesions

DifferentialsNon-Infectious Causes

Patient: 6y.o./ Female Collagen vascular diseases Malignancy

(+) 5x3cm, unilateral, semi-solid, tender, cervical mass on the left retroauricular area, extending to the angle of the mandible

1 week duration

nontender, firm, rubbery, and matted. Persistent or progressive lymphadenopathy that does not respond to antibiotic therapy suggests the need for more extensive evaluation

Weeks to months

(+) cough for 2 days(-) colds(-) fever(-) weight loss(-) failure of weight gain

Prolonged fever, rash, and arthralgias

Fever, weight loss, Musculoskeletal pain, headache, mediastinal mass, testicular enlargement, peripheral blood abnormalities

DifferentialsInfectious Causes

Patient: 6y.o./ Female

Bacterial Infection Viral Infection TB Infection

(+) 5x3cm – progressive in size, unilateral, semi-solid, tender (initially non-tender), fixed, mass on the left retroauricular area, extending to the angle of the mandible

1 week duration

Most often unilateral; but can be bilateral; usually is 3 to 6 cm in diameter, tender, warm, erythematous, nondiscrete, and poorly mobile

variable

most often bilateral some can be generalized; small, rubbery, mobile, discrete, minimally tender, and without erythema or warmth

variable

unilateral nontender firm discrete mass or matted nodes, fixed sometimes accompanied by overlying skin induration; submandibular and supraclavicular lymph node involvement also occurs

Weeks to months

DifferentialsInfectious Causes

Patient: 6y.o./ Female

Bacterial Infection Viral Infection TB Infection

(+) cough for 2 days(-) colds(-) fever(-) weight loss(-) failure to gain weight

history of a recent URI or impetigo; fever, tachycardia, and malaise may be present, the patient usually does not appear toxic

history of an ill contact and current or recent symptoms that may include sore throat, rhinorrhea, nasal congestion, and/or cough

Cough/ wheezing of 2 or more weeksUnexplained fever of 2 or more weeks; loss of appetite, loss of weight, failure to gain weight; failure to regain previous state of health after infection; fatigue, reduced playfulness or activity

T/C PRIMARY TUBERCULOSIS

Clinical Impression

Approach to Diagnosing a TB symptomatic Approach to Diagnosing a TB symptomatic child who has no/unknown exposurechild who has no/unknown exposure

Tuberculosis in Infency and Childhood 3rd ed. 2010 PPS, Inc. p.123

Tuberculosis in Infency and Childhood 3rd ed. 2010 PPS, Inc. p.123

WORK UPS AND MANAGEMENT

Traditional and New Diagnostic Approaches

DIAGNOSTICS APPLICATIONS

Traditional approaches

- Symptom-based-TST-TB Culture-- AFB smear-- Chest radiograph

Probable active TBEvidence of MTB InfectionBacteriologic Confirmation of active TB

Probable Active TB

New Diagnostic Approaches

ORGANISM BASED-Colorimetric cultures systems-- phage based test

-- Microscopic- based observation drug susceptibility (MODs) assay

Bacteriological confirmation of active TBProbable active Tb and detection of rifampin resistanceProbable active TB and detection of resistance

Traditional and New Diagnostic Approaches

DIAGNOSTICS APPLICATIONS

New Diagnostic Approaches

ANTIGEN BASED ASSAYS-LAM detection assayIMMUNE BASED ASSAY-Antibody based assay--MPB-64 skin test-- T- Cell assaysSYMPTON BASED-Symptom based screening-Refined symptom based Diagnosis

Probable active TB

Probable active TBProbable active TBDiagnosis of Latent TB infection

Screening child contacts of adult TB casesProbable Active TB

Diagnosis of TB

• A positive culture with or without a positive smear for M. Tuberculosis is the gold standard for the diagnosis of TB

In the absence of bacteriologic evidence , a child is presumed to have active TB if > 3 crteria are present:

• Exposure to an adult/Adolescence with active TB (EPIDEMIOLOGIC)

• Signs and symptoms suggestive of TB (CLINICAL)• Positive tuberculin test (IMMUNOLOGIC)• Abnormal chest radiograph suggestive of TB (RADIOLOGIC)• Other lab findings suggestive of TB (LABORATORY)

OUR PATIENT

• TST – 12 mm induration• Chest X –ray showed evidence of primary

infection• Signs and symptoms of TB

Chest X- ray of the patient 11/24/10

Management of Tuberculosis

Objectives of Drug Therapy in TB:

1. Cure the patient of TB2. Prevent death from active TB 3. Prevent relapse of TB4. Prevent the development of drug resistance5. Decrease transmission

Phases of Treatment

• Intensive Phase - efficient killing of actively dividing organisms- relief of symptoms- terminates transmision- prevents emergence of drug resistance

• Continuation Phase - kills irregularly dividing bacilli- sterilizes lesions and prevent relapse

Drug Administartion

• The optimal dosing frequency for new patients with pulmonary TB is daily throughout the course of therapy.

Alternative Regimens:(1)A daily intensive phase followed by tree times

weekly continuation phase [2HRZE/4H3R3] , provided that each dose is directly observed

(2)Three times weekly dosing throughout the therapy [2H3R3Z3E3/4H3R3] , provided that every dose is directly observed.

Essential Anti-Tuberculosis DrugsDRUG MOA DOSE RANGE

Single daily dose mkd

3X weekly mkd

INH -Bactericidal agent--Acts on extracellular and intracellular bacillary populations-- presumed to inhibit biosynthesis of mycolic acid (cell wall component ) and effects glycolysis , nucleic acid synthesis

10 -15 Max 300 mg

20-30Max 900 mg

Rifampicin -Bactericidal agent--Acts on extracellular and intracellular bacillary populations-- inhibits nucleic acid synthesis

10-20Max 600 mg

10-20Max 600 mg

Essential Anti-Tuberculosis DrugsDRUG MOA DOSE RANGE

Single daily dose mkd

3X weekly mkd

Pyrazinamide -- weak bactericidal but with potent sterilizing activity within macrophages, areas of acute inflammation

20-40Max 2 g

50 mgMax 2 g

Streptomycin - Bactericidal 20-40 max 1 g

Ethambutol -Bacteriostatic, but with some bactericidal action at higher doses -- acts on intra and extracellular bacillary populations-- presumed to inhibit synthesis of mycolic acid (cell wall component)

15- 25 Max 1.2 g

30-50Max 2.5 g

Essential Anti-Tuberculosis Drugs

DRUG ADVERSE REACTIONS

INH -- peripheral neuropathy-Other neurological disturbance, optic neuritis, toxic psychosis, generalized convulsions-- systematic or cutaneous hypersensitivity reactions during the first week of treatment-- hepatotoxicity

Rifampicin -Gastrointestinal intolerance-- if intermittent adminidtration: rash , fever, thrombocytopenia, flu like symptoms-- increases risk of hepatotoxicity if used with INH

Pyrazinamide -- hypersensitivity reactions--moderate rise in trasaminase levels -- Hyperuricemia-- arthralgia, particularly of shoulders

Essential Anti-Tuberculosis Drugs

DRUG ADVERSE REACTIONS

Streptomycin

-- sterile abscess-- vestibular, auditory function impairment-- hemolytic anemia

Ethambutol

-- retrobulbar neuritis ( reduced visual acuity, contraction of visual fields, green red color blindness)

TREATMENT

21 kg

Isoniazid 200 mg/5mL (10 mkd) Give 5.5 mL once daily 30 minutes before breakfast

Rifampicin 200mg/5mL (10 mkd)- Give 5.5 mL once daily, 30 minutes before breakfast

Pyrazinamide 500 mg/5mL (20 mkd) Give 4.5 mL once daily, 30 minutes before breakfast

Ethambutol 400 mg/tab (20 mkd) - 1 tabGive 1 tab once daily, 30 minutes before breakfast

Supportive Management

• Multivitamins 5 mL once a day• Anticipatory Guidance

Tuberculosis

Tuberculosis A Global Emergency

• One third of the world’s population is infected

• TB kills 5,000 people a day – 2-3 million each year

• HIV and TB co-infection is producing explosive epidemics

• Hundreds of thousands of children will become TB orphans this year

• MDR threatens global TB control

Background

• Tuberculosis (TB) is increasing among adults in many areas

• TB is major cause of childhood morbidity and mortality worldwide

• Limited information on epidemiology of TB in children

Childhood TB

• Why neglected?– Not considered important in global program or

contributing to immediate transmission – Not regarded as public health risk– Difficult to diagnose

• Why is it important?– Health problem in children– May later contribute to epidemic

Leading Infectious Disease Causes of Death, 1998

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TB in Children

• WHO estimate of TB in children– 1.3 million annual cases– 450,000 deaths

• 15% of TB in low-income countries children vs. 6% in United States

Childhood TB as Sentinel Event

• Indicates recent transmission in a community• Rapid progression from infection to disease

“A deterioration in the control of TB thus immediately hurts the youngest generation” (Rieder, 1997)

• Children are future reservoir of disease

Rieder H. Anales Nestle, 1997

Childhood TB diagnosed by:

Combination of :Combination of : Contact with infectious adult caseContact with infectious adult case Symptoms and signsSymptoms and signs Positive tuberculin skin testPositive tuberculin skin test Suspicious CXRSuspicious CXR Bacteriological confirmationBacteriological confirmation Serology Serology

Risk factors : infection to diseaseRisk factors : infection to disease

HIVHIVMalnutritionMalnutritionRecent exposureRecent exposureYoung age Young age

Short incubation periodShort incubation periodMore severeMore severeHighest riskHighest riskMore difficult to diagnoseMore difficult to diagnose

Host factorsHost factors

Effect of HIV?Effect of HIV?

Tuberculous Infection Among Children by Type ofTuberculous Infection Among Children by Type ofContact and Bacteriologic Status of Index Case,Contact and Bacteriologic Status of Index Case,British Columbia and Saskatchewan, 1966-1971British Columbia and Saskatchewan, 1966-1971

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Close

CloseCasual

Casual

Challenges for Surveillance

• Difficult diagnosis of childhood TB• Lack of standard case definition• Increased extrapulmonary disease• Low public health priority of childhood TB

WHO Estimated Total Cases by Age, 2000

Country Total Cases Cases <15 yrs % in Children

India 1,815,740 185,233 10.2

China 1,645,703 86,978 5.3

Indonesia 581,918 15,691 2.7

Bangladesh 325,110 33,166 10.2

Nigeria 261,404 32,310 12.4

Pakistan 244,736 61,905 25.3

Philippines 230,217 12,167 5.3

South Africa 220,486 35,449 16.1

Russian Fed. 183,373 7,778 4.2

Ethiopia 178,349 28,675 16.1

Dem. Rep. Congo 148,598 24,052 16.1

WHO Estimated Total Cases by Age, 2000

Country Total Cases Cases < 15 yrs % in Children

Viet Nam 143,023 7,559 5.3

Kenya 137,603 22,124 16.1

Tanzania 117,489 18,890 16.1

Brazil 113,528 23,520 20.7

Thailand 85,928 2,317 2.7

Myanmar 78,489 8,007 10.2

Zimbabwe 76,296 12,267 16.1

Uganda 75,250 12,099 16.1

Cambodia 75,045 3,966 5.3

Afghanistan 69,342 17,540 25.3

Mozambique 47,909 7,703 16.1

TOTAL 6,856,537 659,397 9.6

Extrapulmonary TB in Children

• Proportion in a given country could be used as measure of case detection– 25-44% of all childhood TB in Ugandan study– 43% of children in Ethiopian study– 21.3% of childhood TB using US surveillance

data

TB and BCG Vaccination

• Efficacy for adult pulmonary TB 0-80% in randomized clinical trials

• Best efficacy against serious childhood disease – 64% protection against TB meningitis– 78% protection effect against disseminated TB

• BCG important for young children, inadequate as single strategy

Colditz GA et al. JAMA 1994; 271: 698-702.

Relationship between TB and HIV Relationship between TB and HIV

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HIV prevalence adults 15HIV prevalence adults 15- 49 years- 49 years

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What about children?What about children?

History of M. tuberculosis

• Phthisis (Greek) known since ancient times• Often thought of as a hereditary condition• 1854 first sanatorium• 1882 Koch demonstrated relationship

between• germ and disease• 1895 Roentgen discovery of diagnostic x-ray• 1940’s-1950’s chemotherapy

Around the World

• An estimated 1.58 million deaths occurred in• 2005 from TB disease• 8.8 million new TB cases estimated for 2005• 1/3 of world population has TB infection

High Burden Countries (WHO)

Transmission and Pathogenesis

Pathogenesis

• Inhale droplet nuclei• Bacteria multiplies• Macrophages consume bacteria, then die• Travel through the bloodstream, lymph

system• Containment-infection• Multiplication-disease

Generation of TB Droplet Nuclei

• One cough produces 500 droplets• The average TB patient generates 75,000droplets per day before therapy• This drops to 25 infectious droplets perday within 2 weeks of effective therapy

Factors Affecting TB transmission

• Characteristics of source case

• Environment• Factors increasing

risk for contacts

Classification System for TB

Risk Factors for the Development of TB Disease

Signs/Symptoms

• Productive cough 3 weeks or longer• Shortness of breath• Chest pain• Hemoptysis• Night sweats/fever/chills• Unexplained weight loss• Fatigue

Suspect TB:

• Chest x-ray• Location of the infiltrate• Presence of a cavity• Hollow areas, dense areas, fluid on• the lung or at margins• Normal x-ray = usually no infectious• TB disease

Chest Radiograph

• Abnormalities often seen in apical or posterior segments of upper lobe or superior segments of lower obe

• May have unusual appearnce in HIV+ patients

Sputum Collection

• Sputum specimens are essential toconfirm TB• Sputum: mucus from within the lung, not• Saliva• 3 specimens on 3 different days• Spontaneous morning sputum moredesirable than induced specimens

Sputum AFB Smear

AFB Smear: Tubercle bacilli

Cultures

• Use to confirm dx of TB• Culture all specimen• Result in 4-14 days when liquid medium

systems used• Susceptibility testing

Drug Susceptibility Testing