General Data:

J.C.N., 12-year-old male, Filipino, Catholic, presently residing at Manatra Buli, Muntinlupa City, was admitted at MCGH for the first time on May 6, 2010.

Chief Complaint:
cough and abdominal pain

History of Present Illness:

9 months PTA fever

cough
Consult: Health Center

Meds: Paracetamol
Salbutamol

Follow-up twice
Med: Paracetamol

7 months PTA

fever, cough, colds vomiting, dizziness hypogastric pain bilateral flank pain dysuria, nocturia dark yellow urine polyuria, oliguria feeling of bladder not fully emptied

Consult: Health Center Dx: Tonsillitis Meds: Paracetamol Salbutamol ?med. for vomiting Amoxicillin

5 months PTA

persistence of symptoms abdominal pain (epigastric, RUQ)

Consult: PGH CXR: Pneumonia Med: Amoxicillin PTB considered Advised ff-up

3 months PTA

condition unimproved urinary symptoms noted gradual abdominal enlargement weight loss night sweats Consult: PGH Dx: UTI Med: Cotrimoxazole Ff-up at PGH Med: Cefaclor

2 months PTA

condition persisted Consult: Ospital ng Muntinlupa

Whole Abdomen Ultrasound: Hepatomegaly with liver parenchymal disease process not ruled out

Bilateral renal parenchymal disease considered.

Pre-aortic possibly mesenteric lymphadenopathy. Ultrasonically normal gallbladder, bile ducts, pancreas, spleen and aorta

Advised consult at Health Center for treatment of Tuberculosis

Few hours PTA

persistence of condition Consult: PGH Impression: t/c Disseminated TB (Pulmo, GI, lymph nodes) Referred to SLH CXR requested

Admitted

Past Medical History:

Acute Gastroenteritis 2 yrs. old, admitted at Ospital ng Muntinlupa x 7 days Measles 4 years old Conjunctivitis 10 yrs. old

Family History:
(+) PTB Father, not compliant to medications

- paternal grandmother died of PTB

(+) Asthma paternal side (+) Hypertension maternal grandfather (-) Diabetes Mellitus (-) Cancer

Immunization History:
No Vaccinations

Personal & Social History/Environment:

Patients parents separated since he was 5 mos. old. He presently lives along railways in a congested area with his mother. There are 5 household members, including the patient, who occupies a small room. He is the youngest among 4 siblings. He is an incoming grade 4 student.

Review of Systems:
- no irritability, no changes in sensorium no convulsion - no head lesions; no eye, nasal nor aural discharge; no throat pain - with shortness of breath - with easy fatigability - no cyanosis

- no diarrhea nor constipation

- no hematuria - no muscle nor joint pains

Physical Examination :
conscious, coherent, weak-looking, in mild cardiorespiratory distress

CR = 122 RR = 25

T = 37.6oC

pink palpebral conjunctivae, anicteric sclerae, matted cervical lymphadenopathy, pale skin

symmetrical chest expansion, tachypneic, no retractions, harsh breath sounds with occasional rales
adynamic precordium, tachycardic, no murmur

globular abdomen, normoactive bowel sounds, direct tenderness on RUQ, hepatomegaly, visible abdominal veins, (+) Kidney Punch Test full and equal pulses

Admitting Diagnosis at the Ward:

Disseminated TB (Hepatic, lymph nodes) Pneumonia

UTI
Severe Malnutrition

Admission:
IVF : Labs: D5 0.3 NaCl CBC w/ platelet count., urinalysis, serum Na, K, Cl, SGOT, SGPT, Alkaline Phosphatase, BUN, Creatinine, sputum AFB smear x 3days PPD Chest x-ray- negative UTZ of whole abdomen Meds: Paracetamol (10 mg/kg/dose) Penicillin G Na (200,000 u/kg/day)

 CBC/ platelet Hgb 8.76 Hct 29.24 WBC 9.5 Neu. 79.80 Lym. 8.80 Plt. 252

5/7/10

5/7/10

5/7/10

Creatinine 54.01 umol/l Urea SGOT SGPT Alk. Phos. 3.03 mmol/l 48.48 U/L 87.13 U/L 1312.57 U/L

Urinalysis
yellow, turbid SG 1.020 PH 6.5 sugar negative protein trace RBC >40/hpf WBC >50/hpf Blood +++ Leukocyte +++

1st Hospital day:

Subjective Afebrile no dyspnea bilateral flank pain dark yellow urine oliguria * Productive cough * hypogastric pain * dysuria, nocturia * polyuria, * feeling of bladder not fully emptied

weak-looking * pallor matted CLAD * prominent rib cage liver edge 6cm below right subcostal margin
Objective

iManagement

Continue present management I and O strictly monitored

2nd Hospital day:

Subjective

Afebrile no dyspnea No abdominal pain

weak-looking * pallor matted CLAD * prominent rib cage liver edge 9cm below right subcostal margin * grade 3/6 systolic murmur at 2nd ICS MCL
Objective

Diagnostics

PT,PTT Urine CS with ARD Blood CS with ARD

* Abdominal CT Scan w/ contrast * 2D Echo * ECG

Management

Pen. G shifted to Cefuroxime (100mkd) Referral to Gastro. & Cardio

5/8/10

5/8/10

PT
Patient = 13.8 Control = 15.2 % Activity = 86.5% INR = 1.08

APPT
Patient = 31.6 Control = 36.2

5th Hospital day:

Subjective

Afebrile pallor Good oral intake

weak-looking * pallor matted CLAD * prominent rib cage liver edge 9cm below right subcostal margin * grade 3/6 systolic murmur at 2nd ICS MCL
Objective

Diagnostics

CBC with platelet Peripheral Blood smear Scour film of the abdomen
INH (9mkd) Rifampicin (15mkd) PZA (20mkd) Streptomycin (25mkd)

* Blood typing * Serum Electrolytes

Management

* Abdominal CT Scan deferred

5/11/10

5/11/10

Peripheral Blood Smear

The smears show microcytic hypochromic red blood cells with anisocytosis and poikilocytosis. The white blood cells are adequate in number with predominance of neutrophils. Likewise seen are many lymphocytes, rare monocytes, and eosinophils, there are no immature blood cells, or inclusions noted. Platelets are adequate with no morphological abnormalities noted.

Blood Type: O+

5/11/10

CBC/ platelet Hgb 9.53 Hct 29.82 WBC 8.4 Neu. 73.80 Lym 16.40 Plt. 288

Scout Film of the Abdomen There are normal bowel gas pattern. The liver and splenic shadows are enlarged. The psoas and flanks stripes are intact. Irregular calcifications are seen in the left lumbar area level of L4 to S1. The osseous structures are unremarkable.

8th Hospital day:

Febrile
Subjective

Harsh Breath sounds, right

Objective

Diagnostics

Repeat CBC with platelet Chest Xray Blood culture and sensitivity
Cefuroxime shifted to Ceftriaxone (100mkd) Pleural Effusion considered

Management

10th Hospital day:

febrile, no oliguria Urine AFB for 3 days Anti-Kochs meds. continued
Management

Subjective

Whole Abdomen Ultrasound Enlarged liver with parenchymal disease TB of the liver not ruled out Slightly enlarged spleen

Enlarged left kidney with parenchymal disease

Normal gallbladder, right kidney and urinary bladder

12th HD

febrile night sweats vomiting, 1 episode harsh BS occasional rhonchi

13th HD

febrile, no dyspnea repeat urinalysis Medications continued

5/18-20/10

acid-fast bacilli present 1+

5/19/10

Urine AFB

Urinalysis Dark red, turbid sp. gr. 1.027 pH 5.5 Sugar negative protein 50 mg/dL RBC >20/hpf WBC >50/hpf Bilirubin 1.0 mg/dL+++ Nitrite 0.1 mg/dL+ hyaline cast many (+4) RBC cast many (+4)

15th Hospital day:

Afebrile no cyanosis
Subjective

* no dyspnea * urinary symptoms

(+)murmur grade 1 -2
Objective

Diagnostics

Urine AFB result

Management

Dibencozide Vitamin B Complex continued

* *

Multivitamins Quadruple anti-Kochs meds.

18th Hospital day:

Subjective

Afebrile no abdominal pain (+) complete bladder emptying

* no dyspnea * no polyuria

pallor
Objective

Diagnostics

repeat CBC with platelet count CXR result

Meds. continued
Management

5/24/10

Chest x-ray Normal Chest Findings

CBC w/ platelet Hgb 9.87 Hct 30.65 WBC 8.29 Neu. 80.3 Lym. 10.2 Plt. 386

25th Hospital day:

* Discharged improved
Home meds: * INH (10mkd)
* Rifampicin (15mkd) * PZA (20mkd) * Streptomycin(21mkd) * Vit. B Complex * Dibencozide

* Follow- up @ OPD Pedia

afebrile, comfortable. No urinary symptoms

Final Diagnosis:

Disseminated TB (Hepatic, Renal, Lymph nodes)

Anemia secondary to Chronic Infection Severe Malnutrition

a common and often deadly infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis in humans attacks the lungs but can also affect other parts of the body most infections in humans result in an asymptomatic, latent infection

one in ten latent infections eventually progresses to active disease which, if left untreated, kills more than 50% of its victims

Epidemiology
One third of the worlds population is infected with Mycobacterium tuberculosis

Each year, about 9 million people develop TB, of whom about 2 million die. Of the 9 million annual TB cases, about 1 million (11%) occur in children (<15 years of age).

Of these childhood cases, 75% occur annually in 22 high-burden countries that together account for 80% of the worlds estimated incident cases. In countries worldwide, the reported percentage of all TB cases occurring in children varies from 3% to >25%.

Causes Mycobacterium tuberculosis - a small aerobic non-motile bacillus - high lipid content - divides every 16 to 20 hours

- classified as a Gram-positive bacterium

- can withstand weak disinfectants & survive in a dry state for weeks

- can grow only within the cells of a host organism, but can be cultured in vitro

Transmission

people suffering from active PTB

cough, sneeze, speak, or spit

infectious aerosol droplets (0.5 to 5 um)

transmit the disease

Transmission - people with prolonged, frequent, or intense contact: high risk of becoming infected (22% infection rate) - people with active but untreated TB can infect 10 15 other people per year - can only occur from people with active not latent TB - depends upon the number of infectious droplets expelled by a carrier, effectiveness of ventilation, duration of exposure, & virulence of M. TB strain

Pathogenesis - Mycobacteria reach the pulmonary alveoli, where they invade & replicate within the endosomes of alveolar macrophages - primary site of infection in the lungs: Ghon focus - bacteria are picked up by dendritic cells (can transport the bacilli to local/mediastinal lymph nodes) - further spread through bloodstream to other tissues & organs where secondary TB lesions can develop in other parts of the lung, peripheral lymph nodes, kidneys, brain, & bone

Risk of TB infection in children

Depends on contact with an adult who has active TB disease - extent and duration of exposure Susceptibility to infection -very young (<2yrs) HIV infection

 Risk of progression from infection to active disease: (often within 12 months of infection) - more common among children <2yrs due to under-developed immune systems - Severe malnutrition - Worm infestation - HIV infection - Other viral infections - eg measles - BCG immunization

Primary TB infection in children

Asymptomatic in 80-90% - 5-10% may develop disease Extra Pulmonary TB is common Transmission of TB- source of infection mostly adults Children represent about 5-15% of all TB cases

Young children with TB differ from Adult

Presentation Infectiousness- generally not infectious Progression to disease- faster, more often, more extrapulmonary Response to treatment Side effect profile

o Often difficult! - Children rarely cough up sputum - gastric aspiration not always possible - Under 2 years of age - other infection/s may mask TB, e.g., pneumonia

Recommended Approach
Careful history identify index case Clinical examination TB Skin Test Bacteriology whenever possible Investigations relevant to the suspected type of TB

How to diagnose TB in children

Diagnosis depends on: History of contact with a smear positive adult Chronic symptoms Clinical picture suggestive symptoms Positive tuberculin skin test Chest X-ray suggestive of TB

Clinical signs and symptoms

General most common clues are:
Failure to gain weight/ failure to thrive Loss of appetite without obvious cause Chronic cough for 2 weeks or more, not responding to a course of antibiotics Painless swelling of the lymph nodes An audible wheeze due to airway compression Unexplained fever

Tools to help with the diagnosis

Tuberculin Skin Test (TST) or Mantoux Test/Purified Protein Derivative (PPD) - intra-dermal injection - read 48-72 hours later - It measures the bodys immune response to TB - Infected not necessarily active TB disease

Chest X Ray

Clinical Manifestations 25% of active cases occurs more commonly in immunosuppressed persons & young children sites:

- pleura in tuberculosis pleurisy

- CNS in meningitis - lymphatic system in scrofula of the neck

- genitourinary system in urogenital TB

- bones & joints in Potts disease of the spine

Tuberculosis of the Cervical Lymph Nodes (Scrofula)

the most common form of extrapulmonary TB in children

through direct extension from a primary pulmonary infection

the cervical chain of nodes becomes the most commonly affected often unilateral; bilateral involvement may occur cervical nodes may also be involved from other tuberculous foci: nasopharynx, middle ear or tonsils diagnosis: (+) tuberculin test, excisional biopsy & culture & fine needle aspiration cytology

Tuberculosis of the Cervical Lymph Nodes. . .

signs & symptoms: absent involved superficial lymph nodes:

- painless, firm, discrete & movable

- becoming adherent to each other - anchored to the surrounding tissues & skin as they enlarge if untreated: either resolve or progress to caseation & necrosis of the lymph node - can rupture & result in a draining sinus tract produces a disfiguring scar (scrofuloderma)

Genitourinary Tuberculosis
2nd most common site for tuberculous infection after the lungs almost always affects the kidneys during the primary exposure to infection but does not present clinically true incidence of renal TB may be underestimated: - radiologic findings may be absent - diagnosis made by urine culture Genital TB- usually secondary to renal tuberculous infection Renal TB-an uncommon complication of primary TB occurring very late, up to 15 20 years after primary infection

Renal Tuberculosis

Pathophysiology:
small tubercle in the glandular & cortical arterioles progress to form necrotizing lesions

Spreads by a hematogenous route from pulmonary disease

disease spreads to the renal tubules & renal medulla tubercles develop (turn of the loop of Henle) larger necrotic irregular cavities Kidneys become fibrotic & scarred

Renal Tuberculosis can be unilateral or bilateral can spread caudad to involve the bladder

can be insidious in onset

75% of patients would present with symptoms related to urinary tract inflammation- dysuria,

hematuria, sterile pyuria, flank pain

suspected in the presence of destructive PTB with persistent, painless, sterile pyuria with associated albuminuria & hematuria

Diagnosis of GUTB GUTB: very uncommon in children symptoms of renal TB do not appear for 3 to 10 or more years after the primary infection frequent painless micturition urgency uncommon unless there is extensive bladder involvement urine normally sterile, contains leukocytes in high proportion of patients overt hematuria: 10% of patients; microscopic hematuria: up to 50% renal & suprapubic pain: rare presenting symptom

Diagnosis of GUTB secondary TB with vague symptoms; often longstanding urinary symptoms with no obvious cause latent period of 20 years or more between infection with the tubercle bacillus & the expression of GUTB characterized with pyuria, albuminuria, hematuria

75% of patients- abnormal chest X-ray on admission

88% (+) skin tests 63%: abnormal excretory urography 16%: renal calcification Renal TB: accompanied by manifestations of the urinary syndrome in 70.4% of cases & by the presence of Mycobacteria TB in 100%

Diagnosis of GUTB most important step: patient history - history of voiding problems & chronic urgency non-responding to antibacterial drug regimens: indicative of GUTB - other symptoms: back, flank, & suprapubic pain, hematuria, frequency, & nocturia - renal colic: uncommon - constitutional symptoms: unusual - symptoms are intermittent & have been present for some time before the patient seeks medical advice

Diagnosis of GUTB microbiologic diagnosis of TB- isolation of the causative organism from urine or biopsy material on conventional solid media or by an automated system (radiometry) positive culture or histological analysis of biopsy specimens possibly combined with PCR- definite diagnosis detection of AFB from urine samples by microscopy

(Ziehl-Neelsen acid fast stain)- not reliable

(bec. of the possible presence of M. smegmatis)

Diagnosis of GUTB - made based on culture studies

-at least 3, but preferably 5, consecutive early morning specimens of urine should be cultured, each onto 2 slants:
(1) a plain Lowenstein-Jensen culture medium to isolate M. TB, BCG, & the occasional nontuberculous mycobacteria (2) a pyruvic egg medium containing penicillin to identify M. bovis

Diagnosis of GUTB

Radiography:
Plain X-ray films of the urinary tract: - may show calcification in the renal areas & in the lower GUT Intravenous urography:

- distortion of a calyx (fibrosed & completely occluded, multiple small calyceal deformities, or severe calyceal & parenchymal destruction)
Ultrasonography: - may reveal renal calyceal dilation & more overt evidence of obstruction Computed tomography & nuclear magnetic imaging

Treatment of GUTB 6-month regimens for the treatment of uncomplicated GUTB

Intensive phase
3 months INH, RMP, EMB (or SM) daily

Continuation phase
3 months INH, RMP Twice or thrice per week

2 months INH, RMP, PZA, EMB daily

4 months INH, RMP Twice or thrice per week