case presentation

Case Presentation

ByDr. M. Waqqas Akram

FCPS II Resident Department of Pediatrics

BBH, Rawalpindi

Profile

Name: Imran

Age: 14 yrs

Sex: Male

Residence: Sadiqabad, Rawalpindi.

Date of Admission: 1st Dec. 2008

Presenting Complaints

Productive cough 1 yr

Progressive breathlessness

History of Present Illness

Cough – early morning & after activity

Copious and tenacious sputum

Sputum volume around 2-3 cups/day

Purulent & foul smelling

Breathlessness OrthopneaOccasional cyanosisWheezeHigh grade feverNo H/O hemoptysis, stridor & chest pain

Systemic Inquiry

Bulky and greasy stools

Lack of appetite and weight loss

No H/O Nasal obstruction or nasal dischargeEarache & discharge, Polyuria, polydypsia, Jaundice, Hemetemesis, petechiae & bruises

Past History

Recurrent pneumonia from 1 m of age

Frequent hospitalizations

Adverse effects on growth & development

Usual treatment with antibiotics

Received ATT twice at the age of 5 & 9yrs

Birth History

Antenatal history was unremarkable

Spontaneous vertex delivery at home

No perinatal complications

Passed meconium within 24hrs after birth

Developmental History

Delayed motor milestones

Immunization History

Vaccinated according to EPI schedule

BCG scar +ve

14yrs 12yrs 10yrs 6yrs 4yrs 2yrs

Social History

Discontinuation of schooling

Limitation of physical activity

Feels low and lands into depression during exacerbation of symptoms

Fears for the future

Financial considerations

Other siblings get neglected

Examination:General Physical Examination

An ill looking young boy sitting on the bed in respiratory distress

Vitals R/R: 45/min Pulse: 102/min Temp: 99 F Blood Pressure: 100/60 mmHg

General Physical Signs

Grade 4 clubbing

Pallor

Cyanosis

Edema feet

Absent secondary sexual characters

No lymphadenopathy and stigmata of chronic liver disease

Anthropometric Measurements

Height: 132 cm < 5th centile

Weight: 24 kg < 5th centile

OFC : 51 cm < 5th centile

Systemic Examination

Respiratory System:Inspection:

Barrel shaped chest

Pectus Carinatum

Bilaterally equal chest movements

Palpation:

Central trachea

Chest expansion 1.8 cm

Normal & equal vocal fremitus on both sides

PercussionResonant on both sides

AuscultationLow pitched bronchial breathing

B/L coarse crepts and rhonchi

Vocal resonance normal and equal on both sides

No whispering pectoriloquy

Examination of CVS

Pulse102/min, Regular, Normal volume & characterNo radiofemoral delay

JVPRaised

Precordium Inspection:

No bulge, prominent veins & scar marks Pulsations in epigastrium

PalpationApex beat - normal Heave in epigastriumNo parasternal heave, palpable heart sounds or thrill

Auscultation

S1 S2 audible, normal intensity & characterNo murmur

Abdominal Examination

InspectionNormal shaped abdomen with Central umblicusNo prominent veins or scar marksIntact hernial orifices

Palpation Soft & non tenderHepatomegalyNo other visceromegaly

PercussionNo evidence of free fluid in peritoniumLiver span 6cm

AuscultationNormal bowel soundsNo bruit

Examination of the CNS

Higher Mental Functions

Fully conscious, well orientedNormal behaviourGood memory & general intelligence

Cranial NervesIntact

Motor System

Normal bulk & nutrition of musclesTone & power is normal in all muscle groupsDeep & superficial reflexes intactNo cerebellar signs

Sensory SystemIntact primary & cortical sensations

Provisional Diagnosis

Cystic Fibrosis

Differential Diagnosis

Primary Cilliary DyskinesiaImmunodeficiency SyndromeBronchial AsthmaResistant Pulmonary Tuberculosis

Investigations

Diagnostic Supportive

CT Scan Chest

DNA testing for CFTR MutationsF 508 MutationSweat Chloride TestSerum AmylaseNormal72 hrs stool AnalysisPulmonary Function TestsObstructive pattern with reduced FVC & FEV1 / FVC 76%Sputum for Microbiologic StudiesPseudomonas E.coli

Supportive Investigations

Blood CP LFTs Serum Electrolytes Random blood sugar and Glucose

tolerance test RFTs ABGs ECG Echocardiography

Cystic Fibrosis:Cystic Fibrosis:

“Cystic fibrosis is an inherited multisystem “Cystic fibrosis is an inherited multisystem disorder Characterized by disorder Characterized by

obstruction & infection of airways obstruction & infection of airways & by maldigestion & its & by maldigestion & its

consequencesconsequences”.”.

Genetics:Genetics:

It is inherited as an autosomal recessive It is inherited as an autosomal recessive traittrait

Gene locus on long arm of chromosome 7Gene locus on long arm of chromosome 7

Cystic fibrosis gene codes for a protein of Cystic fibrosis gene codes for a protein of 1,480 1,480 amino amino acids acids called CF called CF transmembrane regulator transmembrane regulator (CFTR)(CFTR)

CFTR is expressed on ephitheial cells of CFTR is expressed on ephitheial cells of airway, airway, GIT, GIT, sweat glands sweat glands & & genitourinary systemgenitourinary system

Most prevalent mutation of CFTR is Most prevalent mutation of CFTR is deletion of a deletion of a single single phenylalanine phenylalanine residue at amino acid 508 residue at amino acid 508 (508)(508)

Pathogenesis:Pathogenesis:

4 important observations4 important observations

1- Failure to clear mucous secretions 1- Failure to clear mucous secretions

2- Paucity of water in mucus secretions2- Paucity of water in mucus secretions

3- Elevated salt content of sweat & other3- Elevated salt content of sweat & other

serous secretions serous secretions

4- Chronic infection limited to 4- Chronic infection limited to respiratory respiratory tract tract

Membrane of CF epithelial cells are Membrane of CF epithelial cells are unable to unable to secrete chloride ions in response secrete chloride ions in response to cyclic to cyclic AMP AMP mediated signals & mediated signals & excessive amount excessive amount of sodium are absorbed of sodium are absorbed through these through these membranesmembranes

There is inability to secret salt & water in presence of

excessive reabsorption of salt & water

Leads to insufficient water on airway surface

This causes desiccated secretions to become Viscous & elastic & are harder to clear

Secretions are Retained & obstruct airway

Pathology:Pathology:

Lungs:Lungs: Bronchiolitis is the earliest lesionBronchiolitis is the earliest lesionWith time inflammation extends to With time inflammation extends to

larger larger airway causing bronchitis airway causing bronchitis With long standing disease there is With long standing disease there is bronchiolar obilteration, bronchiolar obilteration, bronchiolectasis & bronchiectasesbronchiolectasis & bronchiectasesBronchiectatic cysts & Bronchiectatic cysts &

emphysematous emphysematous bullae bullae or or subpleural blebs, pneumothorax subpleural blebs, pneumothorax may may occur in advanced lung disease occur in advanced lung disease

Tortuous & enlarged bronchial Tortuous & enlarged bronchial arteries arteries occur occur leading to leading to hemoptysis hemoptysis

Medial hypertrophy of small Medial hypertrophy of small pulmonary pulmonary arteries occur in sec. arteries occur in sec. pulm. HTNpulm. HTN

Pancreas:Pancreas:

Small & cystic Small & cystic In 85-90% pts. Lesion progresses to In 85-90% pts. Lesion progresses to

complete or complete or almost complete disruption of acinialmost complete disruption of aciniReplacement of acini with fibrosis & fat. Replacement of acini with fibrosis & fat.

Foci of Foci of calcification may occurcalcification may occur

Intestinal Tract:Intestinal Tract:Minimal changes Minimal changes Esophageal, duodenal glands, Esophageal, duodenal glands,

crypts of crypts of appendix & rectum appendix & rectum distended with distended with mucus secretionsmucus secretions

Biliary System:Biliary System:

Focal biliary cirrhosis, causes Focal biliary cirrhosis, causes occasional occasional cases of prolonged neonatal cases of prolonged neonatal jaundice jaundice becomes more becomes more prevalent extensive with prevalent extensive with age age

Symptomatic multilobular biliary Symptomatic multilobular biliary cirrhosis cirrhosis

Fatty infiltration of liver in 30% ptsFatty infiltration of liver in 30% ptsGallbladder may be hypoplastic with Gallbladder may be hypoplastic with

secretions & stones secretions & stones Atresia of cystic duct & stenosis of Atresia of cystic duct & stenosis of

distal distal common bile ductcommon bile duct

Glands of Male & Female Genitourinary Glands of Male & Female Genitourinary system:system:

Endocervicitis in teenagers & Endocervicitis in teenagers & young young womenwomen

Body & tail of epididymis, vas Body & tail of epididymis, vas deferens & deferens & seminal vesicles are seminal vesicles are abliterated in >95% abliterated in >95% malesmales

Generalized amyloidosis rareGeneralized amyloidosis rare

Clinical Manifestations:Clinical Manifestations:Respiratory Tract:Respiratory Tract:

Symptoms Symptoms COUGH, most constantCOUGH, most constant symptom, dry & hacking symptom, dry & hacking

first &first & later productive later productive Wheezing Wheezing Shortness of breath Shortness of breath Exercise intolerance Exercise intolerance Failure to gain weight Failure to gain weight Rhinorrhea Rhinorrhea Nasal obstructionNasal obstruction

SignsSignsDigital clubbing Digital clubbing Cyanosis Cyanosis

Increased AP diameter of Increased AP diameter of chestchest

Generalized hyper Generalized hyper resonance resonance

Scattered or localized Scattered or localized coarse crackles coarse crackles

Expiratory wheeze Expiratory wheeze Acute sinusitis Acute sinusitis Nasal polyps Nasal polyps

Intestinal Tract:Intestinal Tract:Meconium Ileus:Meconium Ileus:

In 15-20% Newborn with cystic In 15-20% Newborn with cystic fibrosis fibrosis

Abdominal distension, emesis & Abdominal distension, emesis & failure failure to pass meconium to pass meconium appear within first appear within first 24-48 hrs 24-48 hrs of life of life

Meconium peritonitis occurs as a Meconium peritonitis occurs as a complicationcomplication

Meconium Plug SyndromeMeconium Plug Syndrome

Less specific than meconium ileus Less specific than meconium ileus Distal intestinal obstruction Distal intestinal obstruction

syndrome syndrome or meconium ileus or meconium ileus equilent in ileal equilent in ileal obstruction with obstruction with fecal material occurs in fecal material occurs in older ptsolder pts

Intestinal Tract:Intestinal Tract:

Symptoms Symptoms Frequent, bulky, greasyFrequent, bulky, greasystool stool Excessive flatus Excessive flatus Epigastric pain Epigastric pain Acid or bile reflux Acid or bile reflux Failure to gain weight Failure to gain weight Dementia Dementia Peripheral neuropathy Peripheral neuropathy Bleeding diathesis Bleeding diathesis Night blindness Night blindness RicketsRickets

SignsSignsProtuberant abdomenProtuberant abdomenDecreased muscle mass Decreased muscle mass Poor growth Poor growth Delayed maturation Delayed maturation Intussusception Intussusception Fecal impaction ofcecum Fecal impaction ofcecum Subacue appendicitis Subacue appendicitis Periappendiceal abscess Periappendiceal abscess AnasarcaAnasarca (In malnourished)(In malnourished)

Biliary Tract:Biliary Tract:

Biliary cirrhosis symptomatic in 2-Biliary cirrhosis symptomatic in 2-3% pts3% ptsIcterus Icterus Ascites Ascites Hematemesis Hematemesis Hypersplenism Hypersplenism Neonatal Hepatitis like picture Neonatal Hepatitis like picture HepatomegalyHepatomegalyBiliary colicBiliary colic

PancreasPancreas

Exocrine pancreatic insufficiency Exocrine pancreatic insufficiency

Hyperglycemia Hyperglycemia

Glycosuria Glycosuria

Polyuria Polyuria After 10 yrs of After 10 yrs of age age when when

8% 8% acquire acquire diabetes diabetes

Weight loss Weight loss

Recurrent acute pancreatitis Recurrent acute pancreatitis

Genitourinary systemGenitourinary systemAn average of 2 yrs delay in sexual An average of 2 yrs delay in sexual development development

MalesMales>95% azoospermic >95% azoospermic Sexual function unimpaired Sexual function unimpaired Increased incidence of inguinal hernia, Increased incidence of inguinal hernia, hydrocele & undescended testis hydrocele & undescended testis

FemaleFemaleSecondary amenorrhea Secondary amenorrhea Cervicitis Cervicitis Decrease fertility Decrease fertility Good pulmonary functions Good pulmonary functions

pregnancy well toleratedpregnancy well tolerated

Sweat Glands Sweat Glands

During gastroenteritis & During gastroenteritis & warm warm weatherweather

Excessive loss of salt in Excessive loss of salt in sweatsweat

Hypochloremic alklosisHypochloremic alklosis

Diagnosis:Diagnosis:Diagnostic Criteria for Cystic Diagnostic Criteria for Cystic

FibrosisFibrosis

Presence of typical clinical featuresPresence of typical clinical featuresOROR

History of CF in a sibling History of CF in a sibling OROR

Positive newborn screening testPositive newborn screening testPLUSPLUS

Lab evidence for CFTR dysfunction Lab evidence for CFTR dysfunction two elevated sweat CL conc, obtained on two elevated sweat CL conc, obtained on

separate daysseparate daysOROR

Identification of 2 CF mutations Identification of 2 CF mutations OROR

An abnormal nasal potential difference An abnormal nasal potential difference measurementmeasurement

DiagnosisDiagnosisSweat Testing Sweat Testing

> 60mEq/L of chloride in sweat is > 60mEq/L of chloride in sweat is diagnostic for CF diagnostic for CF

when when one or more other one or more other criteria are present criteria are present

Threshold levels of 40mEq/L have been Threshold levels of 40mEq/L have been suggested suggested

Values b/w 40-60mEq/L suggest CF at all ages Values b/w 40-60mEq/L suggest CF at all ages

Other Diagnostic TestsOther Diagnostic Tests

In pts with equivocal or frankly normal sweat In pts with equivocal or frankly normal sweat chloride chloride values, values, following tests following tests

are used are used to confirm diagnosisto confirm diagnosisIncreased potential difference across nasal Increased potential difference across nasal

epithelium epithelium Loss of this difference with topical amiloride Loss of this difference with topical amiloride

application application Absence of a voltage response to a B –Absence of a voltage response to a B –

adrenergic adrenergic agonist agonist Failure to sweat when a combination of Failure to sweat when a combination of

isoproterenol isoproterenol and atropine is and atropine is injected in skin injected in skin

DiagnosisDiagnosisRadiologyRadiologyPulmonary Pulmonary

Hyperinflation of lungHyperinflation of lungBronchial thickening & plugging & ring Bronchial thickening & plugging & ring

shadows (sugg. Bronchiectasis)shadows (sugg. Bronchiectasis)Nodular densities, patchy atelactasis, Nodular densities, patchy atelactasis,

confluent infiltrates confluent infiltrates Prominent hilar lymph nodesProminent hilar lymph nodesDepression of diaphragm Depression of diaphragm Anterior bowing of sternum Anterior bowing of sternum Narrow cardiac shadowNarrow cardiac shadowCystic formation, extensive Cystic formation, extensive

bronchiectasis, dilated pulmonary bronchiectasis, dilated pulmonary artery segments, segmental artery segments, segmental

or lobar or lobar atelactasis atelactasis Paranasal Sinuses Paranasal Sinuses

Pan opacification Pan opacification Failure of frontal sinus to developFailure of frontal sinus to develop

Fetal USGFetal USGIleal obstruction with meconium in 2Ileal obstruction with meconium in 2ndnd trimestertrimester

DiagnosisDiagnosisPulmonary FunctionPulmonary Function

Not obtained till 5-6 yrs of ageNot obtained till 5-6 yrs of ageResidual volume & functional residual Residual volume & functional residual

capacity are increased (early capacity are increased (early finding)finding)

Declining total lung capacity & vital Declining total lung capacity & vital capacity (late finding) capacity (late finding)

Microbiological StudiesMicrobiological Studies

Staph aureus, pseudomonas aeruginosa, Staph aureus, pseudomonas aeruginosa, B. cepaciaB. cepacia

Treatment Treatment 1- Pulmonary therapy1- Pulmonary therapy

2- Nutritional therapy 2- Nutritional therapy

3- Treatment of Complications 3- Treatment of Complications

Pulmonary Treatment:Pulmonary Treatment:Antibiotic therapy Antibiotic therapy Oral Antibiotic Therapy Oral Antibiotic Therapy Indications:Indications:

Presence of respiratory tract symptoms Presence of respiratory tract symptoms

Identification of pathogenic organisms Identification of pathogenic organisms in respiratory tract culturesin respiratory tract cultures

OrganismsOrganismsStaph aureus, H. influenzae, Staph aureus, H. influenzae,

P. aeruginosa, P. aeruginosa, Burkholderi Burkholderi cepaciacepacia

Duration of therapyDuration of therapy2 wks or more2 wks or more

Pulmonary Treatment (Cont…)Pulmonary Treatment (Cont…)Antibiotic TherapyAntibiotic TherapyAerosolized Antibiotic TherapyAerosolized Antibiotic Therapy

Inhaled tobramycin, 300mg twice daily on Inhaled tobramycin, 300mg twice daily on alternate months for 6 monthsalternate months for 6 months

Ticarcillin, 0.5g, BD OR QIDTicarcillin, 0.5g, BD OR QIDColistin, 20-40mg, BD ORColistin, 20-40mg, BD OR QID QID

Intravenous Antibiotic TherapyIntravenous Antibiotic TherapyIndicated in pts. Who have progressive or Indicated in pts. Who have progressive or

unrelenting symptoms or signs despite unrelenting symptoms or signs despite intensive home measures intensive home measures

Period of treatment is 14 daysPeriod of treatment is 14 daysPseudomonas requires 2 drug therapy Pseudomonas requires 2 drug therapy B. cepacia refractory to antibiotic therapyB. cepacia refractory to antibiotic therapy

Pulmonary Treatment (Cont…)Pulmonary Treatment (Cont…)Nebulized TreatmentNebulized Treatment

Bronchodilators Bronchodilators Distilled waterDistilled waterMucolyticsMucolyticsAntibioticsAntibioticsGromolynGromolynCorticosteroidsCorticosteroidsHypertonic 6% salineHypertonic 6% salineNebulized amilorideNebulized amilorideUridine triphosphate Uridine triphosphate Antiprotease proteinsAntiprotease proteinsRecombinant alpha 1 antitryspinRecombinant alpha 1 antitryspinRecombinant human secretory leukoprotease Recombinant human secretory leukoprotease inhibitorinhibitor

Pulmonary Treatment (Cont…)Pulmonary Treatment (Cont…)Bronchodilator TreatmentBronchodilator TreatmentInhaled B2 agonistsInhaled B2 agonistsAnticholinergicsAnticholinergicsOral theophyllineOral theophylline

Anti Inflammatory TreatmentAnti Inflammatory Treatment

Long term use of oral corticosteroids & Long term use of oral corticosteroids & ibuprofenibuprofen

Mucolytic Treatment: Dornase Mucolytic Treatment: Dornase Alpha Alpha (Recombinant (Recombinant Human Human Deoxyribonuclease 1)Deoxyribonuclease 1)

Cleaves extracellular DNA & decreases Cleaves extracellular DNA & decreases viscoelasticity of purulent secretionsviscoelasticity of purulent secretions

Used in chronic suppurative disease or Used in chronic suppurative disease or obstructive obstructive disease disease Dose: 2.5 mg ODDose: 2.5 mg OD

Pulmonary Treatment (Cont…)Pulmonary Treatment (Cont…)Chest Physical TherapyChest Physical Therapy

10-20 min10-20 minOne to 4 time a dayOne to 4 time a dayRoutine aerobic exercisesRoutine aerobic exercises

Endoscopy& Lavage Endoscopy& Lavage Tracheobronchial suctioning or lavageTracheobronchial suctioning or lavage

Expectorants Expectorants Lodides Lodides GuaiphenesinGuaiphenesin

Nutritional TherapyNutritional Therapy90% pts have complete loss of exorine 90% pts have complete loss of exorine pancreatic function & inadequate pancreatic function & inadequate digestion of fats & proteins Dietdigestion of fats & proteins Diet

CF pts require 120% of normal energy CF pts require 120% of normal energy requirement requirement Liberal diet containingLiberal diet containing

FatsFatsSugarSugarSaltSaltMilk productsMilk productsProtein foodsProtein foods

Advanced lung disease Advanced lung disease NG tube or NG tube or gastrostomy gastrostomy

Nutritional Therapy (Cont…)Nutritional Therapy (Cont…)

Pancreatic Enzyme ReplacementPancreatic Enzyme Replacement

Fat absorption improves from 60% without Fat absorption improves from 60% without therapy to 85-90% with therapytherapy to 85-90% with therapy

An upper limit of 10,000 units lipase An upper limit of 10,000 units lipase /kg/day/kg/day

PERT for infants -----500-1000 units lipase PERT for infants -----500-1000 units lipase per gram of dietary fatper gram of dietary fatPERT for children ----500-4000 units lipase PERT for children ----500-4000 units lipase per gram of dietary fatper gram of dietary fat

Complications

AtelectasisPneumothoraxAllergic AspergellosisNontuberculous Mycobacterial infection Bone & joint complicationsAcute & chronic respiratory failure

Management Issues

Is lung transplantation an option for this patient?Is modification of current medical treatment warranted?When should the patient be transferred to adult care?How much the patient should know about the disease?How to counsel the child and the family?

Thank You