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
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