CYSTIC FIBROSIS : summarized

CYSTIC FIBROSIS

DR Sadia Hayat

Cystic fibrosis is an inherited autosomal recessive multisystem disorder of children and adults due to primary defect in CFTR protein encoded by CF gene .F508del mutation is most common.

PATHOGENSIS :

Due to loss of fuction of  CFTR  leads to decreased secretion of chloride and increased reabsorption of sodium and water across epithelial cells

§  RESPIRATORY TRACT : due to defective chloride secretion and excess  reabsorption of sodium and water .Failure to clear mucous secretions , paucity of water in mucous secretions, an elevated salt content of sweat and other secretions .Insufficient water on airway surface to hydrate secretions .dessicated secretions become more viscid and elastic that are harder to clear by mucociliary and other mechanisms .secretions are retained and obstruct airways (first of all bronchioles)

§  GASTROINTESTINAL TRACT , PANCREAS AND LIVER

§  IN 85 % pts pancreatic insufficiency occurs which arisis from reduced bicarbonate secretion ( disturbing optimal ph for pancreatic enzymes),reduction of water content of secretions and plugging of ductules and pancreatic acini .Pancreatitis may occur .

§  In gut defective CFTR leads to reduced chloride and water secretion causes meconium ileus at birth and distal intestinal obstruction syndrome in later life

§  In liver there is increased biliary viscosity and plugging of biliary ductules ,can cause obstructive cirrhosis , portal hypertension and hypersplenism .gallstones and cholecystitis are more common in cystic fibrosis

§  SWEAT DUCTS : failure of chloride and sodium reabsorption from the sweat ducts leading to high sweat salt content

§  VAS DEFERENS : males are azoospermic because of agenesis of vas deferens ,isolated congenital bilateral absence of vas deferens (CBAVD).

CLINICAL FEATURES:

§  Respiratory tract :chronic or recurrent cough ,recurrent lower respiratory tract infections , recurrent wheezing ,recurrent sinusitis ,nasal polyps

§  Gastrointestinal ,pancreatic and hepatobiliary tracts :

§  neonatal :CF may present with intestinal obstruction at birth due to meconium ileus(7-10% pts ), passage of meconium may be delayed (due to meconium  plug),there may be prolonged cholestatic jaundice

§  infants and children :failure to thrive ,flatulence, recurrent abdominal pain and abdominal distension .Malabsorption: fat accompanied by steatorrhea(frequent ,foul smelling ,bulky stools).intussception and rectal prolapse may occur

EXAMINATION:low weight ,anemia, short stature,dry skin (vitamin A deficiency) skin rash (zinc deficiency )  ,abdominal distension , rhinitis, sinusitis and nasal polyps, clubbing, cyanosis, increased AP diameter of chest ,cough, tachypnea and recession ,wheezes or crackles on auscultation ,delayed puberty.

INVESTIGATIONS :

SWEAT CHLORIDE TEST

First line diagnostic test in suspected CF . quanatitaive pilocarpine iontophoresis test is performed. Minimum of 100 mg of sweat should be collected onto filter paper for estimaton of sodium and chloride .

·         Negative (normal) test : Cl<40 mmol/ l

·         Borderline (suggestive) :Cl 40-60 mmol/l

·         Positive (supportive ) Cl >60 mmol/l

·         GENOTYPING (DNA Analysis . CFTR analysis for F508del mutations .negative result reduces likelihood of CF but doesnot exclude it .

·          

·         CBC (anemia, Raised TLC ) ESR/CRP, Blood Culture,

·         Stool Examination for fat globules.

·         Chest X ray :hyperinflation and bronchial thickening and plugging and ring shadows suggesting bronchiectasis (first in upper lobes ) . nodular densities , patchy atelectasis ,prominent hilar lymph nodes .in advanced disease cyst formation, extensive bronchiectasis , dilated pulmonary artery segments , and segmental or lobar atelectasis apparent with advanced disease

·         Microbiology : sputum culture/ cough swab. Common bacterial pathogens are staphylococcus aureus , Pseudomonas aeruginosa , klebsiella pneumonia , Burkholderia cepacia ,and hemophilus influenza

·         CT chest : detects and localizes thickening of bronchial airway walls , mucous plugging ,focal hyperinflation and early bronchiectasis .

TREATMENT :

Main aim is to prevent progression of lung disease ,maintain adequate nutrition ,monitor for and treat complications and provide psychological report Initial efforts after diagnosis should be intensive and shouldinclude baseline assessment, initiation of treatment, clearing ofpulmonary involvement, and education of the patient and parents.Follow-up evaluations are scheduled every 1-3 mo, depending onthe age at diagnosis,

RESPIRATORY:

i)        PHYSIOTHERAPY: twice daily physiotherapy comprising postural drainage and percussion in infants and children and independent airway clearance devices with deep breathing exercises in older children

ii)       

iii)    ANTIBIOTICS: Protection against exposure to methicillin-resistant S.aureus, P. aeruginosa, B. cepacia, and other resistant gramnegative organisms is essential,Indications for oral antibiotic therapy in a patient with CF include the presence of respiratory tract symptoms and identifcation of pathogenic organisms in respiratory tract cultures.

Oral/
IV antibiotics/

inhaled antibiotics may be given.
Empirical therapy includes Azithromycin , Erythromycin .

Staphylococcus aureus :Vancomycin ,Linezolid ,Cephalexin ,Clindamycin Amoxicillin-clavulanate

Haemophilus infuenzae; Amoxicillin

Pseudomonas aeruginosa :Ciprofoxacin

Burkholderia cepacia ;Trimethoprim-sulfamethoxazole

>>Inhaled Aztreonam and tobramycin may be given.

iv)    Pancreatic Enzyme Replacement

v)      Vitamin ADEK and Calcium /Zinc Supplementation

vi)    Keep on 3 monthly followup. Assess growth parameters and asses for infections.

COMPLICATIONS OF CYSTIC FIBROSIS:

Anemia
Short stature
Infertility

Delayed puberty
Edema-hypoproteinemia

RESPIRATORY

Bronchiectasis, bronchitis, bronchiolitis, pneumonia

Atelectasis

Hemoptysis

Pneumothorax

Nasal polyps

Sinusitis

Reactive airway disease

Cor pulmonale

Respiratory failure

Mucoid impaction of the bronchi

Allergic bronchopulmonary aspergillosis

GASTROINTESTINAL

Meconium ileus, meconium plug (neonate)

Meconium peritonitis (neonate)

Rectal prolapse

Pancreatitis

Biliary cirrhosis (portal hypertension: esophageal varices, hypersplenism)

Neonatal obstructive jaundice

Hepatic steatosis

Gastroesophageal reflux

Cholelithiasis

Growth failure (malabsorption)

Vitamin def ciency states (vitamins A, K, E, D)

Insulin deficiency, symptomatic hyperglycemia, diabetes