CYSTIC FIBROSISDR Yusuf Imran

Department OF PEDIATRICS

J.N MEDICAL COLLEGE

AMU - INDIA

INTRODUCTION

• It is the most common life limiting disorders in Caucasians.

• Incidence reported in india : 1 in 40,000

MOLECULAR GNETICS

BASIC DEFECT :

• CF gene identified in 1989

• Location-long arm of chromosome 7 at position 7q.

• >1000 mutations have been recognised.

• BASIC DEFECT IN CF is a mutation in gene for chloride conductance channel ( F508).

PATHOGENESIS

The result is a feature of chloride conductance by epithelial cells

leads to dehydration of mucosal secretions that become too

viscid and difficult to clear.

CLINICAL MANIFESTATIONS

• Age at diagnosis –mean 54 months.

• Age at onset symptoms-mean 11 months.

• SEX –M:F=2:1

SYMPTOMS

Clinical features depend on age at diagnosis and supportive t/t.

AGE 0 – 2 Years

• Recurrent/Persistent pneumonia-(98%)

• Failure to thrive(90%)

• Malabsorption/Steatorrhoea (80%)

• Dehydration (16%)

• Rectal prolapse (16%)

• Muconium ileus (10%) – Newborn

• AGE 2 – 12 Years-

• Malabsorption (85%)

• Recurrent pneumonia (60%)

• Nasal polyposis (6 – 36 % )

• Intussusception (1-5%)

AGE >13 Years- (Teens )

• Chronic pulmonary disease (70%)• Abnormal GTT (20-30%)• DM (7%)• Chronic intestinal obstruction (10-20 %)• Focal biliary cirrhosis and portal HTN (25%)• Gall stones (4-14%)• Azoospermia (98%)

• The spectrum of cystic fibrosis may vary from meconium ilius in the new born period to recurrent pneumonias,malabsorption and intestinal obstruction in early childhood to chronic pulmonary disease,DM and azoospermia of adolescents and adults.

EXAMINATION

• Malnutrition in almost half of the patients (42%)

• Clubbing (75-80%)

• Hyper inflated chest(75-80%)

• Nasal polyps are seen in 5% cases

DIAGNOSIS

• Sweat chloride (>60mEq/L) remains the first line diagnostic test

as gene identification is not readily available in our country.

• DNA testing for most common CFTR (Cystic fibrosis

transmembrane conductance regulator ) mutations.At least two

mutations should be detected.

• SUPPORTIVE INVESTIGATION

1- Serum- low or low normal sodium.Metabolic alkalosis and hypochloremia.

2- Airway colonization- Cystic fibrosis children may be infected with• Pseudomonas aregenosa• Staph auresus• Non typable H.influenza(Sample obtained by nasopharyngeal aspirate/sputum induction)

3. Pancreatic functions tests-

• CF is the commonest cause of Exocrine pancreatic insufficiency.• Stool crematocrit estimation is a crude method.• Stool pancreatic elastase is reported to be sensitive and specific.

4. Obstructive Azoospermia - 98% of post pubertal boys are infertile but not STERILE

5. Imaging studies-Xray/CT CHEST- Hyperinflation with peribronchial thickening.

- Cystic changes - Lobar and segmental collapse

PN sinuses - May show delayed prematization & mucosal thickening

MANAGEMENT

• RESPIRATORY MANAGEMENT

• NUTRITIONAL MANAGEMENT

• ANTICIPATION AND EARLY DIAGNOSIS OF LIVER DISEASE,

DIABETES AND OTHER ORGAN DYSFUNTION.

RESPIRATORY MANAGEMENT

• Aims to limit lung damage a) By decreasing the number of infecting organisms. b) By supressing inflammatory process and hyperactivity of airways.

• This requires adequate hydration, chest physiotherapy, judicious use of A/B and mucolytic agents.

• ANTIBIOTICS -

• Cephazolin 25-50mg/kg for staph aureus.• Ticarcillin, clavunate and Tobramycin for staph +

pseudomonas• Ciprofloxacin for Burkholderia cepacia (i.v -2-4 weeks in

serious hospitalized patients)• Aerosolized drugs can also be used.

• CHEST PHYSIOTHERAPY -

• Postural drainage • Chest clapping• Active cyclic breathing

• MUCOLYTIC AGENTS

• N-acetyl cysteine orally/inhalation helps but has serious

side effects like bronchospasm and haemorrhagic

tracheitis.

• Recombinant DNAase is promising but not available in

India.

• BRONCHODILATOR & INHALATIONAL STEROID THERAPY

25-50% have hyperactive airway disease.

NUTRITIONAL MANAGEMENT

• The aim is to achieve normal growth and development.it includes

1. INCREASING CALORIC INTAKE

2. SUPPLEMENTING FAT SOLUBLE VITAMINS

3. REPLACING PANCREATIC ENZYMES

A. RECOMMENDED CALORIC SUPPLEMENT PER DAY –

• 1-2 YEARS ------------------200 Kcal

• 3-5 YEARS-------------------400 Kcal

• 6-11 YEARS------------------600 Kcal

• >12 YEARS-------------------800 Kcal

B- SUPPLEMENTING FAT SOLUBLE VITAMINS : Due to pancreatic

insufficiency there is increased risk of deficiency of fat soluble

vitamins.

Deficiency of fat soluble vitamins may be there in 40% of children

between 4-8 weeks.

• Recomended doses-

AGE VIT A VIT D

<6 Weeks 2000 IU 200 IU

6 weeks – 6 months 4000 IU 400 IU

> 6 months 8000 IU 800 IU

C. REPLACING PANCREATIC ENZYMES

• Can be given as spherules and capsules with meals.

• Can be sprinkled on food for smaller children who cant

swallow.

• 10,000 IU lipase/kg/day usually checks fat

Malabsorption and leads to normal growth.

MANAGEMENT OF OTHER GI MANIFESTATIONS

• Pain abdomen- For GERD - prokinetic and H2 receptor blockers

• Abdominal distention - Rectal prolapse responds to pancreatic enzymes

and lactulose (1ml/kg).

• Meconium ileus- Maintain electrolytes and gastrograffin enema.

• Intussusception – Surgical treatment.

• Meconium peritonitis – surgical treatment.

• Liver disease- survivors develop cholestatic liver disease.

ursodeoxycholic acid(UDCA) is useful drug and alters the natural history of

cirrhosis in CF patients

PROGNOSIS

• The life expectancy is now increased to 30 years as

projected in new born periods

• Bad prognostic indicators are

• Onset below 2 months of age

• Severe malnutrition at the time of diagnosis.

• > 4 episode of pulmonary exacerbation in a year

• Colonization with pseudomonas

SUMMARY• Etiology – Faulty CFTR gene ∆F 508, >100 mutations.

• Basic Defect – Transmembrane chloride conductance leadind to viscid secretionsl

affecting Lungs,Gut,Testes,Pancreas.

• Diagnosis- Sweat chloride test

Identification of mutant gene

• Management-

1. Respiratory-controlling infections,liquefying secretions,postural drainage.

2. Nutritional-calorie supplementation,fat soluble vitamins,replacing pancreatic enzymes.

3.Management of other complications- Liver cirrhosis and portal hypertention,G.I complications.