Cystic fibrosis
D E FI N I T ION
Autosomal recessive inherited multi-system disease characterized by recurrent
respiratory tract infections, pancreatic insufficiency, malabsorption and male infertility.
AE T IOLOGY
Caused by a defective CFTR gene on chromosome 7q, which encodes a
cAMP-dependent Cl
channel. This channel regulates Na
þ
and Cl
concentrations in
exocrine secretions, especially in the lung and pancreas. Any loss of function mutations
results in thick viscous secretions. Greater than 800 mutations reported, most common is
DF508 phenylalanine deletion (75% cases in UK).
At birth, the lung is normal histologically but as the lung matures there is mucous gland
hyperplasia, recurrent infection leads to fibrosis, consolidation and bronchiectasis.
E P IDEMIOLOGY
Most common life-threatening autosomal inherited condition in Caucasians.
Incidence is 1 in 2500 live births. In UK, 1 in 25 are carriers.
H ISTORY
Lung: Recurrent chest infections, chronic cough, wheeze, sputum, haemoptysis.
Gut: Meconium ileus (in neonates), steatorrhoea (caused by " fat in the stool).
Other: Chronic sinusitis, nasal polyps, male infertility, arthritis.
EXAMINA T I ON
Chest: Chest wall deformities, coarse crepitations and wheeze.
Signs of malnutrition: Anaemia, weight loss, signs of vitamin deficiencies, slow growth,
failure to thrive in children, delayed puberty in adolescents.
Other: Clubbing, nasal polyps, signs of diabetes, hepatomegaly.
INVE S T I G A T IONS
Sweat test: Pilocarpine iontophoresis (low electrical current) stimulates sweat secretion
which is collected and analyzed for Na
þ
and ClCl
levels >60 mmol is diagnostic of
cystic fibrosis).
Neonatal screening: Standard day 6 Guthrie heal prick, blood is tested for immunoreactive
trypsin (raised by 2–5 in babies with cystic fibrosis).
CXR: May be normal in mild disease or show increased bronchial markings, ring shadows,
fibrosis (often upper zone). Consolidation or bronchiectasis in more advanced cases.
Pancreatic assessment: Faecal elastase, faecal fat content, GTT, HbA1c.
Genetic analysis: For CFTR mutations. Rarely necessary.
Lung function tests: To assess lung function and for long-term prognosis.
MANAGEMENT
Multidisciplinary specialist care is necessary.
Respiratory:
. Chest physiotherapy (postural drainage, regular exercise), positive expiratory pressure
masks;
. bronchodilator therapy (if responsive);
. nebulized recombinant human deoxyribonuclease (rhDNase) and hypertonic saline can be
used to assist in mucociliary clearance and may reduce pulmonary exarcebations;
. antibiotic prophylaxis and aggressive treatment of infections (especially Pseudomonas);
. influenza vaccination.
GI: Adequate nutritional intake is vital, using high-calorie oral supplements and oral
pancreatic enzyme replacement, vitamin (especially fat-soluble) supplements.
Endocrine: Insulin replacement therapy if diabetes develops.
Surgical: Single lung or heart–lung transplants is an option in end-stage disease (5-year
survival is 55%).
COM P L IC A T I ONS
Recurrent chest infections, bronchiectasis (particularly Haemophilus,
Staphylococcus and Pseudomonas).
Cystic fibrosis (continued)
Malabsorption, meconium ileus, intussusception, rectal prolapse.
Diabetes mellitus Type I (30% by late teens).
Male infertility (females are fertile but conception may be difficult).
Gallstones.
P ROGNOS I S
Life expectancy is in the third decade, but steadily improving. Those with
pancreatic insufficiency and those colonized by Pseudomonas have poorer prognosis. Gene
replacement therapy may be possible in the future.
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