Cystic fibrosis (CF), also called mucoviscidosis, is an autosomal recessive genetic disease that affects the exocrine function of the lungs, liver, pancreas, small bowel, sweat glands, and the male genital system. This is resulting in progressive disability and multisystem failure.
This article is a general discussion of the disease. Each organ system will be discussed separately.
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recurrent bacterial infection
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pancreas (most common abdominal organ involved 9)
exocrine and endocrine insufficiency
pancreatitis (acute and chronic)
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liver
focal biliary and multilobular cirrhosis
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biliary system
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gastrointestinal tract
meconium ileus: 10-20%
esophageal dysfunction / gastro-esophageal reflux
distension of appendix but reduced risk of appendicitis
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urogenital tract manifestations 11
bilateral seminal vesicle agenesis
hypoplasia or agenesis of the ductus deferens
hypoplasia or agenesis of the tail and body of the epididymis
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Epidemiology
Cystic fibrosis is the most common genetic disease affecting European population with an incidence of approximately 1:2000-3500 live births 5.
Clinical presentation
The diagnosis may be suspected antenatally due to the presence of echogenic bowel on antenatal ultrasound, or due to genetic testing of the parents.
In many countries, the presence of cystic fibrosis is tested for immediately after birth with a sweat test (positive sweat chloride test Cl >60 mEq/L) 5. Alternatively, genetic testing is also available.
The diagnosis usually becomes evident in infancy, with presentations including 12:
recurrent pulmonary infection
steatorrhea
poor weight gain
Pathology
Genetics
Cystic fibrosis is due to a homozygous defect of the CFTR gene located on chromosome 7q31.2. This gene encodes for a transmembrane protein known as cystic fibrosis transmembrane regulator (CFTR) which is responsible for regulating chloride passage across cell membranes. There are at least 6 classes of mutations, the commonest being ∂F508 (66-70%) 6.
In skin, unlike elsewhere, the CFTR protein is responsible for the influx of chloride and increases the sodium channel activity, thus controlling the influx of sodium. The net effect of a normally functioning CFTR is to resorb sodium and chloride. In CF patients, this is lost and therefore the characteristic increase in salt content of sweat (thus the sweat test).
In tissues other than skin, the CFTR protein is responsible for efflux of chloride and inhibition of the sodium channel's activity which controls the influx of sodium. Therefore, under normal circumstances, salt and chloride remain in the lumen and keep water there osmotically. In CF patients, too little chloride is pumped out, too much sodium is resorbed with osmotic resorption of water from the lumen. The result is iso-osmotic, but low volume, secretions, which tend to dry out, or be thick as they still contain all the other constituents.
Treatment and prognosis
Early institution of multidisciplinary treatment is essential and responsible for the dramatic increase in life expectancy, now reaching 40 or more years.
Treatment options include 7,10,13:
dietary changes, including pancreatic enzyme and vitamin supplementation
physiotherapy and airway clearance techniques
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cystic fibrosis transmembrane regulator (CFTR) modulators
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for ∂F508 mutation:
ivacaftor and lumacaftor combination therapy
ivacaftor and tezacaftor combination therapy
elecacaftor-tezacaftor-ivacaftor combination therapy
for G551D mutation: ivacaftor monotherapy
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anti-inflammatory therapy (e.g. azithromycin)
antibiotics, often multiple agents administered for prolonged courses
oral and inhaled corticosteroids
lung transplantation
specific management of complications (e.g. diabetes mellitus, hemoptysis, distal intestinal obstruction syndrome (DIOS), etc.)
Both transplanted and non-transplanted CF patients are at increased risk of some malignancies 8:
gastrointestinal malignancy, in particular esophageal, gastric, small bowel, and colorectal cancer
gallbladder and extrahepatic biliary tree malignancies