Meconium ileus Neonatal intestinal obstruction (meconium plug, atresia) Steatorrhea, malabsorption Hepatic cirrhosis in childhood (including any manifestations such as esophageal varices or portal hypertension) Cholestatic jaundice in infancy Pancreatitis Rectal prolapse Fat-soluble vitamin deficiency states (A, D, E, K) Hypoproteinemia, hypoalbuminemia, peripheral edema
Prolonged, direct-reacting neonatal jaundice MISCELLANEOUS
Digital clubbing Failure to thrive Family history of cystic fibrosis (e.g., in sibling or cousin) Salty taste of skin (typically noted by parent on kissing affected child—from salt crystals formed after evaporation of sweat) Hyponatremic hypochloremic alkalosis in infants Nasal polyps Recurrent sinusitis Aspermia Absent vas deferens presence of known disease-causing DNA mutations are the only criteria required for diagnosis, as clinical symptoms may not be manifested early in life.
Although the sweat test is both specific and sensitive for CF, it is subject to technical problems, and there are false-positiveand false-negative results (Table 137-3). Cutoff diagnostic measurements for infants less than 6 months may be lower. Other supportive tests include the measurement of bioelectrical potential differences across nasal epithelium (not widely available) and measurement of fecal elastase levels. Low fecal elastase levels indicate exocrine pancreatic insufficiency. CF genotyping done by commercial laboratories identifies approximately 95% of patients with CF, but there are mutations that are not identified by standard testing. Not all mutations in CFTR are considered disease-causing and have uncertain prognostic consequences. Some infants identified by newborn screening with borderline sweat tests and mutations of uncertain consequence are considered to have CFTR-related metabolic syndrome (CRMS). Older children that present with atypical clinical features and borderline sweat tests may be considered non-classical CF or mild variant CF.
Identification of carriers (heterozygotes) and prenatal diagnosis of children with the ΔF508 and other common mutations is offered at most medical centers. Present testing techniques can identify more than 90% of carriers. Prenatal detection of a known CF genotype may be accomplished by amniocentesis or chorionic villus sampling.
The treatment of CF is multifactorial, but it is primarily directed toward the gastrointestinal and pulmonary complications. Presently, there is no effective single cure for cystic fibrosis. Therapies targeted at correcting the underlying CFTR defect are under investigation. Recently, a landmark medication known as small-molecule potentiators targeted to improve function of defective CFTR has been approved for a small subset of CF patients who have an abnormal gating mechanism of their CFTR protein. Management of pulmonary complications is directed toward facilitating clearance of secretions from the airways and minimizing the effects of chronic bronchial infection. Airway secretion clearance techniques (chest physiotherapy) help remove mucus from the airways, and aerosolized DNAse and 7% hypertonic saline, both delivered by nebulizer, decrease the viscosity of mucus. Antibiotic therapy is important in controlling chronic infection. Monitoring pulmonary bacterial flora via airway cultures and providing aggressive therapy with appropriate antibiotics (oral, aerosolized, and IV) help to slow the progression of lung disease. Patients often require 2to 3-week courses of high-dose intravenous antibiotics and aggressive chest physiotherapy to treat pulmonary exacerbations. Antibiotics are selected based on organisms identified by sputum culture. If patients are unable to provide sputum, then a throat culture for CF pathogens can be used to direct therapy. Common infecting organisms are Pseudomonas aeruginosa and Staphylococcus aureus.