Snapshot A 3-year-old boy presents to his pediatrician for fever and a cough. He has a history of recurrent pneumonia and chronic diarrhea. His mother states that he has 6-8 foul smelling stools per day. His temperature is 101.0°F (38.3°C), blood pressure is 95/55 mmHg, pulse is 120/min, and respirations are 28/min. Physical exam is notable for scattered rhonchi in the bilateral lung fields with hepatomegaly. Sweat chloride testing is elevated on 2 separate occasions. Introduction Definition autosomal recessive exocrinopathy An autosomal recessive mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, a chloride channel, on chromosome 7 Epidemiology Incidence most commonly affects Caucasians ΔF508 mutation is the most common mutation Etiology Pathogenesis a defect in the CFTR gene leads to impaired chloride and water transport this causes viscous secretions in the respiratory tract exocrine pancreas sweat glands intestines genitourinary tract Associated conditions nasal polyposis infertility in men and subfertility in women pancreatic insufficiency Presentation Symptoms a productive cough respiratory symptoms are more prominent in adulthood recurrent pulmonary infections S. aureus is more common in pediatric patients (treat with vancomycin) Pseudomonal spp. are more common in adults (treat with amikacin, ceftazidime, and ciprofloxacin) chronic sinusitis chronic productive cough dyspnea on exertion bronchiectasis gastrointestinal symptoms are more prominent in infancy chronic and frequent diarrhea greasy stool with flatulence from malabsorption secondary to pancreatic insufficiency can lead to rectal prolapse meconium ileus in infants (15%) signs of fat-soluble vitamin deficiency Physical exam failure to thrive (50%) respiratory compromise (50%) "salty taste" cyanosis digital clubbing rhonchi rales hyperresonance to percussion nasal polyposis infertility DIAGNOSIS Making the diagnosis is based on clinical symptoms that are consistent with cystic fibrosis in at least 1 organ system evidence of CFTR gene dysfunction elevated sweat chloride test ≥ 60 mmol/L on 2 occasions sufficient to confirm the diagnosis in patients with clinical symptoms suggestive of cystic fibrosis abnormal nasal potential difference genetic testing Treatment Conservative chest physical therapy indication to clean airways and decrease the risk of airway infection fat-soluble vitamin supplementation indication to decrease the risk of fat-soluble vitamin deficiency vaccinations indication used as a preventative measure for pulmonary infection vaccinations influenza pneumococcal Medical antibiotics indication to treat and prevent pulmonary infection pancreatic enzyme replacement therapy indication to manage pancreatic insufficiency Complications Bronchopulmonary lower airway infection (e.g., Pseudomonas) bronchiectasis Gastrointestinal cholestasis intestinal atresia malnutrition and malabsorption intestinal impaction meconium ileus Hepatobiliary pancreatic insufficiency Endocrine diabetes infertility due to congenital absence of the vas deferens decreased fertility in females Prognosis Most of the morbidity and mortality associated with this condition is secondary to pulmonary disease