Cystic Fibrosis (CF)

Cystic fibrosis (CF) is the most common life-threatening autosomal-recessive genetic disorder in the United States, affecting approximately 1 in 4000 births. Rates are higher in some European nations.¹ Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene result in the formation of a dysfunctional protein. Pulmonary disease, digestive symptoms due to pancreatic insufficiency, male infertility due to bilateral absence of the vas deferens, and increased chloride loss in sweat are all characteristics of CF.² In most cases, symptoms develop at or shortly after birth; respiratory infections and poor weight gain are the most common manifestations. Recurrent respiratory infections and pancreatic insufficiency indicate the presence of CF. Complications (eg, liver disease, hemoptysis, CF-related diabetes, nasal polyps, intestinal obstruction, and allergic bronchopulmonary aspergillosis) develop in almost every organ and worsen with age.³ 

Newborns with CF may present with meconium ileus, persistent neonatal jaundice, and early lung infection. Anemia, failure to thrive, poor weight gain, repeated sinopulmonary infections, undescended testicles in male children, and a distal intestinal obstructive syndrome with or without pancreatic insufficiency are other manifestations of CF seen in infants and children. Although clinical signs and symptoms may not develop until later, the median age at diagnosis is 6 to 8 months. Exacerbations of one or more symptoms are common in adults with CF.⁴ 

Respiratory Manifestations

Recurrent wheezing, pneumonia, dyspnea on exertion, bronchiolitis, hemoptysis, atypical asthma, allergic bronchopulmonary aspergillosis, and Pseudomonas aeruginosa infection are frequent features of CF in the respiratory tract.^4,5 Chronic rhinosinusitis, chronic postnasal drip, nasal polyps, and pan-opacification of the paranasal sinuses are symptoms of sinus involvement in CF.⁴ 

The most common cause of mortality is chronic, progressive pulmonary disease (77% of cases), manifesting as chronic endobronchial bacterial infection, exacerbations of infections, and structural alterations of the lungs.^6. 

The course of chronic lung illness and paranasal sinus disease differs across patients with CF, and CF can be difficult to distinguish from recurrent attacks of bronchitis and/or pneumonia, particularly in preschool children. Even when the result of neonatal screening is negative, children with prolonged coughing, sputum formation, wheezing, consistently abnormal radiological results, consistently positive bacterial cultures of respiratory secretions, or clubbing of the fingers should be tested for CF.⁶ 

Gastrointestinal Manifestations

Abdominal distension, steatorrhea, biliary cirrhosis, and volvulus or intussusception are common gastrointestinal symptoms and signs.⁵ Exocrine pancreatic insufficiency, which affects 85% of individuals with CF, causes copious amounts of fatty, shiny, foul-smelling, pulpy feces; abdominal complaints; dystrophy; and deficiencies of fat-soluble vitamins and trace elements. Chronic and/or recurrent pancreatitis is more likely to occur in patients with primary pancreatic insufficiency.⁶ 

Some patients have gastro-esophageal reflux. Small-intestinal manifestations include meconium ileus, seen in approximately 10% of newborns with CF; distal intestinal obstruction syndrome; celiac disease;  malabsorption despite sufficient enzymes; and Crohn’s disease.⁷ Large-intestinal manifestations include constipation and rectal prolapse. Hepatobiliary manifestations include fatty liver, which is mostly asymptomatic; focal biliary cirrhosis; gallstones; periportal fibrosis; liver cirrhosis; and portal hypertension.^4,7

Genitourinary Manifestations

Genitourinary manifestations include undescended testes and congenital bilateral absence of the vas deferens in males, and reduced fertility in females.⁵ Male infertility is a result of absence of the vas deferens; fertility in females is decreased by thickening of the cervical mucus.⁴ 

Manifestations in Other Organ Systems 

Musculoskeletal manifestations include kyphoscoliosis, osteopenia/osteoporosis, and arthropathy. Hematological manifestations include iron deficiency anemia and anemia of chronic disease resulting in splenomegaly. Renal manifestations consist of kidney stones, nephrocalcinosis, hyperoxaluria, and hypocitraturia. Skin manifestations include salty sweat, digital clubbing, and cyanosis. Acrodermatitis enteropathica due to zinc deficiency and scaly dermatitis due to fatty acid deficiency are other skin diseases caused by malabsorption.⁴ 

References

1. Farrell PM, White TB, Ren CL, et al. Diagnosis of cystic fibrosis: consensus guidelines from the Cystic Fibrosis Foundation. J Pediatr. 2017;181:S4-S15.e1. doi:10.1016/j.jpeds.2016.09.064
2. Padoan R, Quattrucci S, Amato A, et al. The diagnosis of cystic fibrosis in adult age. Data from the Italian Registry. Diagnostics (Basel). 2021;11(2):321. doi:10.3390/diagnostics11020321
3. De Boeck K. Cystic fibrosis in the year 2020: a disease with a new face. Acta Paediatr. 2020;109(5):893-899. doi:10.1111/apa.15155
4. Yu E, Sharma S. Cystic fibrosis. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2021. Accessed January 14, 2022.
5. Brown SD, White R, Tobin P. Keep them breathing: cystic fibrosis pathophysiology, diagnosis, and treatment. JAAPA. 2017;30(5):23-27. doi:10.1097/.01.JAA.0000515540.36581.92
6. Naehrig S, Chao CM, Naehrlich L. Cystic fibrosis. Dtsch Arztebl Int. 2017;114(33-34):564-574. doi:10.3238/arztebl.2017.0564
7. Davies JC, Alton EW, Bush A. Clinical review: cystic fibrosis. BMJ. 2007;335(7632):1255-1259. doi:10.1136/bmj.39391.713229.AD

Reviewed by Kyle Habet, MD, on 1/26/2022.

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Harshi Dhingra, MD

Harshi Dhingra is a licensed medical doctor with specialization in Pathology. She is currently employed as faculty in a medical school with a tertiary care hospital and research center in India. Dr. Dhingra has over a decade of experience in diagnostic, clinical, research, and teaching work, and has written several publications and citations in indexed peer reviewed journals. She holds medical degrees for MBBS and an MD in Pathology.