Cystic Fibrosis (CF)


The CFTR mutation in cystic fibrosis (CF) affects the CF transmembrane conductance regulator, which results in abnormal secretion of chloride and increased reabsorption of sodium into the cellular space. The main manifestation of this defective ionic transportation mechanism is thick, viscous secretions from exocrine tissues. The resultant mucus plugging affects various organs in the body and leads to several complications.1  

Complications Associated With Gastrointestinal Disease

Pancreatic insufficiency – Pancreatic insufficiency is the most common gastrointestinal complication of CF, affecting approximately 85% of patients. The major consequences of pancreatic insufficiency are steatorrhea, malnutrition, and deficiencies in fat-soluble vitamins (A, D, E, and K).2 

Pancreatitis

Develops in approximately 15% to 20% of patients and is more common in patients without pancreatic insufficiency.3 

Meconium ileus

Presents in up to 20% of infants and is one of the earliest manifestations of CF. It is due to a mechanical obstruction of the small intestine at the terminal ileum due to inspissated meconium. Features of intestinal obstruction are bilious emesis with or without abdominal distension at the time of initiation of feeds. Meconium ileus may be diagnosed antenatally based on characteristic sonographic findings, including hyperechoic masses in the terminal ileum, dilated bowel, and nonvisualization of the gallbladder. Severe complications of meconium ileus are prenatal volvulus, ischemic necrosis, intestinal atresia, or perforation and extrusion of meconium into the peritoneum.4 

Fibrosing colonopathy

A severe intestinal fibrotic process characterized by dense submucosal fibrosis associated with strictures in the large bowel in patients with CF. It almost exclusively occurs in patients receiving pancreatic enzyme replacement therapy. Management involves lowering the dosage of pancreatic enzymes to 500 to 2500 lipase units/kg per meal and may require surgical intervention.5 

Small bowel bacterial overgrowth

Defined as an excess of bacteria in the small intestine resulting in chronic diarrhea and malabsorption.6 Patients with CF are susceptible to this condition due to their medications, namely acid-suppressing agents and chronic antibiotic use, and decreased intestinal motility.7

Hepatobiliary disease

Although less than one-third of patients with CF have clinically significant biliary disease, hepatobiliary complications are potentially life-threatening, accounting for approximately 2.5% of overall mortality. Steatosis is a common finding, occurring in 23% to 67% of patients with CF. Most patients will have some biochemical indication of hepatobiliary disease (elevated transaminases or gamma-glutamyl transferase [GGT]), however, it is usually not clinically significant. Serious hepatobiliary complications include focal biliary cirrhosis and multinodular cirrhosis.8 

Other gastrointestinal complications

Other gastrointestinal complications associated with CF include constipation, distal intestinal obstruction syndrome, appendiceal disease, rectal prolapse, and Clostridium difficile colitis.9,10 

Chronic infections

Mucus plugging and chronic lower respiratory tract infections result in bronchiectasis and chronic obstructive pulmonary disease. Poorly managed pulmonary disease is the primary cause of death in patients with CF. Important pathogens responsible for chronic respiratory tract infections in CF are Staphylococcus aureus (methicillin-sensitive), Pseudomonas aeruginosa, methicillin-resistant S aureus (MRSA), and Haemophilus influenzae.11 

Bronchiectasis

After a patient has become colonized with a respiratory pathogen and infection has been established, the normal host response is to recruit neutrophils to combat the infection. Patients with CF possess a unique population of airway neutrophils that display high levels of protease elastase exocytosis, which overwhelms the antiprotease activity of the lung and contributes to tissue destruction, resulting in bronchiectasis.12  

References

1. Yu E, Sharma S. Cystic fibrosis. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2021. Accessed January 5, 2022.

2. Singh VK, Schwarzenberg SJ. Pancreatic insufficiency in cystic fibrosis. J Cyst Fibros. 2017;16 Suppl 2:S70-S78. doi:10.1016/j.jcf.2017.06.011

3. De Boeck K, Weren M, Proesmans M, Kerem E. Pancreatitis among patients with cystic fibrosis: correlation with pancreatic status and genotype. Pediatrics. 2005;115(4):e463-e469. doi:10.1542/peds.2004-1764

4. Parikh NS, Ibrahim S, Ahlawat R. Meconium ileus. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2021. Accessed January 5, 2022.

5. Fibrosing colonopathy. ScienceDirect. Accessed January 5, 2022. 

6. Dukowicz AC, Lacy BE, Levine GM. Small intestinal bacterial overgrowth: a comprehensive review. Gastroenterol Hepatol (N Y). 2007;3(2):112-122.

7. Fridge JL, Conrad C, Gerson L, Castillo RO, Cox K. Risk factors for small bowel bacterial overgrowth in cystic fibrosis. J Pediatr Gastroenterol Nutr. 2007;44(2):212-218. doi:10.1097/MPG.0b013e31802c0ceb

8. Moyer K, Balistreri W. Hepatobiliary disease in patients with cystic fibrosis. Curr Opin Gastroenterol. 2009;25(3):272-278. doi:10.1097/MOG.0b013e3283298865

9. Littlewood JM. Gastrointestinal complications. Br Med Bull. 1992;48(4):847-859. doi:10.1093/oxfordjournals.bmb.a072581

10. Welkon CJ, Long SS, Thompson CM Jr, Gilligan PH. Clostridium difficile in patients with cystic fibrosis. Am J Dis Child. 1985;139(8):805-808. doi:10.1001/archpedi.1985.02140100067032

11. Patient registry. Cystic Fibrosis Foundation. Accessed January 5, 2022.

12. Margaroli C, Garratt LW, Horati H, et al. Elastase exocytosis by airway neutrophils is associated with early lung damage in children with cystic fibrosis. Am J Respir Crit Care Med. 2019;199(7):873-881. doi:10.1164/rccm.201803-0442OC

Reviewed by Hasan Avcu, MD, on 1/6/2022.

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