UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2015 UpToDate®

Cystic fibrosis: Overview of gastrointestinal disease

Authors
Sabina Sabharwal, MD, MPH
Drucy Borowitz, MD
Section Editors
George B Mallory, MD
Melvin B Heyman, MD, MPH
Deputy Editor
Alison G Hoppin, MD

INTRODUCTION

Cystic fibrosis (CF) generally is thought of as a lung disease since much of the associated morbidity and mortality is related to pulmonary complications. A discussion of the pulmonary manifestations of CF is presented separately. (See "Cystic fibrosis: Clinical manifestations of pulmonary disease" and "Cystic fibrosis: Overview of the treatment of lung disease".)

The underlying pathophysiology of CF is related to abnormal chloride and bicarbonate transport caused by mutations in the CF transmembrane conductance regulator gene (CFTR) located on chromosome 7. The mutations cause the production of abnormally tenacious mucus and secretions in the lungs, gastrointestinal tract, pancreas, and hepatobiliary system. As a result, the lumens of these organs become obstructed leading to the clinical findings associated with this disease process. (See "Cystic fibrosis: Genetics and pathogenesis".)

Gastrointestinal complications have become an increasingly important cause of morbidity in patients with CF, in part because of improved life expectancy. Some of the complications, such as gastroesophageal reflux and constipation, are not unique to the CF population, but they are more common and warrant special considerations in diagnosis and management in the CF population. This topic review provides an overview of the gastrointestinal manifestations of CF. Pancreatic insufficiency, which is one of the most clinically important gastrointestinal issues, and other nutritional issues are addressed separately. (See "Cystic fibrosis: Assessment and management of pancreatic insufficiency" and "Cystic fibrosis: Nutritional issues".)

GASTROINTESTINAL TRACT

Gastroesophageal reflux disease (GERD) — Gastroesophageal reflux disease (GERD) appears to be more common in individuals with CF as compared with the general population [1,2]. Symptomatic GERD is reported in 30 to 40 percent of individuals with CF, and "silent" GERD detected by esophageal monitoring has been reported in up to 90 percent of individuals with severe pulmonary disease [3]. However, the magnitude of the association has not been well-defined, since GERD is common in otherwise healthy individuals and because CF is associated with other gastrointestinal disorders that may contribute to or be confused with GERD (table 1). (See "Clinical manifestations and diagnosis of gastroesophageal reflux disease in children and adolescents".)

The principal mechanism causing GERD in children with CF appears to transient relaxation of the lower esophageal sphincter (LES), which is also the most common mechanism leading to GERD in patients without CF. Several other mechanisms may also contribute to GERD in individuals with CF:

                                   

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Apr 2015. | This topic last updated: Apr 16, 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2015 UpToDate, Inc.
References
Top
  1. Sabati AA, Kempainen RR, Milla CE, et al. Characteristics of gastroesophageal reflux in adults with cystic fibrosis. J Cyst Fibros 2010; 9:365.
  2. Cystic Fibrosis Foundation Patient Registry, Annual data report, 2012. Available at: http://www.cff.org/UploadedFiles/research/ClinicalResearch/PatientRegistryReport/2012-CFF-Patient-Registry.pdf (Accessed on November 05, 2014).
  3. Button BM, Roberts S, Kotsimbos TC, et al. Gastroesophageal reflux (symptomatic and silent): a potentially significant problem in patients with cystic fibrosis before and after lung transplantation. J Heart Lung Transplant 2005; 24:1522.
  4. Pauwels A, Blondeau K, Dupont LJ, Sifrim D. Mechanisms of increased gastroesophageal reflux in patients with cystic fibrosis. Am J Gastroenterol 2012; 107:1346.
  5. Woodley FW, Machado RS, Hayes D Jr, et al. Children with cystic fibrosis have prolonged chemical clearance of acid reflux compared to symptomatic children without cystic fibrosis. Dig Dis Sci 2014; 59:623.
  6. Pauwels A, Blondeau K, Mertens V, et al. Gastric emptying and different types of reflux in adult patients with cystic fibrosis. Aliment Pharmacol Ther 2011; 34:799.
  7. Palm K, Sawicki G, Rosen R. The impact of reflux burden on Pseudomonas positivity in children with cystic fibrosis. Pediatr Pulmonol 2012; 47:582.
  8. Stringer DA, Sprigg A, Juodis E, et al. The association of cystic fibrosis, gastroesophageal reflux, and reduced pulmonary function. Can Assoc Radiol J 1988; 39:100.
  9. Navarro J, Rainisio M, Harms HK, et al. Factors associated with poor pulmonary function: cross-sectional analysis of data from the ERCF. European Epidemiologic Registry of Cystic Fibrosis. Eur Respir J 2001; 18:298.
  10. Button BM, Heine RG, Catto-Smith AG, et al. Chest physiotherapy in infants with cystic fibrosis: to tip or not? A five-year study. Pediatr Pulmonol 2003; 35:208.
  11. van der Doef HP, Arets HG, Froeling SP, et al. Gastric acid inhibition for fat malabsorption or gastroesophageal reflux disease in cystic fibrosis: longitudinal effect on bacterial colonization and pulmonary function. J Pediatr 2009; 155:629.
  12. Canani RB, Cirillo P, Roggero P, et al. Therapy with gastric acidity inhibitors increases the risk of acute gastroenteritis and community-acquired pneumonia in children. Pediatrics 2006; 117:e817.
  13. Laheij RJ, Sturkenboom MC, Hassing RJ, et al. Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs. JAMA 2004; 292:1955.
  14. Eom CS, Jeon CY, Lim JW, et al. Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis. CMAJ 2011; 183:310.
  15. Filion KB, Chateau D, Targownik LE, et al. Proton pump inhibitors and the risk of hospitalisation for community-acquired pneumonia: replicated cohort studies with meta-analysis. Gut 2014; 63:552.
  16. Boesch RP, Acton JD. Outcomes of fundoplication in children with cystic fibrosis. J Pediatr Surg 2007; 42:1341.
  17. Sheikh SI, Ryan-Wenger NA, McCoy KS. Outcomes of surgical management of severe GERD in patients with cystic fibrosis. Pediatr Pulmonol 2013; 48:556.
  18. Fathi H, Moon T, Donaldson J, et al. Cough in adult cystic fibrosis: diagnosis and response to fundoplication. Cough 2009; 5:1.
  19. Gelfond D, Ma C, Semler J, Borowitz D. Intestinal pH and gastrointestinal transit profiles in cystic fibrosis patients measured by wireless motility capsule. Dig Dis Sci 2013; 58:2275.
  20. Rovner AJ, Schall JI, Mondick JT, et al. Delayed small bowel transit in children with cystic fibrosis and pancreatic insufficiency. J Pediatr Gastroenterol Nutr 2013; 57:81.
  21. Borowitz SM, Sutphen JL. Recurrent vomiting and persistent gastroesophageal reflux caused by unrecognized constipation. Clin Pediatr (Phila) 2004; 43:461.
  22. Goralski JL, Lercher DM, Davis SD, Dellon ES. Eosinophilic esophagitis in cystic fibrosis: a case series and review of the literature. J Cyst Fibros 2013; 12:9.
  23. Maisonneuve P, Marshall BC, Knapp EA, Lowenfels AB. Cancer risk in cystic fibrosis: a 20-year nationwide study from the United States. J Natl Cancer Inst 2013; 105:122.
  24. Carlyle BE, Borowitz DS, Glick PL. A review of pathophysiology and management of fetuses and neonates with meconium ileus for the pediatric surgeon. J Pediatr Surg 2012; 47:772.
  25. Fakhoury K, Durie PR, Levison H, Canny GJ. Meconium ileus in the absence of cystic fibrosis. Arch Dis Child 1992; 67:1204.
  26. Gorter RR, Karimi A, Sleeboom C, et al. Clinical and genetic characteristics of meconium ileus in newborns with and without cystic fibrosis. J Pediatr Gastroenterol Nutr 2010; 50:569.
  27. Leeuwen L, Magoffin AK, Fitzgerald DA, et al. Cholestasis and meconium ileus in infants with cystic fibrosis and their clinical outcomes. Arch Dis Child 2014; 99:443.
  28. Li Z, Lai HJ, Kosorok MR, et al. Longitudinal pulmonary status of cystic fibrosis children with meconium ileus. Pediatr Pulmonol 2004; 38:277.
  29. Efrati O, Nir J, Fraser D, et al. Meconium ileus in patients with cystic fibrosis is not a risk factor for clinical deterioration and survival: the Israeli Multicenter Study. J Pediatr Gastroenterol Nutr 2010; 50:173.
  30. Karimi A, Gorter RR, Sleeboom C, et al. Issues in the management of simple and complex meconium ileus. Pediatr Surg Int 2011; 27:963.
  31. Copeland DR, St Peter SD, Sharp SW, et al. Diminishing role of contrast enema in simple meconium ileus. J Pediatr Surg 2009; 44:2130.
  32. Noblett HR. Treatment of uncomplicated meconium ileus by Gastrografin enema: a preliminary report. J Pediatr Surg 1969; 4:190.
  33. Farrelly PJ, Charlesworth C, Lee S, et al. Gastrointestinal surgery in cystic fibrosis: a 20-year review. J Pediatr Surg 2014; 49:280.
  34. Houwen RH, van der Doef HP, Sermet I, et al. Defining DIOS and constipation in cystic fibrosis with a multicentre study on the incidence, characteristics, and treatment of DIOS. J Pediatr Gastroenterol Nutr 2010; 50:38.
  35. Colombo C, Ellemunter H, Houwen R, et al. Guidelines for the diagnosis and management of distal intestinal obstruction syndrome in cystic fibrosis patients. J Cyst Fibros 2011; 10 Suppl 2:S24.
  36. Khoshoo V, Udall JN Jr. Meconium ileus equivalent in children and adults. Am J Gastroenterol 1994; 89:153.
  37. Littlewood JM. Cystic fibrosis: gastrointestinal complications. Br Med Bull 1992; 48:847.
  38. Dray X, Bienvenu T, Desmazes-Dufeu N, et al. Distal intestinal obstruction syndrome in adults with cystic fibrosis. Clin Gastroenterol Hepatol 2004; 2:498.
  39. Lin LY, Wong JU. Images in clinical medicine. Meconium-like ileus in cystic fibrosis. N Engl J Med 2012; 366:2017.
  40. Andersen HO, Hjelt K, Waever E, Overgaard K. The age-related incidence of meconium ileus equivalent in a cystic fibrosis population: the impact of high-energy intake. J Pediatr Gastroenterol Nutr 1990; 11:356.
  41. Blackman SM, Deering-Brose R, McWilliams R, et al. Relative contribution of genetic and nongenetic modifiers to intestinal obstruction in cystic fibrosis. Gastroenterology 2006; 131:1030.
  42. Ferry, G, Klish, WJ, Borowitz, D, et al. Consensus Conference: Gastrointestinal Problems in Cystic Fibrosis. In: Clinical Practice Guidelines for Cystic Fibrosis, vol II, Cystic Fibrosis Foundation, Bethesda, MD, 1991.
  43. Rosenstein BJ, Langbaum TS. Incidence of distal intestinal obstruction syndrome in cystic fibrosis. J Pediatr Gastroenterol Nutr 1983; 2:299.
  44. Gregory PC. Gastrointestinal pH, motility/transit and permeability in cystic fibrosis. J Pediatr Gastroenterol Nutr 1996; 23:513.
  45. Parmley RR, Gendler SJ. Cystic fibrosis mice lacking Muc1 have reduced amounts of intestinal mucus. J Clin Invest 1998; 102:1798.
  46. Gyömörey K, Rozmahel R, Bear CE. Amelioration of intestinal disease severity in cystic fibrosis mice is associated with improved chloride secretory capacity. Pediatr Res 2000; 48:731.
  47. Mailleau C, Paul A, Colin M, et al. Glycoconjugate metabolism in a cystic fibrosis knockout mouse model. Mol Genet Metab 2001; 72:122.
  48. Gustafsson JK, Ermund A, Ambort D, et al. Bicarbonate and functional CFTR channel are required for proper mucin secretion and link cystic fibrosis with its mucus phenotype. J Exp Med 2012; 209:1263.
  49. O'Halloran SM, Gilbert J, McKendrick OM, et al. Gastrografin in acute meconium ileus equivalent. Arch Dis Child 1986; 61:1128.
  50. Zahra M, Frederick C, Thomas R, et al. Gastrografin enemas for treatment of distal intestinal obstruction syndrome in children and adults with cystic fibrosis. J Pharm Nutr Sci 2014; 4:76.
  51. Speck K, Charles A. Distal intestinal obstructive syndrome in adults with cystic fibrosis: a surgical perspective. Arch Surg 2008; 143:601.
  52. Smyth RL, van Velzen D, Smyth AR, et al. Strictures of ascending colon in cystic fibrosis and high-strength pancreatic enzymes. Lancet 1994; 343:85.
  53. Prescott P, Bakowski MT. Pathogenesis of fibrosing colonopathy: the role of methacrylic acid copolymer. Pharmacoepidemiol Drug Saf 1999; 8:377.
  54. FitzSimmons SC, Burkhart GA, Borowitz D, et al. High-dose pancreatic-enzyme supplements and fibrosing colonopathy in children with cystic fibrosis. N Engl J Med 1997; 336:1283.
  55. van der Doef HP, Kokke FT, Beek FJ, et al. Constipation in pediatric cystic fibrosis patients: an underestimated medical condition. J Cyst Fibros 2010; 9:59.
  56. Rubinstein S, Moss R, Lewiston N. Constipation and meconium ileus equivalent in patients with cystic fibrosis. Pediatrics 1986; 78:473.
  57. Baker SS, Borowitz D, Duffy L, et al. Pancreatic enzyme therapy and clinical outcomes in patients with cystic fibrosis. J Pediatr 2005; 146:189.
  58. Kopelman H, Forstner G, Durie P, Corey M. Origins of chloride and bicarbonate secretory defects in the cystic fibrosis pancreas, as suggested by pancreatic function studies on control and CF subjects with preserved pancreatic function. Clin Invest Med 1989; 12:207.
  59. Tabbers MM, DiLorenzo C, Berger MY, et al. Evaluation and treatment of functional constipation in infants and children: evidence-based recommendations from ESPGHAN and NASPGHAN. J Pediatr Gastroenterol Nutr 2014; 58:258.
  60. O'Brien CE, Anderson PJ, Stowe CD. Use of the chloride channel activator lubiprostone for constipation in adults with cystic fibrosis: a case series. Ann Pharmacother 2010; 44:577.
  61. O'Brien CE, Anderson PJ, Stowe CD. Lubiprostone for constipation in adults with cystic fibrosis: a pilot study. Ann Pharmacother 2011; 45:1061.
  62. Holmes M, Murphy V, Taylor M, Denham B. Intussusception in cystic fibrosis. Arch Dis Child 1991; 66:726.
  63. Holsclaw DS, Rocmans C, Shwachman H. Intussusception in patients with cystic fibrosis. Pediatrics 1971; 48:51.
  64. Chen CH, Chang CC, Yang BY, et al. Acute appendicitis mimicking intestinal obstruction in a patient with cystic fibrosis. J Formos Med Assoc 2012; 111:580.
  65. Shields MD, Levison H, Reisman JJ, et al. Appendicitis in cystic fibrosis. Arch Dis Child 1991; 66:307.
  66. Al-Abed Y, Hameed W, Roy J, Kumar AP. Appendicitis in an adult patient with cystic fibrosis: a diagnostic challenge. Gut 2007; 56:1799.
  67. Coughlin JP, Gauderer MW, Stern RC, et al. The spectrum of appendiceal disease in cystic fibrosis. J Pediatr Surg 1990; 25:835.
  68. McCarthy VP, Mischler EH, Hubbard VS, et al. Appendiceal abscess in cystic fibrosis. A diagnostic challenge. Gastroenterology 1984; 86:564.
  69. Lardenoye SW, Puylaert JB, Smit MJ, Holscher HC. Appendix in children with cystic fibrosis: US features. Radiology 2004; 232:187.
  70. Fridge JL, Conrad C, Gerson L, et al. Risk factors for small bowel bacterial overgrowth in cystic fibrosis. J Pediatr Gastroenterol Nutr 2007; 44:212.
  71. Lewindon PJ, Robb TA, Moore DJ, et al. Bowel dysfunction in cystic fibrosis: importance of breath testing. J Paediatr Child Health 1998; 34:79.
  72. Schneider AR, Klueber S, Posselt HG, et al. Application of the glucose hydrogen breath test for the detection of bacterial overgrowth in patients with cystic fibrosis--a reliable method? Dig Dis Sci 2009; 54:1730.
  73. Lisowska A, Wójtowicz J, Walkowiak J. Small intestine bacterial overgrowth is frequent in cystic fibrosis: combined hydrogen and methane measurements are required for its detection. Acta Biochim Pol 2009; 56:631.
  74. Gelfond D, Borowitz D. Gastrointestinal complications of cystic fibrosis. Clin Gastroenterol Hepatol 2013; 11:333.
  75. El-Chammas KI, Rumman N, Goh VL, et al. Rectal prolapse and cystic fibrosis. J Pediatr Gastroenterol Nutr 2015; 60:110.
  76. KULCZYCKI LL, SHWACHMAN H. Studies in cystic fibrosis of the pancreas; occurrence of rectal prolapse. N Engl J Med 1958; 259:409.
  77. Stern RC, Izant RJ Jr, Boat TF, et al. Treatment and prognosis of rectal prolapse in cystic fibrosis. Gastroenterology 1982; 82:707.
  78. Coutinho CA, Marson FA, Marcelino AR, et al. TNF-alpha polymorphisms as a potential modifier gene in the cystic fibrosis. Int J Mol Epidemiol Genet 2014; 5:87.
  79. Smyth RL, Croft NM, O'Hea U, et al. Intestinal inflammation in cystic fibrosis. Arch Dis Child 2000; 82:394.
  80. Werlin SL, Benuri-Silbiger I, Kerem E, et al. Evidence of intestinal inflammation in patients with cystic fibrosis. J Pediatr Gastroenterol Nutr 2010; 51:304.
  81. Bruzzese E, Raia V, Gaudiello G, et al. Intestinal inflammation is a frequent feature of cystic fibrosis and is reduced by probiotic administration. Aliment Pharmacol Ther 2004; 20:813.
  82. Dumoulin EN, Van Biervliet S, Langlois MR, Delanghe JR. Proteolysis is a confounding factor in the interpretation of faecal calprotectin. Clin Chem Lab Med 2015; 53:65.
  83. Hoffman LR, Pope CE, Hayden HS, et al. Escherichia coli dysbiosis correlates with gastrointestinal dysfunction in children with cystic fibrosis. Clin Infect Dis 2014; 58:396.
  84. Duytschaever G, Huys G, Bekaert M, et al. Cross-sectional and longitudinal comparisons of the predominant fecal microbiota compositions of a group of pediatric patients with cystic fibrosis and their healthy siblings. Appl Environ Microbiol 2011; 77:8015.
  85. Schippa S, Iebba V, Santangelo F, et al. Cystic fibrosis transmembrane conductance regulator (CFTR) allelic variants relate to shifts in faecal microbiota of cystic fibrosis patients. PLoS One 2013; 8:e61176.
  86. Fallahi G, Motamed F, Yousefi A, et al. The effect of probiotics on fecal calprotectin in patients with cystic fibrosis. Turk J Pediatr 2013; 55:475.
  87. Di Nardo G, Oliva S, Menichella A, et al. Lactobacillus reuteri ATCC55730 in cystic fibrosis. J Pediatr Gastroenterol Nutr 2014; 58:81.
  88. Hasosah M, Davidson G, Jacobson K. Persistent elevated tissue-transglutaminase in cystic fibrosis. J Paediatr Child Health 2009; 45:172.
  89. Fluge G, Olesen HV, Gilljam M, et al. Co-morbidity of cystic fibrosis and celiac disease in Scandinavian cystic fibrosis patients. J Cyst Fibros 2009; 8:198.
  90. Lloyd-Still JD. Crohn's disease and cystic fibrosis. Dig Dis Sci 1994; 39:880.
  91. Condino AA, Hoffenberg EJ, Accurso F, et al. Frequency of ASCA seropositivity in children with cystic fibrosis. J Pediatr Gastroenterol Nutr 2005; 41:23.
  92. Ahmed N, Corey M, Forstner G, et al. Molecular consequences of cystic fibrosis transmembrane regulator (CFTR) gene mutations in the exocrine pancreas. Gut 2003; 52:1159.
  93. Nousia-Arvanitakis S. Cystic fibrosis and the pancreas: recent scientific advances. J Clin Gastroenterol 1999; 29:138.
  94. De Boeck K, Weren M, Proesmans M, Kerem E. Pancreatitis among patients with cystic fibrosis: correlation with pancreatic status and genotype. Pediatrics 2005; 115:e463.
  95. Ooi CY, Dorfman R, Cipolli M, et al. Type of CFTR mutation determines risk of pancreatitis in patients with cystic fibrosis. Gastroenterology 2011; 140:153.
  96. Morinville VD, Husain SZ, Bai H, et al. Definitions of pediatric pancreatitis and survey of present clinical practices. J Pediatr Gastroenterol Nutr 2012; 55:261.
  97. Cohn JA, Friedman KJ, Noone PG, et al. Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis. N Engl J Med 1998; 339:653.
  98. Sharer N, Schwarz M, Malone G, et al. Mutations of the cystic fibrosis gene in patients with chronic pancreatitis. N Engl J Med 1998; 339:645.
  99. Rowntree RK, Harris A. The phenotypic consequences of CFTR mutations. Ann Hum Genet 2003; 67:471.
  100. Moran A, Dunitz J, Nathan B, et al. Cystic fibrosis-related diabetes: current trends in prevalence, incidence, and mortality. Diabetes Care 2009; 32:1626.
  101. Moran A, Brunzell C, Cohen RC, et al. Clinical care guidelines for cystic fibrosis-related diabetes: a position statement of the American Diabetes Association and a clinical practice guideline of the Cystic Fibrosis Foundation, endorsed by the Pediatric Endocrine Society. Diabetes Care 2010; 33:2697.
  102. Moran A, Pillay K, Becker DJ, et al. ISPAD Clinical Practice Consensus Guidelines 2014. Management of cystic fibrosis-related diabetes in children and adolescents. Pediatr Diabetes 2014; 15 Suppl 20:65.