What is DIOS?

Patient Presentation
A 17-year-old male with cystic fibrosis came to the emergency room with acute onset of abdominal pain. The patient had started 2 hours previously in the periumbilical area. It was described as a constant pain and generally didn’t radiate. He had nausea and emesis of food and fluid but it was not bilious or bloody. He denied any bad tastes in his mouth or other reflux symptoms. His last bowel movement was 2 days previously and was described as hard stools. He said he generally was eating and drinking normally.

The past medical history showed that he was diagnosed with cystic fibrosis with his newborn screening and had meconium ileus. He generally took his medications but over the past couple of years “forgot sometimes.” He had a history of constipation and had distal intestinal obstruction syndrome 4 months previously. His appendix was in place. His lung function was monitored closely and he had needed hospitalization for aggressive pulmonary therapy a few times in his lifetime. The family history was non-contributory. The review of systems was negative for fever, chills, and urinary frequency/urgency. He denied recent sexual activity.

The pertinent physical exam showed a thin male in distress from abdominal pain. His respiratory rate was 36 with a saturation of 93%, heart rate was 96, blood pressure was 132/76, and temperature of 99°F. HEENT was normal. Heart was slightly tachycardic without murmur. He was slightly barrel chested with coarse breath sounds. His abdomen was soft with pain in the periumbilical to right lower quadrant area. He had no guarding. There was a mass in the right lower quadrant, but no hepatosplenomegaly. He did not have specific guarding at McBurney’s point, nor peritoneal signs. His genitourinary examination showed no testicular pain or masses and no hernias. Rectal examination revealed no masses and guaiac negative stool.

The work-up included a normal complete blood count, urinalysis, and complete metabolic panel. A surgeon was consulted who felt this was most likely constipation or distal intestinal obstruction syndrome and not appendicitis but imaging was necessary.
The radiologic evaluation on plain film showed dilated loops of bowel and a heavy stool burden. A computed tomographic study of the abdomen showed no appendicitis.

The diagnosis of distal intestinal obstruction syndrome was made. The patient’s clinical course was given intravenous fluids, and non-opiate pain medication. Two hyperosmotic enemas administered by radiology along with laxatives eventually improved his symptoms and he was discharged 3 days later. He was re-educated regarding the importance of taking all of his medication daily and maintaining good hydration.

Case Image

Figure 121 – Supine view of the abdomen (above) reveals multiple dilated loops of distal small bowel and a colon packed with stool. The findings were compatible with a distal small bowel obstruction due to distal intestinal obstruction syndrome. A lateral view of the abdomen (below) taken during a hyperosmolar contrast enema, shows in the center of the image multiple filling defects in the terminal ileum due to it being packed with stool, which is a classic appearance of distal intestinal obstruction syndrome. The enema flushed this stool out of the terminal ileum and the obstruction was relieved.

Discussion
Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane receptor (CFTR). It is found in the epithelium of the bronchi, intestine, pancreatic duct and biliary tree. It regulates chloride, bicarbonate and water secretion. The heterozygous state helps prevent against secretory diarrhea, but the homozygous state causes thickened secretions in the hollow tubes of the lungs and digestive tract. There are multiple mutations (> 2000) which have been currently classified into classes depending on their protein production and activity. CF patients generally are living longer with improved morbidity because of new treatments including lung transplantation but they also are at higher risk of having gastrointestinal problems over their lifespan. Gastrointestinal problems in patients with CF include:

  • Pancreas
    • Second most frequent organ affected after the lung
    • Concentrated pancreatic juice and thickened secretions can increase obstruction leading to acute or chronic injury and inflammation
      • Pancreatic insufficiency
        • Most (~90%) patients have exocrine pancreatic insufficiency
        • Greasy stools, abdominal bloating, flatulence, diarrhea and poor weight gain are symptoms
        • Treatment is pancreatic enzyme replacement therapy (PERT), proton pump inhibitors are used sometimes also
        • Fat soluble vitamins (A, D, E, and K) can occur and usually are also supplemented
      • Poor nutrition
        • Patients have increased nutrition needs because of the exocrine pancreatic insufficiency, potential vitamin deficiencies, increased caloric needs (additional 20-50%)
        • Patients who cannot consume the necessary nutrition orally are often treated with feeding tubes
      • Acute pancreatitis
        • Severe epigastric pain along with increased serum lipase and amylase levels
        • Affects up to 20% of CF patients
        • Occurs more often in patients with exocrine pancreatic sufficiency than those with insufficiency
      • Chronic pancreatitis
        • Pancreatic atrophy, fatty replacement, calcification and fibrosis on imaging
      • Pancreatic cysts
        • Can be single or multiple, large or small
      • Diabetes mellitis
        • Diffuse scaring causes endocrine pancreatic insufficiency and diabetes
        • Risk increases with age
  • Hepatobiliary tract
    • Hepatobiliary disease complications are some of the most serious after lung complications
      • Fatty liver disease
        • More common in children and adolescents than adults
        • Usually transient
      • Focal biliary cirrhosis
        • Thickened bile and slow flow causes inflammation and fibrosis
        • 11-70% of adults will have it but often it is not clinically discernable
        • Primary treatment is ursodoxycholic acid to increase bile flow. Liver transplantation is also a potential option
      • Large bile duct disease
        • Stasis in large bile duct causes a variety of problems including bile stones, inflammation and strictures
        • Treatment is stone removal and stricture dilatation
      • Cholelithiasis
        • The stones can be cholesterol stones or pigment stones
      • Microgallbladder
        • Found in 30% of CF patients
  • Gastrointestinal lumen
    • Appendicitis
      • The appendix itself can have an increased luminal volume because of increased mucous in asymptomatic CF patients and it is thought that this may be protective against appendicitis
      • Can be confused with Distal Intestinal Obstruction Syndrome (DIOS – see below)
    • Constipation
      • Common in CF patients (40-50%)
      • On radiographs, fecal mass throughout the colon (N.B. note location) without air fluid levels are more common with constipation in comparison to DIOS
    • Fibrosing colonopathy
      • Associated with increased amounts of PERT. It is less common today than previously with changes in PERT dosing
      • Occurs 12-15 months after starting increased amounts of PERT
      • Symptoms similar to colitis, inflammatory bowel disease or DIOS
      • Fibrosis can be in concentric rings (especially ascending colon) but can involve the entire colon
    • Gastroesophageal reflux disease (GERD)
      • Increased risk because of prolonged gastric emptying time, coughing increasing abdominal pressure, lung percussion therapy increasing abdominal pressure and various medications
      • Patients are treated aggressively because even with gastroesophageal reflux patients are at risk of refluxing into the lung and compromising respiratory function
      • GERD can cause bronchiolitis obliterans syndrome
      • In addition to usual GERD treatment, along with positioning for pulmonary toilet and judicious choices of medications, fundoplication may be necessary
    • Ulcer disease
      • Includes peptic and duodenal ulcers
    • Intussception
      • More common in CF patients than the general population
      • Ileocolic intussception is the most common with thickened secretions being the proposed lead point
      • Presents as acute abdominal pain and obstruction and can also resolve spontaneously
      • Can be confused with DIOS
      • Treatment is by enema
    • Gastrointestinal malignancy
      • There is an increased risk of gastrointestinal malignancies overall
      • There is an increased risk for those CF patients who have had a lung transplant
    • Meconium ileus
      • Thickened secretions occlude the gastrointestinal lumen in the terminal ileum (N.B. note location)
      • Affects 10-20% of newborn CF patients. If a full term infant has meconium ileus there is an 80-90% chance they have CF. Premature infants can also have meconium ileus though
      • Treatment is aggressive and can be fatal if untreated. Intravenous hydration, nasogastric decompression, antibiotics and hyperosmolar enemas
      • Classified as simple or complex
        • Simple (50% of patients)
          • Failure to pass meconium by 48 hours without complications
        • Complex (50% of patients)
          • Has one or more complications including intestinal atresia or microcolon, bowel necrosis, perforation, meconium peritonitis, pseudocyst formation, or volvulus
    • Meconium plug
      • Thickened secretions occlude the gastrointestinal lumen in the colon (N.B. note location)
      • Treatment by hyperosmolar enemas
    • Rectal prolapse
      • Occurs in toddlers (1-2.5 years)
      • Used to be a common presentation before universal newborn screening
      • Treatment is usually conservative with treatment of constipation or other ways to decrease abdominal pressure
    • Pneumotosis intestinalis
      • Usually asymptomatic with submucosal or subserosal air that appears linearly in the bowel wall
      • Usually not treated
    • Small intestine bacterial overgrowth
      • Patients can have discomfort, bloating and flatuance
      • The small intestine has decreased motility in many CF patients (but not other areas of the gastrointestinal tract) and therefore the bacterial overgrowth is seen primarily in the small intestine.
        Treatment includes antibiotics. Probiotics are also used sometimes as are prokinetic agents in children.

    Learning Point

  • Distal Intestinal Obstruction Syndrome (DIOS)
      • DIOS has thickened secretions that occlude the gastrointestinal lumen in the ileocecum (N.B. note location)
      • Has also been called meconium ileus equivalent
      • Occurs in any age after newborn period, more common in teens and adults
      • Affects 16-21% of CF patients but up to 50% of those who had meconium ileus as an infant. Risk increases with lung transplant and increased 10x with previous episode of DIOS
      • Patients have acute colicky abdominal pain that is located periumbilically to right lower quadrant with the pain usually being progressive
      • Patients also have bilious emesis or air fluid levels on radiographs
      • Palpation of a mass in the right lower abdominal occurs but this can also be palpated without ileus or obstruction
      • Plain radiographs show dilated loops of bowel with or without air fluid levels with “soap bubbles” in the intraluminal fecal material in the small intestine
      • Differential diagnosis mainly is constipation, intussception and appendicitis
      • Treatment is intravenous or oral hydration, osmotic laxatives, stool softened. Potentially hyperosmotic enemas administered radiographically or surgical intervention may be needed

    Questions for Further Discussion
    1. What are indications for lung transplantation in patients with cystic fibrosis?
    2. How is pulmonary toilet performed for patients with cystic fibrosis?
    3. What are some of the physical examination findings in patients with cystic fibrosis?

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for this topic: Cystic Fibrosis

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    To view videos related to this topic check YouTube Videos.

    Demeyer S, De Boeck K, Witters P, Cosaert K.Beyond pancreatic insufficiency and liver disease in cystic fibrosis. Eur J Pediatr. 2016 Jul;175(7):881-94.

    Assis DN, Freedman SD. Gastrointestinal Disorders in Cystic Fibrosis. Clin Chest Med. 2016 Mar;37(1):109-18.

    Kelly T, Buxbaum J. Gastrointestinal Manifestations of Cystic Fibrosis. Dig Dis Sci. 2015 Jul;60(7):1903-13.

    Classification of CFTR Mutations. CFTR.info. Available from the internet at:https://http://www.cftr.info/about-cf/cftr-mutations/the-six-classes-of-cftr-defects/ (rev. 2017, cited 10/17/18)

    Author
    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa

  • What is DIOS?

    Patient Presentation
    A 17-year-old male with cystic fibrosis came to the emergency room with acute onset of abdominal pain. The patient had started 2 hours previously in the periumbilical area. It was described as a constant pain and generally didn’t radiate. He had nausea and emesis of food and fluid but it was not bilious or bloody. He denied any bad tastes in his mouth or other reflux symptoms. His last bowel movement was 2 days previously and was described as hard stools. He said he generally was eating and drinking normally.

    The past medical history showed that he was diagnosed with cystic fibrosis with his newborn screening and had meconium ileus. He generally took his medications but over the past couple of years “forgot sometimes.” He had a history of constipation and had distal intestinal obstruction syndrome 4 months previously. His appendix was in place. His lung function was monitored closely and he had needed hospitalization for aggressive pulmonary therapy a few times in his lifetime. The family history was non-contributory. The review of systems was negative for fever, chills, and urinary frequency/urgency. He denied recent sexual activity.

    The pertinent physical exam showed a thin male in distress from abdominal pain. His respiratory rate was 36 with a saturation of 93%, heart rate was 96, blood pressure was 132/76, and temperature of 99°F. HEENT was normal. Heart was slightly tachycardic without murmur. He was slightly barrel chested with coarse breath sounds. His abdomen was soft with pain in the periumbilical to right lower quadrant area. He had no guarding. There was a mass in the right lower quadrant, but no hepatosplenomegaly. He did not have specific guarding at McBurney’s point, nor peritoneal signs. His genitourinary examination showed no testicular pain or masses and no hernias. Rectal examination revealed no masses and guaiac negative stool.

    The work-up included a normal complete blood count, urinalysis, and complete metabolic panel. A surgeon was consulted who felt this was most likely constipation or distal intestinal obstruction syndrome and not appendicitis but imaging was necessary.
    The radiologic evaluation on plain film showed dilated loops of bowel and a heavy stool burden. A computed tomographic study of the abdomen showed no appendicitis.

    The diagnosis of distal intestinal obstruction syndrome was made. The patient’s clinical course was given intravenous fluids, and non-opiate pain medication. Two hyperosmotic enemas administered by radiology along with laxatives eventually improved his symptoms and he was discharged 3 days later. He was re-educated regarding the importance of taking all of his medication daily and maintaining good hydration.

    Case Image

    Figure 121 – Supine view of the abdomen (above) reveals multiple dilated loops of distal small bowel and a colon packed with stool. The findings were compatible with a distal small bowel obstruction due to distal intestinal obstruction syndrome. A lateral view of the abdomen (below) taken during a hyperosmolar contrast enema, shows in the center of the image multiple filling defects in the terminal ileum due to it being packed with stool, which is a classic appearance of distal intestinal obstruction syndrome. The enema flushed this stool out of the terminal ileum and the obstruction was relieved.

    Discussion
    Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane receptor (CFTR). It is found in the epithelium of the bronchi, intestine, pancreatic duct and biliary tree. It regulates chloride, bicarbonate and water secretion. The heterozygous state helps prevent against secretory diarrhea, but the homozygous state causes thickened secretions in the hollow tubes of the lungs and digestive tract. There are multiple mutations (> 2000) which have been currently classified into classes depending on their protein production and activity. CF patients generally are living longer with improved morbidity because of new treatments including lung transplantation but they also are at higher risk of having gastrointestinal problems over their lifespan. Gastrointestinal problems in patients with CF include:

  • Pancreas
    • Second most frequent organ affected after the lung
    • Concentrated pancreatic juice and thickened secretions can increase obstruction leading to acute or chronic injury and inflammation
      • Pancreatic insufficiency
        • Most (~90%) patients have exocrine pancreatic insufficiency
        • Greasy stools, abdominal bloating, flatulence, diarrhea and poor weight gain are symptoms
        • Treatment is pancreatic enzyme replacement therapy (PERT), proton pump inhibitors are used sometimes also
        • Fat soluble vitamins (A, D, E, and K) can occur and usually are also supplemented
      • Poor nutrition
        • Patients have increased nutrition needs because of the exocrine pancreatic insufficiency, potential vitamin deficiencies, increased caloric needs (additional 20-50%)
        • Patients who cannot consume the necessary nutrition orally are often treated with feeding tubes
      • Acute pancreatitis
        • Severe epigastric pain along with increased serum lipase and amylase levels
        • Affects up to 20% of CF patients
        • Occurs more often in patients with exocrine pancreatic sufficiency than those with insufficiency
      • Chronic pancreatitis
        • Pancreatic atrophy, fatty replacement, calcification and fibrosis on imaging
      • Pancreatic cysts
        • Can be single or multiple, large or small
      • Diabetes mellitis
        • Diffuse scaring causes endocrine pancreatic insufficiency and diabetes
        • Risk increases with age
  • Hepatobiliary tract
    • Hepatobiliary disease complications are some of the most serious after lung complications
      • Fatty liver disease
        • More common in children and adolescents than adults
        • Usually transient
      • Focal biliary cirrhosis
        • Thickened bile and slow flow causes inflammation and fibrosis
        • 11-70% of adults will have it but often it is not clinically discernable
        • Primary treatment is ursodoxycholic acid to increase bile flow. Liver transplantation is also a potential option
      • Large bile duct disease
        • Stasis in large bile duct causes a variety of problems including bile stones, inflammation and strictures
        • Treatment is stone removal and stricture dilatation
      • Cholelithiasis
        • The stones can be cholesterol stones or pigment stones
      • Microgallbladder
        • Found in 30% of CF patients
  • Gastrointestinal lumen
    • Appendicitis
      • The appendix itself can have an increased luminal volume because of increased mucous in asymptomatic CF patients and it is thought that this may be protective against appendicitis
      • Can be confused with Distal Intestinal Obstruction Syndrome (DIOS – see below)
    • Constipation
      • Common in CF patients (40-50%)
      • On radiographs, fecal mass throughout the colon (N.B. note location) without air fluid levels are more common with constipation in comparison to DIOS
    • Fibrosing colonopathy
      • Associated with increased amounts of PERT. It is less common today than previously with changes in PERT dosing
      • Occurs 12-15 months after starting increased amounts of PERT
      • Symptoms similar to colitis, inflammatory bowel disease or DIOS
      • Fibrosis can be in concentric rings (especially ascending colon) but can involve the entire colon
    • Gastroesophageal reflux disease (GERD)
      • Increased risk because of prolonged gastric emptying time, coughing increasing abdominal pressure, lung percussion therapy increasing abdominal pressure and various medications
      • Patients are treated aggressively because even with gastroesophageal reflux patients are at risk of refluxing into the lung and compromising respiratory function
      • GERD can cause bronchiolitis obliterans syndrome
      • In addition to usual GERD treatment, along with positioning for pulmonary toilet and judicious choices of medications, fundoplication may be necessary
    • Ulcer disease
      • Includes peptic and duodenal ulcers
    • Intussception
      • More common in CF patients than the general population
      • Ileocolic intussception is the most common with thickened secretions being the proposed lead point
      • Presents as acute abdominal pain and obstruction and can also resolve spontaneously
      • Can be confused with DIOS
      • Treatment is by enema
    • Gastrointestinal malignancy
      • There is an increased risk of gastrointestinal malignancies overall
      • There is an increased risk for those CF patients who have had a lung transplant
    • Meconium ileus
      • Thickened secretions occlude the gastrointestinal lumen in the terminal ileum (N.B. note location)
      • Affects 10-20% of newborn CF patients. If a full term infant has meconium ileus there is an 80-90% chance they have CF. Premature infants can also have meconium ileus though
      • Treatment is aggressive and can be fatal if untreated. Intravenous hydration, nasogastric decompression, antibiotics and hyperosmolar enemas
      • Classified as simple or complex
        • Simple (50% of patients)
          • Failure to pass meconium by 48 hours without complications
        • Complex (50% of patients)
          • Has one or more complications including intestinal atresia or microcolon, bowel necrosis, perforation, meconium peritonitis, pseudocyst formation, or volvulus
    • Meconium plug
      • Thickened secretions occlude the gastrointestinal lumen in the colon (N.B. note location)
      • Treatment by hyperosmolar enemas
    • Rectal prolapse
      • Occurs in toddlers (1-2.5 years)
      • Used to be a common presentation before universal newborn screening
      • Treatment is usually conservative with treatment of constipation or other ways to decrease abdominal pressure
    • Pneumotosis intestinalis
      • Usually asymptomatic with submucosal or subserosal air that appears linearly in the bowel wall
      • Usually not treated
    • Small intestine bacterial overgrowth
      • Patients can have discomfort, bloating and flatuance
      • The small intestine has decreased motility in many CF patients (but not other areas of the gastrointestinal tract) and therefore the bacterial overgrowth is seen primarily in the small intestine.
        Treatment includes antibiotics. Probiotics are also used sometimes as are prokinetic agents in children.

    Learning Point

  • Distal Intestinal Obstruction Syndrome (DIOS)
      • DIOS has thickened secretions that occlude the gastrointestinal lumen in the ileocecum (N.B. note location)
      • Has also been called meconium ileus equivalent
      • Occurs in any age after newborn period, more common in teens and adults
      • Affects 16-21% of CF patients but up to 50% of those who had meconium ileus as an infant. Risk increases with lung transplant and increased 10x with previous episode of DIOS
      • Patients have acute colicky abdominal pain that is located periumbilically to right lower quadrant with the pain usually being progressive
      • Patients also have bilious emesis or air fluid levels on radiographs
      • Palpation of a mass in the right lower abdominal occurs but this can also be palpated without ileus or obstruction
      • Plain radiographs show dilated loops of bowel with or without air fluid levels with “soap bubbles” in the intraluminal fecal material in the small intestine
      • Differential diagnosis mainly is constipation, intussception and appendicitis
      • Treatment is intravenous or oral hydration, osmotic laxatives, stool softened. Potentially hyperosmotic enemas administered radiographically or surgical intervention may be needed

    Questions for Further Discussion
    1. What are indications for lung transplantation in patients with cystic fibrosis?
    2. How is pulmonary toilet performed for patients with cystic fibrosis?
    3. What are some of the physical examination findings in patients with cystic fibrosis?

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for this topic: Cystic Fibrosis

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    To view videos related to this topic check YouTube Videos.

    Demeyer S, De Boeck K, Witters P, Cosaert K.Beyond pancreatic insufficiency and liver disease in cystic fibrosis. Eur J Pediatr. 2016 Jul;175(7):881-94.

    Assis DN, Freedman SD. Gastrointestinal Disorders in Cystic Fibrosis. Clin Chest Med. 2016 Mar;37(1):109-18.

    Kelly T, Buxbaum J. Gastrointestinal Manifestations of Cystic Fibrosis. Dig Dis Sci. 2015 Jul;60(7):1903-13.

    Classification of CFTR Mutations. CFTR.info. Available from the internet at:https://http://www.cftr.info/about-cf/cftr-mutations/the-six-classes-of-cftr-defects/ (rev. 2017, cited 10/17/18)

    Author
    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa

  • What is DIOS?

    Patient Presentation
    A 17-year-old male with cystic fibrosis came to the emergency room with acute onset of abdominal pain. The patient had started 2 hours previously in the periumbilical area. It was described as a constant pain and generally didn’t radiate. He had nausea and emesis of food and fluid but it was not bilious or bloody. He denied any bad tastes in his mouth or other reflux symptoms. His last bowel movement was 2 days previously and was described as hard stools. He said he generally was eating and drinking normally.

    The past medical history showed that he was diagnosed with cystic fibrosis with his newborn screening and had meconium ileus. He generally took his medications but over the past couple of years “forgot sometimes.” He had a history of constipation and had distal intestinal obstruction syndrome 4 months previously. His appendix was in place. His lung function was monitored closely and he had needed hospitalization for aggressive pulmonary therapy a few times in his lifetime. The family history was non-contributory. The review of systems was negative for fever, chills, and urinary frequency/urgency. He denied recent sexual activity.

    The pertinent physical exam showed a thin male in distress from abdominal pain. His respiratory rate was 36 with a saturation of 93%, heart rate was 96, blood pressure was 132/76, and temperature of 99°F. HEENT was normal. Heart was slightly tachycardic without murmur. He was slightly barrel chested with coarse breath sounds. His abdomen was soft with pain in the periumbilical to right lower quadrant area. He had no guarding. There was a mass in the right lower quadrant, but no hepatosplenomegaly. He did not have specific guarding at McBurney’s point, nor peritoneal signs. His genitourinary examination showed no testicular pain or masses and no hernias. Rectal examination revealed no masses and guaiac negative stool.

    The work-up included a normal complete blood count, urinalysis, and complete metabolic panel. A surgeon was consulted who felt this was most likely constipation or distal intestinal obstruction syndrome and not appendicitis but imaging was necessary.
    The radiologic evaluation on plain film showed dilated loops of bowel and a heavy stool burden. A computed tomographic study of the abdomen showed no appendicitis.

    The diagnosis of distal intestinal obstruction syndrome was made. The patient’s clinical course was given intravenous fluids, and non-opiate pain medication. Two hyperosmotic enemas administered by radiology along with laxatives eventually improved his symptoms and he was discharged 3 days later. He was re-educated regarding the importance of taking all of his medication daily and maintaining good hydration.

    Case Image

    Figure 121 – Supine view of the abdomen (above) reveals multiple dilated loops of distal small bowel and a colon packed with stool. The findings were compatible with a distal small bowel obstruction due to distal intestinal obstruction syndrome. A lateral view of the abdomen (below) taken during a hyperosmolar contrast enema, shows in the center of the image multiple filling defects in the terminal ileum due to it being packed with stool, which is a classic appearance of distal intestinal obstruction syndrome. The enema flushed this stool out of the terminal ileum and the obstruction was relieved.

    Discussion
    Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane receptor (CFTR). It is found in the epithelium of the bronchi, intestine, pancreatic duct and biliary tree. It regulates chloride, bicarbonate and water secretion. The heterozygous state helps prevent against secretory diarrhea, but the homozygous state causes thickened secretions in the hollow tubes of the lungs and digestive tract. There are multiple mutations (> 2000) which have been currently classified into classes depending on their protein production and activity. CF patients generally are living longer with improved morbidity because of new treatments including lung transplantation but they also are at higher risk of having gastrointestinal problems over their lifespan. Gastrointestinal problems in patients with CF include:

  • Pancreas
    • Second most frequent organ affected after the lung
    • Concentrated pancreatic juice and thickened secretions can increase obstruction leading to acute or chronic injury and inflammation
      • Pancreatic insufficiency
        • Most (~90%) patients have exocrine pancreatic insufficiency
        • Greasy stools, abdominal bloating, flatulence, diarrhea and poor weight gain are symptoms
        • Treatment is pancreatic enzyme replacement therapy (PERT), proton pump inhibitors are used sometimes also
        • Fat soluble vitamins (A, D, E, and K) can occur and usually are also supplemented
      • Poor nutrition
        • Patients have increased nutrition needs because of the exocrine pancreatic insufficiency, potential vitamin deficiencies, increased caloric needs (additional 20-50%)
        • Patients who cannot consume the necessary nutrition orally are often treated with feeding tubes
      • Acute pancreatitis
        • Severe epigastric pain along with increased serum lipase and amylase levels
        • Affects up to 20% of CF patients
        • Occurs more often in patients with exocrine pancreatic sufficiency than those with insufficiency
      • Chronic pancreatitis
        • Pancreatic atrophy, fatty replacement, calcification and fibrosis on imaging
      • Pancreatic cysts
        • Can be single or multiple, large or small
      • Diabetes mellitis
        • Diffuse scaring causes endocrine pancreatic insufficiency and diabetes
        • Risk increases with age
  • Hepatobiliary tract
    • Hepatobiliary disease complications are some of the most serious after lung complications
      • Fatty liver disease
        • More common in children and adolescents than adults
        • Usually transient
      • Focal biliary cirrhosis
        • Thickened bile and slow flow causes inflammation and fibrosis
        • 11-70% of adults will have it but often it is not clinically discernable
        • Primary treatment is ursodoxycholic acid to increase bile flow. Liver transplantation is also a potential option
      • Large bile duct disease
        • Stasis in large bile duct causes a variety of problems including bile stones, inflammation and strictures
        • Treatment is stone removal and stricture dilatation
      • Cholelithiasis
        • The stones can be cholesterol stones or pigment stones
      • Microgallbladder
        • Found in 30% of CF patients
  • Gastrointestinal lumen
    • Appendicitis
      • The appendix itself can have an increased luminal volume because of increased mucous in asymptomatic CF patients and it is thought that this may be protective against appendicitis
      • Can be confused with Distal Intestinal Obstruction Syndrome (DIOS – see below)
    • Constipation
      • Common in CF patients (40-50%)
      • On radiographs, fecal mass throughout the colon (N.B. note location) without air fluid levels are more common with constipation in comparison to DIOS
    • Fibrosing colonopathy
      • Associated with increased amounts of PERT. It is less common today than previously with changes in PERT dosing
      • Occurs 12-15 months after starting increased amounts of PERT
      • Symptoms similar to colitis, inflammatory bowel disease or DIOS
      • Fibrosis can be in concentric rings (especially ascending colon) but can involve the entire colon
    • Gastroesophageal reflux disease (GERD)
      • Increased risk because of prolonged gastric emptying time, coughing increasing abdominal pressure, lung percussion therapy increasing abdominal pressure and various medications
      • Patients are treated aggressively because even with gastroesophageal reflux patients are at risk of refluxing into the lung and compromising respiratory function
      • GERD can cause bronchiolitis obliterans syndrome
      • In addition to usual GERD treatment, along with positioning for pulmonary toilet and judicious choices of medications, fundoplication may be necessary
    • Ulcer disease
      • Includes peptic and duodenal ulcers
    • Intussception
      • More common in CF patients than the general population
      • Ileocolic intussception is the most common with thickened secretions being the proposed lead point
      • Presents as acute abdominal pain and obstruction and can also resolve spontaneously
      • Can be confused with DIOS
      • Treatment is by enema
    • Gastrointestinal malignancy
      • There is an increased risk of gastrointestinal malignancies overall
      • There is an increased risk for those CF patients who have had a lung transplant
    • Meconium ileus
      • Thickened secretions occlude the gastrointestinal lumen in the terminal ileum (N.B. note location)
      • Affects 10-20% of newborn CF patients. If a full term infant has meconium ileus there is an 80-90% chance they have CF. Premature infants can also have meconium ileus though
      • Treatment is aggressive and can be fatal if untreated. Intravenous hydration, nasogastric decompression, antibiotics and hyperosmolar enemas
      • Classified as simple or complex
        • Simple (50% of patients)
          • Failure to pass meconium by 48 hours without complications
        • Complex (50% of patients)
          • Has one or more complications including intestinal atresia or microcolon, bowel necrosis, perforation, meconium peritonitis, pseudocyst formation, or volvulus
    • Meconium plug
      • Thickened secretions occlude the gastrointestinal lumen in the colon (N.B. note location)
      • Treatment by hyperosmolar enemas
    • Rectal prolapse
      • Occurs in toddlers (1-2.5 years)
      • Used to be a common presentation before universal newborn screening
      • Treatment is usually conservative with treatment of constipation or other ways to decrease abdominal pressure
    • Pneumotosis intestinalis
      • Usually asymptomatic with submucosal or subserosal air that appears linearly in the bowel wall
      • Usually not treated
    • Small intestine bacterial overgrowth
      • Patients can have discomfort, bloating and flatuance
      • The small intestine has decreased motility in many CF patients (but not other areas of the gastrointestinal tract) and therefore the bacterial overgrowth is seen primarily in the small intestine.
        Treatment includes antibiotics. Probiotics are also used sometimes as are prokinetic agents in children.

    Learning Point

  • Distal Intestinal Obstruction Syndrome (DIOS)
      • DIOS has thickened secretions that occlude the gastrointestinal lumen in the ileocecum (N.B. note location)
      • Has also been called meconium ileus equivalent
      • Occurs in any age after newborn period, more common in teens and adults
      • Affects 16-21% of CF patients but up to 50% of those who had meconium ileus as an infant. Risk increases with lung transplant and increased 10x with previous episode of DIOS
      • Patients have acute colicky abdominal pain that is located periumbilically to right lower quadrant with the pain usually being progressive
      • Patients also have bilious emesis or air fluid levels on radiographs
      • Palpation of a mass in the right lower abdominal occurs but this can also be palpated without ileus or obstruction
      • Plain radiographs show dilated loops of bowel with or without air fluid levels with “soap bubbles” in the intraluminal fecal material in the small intestine
      • Differential diagnosis mainly is constipation, intussception and appendicitis
      • Treatment is intravenous or oral hydration, osmotic laxatives, stool softened. Potentially hyperosmotic enemas administered radiographically or surgical intervention may be needed

    Questions for Further Discussion
    1. What are indications for lung transplantation in patients with cystic fibrosis?
    2. How is pulmonary toilet performed for patients with cystic fibrosis?
    3. What are some of the physical examination findings in patients with cystic fibrosis?

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for this topic: Cystic Fibrosis

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    To view videos related to this topic check YouTube Videos.

    Demeyer S, De Boeck K, Witters P, Cosaert K.Beyond pancreatic insufficiency and liver disease in cystic fibrosis. Eur J Pediatr. 2016 Jul;175(7):881-94.

    Assis DN, Freedman SD. Gastrointestinal Disorders in Cystic Fibrosis. Clin Chest Med. 2016 Mar;37(1):109-18.

    Kelly T, Buxbaum J. Gastrointestinal Manifestations of Cystic Fibrosis. Dig Dis Sci. 2015 Jul;60(7):1903-13.

    Classification of CFTR Mutations. CFTR.info. Available from the internet at:https://http://www.cftr.info/about-cf/cftr-mutations/the-six-classes-of-cftr-defects/ (rev. 2017, cited 10/17/18)

    Author
    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa