Gastrointestinal pathology occurs in almost all individuals with cystic fibrosis. For this reason, awareness of disease processes which may affect the bowel, pancreas, liver and gallbladder is important in the diagnosis and treatment of children with CF. Here, the author reviews the gastrointestinal pathology and their radiologic signs.
Dr. Benya is in the Department of Radiology, Section of
Pediatric Radiology at the University of Chicago Children's
Hospital in Chicago, IL.
Cystic fibrosis (CF) is a common, lethal genetic syndrome caused
by mutation of the cystic fibrosis transmembrane conductance
regulator gene (CFTR).1-3 CFTR encodes for a protein which acts as
a cyclic adenosine monophosphate-regulated chloride channel.
Impaired chloride conductance leads to abnormal water transport
across the apical membrane of epithelial cells.4 Consequently,
epithelial cell secretions in patients with CF are increased in
viscosity in various organs, including the lungs, bowel, pancreas,
and liver. Gastrointestinal pathology occurs in almost all
individuals with CF.5 For this reason, awareness of disease
processes which may affect the bowel, pancreas, liver, and
gallbladder is important in the diagnosis and treatment of children
Meconium ileus-Ten to fifteen percent of children born with CF
will present with neonatal bowel obstruction due to meconium
ileus.6,7 Meconium ileus results from impaction and obstruction of
the terminal ileum by inspissated meconium pellets. Approximately
one-half of cases will be complicated with an associated small
bowel atresia or stenosis, volvulus, meconium peritonitis, or
pseudocyst.6,8 Meconium ileus is diagnosed in the newborn by a
contrast enema; diagnostic findings include a microcolon and
meconium pellets in the terminal ileum (figures 1 and 2).
Uncomplicated meconium ileus may be treated with a contrast
enema.9 As shown by the results from a recent survey of pediatric
radiology departments in the USA and Canada,10 the enema techniques
and contrast media used in the treatment of meconium ileus varied
widely. The rate of successful nonoperative reduction was
significantly higher with use of gastrografin and with the use of
additives (Tween-80 and Mucomyst) in the contrast material. The
osmolality, mode of administration, and catheter size, however, did
not correlate with the success rate of nonoperative reduction.
Repeat enemas may be necessary to clear the viscous meconium lodged
in the distal small bowel. Filling of the dilated ileum, as well as
the colon, increased the success rate of nonoperative
Distal intestinal obstruction syndrome-Children or adolescents
with CF who have distal intestinal obstruction syndrome (DIOS),
also referred to as meconium ileus equivalent, typically will
present with abdominal pain and obstruction. The prevalence of DIOS
in CF ranges from 10% to 47%;5,11 it has not been found to be more
common in individuals who had meconium ileus as a neonate.12 In
this disorder, thick bowel contents in the terminal ileum and cecum
cause a partial or complete distal intestinal obstruction.
Inspissated intestinal secretions, undigested food, dysmotility,
dehydration, and noncompliance with pancreatic enzyme replacement
therapy could all play a role in its occurrence.5,11
Abdominal films will show marked fecal material in the right
abdomen with partial or complete small bowel obstruction (figure
3). DIOS may be treated with oral administration of gastrografin,13
N-acetylcysteine, or intestinal lavage solution, or by gastrografin
or N-acetylcysteine enema (figure 3).5,11
Intussusception-While intussusception is an uncommon
complication in children with CF, only occurring in approximately
1% of cases,14 it must be considered in the child with CF who
presents with abdominal pain and/or signs of obstruction. Blood in
the stools is not typically seen. The etiology is believed to be
adherent fecal material which acts as a lead point to produce an
intussusception, most commonly ileocolic. Diagnosis of
intussusception may be made by ultrasound or contrast enema
examination (figure 4).
Contrast enema reduction should be attempted in the appropriate
Colonic stricture-In 1994, Smyth and colleagues15 reported a
series of cases of children with CF who presented with intestinal
obstruction that failed to respond to medical management. At
surgery, these patients were found to have stricture of the
ascending colon with mucosal and submucosal fibrosis. Additional
reports followed,16-18 and the term fibrosing colonopathy was
coined to describe this condition. Histologically, these lesions
differ from Crohn's disease, which also may occur with increased
incidence in children and adults who have CF.19
The etiology of these strictures is not definitively known. The
use of high-strength, enteric-coated pancreatic enzymes has been
implicated as a possible causative factor in their development;
however, not all patients found to have colonic strictures had
received high-concentration pancreatic enzymes.17,19 Predisposing
factors for the development of irreversible colonic stricture
appear to include young age, previous intestinal surgery, and
prolonged administration of high-dose lipase products.19
Colonic strictures are characterized by mucosal irregularity,
nodular thickening, loss of haustral markings, and longitudinal
shortening of the colon with focal or diffuse narrowing appreciated
on barium enema (figure 5).18 These strictures appear to begin in
the region of the cecum and ascending colon but may extend into the
distal colon and rectum. Acute inflammatory changes in the colon
usually are minimal or absent.18 However, Ablin and Ziegler20
reported a case of an ulcerative-type colitis in a child who was
being given high-strength pancreatic enzymes.
Mucosal abnormalities-The mucosal appearance of the duodenum in
older children and adolescents with CF frequently is abnormal;
typical findings include thickened folds and nodular filling
defects on upper gastrointestinal series, possibly due to retained,
abnormally thick mucus or inflamed mucosa caused by unbuffered
gastric acid in the duodenum (figure 6).6,21 The small bowel also
may show evidence of thickening and distortion of mucosal folds,
and a redundant mucosal pattern may be seen in the colon (figure
Gastroesophageal reflux-Pathologic gastroesophageal reflux (GER)
is commonly associated with CF (figure 8). In a study by Cucchiara
and colleagues,22 the predominant mechanism of reflux in CF
patients was transient inappropriate lower esophageal sphincter
relaxation. Recognition and treatment of GER in CF patients is
especially important because it can exacerbate existing pulmonary
Pneumatosis intestinalis-The presence of intramural gas in the
bowel wall, known as pneumatosis intestinalis (PI), is associated
with many chronic lung diseases, including CF (figure 8). The
development of PI is believed to occur as a result of air block
phenomena following the dissection of air into the pulmonary
interstitium, the mediastinum, and along vascular sheaths,
terminating in the bowel wall. Hernanz-Schulman et al23 reported
that pneumomediastinum, pneumothorax, or pulmonary interstitial
emphysema was found in 95% of CF patients with PI, and only 62% of
CF patients without it.
Rectal prolapse-In one series of 605 children with CF, rectal
prolapse was found to occur in 18.5%.24 Most cases of rectal
prolapse in the United States are not related to CF but rather to
acute diarrhea, chronic constipation, or neurologic/anatomic
defects.25 Nonetheless, it is important to recognize that rectal
prolapse may occur prior to the diagnosis of CF and, thus, when a
child presents with rectal prolapse and no other associated
diseases, a sweat chloride test should be performed to exclude
Pancreatic insufficiency-Eighty-five percent of children with CF
have evidence of exocrine pancreatic insufficiency5 with symptoms
of fat- and protein malabsorption and fecal loss. In CF patients,
the pancreatic ducts often become obstructed by secretions
containing an increased concentration of protein. Over time, this
obstruction leads to acinar atrophy with replacement of the
pancreas by fatty- and fibrous tissue and resultant pancreatic
exocrine gland dysfunction. The extent of pancreatic involvement
does not appear to correlate with the severity of pulmonary
A spectrum of changes may be appreciated when imaging the
pancreas of an individual with CF. Sonographic studies of the
pancreas frequently show diffusely increased echogenicity due to
fatty replacement (figure 9A).27,28 CT examination also may show
complete or partial replacement of the pancreas by fat (figure
9B).28 Additional findings may include calcifications,27,28
microcysts, and, rarely, macrocysts (figure 10).29 Tjon A Tham and
colleagues26 described three patterns of pancreatic change on MR
imaging: 1) a lobulated, enlarged pancreas with complete
replacement by fatty tissue; 2) a small, atrophic pancreas with
partial replacement by fatty tissue; and 3) diffuse atrophy of the
pancreas without fatty replacement.
Abdominal pain-acute or chronic-may be due to pancreatitis and
is most frequently seen in those individuals with some residual
Gallbladder pathology-The gallbladder of individuals with CF
frequently shows abnormalities on imaging studies; the likelihood
of finding such abnormalities increases with the age of the
patient. The gallbladder often is imaged as small and shrunken
(figure 11), containing thick, colorless bile.5 Additional
abnormalities include the presence of sludge and/or gallstones in
the gallbladder. In a study by L'Heureux et al, gallstones were
found to be present in 11.9% of CF patients who underwent oral
cholestography;31 these also may be identified sonographically.
Possible etiologies for gallstone formation include interrupted
enterohepatic circulation due to ileal resection in children with
meconium ileus, or with DIOS and resultant ileal dysfunction.32
While CF patients with gallstones and gallbladder pathology may
develop cholecystitis,7 these functional and anatomic abnormalities
of the gallbladder usually are not associated with any
In a review of sonograms performed on 27 children with CF,
Quillin and colleagues33 found 33% of these children had
gallbladder abnormalities including small gallbladders and the
presence of sludge in the gallbladder. In their series, the
investigators found no gallbladder wall thickening or
Liver pathology-Focal biliary cirrhosis is recognized on liver
biopsy and autopsy specimens in 50% of individuals with CF,34
though only 4% to 6% of CF patients manifest symptoms of cirrhosis
and portal hypertension.7 Three histologic patterns of liver
disease have been identified in CF: steatosis, focal biliary
fibrosis, and multilobular cirrhosis.33,35 Of the three, only focal
biliary fibrosis is specific for CF.33
At sonography, the liver may show increased echogenicity (figure
12A), periportal hyperechogenicity, heterogeneous echogenicity,33
and nodularity.35 On CT examination of the liver, low attenuation
due to fatty infiltration (figure 12b) or cirrhosis (figure 13) may
be identified. It has been suggested that imaging findings in the
liver may reflect the histologic changes of steatosis, biliary
fibrosis, and cirrhosis.33 AR
1. Rommens JM, Ianuzzi MC, Kerem B-S, et al: Identification of
the cystic fibrosis gene: Chromosome walking and jumping. Science
2. Riordan JR, Rommens JM, Kerem B-S, et al: Identification of
the cystic fibrosis gene: Closing and characterization of
complimentary DNA. Science 245:1066-1073, 1989.
3. Kerem B-S, Rommens JM, Buchanan JA, et al: Identification of
the cystic fibrosis gene: Genetic analysis. Science 245:1073-1080,
4. Bear CE, Li C, Karner L, et al: Purification and functional
reconstitution of the cystic fibrosis transmembrane conductance
regulator. Cell 68:809-818, 1992.
5. Park RW, Grand RJ: Gastrointestinal manifestations of cystic
fibrosis: A review. Gastroenterology 81:1143-1161, 1981.
6. Grossman H, Berdon WE, Baker DH: Gastrointestinal findings in
cystic fibrosis. AJR 97(1):227-238, 1966.
7. Shwachman H: Gastrointestinal manifestations of cystic
fibrosis. PCNA 22(4):787-805, 1975.
8. Donnison AB, Shwachman H, Gross RE: A review of 164 children
with meconium ileus seen at the Children's Hospital Medical Center,
Boston. Pediatrics 37(5):833-850, 1996.
9. Noblett HR: Treatment of uncomplicated meconium ileus by
gastrografin enema: A preliminary report. J Pediatr Surg 4:190-197,
10. Kao SCS, Franken EA, Jr.: Nonoperative treatment of simple
meconium ileus: A survey of the Society for Pediatric Radiology.
Pediatr Radiol 25:97-100, 1995.
11. Littlewood JM: Abdominal pain in cystic fibrosis. JR Soc Med
88(suppl 25):9-17, 1995.
12. Rubinstein S, Moss R, Lewiston N: Constipation and meconium
ileus equivalent in patients with cystic fibrosis. Pediatrics
13. O'Halloran SM, Gilbert F, McKendrick OM, et al: Gastrografin
in acute meconium ileus equivalent. Arch Dis Childhood
14. Holsclaw DS, Rocmans C, Shwachman H: Intussusception in
patients with cystic fibrosis. Pediatrics 48(1):51-58, 1971.
15. Smyth RL, van Velzen D, Smyth AR, et al: Strictures of
ascending colon in cystic fibrosis and high-strength pancreatic
enzymes. Lancet 343:85-86, 1994.
16. Pettei MJ, Leonidas JC, Levine JJ, et al: Pancolonic disease
in cystic fibrosis and high-dose pancreatic enzyme therapy. J
Pediatr 125:587-589, 1994.
17. Jones R, Franklin K, Spicer R, et al: Colonic strictures in
children with cystic fibrosis on low-strength pancreatic enzymes.
Lancet 346:499, 1995.
18. Zerin lM, Kuhn-Fulton J, White SJ, et al: Colonic strictures
in childhood with cystic fibrosis. Radiology 194:223-226, 1995.
19. Lloyd-Still J: Editorial: Cystic fibrosis and colonic
strictures. J Clin Gastroenterol 21(1):2-5, 1995.
20. Ablin DS, Ziegler M: Ulcerative type of colitis associated
with the use of high strength pancreatic enzyme supplements in
cystic fibrosis. Pediatr Radiol 25: 113-116, 1995.
21. Taussig LM, Saldino RM, di Sant'Agrese PA: Radiographic
abnormalities of the duodenum and small bowel in cystic fibrosis of
the pancreas (mucouscidosis). Radiology 106:369-376, 1973.
22. Cucchiara S, Santamaria F, Andreotti MR, et al: Mechanisms
of gastroesophageal reflux in cystic fibrosis. Arch Dis Childhood
23. Hernanz-Schulman M, Kirkpatrick J, Schwachman H, et al:
Pneumatosis intestinalis in cystic fibrosis. Radiology 160:497-499,
24. Stern RC, Izant RJ, Jr., Boat TF, et al: Treatment and
prognosis of rectal prolapse with cystic fibrosis. Gastroenterology
25. Zempsky WT, Rosenstein BJ: The cause of rectal prolapse in
children. Am J Dis Child 142:338-339, 1988.
26. Tjon A Tham RTD, Heyermen HGM, Falke THM, et al: Cystic
fibrosis: MR imaging of the pancreas. Radiology 179:183-186,
27. Phillips HE, Lox KL, Reid MH, et al: Pancreatic sonography
in cystic fibrosis. AJR 137:69-72, 1981.
28. Daneman A, Gaskin K, Martin DJ, et al: Pancreatic changes in
cystic fibrosis: CT and sonographic appearances. AJR 141:653-655,
29. Hernanz-Schulman M, Teele RL, Perez-Atajde A, et al:
Pancreatic cystosis in cystic fibrosis. Radiology 158:629-631,
30. Shwachman H, Lebenthel E, Khaw K: Recurrent acute
pancreatitis in patients with cystic fibrosis with normal enzymes.
Pediatrics 55:86-94, 1975.
31. L'Heureux PR, Isenberg JN, Sharp HL, et al: Gallbladder
disease in cystic fibrosis. AJR 128:953-956, 1977.
32. Carty H: Abdominal radiology in cystic fibrosis. JR Soc Med
88(suppl 25):18-23, 1995.
33. Quillin SP, Siegel MJ, Rothbaum R: Hepatobiliary sonography
in cystic fibrosis. Pediatr Radiol 23:533-535, 1993.
34. Abramson SJ, Baker DH, Amodio JB, et al: Gastrointestinal
manifestations of cystic fibrosis. Semin Roentgenol 22(2):97-113,
35. McHugo JM, McKeown C, Brown MT, et al: Ultrasound findings
in children with cystic fibrosis. Br J Radiol 60:137-141, 1987.