Version May 2024
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 pathogenic 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. A study that focused on gastrointestinal symptoms in people with CF found that symptoms of constipation, bloating, and abdominal pain were common and their frequency increased with age [1]. Some of the complications, such as gastroesophageal reflux and constipation, are not unique to the CF population but are more common in people with CF and warrant special considerations in diagnosis and management in the CF population. Some conditions that are unique to CF, such as distal intestinal obstruction syndrome (DIOS), require specialized knowledge to appropriately diagnose and treat.
This topic review provides an overview of the gastrointestinal manifestations of CF. Some of these manifestations are discussed in more detail in separate topic reviews:
●(See "Cystic fibrosis: Assessment and management of pancreatic insufficiency".)
●(See "Cystic fibrosis: Hepatobiliary disease".)
●(See "Cystic fibrosis-related diabetes mellitus".)
●(See "Cystic fibrosis: Nutritional issues".)
CF-associated pulmonary disease and other aspects of CF care are discussed separately:
●(See "Cystic fibrosis: Clinical manifestations of pulmonary disease".)
●(See "Cystic fibrosis: Overview of the treatment of lung disease".)
●(See "Cystic fibrosis: Management of pulmonary exacerbations".)
●(See "Cystic fibrosis: Antibiotic therapy for chronic pulmonary infection".)
●(See "Cystic fibrosis: Treatment with CFTR modulators".)
●(See "Cystic fibrosis: Clinical manifestations and diagnosis".)
●(See "Cystic fibrosis: Genetics and pathogenesis".)
●(See "Cystic fibrosis: Management of advanced lung disease".)
GASTROESOPHAGEAL REFLUX DISEASE — Gastroesophageal reflux disease (GERD) is more commonly diagnosed in individuals with CF than in the general population [2,3]. Heartburn and regurgitation are reported in 30 to 40 percent of pretransplant adults with CF, and "silent" GERD detected by esophageal monitoring was reported in up to 90 percent of adults with severe pulmonary disease [4].
The principal mechanism causing GERD in individuals with CF appears to be transient relaxation of the lower esophageal sphincter, 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:
●Increased intraabdominal pressure due to chronic coughing, wheezing, and lung hyperinflation
●Decreased basal tone of the lower esophageal sphincter [5]
●Gastric hyperacidity and impaired clearance of acid from the esophagus by saliva [6]
●Delayed gastric emptying, with or without CF-related diabetes (CFRD) [7-9]
●Supine positioning during chest physiotherapy
The approach to diagnosis and treatment of GERD for people with CF differs depending on whether the primary concern is gastrointestinal symptoms versus pulmonary symptoms, as outlined below.
GERD and gastrointestinal symptoms
●Clinical manifestations and diagnosis – The clinical manifestations and methods to diagnose GERD in individuals with CF are the same as those for individuals without CF. Symptoms typically include chronic heartburn, acid brash, and/or regurgitation. The diagnosis is generally made based on clinical symptoms and symptomatic response to acid-suppressing medications. (See "Clinical manifestations and diagnosis of gastroesophageal reflux disease in children and adolescents".)
Esophageal monitoring (pH probe, multichannel intraluminal impedance testing [MII], or catheter-free methods) may be useful to support the diagnosis of GERD in selected cases but has limited value in excluding other causes of the symptoms or predicting treatment outcomes. Impedance probes may be useful to evaluate nonacid reflux or to assess the efficacy of acid suppression. Esophageal monitoring may be difficult in people with CF because of nasal polyps and sinusitis issues, and the presence of the monitor may exacerbate cough or become displaced as a result of cough.
Contrast radiography (eg, barium swallow) is not useful for the diagnosis of GERD, due to low specificity and sensitivity.
●Differential diagnosis – In patients with CF, it is also important to consider other causes of gastrointestinal dysfunction that may contribute to or mimic GERD (table 1). These include gastrointestinal dysmotility or gastroparesis. Small bowel transit appears to be delayed in patients with CF, and dysmotility may contribute to GERD or mimic its symptoms [10,11]. In addition, CFRD is common among adolescents and adults with CF and can cause gastroparesis, which promotes gastroesophageal reflux. CFRD also is associated with symptoms that might be attributed to GERD, including weight loss and worsening pulmonary function. Rarely, constipation can be associated with gastroesophageal reflux in patients without CF [12]. (See 'Cystic fibrosis-related diabetes' below and 'Constipation' below.)
In patients with intractable symptoms or if surgical intervention is contemplated, esophagogastroduodenoscopy should be performed to evaluate for other potential causes of GERD-like symptoms, including eosinophilic esophagitis. One case series showed that eosinophilic esophagitis is underreported in CF [13].
●Management – The principles of management of GERD in individuals with CF are similar to those in otherwise healthy individuals. (See "Management of gastroesophageal reflux disease in children and adolescents" and "Medical management of gastroesophageal reflux disease in adults".)
Data and considerations specific to individuals with CF are:
•Acid suppression – Inhibition of gastric acid secretion using proton pump inhibitors (PPIs) is an appropriate treatment strategy for people with CF and GERD. However, the goal of therapy with PPI must be considered prior to initiating this therapy. Acid suppression has been used in CF in attempts to treat heartburn/peptic symptoms of reflux, improve pulmonary function, and normalize the pH of the intestine to improve pancreatic enzyme replacement therapy (PERT) efficacy, as outlined below. As there is increasing evidence for significant side effects associated with long-term PPI use, the specific goals of PPI therapy must be considered and reassessment of the efficacy of PPI therapy must be done regularly to determine if the PPI should be continued or weaned off. Several clinical considerations are relevant to this decision:
-Unclear effects on pulmonary disease – It is unclear whether acid suppression has beneficial or adverse effects on pulmonary function in people with CF and GERD, as discussed below. (See 'GERD and pulmonary disease' below.)
-Negative effects on bone health – There are theoretical concerns that chronic use of PPIs may have adverse effects on bone health, and this is of particular concern because CF patients are already at increased risk for osteoporosis. These concerns are based on a possible association between PPI use and risk of fractures in older adults without CF, but the evidence is conflicting and these patients have many reasons for increased fracture risk (see "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Calcium and fracture risk'). Important measures to prevent and monitor for bone disease in patients with CF are discussed in a separate topic review. (See "Cystic fibrosis: Nutritional issues", section on 'Bone disease'.)
-Benefits for fat absorption – Acid suppression can improve fat absorption in some patients with pancreatic insufficiency who have fat malabsorption despite adequate doses of PERT. (See "Cystic fibrosis: Assessment and management of pancreatic insufficiency", section on 'Dosing considerations'.)
-Chronic treatment and monitoring – If there is no improvement in GERD symptoms during a treatment trial, the PPI can be discontinued. Many patients with CF are on acid suppression to enhance the effect of PERT. If PPIs are used, the patient should be monitored for response and for potential adverse effects, including increased pulmonary exacerbations, vitamin B12 deficiency, hypomagnesemia, and bone heath. (See "Management of gastroesophageal reflux disease in children and adolescents", section on 'Proton pump inhibitors'.)
•Diet – The role for dietary changes in managing GERD in CF is evolving. Prior to the use of highly effective CF transmembrane conductance regulator (CFTR) modulator therapy such as elexacaftor-tezacaftor-ivacaftor (ETI), reducing fat in the diet or suggesting weight loss for overweight patients was generally avoided in people with CF. However, because ETI improves nutrition and weight gain, some patients may benefit from counseling to avoid excessive weight gain and/or limit fat intake. Consultation with the CF dietitian is important. Some patients may benefit from limiting caffeinated or carbonated beverages or foods that contribute to reflux such as citrus fruits, tomato-based sauces, spicy food, or other foods that exacerbate symptoms.
•Physiotherapy – Chest physiotherapy should be performed prior to meals since physiotherapy on a full stomach promotes the development of reflux. The head-down position should not be used.
•Surgery – Antireflux surgery can be considered in patients with complications of GERD that are refractory to medical management, including erosive esophagitis, esophageal strictures, or poor weight gain (if attributable to GERD). However, the outcomes of antireflux surgery for this patient population are not well studied and a few reports suggest poor outcomes. As an example, in a report of children with CF and GERD, nearly one-half of the children had ongoing symptoms of GERD after antireflux surgery (fundoplication) and there was little improvement in pulmonary function [14]. In addition, 12 percent had complications that required a subsequent surgical procedure. Some patients may have dysphagia postoperatively, and this could contribute to poor nutritional status.
Before considering surgical intervention for GERD, other causes of the symptoms should be carefully excluded (table 1). In particular, the patient should be evaluated for CFRD and/or gastroparesis (with an oral glucose tolerance test and gastric emptying study, respectively), as well as other causes of esophageal symptoms (with an upper endoscopy), as discussed in the differential diagnosis section above.
If antireflux surgery is undertaken, optimal pulmonary status should be achieved prior to surgery. (See "Management of gastroesophageal reflux disease in children and adolescents", section on 'Surgery'.)
•Surveillance – Barrett's esophagus has been reported in patients with CF and is a risk factor for esophageal cancer. Although not a common occurrence, the standardized incidence ratio of esophageal cancer in patients with CF is 2.8 relative to the general population [15]. It is unclear whether the risk of Barrett's esophagus and esophageal cancer is sufficiently high in patients with CF and GERD to warrant routine surveillance esophagogastroduodenoscopy.
GERD and pulmonary disease — GERD is hypothesized to contribute to lung disease in CF because of microaspiration, reflex bronchospasm, or enhanced airway inflammation. This hypothesis is based on an observed association between GERD and pulmonary disease in multiple studies. However, there is no convincing evidence that the association is causal or that treatment for GERD has any beneficial effect on pulmonary function.
●Evidence – The association between GERD and pulmonary disease is supported by multiple observational studies [16,17], including a report of more than 7000 CF patients in a European registry, in which GERD was associated with slightly worse pulmonary function [18]. The possibility of a causal association is supported by a small randomized study in infants, in which those treated with modified chest physiotherapy (without head-down tilt, to minimize GERD) experienced fewer respiratory exacerbations and slower decline in pulmonary function over five years compared with infants treated with standard chest physiotherapy (with head-down tilt) [19].
●Evaluation – It may be very difficult to determine whether GERD impacts pulmonary function in people with CF. An esophageal pH monitoring study may provide evidence of significant reflux, but such a finding does not necessarily mean that the reflux is causing the pulmonary decline. Delayed gastric emptying and duodenogastroesophageal reflux may be more important factors in the risk of aspiration than the presence of acid reflux [7]. Motility testing and diagnostic bronchoalveolar lavage are tools being considered at institutions with large populations of people with CF.
●Treatment
•Acid suppression – There is little evidence to support medical management of GERD-related microaspiration. The relative benefits and risks of acid-suppressing therapy on pulmonary disease in CF remain unclear. No adequately powered randomized trials have been conducted, and evidence is limited and contradictory. On the one hand, a few small observational studies describe improvement in pulmonary function after treatment for GERD, including a retrospective study of 218 pediatric patients with CF in which those treated with acid-suppressing drugs experienced a smaller decline in pulmonary function and delayed acquisition of Pseudomonas aeruginosa compared with those who were not treated with acid-suppressing drugs [20]. On the other hand, other studies raise the possibility that acid-suppressing drugs might slightly increase the risk of pulmonary infections, based on a very small trial in patients with CF [21] or much larger but inconclusive studies in populations without CF. (See "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Pneumonia'.)
•Surgery – There are also few data to support antireflux surgery as an intervention for pulmonary disease in people with CF, and reports vary in their conclusions [14,22,23]. In some cases, the observed benefits of surgery may be due to the implementation of gastrostomy feeds rather than to treatment of GERD.
An important exception is the patient with CF who has had lung transplantation. Because reflux injury to the lung can present as bronchiolitis obliterans, early surgical management of GERD can be considered in the postoperative lung transplant patient and particularly if there is unexplained graft dysfunction or rejection unresponsive to standard therapy [4,24,25]. Developing a formalized pre- and post-transplant esophageal and gastric motility study process may provide guidance of patients at risk for chronic lung allograft dysfunction [26].
INTESTINAL DISEASE
Meconium ileus — Meconium ileus (MI) is a disorder of the neonate caused by the obstruction of the small intestine at the level of the terminal ileum with inspissated meconium. The widespread use of prenatal carrier testing and prenatal detection of MI by ultrasound enables clinicians to counsel patients and plan proactive management of this complication of CF [27]. (See "Fetal abdomen: Differential diagnosis of abnormal echogenicity and calcification".)
Approximately 10 percent of patients with CF present as neonates with MI; in most cases, these patients have CF transmembrane conductance regulator gene (CFTR) mutations associated with inadequate CFTR production or folding ("severe" genotypes). Conversely, most series suggest that 80 to 90 percent of infants with MI have CF [28], although a few series report higher proportions of non-CF MI, particularly in low birth weight infants [29].
●Presentation and diagnosis – Infants with MI generally present during the first three days of life with abdominal distension and failure to pass meconium, with or without vomiting. Affected infants are initially stabilized with nasogastric decompression and correction of fluid and electrolyte abnormalities. An abdominal plain film should be performed to look for evidence of dilated bowel loops, perforation, calcifications, or other abnormalities (image 1). If there is no evidence of perforation, hyperosmotic contrast enema radiography is performed to confirm the diagnosis, using a water-soluble agent. In patients with MI, the contrast radiograph typically reveals a small-caliber colon (microcolon of disuse) and meconium pellets in the terminal ileum. The ileum proximal to the obstruction is dilated (image 2).
MI is divided into two categories, which inform management and prognosis:
•MI is "complex" if it is complicated by gastrointestinal pathology, including intestinal perforation, meconium peritonitis, atresia, or volvulus. Prenatal perforation may cause meconium peritonitis, which can cause calcifications visible on abdominal radiography. Approximately 40 percent of MI in newborns with CF is complex [29].
•MI is "simple" if there is no associated gastrointestinal pathology.
●Disease associations – All infants with MI should have a definitive diagnostic test for CF. A sweat test may be obtained after 48 hours of age, although it is difficult to collect sweat in an infant under approximately 2.5 kg or infants who are stressed or in a warmer bed. If an adequate quantity of sweat cannot be obtained, genetic testing may be helpful. Infants with MI are likely to have a negative newborn screen for CF, for unclear reasons. (See "Cystic fibrosis: Clinical manifestations and diagnosis", section on 'Diagnosis'.)
Infants with MI are at increased risk for developing cholestasis, but the cholestasis is transient in most cases and does not appear to predict clinically significant hepatobiliary disease [30] (see 'Cystic fibrosis-related liver disease' below). One analysis suggests that patients who present with MI have higher rates and shorter times to obstructive lung disease [31]. However, others have shown long-term outcomes for infants with MI are similar to those without MI [32].
●Management
•Nonoperative management – If simple MI is confirmed by the diagnostic enema, it is usually managed by administration of hyperosmolar enema (typically, diluted sodium meglumine diatrizoate, Gastrografin), closely monitored by fluoroscopy. The hyperosmolar contrast often breaks up the meconium mass and clears the obstruction. This approach is successful in 20 to 40 percent of neonates with simple MI [33-35]. Complications occur in 2 to 10 percent of these procedures and include intestinal perforation and fluid shifts with hypotension and shock. Patients should be well hydrated and have an intravenous line in place before performing the procedure. Historical series reported higher success rates (60 to 80 percent) but with higher complication rates as compared with more recent series [36]. The higher rates of success and complications in historical series may both depend on use of higher instillation pressures, multiple attempts, and the experience of the radiologist.
•Operative management – Surgical approaches are used for complicated MI and for some cases of simple MI that do not clear with nonoperative intervention. Operative procedures include simple enterotomy with lavage; double enterostomy; and/or resection of dilated, perforated, or atretic bowel, with diversion ileostomy [33,37]. The most conservative operation that relieves the obstruction should be performed. Loss of intestine in a patient with CF may have deleterious consequences to future nutrition, out of proportion to what is seen in children without CF. A pediatric surgeon with experience in CF is optimal. Patients with CF and ileostomies are at increased risk of sodium loss, and careful attention should be paid to sodium requirements and replacement. Total body sodium depletion, which can occur in the face of normal serum sodium, should be considered in infants with ileostomies who are not gaining weight.
For all patients, growth and nutrition should be closely monitored and optimized because loss of weight or poor growth may have long-term detrimental impact on pulmonary outcomes. Breastfeeding may be protective [38]. In a retrospective multicenter study of infants with meconium ileus, risk factors for adverse outcomes within the first year of life included high blood immunoreactive trypsinogen, prenatally diagnosed intestinal obstruction, a severe postsurgical clinical picture, and early liver disease [38].
Distal intestinal obstruction syndrome — Distal intestinal obstruction syndrome (DIOS), formerly known as "meconium ileus equivalent," is characterized by an acute complete or incomplete obstruction of the ileocecum by inspissated intestinal contents [39,40]. DIOS is unique to CF. DIOS must be distinguished from constipation, which is characterized by gradual onset of fecal impaction of the colon, starting at the sigmoid and extending proximally. DIOS can occur at any age, but it is more common in those with pancreatic insufficiency [41].
●Epidemiology – DIOS occurs in 10 to 47 percent of CF patients, depending upon the criteria used to make the diagnosis [42-44]. Although older series report that most cases occur in adolescents and young adults [45], young children can also have DIOS. DIOS may be recurrent and is associated with more severe genotypes but also appears to be influenced by nongenetic factors [46]. The development of DIOS is not associated with pulmonary exacerbations [47].
Risk factors for developing DIOS include severe genotype (eg, F508del), pancreatic insufficiency, poorly controlled fat malabsorption, dehydration, and prior episodes of DIOS [40]. DIOS also is more common in patients who use opioids or have undergone organ transplantation. Reports conflict as to whether it is more common in patients with a history of MI [37,39].
●Pathogenesis – DIOS is caused by inspissated intestinal contents that completely or partially block the small intestinal lumen, most commonly at the ileocecal junction. The pathogenesis of DIOS is not fully understood, but several mechanisms have been suggested:
•Insufficient pancreatic enzyme activity – Approximately 90 percent of patients with DIOS have pancreatic insufficiency [39,48]. Some but not all studies suggest that inadequate doses of pancreatic enzymes might contribute to the risk of DIOS [42,45]. The proposed mechanism is that malabsorbed fat may slow intestinal transit and alter the viscosity of the luminal contents [40,49].
•Dysmotility – Intestinal dysmotility, either intrinsic or iatrogenic, has also been suggested as a factor in the development of this disorder. This factor might also explain the high rate of recurrence in some patients. The presence of constipation in 42 percent of individuals with DIOS also supports this reasoning [41]. (See 'Constipation' below.)
•Other – Other factors that may have a role in the development of DIOS are abnormal mucins and water and electrolyte composition of the intestinal contents [50-52]. This has been demonstrated in CF mouse models, in which ileal mucus is denser, more adherent, and less penetrable as compared with wild-type mice. These properties can be normalized by admixture with a highly concentrated sodium bicarbonate buffer [53].
•While acute episodes of dehydration and changes in diet have been associated with the development of DIOS, a common set of precipitating factors has not been identified.
●Clinical manifestations – The most common manifestation of DIOS is cramping abdominal pain, generally located in the right lower quadrant (RLQ). The onset of symptoms can be acute or intermittent, and the symptoms tend to become progressively severe over time. Other features include abdominal distension, flatulence, weight loss, and poor appetite. Vomiting may ensue when complete obstruction develops. Patients usually are constipated but also may have diarrhea or even a normal stool pattern. On examination, a mass may be palpated in the RLQ.
●Diagnosis – DIOS can be diagnosed in patients with CF who present with the classical triad of:
•Abdominal pain and distension.
•An RLQ mass.
•Plain abdominal radiographs showing accumulation of stool in the distal small intestine and right colon, usually with little or no stool distal to this obstruction. The stool is usually described as "bubbly" or granular in appearance (image 3) [41]. Other characteristic findings on plain film include air-fluid levels and small bowel dilatation.
DIOS is a condition unique to CF and is largely unknown to primary care clinicians, emergency department clinicians, and gastroenterologists with limited experience with CF. For this reason, it is important to educate patients and their families about the possibility and symptoms of DIOS and recommend that they contact the CF clinician if they develop symptoms concerning for DIOS and are receiving care outside the CF center.
Other forms of imaging also can aid in the diagnosis. An abdominal ultrasound can identify an obstructing mass but cannot always rule out appendicitis or intussusception, as discussed below [42]. On computed tomography (CT) scan, findings characteristic of DIOS include proximal small-bowel dilation and inspissated fecal material in the distal ileum (image 4); the scan also helps to exclude other causes of the symptoms. Alternatively, a water-soluble contrast enema can be useful for diagnosis; the absence of contrast material in the terminal ileum is suggestive of DIOS. Such enemas are hyperosmolar and can be therapeutic as well as diagnostic; the technique and risks are discussed below.
●Differential diagnosis – DIOS should be distinguished from chronic constipation, in which the onset of symptoms is more gradual and the stool mass is more distal or distributed evenly throughout the colon, although the two conditions often co-occur. Intussusception is a particularly important consideration, especially for patients with vomiting or other signs of complete obstruction. Patients who have had previous abdominal surgery are at risk for bowel obstruction secondary to adhesions. Other causes of symptoms that can mimic DIOS include appendicitis, volvulus, ovarian disease, Crohn disease, and fibrosing colonopathy [40]. Some authors suggest that the prevalence of Crohn disease is increased in individuals with CF, and ileocecal Crohn disease may mimic DIOS (see 'Associations with other gastrointestinal diseases' below). Fibrosing colonopathy has become much less common but is also in the differential diagnosis (see 'Fibrosing colonopathy' below). Gastrointestinal cancer is increasingly recognized in adults with CF (see below) and, although rare, should be considered in patients with recurrent symptoms or episodes of bowel obstruction that do not resolve [15]. If the diagnosis of DIOS is unclear, other diagnostic studies should be performed to evaluate for these disorders, based upon the patient's clinical findings (table 1). In addition to imaging, laboratory testing to exclude other causes of abdominal pain may include a complete blood count, liver enzymes, urinalysis and culture, and serum amylase and lipase. Of note, pancreatitis is common among CF patients with pancreatic sufficiency but is rare among those with pancreatic insufficiency (see 'Pancreatitis' below). (See 'Constipation' below and "Acute appendicitis in children: Clinical manifestations and diagnosis" and "Intussusception in children" and "Ovarian cysts in infants, children, and adolescents".)
●Management – Treatment is generally tailored to the severity of the episode. Initial management for both surgical and nonsurgical cases should be aimed at correcting any fluid and electrolyte abnormalities. Patients who are not vomiting and who tolerate the volumes needed for clearance of DIOS usually can be treated with nasogastric lavage. Patients who cannot tolerate oral or nasogastric liquids or are vomiting should be managed with enemas. In these cases, oral or nasogastric lavage should not be attempted and a nasogastric tube should be considered for decompression [40]. Patients with signs of peritonitis may require surgery and should be urgently evaluated by a surgeon.
•Oral or nasogastric therapy – Patients who are not vomiting typically have incomplete (impending) DIOS and usually respond to oral rehydration and osmotic laxatives administered orally or via nasogastric tube. However, note that partial obstruction may lead to aspiration, which can be life-threatening for people with CF. Close monitoring during therapy is critical. For these patients, each of the following approaches has been used successfully in patients with DIOS severe enough to warrant hospitalization [40]:
-A balanced electrolyte intestinal lavage solution (such as GoLYTELY) is administered either orally or nasogastrically (particularly in children) at a rate of 20 to 40 mL/kg per hour (maximum 1 L/hour) over eight hours. Children generally require a total of 2 to 3 liters and adults 5 to 6 liters [42].
-Diatrizoate meglumine and diatrizoate sodium (Gastrografin) can be administered orally or by nasogastric tube [54]. For children younger than six years, an appropriate dose is 50 mL of Gastrografin in 200 mL of water or juice. For older patients, 100 mL of Gastrografin is diluted in 400 mL of water or juice. In each age group, one-half of this dose is given on subsequent days if needed to complete the clean-out. In the past, N-acetylcysteine was used orally in a similar fashion, but there is better clinical evidence supporting the use of Gastrografin for DIOS [40].
•Enemas – Patients presenting with bilious vomiting or other signs and symptoms of complete intestinal obstruction, or for those who do not respond to the above measures, should be managed with hyperosmolar contrast enemas, with or without laxatives. This is typically done by administering an enema of a hyperosmolar contrast agent (sodium meglumine diatrizoate, Gastrografin), which is both diagnostic and therapeutic [39,40]. The enema consists of 100 mL of Gastrografin diluted in 400 mL water; it is administered under fluoroscopic guidance to visually confirm clearance of the obstruction as the enema refluxes retrograde through the ileocecal junction (image 5) [55]. There is considerable interindividual variability in the volume of enema required to fill the colon; in some cases, enema volumes up to 3500 mL have been reported [55]. Tween-80 (polysorbate 80, a soap- or solvent-like compound) may be added to the Gastrografin. The amount of Gastrografin and Tween 80 varies from patient to patient, and some patients may require more than one enema, usually given 12 to 24 hours after the initial therapy [55]. Ideally, these enemas are supervised by radiologists with expertise in managing DIOS.
Risks associated with hyperosmolar enemas include perforation, bowel ischemia, and depletion of intravascular fluid with hypotension and shock, or bowel perforation [40]. As a result, this procedure should be performed only by a radiologist experienced in the technique. Mineral oil and sodium phosphate enemas usually are not effective for the distal ileal obstruction found in DIOS. If the obstruction fails to resolve, other causes should be considered, as discussed in the differential diagnosis section above.
For the rare patient who does not respond to the medical management described above or develops evidence of intestinal ischemia, surgical laparotomy and decompression is indicated [56] and other causes of bowel obstruction should be considered. The most conservative operation that relieves the obstruction should be performed to preserve as much intestine as possible; surgeons with experience in CF are preferred.
Once the inspissated plug has been eliminated, treatment aimed at preventing further episodes should be instituted since DIOS frequently recurs. One approach that is usually well tolerated is chronic administration of oral polyethylene glycol 3350 at a dose of 0.5 to 1 gram/kg/day (maximum 40 grams/day) for 6 to 12 months [40]. The clinician should also optimize pancreatic enzyme treatment and adherence to the regimen, encourage adequate hydration, and consider other potential contributors, such as constipation and small intestinal bacterial overgrowth. (See "Cystic fibrosis: Assessment and management of pancreatic insufficiency" and 'Small intestine bacterial overgrowth' below.)
Fibrosing colonopathy — Fibrosing colonopathy, a severe intestinal fibrotic process associated with strictures and, in some cases, ascites, was reported in the early 1990s in patients with CF who took large doses of PERT [57]. As a result, a maximum dose of 2500 lipase units/kg/meal (or 10,000 lipase units/kg/day) was recommended. However, the exact cause of the strictures remains unclear. A methacrylic acid copolymer in the enteric coating of some products was suspected [58] but was not confirmed in a case-control study [59]. Reports of enzyme-associated colonopathy have been rare since attention has been paid to not prescribe excessive doses of PERT. In addition, the US Food and Drug Administration has required that all PERT products comply with modern chemistry, manufacturing, and control criteria, including predictable amounts of enzyme content. As part of that approval process, a large phase IV study is underway to determine whether the current products are linked to fibrosing colonopathy (NCT01652157). (See "Cystic fibrosis: Assessment and management of pancreatic insufficiency", section on 'Pancreatic enzyme replacement therapy'.)
Constipation — Constipation is a common problem in individuals with CF, occurring in 25 to 50 percent of patients [60,61], and is a common reason for flatulence and abdominal pain [62]. The underlying mechanisms are probably similar to DIOS and include abnormal intestinal fluid composition, dysmotility, and pancreatic insufficiency. Patients may be having regular bowel movements yet have a large intracolonic fecal load. Although constipation has been attributed to either inadequate or excessive doses of PERT, a large study found no correlation between PERT dosage and constipation [62]. Similarly, patients with either pancreatic sufficiency or insufficiency have a relatively dehydrated bowel and are prone to constipation [63]. Constipation is probably responsible for the increased risk of rectal prolapse in children with CF, but this complication is now rare. (See 'Rectal prolapse' below.)
Constipation in individuals with CF is generally managed with osmotic laxatives such as polyethylene glycol 3350 (eg, Miralax) or with electrolytes [64]. PERT dosage should be evaluated to ensure that it is appropriate. Stimulant laxatives such as senna and bisacodyl can be added intermittently if needed. (See "Chronic functional constipation and fecal incontinence in infants, children, and adolescents: Treatment", section on 'Details on medications'.)
Several second-line medications are now available for the treatment of chronic idiopathic constipation [65]. Few have been tested in people with CF, but these may be considered in patients with severe constipation.
●Lubiprostone has some theoretical appeal for use in patients with CF because it is purported to activate alternative type-2 chloride channels, thus increasing ion transport despite the nonfunctional CFTR. A small observational study reported modest benefits of lubiprostone in adult patients with CF, but the benefits and risks have not been fully evaluated and there have been no large-scale randomized clinical trials evaluating its efficacy in CF patients [66,67].
●Linaclotide is approved for people six years and older with chronic constipation. It has not been widely used to treat constipation in CF, because the primary mechanism of action is via the CFTR. However, a study using a CF mouse model demonstrated that linaclotide improves gastrointestinal transit by increasing luminal fluidity by inhibiting sodium/hydrogen exchanger 3-mediated sodium absorption [68].
●Plecanatide is a pH-dependent guanylate cyclase-C agonist approved for use in adults with chronic constipation [65]. No studies in people with CF have been published.
●Prucalopride is a selective agonist of serotonin 5-HT4 receptors, approved only for use in adults. Along with increasing intestinal secretions and peristalsis, it may also increase gastrointestinal motility [65]. Again, no data are available in people with CF. (See "Management of chronic constipation in adults", section on 'Pharmacologic therapy'.)
Intussusception — Intussusception occurs in approximately 1 percent of patients with CF. The intussusception usually is caused by inspissated bowel contents that serve as a lead point. Accordingly, the risk factors are similar to those for DIOS and may include inadequate pancreatic enzyme supplementation. Clinically, it is characterized by colicky abdominal pain, vomiting, a palpable mass, and sometimes rectal bleeding [69,70]. The presenting symptoms may be difficult to distinguish from those of complete DIOS.
Diagnosis can be made with ultrasound, or with a contrast enema, which may also be therapeutic. Surgery is required if less invasive management is unsuccessful or the patient develops signs of peritonitis [42]. (See "Intussusception in children".)
Rotavirus vaccine may be given to most infants with CF following the standard precautions. The vaccine is contraindicated for those with a history of intussusception. (See "Rotavirus vaccines for infants", section on 'Precautions'.)
Appendiceal disease — Appendicitis occurs somewhat less frequently in patients with CF compared with the general population, but diagnosis is challenging because the presentation is more often atypical and can mimic symptoms of DIOS or other CF-related intestinal diseases [71-74]. In a series of 33 CF patients with appendiceal disease, only 15 (45 percent) presented with classic symptoms of abdominal pain shifting to the RLQ, focal RLQ abdominal pain, and elevated white blood cell count [75]. An additional four patients (12 percent) had acute appendicitis presenting with mild or atypical symptoms. The remaining 14 patients had tense mucoid distension of the appendix, which presented with chronic intermittent focal RLQ pain without fever or with intussusception. In these cases, the tense mucoid distension was responsible for the symptoms, which resolved after resection. In other patients with CF, mucoid distension of the appendix is asymptomatic and is found incidentally at autopsy [74,76].
Small intestine bacterial overgrowth — Small intestine bacterial overgrowth (SIBO) is a condition in which the quantity of bacterial content in the upper gastrointestinal tract significantly increases. Bacteria can transform normal nutrients into nonabsorbable and toxic substances, leading to enterocyte damage, malabsorption, and eventually malnutrition. SIBO can contribute to fat malabsorption and malnutrition by deconjugating bile salts and interfering with their ability to emulsify fats in the intestinal lumen. Clinical symptoms of SIBO may be nonspecific and include bloating, flatulence, abdominal pain, watery diarrhea, dyspepsia, and weight loss or failure to gain weight. This condition was first recognized in patients following gastrointestinal surgery but now is described in other clinical settings, including in patients with malnutrition or disorders affecting gastrointestinal motility. (See "Cystic fibrosis: Nutritional issues", section on 'Small intestine bacterial overgrowth'.)
Individuals with CF are susceptible to SIBO because of decreased intestinal motility, altered bacterial flora due to chronic use of antibiotics, use of acid-suppressing agents, and because the underlying CFTR defect contributes to dysbiosis in the gastrointestinal tract as well as in the airways [10,77]. Malnutrition also may contribute to the risk.
Up to 35 percent of individuals with CF have some degree of SIBO, as determined by breath hydrogen testing [77,78]. However, the clinical significance of an abnormal breath hydrogen test is unclear. Other studies suggest that patients with CF often have false-positive breath hydrogen tests, perhaps because of underlying malnutrition or dysmotility rather than abnormal bacterial colonization per se [79]. The disorder may be diagnosed by breath testing for hydrogen and methane, but this technique is only moderately accurate [78-80]. (See "Small intestinal bacterial overgrowth: Clinical manifestations and diagnosis".)
Because accurate, definitive tests to establish the presence of SIBO are lacking, empiric trials of treatment may be given to patients who are suspected of having SIBO. Oral antibiotics that are either absorbable or nonabsorbable can be used [81]. Sometimes, this treatment trial results in dramatic improvement in gastrointestinal symptoms and/or in nutritional status. Antibiotic selection and other treatment considerations for SIBO are discussed separately. (See "Small intestinal bacterial overgrowth: Management".)
Rectal prolapse — In the modern era, rectal prolapse is an uncommon complication of CF. Rectal prolapse occurs in approximately 3 percent of children with CF; conversely, approximately 3 percent of children with rectal prolapse have CF [82]. In the past, rectal prolapse was much more common, occurring in up to 20 percent of individuals with classic CF, presumably because of later diagnosis in the absence of newborn screening programs and possibly suboptimal treatment with pancreatic enzyme therapy [83,84].
Rectal prolapse in patients with CF has been associated with constipation, diarrhea, and malnutrition. It occurs most frequently in toddler-aged children who are toilet training but can occur at any age. It can be triggered by cough in older patients. The prolapse may involve only the mucosa or may involve all layers of the anorectum. Families should be taught how to manually reduce the prolapse to prevent bowel edema. For the majority of cases that are associated with constipation, treatment with daily doses of osmotic laxatives is appropriate to prevent recurrence. In severe cases, large amounts of osmotic laxative may be needed. Recurrence of rectal prolapse may indicate the need to verify adherence to pancreatic enzyme replacement or increase the dose [47,84]. Surgical intervention rarely is indicated. (See "Rectal prolapse in children".)
Clostridioides difficile colitis — People with CF appear to have a high carriage rate of nontoxigenic Clostridioides difficile [85]; however, they are also at risk for life-threatening complications from toxigenic C. difficile, and symptoms may be atypical [86]. This risk may be higher in those with CF who have undergone lung transplantation [87]. The recommendations for C. difficile evaluation and management for the general population should be followed, with a high index of suspicion in seriously ill, hospitalized patients or those who have undergone lung transplantation. (See "Clostridioides difficile infection in children: Clinical features and diagnosis" and "Clostridioides difficile infection in children: Treatment and outcome" and "Clostridioides difficile infection in adults: Clinical manifestations and diagnosis" and "Clostridioides difficile infection in adults: Treatment and prevention".)
Effects of CFTR modulators on gastrointestinal function — The management of CF has been radically changed by the introduction of CFTR modulators. Although the clinical trials of these agents frequently emphasize pulmonary function preservation, studies of early modulators, particularly ivacaftor, showed a variable impact of modulators on nutrition and gastrointestinal symptoms, particularly in young children [88-91]. All modulators approved thus far by the US Food and Drug Administration have variable impact on the metabolism of some other medications. Providers working with patients with CF on CFTR modulators should review potential drug interactions using the drug interactions program or consult a pharmacist knowledgeable in this area.
With the advent of a triple combination CFTR modulator (elexacaftor-tezacaftor-ivacaftor [ETI]) in 2019, effective CFTR modulator therapy is available for most genotypes, including homozygous or heterozygous F508del variants. These modulators improve weight gain in the majority of people with CF [92]. The mechanism for this improvement and the impact of this combination of modulators on gastrointestinal symptoms are not yet known; other treatments for CF-related gastrointestinal disease should be continued until more information is available. In one study of adolescents and adults with CF, treatment with ETI for six months did not improve gastrointestinal symptoms or markers of pancreatic function [93]. Thus, people with CF may still require management for gastrointestinal disease despite the beneficial effects of ETI on pulmonary function. (See "Cystic fibrosis: Treatment with CFTR modulators".)
Intestinal inflammation, microbiome, and probiotics — Although gastrointestinal symptoms have been thought to be related to malabsorption in patients with CF, even patients with adequate PERT continue to complain of gastrointestinal symptoms. These observations have prompted investigation into whether intestinal inflammation might contribute to gastrointestinal pathology in CF.
Several lines of evidence tend to support this hypothesis. One study showed that gastrointestinal symptoms are associated with polymorphisms in tumor necrosis factor alpha (TNF-alpha), a proinflammatory cytokine produced by macrophages and known to be involved with the pulmonary inflammatory cascade in CF lung disease [94]. Another study showed that immune activation occurs in the gut of patients with CF, and that this may result from the underlying basic cellular defect in CF [95]. A third study found that adults with CF had varying degrees of inflammatory findings including edema, mucosal breaks, and ulcerations, as seen on wireless capsule endoscopy [96]. Finally, fecal calprotectin, a protein released during neutrophil activation and a marker of intestinal inflammation, is elevated in patients with CF compared with healthy controls [97]. However, in vitro studies suggest that trypsin can digest calprotectin; this presents a challenge when interpreting elevated calprotectin levels in individuals with pancreatic insufficiency [98].
Patients with CF have an intestinal microbiome that differs from individuals without CF, and this may correlate with fecal measures of nutrient malabsorption and markers of inflammation [99-101]. Thus, there is interest in whether manipulating the intestinal microbiome through the use of probiotics could have a beneficial effect on intestinal inflammation. A meta-analysis concluded that probiotics reduce fecal calprotectin, although results for other biomarkers were not significant compared with placebo [102]. No conclusions could be drawn about effects on gastrointestinal symptoms and evidence was considered low-quality. Further studies will be needed to determine which probiotics are effective and to understand the mechanism for any effect of probiotics on fecal calprotectin levels in CF patients.
Associations with other gastrointestinal diseases — Celiac disease and inflammatory bowel disease (IBD) have been reported in patients with CF and cause gastrointestinal symptoms that may mimic some of the other CF-associated disorders outlined above.
The possibility of celiac disease should be considered in CF patients with growth failure and malabsorptive stools despite proper PERT dosing. In patients with CF and in the general population, serologic testing for tissue transglutaminase (tTG) antibodies is typically used to screen for celiac disease, but intestinal biopsy is required for definitive diagnosis. Occasionally, tTG is elevated in patients without histologic evidence of celiac disease on biopsy, in patients with or without CF [103]. It remains unclear whether patients with CF are at increased risk for celiac disease as compared with the general population. One Scandinavian study reported that the prevalence of celiac disease was three times higher among patients with CF as compared with the general population [104], but this finding has not been reported in other populations. (See "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in children".)
Similarly, the possibility of IBD should be considered in patients who have growth failure, blood in the stool, and/or persistent abdominal complaints despite adequate PERT therapy. One retrospective review reported that patients with CF had a higher prevalence of IBD, and particularly of Crohn disease, compared with the general population [105]. Of note, serologic testing is not reliable for the diagnosis of IBD and may be particularly unreliable in patients with CF [106]. A biopsy that definitely demonstrates features consistent with Crohn disease or ulcerative colitis is required for the diagnosis; inflammation alone is not sufficient for a diagnosis of IBD.
PANCREATIC DISEASE — Pancreatic dysfunction is a key manifestation of CF. All patients with CF have decreased secretin-stimulated flow through their pancreatic ducts [107]. In those with severe phenotypes, flow is so diminished that abnormally tenacious mucus and secretions obstruct the pancreatic lumen. This blockage interferes with secretion of pancreatic enzymes, causing exocrine pancreatic insufficiency. It also leads to autolysis and progressive destruction of pancreatic islets; a large percentage of these patients eventually develop abnormal glucose tolerance and CF-related diabetes (CFRD). Patients with milder variants also have decreased flow but usually have enough duct patency to allow enzymes to pass; clinically, these patients are pancreatic-sufficient. However, patients with pancreatic sufficiency may have intermittent blockages and inflammation of the pancreas, causing pancreatitis.
Pancreatic insufficiency — Pancreatic insufficiency is the most common gastrointestinal complication of CF. It affects approximately 85 percent of patients at some time in their lives and is present from birth in most of these patients [108]. The major consequences of pancreatic insufficiency are due to fat malabsorption secondary to decreased production of pancreatic enzymes. The diagnosis and management of pancreatic insufficiency in this population, including strategies for pancreatic enzyme replacement and fibrosing colonopathy, are discussed separately. (See "Cystic fibrosis: Assessment and management of pancreatic insufficiency".)
Pancreatic insufficiency is an important contributor to the nutritional problems in patients with CF, which include growth failure, fat-soluble vitamin deficiencies, and bone disease. These issues are discussed in detail elsewhere. (See "Cystic fibrosis: Nutritional issues".)
Pancreatitis — Pancreatitis develops in approximately 15 to 20 percent of CF patients with pancreatic sufficiency and is rare among those with pancreatic insufficiency [109-111]. CF transmembrane conductance regulator gene (CFTR) mutations are grouped as class I through VI based on cellular phenotype. Milder CFTR genotypes, or those associated with pancreatic sufficiency, are at increased risk of pancreatitis [112]. Accordingly, most patients who develop pancreatitis have at least one "mild" (class IV or V) mutation in the CFTR (table 2) [112]. The risk is exacerbated by alcohol or smoking, each of which has been shown to reduce CFTR function [113,114]. In some such patients, defective ductular and acinar pancreatic secretion leads to recurrent or chronic pancreatitis, which, in turn, causes a decline of pancreatic exocrine function. Among patients with pancreatic sufficiency at the time of the first episode of pancreatitis, approximately 20 percent subsequently experience a decline of pancreatic function and become pancreatic-insufficient. (See "Cystic fibrosis: Assessment and management of pancreatic insufficiency", section on 'Epidemiology'.)
Pancreatitis in CF patients typically presents during late adolescence or early adulthood. On rare occasions, pancreatitis may be the initial presenting symptom of CF. Acute pancreatitis is diagnosed by the combination of abdominal pain compatible with pancreatitis, serum amylase, and/or lipase values ≥3 times upper limits of normal and imaging findings of acute pancreatitis [115].
An increased prevalence of CFTR mutations has been observed in patients with idiopathic acute pancreatitis, acute recurrent pancreatitis, and chronic pancreatitis, suggesting that certain CFTR genotypes (perhaps in combination with environmental or genetic cofactors) predispose to this complication [116-118]. There are specific CFTR variants that may not be associated with CF but regulate bicarbonate permeation in cells and are associated with increased risk of pancreatitis [119]. The consequences depend on the severity of the mutation and zygosity [118]. Patients with CFTR mutations and chronic pancreatitis who do not fit the diagnostic criteria for CF often can be categorized as having either "nonclassic CF" or "CFTR-related disease." (See "Pancreatitis associated with genetic risk factors", section on 'CFTR gene' and "Cystic fibrosis: Clinical manifestations and diagnosis", section on 'Definitions'.)
Preliminary evidence suggests that CFTR modulator therapy may restore pancreatic function in young children. In one study of children 12 to 24 months of age with gating mutations, treatment with ivacaftor improved exocrine pancreatic function (as measured by fecal elastase) and many children reached a fecal elastase level consistent with pancreatic sufficiency [120]. Other studies suggest that the pancreatic exocrine dysfunction may be less reversible with advancing age: In children two to five years of age treated with ivacaftor, fecal elastase increased only in those with pancreatic sufficiency [121]. In children six years and older, most patients did not experience improvements in pancreatic function in a short-term trial of tezacaftor-ivacaftor [122]. However, in a case series in children 6 to 11 years with pancreatic insufficiency, pancreatic function gradually improved in 7 of 17 children over several years of treatment with ivacaftor [123]. Thus, it appears that restoration of exocrine pancreatic function with CFTR modulators primarily occurs in very young individuals and patients should generally be advised that CFTR modulator therapy will not allow them to stop pancreatic enzyme therapy. Data regarding the effects of elexacaftor-tezacaftor-ivacaftor (ETI) on pancreatic function in children are not yet available. One study in adolescents and adults reported that treatment with ETI for six months did not improve markers of pancreatic function [93]. (See "Cystic fibrosis: Treatment with CFTR modulators".)
Cystic fibrosis-related diabetes — CFRD is a distinct form of diabetes mellitus that is a common and clinically important complication of CF. The primary cause is a relative insulin deficiency related to destruction of pancreatic islets. Insulin resistance also may play a role, especially in association with acute exacerbations or chronic progression of pulmonary disease. CFRD affects approximately 20 percent of adolescents with CF and almost 50 percent after 30 years of age [124]. Other risk factors for developing CFRD include severe genotype (eg, F508del homozygotes), exocrine pancreatic insufficiency, and female sex.
CFRD is associated with clinically important declines in pulmonary function and nutritional status and with increased mortality. These effects can be attenuated or reversed by treatment with insulin therapy. Therefore, annual screening for CFRD is recommended for all individuals with CF using an oral glucose tolerance test since hemoglobin A1c is not reliable, beginning by 10 years of age [125,126].
Individuals with CF who are pancreatic-sufficient and have chronic or recurrent pancreatitis can also develop diabetes, but the pathophysiology is different than that of CFRD. In one study of 18 patients whose presentation of CF was pancreatitis, five had impaired glucose tolerance at diagnosis of CF and two had insulin-dependent diabetes [127]. Providers managing people with CF-related pancreatitis may consider oral glucose tolerance testing after recovery from an acute exacerbation.
The pathophysiology, diagnosis, and treatment of CFRD are discussed in detail in a separate topic review. (See "Cystic fibrosis-related diabetes mellitus".)
HEPATOBILIARY DISEASE
Cystic fibrosis-related liver disease — CF-related liver disease (CFLD) has been used to describe a wide range of manifestations, from mild elevations of transaminases to cirrhosis with portal hypertension (table 3). Severe CFLD usually presents during childhood and tends to progress rapidly. Other clinical manifestations of CFLD include neonatal cholestasis or hepatic steatosis. Screening, diagnosis, and management of CFLD, and the hepatic effects of CFTR modulators, are discussed in detail in a separate topic review. (See "Cystic fibrosis: Hepatobiliary disease".)
Gallbladder disease — CF is associated with microgallbladder, cholelithiasis (gallstones), and cholecystitis. These disorders are discussed in a separate topic review. (See "Cystic fibrosis: Hepatobiliary disease", section on 'Gallbladder disease'.)
GASTROINTESTINAL CANCER — People with CF have an increased risk of digestive tract cancers, including cancers of the small bowel, colon, pancreas, and biliary tract [15,128]. CF has been declared a hereditary colon cancer syndrome by the Cystic Fibrosis Foundation. This risk is increased in people with CF who have had organ transplantation [15,128]. The Cystic Fibrosis Foundation Task Force states that screening for colorectal cancer should begin within two years of transplant or even before transplant. Prospective study of colonoscopy in people with CF demonstrated increased incidence of polyps in those 40 years old and above; 50 percent of the polyps were adenomatous and 25 percent were advanced adenomas [129]. In this study, 3 percent had colon cancer at initial screen.
The CF Foundation has developed Colorectal Cancer Screening Clinical Care Guidelines for adults with CF [130]. The guideline recommends colonoscopy for screening, beginning at age 40 years, or at 30 years for those who have had an organ transplant. The screening should be repeated every five years. If any adenomatous polyps are identified, the colonoscopy should be repeated in three years or less, depending on characteristics of the individual case. The guideline includes an intensive bowel preparation protocol that should be used for CF patients because it is very difficult to achieve a satisfactory colonic lavage in these individuals [131].
In a study from the United Kingdom CF registry, 14.3 percent of cancers occurred in people who had undergone solid organ transplant [132]. The risk for gastrointestinal cancers was increased fourfold in individuals with CF-related diabetes (CFRD).
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cystic fibrosis" and "Society guideline links: Chronic pancreatitis and pancreatic exocrine insufficiency".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Cystic fibrosis (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Gastrointestinal tract – Common causes of gastrointestinal symptoms in cystic fibrosis (CF) are summarized in the table (table 1).
•Gastroesophageal reflux disease (GERD) – Symptomatic GERD is reported in approximately one-third of individuals with CF. Whether GERD affects the course of CF-related pulmonary disease is unclear. Decisions about treatment with acid-suppressing medications depends on considerations about several different potential risks and benefits and the clinical characteristics of the individual patient. Several other gastrointestinal disorders that are associated with CF may contribute to or be confused with GERD (table 1). (See 'Gastroesophageal reflux disease' above.)
•Distal intestinal obstruction syndrome (DIOS) – DIOS is caused by inspissated intestinal contents that completely or partially block the small intestinal lumen, most commonly at the ileocecal junction. It tends to occur in patients with pancreatic insufficiency. Symptoms include progressive cramping abdominal pain in the right lower quadrant (RLQ), often with a RLQ mass and vomiting. The differential diagnosis includes constipation, ileocecal Crohn disease and appendicitis (table 1). Management focuses on correcting fluid and electrolyte abnormalities, if present, and removing the inspissated plug using osmotic agents. (See 'Distal intestinal obstruction syndrome' above.)
•Intussusception – Intussusception occurs in approximately 1 percent of patients with CF and usually is caused by inspissated bowel contents that serve as the lead point. Symptoms include colicky abdominal pain, vomiting, and a palpable mass, which may be difficult to distinguish from those of complete DIOS. The diagnosis can be made with ultrasound or with a contrast enema, which may also be therapeutic. (See 'Intussusception' above.)
•Small intestine bacterial overgrowth (SIBO) – SIBO occurs in individuals with CF because of several contributing factors. Symptoms are nonspecific and include bloating, flatulence, abdominal pain, watery diarrhea, dyspepsia, and weight loss or failure to gain weight. The diagnosis is usually based on clinical history and an empiric trial of antibiotics. (See 'Small intestine bacterial overgrowth' above.)
•Rectal prolapse – Rectal prolapse occurs in approximately 3 percent of children with CF. It may be associated with constipation, diarrhea, malnutrition, and insufficient PERT dosing. Treatment includes manual reduction and daily osmotic laxatives; surgery is rarely necessary. (See 'Rectal prolapse' above.)
•Cancer risk – People with CF have an increased risk of digestive tract cancers, including cancers of the colon, small bowel, colon, pancreas, and biliary tract. Because of their increased risk for colorectal cancer, routine screening colonoscopy is recommended beginning at age 40 years, or at 30 years for those who have had an organ transplant. (See 'Gastrointestinal cancer' above.)
●Pancreatic disease
•Pancreatic insufficiency – Approximately 85 percent of patients with CF have pancreatic insufficiency, which may cause fat malabsorption with steatorrhea, growth failure, and fat-soluble vitamin deficiencies. Diagnosis and management of pancreatic insufficiency, including strategies for pancreatic enzyme replacement, is discussed separately. (See "Cystic fibrosis: Assessment and management of pancreatic insufficiency".)
Patients who do not have pancreatic insufficiency still tend to have some impairment in pancreatic exocrine function. Flow through the duct is decreased but not enough to block enzyme secretions. However, these patients still have relatively dehydrated secretions, which can contribute to constipation and intermittent pancreatic ductal blockages. (See 'Pancreatic disease' above.)
•Pancreatitis – Pancreatitis develops in approximately 15 to 20 percent of CF patients with pancreatic sufficiency and is rare among those with pancreatic insufficiency. Some patients experience a decline in pancreatic function following pancreatitis. (See 'Pancreatitis' above.)
•CF-related diabetes (CFRD) – Chronic pancreatic disease often causes progressive endocrine pancreatic dysfunction and CFRD. The risk of developing CFRD increases markedly with advancing age; CFRD affects approximately 20 percent of adolescents with CF and almost 50 percent after 30 years of age. Annual screening for CFRD is recommended starting at 10 years of age; screening and management are discussed in a separate topic review. (See "Cystic fibrosis-related diabetes mellitus".)
●Hepatobiliary disease – CF-related liver disease (CFLD) has multiple presentations, including neonatal cholestasis, hepatic steatosis, and focal biliary cirrhosis (table 3). Among these, focal biliary cirrhosis is most likely to cause progressive liver disease. CF is associated with microgallbladder, cholelithiasis (gallstones), and cholecystitis. These disorders are discussed in a separate topic review. (See "Cystic fibrosis: Hepatobiliary disease".)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Drucy Borowitz, MD, Julie P Katkin, MD, and Karen Schultz, MD, who contributed to earlier versions of this topic review.
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