Chapter 21: Gastrointestinal Tract

GASTROESOPHAGEAL REFLUX & GERD

Clinical Findings

A. Infants With Gastroesophageal Reflux

Gastroesophageal (GE) reflux is common in young infants and is a physiological event. Frequent postprandial regurgitation, ranging from effortless to forceful, is the most common infant symptom. Infant GER is usually benign, and it is expected to resolve by 12–18 months of life.

Reflux of gastric contents into the esophagus occurs during spontaneous relaxations of the lower esophageal sphincter that are unaccompanied by swallowing. Factors promoting reflux in infants include small stomach capacity, frequent large-volume feedings, short esophageal length, supine positioning, and slow swallowing response to the flow of refluxed material up the esophagus. Infants’ individual responses to the stimulus of reflux, particularly the maturity of their self-settling skills, are important factors determining the severity of reflux-related symptoms.

When infants develop symptoms such as failure to thrive, food refusal, pain behavior, GI bleeding, upper or lower airway-associated respiratory symptoms, or Sandifer syndrome, these indicate gastroesophageal reflux disease (GERD).

B. Older Children With Reflux

Older children with GERD complain of adult-type symptoms such as regurgitation into the mouth, heartburn, and dysphagia. Esophagitis can occur as a complication of GERD and requires endoscopy with biopsy for diagnostic confirmation. Children with asthma, cystic fibrosis, developmental handicaps, hiatal hernia (HH), and repaired tracheoesophageal fistula are at increased risk of GERD and esophagitis.

C. Extraesophageal Manifestations of Reflux Disease

Upper airway symptoms (hoarseness, sinusitis, laryngeal erythema, and edema), apnea or apparent life-threatening events (ALTEs), lower airway symptoms (asthma, recurrent pneumonia, recurrent cough), dental erosions, and Sandifer syndrome have all been linked to GERD, although proof of cause-and-effect relationship is challenging.

D. Diagnostic Studies

History and physical examination alone should help differentiate infants with benign, recurrent vomiting (physiologic GER) from those who have red flags for GERD or other underlying primary conditions that may present with recurrent emesis at this age. Warning signs that warrant further investigation in the infant with recurrent vomiting include bile-stained emesis, GI bleeding, onset of vomiting after 6 months, failure to thrive, diarrhea, fever, hepatosplenomegaly, abdominal tenderness or distension, or neurologic changes.

An upper GI series should be considered when anatomic etiologies of recurrent vomiting are considered, but should not be considered to be a test for GERD.

In older children with heartburn or frequent regurgitation, a limited trial of acid-suppressant therapy may be both diagnostic and therapeutic. If a child has symptoms requiring ongoing acid suppressant therapy, or if symptoms fail to improve with empiric therapy, consider referral to a pediatric gastroenterologist to assist in evaluation for complicated GERD, or nonreflux diagnoses including eosinophilic esophagitis (EoE).

Esophagoscopy and mucosal biopsies are useful to evaluate for mucosal injury secondary to GERD (Barrett esophagus, stricture, erosive esophagitis), or to evaluate for nonreflux diagnoses that present with reflux-like symptoms, including EoE. Endoscopic evaluation is not requisite for the evaluation of all infants and children with suspected GERD.

Intraluminal esophageal pH monitoring (pH probe) and combined multiple intraluminal impedance and pH monitoring (pH impedance probe) are indicated to quantify reflux, and to evaluate for objective evidence of symptom associations with regards to atypical reflux presentations. pH impedance studies may have higher diagnostic yield in evaluating for respiratory or atypical complications of reflux disease, or in evaluating for breakthrough reflux symptoms while a patient is on acid-suppressant therapy.

Treatment & Prognosis

Reflux resolves spontaneously in 85% of affected infants by 12 months of age, coincident with assumption of erect posture and initiation of solid feedings. Until then, regurgitation volume may be reduced by offering small feedings at frequent intervals and by thickening feedings with rice cereal (2–3 tsp/oz of formula). In infants with unexplained crying or fussy behavior, no evidence supports empiric use of acid suppression.

Acid suppression may be used to treat suspected esophageal or extraesophageal complications of acid reflux in infants and older children. Therapeutic options include histamine-2 (H₂)–receptor antagonists or proton pump inhibitors (PPIs). PPI therapy has been shown to significantly heal both esophageal mucosal injury and symptoms from GERD within 8–12 weeks. Potential risk factors associated with long-term PPI therapy include risk for infection (pneumonia, Clostridium difficile–associated diarrhea), and an increased risk for osteoporosis has been demonstrated in adults. Although there are no standardized recommendations regarding prophylaxis or surveillance for these complications in pediatric patients on long-term PPI therapy, one should consider weaning or discontinuing treatment if it is no longer required. There is no sufficient evidence to support the routine use of prokinetic agents for treatment of pediatric GERD.

Spontaneous resolution is less likely in older children with GERD and those with underlying neurodevelopmental disorders. Episodic symptoms may be controlled with intermittent use of acid blockers and those with persistent symptoms may require chronic acid suppression. Complications of reflux esophagitis or chronic GERD include feeding dysfunction, esophageal stricture, and anemia (Figure 21–1). Barrett esophagus, a precancerous condition, is very uncommon in children, but it may occur in patients with an underlying primary diagnosis that offers high risk for GERD.

Antireflux surgery (Nissen fundoplication) may be considered in a child with GERD who (1) fails medical therapy; (2) is dependent on persistent, aggressive medical therapy; (3) is symptomatic and nonadherent to medical therapy; and (4) has persistent, severe respiratory complications of GERD or other life-threatening complications of GERD. Potential complications after antireflux surgery include dumping syndrome, gas bloat syndrome, persistent retching or gagging, or wrap failure.

EOSINOPHILIC ESOPHAGITIS

Clinical Findings

A. Symptoms and Signs

This recently recognized entity occurs in all ages and more frequently affects boys. Common initial presentations in young children include feeding dysfunction and vague nonspecific symptoms of GERD such as abdominal pain, vomiting, and regurgitation. If a history of careful and lengthy chewing, long mealtimes, washing food down with liquid or avoiding highly textured foods is encountered, one may suspect EoE. In adolescent’s symptoms of solid food dysphagia, and acute and recurrent food impactions predominate. If a child’s symptoms are unresponsive to medical and/or surgical management of GERD, EoE should be strongly considered as a diagnostic possibility. A family or personal history of atopy, asthma, dysphagia, esophageal dilation, or food impaction is often present.

B. Laboratory Findings

Peripheral eosinophilia may or may not be present. The esophageal mucosa usually appears abnormal with features of thickening, mucosal fissures, strictures, and rings. The esophagus is often sprinkled with pinpoint white exudates that superficially resemble Candida infection. On microscopic examination the white spots are composed of eosinophils (Figure 21–2). A lengthy stricture can be seen at the time of endoscopy but esophagrams may capture this more often. Serum IgE may be elevated, but this is not a diagnostic finding. Specific allergens can often be identified by skin testing, and patient can sometimes identify foods that precipitate pain and dysphagia.

Differential Diagnosis

The most common differential conditions are peptic esophagitis, congenital esophageal stricture, and Candida esophagitis. Patients with eosinophilic gastroenteropathy can also present with gastric outlet obstruction or intestinal caused by large local infiltrates of eosinophils in the antrum, duodenum, and cecum.

Diagnosis

The diagnosis of EoE is based on both clinical and histopathological features. Symptoms referable to esophageal dysfunction must be seen in association with esophageal eosinophilia and a normal gastric and duodenal mucosa. Other causes for esophageal eosinophilia, in particular, GERD, must be ruled out. A preendoscopy trial of PPIs is not required to make the diagnosis.

Treatment

Dietary exclusion of offending allergens (elemental diet, removal of allergenic foods) is effective treatment, but adherence in older children can be difficult. Topical corticosteroids are an effective treatment. Steroids are puffed in the mouth and swallowed from a metered dose pulmonary inhaler; this method of administration is completely opposite of how topical steroids are administered for the treatment of asthma. Patients should not rinse their mouth or eat for 30 minutes to maximize the effectiveness. The association of EoE and esophageal malignancy has not been identified. Parent and family support is available at American Partnership for Eosinophilic Disorders APFED.org.

ACHALASIA OF THE ESOPHAGUS

A. Symptoms and Signs

Achalasia occurs rarely in pediatrics, with an incidence of 0.11 per 100,000 and most commonly in children who are older than 5 years. Cases during infancy have been reported, but overall less than 5% of achalasia occurs in patients less than 15 years of age. Common symptoms reported were emesis (84.6%), dysphagia (69.2%), weight loss (46.0%), and chronic cough (46.1%). Patients may eat slowly and often require large amounts of fluid when ingesting solid food. Familial cases occur in Allgrove syndrome (alacrima, adrenal insufficiency, and achalasia) and familial dysautonomia.

B. Imaging and Manometry

Barium esophagram shows a dilated esophagus with a tapered “beak” at the GE junction. Fluoroscopy shows irregular tertiary contractions of the esophageal wall, indicative of disordered esophageal peristalsis. Esophageal manometry classically shows high resting pressure of the lower esophageal sphincter, failure of sphincter relaxation after swallowing, and abnormal esophageal peristalsis, though these findings may be sporadic, with partial or normal relaxations present in some swallows. Use of high-resolution manometry has become the standard in diagnosis and the Chicago classification into types I, II, and III have been used to indicate prognosis.

C. Differential Diagnosis

Congenital or peptic stricture, webs, and masses of the esophagus may mimic achalasia. EoE commonly presents with symptoms of dysphagia and food impaction, similar to achalasia. Cricopharyngeal achalasia or spasm is a rare cause of dysphagia in children, but it shares some clinical features of primary achalasia of the LES. Intestinal pseudo-obstruction, multiple endocrine neoplasia type 2b, systemic amyloidosis, and postvagotomy syndrome cause esophageal dysmotility similar to achalasia. Teenage girls may be suspected of having an eating disorder. In Chagas disease, caused by the parasite Trypanosoma cruzi, nNOS and ganglion cells are diminished or absent in the muscular layers of the LES causing an acquired achalasia.

Treatment & Prognosis

Based on studies in adults, prognosis is typically best in patients with type II achalasia, followed by type I and worst in type III. Endoscopic injection of botulinum toxin paralyzes the lower esophageal sphincter and may temporarily relieve obstruction but in a recent small study in adults was no better than sham operation and has only been recommended as a short-term bridge to more definitive therapy in medically unstable patients. Pneumatic dilation trials in children are limited, but a single-center experience of endoscopic dilation showed a long-term success rate of up to 87% with one to three dilations. However, a large recent cohort of pediatric to young adult achalasia patients comparing surgical treatment with a Heller myotomy to endoscopic dilation found a similar complication rate but with increased need for reintervention (65% vs 16%) and propose that surgical myotomy be considered the treatment for pediatric achalasia. Postoperative GERD is common, and in the meta-analysis fundoplication was performed in 82% cases, though rates of postoperative GERD were not significantly different between those with and without fundoplication. In a large retrospective pediatric study, general response rates of pneumatic dilation compared to Heller myotomy were not significantly different, though some suggest that children older than 6 years may have better outcomes with pneumatic dilation. Per-oral endoscopic myotomy (POEM) has been increasingly utilized as a less invasive alternative to surgical treatment, with several studies now showing long-term resolution of symptoms and similar rates of adverse events, as well as improved durability of response compared to balloon dilation. Self-expanding metal stents has been reported in childhood refractory cases but have not been recommended in adults.

CAUSTIC BURNS OF THE ESOPHAGUS

Clinical Findings

A. Symptoms and Signs

Ingestion of caustic solids or liquids (pH < 2 or pH > 12) produces esophageal lesions ranging from superficial inflammation to deep necrosis with ulceration, perforation, mediastinitis, or peritonitis. Meta-analysis encompassing more than 11,000 ingestions indicates a slight male predominance and a mean age of ingestion of 2.78 years. Acidic substances typically have a sour taste and therefore lead to limited injury because of the small volume ingested. Their pathogenesis is due to superficial coagulative necrosis with eschar formation. Conversely, the more benign taste of alkali ingestions may allow for larger volume ingestions and subsequent liquifactive necrosis that can lead to deeper mucosal penetration. Factors that determine the severity of injury include the amount ingested, the physical state of the agent, and the duration of mucosal exposure time, making powdered or gel formulations of dishwashing detergent especially dangerous. Ingestions of liquid detergent capsules or pods have become more common, due in part to their bright coloring and benign taste. They tend to cause more respiratory than esophageal injury, though a recent study found endoscopic injury present in 24%. The lips, mouth, and airway should be examined in suspected caustic ingestion, although up to 12% of children without oral lesions can have significant esophageal injury.

B. Imaging Studies

Esophagoscopy is often performed; however, timing is important as endoscopy may not indicate the true severity of injury if it is performed too early (< 24–48 hours) and may increase the risk of perforation if it is performed too late (> 72 hours) due to formation of granulation tissue. Grading of esophageal lesions into first degree (superficial injury, erythema only), second degree (transmucosal with erythema, ulceration, and sloughing), and third degree (transmural with circumferential sloughing and deep mucosal ulceration) can help predict prognosis. Circumferential lesions carry the highest risk of stricture formation. In a recent large single-center study, 34% of ingestions in children were grade 2 or 3, with 50% of these requiring one or more endoscopic dilations. If dilation is felt to be necessary, it should not be performed in the acute phase of injury, though a recent study showed that early initiation of dilations by 15 days decreased the duration and number of dilations ultimately needed. Among elements of the CBC, elevation of red cell distribution width (RDW) above a cutoff of 12.2 was shown to be the most sensitive indicator of esophageal injury at endoscopy with sensitivity of 84.2% and OR of 7.74. In addition, even without clinical findings, endoscopic esophageal lesions have been found in up to 35% and gastric lesions in up to 14% of patients. Plain radiographs of the chest and abdomen may be performed if there is clinical suspicion of perforation. Contrast studies of the esophagus should be performed when endoscopic evaluation is not available, though they are unlikely to detect grades 1 and 2 lesions. Recent data has shown the utility of a 99mTc sucralfate scan in predicting the presence of significant esophageal injury on endoscopy after caustic ingestion.

Treatment & Prognosis

Clinical observation is always prudent, as it is often difficult to predict the severity of esophageal injury at presentation. A large study of almost 1000 pediatric ingestions treated conservatively without steroids, endoscopy, or nasogastric tube showed a stricture rate of 23%. Vomiting should not be induced and administration of buffering agents should be avoided to prevent an exothermic reaction in the stomach. Intravenous corticosteroids (eg, methylprednisolone, 1–2 mg/kg/day) are given immediately to reduce oral swelling and laryngeal edema. A study using high dose (1 g/1.73 m²) methylprednisone for the first 3 days after ingestion, however, showed a significant decrease in the occurrence of esophageal strictures. Treatment may be stopped if there are only first-degree burns at endoscopy. Broad-spectrum antibiotic coverage with third-generation cephalosporins may be considered to decrease stricture formation by preventing bacterial colonization into necrotic tissue. Acid-blockade is often used to decrease additional injury from acid reflux.

Nonobstructive esophageal narrowings occur at the thoracic inlet, GE junction, or point of compression where the left bronchus crosses the esophagus. Strictures occur only with full-thickness esophageal necrosis and prevalence of stricture formation varies from 10% to 50%. In refractory cases, fully covered, self-expanding, removable esophageal stents, now available in pediatric sizes, may offer additional options for recurrent caustic strictures. Topical mitomycin-C has been effective in treatment of refractory caustic strictures of the esophagus and a recent randomized, prospective trial showed benefit in terms of number of dilations (3.25 vs 6.25), cost and ultimate success rate (81.6% vs 40%). Animal models utilizing 5-fluorouracil in the early management of caustic esophageal injuries have also shown promise in preventing fibrosis and stricture formation. Surgical replacement of the esophagus by colonic interposition or gastric tube may be needed for long strictures resistant to dilation, though stricture rates may be as high as 47% and leaks as high as 18%. Study of histopathology of caustic injuries in children has shown changes of chronic esophagitis in 85%, reactive atypia in 13% and squamous dysplasia in 2%. Patients with history of caustic esophageal injury are estimated to have as much as a 1000-fold increase risk for esophageal carcinoma, though no formal surveillance guidelines have been established.

FOREIGN BODIES IN THE ALIMENTARY TRACT

Accidental foreign body ingestions are a common occurrence in pediatrics. The rate of children presenting to Emergency Department with foreign body ingestion has increased in the last two decades in the United States. Fortunately, 80%–90% of foreign bodies pass spontaneously with only 10%–20% requiring endoscopic or surgical management. At presentation the most common symptoms of an ingested foreign body are dysphagia, odynophagia, drooling, regurgitation, and chest or abdominal pain, but patients may be completely asymptomatic. Respiratory symptoms, such as cough, become prominent for foreign bodies retained in the esophagus for more than 1 week. A high index of suspicion should be maintained for toddlers presenting with these symptoms, even without a witnessed ingestion. If the ingestion is witnessed, the timing of the event is important to note as it will have implications for the timing of endoscopic removal.

Coins are the most common foreign body ingested by children (Figure 21–3). Ingested foreign bodies tend to lodge in narrowed areas—valleculae, thoracic inlet, GE junction, pylorus, ligament of Treitz, and ileocecal junction, or at the site of congenital or acquired intestinal stenoses. Evaluations to detect swallowed foreign body start with plain radiography. Radio-opaque objects will be easily visualized. Non–radio-opaque objects, such as plastic toys, may not appear on standard radiograph. If there is particular concern, based on patient symptoms, for a retained esophageal foreign body that is non–radio-opaque, a contrast esophagram is a useful test. Use of contrast, however, may delay or increase the risk of anesthesia due to aspiration concerns.

Most foreign bodies can be removed from the esophagus or stomach of a child by flexible endoscopy. During removal of an esophageal foreign body, the increased risk of airway aspiration supports intubation with an endotracheal tube. Esophageal foreign bodies should be removed within 24 hours to avoid injury to the esophagus. The urgency of removal of esophageal foreign bodies is dictated by the severity of patient symptoms and the ability to swallow oral secretions.

Disk-shaped button batteries lodged in the esophagus are especially concerning and should be removed immediately. Button batteries may cause an electrical thermal injury in as little as 2 hours and can cause many severe complications including death, aortoesophageal fistula, tracheoesophageal fistula, esophageal perforation, esophageal stricture, vocal cord paralysis, and discitis. Although most button batteries in the stomach will pass uneventfully, greater attention is required for larger batteries (> 20 mm) in younger children (< 5 years of age), as there is greater risk for injury sustained to the esophagus and the battery is less likely to successfully traverse the pylorus. In these cases, endoscopic evaluation with gastric batteries may still be considered in order to evaluate the esophagus for signs of injury and to remove the gastric battery. Rates of significant injury and death due to swallowed button batteries have increased in recent years with the transition toward production of higher-voltage lithium batteries.

Esophageal food impaction should always raise the question of underlying esophagitis. In particular, EoE has been shown to be present in up to 75% of pediatric patients presenting initially with esophageal food impaction.

Smooth foreign bodies in the stomach, such as buttons or coins, may be monitored without attempting removal for up to several weeks if the child is free of symptoms. Screws and nails are examples of objects with a blunt end that is heavier than the sharp end. These asymmetrically weighted objects will generally pass without incident and so need for endoscopic removal must be considered on a case-by-case basis. In contrast, double-sided sharp objects that are weighted equally on each end, such as fishbones and wooden toothpicks, should be removed as they can migrate through the wall of the GI tract into the pericardium, liver, and inferior vena cava. Large, open safety pins should be removed from the stomach because they may not pass the pyloric sphincter and may cause perforation. Objects longer than 5 cm may be unable to pass the ligament of Treitz and should be removed. Magnets require consideration for removal only if there has been more than one ingested, or if a single magnet was ingested along with a metallic object, because of the risk of fistula or erosion of mucosal tissue trapped between two adherent foreign bodies. Rare earth metal magnets, or neodymium magnets, are very powerful small magnets that are sold in bulk and have caused multiple cases of bowel perforation necessitating surgical intervention. Ingestion of multiple magnets should lead to immediate endoscopic removal if technically feasible. If not, their migration through the GI tract should be followed radiographically until they are passed.

The use of balanced electrolyte lavage solutions containing polyethylene glycol may help the passage of small, smooth foreign bodies lodged in the intestine. Lavage is especially useful in hastening the passage of foreign bodies that may contain an absorbable toxic material such as a heavy metal.

HIATAL & PARAESOPHAGEAL HERNIA

Hiatal hernias (HHs) are classified into four types, encompassing both sliding hiatal hernias and paraesophageal hiatal hernias. Type I is a sliding hiatal hernia, in which the GE junction and a portion of the proximal stomach is displaced above the diaphragmatic hiatus. Sliding HHs are common, with a recent study showing a prevalence of nearly 21% of all EGD’s performed and a correlation between HHs and clinical symptoms of heartburn and regurgitation in children > 48 months. Paraesophageal hiatal hernias encompass types II, III, and IV of HHs, in which the esophagus and GE junction are in their normal anatomic position, but the gastric cardia is herniated through the diaphragmatic hiatus. In type II, the gastric fundus herniates alongside the thoracic esophagus while the GE junction remains within the abdomen. In type III there is some sliding of the GE junction up into the chest, thus is a hybrid of type I and II. In type IV there is herniation of other abdominal contents, such as colon, omentum, or spleen into the chest as well. Most hiatal hernias are acquired, with congenital paraesophageal hernias being rare in childhood. Patients may present with recurrent pulmonary infections, vomiting, anemia, failure to thrive, or dysphagia. The most common cause of acquired paraesophageal hernia is previous fundoplication surgery, though they have also been described following blunt abdominal trauma and EA/TEF repair. Following fundoplication, the degree of circumferential surgical dissection of the esophageal hiatus is the most important risk factor, with one prospective study demonstrating a reduction in the 5 year herniation rate from 36.5% to 12.2% with limited dissection.

Radiographic studies typically reveal a cystic mass in the posterior mediastinum or a dilated esophagus. The diagnosis is typically made with an upper GI series or a CT scan of the chest and abdomen, though diagnosis via ultrasound in the prenatal period has been reported. Presence of a ring in the lower esophagus on upper GI has been found to be associated with HH in 96% of children and should increase the index of suspicion. Recently, use of pH Impedance probe testing has been proposed as an effective method to identify HH in children, where inversion of the usual acid:nonacid reflux ratio to > 1.0 had a sensitivity of 93.8% and specificity of 79.6%. Treatment in symptomatic cases is generally surgical, with laparoscopic repair being used more commonly. Controversy exists about using biosynthetic mesh for repair, as it decreases the risk of recurrent hernia but also increases esophageal erosion in children. Fundoplication is generally indicated at the time of repair, as rates of significant GERD requiring surgical intervention have been reported as high as 60%.

PYLORIC STENOSIS

The cause of postnatal pyloric muscular hypertrophy with gastric outlet obstruction is unknown. The incidence is 1–8 per 1000 births, with a 4:1 male predominance. Recent studies suggest that erythromycin in the neonatal period is associated with a higher incidence of pyloric stenosis.

Clinical Findings

A. Symptoms and Signs

Projectile postprandial vomiting usually begins between 2 and 4 weeks of age but may start as late as 12 weeks. Vomiting starts at birth in about 10% of cases and onset of symptoms may be delayed in preterm infants. Vomitus is rarely bilious but may be blood-streaked. Infants are usually hungry and nurse avidly. The upper abdomen may be distended after feeding, and prominent gastric peristaltic waves from left to right may be seen. An oval mass, 5–15 mm in longest dimension can be felt on deep palpation in the right upper abdomen, especially after vomiting. This palpable “olive,” however, was only present in 13.6% of patients studied.

B. Laboratory Findings

Hypochloremic alkalosis with potassium depletion is the classic metabolic findings, though low chloride may be seen in as few as 23% and alkalosis in 14.4%. These findings may not be as common in younger infants and their absence should not dissuade from the diagnosis in the appropriate clinical setting. Dehydration causes elevated hemoglobin and hematocrit. Mild unconjugated bilirubinemia occurs in 2%–5% of cases.

C. Imaging

Ultrasonography shows a hypoechoic muscle ring greater than 4 mm thickness with a hyperdense center and a pyloric channel length greater than 15 mm. A barium upper GI series reveals retention of contrast in the stomach and a long narrow pyloric channel with a double track of barium. The hypertrophied muscle mass produces typical semilunar filling defects in the antrum. Infants presenting younger than 21 days may not fulfill these classic ultrasonographic criteria and may require clinical judgment to interpret “borderline” measures of pyloric muscle thickness.

Treatment & Prognosis

Pyloromyotomy is the treatment of choice and consists of incision down to the mucosa along the pyloric length. Treatment of dehydration and electrolyte imbalance is mandatory before surgical treatment, even if it takes 24–48 hours. Patients often vomit postoperatively as a consequence of gastritis, esophagitis, or associated GE reflux. The outlook after surgery is excellent, though patients may show as much as a four times greater risk for development of chronic abdominal pain of childhood.

GASTRIC & DUODENAL ULCER

General Considerations

Gastric and duodenal ulcers occur at any age. In the United States, most childhood gastric and duodenal ulcers are associated with underlying illness, toxins, or drugs such as NSAIDS that cause breakdown in mucosal defenses.

Worldwide, the most common cause of gastric and duodenal ulcer is mucosal infection with the bacterium H pylori. The prevalence of H Pylori infection varies greatly by country and increases with poor sanitation, crowded living conditions, and family exposure. Infection is thought to be acquired in childhood, but only in a small percentage of infected persons will infection lead to nodular gastritis, peptic ulcer, or in the case of long-standing infection, gastric lymphoid tumors and gastric adenocarcinoma. Some bacterial virulence factors have been identified, but the host and bacterial characteristics that contribute to disease progression are still largely unknown. In contrast to ulcers secondary to H pylori, non–H pylori ulcers tend to present at a younger age and are more likely to recur. In a large study of over 1000 children undergoing endoscopy, 5.4% had ulcers, with 47% of these due to H pylori, 16.5% related to NSAIDs, and 35.8% unrelated to either H pylori or NSAIDs. Recent evidence suggests that the prevalence of non–H pylori peptic ulcers is increasing.

Illnesses predisposing to secondary ulcers include central nervous system (CNS) disease, burns, sepsis, multiorgan system failure, chronic lung disease, Crohn disease (CrD), cirrhosis, and rheumatoid arthritis. The most common drugs causing secondary ulcers are aspirin, alcohol, and NSAIDs. NSAID use may lead to ulcers throughout the GI tract but most often in the stomach and duodenum. Severe ulcerative lesions in full-term neonates have been found to be associated with maternal antacid use in the last month of pregnancy.

Clinical Findings

A. Symptoms and Signs

In children younger than 6 years, vomiting and upper GI bleeding are the most common symptoms. Older children are more likely to complain of epigastric abdominal pain. Ulcers in the pyloric channel may cause gastric outlet obstruction. Chronic blood loss may cause iron-deficiency anemia. Deep penetration of the ulcer may erode into a mucosal arteriole and cause acute hemorrhage. Penetrating duodenal ulcers (especially common during cancer chemotherapy, immunosuppression, and in the intensive care setting) may perforate the duodenal wall, resulting in peritonitis or abscess.

B. Diagnostic Studies

Upper GI endoscopy is the most accurate diagnostic examination. The typical endoscopic appearance of an ulcer is a white exudative base with erythematous margins (Figure 21–4). Histopathologic assessment of biopsies obtained at endoscopy provides the opportunity to distinguish between different causes of ulcer disease, including H pylori infection, eosinophilic GI disease, celiac disease (CD), and Crohn disease. Endoscopic diagnosis of active H pylori infection may be achieved by histologic examination of gastric biopsies or measurement of urease activity on gastric tissue specimens. Additional noninvasive methods of diagnosis of active H pylori infection include evaluation of breath for radiolabeled carbon dioxide after administration of radiolabeled urea by mouth and detection of H pylori antigen in the stool. False-negative results for the latter two tests have been described when the patient is taking a PPI. Serum antibodies against H pylori have poor sensitivity and specificity, and do not prove that there is active infection or that treatment is needed. For severe or recurrent ulcerations not caused by H pylori, stress, or medications, a serum gastrin level may be considered to evaluate for a gastrin-secreting tumor (Zollinger-Ellison syndrome), though mild to moderate elevation in gastrin levels can be seen with use of PPI drugs. Upper GI barium radiographs may show an ulcer crater. Radiologic signs suggestive of peptic disease in adults (duodenal spasticity and thick irregular folds) are not reliable indicators in children.

Treatment

Treatment of symptomatic H pylori infection requires eradication of the organism, a goal that remains elusive in children. The optimal medical regimen is still undetermined. Standard first-line triple therapy for eradication of H pylori has traditionally been a 7–10 day treatment course involving simultaneous use two oral antibiotics (most commonly, amoxicillin and clarithromycin) and PPI. However, rising rates of resistance to clarithromycin have rendered this combination ineffective in certain parts of the world. As a result, alternative combinations of antimicrobials (metronidazole and tetracycline) have been evaluated. The addition of bismuth to two antibiotics and PPI (bismuth quadruple therapy) may increase efficacy. Because resistance to antibiotics varies greatly by country, regional antibiotic resistance patterns for H pylori should be a guide in selecting initial therapy. Antimicrobial susceptibility testing can be performed on gastric biopsy specimens using a variety of techniques. Test of cure can be achieved by either the urease breath test or fecal H pylori antigen test.

CONGENITAL DIAPHRAGMATIC HERNIA

Herniation of abdominal contents through the diaphragm usually occurs through a posterolateral defect involving the left side of the diaphragm (foramen of Bochdalek). In about 9% of cases, the diaphragmatic defect is retrosternal (foramen of Morgagni). In eventration of the diaphragm, a subtype of CDH, a leaf of the diaphragm with hypoplastic muscular elements balloons into the chest and is asymptomatic or leads to milder symptoms. Hernias result from failure of the embryologic diaphragmatic anlagen to fuse and divide the thoracic and abdominal cavities at 8–10 weeks’ gestation. The herniation of abdominal contents into the thoracic cavity can lead to pulmonary hypoplasia and significant cardiovascular dysfunction after birth, in particular severe persistent pulmonary hypertension.

Diagnosis of CDH is typically made prenatally by ultrasound. Associated congenital malformations, most commonly cardiovascular, may be detected prenatally. With the advent of improved care of the immediate complication of cardiopulmonary disease in the newborn period, including the use of inhaled nitric oxide, high-frequency oscillatory ventilation, and extracorporeal membrane oxygenation, survival has improved for infants with CDH and is as high as 70%–90% in some centers. Antenatal intervention with fetal tracheal occlusion may improve survival in CDH associated with severe pulmonary hypoplasia. Operative repair of the diaphragmatic defect is usually performed in the newborn period once cardiopulmonary stabilization is achieved, with increasing utilization of laparoscopic and thoracoscopic minimally invasive approaches. Long-term health issues in CDH survivors include chronic pulmonary disease, pulmonary hypertension, neurodevelopmental delays, hearing loss, and GER.

CONGENITAL DUODENAL OBSTRUCTION

General Considerations

Obstruction is generally classified into intrinsic and extrinsic causes, although rare cases of simultaneous intrinsic and extrinsic anomalies have been reported.

Etiologies of extrinsic duodenal obstruction include congenital peritoneal bands associated with intestinal malrotation, annular pancreas, or duodenal duplication. Intrinsic duodenal obstruction is more common and is typically associated with congenital atresia, stenosis, or mucosal webs (so-called “wind sock deformity”). In about two-thirds of patients with congenital duodenal obstruction, there are other associated anomalies.

Imaging Studies

Diagnosis of congenital duodenal obstructions is often made prenatally by ultrasound. Prenatal diagnosis predicts complete obstruction in 77% of cases and is associated with polyhydramnios, prematurity, and higher risk of maternal-fetal complications. Presence of a “double bubble” on ultrasound and an echogenic band in the second portion of the duodenum are 100% sensitive and specific for an annular pancreas. Postnatal abdominal plain radiographs show gaseous distention of the stomach and proximal duodenum (the “double-bubble” radiologic sign). With protracted vomiting, there is less air in the stomach and less abdominal distention. Absence of distal intestinal gas suggests atresia or severe extrinsic obstruction, whereas a pattern of intestinal air scattered over the lower abdomen may indicate partial duodenal obstruction. Barium enema may be helpful in determining the presence of malrotation or atresia in the lower GI tract, as well as evaluating for radiographic evidence of Hirschsprung disease, which may also present with abdominal distension and vomiting.

Clinical Findings

A. Duodenal Atresia

Maternal polyhydramnios is common and often leads to prenatal diagnosis by ultrasonography. Vomiting (usually bile-stained) and epigastric distention begin within a few hours of birth. Meconium may be passed normally. Duodenal atresia is often associated with other congenital anomalies (30%), including esophageal atresia, intestinal atresias, and cardiac and renal anomalies. Preterm birth (25%–50%) and Down syndrome (20%–30%) are also associated with duodenal atresia.

B. Duodenal Stenosis

In this condition, duodenal obstruction is not complete. Onset of obvious obstructive symptoms may be delayed for weeks or years. Although the stenotic area is usually distal to the ampulla of Vater, the vomitus does not always contain bile. Duodenal stenosis or atresia is the most common GI tract malformation in children with Down syndrome, occurring in 3.9%.

C. Annular Pancreas

Annular pancreas is a rotational defect in which normal fusion of the dorsal and ventral pancreatic anlagen does not occur, and a ring of pancreatic tissue encircles the duodenum. The presenting symptom is duodenal obstruction. Down syndrome and congenital anomalies of the GI tract occur frequently. Polyhydramnios is common. Symptoms may develop late in childhood or even in adulthood if the obstruction is not complete in infancy. Treatment consists of duodenoduodenostomy or duodenojejunostomy without operative dissection or division of the pancreatic annulus. Pancreatic function is normal.

Treatment & Prognosis

In almost all settings, surgical intervention (either laparoscopic or open) is required for congenital duodenal obstructive lesions. Typically, duodenoduodenostomy is performed to bypass the area of stenosis or atresia. For duodenal stenoses, however, there have been isolated reports of successful endoscopic treatment with balloon dilation. Thorough surgical exploration is typically done to ensure that no lower GI tract anomalies are present. More recent reports document the safety and utility of a laparoscopic approach. The mortality rate is increased in infants with preterm birth, Down syndrome, and associated congenital anomalies. Duodenal dilation and hypomotility from antenatal obstruction may cause duodenal dysmotility with obstructive symptoms even after surgical treatment. Placement of transanastomotic feeding tubes at the time of the initial repair has been found to result in more rapid progression to full enteral feeds and decreased need for parenteral nutrition (PN). The overall prognosis for these patients is good, with the majority of their mortality risk due to associated anomalies other than duodenal obstruction.

INTESTINAL ATRESIA & STENOSIS

Excluding anal anomalies, intestinal atresia or stenosis accounts for one-third of all cases of neonatal intestinal obstruction (see Chapter 2). Antenatal ultrasound can identify intestinal atresia in utero; polyhydramnios occurs in most affected pregnancies. Sensitivity of antenatal ultrasound is greater in more proximal atresias. Other congenital anomalies may be present in up to 54% of cases and 52% are delivered preterm. In apparently isolated atresia cases, occult congenital cardiac anomalies have been reported in as many as 30%. In one large population-based study, the prevalence was 2.9 per 10,000 births, although there is some evidence that the prevalence may be increasing. The localization and relative incidence of atresias and stenoses are listed in Table 21–1. Although jejunal and ileal atresias are often grouped together, there are data to suggest that jejunal atresias are associated with increased morbidity and mortality compared to ileal atresia. These differences may be related to increased compliance of the jejunal wall, resulting in more proximal dilation and subsequent loss in peristaltic activity.

Bile-stained vomiting and abdominal distention begin in the first 48 hours of life. Multiple sites in the intestine may be affected and the overall length of the small intestine may be significantly shortened. Radiographic features include dilated loops of small bowel and absence of colonic gas. Barium enema reveals narrow-caliber microcolon because of lack of intestinal flow distal to the atresia. In over 10% of patients with intestinal atresia, the mesentery is absent and the superior mesenteric artery (SMA) cannot be identified beyond the origin of the right colic and ileocolic arteries. The ileum coils around one of these two arteries, giving rise to the so-called Christmas tree deformity on contrast radiographs. The tenuous blood supply often compromises surgical anastomoses. The differential diagnosis of intestinal atresia includes Hirschsprung disease, paralytic ileus secondary to sepsis, midgut volvulus, and meconium ileus. Surgery is mandatory. Postoperative complications include short bowel syndrome (SBS) in 15% and small bowel hypomotility secondary to antenatal obstruction. Overall mortality has been reported at 8%, with increased risk in low-birth-weight and premature infants.

INTESTINAL MALROTATION

General Considerations

The midgut extends from the duodenojejunal junction to the mid-transverse colon. It is supplied by the SMA, which runs in the root of the mesentery. During gestation, the midgut elongates into the umbilical sac, returning to an intra-abdominal position during the 10th week of gestation. The root of the mesentery rotates in a counterclockwise direction during retraction causing the colon to cross the abdominal cavity ventrally. The cecum moves from the left to the right lower quadrant, and the duodenum crosses dorsally becoming partly retroperitoneal. When rotation is incomplete, the dorsal fixation of the mesentery is defective and shortened, so that the bowel from the ligament of Treitz to the mid-transverse colon may rotate around its narrow mesenteric root and occlude the SMA (volvulus). From autopsy studies it is estimated that up to 1% of the general population may have intestinal malrotation, which is diagnosed in the first year of life in 70%–90% of patients.

Clinical Findings

A. Symptoms and Signs

Malrotation with volvulus accounts for 10% of neonatal intestinal obstructions. Most infants present in the first 3 weeks of life with bile-stained vomiting or with overt small bowel obstruction. Intrauterine volvulus may cause intestinal obstruction or perforation at birth. The neonate may present with ascites or meconium peritonitis. Later presenting signs include intermittent intestinal obstruction, malabsorption, protein-losing enteropathy, or diarrhea. Associated congenital anomalies, especially cardiac, occur in over 25% of symptomatic patients. Many of these may be found in a subgroup of malrotation patients with heterotaxy syndromes, with associated asplenia or polysplenia. Older children and adults with undiagnosed malrotation typically present with chronic GI symptoms of nausea, vomiting, diarrhea, abdominal pain, dyspepsia, bloating, and early satiety.

B. Imaging

An upper GI series is considered the gold standard for diagnosis, with a reported sensitivity of 96%, and classically shows the duodenojejunal junction and the jejunum on the right side of the spine. The diagnosis of malrotation can be further confirmed by barium enema, which may demonstrate a mobile cecum located in the midline, right upper quadrant, or left abdomen. Plain films of the abdomen in the newborn period may show a “double-bubble” sign, resulting in a misdiagnosis of duodenal atresia. CT scan and ultrasound of the abdomen may be used to make the diagnosis as well and are characterized by the “whirlpool sign” denoting midgut volvulus. Reversal of the normal position of the SMA and superior mesenteric vein (SMV) may be seen in malrotation, though normal position may be found in up to 29% of patients. Identification of the third portion of the duodenum within the retroperitoneum makes malrotation very unlikely.

Treatment & Prognosis

Surgical treatment of malrotation is the Ladd procedure. In young infants the Ladd procedure should be performed even if volvulus has not occurred. The duodenum is mobilized, the short mesenteric root is extended, and the bowel is then fixed in a more normal distribution. Treatment of malrotation discovered in children older than 12 months is uncertain. Because volvulus can occur at any age, surgical repair is usually recommended, even in asymptomatic children. Laparoscopic repair of malrotation is possible but is technically difficult and is never performed in the presence of volvulus.

Midgut volvulus is a surgical emergency. Bowel necrosis results from occlusion of the SMA. When necrosis is extensive, it is recommended that a first operation include only reduction of the volvulus with lysis of mesenteric bands. Resection of necrotic bowel should be delayed if possible until a second-look operation 24–48 hours later can be undertaken in the hope that more bowel can be salvaged. The prognosis is guarded if perforation, peritonitis, or extensive intestinal necrosis is present. Mid-gut volvulus is one of the most common indications for small bowel transplant in children, responsible for 10% of cases in a recent series.

SHORT BOWEL SYNDROME

General Considerations

Short bowel syndrome (SBS) is defined as a condition resulting from reduced intestinal absorptive surface that leads to alteration in intestinal function that compromises normal growth, fluid/electrolyte balance, or hydration status. The vast majority of pediatric patients with SBS have undergone neonatal surgical resection of intestine. The most common etiologies in children are necrotizing enterocolitis (45%); intestinal atresias (23%); gastroschisis (15%); volvulus (15%); and, less commonly, congenital short bowel, long-segment Hirschsprung disease, and ischemic bowel. In many instances, infants with SBS require PN in order to provide adequate caloric, fluid, and electrolyte delivery in the setting of insufficient intestinal absorptive function. The requirement of supplemental PN for more than 2–3 months in the setting of SBS or any other underlying disorder qualifies the diagnosis of intestinal failure (IF).

The goal in management of the patient with SBS is to promote growth and adaptation of the intestine such that adequate nutrition can be delivered and absorbed enterally. Many factors, including patient’s gestational age, postsurgical anatomy (including residual small bowel length and presence of ileocecal valve and/or colon), presence of small bowel bacterial overgrowth, and underlying surgical disease, influence the process and likelihood of bowel adaptation and achievement of enteral autonomy. No specific anatomic bowel length measurements offer 100% certainty in predicting clinical outcomes in SBS.

Symptoms & Signs

Typical signs for the patient with SBS are related to their underlying malabsorptive state, including diarrhea, dehydration, electrolyte or micronutrient deficiency states, and growth failure. Patients with SBS are also at risk for small bowel obstruction, bowel dilation and dysmotility (with secondary small bowel bacterial overgrowth), hepatobiliary disorders including cholelithiasis, nephrolithiasis due to calcium oxalate stones, oral feeding challenges, and GI mucosal inflammatory problems including noninfectious colitis and anastomotic ulcerations. For patients with IF, complications related to underlying PN therapy are common and can be life threatening. PN-associated liver disease (PNALD) is a progressive cholestatic liver injury that occurs in pediatric patients on PN and may progress to end-stage liver disease in 10% of affected patients. Recurrent catheter-related bloodstream infections are relatively common in pediatric patients with SBS and IF. Other complication-related central venous catheters including occlusions may require intervention.

Treatment & Prognosis

Goal in management of SBS is to promote growth and adaptation while minimizing and/or treating complications of the underlying intestinal disorder or PN therapy. Intestinal rehabilitation for the child with SBS and IF refers to the multidisciplinary team approach to individual patient care, involving gastroenterology, nutrition, and surgery, and has been shown to improve outcomes. Enteral nutrition should be catered to favor absorption, commonly requiring continuous delivery of an elemental formula through a gastrostomy tube. Commonly prescribed pharmacologic adjuncts include acid suppressive therapy, antimotility and antidiarrheal agents, and antibiotics for the treatment of small bowel bacterial overgrowth. Recently, a glucagon-like peptide-2 analog (teduglutide) has been approved for use in pediatric patients, having been shown to reduce the volume of PN prescribed in patients with IF/SBS. This therapy offers the potential to accelerate intestinal adaptation and PN weaning.

Management for the patient with SBS and IF should include strategies to manage or prevent complications related to PN therapy, including infection and liver disease. Antimicrobial lock solutions distilled into central venous catheters using either ethanol or antibiotics may have a role in reducing infection rates. Compelling evidence over the past several years suggests that modification of parenteral lipid solution, either through reduction in dose of soy-based intralipid or replacement with a third-generation lipid solution (Omegaven or SMOF lipid), improves outcomes associated with PNALD in pediatric patients.

Autologous bowel reconstructive surgery (bowel lengthening) should be considered in a patient who is failing to advance enterally and has anatomy amendable to surgical intervention, typically with regards to adequate bowel dilation. Both the serial transverse enteroplasty (STEP) procedure and longitudinal intestinal lengthening and tailoring (Bianchi) procedure have been successful in allowing weaning from TPN in up to 50% of patients in reported series. In recent years, the STEP procedure has gained favor as being potentially less technically demanding and repeatable, if the bowel dilates sufficiently after the initial procedure.

When medical, nutritional, and surgical managements fail, intestinal transplantation may be considered for a child with refractory and life-threatening complications of IF. Current outcome data after pediatric intestinal transplantation suggest 1- and 3-year survival rates of 83% and 60%, respectively.

INTUSSUSCEPTION

Intussusception is the invagination of one segment of intestine into another. Intussusception can occur anywhere along the small and large bowel and usually starts just proximal to the ileo-cecal valve and extends for varying distances into the colon. It is the most frequent cause of intestinal obstruction in the first 2 years of life and three times more common in males. Symptoms related to obstruction and ischemia are due to swelling, hemorrhage, vascular compromise, and necrosis of the intussuscepted ileum. In 85% of cases the cause is idiopathic but the likelihood of identifying a cause of intussusception increases with the age of the patient. Implicated primary causes of intussusception include small bowel polyp, Meckel diverticulum, omphalomesenteric remnant, duplication, lymphoma, lipoma, parasites, foreign bodies, and viral enteritis with hypertrophy of Peyer patches. Intussusception of the small bowel can also be seen in celiac disease, cystic fibrosis, and Henoch-Schönlein purpura. In children older than 6 years, lymphoma is the most common cause of intussusception.

Clinical Findings

Classically, a previously healthy infant 3–12 months of age develops recurring paroxysms of abdominal pain with screaming and drawing up of the knees. Vomiting and diarrhea occur soon afterward (90% of cases), and bloody bowel movements with mucus appear within the next 12 hours (50%). The child is characteristically lethargic between paroxysms and may be febrile. The abdomen is tender and often distended. A sausage-shaped mass may be palpated, usually in the upper mid abdomen. In older children, sudden attacks of abdominal pain may be related to chronic recurrent intussusception with spontaneous reduction.

Diagnosis & Treatment

The constellation of abdominal pain, lethargy, vomiting, and a suspicious abdominal radiograph was found to have a sensitivity of 95% in identifying intussusceptions in children. Abdominal radiographs alone, however, are poorly sensitive for the diagnosis of intussusception. Abdominal ultrasound carries sensitivity for diagnosis of intussusception of 98%–100%. Barium enema and air enema are both diagnostic and therapeutic. Reduction of the intussusception by barium enema should not be attempted if signs of strangulated bowel, perforation, or toxicity are present. Air insufflation of the colon under fluoroscopic guidance is a safe alternative to barium enema that has excellent diagnostic sensitivity and specificity without the risk of contaminating the abdominal cavity with barium. Rates of successful reduction by air enema approach 75%. When initial enema reduction is successful, recurrence of intussusception within 24–48 hours occurs in less than 5% of patients. The rate of perforation with either liquid or air enema is approximately 1%. Care is required in patient selection for either air or barium enema because if ischemic damage to the intestine is suspected based on symptom severity (shock or sepsis), the risk of perforation increases and surgical reduction is preferred. Surgery is thus required for extremely ill patients, in patients with evidence of bowel perforation, or in those in whom hydrostatic or pneumatic reduction has been unsuccessful (25%). Surgery has the advantage of identifying a lead point such as Meckel diverticulum, lymphoma, or small bowel polyp. Surgical reduction of intussusception is associated with a lower recurrence rate than pneumatic reduction.

Prognosis

The likelihood of successful reduction by enema decreases if symptom duration is greater than 24 hours. Of those requiring surgical reduction, the risk of subsequent bowel resection increased from 17% to 39% in patients with symptoms greater than 24 hours. Overall mortality rate with treatment is 1%–2%.

INGUINAL HERNIA

Inguinal hernias may present at any age, are most often indirect, and occur more frequently (9:1) in boys. The incidence in preterm male infants is close to 5% and is reported in 30% of male infants weighing 1000 g or less.

Clinical Findings

In most cases, a hernia is a painless inguinal swelling. Parents may be the only one to see the mass, as it may retract when the infant is active, cold, frightened, or agitated. A history of inguinal fullness associated with coughing or long periods of standing, or presence of a firm, globular, and tender swelling, sometimes associated with vomiting and abdominal distention are clinical clues. In some instances, a herniated loop of intestine may become partially obstructed leading to severe pain. Rarely, bowel becomes trapped in the hernia sac, and complete intestinal obstruction occurs. Gangrene of the hernia contents or testis may occur. In girls, the ovary may prolapse into the hernia sac presenting as a mass below the inguinal ligament. A suggestive history often is the only criterion for diagnosis, along with the “silk glove” feel of the rubbing together of the two walls of the empty hernia sac.

Differential Diagnosis

Inguinal lymph nodes may be mistaken for a hernia. Nodes are usually multiple with more discrete borders. A hydrocele of the cord should transilluminate. An undescended testis is usually mobile in the canal and is associated with absence of the gonad in the scrotum.

Treatment

Incarceration of an inguinal hernia is more likely to occur in boys and in children younger than 10 months. Manual reduction of incarcerated inguinal hernias can be attempted after the sedated infant is placed in the Trendelenburg position with an ice bag on the affected side. Manual reduction is contraindicated if incarceration has been present for more than 12 hours or if bloody stools are noted. Surgery is indicated if a hernia has ever incarcerated. Hydroceles frequently resolve by age 2 years.

UMBILICAL HERNIA

Umbilical hernias are more common in full-term, African-American infants. Small bowel may incarcerate in small-diameter umbilical hernias. Most umbilical hernias regress spontaneously if the fascial defect has a diameter of less than 1 cm. Hernias persisting after age 4 years should be treated surgically.

PATENT OMPHALOMESENTERIC DUCT

The omphalomesenteric duct connects the fetal yolk sac to the developing gut. This duct is usually obliterated early in embryologic development, but failure of this process can lead to a variety of structures that originate from the embryonic duct remnant connecting the ileum to the undersurface of the umbilicus. If the remnant is patent, it can lead to herniation of intestinal contents into the umbilical cord or lead to fecal discharge from the umbilicus. A fibrous cord may become the focal point for volvulus and resulting intestinal obstruction. Mucoid umbilical discharge may indicate a mucocele in the omphalomesenteric remnant with an opening at the umbilicus. A closed mucocele may protrude through the umbilicus and appear as a polypoid mass that may be mistaken for an umbilical granuloma because it is firm and bright red. Surgical excision of omphalomesenteric remnants is indicated. Ultrasound examination or abdominal computed tomography (CT) can help confirm the diagnosis of an omphalomesenteric duct remnant.

MECKEL DIVERTICULUM

Meckel diverticulum is the most common form of omphalomesenteric duct remnant. It occurs in 1.5% of the population and in the majority of cases causes no symptoms. If complications occur, they are three times more common in males than in females. More than 50% of complications occur in the first 2 years of life.

Clinical Findings

A. Symptoms and Signs

Forty to 60% of symptomatic patients have painless episodes of maroon or melanotic rectal bleeding. Bleeding is due to deep ileal ulcers adjacent to the diverticulum caused by acid secreted by heterotopic gastric tissue and may be voluminous enough to cause shock and anemia. Occult bleeding is less common. Intestinal obstruction occurs in 25% of symptomatic patients as a result of ileocolonic intussusception. Intestinal volvulus may occur around a fibrous remnant of the vitelline duct extending from the tip of the diverticulum to the abdominal wall. Meckel diverticula may be trapped in an inguinal hernia.

B. Imaging

Diagnosis of Meckel diverticulum is made with a Meckel scan. Technetium-99m (^99mTc)-pertechnetate is taken up by the heterotopic gastric mucosa in the diverticulum and outlines the diverticulum on a nuclear scan. Giving pentagastrin or cimetidine before administering the radionuclide increases ^99mTc-pertechnetate uptake and retention by the heterotopic gastric mucosa, and can increase the sensitivity of the test.

Treatment & Prognosis

Treatment is surgical and the prognosis for Meckel diverticulum is good.

ACUTE APPENDICITIS

General Considerations

Acute appendicitis is the most common indication for emergency abdominal surgery in childhood. The frequency increases with age and peaks between 15 and 30 years. Obstruction of the appendix by fecalith (25%) is a common predisposing factor. Parasites may rarely cause obstruction (especially ascarids). Most of the remaining cases are idiopathic. The incidence of perforation is high in childhood (40%), especially in children younger than 2 years, in whom pain is often poorly localized and symptoms nonspecific. To avoid delay in diagnosis, it is important to maintain close communication with parents and perform a thorough initial physical examination with sequential examinations at frequent intervals over several hours to correctly interpret the evolving symptoms and signs.

Clinical Findings

A. Symptoms and Signs

Typical patients have fever and periumbilical abdominal pain, which then localizes to the right lower quadrant with signs of peritoneal irritation. Anorexia, vomiting, constipation, and diarrhea also occur. Contrary to the vomiting of acute gastroenteritis, which usually precedes abdominal pain, vomiting in appendicitis usually follows the onset of pain and is often bilious. The clinical picture is frequently atypical, especially in young children and infants. A rectal examination may clarify the site of tenderness or reveal a localized appendiceal mass. Serial examinations are critical in differentiating appendicitis from the many other conditions that transiently mimic its symptoms.

B. Laboratory Findings

The white blood cell count is seldom higher than 15,000/μL. Pyuria, fecal leukocytes, and guaiac-positive stool are sometimes present. The combination of elevated C-reactive protein (CRP) and leukocytosis has been reported to have positive predictive value of 92% for acute appendicitis, although having normal values for both measures does not exclude the diagnosis.

C. Imaging

A radio-opaque fecalith reportedly is present in two-thirds of cases of ruptured appendix. In experienced hands, ultrasonography of the appendix shows a noncompressible, thickened appendix in 93% of cases. Abdominal CT after rectal instillation of contrast with thin cuts in the area of the appendix may be diagnostic. An otherwise normal abdominal CT scan with a nonvisualized appendix has still been reported to have a negative predictive value of 99%. Analysis of diagnostic strategies for pediatric patients with suspected appendicitis has shown abdominal ultrasound, followed by CT scan for negative studies, to be the most cost-effective diagnostic approach compared to CT or ultrasound alone.

Differential Diagnosis

Pneumonia, pleural effusion, urinary tract infection, right-sided kidney stone, cholecystitis, perihepatitis, and pelvic inflammatory disease may mimic appendicitis. Acute gastroenteritis with Yersinia enterocolitica may present as pseudoappendicitis in 17% of cases. Other medical and surgical conditions causing acute abdomen should also be considered (see Table 21–7).

Treatment & Prognosis

Exploratory laparotomy or laparoscopy is indicated when the diagnosis of acute appendicitis cannot be ruled out after a period of close observation. Postoperative antibiotic therapy is reserved for patients with gangrenous or perforated appendix. The mortality rate is less than 1% during childhood, despite the high incidence of perforation. In uncomplicated nonruptured appendicitis, a laparoscopic approach is associated with a shortened hospital stay.

DUPLICATIONS OF THE GASTROINTESTINAL TRACT

Enteric duplications are congenital spherical or tubular structures found most commonly in the ileum but can also be found in the duodenum, rectum, and esophagus. Most duplications do not communicate with the intestinal lumen. Some duplications (neuroenteric cysts) are attached to the spinal cord and are associated with hemivertebrae and anterior or posterior spina bifida. Symptoms of vomiting, abdominal distention, colicky pain, rectal bleeding, partial or total intestinal obstruction, or an abdominal mass may start in infancy. Diarrhea and malabsorption may result from bacterial overgrowth in communicating duplications. Physical examination may reveal a rounded, smooth, movable mass, and barium radiograph or CT of the abdomen may show a noncalcified cystic mass displacing other organs. ^99mTc-pertechnetate scan may help identify duplications containing gastric mucosa. Duplications of the ileum can give rise to an intussusception. Prompt surgical treatment is indicated.

CONGENITAL AGANGLIONIC MEGACOLON (HIRSCHSPRUNG DISEASE)

General Considerations

Hirschsprung disease results from an absence of ganglion cells in the mucosal and muscular layers of the colon. Neural crest cells fail to migrate into the gut mesodermal layers during gestation, possibly secondary to abnormal end-organ cell surface receptors or local deficiency of nitric oxide synthesis. Ganglion cell absence results in failure of the colonic muscles to relax in front of an advancing bolus. In 80% of individuals, aganglionosis is restricted to the rectosigmoid colon (short-segment disease); in 15%–20%, aganglionosis extends proximal to the sigmoid colon (long-segment disease); in about 5%, aganglionosis affects the entire large intestine (total colonic aganglionosis). Segmental aganglionosis is possible but rare.

Aganglionic segments have normal or slightly narrowed caliber with dilation of the normal colon proximal to the obstructing aganglionic segment. The mucosa of the dilated colonic segment may become thin and inflamed, causing diarrhea, bleeding, and protein loss (enterocolitis).

A familial pattern has been described, particularly in total colonic aganglionosis. The incidence of Hirschsprung disease is 1 in 5000 live births; it is four times more common in boys than girls. A chromosomal abnormality is present in approximately 12% of individuals with Hirschsprung disease. Mutations in the ret proto-oncogene have been identified in about 15% of nonsyndromic cases. The most common chromosomal abnormality associated with Hirschsprung disease is Down syndrome; 2%–10% of all individuals with Down syndrome may have Hirschsprung disease.

Clinical Findings

A. Symptoms and Signs

Failure of the newborn to pass meconium, followed by vomiting, abdominal distention, and reluctance to feed suggest the diagnosis of Hirschsprung disease. Most children with Hirschsprung disease do not pass stool in the first 24 hours of their life. Enterocolitis manifested by fever, explosive diarrhea, and prostration is reported in approximately 50% of affected newborns. Enterocolitis may lead to inflammatory and ischemic changes in the colon, with perforation and sepsis. In some patients, especially those with short segments involved, symptoms are not obvious at birth. In later infancy, alternating obstipation and diarrhea predominate. The older child is more likely to have constipation alone. Symptoms can include foul-smelling or ribbon-like stools, a distended abdomen with prominent veins and visible peristaltic waves with palpable fecal masses. Intermittent bouts of intestinal obstruction, hypoproteinemia, and failure to thrive are common. Encopresis is rare. On digital rectal examination, the anal canal and rectum are devoid of fecal material despite obvious retained stool on abdominal examination or radiographs. If the aganglionic segment is short, there may be a gush of flatus and stool as the finger is withdrawn. Infants of diabetic mothers may have similar symptoms, and in this setting small left colon syndrome should be suspected. Meglumine diatrizoate (Gastrografin) enema is both diagnostic and therapeutic in small left colon syndrome as it reveals a meconium plug in the left colon, which is often passed during the diagnostic radiograph. The left colon is narrow but usually functional.

B. Laboratory Findings

On rectal suction biopsy samples, ganglion cells are absent in both the submucosal and muscular layers of involved bowel. Special stains may show nerve trunk hypertrophy and increased acetylcholinesterase activity. Ganglionated bowel above the aganglionic segment is sometimes found to contain more than normal numbers of ganglion cells in abnormal locations (neuronal dysplasia).

C. Imaging

Plain abdominal radiographs may reveal dilated proximal colon and absence of gas in the pelvic colon. Barium enema using a catheter without a balloon and with the tip inserted barely beyond the anal sphincter usually demonstrates a narrow distal segment with a sharp transition to the proximal dilated (normal) colon. Transition zones may not be seen in neonates since the normal proximal bowel has not had time to become dilated. Retention of barium for 24–48 hours is not diagnostic of Hirschsprung disease in older children as it typically occurs in retentive constipation as well.

D. Special Examinations

Rectal manometric testing reveals failure of rectoanal inhibitory reflex (RAIR), relaxation of the internal anal sphincter after distention of the rectum in all patients with Hirschsprung disease, regardless of the length of the aganglionic segment. In some patients, a nonrelaxing internal anal sphincter is the only abnormality. This condition is often called “ultrashort segment Hirschsprung disease.”

Differential Diagnosis

Hirschsprung disease accounts for 15%–20% of cases of neonatal intestinal obstruction. It must be differentiated from the small left colon syndrome by biopsy. In childhood, Hirschsprung disease must be differentiated from retentive constipation, hypothyroidism, intestinal pseudo-obstruction, and other motility disorders. In older infants and children, it can also be confused with CD because of the striking abdominal distention and failure to thrive.

Treatment & Prognosis

Treatment is surgical. Depending on the child’s size and state of health, a diverting colostomy (or ileostomy) may be performed or the surgeon may undertake a primary repair. In unstable infants, resection of the aganglionic segment may be postponed. At the time of definitive surgery, the transition zone between ganglionated and nonganglionated bowel is identified. Aganglionic bowel is resected, and a pull-through of ganglionated bowel to the preanal rectal remnant is made. In children with ultrashort segment disease, an internal anal sphincter myotomy, or botulinum toxin injection of the internal anal sphincter may control symptoms.

Complications after surgery include fecal retention, fecal incontinence, anastomotic breakdown, or anastomotic stricture. Postoperative obstruction may result from inadvertent retention of a distal aganglionic colon segment or postoperative destruction of ganglion cells secondary to vascular impairment. Neuronal dysplasia of the remaining bowel may produce a pseudo-obstruction syndrome. Enterocolitis occurs postoperatively in 15% of patients. Recent studies have shown that patients even after surgical correction have an altered microbiome; the role this may play in enterocolitis or other long-term issues for children is still under investigation.

CONSTIPATION

Chronic constipation in childhood is defined as two or more of the following characteristics for 2 months: (1) fewer than three bowel movements per week; (2) more than one episode of encopresis per week; (3) impaction of the rectum with stool; (4) passage of stool so large it obstructs the toilet; (5) retentive posturing and fecal withholding; and (6) pain with defecation. Retention of feces in the rectum can result in overflow incontinence (encopresis) in 60% of children with constipation. Most constipation in childhood is a result of voluntary or involuntary retentive behavior (chronic retentive constipation). About 2% of healthy primary school children have chronic retentive constipation. The ratio of males to females may be as high as 4:1.

Clinical Findings

Infants younger than 3 months often grunt, strain, and turn red in the face while passing normal stools. Failure to appreciate this normal developmental pattern may lead to the unwise use of laxatives or rectal stimulation. Infants and children may, however, develop the ability to ignore the sensation of rectal fullness and retain stool. Many factors reinforce this behavior, which results in impaction of the rectum and overflow incontinence. Among these are painful defecation; skeletal muscle weakness; psychological issues, especially those relating to control and authority; modesty and distaste for school bathrooms; medications; and other factors listed in Table 21–2. The dilated rectum gradually becomes less sensitive to fullness, thus perpetuating the problem.

Differential Diagnosis

One must distinguish between chronic retentive constipation from Hirschsprung disease as summarized in Table 21–3.

Treatment

In children with poor diets increased intake of high-residue foods such as bran, whole wheat, fruits and vegetables, and water may be sufficient therapy in mild constipation. If diet change alone is ineffective, medications may be required. Polyethylene glycol solution (MiraLax^TM), 0.8–1 g/kg/day, lactulose 1–2 g/kg/day, and milk of magnesia for 2–5 years old: 400–1200 mg/day, 6–11 years old: 1200–2400 mg/day are safe stool softeners in infants and children. Stimulant laxatives such as Senna or Bisacodyl can be considered as an additional or second-line treatment. A recent study showed lubiprostone was efficacious and well tolerated in children and adolescents with functional constipation. Lubiprostone is a prostone that, acting locally as a specific activator of chloride channel protein-2 in the GI epithelium, promotes intestinal secretion of chloride ions and fluid, enhancing GI motility. If encopresis is present, treatment should start with relieving fecal impaction. Disimpaction can be achieved in several ways, including medications such as saline enemas, and nonabsorbable osmotic agents such as polyethylene glycol, (1 g/kg/day) and milk of magnesia (1–2 mL/kg/day). Effective stool softeners should thereafter be given regularly in doses sufficient to induce very soft daily bowel movements. After several weeks to months of regular soft stools, stool softeners can be tapered and stopped. Mineral oil should not be given to nonambulatory infants, physically handicapped or bed-bound children, or any child with GE reflux. Aspiration of mineral oil may cause lipid pneumonia. Recurrence of encopresis is common and should be treated promptly with a short course of stimulant laxatives or an enema. Psychiatric consultation may be indicated for patients with resistant symptoms or severe emotional disturbances.

ANAL FISSURE

Anal fissure is a slit-like tear in the squamous epithelium of the anus, which usually occurs secondary to the passage of large, hard fecal masses, typically at the superior and inferior aspects of the anus. Anal stenosis, anal crypt abscess, and trauma can be contributory factors. Sexual abuse must be considered in children with large, irregular, or multiple anal fissures. Anal fissures may be the presenting sign of Crohn disease in older children.

The infant or child with anal fissure typically cries with defecation and will try to hold back stools. Sparse, bright red bleeding is seen on the outside of the stool or on the toilet tissue following defecation. The fissure can often be seen if the patient is examined in a knee-chest position with the buttocks spread apart. When a fissure cannot be identified, it is essential to rule out other causes of rectal bleeding such as juvenile polyp, perianal inflammation due to group A β-hemolytic streptococcus, or inflammatory bowel disease (IBD). Anal fissures should be treated promptly to break the constipation, fissure, pain, retention, and constipation cycle. A stool softener should be given. Warm sitz baths after defecation may be helpful. Rarely, silver nitrate cauterization or surgery is indicated. Anal surgery should be avoided in patients with Crohn disease because of the high risk of recurrence and progression after surgery.

CONGENITAL ANORECTAL ANOMALIES

1. Anterior Displacement of the Anus

Anterior displacement of the anus is a common anomaly of infant girls. Its usual presentation in infants is constipation and straining with stool with the introduction of solids. On physical examination, the anus looks normal but is ventrally displaced, located close to the vaginal fourchette (in females) or to the base of the scrotum (in males). The diagnosis is made in girls if the distance from the vaginal fourchette to the center of the anal opening is less than 34% of the total distance from fourchette to coccyx. In boys, the diagnosis is made if the distance from the base of the scrotum to the anal aperture is less than 46% of the total distance from scrotum to coccyx. Often on internal digital examination a posterior “rectal shelf” will be appreciated. In severe anterior displacement, when the anal opening is located less than 10% of the distance from the vaginal fourchette to the coccyx, the anal sphincter muscle may not completely encircle the anal opening and severe obstipation similar to that seen in imperforate anus may occur. Indeed, extreme anterior displacement of the anus may be a form of imperforate anus. Surgery is not needed in most cases. Stool softeners or occasional glycerin suppositories usually relieve straining. This problem improves significantly by age 3–4 years as normal toddler lordosis disappears.

2. Anal Stenosis

Anal stenosis usually presents in the newborn period. The anal aperture may be very small and filled with a dot of meconium. Defecation is difficult, with ribbon-like stools, blood and mucus per rectum, fecal impaction, and abdominal distention. Anal stenosis occurs in about 3 of 10,000 live births, with slightly more males affected. Anal stenosis may not be apparent at birth because the anus looks normal. Rectal bleeding in a straining infant often leads to a rectal examination, which reveals a tight ring in the anal canal. Dilation of the anal ring is usually curative but may have to be repeated daily for several weeks.

3. Imperforate Anus

Imperforate anus typically develops during the fifth to seventh week of pregnancy and occurs in 1 of 5000 live births, slightly more common males. Almost 50% of babies with imperforate anus have additional defects, often in association with a particular syndrome.

Defects are generally classified as low (rectoperineal malformation) where the rectum may not connect to the anus, a membrane may be present over the anal opening, or the anal opening may be narrow or misplaced. A high lesion is classified where the rectum may connect to part of the urinary tract or the reproductive system through a fistula. Infants with low imperforate anus fail to pass meconium. There may be a greenish bulging membrane obstructing the anal aperture. Perforation of the anal membrane is a relatively simple surgical procedure. A skin tag shaped like a “bucket handle” is seen on the perineum of some males below which a stenotic aperture can be seen. The aperture is sometimes surrounded by normal anal musculature, but in many cases the aperture is a rectoperineal fistula and the anal musculature is displaced posteriorly or is absent. Eighty to 90% of patients with low imperforate anus are continent after surgery.

In high imperforate anus, physical examination usually shows no anal musculature. There may be a rectoperineal, rectovesicular, rectourethral, or rectovaginal fistula; hypoplastic buttocks; cloacal anomalies; and sometimes evidence of distal neurologic deficit. It is critical in these cases to fully evaluate the complex anatomy and neurologic function before attempting corrective surgery. A diverting colostomy is usually performed to protect the urinary tract and relieve obstruction. After reparative surgery, only 30% of patients with high imperforate anus achieve fecal continence.

CLOSTRIDIUM DIFFICILE INFECTION IN CHILDREN

Pathogenesis

C difficile is a spore-forming gram-positive bacillus that causes human disease via the secretion of enterotoxins that cause necrotizing inflammation of the colon. Interestingly, asymptomatic C difficile colonization of the human GI tract occurs commonly in infants and can occur in older children and adults as well. To some extent, C difficile may reside in balance with the constituent intestinal microbiome in a health host. Disruption of normal commensal intestinal bacteria or interruption of host immune defense, via intestinal injury or host immune suppression, then appears to give C difficile a potential foothold in the human gut where it can lead to disease. Hospitalization is a critical risk factor for C difficile disease. Additional risk factors in children include previous antibiotic use and a variety of chronic diseases including IBD, cystic fibrosis, Hirschsprung disease, solid-organ transplant recipients, oncology patients, and immunodeficient hosts. For reasons that are incompletely understood, community-acquired symptomatic C difficile infection in healthy children is increasing in incidence.

In recent years there has been an alarming increase in the incidence, morbidity, and mortality of C difficile reported in Europe, Canada, and the United States. At least a portion of this increase seems to be due to the expansion of a new strain of C difficile, identified as the North American Pulsed Field type 1 (NAP1) C difficile, which has been found to have increased toxin production, sporulation, and antibiotic resistance. Surveillance from children’s hospitals seems to mirror the increase in incidence of C difficile in adults but not necessarily the increase in morbidity and mortality. Pediatric hospitalizations in the United States due to C difficile have almost doubled between 1997 and 2006. The NAP1 strain was identified in 19% of C difficile isolates in a recent pediatric study.

Clinical Findings

C difficile disease in children represents a spectrum of clinical symptoms, ranging from asymptomatic colonization to persistent, watery diarrhea to pseudomembranous colitis. Recognizing that antibiotic exposure remains a critical risk factor, the onset of colitis ranges from 1 to 14 days after initiation of antibiotic therapy to as many as 30 days after antibiotics have been discontinued. Clindamycin was one of the first antibiotics associated with pseudomembranous colitis, but all antibiotics are now recognized to be potential causes, although erythromycin seems less likely than most. In pediatric patients, amoxicillin and cephalosporins are commonly associated with pseudomembranous enterocolitis, probably because of their widespread use.

The patient with pseudomembranous colitis characteristically has fever, abdominal distention, tenesmus, diarrhea, and generalized abdominal tenderness. Chronic presentations with low-grade fever, diarrhea, and abdominal pain have been described. Diarrheal stools contain sheets of neutrophils and sometimes gross blood. Plain abdominal radiographs show a thickened colon wall and ileus. Endoscopically, the colon appears to be covered by small, raised white plaques (pseudomembranes) with areas of apparently normal bowel in between (Figure 21–5). Biopsy specimens show “exploding crypts or volcano lesion”—an eruption of white cells that appears to be shooting out of affected crypts. Stool cultures often show overgrowth of Staphylococcus aureus, which is probably an opportunistic organism growing in the necrotic tissue. C difficile can be cultured in specialized laboratories. Identification of stool toxins is the usual method of diagnosis. Use of real-time polymerase chain reaction (PCR) for toxin identification has been replacing more traditional enzyme immunoassay (EIA) methods of stool toxin detection, because of improved sensitivity. Interpretation of C difficile diagnostic testing in infants remains controversial because asymptomatic colonization is well recognized in the first year of life.

Treatment

Standard treatment of pseudomembranous colitis consists of stopping antibiotics and instituting therapy with oral metronidazole (30 mg/kg/day) or vancomycin (30–50 mg/kg/day). Vancomycin is many times more expensive than metronidazole and no more efficacious. Metronidazole can be given intravenously in patients with vomiting or ileus. With increasing virulence and antibiotic resistance being reported, alternative therapies, such as rifaximin and nitazoxanide, are being used and show similar response rates as oral vancomycin. Relapse occurs after treatment in 10%–50% of patients because of exsporulation of residual spores in the colon. Spores are very hardy and may remain viable on inanimate surfaces for up to 12 months. Retreatment with the same antibiotic regimen is usually effective, but multiple relapses are possible and may be a significant management problem. Adjunctive strategies, such as Saccharomyces boulardii probiotic therapy, cholestyramine as a toxin-binder, and pulsed courses of antibiotics, have been used for refractory disease. Fecal bacteriotherapy, known popularly as fecal microbiota transplantation, is now a widely accepted and effective treatment for the treatment of recurrent C difficile infection in adults, and is increasingly being utilized in the pediatric population. As clinical experience increases with this novel therapy, a more accurate understanding of appropriate indications, contraindications, and potential risks may be further realized.

PERITONITIS

Primary bacterial peritonitis accounts for less than 2% of childhood peritonitis. The most common causative organisms are Escherichia coli, other enteric organisms, hemolytic streptococci, and pneumococci. Primary peritonitis occurs in patients with splenectomy, splenic dysfunction, or ascites (nephrotic syndrome, advanced liver disease, kwashiorkor). It can also occur in infants with pyelonephritis or pneumonia.

Secondary peritonitis is much more common. It is associated with peritoneal dialysis, abdominal trauma, or ruptured viscus. The organisms associated with secondary peritonitis vary with the cause. Organisms such as Staphylococcus epidermidis and Candida may cause secondary peritonitis in patients receiving peritoneal dialysis. Multiple enteric organisms may be isolated after abdominal injury, bowel perforation, or ruptured appendicitis. Intra-abdominal abscesses may form in pelvic, subhepatic, or subphrenic areas.

Symptoms of peritonitis include abdominal pain, fever, nausea, vomiting, acidosis, and shock. The abdomen is tender, rigid, and distended, with involuntary guarding. Bowel sounds may be absent. Most peritonitis is an acute medical emergency. In patients receiving peritoneal dialysis, peritonitis can be a chronic infection causing milder symptoms.

Leukocyte count is high initially (> 20,000/μL) and later it may fall to neutropenic levels, especially in primary peritonitis. Abdominal imaging can confirm the presence of ascites. Bacterial peritonitis should be suspected if paracentesis fluid contains more than 500 leukocytes/μL or more than 32 mg/dL of lactate; if it has a pH less than 7.34; or if the pH is over 0.1 pH unit less than arterial blood pH. Diagnosis is made by Gram stain and culture, preferably of 5–10 mL of fluid for optimal yield.

Antibiotic treatment and supportive therapy for dehydration, shock, and acidosis are indicated. Surgical treatment of the underlying cause of secondary peritonitis is critical. Removal of infected peritoneal dialysis catheters in patients with secondary peritonitis is sometimes necessary and almost always required if Candida infection is present.

CHYLOUS ASCITES

Neonatal chylous ascites may be due to congenital infection or developmental abnormality of the lymphatic system (intestinal lymphangiectasia). If the thoracic duct is involved, chylothorax may be present. Later in life, chylous ascites may result from congenital lymphangiectasia, retroperitoneal or lymphatic tumors, peritoneal bands, abdominal trauma, intestinal malrotation or infection, or it may occur after cardiac or abdominal surgery.

Both congenital and acquired lymphatic obstructions cause chylous ascites, diarrhea, and failure to thrive. The abdomen is distended, with a fluid wave and shifting dullness. Unilateral or generalized peripheral edema may be present. Laboratory findings include hypoalbuminemia, hypogammaglobulinemia, and lymphopenia. Ascitic fluid contains lymphocytes and has the biochemical composition of chyle if the patient has just been fed; otherwise, it is indistinguishable from ascites secondary to cirrhosis. Chylous ascites must be differentiated from ascites due to liver disease and in the older child, from constrictive pericarditis, chronically elevated right heart pressure, malignancy, infection, or inflammatory diseases causing lymphatic obstruction. In the newborn, urinary ascites from anatomic abnormalities of the kidney or collecting system must be considered. A simple test to diagnose urinary ascites is a urea nitrogen or creatinine concentration of abdominal fluid. Neither of these is present in chylous or hepatic ascites.

Chylous ascites is associated with fat malabsorption and protein loss with resultant edema. Little can be done to correct congenital abnormalities due to hypoplasia, aplasia, or ectasia of the lymphatics unless they are surgically resectable. More recently, somatostatin and fibrin glue have been tried with varying success. Treatment is supportive, consisting mainly of a high-protein diet and careful attention to infections. Shunting of peritoneal fluid into the venous system is sometimes effective. A fat-free diet supplemented with medium-chain triglycerides decreases the formation of chylous ascites. Total parenteral nutrition (TPN) may rarely be necessary. Infusions of albumin generally provide only temporary relief and are rarely used for chronic management. In the neonate, congenital chylous ascites may spontaneously disappear following one or more paracenteses and a medium-chain triglyceride diet.

JUVENILE POLYPS

Juvenile polyps belong to the hamartomatous category of polyps and are usually pedunculated and solitary (Figure 21–6). The head of the polyp is composed of hyperplastic glandular and vascular elements, often with cystic transformation. Juvenile polyps are benign, and 80% occur in the rectosigmoid. Juvenile polyps are the most common type of intestinal polyps in children and occur most commonly between ages 3 and 5 years of age and rarely before 1 year. The painless passage of small amounts of bright red blood with mucus on a normal or constipated stool is the most frequent manifestation. Abdominal pain is rare, but low-lying polyps may prolapse during defecation. Colonoscopy is diagnostic and therapeutic when polyps are suspected. After removal of a single juvenile polyp by electrocautery, nothing further should be done if histologic findings confirm the diagnosis. Risk of developing further juvenile polyps is low. Other polyposis syndromes are summarized in Table 21–4.

Rarely, many juvenile polyps may be present in the colon, causing anemia, diarrhea with mucus, and protein loss. An individual may be diagnosed with juvenile polyposis syndrome (JPS) if there are more than five juvenile polyps in the colon, multiple juvenile polyps elsewhere in the GI tract, or any number of juvenile polyps with a family history of juvenile polyposis syndrome. JPS does confer an increased risk of colorectal cancer and surveillance with endoscopy is required. Other hamartomatous polyp syndromes include Peutz-Jeghers syndrome and the PTEN hamartoma tumor syndrome. Peutz-Jeghers syndrome is associated with polyps commonly in the small intestine and colon but can also been seen in the stomach and in other organs. A distinctive mucocutaneous pigmentation (freckling) may appear along the vermillion border of the lips, buccal mucosa, and hands and feet but can disappear by age 5. Due to the higher risk of both GI and non-GI malignancies, routine cancer surveillance is necessary. In addition, 50% will develop intussusception at some point in their lifetime and prompt investigation for intussusception is needed in the case of symptoms suggesting intestinal obstruction. Phosphatase and tensin homolog (PTEN) hamartoma syndrome involves a spectrum of hamartomatous conditions that are associated with mutations in the PTEN gene such as Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, and Proteus syndrome. Besides hamartomas and other benign tumors throughout the body, an increased risk of intestinal and extraintestinal cancers in those with PTEN mutations exists.

CANCERS OF THE ESOPHAGUS, SMALL BOWEL, & COLON

Esophageal cancer is rare in childhood. Cysts, leiomyomas, and hamartomas predominate. Caustic injury of the esophagus increases the very long-term risk of squamous cell carcinoma. Chronic peptic esophagitis is associated with Barrett esophagus, a precancerous lesion. Simple GE reflux in infancy without esophagitis is not a risk for esophageal cancer. The most common gastric or small bowel cancer in children is lymphoma or lymphosarcoma. Intermittent abdominal pain, abdominal mass, intussusception, or a celiac-like presentation may be present. Carcinoid tumors are usually benign and most often an incidental finding in the appendix. The carcinoid syndrome (flushing, sweating, hypertension, diarrhea, and vomiting), associated with serotonin secretion, only occurs with rare metastatic carcinoid tumors. Colonic adenocarcinoma is rare in childhood. The low 5-year survival rate relates to the nonspecificity of presenting complaints and the large percentage of undifferentiated types. Children with a family history of colon cancer, chronic ulcerative colitis (UC), or familial polyposis syndromes including familial adenomatous polyposis or JPS are at greater risk.

MESENTERIC CYSTS

Mesenteric and omental cysts are rare intra-abdominal masses in children. These cysts may be small or large, single or multiloculated. They are thin-walled and contain serous, chylous, or hemorrhagic fluid. They are commonly located in the small bowel mesentery but are also found in the mesocolon. Most mesenteric cysts cause no symptoms and are found incidentally. Traction on the mesentery may lead to colicky abdominal pain, which can be mild and recurrent but may appear acutely with vomiting. Volvulus may occur around a cyst, and hemorrhage into a cyst may be mild or hemodynamically significant. A rounded mass can occasionally be palpated or seen on radiograph displacing adjacent intestine. Abdominal ultrasonography is usually diagnostic. Surgical removal is indicated. Malignant transformation of mesenteric cysts has been reported in adults, and therefore surgical removal is indicated even in asymptomatic cases.

INTESTINAL HEMANGIOMAS & VASCULAR MALFORMATIONS

GI hemangiomas and vascular malformations are uncommon causes of bleeding. Like their skin counterparts, intestinal hemangiomas are typically not present at birth. They tend to appear in the first 2 months of life, cause bleeding in the first year as they undergo a rapidly proliferating growth phase, and then can involute. Vascular malformations include capillary, arterial, venous, and mixed lesions, and are present from birth with risk of bleeding throughout life. The physically largest subtype of vascular lesion is the cavernous malformation, which may protrude into the lumen as a polypoid lesion or may invade the intestine from mucosa to serosa.

Clinical Presentation

Intestinal vascular lesions are most often found in the small bowel. These lesions may cause acute or occult blood loss or may present as intussusception, intestinal narrowing, or intramural hematoma. Thrombocytopenia and consumptive coagulopathy are complications of rapidly growing hemangiomas. Intestinal vascular lesions are usually found in isolation, but associated syndromes include the Blue rubber bleb nevus syndrome, the Osler-Rendu-Weber syndrome, and the Klippel-Trenaunay-Weber syndrome. The diagnosis of GI bleeding can be challenging, particularly when bleeding is occult or intermittent. Physical examinations are typically not helpful unless there are other skin hemangiomas present in the young child that may point to an intestinal hemangioma. Vascular protocols with CT or magnetic resonance imaging (MRI) may identify larger vascular lesions. Endoscopic techniques remain crucial to the diagnosis of intestinal vascular lesions. Video capsule endoscopy and small bowel enteroscopy techniques have allowed for diagnosis and potential therapy of small bowel vascular lesions that were previously inaccessible using conventional endoscopy.

Treatment

Vascular malformations of the skin and liver have been treated medically with corticosteroids, propranolol, sirolimus, angiotensin converting enzyme inhibitors, interferon, and vincristine. There is relatively little experience with using these medical techniques for intestinal hemangiomas. Endoscopic techniques for treatment of vascular lesions include banding, submucosal injections of sclerosants, and electrocautery methods. Vascular embolization is a consideration for rapid blood loss in the setting of gastrointestinal vascular malformations. Finally, surgical resection of the vascular lesion and surrounding bowel may be required for lesions in the mid-small bowel that are not accessible by endoscopy or for large lesions that are not amenable to endoscopic therapies.

ACUTE DIARRHEA

Viruses are the most common cause of acute gastroenteritis in developing and developed countries. Bacterial and parasitic enteric infections are discussed in Chapters 42 and 43. Of the viral agents causing enteric infection, Rotavirus and Caliciviridae (Norovirus and Sapovirus) are the most common, followed by enteric adenovirus, and Astrovirus. As with most viral pathogens, rotavirus affects the small intestine, causing voluminous watery diarrhea without leukocytes or blood. In the United States, rotavirus primarily affects infants between 3 and 15 months of age. The peak incidence in the United States is in the winter with sporadic cases occurring at other times. The virus is transmitted via the fecal-oral route and survives for hours on hands and for days on environmental surfaces. Rotavirus had been the most common viral source accounting for between 1/3 and 2/3 of hospitalizations prior to vaccine introduction.

1. Rotavirus Infection

The incubation period for rotavirus is 1–3 days. Symptoms caused by rotavirus are similar to other viral pathogens. Vomiting is the first symptom in 80%–90% of patients, followed within 24 hours by low-grade fever and watery diarrhea. Diarrhea is often preceded by vomiting and usually lasts 4–8 days but may last longer in young infants or immunocompromised patients. Fever is present in up to a third of patients. Rotavirus and adenoviruses can be detected in feces using EIA or latex agglutination. The specific identification of rotavirus is not required in every case, however, as treatment is nonspecific. Additional laboratory testing is also generally unnecessary but, when obtained, it will usually show a normal white blood cell count. Hyper- or hyponatremia may occur with dehydration. Metabolic acidosis can occur from bicarbonate loss in the stool, ketosis from poor intake, and in severe cases lactic acidemia occurs from hypotension and hypoperfusion. Stools do not contain blood or white blood cells.

As is with most other viral causes of acute diarrhea, treatment is nonspecific and supportive. Replacement of fluid and electrolyte deficits, along with ongoing losses, especially in small infants is necessary. (Oral and intravenous therapies are discussed in Chapter 23.) The use of oral rehydration solutions is appropriate in most cases. The use of clear liquids or hypocaloric (dilute formula) diets for more than 48 hours is not advisable. Early initiation of refeeding is recommended. Intestinal lactase levels may be reduced during rotavirus infection. Therefore, the brief use of a lactose-free diet may be associated with a shorter period of diarrhea but is not critical to successful recovery in healthy infants. Reduced fat intake during recovery may decrease nausea and vomiting.

Antidiarrheal medications are ineffective (kaolin-pectin combinations) and in some circumstances can be dangerous (loperamide, tincture of opium, diphenoxylate with atropine). Bismuth subsalicylate preparations may reduce stool volume but are not critical to recovery and are generally not recommended especially in young children due to the salicylate component and potential risk of Reye syndrome. Oral immunoglobulin or specific antiviral agents have occasionally been useful in limiting duration of disease in immunocompromised patients.

Most children are infected with rotavirus more than once, with the first infection being the most severe. Some protective immunity is imparted by the first infection. Prevention of infection occurs primarily by good hygiene and prevention of fecal-oral contamination. As treatment for rotavirus is nonspecific, prevention of illness is critical. The American Academy of Pediatrics issued guidelines in January 2007 recommending the routine use of bovine-based pentavalent rotavirus vaccine to be given orally to infants at 2, 4, and possibly 6 months of age, depending on which vaccine is used. Prevention is the key, and two rotavirus vaccines are commercially available, which are administered in multiple doses typically from 2 to 6 months of age.

2. Other Viral Infections Causing Acute Diarrhea

Other viral pathogens causing diarrhea in children can be identified in stool by electron microscopy, viral culture, or enzyme-linked immunoassay. Depending on the geographic norovirus and enteric adenoviruses are the next most common viral pathogens in infants. The symptoms of enteric adenovirus infection are similar to those of rotavirus, but infection is not seasonal and the incubation period more prolonged (8–10 days) with more prolonged duration of illness of typically 8–10 days, but up to 2 weeks.

Norovirus is now thought to be the leading source of community acquired diarrhea, and is highly contagious. Recent estimates suggest it is responsible for up to 800 deaths, 71,000 hospitalizations, 400,000 emergency department visits, 1.9 million outpatient visits, and 21 million morbidities annually. Norovirus is a small RNA virus that mainly causes vomiting but can also cause diarrhea in older children and adults, usually in common source outbreaks. The duration of symptoms is short, usually 24–48 hours. Other potentially pathogenic viruses include astroviruses, corona-like viruses, and other small round viruses. There is no FDA-approved assay for norovirus.

Cytomegalovirus rarely causes diarrhea in immunocompetent children but may cause erosive enteritis or colitis in immunocompromised hosts. Cytomegalovirus enteritis is particularly common after solid-organ and bone marrow transplant and in the late stages of human immunodeficiency virus (HIV) infection, but can be seen in patients taking immunosuppressive medication.

Probiotics may be effective in treating acute viral gastroenteritis in healthy children with potential reduction in duration and frequency of the illness. A diversity of opinions exist that range from the Center for Disease Control that states “not recommended” to that from the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition that “strongly” recommends use. Probiotics should be used with caution, however, in immunocompromised or seriously ill children, in particular those with a central venous catheter.

CHRONIC DIARRHEA

Bowel habits are variable, making the specific diagnosis of chronic diarrhea difficult. Some healthy infants may have five to eight stools daily. A gradual or sudden increase in the number and volume of stools to more than 15 g/kg/day combined with an increase in fluidity should raise a suspicion that an organic cause of chronic diarrhea is present. Diarrhea may result from (1) interruption of normal cell transport processes for water, electrolytes, or nutrients; (2) decrease in surface area available for absorption secondary to shortened bowel or mucosal disease; (3) increase in intestinal motility; (4) increase in unabsorbable, osmotically active molecules in the intestinal lumen; (5) increase in intestinal permeability, leading to increased loss of water and electrolytes; and (6) stimulation of enterocyte secretion by toxins or cytokines. The most common entities causing chronic diarrhea are listed as follows. Malabsorption syndromes, which also cause chronic or recurrent diarrhea, are considered separately.

1. Causes of Chronic Diarrhea

A. Antibiotic Therapy

Acute and chronic diarrhea is reported in up to 60% of children receiving antibiotics. Only a small fraction of these patients have C difficile–related pseudomembranous enterocolitis. Eradication of normal gut flora and overgrowth of other organisms may cause antibiotic-associated diarrhea. Most antibiotic-associated diarrhea is watery, is not associated with systemic symptoms, and decreases when antibiotic therapy is stopped. Data are mixed regarding the use of probiotics, though some suggest their use may decrease the incidence and severity of this diarrhea by helping to restore intestinal microbial balance.

B. Extraintestinal Infections

Infections of the urinary tract and upper respiratory tract (especially otitis media) are at times associated with diarrhea, though the mechanism is incompletely understood. Antibiotic treatment of the primary infection, toxins released by infecting organisms, and local irritation of the rectum (in patients with bladder infection) may play a role.

C. Malnutrition

Malnutrition is associated with an increased frequency of enteral infections. Decreased bile acid synthesis, decreased pancreatic enzyme output, decreased disaccharidase activity, altered motility, and changes in the intestinal flora all may contribute to diarrhea. In addition, severely malnourished children are at higher risk of enteric infections because of depressed cellular and humoral immune functions. Protein-calorie malnutrition can result in villous atrophy, and represent an important cause of malabsorption.

D. Diet and Medications

Relative deficiency of pancreatic amylase in young infants causes osmotic diarrhea after starchy foods. Fruit juices, especially those high in fructose or sorbitol, produce diarrhea because these osmotically active sugars are poorly absorbed. Intestinal irritants (spices and foods high in fiber) and histamine-containing or histamine-releasing foods (eg, citrus fruits, tomatoes, fermented cheeses, red wines, and scombroid fish) may also cause diarrhea.

FODMAPs (Fermentable, Oligo-, Di-, Mono-saccharides And Polyols) are a group of poorly absorbed short-chain carbohydrates that are not uncommonly malabsorbed. Lactose and fructose are classic examples of FODMAPs. Malabsorption of foods higher in FODMAPs can cause symptoms of chronic intermittent diarrhea. It has been implicated as a cause of diarrhea and other symptoms (bloating, gassiness, abdominal pain) in certain individuals with a prior diagnosis of irritable bowel syndrome. Removal of certain FODMAPS from the diet may improve symptoms.

Laxative abuse in association with eating disorders or Munchausen syndrome by proxy can cause unpredictable diarrhea. A high concentration of magnesium in the stool may indicate overuse of milk of magnesia or other magnesium-containing laxatives. Detection of other laxative preparations in the stool or circulation requires sophisticated analysis not available in most laboratories. A high index of suspicion and careful observation may be required to make this diagnosis.

E. Allergic Diarrhea

Diarrhea resulting from allergy to dietary proteins is a frequently entertained but rarely proven diagnosis. GI symptoms from cow’s milk protein allergy are more common in infants younger than 12 months.

In contrast to the self-limited cow’s milk protein hypersensitivity of infancy, infants and older children may develop more severe diarrhea caused by a systemic allergic reaction. For instance, food protein–induced enterocolitis syndrome (FPIES) is a life-threatening condition occurring during infancy manifested by large-volume diarrhea, acidosis, and shock as a result of an allergic reaction to common food proteins such as milk and soy. Patients require hospitalization for volume resuscitation and strict avoidance of allergens. Reintroduction of allergens should be performed in a controlled setting by an experienced allergist.

Infants and children may develop an enteropathy secondary to milk protein, resulting in flattening of small bowel villi, steatorrhea, hypoproteinemia, occult blood loss, and chronic diarrhea. Skin testing is not reliable since it detects circulating antibodies, not the T-cell–mediated responses that are likely responsible for food sensitivity reactions. Double-blind oral challenge with the suspected food under careful observation is often necessary to confirm this intestinal protein allergy. Small bowel biopsy findings are nonspecific. The diagnosis is often confirmed by either double-blind oral challenge with the suspected food or dietary elimination of the food followed by disappearance of occult blood in the stool and improvement in other symptoms. Consultation with an allergist is recommended for long-term management of patients with this disease.

Anaphylactic, immunoglobulin E (IgE)–mediated reactions to foods can occur in both young and older children. After ingestion, the patient quickly develops vomiting, then diarrhea, pallor, and hypotension. In these cases, radioallergosorbent test (RAST) and skin testing are positive. Food challenges should be undertaken in a setting in which resuscitation can be performed as there is often a progressively more severe reaction with subsequent ingestions. The close association between ingestion and symptoms usually leaves little doubt about the diagnosis.

F. Chronic Nonspecific Diarrhea

Chronic nonspecific diarrhea, also called toddler’s diarrhea, is the most common cause of loose stools in otherwise thriving children. The typical patient is a healthy, thriving child aged 6–20 months who has three to six loose stools per day during the waking hours. They do not have blood in their stools. They grow normally and may have a family history of functional bowel disease. No organic etiology is found for their diarrhea, with stool tests for blood, white blood cells, fat, parasites, and bacterial pathogens being negative. Diarrhea may worsen with a low-residue, low-fat, or high-carbohydrate diet and during periods of stress and infection. Excessive fruit juice ingestion seems to worsen symptoms. This syndrome resolves spontaneously usually by age 3½ years or after potty training. Possible causes of this diarrhea include abnormalities of bile acid absorption in the terminal ileum, excess intake of osmotically active carbohydrates, and abnormal motor function. A change in dietary fiber (either increasing fiber if deficient or decreasing fiber if excessive), a slight increase in dietary fat, and restriction of osmotically active carbohydrates like fruit juices will often help control symptoms. If these measures fail, loperamide (0.1–0.2 mg/kg/day in two or three divided doses) can be used as needed for symptomatic relief. Cholestyramine has also been used in some cases.

G. Immunologic Causes of Chronic Diarrhea

Chronic diarrhea is common in immune deficiency states, especially immunoglobulin A (IgA) deficiency and T-cell abnormalities. It can be due to an autoimmune enteropathy associated with the immune deficient state or could be due to chronic infection. The infectious causes of the diarrhea include common bacterial, viral, fungal, or parasitic organisms usually considered nonpathogenic (rotavirus, Blastocystis hominis, Candida), or unusual organisms (cytomegalovirus, Cryptosporidium, Isospora belli, Mycobacterium spp., microsporidia).

Between 50% and 60% of patients with common variable immune deficiency have enteropathy characterized by intestinal villous atrophy. Lymphonodular hyperplasia of the small intestine is also prominent. Patients with congenital or Bruton-type agammaglobulinemia usually have diarrhea and abnormal intestinal morphology. Patients with isolated IgA deficiency can have chronic diarrhea, a celiac disease–like picture, lymphoid nodular hyperplasia, and are prone to giardiasis. Patients with isolated defects of cellular immunity, combined cellular and humoral immune incompetence, and HIV infection may have severe chronic diarrhea leading to malnutrition but often the cause cannot be identified. Chronic granulomatous disease may be associated with intestinal symptoms suggestive of chronic IBD. Specific treatments are available for many of the unusual pathogens causing diarrhea in the immunocompromised host. Thus, a vigorous diagnostic search for specific pathogens is warranted in these individuals. In addition, treatment must be directed toward correcting the immunologic defect.

H. Other Causes of Chronic Diarrhea

Most infections of the GI tract are acute and resolve spontaneously or with specific antibiotic therapy. Organisms most prone to cause chronic or recurrent diarrhea in immunocompetent children are Giardia lamblia, Entamoeba histolytica, Salmonella species, and Yersinia. Infection with these organisms requires a small inoculum. Some patients may develop a postinfectious diarrhea, with persistent diarrhea present despite the eradication of the offending organism, either viral or bacterial. Bacterial overgrowth of the small bowel in patients with SBS, those undergoing chemotherapy, or with anatomic abnormalities may experience chronic diarrhea.

Pancreatic insufficiency due to cystic fibrosis or Shwachman-Diamond syndrome may result in chronic diarrhea, typically in conjunction with failure to thrive. Certain tumors of childhood (neuroblastoma, ganglioneuroma, metastatic carcinoid, pancreatic VIPoma, or gastrinoma) may secrete substances such as gastrin and vasoactive intestinal polypeptide (VIP) that promote small intestinal secretion of water and electrolytes. Conditions that result in increased or disordered intestinal motility such as hyperthyroidism or irritable bowel syndrome may also present with diarrhea. Children may present with large-volume, chronic, and intermittent watery diarrhea that does not cease when they discontinue oral feedings.

GASTROINTESTINAL BLEEDING

At the first evaluation of a child with GI bleeding history, physical examination, and initial examination are key to identifying the bleeding source. In large-volume, acute GI bleeding the primary focus, however, should center on stabilizing the patient to ensure adequate hemodynamic support.

History

A number of substances simulate hematochezia or melena (Table 21–5). The presence of blood should be confirmed chemically with guaiac testing. Coughing, tonsillitis, lost teeth, menarche, or epistaxis may cause what appears to be occult or overt GI bleeding. A careful history of the specifics surrounding the bleeding is critical, including the site, volume and color of blood, history of NSAID use, and use of other medications should be ascertained. Inquiry about associated dysphagia, epigastric pain, or retrosternal pain should be made and, if present, suggest GER or a peptic cause of bleeding.

Other important aspects of the history include foreign-body/caustic ingestion, history of chronic illnesses (especially liver/biliary disease), personal or family history of food allergy/atopy, associated symptoms (pain, vomiting, diarrhea, fever, weight loss), and family history of GI disorders (IBD, CD, liver disease, bleeding/coagulation disorder). In the presence of massive upper GI bleeding in the toddler, a high index of suspicion for button battery injury must be maintained despite the lack of any known history of ingestion. Other, more obscure causes of GI bleeding in children include Dieulafoy syndrome and heterotopic pancreas. Table 21–6 lists more common causes of GI bleeding by age and presentation.

Physical Examination

The first objective of the examination is to determine if the child is acutely or chronically ill and initiate supportive measures as needed. Physical signs of portal hypertension, intestinal obstruction, or coagulopathy are particularly important. The nasal passages should be inspected for signs of recent epistaxis, the vagina for menstrual blood, and the anus for fissures and hemorrhoids. Skin examination should assess for hemangiomas, eczema, petechiae, or purpura. Clinical assessment of vital signs and perfusion should be assessed to establish need for transfusion.

Laboratory Findings

Initial laboratory tests should include a complete blood cell count (CBC), prothrombin time (PT), and partial thromboplastin time (PTT), at minimum. In specific cases, it may be prudent to add a liver profile (with suspected variceal bleeding), erythrocyte sedimentation rate (ESR)/CRP (with possible IBD), BUN/creatinine (for possible hemolytic uremic syndrome). A BUN to creatinine ratio of more than 30 has been shown to indicate a 10-fold increase in the risk of upper versus lower GI bleeding. In patients with Henoch-Schonlein Purpura, a neutrophil-to-lymphocyte ratio of > 2.86 was found to be a predictor of subsequent GI bleeding, with sensitivity of 73% and specificity of 68%. Low MCV in association with anemia suggests chronic GI losses and may warrant addition of iron studies. Serial determination of hematocrit is essential to assess ongoing bleeding. Detection of blood in the gastric aspirate confirms a bleeding site proximal to the ligament of Treitz. However, its absence does not rule out the duodenum as the source. Testing the stool for occult blood will help monitor ongoing losses. In a large study of over 600 cases of pediatric upper GI bleeding, only 4% who were found to have significant drop in hemoglobin levels required transfusion or emergent endoscopic or surgical intervention. In this series, having one or more risk factors, including melena, hematochezia, unwell appearance, and/or large amount of fresh blood in the emesis, had a sensitivity of 100% in identifying the significant bleeds. Elevation of fecal calprotectin levels have been associated with bleeding from both IBD and juvenile polyposis.

Imaging Studies

In infants with acute onset of bloody stools, multiple-view plain x-rays of the abdomen are helpful in assessing for pneumatosis intestinalis or signs of obstruction. Children younger than 2 years with a history and examination suggestive of intussusception should undergo air or water-soluble contrast enema. Painless, large-volume bleeding may prompt performance of a ⁹⁹Tc-pertectnetate nuclear scan to assess for a Meckel diverticulum. Pretreatment with an H₂-receptor antagonist may be helpful in increasing the sensitivity of this study; however, a negative scan does not preclude the diagnosis. CT scan of the abdomen with oral and IV contrast may be indicated to look for structural and inflammatory causes of bleeding. More recently, CT enterography has been proposed as a useful tool in cases of lower GI bleeding in children. Persistent bleeding without a clear source may prompt consideration of a radioisotope-tagged red blood cell (RBC) scan with ^99mTc-sulfur colloid, though the bleeding must be active at the time of the study, with a rate of at least 0.1 mL/min. Angiography is generally less sensitive, requiring 1–2 mL/min.

Treatment

In severe bleeding, the ABCs of resuscitation should be performed. Adequate IV access is critical in these cases. If a hemorrhagic diathesis is detected, vitamin K and additional blood products should be administered to correct any underlying coagulopathy. In severe bleeding, the need for volume replacement is monitored by measurement of central venous pressure. In less severe cases, vital signs, serial hematocrits, and gastric aspirates are sufficient.

In suspected upper GI bleeding, gastric lavage with saline should be performed, but there is no value of lavage in controlling bleeding. After stabilization, EGD may be considered to identify the bleeding site, and performance of endoscopy has been associated with lower readmission rates after an initial GI bleeding event. A large retrospective study of endoscopy performed for upper GI bleeding in children found that a definitive source for bleeding was identified in 57%, with a suspected source in another 30%. Risk factors for a nondiagnostic endoscopy in this series were a history of bleeding of less than 1 month and a delay of greater than 48 hours between presentation and endoscopy. Acid suppression with intravenous H₂-antagonists or, preferably PPIs, may be helpful in suspected peptic causes of bleeding. A recent randomized trial of pediatric patients with endoscopically treated bleeding compared continuous esomeprazole therapy for 72 hours to second-look endoscopy and bolus esomeprazole and showed them to have no significant difference in rebleeding rates (4.6% vs 6.3%). Colonoscopy may identify the source of bright red rectal bleeding, but it should be performed emergently only if the bleeding is severe and if abdominal radiographs show no signs of obstruction. Colonoscopy on an unprepped colon is often inadequate for making a diagnosis. Capsule endoscopy may help identify the site of bleeding if colonoscopy and upper endoscopy findings are negative. Push or balloon enteroscopy may be helpful to perform therapeutic interventions, obtain biopsies, or mark small bowel lesions (prior to laparotomy/laparoscopy) identified on capsule endoscopy. Use of balloon enteroscopy in conjunction with capsule endoscopy in children with occult GI bleeding has been found to have a diagnostic yield of 95%.

Persistent vascular bleeding (varices [Figure 21–7], vascular anomalies) may be relieved temporarily using intravenous octreotide (1–4 mcg/kg/h) and may be used for up to 48 hours with careful monitoring of glucose homeostasis. Bleeding from esophageal varices may be stopped by compression with a Sengstaken-Blakemore tube. Endoscopic sclerosis or banding of bleeding varices are both effective, with equivalent success rates (87%–89%) and complication rates (10%–19%) between methods. Use of cyanoacrylate for gastric varices in children has been shown to be safe and effective in small, single-center studies.

If conservative measures are ineffective in stopping ulcer bleeding, endoscopic therapy with argon plasma coagulation, local injection of epinephrine, electrocautery, or application of hemostatic clips may be employed. Newer, over-the-scope clips have recently been shown to be safe and effective in pediatric patients as young as 4 years of age and as small as 17.4 kg. Though there are no studies yet published in children, use of hemostatic powder shows promise as effective and less technically challenging then other forms of endoscopic hemostasis. As in adults, use of only one modality in nonvariceal bleeding has been shown to increase the risk of rebleeding. If bleeding remains refractory to therapy, emergency surgery may be necessary. Alternatively, endovascular therapy with selective coiling of involved vessels by interventional radiology has been shown to be effective in children with refractory bleeding. A single dose of cyclophosphamide has been shown to be effective in steroid-resistant GIB in Henoch-Schönlein purpura. In some cases, angiography and selective embolization have been used successfully in unidentified and refractory bleeding.

VOMITING

Vomiting is an extremely complex activity that is triggered by stimulation of chemoreceptors and mechanoreceptors in the wall of the GI tract, activated by contraction and distension. The vomiting center, paraventricular nuclei, in the brain controls the emetic response. These nuclei receive afferent input from abdominal splanchnic nerves, the vagus nerve, vestibulolabyrinthine receptors, the cerebral cortex, and chemoreceptor trigger zone (CTZ). Vagal afferents from the gut to brain are stimulated by ingested drugs and toxins, mechanical stretch, inflammation, and local neurotransmitters. Once the vomiting response is triggered, a pattern of somatic muscle action occurs with abdominal, thoracic, and diaphragm muscles contracting against a closed glottis. The resulting increased intra-abdominal pressure reverses the negative pressure of the esophagus and forces gastric contents upward. The vomiting response also alters intestinal motility by generating a retroperistaltic contractile complex that moves intestinal contents toward the esophagus.

Vomiting is the presenting sign of many pediatric conditions. The most common cause of vomiting in childhood is acute viral gastroenteritis. However, obstruction and acute or chronic inflammation of the GI tract are also major causes. CNS inflammation, increased intracranial pressure, or mass effect may cause vomiting. Metabolic derangements associated with inborn errors of metabolism, sepsis, and drug intoxication can stimulate either the CTZ or the brain directly to promote vomiting.

Control of vomiting with medication is rarely necessary in acute gastroenteritis, but it may relieve nausea and vomiting and decrease the need for intravenous fluids and/or hospitalization. Antihistamines and anticholinergics are appropriate for motion sickness because of their labyrinthine effects. 5-HT₃–receptor antagonists (ondansetron, granisetron) are useful for vomiting associated with surgery and chemotherapy. Benzodiazepines, corticosteroids, and substituted benzamides are also used in chemotherapy-induced vomiting. Butyrophenones (droperidol, haloperidol) are powerful drugs that block the D₂ receptor in the CTZ and are used for intractable vomiting in acute gastritis, chemotherapy, and after surgery. Phenothiazines are helpful in chemotherapy, cyclic vomiting, and acute GI infection but are not recommended for outpatient use because of extrapyramidal side effects.

1. Cyclic Vomiting Syndrome

Clinical Findings

Cyclic vomiting syndrome (CVS) is defined as three or more recurrent episodes of stereotypical vomiting in children usually older than 1 year. The emesis is forceful and frequent, occurring up to six times per hour for up to 72 hours or more. Episode frequency ranges from two to three per month to less than one per year. Nausea, retching, and small-volume bilious emesis continue even after the stomach is emptied. Hematemesis secondary to forceful vomiting and a Mallory-Weiss tear (tear or laceration of the mucous membrane at the gastroesophageal junction) may occur. Patients experience abdominal pain, anorexia, and, occasionally, diarrhea. Autonomic symptoms, such as pallor, sweating, temperature instability, and lethargy, are common and give the patient a very ill appearance. The episodes end suddenly, often after a period of sleep. In some children, dehydration, electrolyte imbalance, and shock may occur. Between episodes, the child is completely healthy.

The cause of CVS is unknown; however, a relationship to migraine headaches has long been recognized. Family history is positive for migraine in 50%–70% of cases, and many patients develop migraine headaches as adults. Research suggests that abnormalities of neurotransmitters and hormones provoke CVS. About one-quarter of patients have typical migraine symptoms during episodes: premonitory sensation, headache, photophobia, and phonophobia. Identifiable triggers are similar to migraines and include infection, positive or negative emotional stress, diet (chocolate, cheese, monosodium glutamate), menses, sleep deprivation, or motion sickness.

Differential Diagnosis

Conditions that mimic CVS include drug toxicity, increased intracranial pressure, seizures, brain tumor, Chiari malformation, recurrent sinusitis, choledochal cyst, gallstones, recurrent small-bowel obstruction, IBD, familial pancreatitis, obstructive uropathy, recurrent urinary infection, diabetes, mitochondrial diseases, disorders of fatty and organic acid metabolism, adrenal insufficiency, and Munchausen syndrome by proxy. Chronic marijuana use has been associated with chronic vomiting (cannabinoid hyperemesis syndrome) and can mimic CVS. Although tests for reflux are often positive in these patients, it is unlikely that reflux and CVS are related.

Treatment

Avoidance of triggers prevents episodes in some patients. Sleep can also end an episode although some children awaken and resume vomiting. Diphenhydramine or lorazepam is used at the onset of spells in some children to reduce nausea and induce sleep. Early use of antimigraine medications (sumatriptan), antiemetics (ondansetron), or antihistamines can abort spells in some patients. Once a spell is well established, intravenous fluids may be required to end it. With careful supervision, some children with predictable spells can receive intravenous fluids at home. Several approaches usually are tried before an effective therapy is found. Preventing spells with prophylactic propranolol, amitriptyline, antihistamines, or anticonvulsants are effective in some patients with frequent or disabling spells. Some patients require the additions of the mitochondrial-targeted cofactors coenzyme Q10 and L-carnitine to help manage their vomiting episodes.

ABDOMINAL PAIN

Approximately 2%–4% of all pediatric office visits occur because of unexplained, recurrent abdominal pain. Functional GI disorders have been reported in roughly 10%–30% of children/adolescents and 30%–40% of infants and toddlers. Criteria were published in 2016 in order to incorporate new findings in the literature including new information on gut-brain interactions and microenvironments. The descriptive term “recurrent abdominal pain” has been discarded for the more meaningful terms. Those with pain as a significant component have been termed functional abdominal pain disorder (FAPD) that encompasses several entities: functional dyspepsia (with subtypes of epigastric pain vs postprandial distress), irritable bowel syndrome (characterized by altered form and frequency of stools and improvement with defecation), abdominal migraines, and functional abdominal pain.

Clinical Findings

A. Symptoms and Signs

Children with functional abdominal pain experience recurrent attacks of abdominal pain or discomfort at least once per week for at least 2 months. Functional abdominal pain used to be lumped into a broad category of abdominal pain without a source and without any red flag signs. Classifications of the abdominal pain depend on the characteristics of the pain such as location of pain, association with bowel habits, and associated symptoms. The pain is usually localized to the periumbilical area but may also be more generalized. The pain occurs primarily during the day but may prevent children from falling asleep at night. It may be associated with pallor, nausea, or vomiting, and also with dramatic reactions such as frantic crying, clutching the abdomen, and doubling over. Parents may become alarmed and take their children into the emergency departments, where the evaluation is negative for an acute abdomen. School attendance may suffer, and enjoyable family events may be disrupted.

Alarm symptoms that would suggest a more severe organic etiology are absent. These include dysphagia, persistent vomiting, GI blood loss, associated rashes, or joint complaints, weight loss, stunting, or fevers.

Functional abdominal pain usually bears little relationship to bowel habits and physical activity. However, some patients have a symptom constellation suggestive of irritable bowel syndrome, including bloating, postprandial pain, lower abdominal discomfort, and erratic stool habits with a sensation of obstipation or incomplete evacuation of stool. A precipitating or stressful situation in the child’s life at the time the pains began can sometimes be elicited. School phobia may be a precipitant.

A careful and thorough physical examination that includes a rectal examination is essential and usually normal. Complaints of abdominal tenderness elicited during palpation may be inconsistent, out of proportion to visible signs of distress, and distractable.

B. Laboratory Findings

Complete blood count, sedimentation rate, and stool test for occult blood are usually a sufficient evaluation. Extraintestinal sources such as kidney, spleen, and genitourinary tract may require assessment. In the adolescent female patient, ultrasound of the abdomen and pelvis may be helpful to detect gallbladder or ovarian pathology. If the pain is atypical, further testing suggested by symptoms and family history should be done. This may include additional imaging studies or endoscopic analysis. Any concern for lower tract inflammation, and IBD in particular may prompt consideration for the use fecal inflammatory markers such as lactoferrin and calprotectin.

Differential Diagnosis

Abdominal pain secondary to disorders causing acute abdomen are listed in Table 21–7. Pinworms, mesenteric lymphadenitis, and chronic appendicitis are improbable causes of recurrent abdominal pain. H pylori infection does not cause recurrent abdominal pain. Lactose intolerance usually causes abdominal distention, gas, and diarrhea with milk ingestion. At times, however, abdominal discomfort may be the only symptom. The incidence of peptic gastritis, esophagitis, duodenitis, and ulcer disease is probably underappreciated. Though esophageal eosinophilia typically presents with dysphagia and primarily esophageal symptoms in adolescents and adults, it can present with abdominal pain in younger children. Abdominal migraine and cyclic vomiting are conditions with an episodic character often associated with headaches or vomiting.

Treatment & Prognosis

Treatment of FAPD consists of reassurance based on a thorough history and physical examination and a sympathetic, age-appropriate explanation of the nature of functional pain. It is important to acknowledge that the child is experiencing pain. The concept of “visceral hyperalgesia” or increased pain signaling from physiologic stimuli such as gas, acid secretion, or stool is one that parents can understand and helps them respond appropriately to the child’s complaints. Another analogy might be to compare a child’s abdominal pain to usual headaches that another person may experience, in that the workup can be normal even though there is pain. Reassurance without education is rarely helpful. Regular activity should be resumed, especially school attendance. Therapy for psychosocial stressors, including biofeedback therapy, may be necessary. In specific patients, targeted therapy based on symptoms may be helpful. For abdominal migraines, treatments for migraine headaches may also be of benefit.

Numerous dietary modifications have been proposed as treatment for functional disorders, but data is a lacking as to their effectiveness. For instance, restriction of lactose and fructose and low fermentable oligo-di-mono-saccharides and polyols (FODMAP) diets may benefit some patients, whereas a positive impact of fiber, prebiotics, and probiotics on symptoms has not been shown. Biopsychosocial therapy, cognitive behavioral therapy, and hypnosis may offer benefit.

Likewise, pharmacologic studies of pediatric patients with FAPD have been underpowered and yielded inconsistent results. For instance, peppermint oil has shown benefit in reducing frequency and severity of pain, a finding that may be attributed to inhibition of calcium channels and reduction in colonic spasm. In contrast, although studies examining the impact of antispasmotic medications in adults have shown promise, these have yet to be replicated in children. One prospective study and other retrospective studies suggest efficacy for some patients with the use of cyproheptadine. Studies examining the impact of tricyclic antidepressants, calcium channel blockers, serotonin antagonists, melatonin, and antibiotics have been studied in the treatment of FAPDs have shown no significant improvement on symptoms. Interestingly, pooled data from a recent systematic review examining the placebo effect shows improvement in pain scales in 41% and resolution of pain in 17%.

ACUTE ABDOMEN

An acute abdomen is a constellation of findings indicating an intra-abdominal process that may require surgery. When this develops, a high degree of urgency exists to identify an underlying cause. The localized or generalized pain of an acute abdomen intensifies over time and is rarely relieved without definitive treatment. The abdomen may be distended and tense, and bowel sounds are often reduced or absent. Patients appear ill and are reluctant to be examined or moved. The acute abdomen is usually a result of infection of intra-abdominal or pelvic organs, but can also occur with intestinal obstruction, appendicitis intestinal perforation, inflammatory conditions, trauma, and some metabolic disorders. Some of the conditions causing acute abdomen are listed in Table 21–7. Reaching a timely and accurate diagnosis is critical and requires skill in physical diagnosis, recognition of the symptoms of a large number of conditions, and a judicious selection of laboratory and radiologic tests. (Acute appendicitis is discussed earlier in the section Disorders of the Small Intestine.)

MALABSORPTION SYNDROMES

Malabsorption of ingested food has many causes (Table 21–8). Shortened length (usually via surgical resection) and mucosal damage (CD) both reduce surface area. Impaired motility interferes with normal propulsive movements and with mixing of food with pancreatic and biliary secretions and permits anaerobic bacterial overgrowth. Bacterial overgrowth may lead to increased carbohydrate fermentation and acidic diarrhea. Bacterial overgrowth may also increase bacterial bile acid deconjugation leading to fat malabsorption as seen in intestinal pseudo-obstruction or postoperative blind loop syndrome. Impaired intestinal lymphatic (congenital lymphangiectasia) or venous drainage also causes malabsorption. Diseases reducing pancreatic exocrine function (cystic fibrosis, Shwachman syndrome) or the production and flow of biliary secretions (biliary atresia) cause nutrient malabsorption. Malabsorption of specific nutrients may also be genetically determined (acrodermatitis enteropathica, disaccharidase deficiency, glucose-galactose malabsorption, and abetalipoproteinemia).

Clinical Findings

Diarrhea, vomiting, anorexia, abdominal pain, failure to thrive, and abdominal distention are common. With fat malabsorption, stools are typically bulky, foul, greasy, and pale; in contrast, osmotic diarrhea stools are loose, watery, and acidic. Stool microscopic examination for neutral fat (pancreatic insufficiency as in cystic fibrosis) and fatty acids (as in mucosal injury, liver disease) may be useful.

Fat-soluble vitamin deficiency occurs with long-standing fat malabsorption and is manifested by prolonged PT (vitamin K) and low levels of serum carotene (vitamin A), vitamin E, and 25-hydroxy vitamin D. Loss of serum proteins is suggested by elevated fecal α1-antitrypsin levels. Disaccharide or monosaccharide malabsorption manifests by acidic stool with pH less than 5.5 due to lactic acid and reducing substances. Specific enzyme deficiencies may be evaluated by breath hydrogen test, or specific disaccharidase activity measurement from small intestinal biopsy. Other screening tests suggesting a specific diagnosis include sweat chloride concentration (cystic fibrosis), intestinal mucosal biopsy (celiac disease, lymphangiectasia, IBD), liver and gallbladder function tests, and fecal elastase. Common disorders associated with malabsorption in pediatric patients are detailed below.

1. Protein-Losing Enteropathy

Loss of plasma proteins into the GI tract occurs in association with intestinal inflammation, intestinal graft-versus-host disease, acute and chronic intestinal infections, venous and lymphatic obstruction or malformations, and intestinal malignancy (Table 21–9). Chronic elevation of venous pressure in children with the Fontan procedure and elevated right-sided heart pressures may produce protein-losing enteropathy.

Clinical Findings

Signs and symptoms are mainly caused by hypoproteinemia or fat malabsorption: edema, ascites, poor weight gain, anemia, lymphopenia, and fat-soluble vitamins (A, D, E, K) and mineral deficiencies. Serum albumin and globulins may be decreased. Fecal α₁-antitrypsin is elevated (> 3 mg/g dry weight stool; slightly higher in breast-fed infants). In the presence of intestinal bleeding, fecal α₁-antitrypsin measurements are falsely high.

Differential Diagnosis

Hypoalbuminemia may be due to increased catabolism, poor protein intake, impaired hepatic protein synthesis, or congenital malformations of lymphatics outside the GI tract, and protein losses in the urine from nephritis and nephrotic syndrome.

Treatment

Albumin infusion, diuretics, and a high-protein, low-fat diet may control symptoms. Nutritional deficiencies should be corrected, and the underlying cause treated.

2. Celiac Disease (Gluten Enteropathy)

Celiac disease (CD) is an immune-mediated enteropathy triggered by gluten, a protein in wheat, rye, and barley. CD presents any time after gluten is introduced in the diet. Disease frequency approaches 1 in 100. Risk factors include type 1 diabetes (4%–10%), Down syndrome (5%–12%), Turner syndrome (4%–8%), IgA deficiency (2%–8%), autoimmune thyroiditis (8%), and family history of CD (5%–10%). Almost all CD patients express HLA-DQ2 or DQ8 tissue antigens.

Clinical Findings

A. Symptoms and Signs

1. Gastrointestinal manifestations

In the classic form of CD, GI symptoms begin soon after gluten-containing foods are introduced in the diet, between 6 and 24 months of age. Chronic diarrhea, abdominal distention, irritability, anorexia, vomiting, and poor weight gain are typical. Celiac crisis, with dehydration, hypotension, hypokalemia, and explosive diarrhea, is rare. Older children may have oral ulcers, chronic abdominal pain, vomiting, diarrhea or constipation, and bloating.

2. Nongastrointestinal manifestations

Adolescents with CD may present with delayed puberty or short stature, and females with delayed menarche. CD should be considered in children with unexplained iron-deficiency anemia, decreased bone mineral density, elevated liver function enzymes, arthritis, epilepsy with cerebral calcifications, or intensely pruritic rash typically on the elbows, forearms, and knees suggestive of dermatitis herpetiformis. The benefit of early screening and treatment in asymptomatic individuals is unclear.

B. Laboratory Findings

1. Serologic and genetic testing

Patients over 2 years old who are suspected of celiac disease should be screened with serum IgA and tissue transglutaminase (TTG) IgA, which is highly sensitive and specific. In children under 2 years old, the deamidated gliadin peptide IgG should also be sent. In IgA deficiency, the deamidated gliadin peptide IgG or the IgG-based versions of the TTG or antiendomysial antibodies should also be sent. Testing for HLA-DQ2 and DQ8 has a high negative predictive value, and family members who test negative are unlikely to ever develop CD.

2. Stools

May have partially digested fat or be acidic.

3. Hypoalbuminemia

Can be severe enough to lead to edema.

4. Anemia

Low MCV and evidence of iron deficiency is common.

5. Insufficient Hepatitis B surface Ab after immunization

Up to 30%–70% of patients with CD are estimated to be nonresponsive to hepatitis B vaccination before treatment with gluten-free diet.

C. Biopsy Findings

Characteristic duodenal biopsy findings on light microscopy are oftentimes patchy villous atrophy with increased numbers of intraepithelial lymphocytes.

Differential Diagnosis

The differential diagnosis includes food allergy, non-celiac gluten sensitivity, Crohn disease, postinfectious diarrhea, primary lactose intolerance, functional abdominal pain, irritable bowel syndrome, immunodeficiencies, and graft-versus-host disease.

Treatment

A. Diet

Treatment is strict dietary gluten restriction for life. All sources of wheat, rye, and barley are eliminated. Most, but not all, patients tolerate oats as long as the manufacturer takes precautions to avoid cross-contamination in processing. The intestinal mucosa improves after 6–12 months of treatment while secondary lactose intolerance resolves within a few weeks. Supplemental calories, vitamins, and minerals are indicated only in the acute phase. CD-related antibody titers decrease on a gluten-free diet, but may take 12 months or longer to normalize.

Prognosis

Adherence to gluten-free diet is difficult and difficult to assess, but is associated with regrowth of villi, resolution of symptoms, and normal life. Individuals with poor adherence to gluten-free diet may be at increased risk for fractures, iron deficiency anemia, infertility, and enteropathy-associated T-cell lymphoma.

3. Carbohydrate Malabsorption

Carbohydrate malabsorption is typically a nonimmune-mediated intolerance to dietary carbohydrates due to a deficiency in an enzyme or transporter, or due to excess consumption overloading a functional transporter. These systems are located on the small bowel epithelial brush border. The non-absorbed molecules cause osmotic diarrhea and are fermented in the gut producing gas. As a result, clinical symptoms include abdominal distention, bloating, flatulence, abdominal discomfort, nausea, and watery diarrhea. Stools will test positive for reducing substances, except for sucrose, which is not a reducing sugar.

A. Disaccharidase Deficiency

Starches and the disaccharides sucrose and lactose are the most important dietary carbohydrates. Dietary disaccharides and the oligosaccharide products of pancreatic amylase action on starch require hydrolysis by intestinal brush border disaccharidases for absorption. Disaccharidase levels are highest in the jejunum and proximal ileum. Characteristics of primary disaccharidase deficiency include permanent disaccharide intolerance, absence of intestinal injury, and frequent positive family history.

B. Lactase Deficiency

All human ethnic groups are lactase-sufficient at birth making congenital lactase deficiency extremely rare. Genetic or familial lactase deficiency appears after 5 years of age. Genetic lactase deficiency develops in virtually all Asians, Alaskan natives, Native Americans, 80% of Africans, 70% of African Americans, and 30%–60% of Caucasian Americans. Transient or secondary lactase deficiency caused by mucosal injury such as an acute viral gastroenteritis is common and resolves within a few weeks. Lactose ingestion in lactase deficient individuals causes variable degrees of diarrhea, abdominal distention, flatus, and abdominal pain. Stools are liquid or frothy and acidic, and may test positive for reducing substances. Diagnostic tests include genetic testing and lactose breath test. Symptoms resolve with dietary avoidance of lactose or with lactase supplementation.

C. Sucrase-Isomaltase Deficiency

This condition is inherited in a rare autosomal recessive fashion and found most commonly in Greenland, Iceland, and among Alaskan natives. Infants may present with abdominal distention, failure to thrive, and watery, acidic diarrhea. Diagnosis is made by oral sucrose breath hydrogen testing (1 g/kg), or by testing a snap frozen intestinal biopsy for enzyme activity. Treatment is avoidance of sucrose and starches rich in amylopectin, or the use of sacrosidase enzyme supplement.

4. Monosaccharide Malabsorption

The most important monosaccharides are fructose, glucose, and galactose.

A. Glucose-Galactose Malabsorption

Glucose-galactose malabsorption is a rare disorder in which the sodium-glucose transport protein is defective. Transport of glucose in the intestinal epithelium and renal tubule is impaired. Diarrhea begins with the first feedings, accompanied by reducing sugar in the stool and acidosis. Glycosuria and aminoaciduria may occur and the glucose tolerance test is abnormal. Small bowel histology appears normal. Diarrhea subsides promptly on withdrawal of glucose and galactose from the diet and is mandatory treatment for the congenital disease. The acquired, transient form of glucose-galactose malabsorption occurs mainly in infants younger than 6 months, usually following acute viral or bacterial enteritis, and may require PN until healing. A carbohydrate-free base formula is used with added fructose. Prognosis is good if diagnosed early. Tolerance for glucose and galactose improves with age.

B. Dietary Fructose Intolerance

Fructose malabsorption occurs when fructose is in excess of glucose, often with consumption of high-fructose corn syrup. Malabsorbed fructose leads to symptoms such as abdominal pain, bloating, flatulence, and diarrhea. Diagnosis is made with a fructose breath hydrogen test.

C. Intestinal Lymphangiectasia

This form of protein-losing enteropathy results from obstruction of intestinal lymphatics and leakage of lymph into the bowel lumen. Congenital lymphangiectasia is associated with abnormalities of the lymphatics in the extremities. Malrotation with volvulus can also cause intestinal lymphangiectasia.

Clinical Findings

Peripheral edema, diarrhea, abdominal distention, chylous effusions, and repeated infections are common. Laboratory findings include low calcium, magnesium, albumin, immunoglobulin levels, lymphocytopenia, and anemia and elevated fecal α₁-antitrypsin. Imaging may show bowel wall edema, and biopsy may reveal dilated lacteals in the villi and lamina propria. If only the lymphatics of the deeper layers of bowel or intestinal mesenteries are involved, laparotomy may be necessary to establish the diagnosis. Capsule endoscopy shows diagnostic brightness secondary to the fat-filled lacteals.

Differential Diagnosis

Causes of protein losing enteropathy should be considered.

Treatment & Prognosis

A high-protein diet (6–7 g/kg/day may be needed) enriched with medium-chain triglycerides as a fat source usually allows for adequate nutrition and growth. Vitamin and calcium supplements should be given. Parenteral nutritional supplementation may be needed temporarily. Surgery may be curative if the lesion is localized to a small area of the bowel or in cases of constrictive pericarditis or obstructing tumors. IV albumin and immune globulin may be needed but usually not chronically. The serum albumin may not normalize. The prognosis is not favorable, although remission may occur with age. Malignant degeneration of the abnormal lymphatics may occur, and intestinal B-cell lymphoma may develop.

5. Cow’s Milk Protein Intolerance

Milk protein intolerance refers to nonallergic food sensitivity and is more common in males than females and in young infants with a family history of atopy. The estimated prevalence is 0.5%–1.0%. Symptoms may occur while an infant is still exclusively breast-fed. The most commonly heard history reports a healthy, well appearing infant, who when fed formula or breast milk with cow’s milk protein, develops flecks of blood in the stool or loose mucoid, blood streaked stools. A family history of atopy is common but skin testing is not reliable or indicated since this is not thought to be an IgE-mediated disease. Removal of cow’s milk protein is the treatment. Maternal avoidance of milk protein will usually suffice if breast-fed. If formula-fed, substituting a protein hydrolysate formula for cow’s milk–based formula is indicated. Allergic colitis in young infants is self-limited, usually disappearing by 8–12 months of age. Since no long-term consequences of this problem have been identified, when symptoms are mild and the infant is thriving, no treatment may be needed. Histology, not required for diagnosis, shows mild lymphonodular hyperplasia, mucosal edema, and eosinophilia on rectal biopsy.

In older children, milk protein sensitivity may induce eosinophilic gastroenteritis with protein-losing enteropathy, iron deficiency, hypoalbuminemia, and hypogammaglobulinemia. A celiac-like syndrome with villous atrophy, malabsorption, hypoalbuminemia, occult blood in the stool, and anemia can occur.

6. Pancreatic Insufficiency

The most common cause of pancreatic exocrine insufficiency in childhood is cystic fibrosis. Decreased secretion of pancreatic digestive enzymes is caused by obstruction of the exocrine ducts by thick secretions, which destroys pancreatic acinar cells. Other conditions associated with exocrine pancreatic insufficiency are discussed in Chapter 22.

7. Other Genetic Disorders Causing Malabsorption

A. Abetalipoproteinemia

Abetalipoproteinemia is a rare autosomal recessive condition in which the secretion of triglyceride-rich lipoproteins from the small intestine (chylomicrons) and liver (very low-density lipoproteins) is limited or absent. Profound steatosis of intestinal enterocytes (and hepatocytes) and severe fat malabsorption occur. Deficiencies of fat-soluble vitamins develop with neurologic complications of vitamin E deficiency and atypical retinitis pigmentosa. Serum cholesterol level is very low, and red cell membrane lipids are abnormal, causing acanthosis of red blood cells, two findings that may be the key to diagnosis.

B. Acrodermatitis Enteropathica

Acrodermatitis enteropathica is an autosomal recessive condition in which the intestine has a selective inability to absorb zinc. The condition usually becomes obvious at the time of weaning from breast-feeding and is characterized by rash on the extremities, rashes around the body orifices, eczema, profound failure to thrive, steatorrhea, diarrhea, and immune deficiency. Zinc supplementation by mouth results in rapid improvement.

INFLAMMATORY BOWEL DISEASE

General Considerations

IBD, a chronic relapsing inflammatory disease, is most commonly differentiated into Crohn disease (CrD) and ulcerative colitis (UC). The etiology is multifactorial, involving a complex interaction of environmental and genetic factors leading to maladaptive immune responses to flora in the GI tract. With 5%–30% of patients identifying a family member with IBD, and a 10–20 relative risk of a sibling developing IBD, a genetic association is certain in most. Very early onset IBD, before age 2, is more likely to be monogenic and severe.

Clinical Findings

A. Symptoms and Signs

Inflammation causes abdominal pain, diarrhea, bloody stools, fever, anorexia, fatigue, and weight loss. CrD may also present as a stricturing process with abdominal pain and intestinal obstruction, or as a penetrating/fistulizing form with abscess, perianal disease, or symptoms similar to acute appendicitis. UC usually presents with abdominal pain and bloody diarrhea.

CrD can affect any part of the GI tract from lips to anus. Childhood CrD most often affects the terminal ileum and colon. UC is limited to the colon, and in children it usually involves the entire colon (pancolitis). The younger the age at onset, the more severe the course is likely to be.

Extraintestinal manifestations are common in both forms of IBD and may precede the intestinal complaints. These include uveitis, recurrent oral aphthous ulcers, arthritis, growth and pubertal delay, liver involvement (typically primary sclerosing cholangitis), rash (erythema nodosa and pyoderma gangrenosum), and iron deficiency anemia.

B. Diagnostic Testing

Diagnosis is based on symptoms, relapsing course, radiographic, endoscopic, and histologic findings, and exclusion of other disorders. No single test is diagnostic. Patients often have low hemoglobin, iron, and serum albumin levels, and elevated ESR and CRP and fecal calprotectin. IBD-related serum antibodies are frequently present; antibodies to Saccharomyces cerevisiae (ASCA) in 60% of CrD, and perinuclear antineutrophil cytoplasmic antibodies (pANCAs) in 70% of UC. These, and other IBD-related antibodies, may be helpful in differentiating CrD from UC, but they are neither sensitive nor specific enough to be diagnostic. Abdominal imaging with CT, magnetic resonance enterography, US, and video capsule may reveal small bowel disease and exclude other etiologies. Findings include thickening of the bowel wall, stricturing, mucosal ulceration, enteric fistulas, and mucosal and mural edema.

Upper endoscopy and ileocolonoscopy are the most useful diagnostic modalities, revealing severity and extent of upper intestinal, ileal, and colonic involvement. Granulomas are found in 25%–50% of CrD cases. Deep linear ulcers, white exudate (Figure 21–8), aphthous lesions (Figure 21–9), patchy involvement, and perianal disease suggest CrD. Superficial and continuous involvement of the colon sparing the upper GI tract are most consistent with UC. Both forms of IBD may have mild gastritis.

Differential Diagnosis

When extraintestinal symptoms predominate, CrD can be mistaken for rheumatoid arthritis, systemic lupus erythematosus or other vasculitides, CD, or hypopituitarism. The acute onset of ileocolitis may be mistaken for intestinal obstruction, appendicitis, lymphoma, infectious diarrhea. Malabsorption symptoms suggest CD, peptic ulcer, Giardia, food protein allergy, anorexia nervosa, or growth failure from endocrine causes. Perianal disease may suggest child abuse. Crampy diarrhea and blood in the stool can also occur with infection such as Shigella, Salmonella, Yersinia, Campylobacter, E histolytica, enteroinvasive E coli (E coli O157), Aeromonas hydrophila, C difficile, and, if immunocompromised, CMV. Mild IBD mimics irritable bowel syndrome, or lactose intolerance. Consider Behçet disease if there are deep intestinal ulcers, oral aphthous ulcerations along with at least two of the following: genital ulcers, synovitis, posterior uveitis, meningoencephalitis, and pustular vasculitis. Chronic granulomatous disease and sarcoidosis also cause granulomas.

Complications

A. Crohn Disease

Nutritional complications include failure to thrive, short stature, decreased bone mineralization, and specific nutrient deficiencies, including iron, calcium, zinc, vitamin B₁₂, and vitamin D. Prolonged corticosteroid therapy may impact growth and bone mineral density. Intestinal obstruction, fistulae, abdominal abscess, perianal disease, pyoderma gangrenosum, arthritis, and amyloidosis occur. Crohn colitis increases risk for colon adenocarcinoma.

B. Ulcerative Colitis

Even with the typical presentation of UC, up to 35% will develop CrD. Arthritis, uveitis, pyoderma gangrenosum, and malnutrition can occur. Growth failure and delayed puberty are less common than in CrD, while liver disease (chronic active hepatitis, sclerosing cholangitis) is more common. Adenocarcinoma of the colon occurs with an incidence of 1%–2% per year after the first 7–8 years of disease in patients with pancolitis and is significantly higher in patients with UC and sclerosing cholangitis.

Treatment

A. Medical Treatment

Therapy for pediatric IBD involves induction of remission, maintenance of remission, and addressing nutritional deficiencies to promote normal growth and development. Treatment includes diet, anti-inflammatory, immunomodulatory, antidiarrheal, antibiotic, and biological options. No medical therapy is uniformly effective in all patients. In severe CrD, growth hormone may be needed to attain full height potential.

1. Diet

Enteral nutrition with liquid formula providing more than 85% of caloric needs is an effective therapy for induction and maintenance for CrD and promotes linear growth. Diet therapies are less effective in UC. Ensuring adequate nutrition for replenishing deficits and promoting normal growth (including pubertal growth) can be challenging. In addition to total calories, micronutrient, calcium, and vitamin deficiencies should be replenished. Restrictive or bland diets are counterproductive because they usually result in poor intake. A high-protein, high-carbohydrate diet with normal amounts of fat is recommended. A diet with decreased fiber may reduce symptoms during active colitis or partial intestinal obstruction; however, once the colitis is controlled, increased fiber may benefit mucosal health via bacterial production of fatty acids. Low-lactose diet or lactase replacement may be needed temporarily for small bowel CrD. Ileal disease may require antibiotics to treat bacterial overgrowth and extra fat-soluble vitamins due to increased losses. In severe CrD, supplemental calories from formulas taken orally or by NG tube promote catch-up growth.

2. Aminosalicylates (ASA)

Multiple preparations of 5-ASA derivatives are available and used to induce and maintain remission in mild CrD and UC. Common preparations including 5-ASA products such as sulfasalazine (50 mg/kg/day), or balsalazide (0.75–2.5 g PO tid) or mesalamine products (adult dose range 2.4–4.8 g/day), are available in tablets, granules, and delayed release formulations targeting specific locations in the GI tract. Side effects include skin rash; nausea; headache and abdominal pain; hair loss; diarrhea; and rarely nephritis, pericarditis, serum sickness, hemolytic anemia, aplastic anemia, and pancreatitis. Sulfasalazine, in which sulfa delivers the 5-ASA, may cause sulfa-related side effects including photosensitivity and rash.

3. Corticosteroids

Patients with moderate to severe CrD and UC generally respond quickly to corticosteroids. Methylprednisolone (1 mg/kg/day) may be given intravenously when disease is severe. For moderate disease, prednisone (1 mg/kg/day, orally in one to two divided doses), or budesonide in preparations targeting the ileocecal area or colon may quickly improve symptoms but should be tapered over 4–8 weeks. Budesonide, due to “single pass” liver clearance, may have less side effects than prednisone. Steroid dependence is an indication for escalating therapy. Corticosteroid enemas and foams are useful topical agents for distal proctitis or left-sided colitis. While on systemic corticosteroids, consideration should be given to calcium and vitamin D supplementation as well as acid suppression to prevent gastritis.

4. Immunomodulators: azathioprine (AZA), 6-mercaptopurine (6MP), and methotrexate (MTX)

If patients experience moderate to severe or are steroid-dependent, immunomodulators may be used as effective agents to maintain remission and reduce corticosteroids use. AZA (2–3 mg/kg/day PO) or 6MP (1–2 mg/kg/day PO) provides effective maintenance therapy for moderate to severe CrD. The optimal dose of AZA or 6MP depends on the enzyme thiopurine methylene transferase (TPMT), which should be measured before starting therapy. For individuals deficient in TPMT, MTX should be used; for intermediate enzyme activity, dose is reduced by 50%. In cases when adherence may be an issue, or when dose adjustments may be necessary, AZA or 6MP metabolites may be measured. Maximum therapeutic efficacy may not be seen for 2–3 months after beginning treatment. Side effects include pancreatitis, hepatotoxicity, and bone marrow suppression.

MTX is effective in CrD but not UC, and with onset of action within 2–3 weeks. Weekly oral or intramuscular dosage ranges from 15 mg/m² up to 25 mg. The most common side effect is nausea, managed with folate 1 mg a day, while serious adverse events include bone marrow, liver, lung, and kidney toxicities. MTX is well known to cause fetal death and deformities.

5. Antibiotics

Metronidazole (15–30 mg/kg/day in three divided doses) and ciprofloxacin treat perianal CrD and bacterial overgrowth. Peripheral neuropathy may occur with prolonged use of metronidazole.

6. Biologicals

Antibody against tumor necrosis factor-α (TNFα) is used for moderate to severe CrD and UC, and for fistulizing or penetrating disease. Formulations are available for IV (infliximab) or intramuscular (adalimumab) administration. Disease recurrence is usually within 12 months of stopping therapy. New biologicals include vedolizumab, an alpha4/beta7 anti-integrin, and ustekinumab, an anti IL12/23 agent. Use of biologics is associated with risk for infusion reactions, injection site reactions, and increased risk for opportunistic infections and for malignancy. Rarely, hepatosplenic T-cell lymphoma is associated with anti-TNF agents and concomitant AZA/6MP.

7. Other agents

Cyclosporine or tacrolimus may be used as a “bridge” to more definitive therapy (such as colectomy for UC). Probiotics and prebiotics are frequently used but with very limited data on efficacy. Tofactinib, an oral JAK inhibitor, has recently received approval for adults with UC.

8. Surveillance

After 7–8 years of colitis, cancer screening with routine colonoscopy and multiple biopsies is recommended. Persistent metaplasia, aneuploidy, or dysplasia indicates need for colectomy.

B. Surgical Treatment

1. Crohn disease

Ileocecal resection is the most common surgery but recurrence is expected. Indications for surgery in CrD include stricture, obstruction, uncontrollable bleeding, perforation, abscess, fistula, and failure of medical management. Up to 50% of patients with CrD eventually require a surgical procedure.

2. Ulcerative colitis

Total colectomy is curative and is recommended for patients with steroid dependence or steroid resistance, uncontrolled hemorrhage, toxic megacolon, high-grade dysplasia, or malignant tumors; elective colectomy may be chosen for prevention of colorectal cancer after 7–8 years of disease. A J-pouch provides better continence, but pouchitis develops in up to 25% of patients, manifested by diarrhea and cramping, and is treated with metronidazole or ciprofloxacin. Liver disease associated with IBD is not improved by colectomy.

Web Resources

http://www.crohnscolitisfoundation.org/.