CURRENT Diagnosis and Treatment Pediatrics, (Current Pediatric Diagnosis & Treatment) 22nd Edition
21. Gastrointestinal Tract
Edward Hoffenberg, MD
David Brumbaugh, MD
Glenn T. Furuta, MD
Gregg Kobak, MD
Edwin Liu, MD
Jason Soden, MD
Robert Kramer, MD
DISORDERS OF THE ESOPHAGUS
GASTROESOPHAGEAL REFLUX & GERD
ESSENTIALS OF DIAGNOSIS & TYPICAL FEATURES
Uncomplicated gastroesophageal reflux (GER) refers to recurrent postprandial spitting and vomiting in healthy infants that resolves spontaneously.
Gastroesophageal reflux disease (GERD) is present when reflux causes secondary symptoms or complications.
Esophageal manifestations of GERD include symptoms (heartburn, regurgitation) and mucosal complications (esophagitis, stricture, Barrett esophagus).
GERD has been implicated in pathogenesis of many extraesophageal symptoms, including upper and lower airway findings. In most settings, objective confirmation of extraesophageal reflux complications is challenging.
Upper gastrointestinal (GI) radiograph is useful to rule out other anatomical GI diseases, but it should not be considered an evaluation for reflux or reflux disease.
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. Low pressures in the lower esophageal sphincter or developmental immaturity of the sphincter are not causes of GER in infants. 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.
An important point in evaluating infants with GER is to determine whether the vomited material contains bile. Bile-stained emesis in an infant requires immediate evaluation as it may be a symptom of intestinal obstruction (malrotation with volvulus, intussusception).
Other symptoms may be associated with GERD in infants, although these situations are far less common than benign, physiologic GER. These clinical presentations include failure to thrive, food refusal, pain behavior, GI bleeding, upper or lower airway-associated respiratory symptoms, or Sandifer syndrome.
B. Older Children With Reflux
GERD is diagnosed when reflux causes persistent symptoms with or without inflammation of the esophagus. Older children with GERD complain of adult-type symptoms of 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, and repaired tracheoesophageal fistula are at increased risk of GERD and esophagitis.
C. Extraesophageal Manifestations of Reflux Disease
GERD is implicated in the pathogenesis of several disorders unrelated to inherent esophageal mucosal injury. In infants, GERD has been linked to the occurrence of apnea or apparent life-threatening events (ALTEs), although the majority of pathologic cases are not reflux associated. Upper airway symptoms (hoarseness, sinusitis, laryngeal erythema, and edema), 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 in many clinical circumstances can be 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 bilious emesis, GI bleeding, onset of vomiting after 6 months, failure to thrive, diarrhea, fever, hepatosplenomegaly, abdominal tenderness or distension, or neurologic changes. Infants with suspected physiologic GER do not require further evaluations unless there is clinical concern for complicated GERD or nonreflux diagnoses.
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 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 probe studies quantify esophageal acid exposure, and pH impedance studies also add detection of bolus fluid transit, including both acidic and nonacidic reflux. pH impedance studies in particular 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). Prethickened “antireflux” formulas are available. In infants with unexplained crying/fussy behavior, there is no evidence to support 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 an 8- to 12-week period. 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. In addition, children with underlying neurodevelopmental disorders are at risk for persistent GERD. Episodic symptoms may be controlled with intermittent use of acid blockers. Patients with persistent symptoms may require chronic acid suppression. Complications of reflux esophagitis or chronic GERD include feeding dysfunction, esophageal stricture, and anemia (see Figure 21-1). Barrett esophagus, a precancerous condition, is uncommon in children, but it may occur in patients with an underlying primary diagnosis that offers high risk for GERD.
Figure 21–1. Esophagitis associated with gastroesophageal reflux disease. Mucosa is erythematous with loss of vascular pattern.
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 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/gagging, or wrap failure.
Sherman PM et al: A global, evidence-based consensus on the definition of gastroesophageal reflux disease in the pediatric population. Am J Gastroenterol 2009 May;104(5):1278–1295 [PMID: 19352345].
Vandenplas Y et al: Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr 2009 Oct;49(4):498–447 [PMID: 19745761].
ESSENTIALS OF DIAGNOSIS & TYPICAL FEATURES
Feeding dysfunction, dysphagia, esophageal food impaction, and heartburn.
Must rule out other causes for esophageal eosinophilia before assigning diagnosis of eosinophilic esophagitis (EoE).
Esophagoscopy may reveal white eosinophilic exudates, ringlike esophageal folds, and esophageal stricture. Esophageal mucosal biopsy shows dense eosinophilic infiltrate of the epithelium.
Elimination of food allergens or swallowed topical steroids are effective treatments for EoE.
A. Symptoms and Signs
This recently recognized entity occurs in all ages and most 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, heartburn 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, or food impaction is not uncommon.
B. Laboratory Findings
Peripheral eosinophilia may or may not be present. The esophageal mucosa usually appears abnormal with features of thickening, longitudinal mucosal fissures, and circumferential mucosal 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). Basal cell layers of the esophageal mucosa are hypertrophied and infiltrated by eosinophils (usually > 15/40 × light microscopic field). A lengthy stricture may be seen, which can split merely with the passage of an endoscope. 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.
Figure 21–2. Esophagitis associated with eosinophilic esophagitis. Mucosa contains linear folds, white exudate, and has loss of vascular pattern.
The most common differential conditions are peptic esophagitis, congenital esophageal stricture, and Candidal esophagitis. EoE may be part of a generalized eosinophilic gastroenteropathy, a very rare, steroid-responsive entity. 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.
The diagnosis of EoE is based on 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.
Dietary exclusion of offending allergens (elemental diet, removal of allergenic foods) is effective treatment. Such diets are useful in young children, but adherence in older children can be difficult. Topical corticosteroids also offer an effective treatment choice. 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. Two puffs of fluticasone from an inhaler twice daily using an age-appropriate metered dose is a common recommendation. Patients should not rinse their mouth or eat for 30 minutes to maximize the effectiveness. Systemic corticosteroids benefit most patients with more acute or severe symptoms. Esophageal dilation may be required to treat strictures. 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.
Liacouras CA et al: Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol 2011;128:3–20 [PMID: 21477849].
Mukkada V, Haas A, Creskoff N, Fleischer D, Furuta GT, Atkins D: Feeding dysfunction in children with eosinophilic esophagitis (EoE). Pediatrics 2010;126:e672–e677 [PMID: 20696733].
ACHALASIA OF THE ESOPHAGUS
ESSENTIALS OF DIAGNOSIS & TYPICAL FEATURES
Gradual onset of distal esophageal obstruction.
Dysphagia, esophageal food impaction, chronic pulmonary aspiration.
Failure of lower esophageal relaxation during swallowing with abnormalities of esophageal peristalsis.
High resting pressure of the lower esophageal sphincter.
A. Symptoms and Signs
Achalasia most commonly occurs in children who are older than 5 years, but cases during infancy have been reported. Common symptoms in one recent study 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. Dysphagia is relieved by repeated forceful swallowing or vomiting. Familial cases occur in Allgrove syndrome (alacrima, adrenal insufficiency, and achalasia, associated with a defect in the AAAS gene on 12q13, encoding the ALADIN protein) and familial dysautonomia. Though no genetic or pathophysiologic basis has been identified, there have been recent case reports of achalasia in pediatric autism patients. Chronic cough, wheezing, recurrent aspiration pneumonitis, anemia, and poor weight gain are common.
B. Imaging and Manometry
Barium esophagram shows a dilated esophagus with a tapered “beak” at the GE junction. Esophageal dilation may not be present in infants because of the short duration of distal obstruction. Fluoroscopy shows irregular tertiary contractions of the esophageal wall, indicative of disordered esophageal peristalsis. Achalasia has also been identified incidentally in patients undergoing GE scintigraphy. 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 some partial or normal relaxations present in some swallows. High-resolution manometry testing in adult patients suggests varying subtypes of achalasia, which may predict likelihood of response to different therapies.
C. Differential Diagnosis
Congenital or peptic esophageal stricture, esophageal webs, and esophageal masses 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 involving the lower esophageal sphincter. Intestinal pseudo-obstruction, multiple endocrine neoplasia type 2b, systemic amyloidosis, and postvagotomy syndrome cause esophageal dysmotility and symptoms 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 lower esophageal sphincter causing an acquired achalasia.
Treatment & Prognosis
Endoscopic injection of botulinum toxin paralyzes the lower esophageal sphincter and temporarily relieves obstruction but has relapse rates of greater than 50%. Pneumatic dilation of the lower esophageal sphincter produces temporary relief of obstruction that may last weeks to years. Pediatric trials are limited, but a recent single center experience of endoscopic dilation showed a long-term success rate of up to 87% with one to three dilations. Because of concerns that dilation may increase inflammation between the esophageal mucosal and muscular layers, however, some have advocated surgical myotomy as the best initial treatment. While, long-lasting functional relief is achieved by surgically dividing the lower esophageal sphincter (Heller myotomy), recurrence risk of obstructive symptoms following myotomy in children has been reported to be as high as 27%. Postoperative GERD is common, leading some to perform a fundoplication or place diaphragm valves at the same time as myotomy. In adult achalasia, per-oral endoscopic myotomy (POEM) has been increasingly utilized as a less invasive alternative to surgical treatment, with isolated case reports in children. In a large retrospective pediatric study, general response rates of pneumatic dilation compared to Heller myotomy were not significantly different, though recent studies suggest that children over 6 may have better outcomes with pneumatic dilation. Self-expanding metal stents have been used with success in adults with achalasia but have not been studied in children.
Because of the shorter duration of esophageal obstruction in children, there is less secondary dilation of the esophagus. Thus, the prognosis for return or retention of some normal esophageal motor function after surgery is better than in adults.
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Betalli P et al: Autism and esophageal achalasia in childhood: a possible correlation? Report on three cases. Dis Esophagus 2012 May 6(3):237–240 [PMID: 22607127].
Di Nardo G et al: Pneumatic balloon dilation in pediatric achalasia: efficacy and factors predicting outcome at a single tertiary pediatric gastroenterology center. Gastrointest Endosc 2012 Nov;76(5):927–932 [PMID: 22921148].
Hallal C et al: Diagnosis, misdiagnosis, and associated diseases of achalasia in children and adolescents: a twelve-year single center experience. Pediatr Surg Int 2012 Dec;28(12):1211–1217 [PMID: 23135808].
Maselli R et al: Peroral endoscopic myotomy (POEM) in a 3-year-old girl with severe growth retardation, achalasia, and Down syndrome. Endoscopy 2012;44(Suppl 2 UCTN):E285–E287 [PMID: 22933258].
Morera C, Nurko S: Heterogeneity of lower esophageal sphincter function in children with achalasia. J Pediatr Gastroenterol Nutr 2012 Jan;54(1):34–40 [PMID: 21694632].
Zhou HB et al: Diaphragm valves reduce gastroesophageal reflux following cardiomyotomy for patients with achalasia. Acta Chir Belg 2012 Jul–Aug;112(4):287–291 [PMID: 23008993].
CAUSTIC BURNS OF THE ESOPHAGUS
ESSENTIALS OF DIAGNOSIS & TYPICAL FEATURES
Reported history of ingestion, with or without evidence of oropharyngeal injury.
Odynophagia, drooling, and food refusal typical of esophageal injury.
Endoscopic evaluation of severity and extent of injury at 24–48 hours postingestion.
Significant risk for development of esophageal strictures, especially in second- and third-degree lesions.
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. Acidic substances typically lead to limited injury because of the small volume ingested due to the sour taste. In addition, acid ingestions often lead to superficial coagulative necrosis with eschar formation. Conversely, the more benign taste of alkali ingestions may allow for larger volume ingestions, subsequent liquefactive necrosis that can lead to deeper mucosal penetration. Beyond the pH, factors that determine the severity of injury from a caustic ingestion include the amount ingested, the physical state of the agent, and the duration of mucosal exposure time. For these reasons, powdered or gel formulations of dishwashing detergent are especially dangerous, because of their innocuous taste, high pH, and tendency to stick to the mucosa. Symptoms of hoarseness, stridor, and dyspnea suggest associated airway injury, while odynophagia, drooling, and food refusal are typical with more severe esophageal injury. 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 a routine part of the evaluation in caustic ingestions to determine the severity and extent of the esophageal injury. Timing of endoscopy is important, however, 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 should be particularly noted, since they carry the highest risk of stricture formation. In a recent large single-center study, 34% of over 200 ingestions in children were grade 2 or 3, with 50% of these eventually requiring one or more endoscopic dilations for stricture formation. If dilation is felt to be necessary, it should not be performed in the acute phase of injury. Elevation of white blood cell count was found in a recent pediatric study to be a sensitive, but not specific, indicator of high-grade injury. In addition, despite the lack of clinical findings, esophageal lesions have been found in up to 35% and gastric lesions in up to 14% of patients. Because of the relative lack of good prognostic indicators of significant injury, most clinical guidelines recommend endoscopic evaluation as part of standard management in pediatric caustic ingestions. 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, as they are unlikely to detect grades 1 and 2 lesions. Some centers have advocated conservative management with upper GI series within 3 weeks of injury, reserving endoscopic evaluation for those with evidence of stricture.
Treatment & Prognosis
Clinical observation is always prudent, as it is often difficult to predict the severity of esophageal injury at presentation. 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/d) are given immediately to reduce oral swelling and laryngeal edema. Many centers advocate continued corticosteroids for the first week to decrease the risk of stricture formation; however, meta-analysis has not been able to show a clinical benefit from this practice. Intravenous fluids are necessary if dysphagia prevents oral intake. Treatment may be stopped if there are only first-degree burns at endoscopy. Whereas speculation suggest that broad-spectrum antibiotic coverage with third-generation cephalosporins may decrease stricture formation by preventing bacterial colonization into necrotic tissue, the use of antibiotics in cases of perforation is mandatory. Acid-blockade is often used to decrease additional injury from acid reflux.
Esophageal strictures develop in areas of anatomic narrowing (thoracic inlet, GE junction, or point of compression where the left bronchus crosses the esophagus), where contact with the caustic agent is more prolonged. Strictures occur only with full-thickness esophageal necrosis and prevalence of stricture formation varies from 10% to 50%. Shortening of the esophagus is a late complication that may cause hiatal hernia. Repeated esophageal dilations may be necessary as a stricture develops, with one review showing 35% requiring more than seven dilations. In that series of 175 patients, there was long-term success in only 16% of patients, with 4.5% having complications of perforation and a 2.8% mortality rate. In complicated cases esophageal stenting may be beneficial during early management. Newer, fully covered, self-expanding, removable esophageal stents, now available in pediatric sizes, may offer additional options for recurrent caustic strictures. Alternatively, in a multicenter analysis, endoscopic administration of topical mitomycin-C was effective in treatment of refractory caustic strictures of the esophagus. Animal models utilizing 5-fluorouricil 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.
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Duman L et al: The efficacy of single-dose 5-fluorouracil therapy in experimental caustic esophageal burn. J Pediatr Surg 2011 Oct;46(10):1893–1897 [PMID: 22008323].
Karagiozoglou-Lampoudi T et al: Conservative management of caustic substance ingestion in a pediatric department setting, short-term and long-term outcome. Dis Esophagus 2011 Feb;24(2):86–91 [PMID: 20659141].
Kaya M, Ozdemir T, Sayan A, Arikan A: The relationship between clinical findings and esophageal injury severity in children with corrosive agent ingestion. Ulus Travma Acil Cerrahi Derg 2010 Nov;16(6):537–540 [PMID: 21153948].
Temiz A, Oguzkurt P, Ezer SS, Ince E, Hicsonmez A: Predictability of outcome of caustic ingestion by esophagogastroduodenoscopy in children. World J Gastroenterol 2012 Mar;18(10): 1098–1103 [PMID: 22416185].
FOREIGN BODIES IN THE ALIMENTARY TRACT
ESSENTIALS OF DIAGNOSIS & TYPICAL FEATURES
Dysphagia, odynophagia, drooling, regurgitation, and chest/abdominal pain are typical symptoms of esophageal foreign body.
Esophageal foreign bodies should be removed within 24 hours of ingestion.
Esophageal button batteries must be removed emergently because of their ability to cause lethal injury.
Most foreign bodies in the stomach will pass spontaneously.
Older infants and toddlers engage their environment, in part, by placing items in their mouth. As a result, foreign body ingestions are a common occurrence in pediatrics. 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. 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 any necessary endoscopic procedures for removal.
The most common foreign body ingested by children is the coin (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. The evaluation of a swallowed foreign body starts 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.
Figure 21–3. Foreign body in esophagus. Coin is lodged in the esophageal lumen.
Esophageal foreign bodies should be removed within 24 hours to avoid ulceration, which can lead to serious complications such as erosion into a vessel or stricture formation. 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 have resulted in death from subsequent aortoenteric fistula formation, even weeks after battery removal. Button batteries in the stomach will generally pass uneventfully, but they should be monitored closely to ensure prompt passage. With larger batteries (> 20 mm) and in younger children (< 5 years of age) endoscopic evaluation with gastric batteries may still be considered in order to evaluate the esophagus for signs of injury and risk of aortoesophageal fistula. 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 months if the child is free of symptoms. Straight pins, 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. Failure of a small, smooth foreign body to exit the stomach after several days suggests the possibility of gastric outlet obstruction.
Most foreign bodies can be removed from the esophagus or stomach by a skilled endoscopist. In some circumstances an alternative technique can be used. An experienced radiologist using fluoroscopy can utilize a Foley catheter with balloon inflated below the foreign body to extract esophageal coins in the upper esophagus while the awake patient is placed in the Trendelenburg position. Contraindications include precarious airway, history that foreign body has been present for several days, and previous esophageal surgery.
Brumbaugh DE et al: Management of button battery-induced hemorrhage in children. J Pediatr Gastroenterol Nutr 2011;52(5): 585–589 [PMID: 215028305].
Hurtado CW, Furuta GT, Kramer RE: Etiology of esophageal food impactions in children. J Pediatr Gastroenterol Nutr 2010;52(1):43–46 [PMID: 20975581].
Hussain SZ et al: Management of ingested magnets in children. J Pediatr Gastroenterol Nutr 2012 Sep;55(3):239–242 [PMID: 22785419].
Kay M, Wyllie R: Pediatric foreign bodies and their management. Curr Gastroenterol Rep 2005 Jun;7(3):212–218 [PMID: 15913481].
Litovitz T, Whitaker N, Clark L, White NC, Marsolec M: Emerging battery-ingestion hazard: clinical implications. Pediatrics 2010; 125(6):1168–1177 [PMID: 20498173].
Waltzman ML: Management of esophageal coins. Curr Opin Pediatr 2006;18(5):571–574 [PMID: 16969175].
DISORDERS OF THE STOMACH & DUODENUM
In paraesophageal hiatal hernias, the esophagus and GE junction are in their normal anatomic position, but the gastric cardia is herniated through the diaphragmatic hiatus alongside the GE junction. In sliding hiatal hernias, the GE junction and a portion of the proximal stomach are displaced above the diaphragmatic hiatus. Sliding hiatal hernias are common. Congenital paraesophageal hernias are rare in childhood; patients may present with recurrent pulmonary infections, vomiting, anemia, failure to thrive, or dysphagia. The most common cause of paraesophageal hernia is previous fundoplication surgery. 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. Presence of a Schatzki ring on upper GI has been found to be associated with hiatal hernia 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 hiatal hernia in children, where inversion of the usual acid:nonacid reflux ratio to more than 1.0 was reported to have a sensitivity of 93.8% and specificity of 79.6%. Treatment in symptomatic cases is generally surgical, with laparoscopic approach being used more commonly. Controversy exists about using biosynthetic mesh in the repair of these hernias, as its use definitely decreases the risk of recurrent hernia but has also been associated with esophageal erosion in children. GE reflux may accompany sliding hiatal hernias, although most produce no symptoms. Fundoplication is indicated if paraesophageal or sliding hiatal hernias produce persistent symptoms, though the presence of a preoperative hiatal hernia has been found to triple the risk of recurrent GERD following fundoplication.
Towbin AJ, Diniz LO: Schatzki ring in pediatric and young adult patients. Pediatr Radiol 2012 Dec;42(12):1437–1440 [PMID: 22886377].
Van Niekerk ML: Laparoscopic treatment of type III para-oesophageal hernia. S Afr J Surg 2011 Feb;49(1):47–48 [PMID: 21933485].
Wu JF et al: Combined multichannel intraluminal impedance and pH: the diagnosis of sliding hiatal hernia in children with gastroesophageal reflux disease. J Gastroenterol 2013 Nov;48(11):1242-8 [PMID: 23397115].
ESSENTIALS OF DIAGNOSIS & TYPICAL FEATURES
Postnatal muscular hypertrophy of the pylorus.
Progressive gastric outlet obstruction, nonbilious vomiting, dehydration, and alkalosis in infants younger than 12 weeks.
Upper GI contrast radiographs or abdominal ultrasound are diagnostic.
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. A positive family history is present in 13% of patients. Recent studies suggest that erythromycin in the neonatal period is associated with a higher incidence of pyloric stenosis in infants younger than 30 days, though the mean age at diagnosis in a large population-based study was 43.1 days. Epidemiological studies identify no increased risk of pyloric stenosis with macrolide antibiotic exposure via breast milk.
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. Constipation, weight loss, fretfulness, dehydration, and finally apathy occur. 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.
Ultrasonography shows a hypoechoic muscle ring greater than 4-mm thick 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. Isolated pylorospasm is common in young infants and by itself is insufficient to make a diagnosis of pyloric stenosis. 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
Ramstedt pyloromyotomy is the treatment of choice and consists of incision down to the mucosa along the pyloric length. The procedure can be performed laparoscopically, with similar efficacy and improved cosmetic results compared to open procedures. An alternative, double Y, form of pyloromyotomy may promote more rapid resolution of vomiting and increased weight gain in the first postoperative week compared to the traditional Ramstedt procedure. Treatment of dehydration and electrolyte imbalance is mandatory before surgical treatment, even if it takes 24–48 hours. Use of IV cimetidine and other acid-blocking agents has been shown in small studies to rapidly correct metabolic alkalosis, allowing more rapid progression to surgery and resolution of symptoms. 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 The postoperative barium radiograph remains abnormal for many months despite relief of symptoms.
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Tutay GJ, Capraro G, Spirko B, Garb J, Smithline H: Electrolyte profile of pediatric patients with hypertrophic pyloric stenosis. Pediatr Emerg Care 2013 Mar 22;29(4):465–468 [PMID: 23528507].
GASTRIC & DUODENAL ULCER
ESSENTIALS OF DIAGNOSIS & TYPICAL FEATURES
Localized erosions of gastric or duodenal mucosa.
Pain and bleeding are the most common symptoms.
Underlying severe illness, Helicobacter pylori infection, and nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common causes.
Diagnosis by endoscopy.
Gastric and duodenal ulcers occur at any age. Boys are affected more frequently than girls. In the United States, most childhood gastric and duodenal ulcers are associated with underlying illness, toxins, or drugs that cause breakdown in mucosal defenses.
Worldwide, the most common cause of gastric and duodenal ulcer is mucosal infection with the bacterium H pylori. Between 10% and 20% of North American children have antibodies against H pylori. Antibody prevalence increases with age, poor sanitation, crowded living conditions, and family exposure. In some developing countries, over 90% of schoolchildren have serologic evidence of past or present infection. 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 adenocarcinoma of the stomach. 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 occur as frequently in girls as boys, 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 HP or NASIDs. 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 upper 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.
A. Symptoms and Signs
In children younger than 6 years, vomiting and upper GI bleeding are the most common symptoms of gastric and duodenal ulcer. Older children are more likely to complain of epigastric abdominal pain. The first attack of acute H pylori gastritis may be accompanied by vomiting and hematemesis. 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). Endoscopy also provides the mechanism for testing of other causes of peptic symptoms such as esophagitis, eosinophilic GI disease, and celiac disease (CD). 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.
Figure 21–4. Gastric ulcer. White exudate coats the ulcer bed of antral ulcer that is surrounded by an erythematous margin.
Acid suppression or neutralization is the mainstay of noninfectious ulcer therapy. Liquid antacids in the volumes needed to neutralize gastric acid are usually unacceptable to children. H2-receptor antagonists and PPIs are more effective and usually produce endoscopic healing in 4–8 weeks.
As an adjunct therapy, 7- to 14-day courses of sucralfate may be helpful as a mucosal protective agent to speed healing and decrease symptoms. Bland “ulcer diets” do not speed healing, but foods causing pain should be avoided. Caffeine should be avoided because it increases gastric acid secretion. Aspirin, alcohol, NSAIDs, and other gastric irritants should be avoided as well.
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. The most common regimen is a triple combination of amoxicillin, clarithromycin, and PPI. Quadruple combinations, involving an additional antibiotic, may yield higher eradication rates. Alternative antibiotics include metronidazole, imidazole, tetracycline, and levofloxacin. Bismuth subsalicylate is commonly used as a substitute for the PPI. Regimens are typically continued for a minimum of 10 days. Sequential therapy, which involves induction with amoxicillin plus PPI for 5 days followed by clarithromycin/metronidazole/PPI for 5 days, may also yield higher eradication rates than standard triple combination therapy. Resistance to antibiotics is common and varies by region of the world. Regional antibiotic resistance patterns for H pylori should be a guide in selecting a treatment regimen for symptomatic infection. Test of cure can be achieved by either the urease breath test or fecal H pylori antigen test.
Endoscopic therapy of bleeding ulcers may be considered for severe or refractory lesions posing a risk for significant morbidity or mortality. Therapeutic options include injection therapy, application of monopolar or bipolar electrocoagulation, placement of clipping devices, or use of argon plasma coagulation.
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CONGENITAL DIAPHRAGMATIC HERNIA
ESSENTIALS OF DIAGNOSIS & TYPICAL FEATURES
Congenital diaphragmatic hernia (CDH) typically is diagnosed prenatally by screening ultrasound.
Pulmonary hypoplasia and cardiovascular dysfunction are clinical challenges in the postnatal period.
After surgical repair, chronic pulmonary disease and GER can be lifelong morbidities.
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 5% 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 leads to similar but 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, are commonly seen. With the advent of improved care 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. Fetal surgery with tracheal occlusion has been attempted to improve fetal pulmonary development. 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. Occasionally, diaphragmatic hernia is first identified in an older infant or child during incidental radiograph or routine physical examination. These children usually have a much more favorable prognosis than neonates. CDH survivors are often found to have significant chronic pulmonary disease as well as GER, the latter possibly resulting from abnormal intrinsic innervation of the lower esophagus.
Mettauer NL et al: One-year survival in congenital diaphragmatic hernia, 1995–2006. Arch Dis Child 2009;94:407 [PMID: 19383869].
Tovar JA: Congenital diaphragmatic hernia. Orphanet J Rare Dis 2012 Jan 3;7:1 [PMID: 22214468].
CONGENITAL DUODENAL OBSTRUCTION
Obstruction is generally classified into intrinsic and extrinsic causes, although rare cases of simultaneous intrinsic and extrinsic anomalies have been reported. Extrinsic duodenal obstruction is usually due to congenital peritoneal bands associated with intestinal malrotation, annular pancreas, or duodenal duplication. In rare cases, a preduodenal portal vein has been associated with extrinsic obstruction as well. Intrinsic obstruction is caused by stenosis, mucosal diaphragm (so-called wind sock deformity), or duodenal atresia. In atresia, the duodenal lumen may be obliterated by a membrane or completely interrupted with a fibrous cord between the two segments. Atresia is more often distal to the ampulla of Vater than proximal. In about two-thirds of patients with congenital duodenal obstruction, there are other associated anomalies.
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, in association with an echogenic band in the second portion of the duodenum was found to be 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.
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. Prematurity (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 prematurity, 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.
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DISORDERS OF THE SMALL INTESTINE
INTESTINAL ATRESIA & STENOSIS
Excluding anal anomalies, intestinal atresia or stenosis accounts for one-third of all cases of neonatal intestinal obstruction (see Chapter 1). 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.
Table 21–1.Localization and relative frequency of congenital gastrointestinal atresias and stenoses.
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 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.
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Walker K et al: A population-based study of the outcome after small bowel atresia/stenosis in New South Wales and the Australian Capital Territory, Australia, 1992–2003. J Pediatr Surg 2008;43:484–488 [PMID: 18358286].
The midgut extends from the duodenojejunal junction to the mid-transverse colon. It is supplied by the superior mesenteric artery (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.
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.
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.
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Sizemore AW, Rabbani KZ, Ladd A, Applegate KE: Diagnostic performance of the upper gastrointestinal series in the evaluation of children with clinically suspected malrotation. Pediatr Radiol 2008;38:518–528 [PMID: 18265969].
Taylor GA: CT appearance of the duodenum and mesenteric vessels in children with normal and abnormal bowel rotation. Pediatr Radiol 2011 Nov;41(11):1378–1383 [PMID: 21594544].
SHORT BOWEL SYNDROME
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 anatomic (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. Although no specific anatomic bowel length measurements offer 100% certainty in predicting clinical outcomes in SBS, residual small intestine less than 30 cm offers at least some prediction that a patient may require long-term, if not indefinite, PN. Serum citrulline level may serve as a reliable biomarker in order to help predict functional intestinal mass.
Symptoms & Signs
Typical symptoms 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. Emerging therapies targeted to promote bowel adaptation include glucagon-like peptide 2 analogues, which show promise in potentially increasing absorption and bowel adaptation in early trials.
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 using either ethanol or antibiotics may have a role in reducing rate of infection. 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 fish-oil based lipid solution (Omegaven), 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.
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ESSENTIALS OF DIAGNOSIS & TYPICAL FEATURES
Intussusception is the most common cause of bowel obstruction in the first 2 years of life.
The most common location for intussusception is ileocolic and 85% of cases are idiopathic.
Ultrasound is the most sensitive and specific diagnostic modality for intussusception.
Air enema is the best therapeutic approach in the stable patient, with successful reduction in 75% of cases.
Intussusception is the invagination of one segment of intestine into another segment. Although intussusception can occur anywhere along the small and large bowel, most commonly the intussusception starts just proximal to the ileocecal valve and extends for varying distances into the colon. The terminal ileum telescopes into the colon. Swelling, hemorrhage, incarceration, vascular compromise, and necrosis of the intussuscepted ileum may occur, as well as intestinal perforation and peritonitis. Intussusception is the most frequent cause of intestinal obstruction in the first 2 years of life. It is three times more common in males than in females. 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, Henoch-Schönlein purpura, lymphoma, lipoma, parasites, foreign bodies, and viral enteritis with hypertrophy of Peyer patches. Intussusception of the small bowel can occur in patients with CD and cystic fibrosis related to the bulk of stool in the terminal ileum. In children older than 6 years, lymphoma is the most common cause of intussusception.
Characteristically, 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. The likelihood of bowel compromise increases with the duration of symptoms. 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, with 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%. 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.
The likelihood of successful reduction by enema decreases if symptom duration is greater than 24 hours. Similarly, of those requiring surgical reduction, the risk of subsequent bowel resection increased from 17% to 39% in patients with symptoms greater than 24 hours. The mortality rate with treatment is 1%–2%. The patient should be observed carefully after hydrostatic or pneumatic reduction because intussusception recurs within 24 hours in 10% of patients. Intussusception in patients older than 5 years confers a greater risk of persistent symptoms, having an underlying lead point and recurrence of intussusception.
Applegate KE: Intussusception in children: evidence-based diagnosis and treatment. Pediatr Radiol 2009 Apr;39(Suppl 2):S140–S143 [PMID: 19308373].
A peritoneal sac precedes the testicle as it descends from the genital ridge to the scrotum. The lower portion of this sac envelops the testis as the tunica vaginalis, and the remainder normally atrophies by the time of birth forming a cord (processus vaginalis). In some cases, peritoneal fluid may become trapped in the tunica vaginalis (noncommunicating hydrocele). If the processus vaginalis remains open, peritoneal fluid or an abdominal structure may be forced into it (indirect inguinal hernia).
Inguinal hernias are most often indirect and occur more frequently (9:1) in boys than in girls. Hernias may present at any age. The incidence in preterm male infants is close to 5% and is reported in 30% of male infants weighing 1000 g or less.
No symptoms are associated with an empty processus vaginalis. 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. Suggestive histories are often the only criterion for diagnosis, along with the “silk glove” feel of the rubbing together of the two walls of the empty hernia sac.
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.
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. Controversy remains about whether the side opposite a unilateral hernia should be surgically explored. Exploration of the unaffected groin can document an open processus vaginalis, but patency does not always guarantee that herniation will occur, especially in patients older than 1 year, in whom the risk of contralateral hernia is about 10%.
Antonoff MB, Kreykes NS, Saltzman DA, Acton RD: American Academy of Pediatrics Section on Surgery hernia survey revisited. J Pediatr Surg 2005 Jun;40(6):1009–1014 [PMID: 15991187].
Zendejas B et al: Incidence of inguinal hernia repairs in Olmsted County, MN: a population-based study. Ann Surg 2013 Mar; 257(3):520–526 [PMID: 23388353].
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. Reducing the hernia and strapping the skin over the abdominal wall defect does not accelerate healing.
PATENT OMPHALOMESENTERIC DUCT
ESSENTIALS OF DIAGNOSIS & TYPICAL FEATURES
Persistent umbilical discharge in an infant may represent a patent omphalomesenteric duct.
Ultrasound is the preferred diagnostic method for patent omphalomesenteric duct.
Surgical excision of the omphalomesenteric remnant is required.
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 an 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. Cauterization of a mucocele is not recommended. Surgical excision of omphalomesenteric remnants is indicated. Ultrasound examination or abdominal computed tomography (CT) can help confirm the diagnosis of omphalomesenteric duct remnants.
Durakbasa CU et al: Symptomatic omphalomesenteric duct remnants in children. Pediatr Int 2010 Jun;52(3):480–484 [PMID: 19863751].
Meckel diverticulum is the most common form of omphalomesenteric duct remnant and is usually located on the antimesenteric border of the mid to distal ileum. It occurs in 1.5% of the population and in the majority of cases causes no symptoms. Familial cases have been reported. 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.
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. In some patients, entrapment of bowel under a band running between the diverticulum and the base of the mesentery occurs. Meckel diverticula may be trapped in an inguinal hernia. Diverticulitis occurs in 10%–20% of symptomatic patients and is clinically indistinguishable from acute appendicitis. Perforation and peritonitis may occur.
Diagnosis of Meckel diverticulum is made with a Meckel scan. Technetium-99 (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. At laparoscopy or laparotomy, the ileum proximal and distal to the diverticulum may reveal ulcerations and heterotopic gastric tissue adjacent to the neck of the diverticulum. The prognosis for Meckel diverticulum is good.
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) and 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.
A. Symptoms and Signs
The typical patient has 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. Levels of interleukin 6 (IL-6) show promise as a potential biomarker for acute appendicitis, usually peaking within 24 hours of onset of pain.
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. A localized fluid collection adjacent to or surrounding the appendix may also be seen. 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 compared to CT or ultrasound alone. Indium-labeled white blood cell scan may localize to an inflamed appendix. Enlarged mesenteric lymph nodes are a nondiagnostic finding.
The presence of pneumonia, pleural effusion, urinary tract infection, right-sided kidney stone, cholecystitis, perihepatitis, and pelvic inflammatory disease may mimic appendicitis. Acute gastroenteritis with Yersinia enterocoliticamay 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. A single intraoperative dose of cefoxitin or cefotetan is recommended for all patients to prevent postoperative infection. Nonoperative management of perforated appendicitis with antibiotic therapy and image-guided drainage of abdominal abscesses has become more commonplace. Failure of nonoperative management may occur in up to 38% of patients and is more commonly associated with bandemia on admission and persistent fever after the initial 24 hours of antibiotics. 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.
Bansal S, Banever GT, Karrer FM, Partrick DA: Appendicitis in children less than 5 years old: influence of age on presentation and outcome. Am J Surg 2012 Dec;204(6):1031–1035 [PMID: 23231939].
Bundy DG et al: Does this child have appendicitis? JAMA 2007;298:438 [PMID: 17652298].
Kharbanda AB et al: Discriminative accuracy of novel and traditional biomarkers in children with suspected appendicitis adjusted for duration of abdominal pain. Acad Emerg Med 2011;18(6):567–574 [PMID: 21676053].
Saito JM et al: Use and accuracy of diagnostic imaging by hospital type in pediatric appendicitis. Pediatrics 2013 Jan;131(1): e37–e44 [PMID: 23266930].
DUPLICATIONS OF THE GASTROINTESTINAL TRACT
Enteric duplications are congenital spherical or tubular structures found most commonly in the ileum. Other common locations of duplication are the duodenum, rectum, and esophagus. Duplications usually contain fluid and sometimes blood if necrosis has taken place. Most duplications are attached to the mesenteric side of the gut and generally do not communicate with the intestinal lumen. The epithelial lining of the duplication is usually of the same type as the bowel from which it originates. 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.
DISORDERS OF THE COLON
CONGENITAL AGANGLIONIC MEGACOLON (HIRSCHSPRUNG DISEASE)
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 mesodermal layers of the gut during gestation, possibly secondary to abnormal end-organ cell surface receptors or local deficiency of nitric oxide synthesis. The absence of ganglion cells 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.
The aganglionic segment has 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 is associated Down syndrome, which occurs in 2%–10% of all individuals.
A. Symptoms and Signs
Failure of the newborn to pass meconium, followed by vomiting, abdominal distention, and reluctance to feed, suggests 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. The stools can be foul-smelling and ribbon-like. The abdomen is distended with prominent veins. Peristaltic waves are visible and fecal masses palpable. Intermittent bouts of intestinal obstruction, hypochromic anemia, 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
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).
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 reflex 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 occasional patients, a nonrelaxing internal anal sphincter is the only abnormality. This condition is often called “ultrashort segment Hirschsprung disease.”
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. The three most commonly performed repairs are the Swenson, Duhamel, and Soave procedures. Several surgical techniques, including laparoscopic pull-through, are in use. 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.
Frykman PK, Short SS: Hirschsprung-associated enterocolitis: prevention and therapy. Semin Pediatr Surg 2012 Nov;21(4): 328–335 [PMID: 22985838].
Parisi MA: In: Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP (eds): Hirschsprung Disease Overview GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2013 [PMID: 20301612].
Rintala RJ, Pakarinen MP: Long-term outcomes of Hirschsprung’s disease. Semin Pediatr Surg 2012 Nov;21(4):336–343 [PMID: 22985839].
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 results in encopresis (involuntary fecal leakage) 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.
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 enemas. Many infants who strain are displaying symptoms of infant dyschezia. The diagnostic criteria for infant dyschezia are at least 10 minutes of straining and crying before successful passage of soft stools in an otherwise healthy infant younger than 6 months. 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 or encopresis. Among these are painful defecation; skeletal muscle weakness; psychological issues, especially those relating to abuse, 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.
Table 21–2.Causes of constipation.
One must distinguish between chronic retentive constipation from Hirschsprung disease as summarized in Table 21–3.
Table 21–3. Differentiation of retentive constipation and Hirschsprung disease.
A careful diet history is important to ensure that the child is consuming adequate dietary fiber and maintaining an adequate fluid intake. If diet change alone is ineffective, medications may be required. Treatment is usually begun with osmotic stool softeners such as milk of magnesia, lactulose, or polyethylene glycol solution (MiraLax). Stimulant laxatives such as standardized extract of senna fruit (Senokot syrup, ExLax) can be used for those with chronic difficulties in which there are concerns about a dilated colon resulting in inefficient empting. If encopresis is present, treatment should start with relieving fecal impaction. Disimpaction can be achieved in several ways, including medications such as hypertonic phosphate or saline enemas, mineral oil (2–3 mL/kg/d), and nonabsorbable osmotic agents such as polyethylene glycol (MiraLax, 1 g/kg/d) and milk of magnesia (1–2 mL/kg/d). Effective stool softeners should thereafter be given regularly in doses sufficient to induce two or three loose bowel movements per day. After several weeks to months of regular loose stools, stool softeners can be tapered and stopped. For many children with retentive constipation behavioral modification is an integral part of management. Regular toilet sittings, ensuring proper foot placement while sitting on the toilet and addressing any underlying fears about toileting by the child. 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. A multiple vitamin supplement is recommended while mineral oil is given. Recurrence of encopresis is common and should be treated promptly to eliminate the fecal impaction and avoid the cycle of impaction, soiling, and retentive behaviors.
Constipation Guidelines Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition: Evaluation and treatment of constipation in infants and children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2006;43:e1 [PMID: 16954945].
Hoekman DR, Benninga MA: Functional constipation in childhood: current pharmacotherapy and future perspectives. Expert Opin Pharmacother 2013 Jan;14(1):41–51 [PMID: 23216375].
Mugie SM, Di Lorenzo C, Benninga MA: Constipation in childhood. Nat Rev Gastroenterol Hepatol. 2011 Aug 2;8(9):502–511 [PMID: 21808283].
Anal fissure is a slit-like tear in the squamous epithelial mucosa of the anal canal between the anocutaneous junction and the dentate line that usually occurs secondary to the passage of large, hard fecal masses. Anal stenosis, anal crypt abscess, and trauma can be contributory factors. Most anal fissures are single in number and occur at the posterior midline. Multiple fissures of the anal canal, lateral fissures, or those that extend proximal to the dentate line should raise the suspicion of a more serious underlying disease process including sexual abuse. Anal fissures may be the presenting sign of CrD 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. Anal dilation relieves sphincter spasm. 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. 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 ribbonlike 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); the rectum may not connect to the anus, a membrane may be present over the anal opening, the anal opening may be narrow or misplaced, or a high lesion 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.
Levitt MA, Pena A: Outcomes from the correction of anorectal malformations. Curr Opin Pediatr 2005;17:394 [PMID: 15891433].
Reisner SH, Sivan Y, Nitzan M, Merlob P: Determination of anterior displacement of the anus in newborn infants and children. Pediatrics 1984;73:216–217 [PMID: 6694879].
CLOSTRIDIUM DIFFICILE INFECTION IN CHILDREN
ESSENTIALS OF DIAGNOSIS & TYPICAL FEATURES
Clostridium difficile in children leads to a spectrum of clinical disease, from asymptomatic colonization to severe pseudomembranous colitis with fever, severe abdominal pain, and bloody diarrhea.
Risk factors for C difficile disease include previous antibiotic use and a variety of chronic diseases, including immunodeficiency, cystic fibrosis, Hirschsprung disease, IBD, oncology patients, and solid-organ transplant recipients.
Community-acquired C difficile disease in healthy hosts is increasing in incidence.
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.
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 now 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.
Figure 21–5. Clostridium difficile–associated pseudomembranes. Colonic mucosa is covered with plaques coated with white exudates.
Standard treatment of pseudomembranous colitis consists of stopping antibiotics and instituting therapy with oral metronidazole (30 mg/kg/d) or vancomycin (30–50 mg/kg/d). 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 transplantation, is now a widely accepted and nearly 100% effective treatment for the treatment of recurrent C difficile infection in adults but experience remains limited in children.
Khalaf N, Crews JD, DuPont HL, Koo HL: Clostridium difficile: an emerging pathogen in children. Discov Med 2012 Aug;14(75):105–113 [PMID: 22935207].
Kim J et al: Epidemiological features of Clostridium difficile-associated disease among inpatients at children’s hospitals in the United States, 2001–2006. Pediatrics 2008;122(6):1266–1170 [PMID: 19047244].
Toltzis P et al: Presence of the epidemic North American Pulsed Field type 1 Clostridium difficile strain in hospitalized children. J Pediatr 2009;154(4):607–608 [PMID: 19324222].
Zilberberg MD, Tillotson GS, McDonald C: Clostridium difficile infections among hospitalized children, United States, 1997–2006. Infect Dis 2010;16(4):604–609 [PMID: 20350373].
DISORDERS OF THE PERITONEAL CAVITY
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 also occurs in infants with pyelonephritis or pneumonia.
Secondary peritonitis is much more common. It is associated with peritoneal dialysis, penetrating abdominal trauma, or ruptured viscus. The organisms associated with secondary peritonitis vary with the cause. Organisms not commonly pathogenic such as Staphylococcus epidermidis and Candida may cause secondary peritonitis in patients receiving peritoneal dialysis. Multiple enteric organisms may be isolated after penetrating abdominal injury, bowel perforation, or ruptured appendicitis. Intra-abdominal abscesses may form in pelvic, subhepatic, or subphrenic areas, but discrete localization of infection is less common in young infants than in adults.
Symptoms of peritonitis include abdominal pain, fever, nausea, vomiting, acidosis, and shock. Respirations are shallow. The abdomen is tender, rigid, and distended, with involuntary guarding. Bowel sounds may be absent. Diarrhea is fairly common in primary peritonitis and less so in secondary peritonitis. 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) with a predominance of immature forms, 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. The blood culture is often positive in primary peritonitis.
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.
European Association for the Study of the Liver: EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis and hepatorenal syndrome in cirrhosis. J Hepatol 2010 Sep;53(3):397–417 [PMID: 20633946].
Koulaouzidis A et al: Spontaneous bacterial peritonitis. World J Gastroenterol 2009 Mar 7;15(9):1042–1049 [PMID: 19266595].
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, or infection, or it may occur after cardiac or abdominal surgery. It may be associated with intestinal malrotation.
A. Symptoms and Signs
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.
B. Laboratory Findings
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.
Complications & Sequelae
Chylous ascites caused by intestinal lymphatic obstruction is associated with fat malabsorption and protein loss. Intestinal loss of albumin and γ-globulin may lead to edema and increase the risk of infection. Rapidly accumulating chylous ascites may cause respiratory complications. The primary infections and malignancies causing chylous ascites may be life threatening.
Treatment & Prognosis
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 very 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 PN (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.
Chye JK et al: Neonatal chylous ascites: report of 3 cases and review of the literature. Pediatr Surg Int 1997;12:296 [PMID: 9099650].
Densupsoontorn N et al: Congenital chylous ascites: the roles of fibrin glue and CD31. Acta Paediatr 2009 Nov;98(11): 1847–1849 [PMID: 19627262].
Olivieri C, Nanni L, Masini L, Pintus C: Successful management of congenital chylous ascites with early octreotide and total parenteral nutrition in a newborn. BMJ Case Rep 2012 Sep 25;2012 [PMID: 23010459].
GASTROINTESTINAL TUMORS & MALIGNANCIES
Juvenile polyps belong to the hamartomatous category of polyps 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. These are the most common type of intestinal polyps in children. Their incidence is highest between ages 3 and 5 years. They are rare before age 1 year and usually occur before age 10. 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 the polyp by electrocautery, nothing further should be done if histologic findings confirm the diagnosis. There is a slight risk of developing further juvenile polyps. Other polyposis syndromes are summarized in Table 21–4.
Figure 21–6. Juvenile polyp. Solitary, smooth polyp coated with exudate and erythematous pattern that lies on the surface of a normal colonic mucosa.
Table 21–4. Gastrointestinal polyposis syndromes.
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 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. Other types of hamartomatous polyp syndromes include Peutz–Jeghers syndrome and the PTEN hamartoma tumor syndrome. Peutz-Jaghers syndrome is associated with polyps commonly in the small intestine and colon but can also been seen in the stomach and in other organs. There is a distinctive mucocutaneous pigmentation (freckling) that appears early on but can disappear by age 5, along the vermillion border of the lips, buccal mucosa, and hands and feet. Besides of 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. PTEN hamartoma syndrome involves a spectrum of hamartomatous conditions that are associated with mutations in the PTEN gene. This includes nearly all Cowden syndrome and some Bannayan-Riley Ruvalcaba syndrome and Proteus syndrome. Besides hamartomas and other benign tumors throughout the body, there is an increased risk of intestinal and extraintestinal cancers.
Barnard J: Screening and surveillance recommendations for pediatric gastrointestinal polyposis syndrome. J Pediatr Gastroenterol Nutr 2009 Apr;48(Suppl 2):575–578 [PMID: 19300132].
Thakkar K, Fishman DS, Gilger MA: Colorectal polyps in childhood. Curr Opin Pediatr 2012 Oct;24(5):632–637. doi: 10.1097/MOP.0b013e328357419f [PMID: 22890064].
Zbuk KM, Eng C: Hamartomatous polyposis syndromes: Nat Clin Pract Gastroenterol Hepatol 2007 Sep;4(9):492–502.
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 cancer of the esophagus.
The most common gastric or small bowel cancer in children is lymphoma or lymphosarcoma. Intermittent abdominal pain, abdominal mass, intussusception, or a celiac-like picture may be present. Carcinoid tumors are usually benign and most often an incidental finding in the appendix. Metastasis is rare. The carcinoid syndrome (flushing, sweating, hypertension, diarrhea, and vomiting), associated with serotonin secretion, only occurs with metastatic carcinoid tumors.
Adenocarcinoma of the colon is rare in childhood. The transverse colon and rectosigmoid are the two most commonly affected sites. 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 are at greater risk.
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.
Tan JJ, Tan KK, Chew SP: Mesenteric cysts: an institution experience over 14 years and review of the literature. Worl J Surg 2009 Sep;33(9):1961–1965 [PMID: 19609826].
INTESTINAL HEMANGIOMAS AND VASCULAR MALFORMATIONS
Hemangiomas and vascular malformations of the GI tract are uncommon causes of GI bleeding in children and adults. Like their skin counterparts, intestinal hemangiomas are typically not present at birth and then appear in the first 2 months of life, undergoing a rapidly proliferating growth phase during the first year, during which they are most likely to cause symptomatic bleeding, before involution thereafter. 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.
These vascular lesions are most often found in the small intestine and may cause acute or occult blood loss. They may also cause intussusception, local stricture, or intramural hematoma. Thrombocytopenia and consumptive coagulopathy are occasional complications of rapidly growing hemangiomas during their rapid proliferation phase. Typically intestinal vascular lesions are 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. The physical examination is 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 have allowed for diagnosis and potential therapy of small bowel vascular lesions that were previously inaccessible endoscopically.
Rapidly proliferating hemangiomas of the skin and liver have been treated medically with corticosteroids, propranolol, 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. 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.
Yoo S: GI-associated hemangiomas and vascular malformations. Clin Colon Rectal Surg 2011 Sep;24(3):193–200 [PMID: 22942801].
MAJOR GASTROINTESTINAL SYMPTOMS & SIGNS
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, a 67-nm double-stranded RNA virus with at least eight serotypes, is the most common. 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.
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 usually lasts 4–8 days but may last longer in young infants or immunocompromised patients. Rotavirus cannot be definitively diagnosed on clinical grounds alone. Rotavirus antigens can be identified in stool or virus can be seen by scanning electron microscopy. The specific identification of rotavirus is not required in every case, however, as treatment is nonspecific. Additionally 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.
Treatment is nonspecific and supportive, aimed at replacement of fluid and electrolyte deficits, along with ongoing losses, especially in small infants. (Oral and intravenous therapy are discussed in Chapter 45.) 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. 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 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 location, enteric adenoviruses (serotypes 40 and 41) or caliciviruses 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 duration of illness may be longer. The Norwalk agent (now called norovirus), a calicivirus, 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.
Cytomegalovirus rarely causes diarrhea in immunocompetent children but may cause erosive colitis or enteritis 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. Probiotics are moderately effective in treating acute viral gastroenteritis in healthy children. Probiotics should be used with extreme caution, however, in immunocompromised, chronically debilitated, or seriously ill children.
American Academy of Pediatrics Committee on Infectious Diseases: Prevention of rotavirus disease: guidelines for the use of rotavirus vaccine. Pediatrics 2007;119:171 [PMID: 17200286].
Bernstein DT: Rotavirus overview. Pediatric Infect Dis J 2009 Mar;28(Suppl 3):S50–S53 [PMID: 19252423].
O’Ryan M et al: An update on management of severe acute infectious gastroenteritis in children. Expert Rev Anti Infect Ther 2010 Jun;8(6):671–682 [PMID: 20521895].
Thomas DW et al: Probiotics and prebiotics in pediatrics. Pediatrics 2010 Dec;126(6):1217–1231 [PMID: 21115585].
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/d 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. Recent data suggest that the use of probiotics 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.
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 immune functions, both cellular and humoral.
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.
Laxative abuse in association with eating disorders or münchausen 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 probably 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 usually help control symptoms. If these measures fail, loperamide (0.1–0.2 mg/kg/d in two or three divided doses) can be used as needed for symptomatic relief.
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.
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Grimwood K et al: Acute and persistent diarrhea. Pediatr Clin North Am 2009 Dec;56(6):1343–1361 [PMID: 19962025].
Ramaswamy K et al: Infectious diarrhea in children. Gastroenterol Clin North Am 2001 Sep;30(3):611–624 [PMID: 11586548].
Vomiting blood and passing blood per rectum are alarming symptoms. The history, physical examination, and initial evaluation are key to identifying the bleeding source. In large-volume, acute GI bleeding the primary focus, however, should first center on stabilizing the patient to ensure adequate hemodynamic support.
The first goal of the history is to determine if GI bleeding is truly blood and if the source is the GI tract. 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. Is the blood in emesis, stool, or both? How much blood is there and what is its color and character? History of NSAID use and 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. Table 21–6 gives further cues in the presentation to help identify the source of bleeding.
Table 21–5. Identification of sites of gastrointestinal bleeding.
Table 21–6. Differential diagnosis of gastrointestinal bleeding in children by symptoms and age at presentation.
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, current and recent medications, associated symptoms (pain, vomiting, diarrhea, fever, weight loss), and family history of GI disorders (IBD, CD, liver disease, bleeding/coagulation disorder). In addition to these historical features, the age of the patient offers additional clues to determine the likely etiology. In the presence of massive upper GI bleeding in the toddler, a high index of suspicion for button battery ingestion must be maintained despite the lack of any known history of ingestion. Table 21–7lists causes of GI bleeding by age and presentation.
Table 21–7. Differential diagnosis of acute abdomen.
The most important aspect of the examination and initial assessment is to determine if the child acutely or chronically ill and initiate supportive measures as rapidly as necessary. The physical examination should be thorough. 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.
A systolic blood pressure below 100 mm Hg and a pulse rate above 100 beats/min in an older child suggest at least a 20% reduction of blood volume. A pulse rate increase of 20 beats/min or a drop in systolic blood pressure greater than 10 mm Hg when the patient sits up is also a sensitive index of volume depletion. Tachycardia may be the initial indication of persistent bleeding.
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), blood urea nitrogen (BUN)/creatinine (for possible hemolytic uremic syndrome), and stool culture/C difficile toxin assay (for acute bloody diarrhea suggestive of infectious colitis). Low mean corpuscular volume (MCV) in association with anemia suggests chronic GI losses and may warrant addition of iron studies as well. Serial determination of vital signs and hematocrit are 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 loss of blood. 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.
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, 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.
In severe bleeding, the ABCs of resuscitation should be performed. Adequate IV access is critical in these cases to ensure that fluid boluses and blood products are able to be delivered. If a hemorrhagic diathesis is detected, vitamin K should be given intravenously and additional blood products should be administered as needed 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, upper intestinal endoscopy may be considered to identify the bleeding site. Endoscopy is superior to barium contrast study for lesions such as esophageal varices, stress ulcers, and gastritis. 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. Colonoscopy may identify the source of bright red rectal bleeding, but it should be performed as an emergency procedure only if the extent of bleeding warrants immediate investigation and if plain abdominal radiographs show no signs of intestinal 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.
Persistent vascular bleeding (varices [Figure 21–7], vascular anomalies) may be relieved temporarily using intravenous octreotide, 1–4 mcg/kg/h. Sustained infusion of octreotide may be used for up to 48 hours if needed with careful monitoring of glucose homeostasis. A single-center review of cases of massive variceal bleeding in children found a significant decrease in transfusion requirements with the use of octreotide. Bleeding from esophageal varices may be stopped by compression with a Sengstaken-Blakemore tube. Endoscopic sclerosis or banding of bleeding varices is effective treatment.
Figure 21–7. Esophageal varices. Serpiginous esophageal varix extending to the esophageal lower esophageal sphincter.
If gastric decompression, acid suppressive therapy, and transfusion 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. If bleeding remains refractory to therapy, emergency surgery may be necessary. In some cases, angiography and selective embolization have been used successfully in unidentified and refractory bleeding.
Al-Hussaini A, Butzner D: Therapeutic applications of octreotide in pediatric patients. Saudi J Gastroenterol 2012 Mar–Apr 2012; 18(2):87–94 [PMID: 22421712].
Alomari AI, Fox V, Kamin D, Afzal A, Arnold R, Chaudry G: Embolization of a bleeding Dieulafoy lesion of the duodenum in a child. Case report and review of the literature. J Pediatr Surg 2013 Jan;48(1):e39–e41 [PMID: 23331838].
Cleveland K, Ahmad N, Bishop P, Nowicki M: Upper gastrointestinal bleeding in children: an 11-year retrospective endoscopic investigation. World J Pediatr 2012 May;8(2):123–128 [PMID: 22573422].
Davis JS, Ryan ML, Fields JM, Neville HL, Perez EA, Sola JE: Use of CT enterography for the diagnosis of lower gastrointestinal bleeding in pediatric patients. J Pediatr Surg 2013 Mar;48(3):681–684 [PMID: 23480934].
Freedman SB, Stewart C, Rumantir M, Thull-Freedman JD: Predictors of clinically significant upper gastrointestinal hemorrhage among children with hematemesis. J Pediatr Gastroenterol Nutr 2012 Jun;54(6):737–743 [PMID: 22108337].
Vomiting is an extremely complex activity and is triggered by stimulation of chemoreceptors and mechanoreceptors in the wall of the GI tract, activated by contraction, distension, and physical damage. The vomiting center, paraventricular nuclei, in the brain controls the emetic response. These nuclei receive afferent input from many sources, 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. Additionally, local feedback loops in the gut also appear capable of initiating vomiting. 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 symptom of many pediatric conditions. It is the pediatrician’s difficult job to find the underlying cause. The most common cause of vomiting in childhood is probably acute viral gastroenteritis. However, obstruction and acute or chronic inflammation of the GI tract and associated structures are also major causes. CNS inflammation, pressure, or tumor 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. Regurgitation associated with GE reflux of infants should be distinguished from vomiting. Occasionally, regurgitated fluid stimulates the pharyngeal afferents and provokes gagging or even a complete vomiting complex.
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.
DeCamp LR et al: Use of anti-emetic agents in acute gastroenteritis: a systematic review and meta-analysis. Arch Pediatr Adolesc Med 2008 Sep;162(9):858–865 [PMID: 18762604].
Levine DA: Anti-emetics for acute gastroenteritis in children. Curr Opin Pediatr 2009 Jun;21(3);294–298 [PMID: 19381093].
1. Cyclic Vomiting Syndrome
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 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.
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 münchausen syndrome by proxy. Although tests for GE reflux are often positive in these patients, it is unlikely that GE reflux and CVS are related.
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 are often 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, or antihistamines such as cyproheptadine is often effective in some patients with frequent or disabling spells. Some patients have been successfully treated with anticonvulsants.
Sudel B, Li BU: Treatment options for cyclic vomiting syndrome. Curr Treat Options Gastroenterol 2005;8:387 [PMID: 16162304].
RECURRENT ABDOMINAL PAIN
Approximately 2%–4% of all pediatric office visits occur because of unexplained, recurrent abdominal pain. In addition, up to 17% of adolescents have been reported to have recurrent abdominal pain. Based on the Rome III criteria, the descriptive term “recurrent abdominal pain” has been discarded for the more meaningful terms that fall into the categories of “functional GI disorders,” which encompasses four entities: functional dyspepsia, irritable bowel syndrome, abdominal migraines, and childhood functional abdominal pain not otherwise specified.
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. Attacks of pain are of variable duration and intensity. Parents or patients commonly report that the pain is constant, all day, every day. 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, pain leading to night awakening, rashes, or joint aches. In addition, these children do not have a history of unintentional weight loss 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 history of functional GI complaints is often found in family members. A family history, however, of IBD, peptic ulcer disease, and CD is absent.
A thorough physical examination that includes a rectal examination is essential and usually normal. Complaints of abdominal tenderness elicited during palpation may be out of proportion to visible signs of distress.
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.
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. Abdominal migraine and cyclic vomiting are less common conditions with an episodic character often associated with vomiting. The incidence of peptic gastritis, esophagitis, duodenitis, and ulcer disease is probably underappreciated.
Treatment & Prognosis
Treatment 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 older patients, and in those with what appears to be visceral hyperalgesia, amitriptyline in low doses may occasionally be helpful. Antispasmodic medications are rarely helpful and should be reserved for patients with more typical irritable bowel complaints.
Chiou E et al: Management of functional abdominal pain and irritable bowel syndrome in children and adolescents. Expert Rev Gastroenterol Hepatol 2010 Jun; 4(3):293–304 [PMID: 20528117].
Drossman DA: The functional gastrointestinal disorders and the Rome III process. Gastroenterology 2006;130:1377–1390 [PMID: 16678553].
Grover M: Functional abdominal pain. Curr Gastroenterol Rep 2010 Oct;12(5):391–398 [PMID: 20694840].
Rasquin A et al: Childhood functional gastrointestinal disorders: child/adolescent. Gastroenterology 2006;130:1527 [PMID: 16678566].
An acute abdomen is a constellation of findings indicating an intra-abdominal process that may require surgery. A degree of urgency is implied when this diagnosis is suspected. The pain of an acute abdomen intensifies over time and is rarely relieved without definitive treatment. Pain is often accompanied by nausea, vomiting, diarrhea, fever, and anorexia. Pain may be localized or generalized. The abdomen may be distended and tense, and bowel sounds reduced or obstructive. Patients appear ill and are reluctant to be examined or moved. The acute abdomen is usually a result of infection of the intra-abdominal or pelvic organs, but it also occurs with intestinal obstruction, intestinal perforation, inflammatory conditions, trauma, and some metabolic disorders. Some of the conditions causing acute abdomen are listed in Table 21–8. 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.)
Table 21–8.Malabsorption syndromes.
Malabsorption of ingested food has many causes (see Table 21–8). Shortened length (usually via surgical resection) and mucosal damage (CD) both reduce surface area. Impaired motility interferes with normal propulsive movements, which affects mixing of food with pancreatic and biliary secretions and permits anaerobic bacterial overgrowth. Bacterial overgrowth may lead to increased carbohydrate fermentation with resultant acidic diarrhea. A second mechanism is 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 cause nutrient malabsorption. Malabsorption of specific nutrients may also be genetically determined (disaccharidase deficiency, glucose-galactose malabsorption, and abetalipoproteinemia).
Diarrhea, vomiting, anorexia, abdominal pain, failure to thrive, and abdominal distention are common. Stools associated with fat malabsorption are characterized as bulky, foul, greasy, and pale; in contrast, those seen with osmotic diarrhea 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.
Quantifying fat malabsorption by timed stool collection compares amount of ingested to excreted fat. Stool loss of 10%–15% of ingested fat is normal in infancy, while loss of 5% of ingested fat is normal for 1- to 10-year-olds. 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 vitamin D. Loss of serum proteins across the intestinal mucosa is suggested by elevated fecal α1-antitrypsin levels. Disaccharide or monosaccharide malabsorption manifests by stool pH less than 5.5 due to lactic acid and reducing substances in the stool. Specific enzyme deficiencies may be evaluated by breath hydrogen test, or small intestinal biopsy showing normal histology and measurement of specific disaccharidase activity. Other screening tests suggesting a specific diagnosis include sweat chloride concentration (cystic fibrosis), intestinal mucosal biopsy (CD, lymphangiectasia, IBD), liver and gallbladder function tests, and pancreatic secretion after stimulation with secretin and cholecystokinin. Some of the most common disorders associated with malabsorption in pediatric patients are detailed as follows.
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 infiltration of the intestine or its lymphatics and vasculature by malignant cells. Chronic elevation of venous pressure in children with the Fontan procedure and elevated right-sided heart pressures may produce protein-losing enteropathy.
Signs and symptoms are mainly those caused by hypoproteinemia and in some instances by fat malabsorption: edema, ascites, poor weight gain, anemia, and specific vitamin (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). Disorders associated with protein-losing enteropathy are listed in Table 21–9. In the presence of intestinal bleeding, fecal α1-antitrypsin measurements are falsely high.
Table 21–9. Disorders associated with protein-losing enteropathy.
Hypoalbuminemia may be due to increased catabolism, poor protein intake, impaired hepatic protein synthesis, or congenital malformations of lymphatics outside the GI tract. Protein losses in the urine from nephritis and nephrotic syndrome may also cause hypoalbuminemia.
Albumin infusion, diuretics, and a high-protein, low-fat diet may control symptoms. Nutritional deficiencies should be addressed. Treatment must be directed toward identifying and treating the underlying cause.
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 anytime after gluten is introduced in the diet, with symptoms of abdominal pain, diarrhea, vomiting, distention, and sometimes constipation. Other manifestations include oral ulcers, a pruritic rash (dermatitis herpetiformis), growth and pubertal delay, iron-deficiency anemia, decreased bone mineralization, and arthritis. Disease frequency in Western populations approaches 1 in 100. Associated conditions 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.
A. Symptoms and Signs
1. Gastrointestinal manifestations—The classic form of CD consists of GI symptoms with onset soon after gluten-containing foods are introduced in the diet, usually 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 chronic abdominal pain, chronic constipation, bloating, and diarrhea that mimic symptoms of lactose intolerance, functional abdominal pain, or irritable bowel syndrome.
2. Nongastrointestinal manifestations—Adolescents may present with delayed puberty or short stature, and in females, delayed menarche. CD should be considered in children with unexplained iron-deficiency anemia, decreased bone mineral density, elevated liver function enzymes, arthritis, or epilepsy with cerebral calcifications. Asymptomatic individuals are identified on screening, such as those with type 1 diabetes. The need for early screening and treatment in asymptomatic individuals is unclear.
B. Laboratory Findings
1. Serologic and genetic testing—Screening tests exist with excellent sensitivity and specificity. In IgA-sufficient patients these are the IgA antitissue transglutaminase, IgA antiendomysial and IgA/IgG antideamidated gliadin peptide antibodies. In the presence of IgA deficiency, IgG-based antitissue transglutaminase and antiendomysium antibodies are available. Genetic testing for HLA-DQ2 and DQ8 has a high negative predictive value, and is useful in assessing risk for CD in family members, but not for screening for the presence of CD.
2. Stools—Stools may have increased levels of partially digested fat and may be acidic from secondary lactose intolerance.
3. Hypoalbuminemia—Hypoalbuminemia can be severe enough to lead to edema.
4. Anemia—Anemia with low MCV and evidence of iron deficiency is common.
C. Biopsy Findings
Patients should remain on a diet containing gluten until biopsy. Characteristic duodenal biopsy findings on light microscopy are villous atrophy with increased numbers of intraepithelial lymphocytes. Findings may be patchy.
The differential diagnosis includes food allergies, Crohn disease, postinfectious diarrhea, immunodeficiencies, graft-versus-host disease, and hypergastrinemia (Zollinger-Ellison syndrome).
Treatment is dietary gluten restriction for life. All sources of wheat, rye, and barley are eliminated. Most, but not all, patients tolerate oats. The intestinal mucosa should normalize by 6–12 months while lactose intolerance resolves often 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.
Corticosteroids are indicated only in patients with celiac crisis with profound anorexia, malnutrition, diarrhea, edema, abdominal distention, and hypokalemia.
Enteropathy-associated T-cell lymphoma of the small bowel occurs with increased frequency in adults with long-standing untreated disease. Individuals with poor adherence to gluten-free diet may be at increased risk for fractures, iron-deficiency anemia, and infertility.
American Celiac Disease Alliance: www.americanceliac.org.
Catassi C, Fasano A: Celiac disease diagnosis: Simple rules are better than complicated algorithms. Am J Med 2010 Aug;123(8): 691–693 [PMID: 20670718].
Husby S et al: European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of celiac disease. J Pediatr Gastroenterol Nutr 2012;54:136–160 [PMID: 22197856].
3. 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 higher in the jejunum and proximal ileum than in the distal ileum and duodenum. Characteristics of primary disaccharidase deficiency include permanent disaccharide intolerance, absence of intestinal injury, and frequent positive family history. Because disaccharidases are located on the luminal surface of intestinal enterocytes, mucosal damage, such as from acute viral enteritis, causes transient secondary disaccharidase deficiency.
A. Lactase Deficiency
Congenital lactase deficiency is extremely rare. All human ethnic groups are lactase-sufficient at birth. Genetic or familial lactase deficiency appears after 5 years of age. In Asians, Alaskan natives, and Native Americans, genetic lactase deficiency develops in virtually 100%. In Africans, the incidence in most tribes is over 80%. In African Americans, the incidence is about 70%, and among Caucasian Americans, between 30% and 60%. Acquired or secondary lactase deficiency caused by intestinal injury due to viral infection, inflammatory disease, radiation, and drugs is common, but transient, resolving within a few weeks.
Lactose ingestion in deficient individuals causes variable degrees of diarrhea, abdominal distention, flatus, and abdominal pain depending on the residual enzyme activity and the dose of lactose. Stools are liquid or frothy with a pH less than 5.5 owing to the presence of organic acids. Reducing substances are present in fresh stools. Diagnostic tests include genetic testing, lactose breath test with a rise in breath hydrogen content due to fermentation of undigested lactose by normal colonic flora, and a lactose load test in which blood glucose fails to rise more than 10 mg/dL after ingestion of 1 g/kg of lactose. Symptoms resolve when dietary lactose is restricted or lactase supplementation is added to milk products or taken with meals to enhance lactose hydrolysis.
B. Sucrase-Isomaltase Deficiency
This condition is inherited in an autosomal recessive fashion and is most common in Greenland, Iceland, and among Alaskan natives. The condition is rare in other groups. Abdominal distention, failure to thrive, and watery diarrhea are the presenting symptoms. Stools are usually watery and acidic. Because sucrose is not a reducing sugar, stool may test negative for reducing substances unless the sucrose is hydrolyzed by colon bacteria. Diagnosis is made by oral sucrose tolerance testing (1 g/kg) with elevated breath hydrogen content, or by testing a snap frozen intestinal biopsy for enzyme activity. There are partial enzyme deficiencies. Treatment is avoidance of sucrose and starches rich in amylopectin, or the use of sacrosidase enzyme supplement.
Treem WR: Clinical aspects and treatment of congenital sucrose-isomaltase deficiency. J Pediatr Gastroenterol Nutr 2012; 55(Suppl 2):S7–S13 [PMID: 23103658].
CSID parent support group: www.csidinfo.com.
QOL Medical, LLC: www.sucraid.net.
4. 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. Small bowel histologic findings are normal. Glycosuria and aminoaciduria may occur. The glucose tolerance test is abnormally flat. Fructose is well tolerated. Diarrhea subsides promptly on withdrawal of glucose and galactose from the diet. The acquired, transient form of glucose-galactose malabsorption occurs mainly in infants younger than 6 months, usually following acute viral or bacterial enteritis.
In the congenital disease, exclusion of glucose and galactose from the diet is mandatory. A carbohydrate-free base formula is used with added fructose. The prognosis is good if diagnosed early. Tolerance for glucose and galactose improves with age. In the secondary (acquired) form, prolonged PN may be required until healing.
Wright EM et al: Active sugar transport in health and disease. J Intern Med 2007;26:32–43 [PMID: 17222166].
5. Dietary Fructose Intolerance
Fructose malabsorption occurs when fructose is in excess of glucose, often with consumption of high-fructose corn syrup. Malabsorbed fructose is fermented by colonic bacteria, and excess hydrogen and other gases are produced. Symptoms include abdominal pain, bloating, flatulence, and diarrhea. These symptoms may mimic irritable bowel syndrome. The capacity for human fructose absorption has a wide range and may be inducible by dietary consumption. Diagnosis is made with a fructose breath hydrogen test and is bolstered by the occurrence of symptoms during the test.
Kyaw MH, Mayberry JF: Fructose malabsorption: true condition or a variance from normality. J Clin Gastroenterol 2011 Jan;45(1):16–21 [PMID: 20818234].
6. Intestinal Lymphangiectasia
This form of protein-losing enteropathy results from a congenital ectasia of the bowel lymphatic system often associated with abnormalities of the lymphatics in the extremities. Obstruction of lymphatic drainage of the intestine leads to rupture of the intestinal lacteals with leakage of lymph into the lumen of the bowel. Fat loss in the stool may be significant. Chronic loss of lymphocytes and immunoglobulins increases the susceptibility to infections.
Peripheral edema, diarrhea, abdominal distention, chylous effusions, and repeated infections are common. Laboratory findings include reduced serum albumin, decreased immunoglobulin levels, lymphocytopenia, and anemia. Serum calcium and magnesium are frequently depressed as these cations are lost in complex with unabsorbed fatty acids. Lymphocytes may be seen on a stool smear. Fecal α1-antitrypsin is elevated. Radiographic studies reveal an edematous small bowel wall, and biopsy findings 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 (camera) endoscopy shows diagnostic brightness secondary to the fat-filled lacteals.
Other causes of protein-losing enteropathy must be considered, although an associated lymphedematous extremity strongly favors this diagnosis.
Treatment & Prognosis
A high-protein diet (6–7 g/kg/d may be needed) enriched with medium-chain triglycerides as a fat source usually allows for adequate nutrition and growth in patients with intestinal mucosal lymphangiectasia. The serum albumin may not normalize. 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 also be used to control symptoms but are usually not needed chronically. The prognosis is not favorable, although remission may occur with age. Malignant degeneration of the abnormal lymphatics may occur, and intestinal lymphoma of the B-cell type may be a long-term complication.
7. 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 the infant is still exclusively breast-fed. The most common form is a healthy infant with flecks of blood in the stool. Infants may present with loose mucoid stools that are blood streaked but otherwise appear well. These symptoms typically occur as a result of cow’s milk protein that is either present in formula or breast milk. A family history of atopy is common in these infants. Skin testing is not reliable and not indicated. Treatment consists of eliminating the source of the protein; in the breast-fed infant, maternal avoidance of milk protein will usually reduce signs of colitis. Substituting a protein hydrolysate formula for cow’s milk-based formula may reduce symptoms. A more severe form of FPIES may require steroids. 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, some suggest that if the symptoms are mild and the infant is thriving, no treatment may be indicated. Colonoscopy is not required for diagnosis, but rectal biopsies, if performed, show mild lymphonodular hyperplasia, mucosal edema, and eosinophilia.
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.
De Greef E et al: Diagnosis and management of cow’s milk protein allergy in infants. World J Pediatr 2012 Feb;8(1):19–24 [PMID: 22282379].
Leonard SA, Nowak-Wegrzyn A: Food protein-induced enterocolitis syndrome: an update on natural history and review of management. Ann Allergy Asthma Immunol 2011 Aug;107(2):95–101 [PMID: 21802016].
8. 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. Destruction of acinar cells may occur before birth. Some genotypes of cystic fibrosis have partially or completely preserved pancreatic exocrine function. Other conditions associated with exocrine pancreatic insufficiency are discussed in Chapter 22.
9. Other Genetic Disorders Causing Malabsorption
Abetalipoproteinemia is an autosomal recessive condition in which the secretion of triglyceride-rich lipoproteins from the small intestine (chylomicrons) and liver (very low-density lipoproteins) is abnormal. Profound steatosis of the 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, which 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
Inflammatory bowel disease (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. The genetic association is clear, with 5%–30% of patients identifying a family member with IBD, and a 10–20 relative risk of a sibling developing IBD. The 15%–36% concordance rate for monozygotic twins indicates that genetics is important but not sufficient for development of IBD.
A. Symptoms and Signs
Most commonly, inflammation causes abdominal pain, diarrhea, bloody stools, fever, anorexia, fatigue, and weight loss. CrD may also cause a stricturing process with abdominal pain and intestinal obstruction, or as a penetrating/fistulizing process with abscess, perianal disease, or symptoms similar to acute appendicitis. UC usually presents with crampy abdominal pain, diarrhea, and blood in the stool.
CrD can affect any part of the GI tract from the lips to the anus. In pediatrics, CrD most often affects the terminal ileum and colon although it may have a patchy distribution with skip areas of uninvolved bowel. UC is limited to the colon, and in children it usually involves the entire colon (pancolitis) without skip areas. The younger the age of onset, the more likely the course will be severe.
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 typical presentation, course, radiographic, endoscopic, and histologic findings, and exclusion of other disorders. No single test is diagnostic. Patients with IBD often have low hemoglobin, iron, and serum albumin levels, and elevated ESR and CRP and fecal calprotectin. IBD-related serum antibodies are present in most, with antibodies to Saccharomyces cerevisiae (ASCA) in 60% of patients with CrD, while serum perinuclear antineutrophil cytoplasmic antibodies (pANCAs) are present in approximately 70% of UC patients. 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. Barium upper GI radiographs with small bowel follow-through may reveal small bowel disease, especially terminal ileal thickening with separation of bowel loops, and enteric fistulas. Abdominal imaging with US, CT, or magnetic resonance may show mucosal and mural edema and exclude other etiologies.
Upper endoscopy and ileocolonoscopy are the most useful diagnostic modalities, revealing severity and extent of upper intestinal, ileal, and colonic involvement. Video capsule provides images of the entire small bowel. Granulomas are found in only 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 and/or duodenitis.
Figure 21–8. Ulcerative colitis. White exudate is present overlying an abnormal colonic mucosa that has lost its typical vascular pattern.
Figure 21–9. Crohn colitis. Discrete aphthous lesions are scattered across a thickened mucosa with some areas with normal vascular pattern.
When extraintestinal symptoms predominate, CrD can be mistaken for rheumatoid arthritis, systemic lupus erythematosus, CD, or hypopituitarism. The acute onset of ileocolitis may be mistaken for intestinal obstruction, appendicitis, lymphoma, amebiasis, or tuberculosis. Malabsorption symptoms suggest CD, peptic ulcer, Giardia infection, 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, Giardia, and C difficile, and, if immunocompromised, CMV. Mild IBD mimics irritable bowel syndrome, or lactose intolerance. Eosinophilic gastroenteropathy and vasculitic lesions should also be considered. Behçet disease should be considered if there are deep intestinal ulcers, and is characterized by 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.
A. Crohn Disease
Nutritional complications from chronic active disease, malabsorption, anorexia, protein-losing enteropathy, bile salt malabsorption, or secondary lactose intolerance include failure to thrive, short stature, decreased bone mineralization, and specific nutrient deficiencies, including iron, calcium, zinc, vitamin B12, and vitamin D. In addition, corticosteroid therapy may impact growth and bone mineral density. Most patients achieve reasonable final adult height. Intestinal obstruction, fistulae, abdominal abscess, perianal disease, pyoderma gangrenosum, arthritis, and amyloidosis occur. Crohn colitis carries a risk for adenocarcinoma of the colon.
B. Ulcerative Colitis
Even with the typical features and course of UC, up to 3%–5% of patients may have an ultimate diagnosis of CrD. Arthritis, uveitis, pyoderma gangrenosum, and malnutrition all 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 both UC and sclerosing cholangitis.
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 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—Ensuring adequate nutrition for normal growth as well as for puberty 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. Supplemental calories in the form of liquid diets or enteral (nasogastric [NG] tube supplements) are well tolerated and promote catch-up growth in severe CrD. Bowel rest with liquid or elemental diet or PN is a therapy for CrD, and it promotes linear growth and sexual development. Diet therapies are less effective in UC.
2. Aminosalicylates (ASA)—Multiple preparations of 5-ASA derivatives are available and are used to induce and maintain remission in mild CrD and UC. Common preparations including 5-ASA products such as sulfasalazine (50 mg/kg/d), or balsalazide (0.75–2.5 g PO tid) or mesalamine products, are available in tablets, granules, and delayed release formulations targeting specific locations in the GI tract (adult dose range 2.4–4.8 g/d). 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/d) may be given intravenously when disease is severe. For moderate disease, prednisone (1 mg/kg/d, orally in one to two divided doses) is given until symptomatic response, followed by gradual tapering over 4–8 weeks. A flare is common during the taper, requiring reinduction and a slower taper course. Steroid dependence is an indication for use of an immunomodulator. Ileocecal CrD is effectively treated with budesonide (9 mg QAM), with less side effects than systemic steroids, due to “single-pass” clearance by the liver. 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 IBD is moderate to severe, or the patient is steroid-dependent, immunomodulators are effective in maintaining remission and reducing the need for corticosteroids. AZA (2–3 mg/kg/d PO) or 6MP (1–2 mg/kg/d 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 assessed before starting therapy to determine dosing. For individuals deficient in TPMT, MTX should be used; for intermediate enzyme activity, dose is reduced by 50%. In cases where adherence may be an issue, or where dose adjustments may be necessary, AZA or 6MP metabolites may be measured in red blood cells by specialized testing. Maximum therapeutic efficacy may not be seen for 2–3 months after beginning treatment. Side effects include pancreatitis, hepatotoxicity, and bone marrow suppression.
MTX, effective in CrD but not UC, has a more rapid onset of action, usually 2–3 weeks, and is given in weekly doses, orally or intramuscularly. Most common side effect is nausea, 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/d in three divided doses) and ciprofloxacin have been used to treat perianal CrD and bacterial overgrowth. Peripheral neuropathy may occur with prolonged use of metronidazole.
6. Biologicals—Infliximab, a chimeric monoclonal antibody against tumor necrosis factor-α (TNFα) is used for moderate to severe CrD and UC, and for fistulizing disease. Adalimumab and certolizumab are similar injectable agents. Recurrence of disease often occurs within 12 months of stopping therapy. 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 use of biological with AZA/6MP.
7. Other agents—Cyclosporine or tacrolimus may be used as a “bridge” to more definitive therapy (such as colectomy for UC). Thalidomide has been used, especially in patients with oral and vaginal ulcers secondary to CrD, but is a known teratogen. Probiotics and prebiotics are frequently used but with very limited data on efficacy.
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 is not curative. 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, and repeated surgery is common.
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. Colectomy may also be performed for prevention of colorectal cancer after 7–8 years of disease. Colectomy usually requires a temporary ileostomy with J-pouch formation. After ileostomy takedown, pouchitis develops in up to 25% of patients, manifested by diarrhea and cramping, but it usually responds to metronidazole or ciprofloxacin. Liver disease associated with UC (sclerosing cholangitis) is not improved by colectomy.
The ImproveCareNow network develops collaborative, data-driven improvements in the health of children with IBD. Remission rates have increased to greater than 75%.
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