Viruses are the most common cause of acute gastroenteritis in developing and developed countries. Bacterial and parasitic enteric infections are discussed in Chapters 42 and 43. Of the viral agents causing enteric infection, Rotavirus and Caliciviridae (Norovirus and Sapovirus) are the most common, followed by enteric adenovirus, and Astrovirus. As with most viral pathogens, rotavirus affects the small intestine, causing voluminous watery diarrhea without leukocytes or blood. In the United States, rotavirus primarily affects infants between 3 and 15 months of age. The peak incidence in the United States is in the winter with sporadic cases occurring at other times. The virus is transmitted via the fecal-oral route and survives for hours on hands and for days on environmental surfaces. Rotavirus had been the most common viral source accounting for between 1/3 and 2/3 of hospitalizations prior to vaccine introduction.
The incubation period for rotavirus is 1–3 days. Symptoms caused by rotavirus are similar to other viral pathogens. Vomiting is the first symptom in 80%–90% of patients, followed within 24 hours by low-grade fever and watery diarrhea. Diarrhea is often preceded by vomiting and usually lasts 4–8 days but may last longer in young infants or immunocompromised patients. Fever is present in up to a third of patients. Rotavirus and adenoviruses can be detected in feces using EIA or latex agglutination. The specific identification of rotavirus is not required in every case, however, as treatment is nonspecific. Additional laboratory testing is also generally unnecessary but, when obtained, it will usually show a normal white blood cell count. Hyper- or hyponatremia may occur with dehydration. Metabolic acidosis can occur from bicarbonate loss in the stool, ketosis from poor intake, and in severe cases lactic acidemia occurs from hypotension and hypoperfusion. Stools do not contain blood or white blood cells.
As is with most other viral causes of acute diarrhea, treatment is nonspecific and supportive. Replacement of fluid and electrolyte deficits, along with ongoing losses, especially in small infants is necessary. (Oral and intravenous therapies are discussed in Chapter 23.) The use of oral rehydration solutions is appropriate in most cases. The use of clear liquids or hypocaloric (dilute formula) diets for more than 48 hours is not advisable. Early initiation of refeeding is recommended. Intestinal lactase levels may be reduced during rotavirus infection. Therefore, the brief use of a lactose-free diet may be associated with a shorter period of diarrhea but is not critical to successful recovery in healthy infants. Reduced fat intake during recovery may decrease nausea and vomiting.
Antidiarrheal medications are ineffective (kaolin-pectin combinations) and in some circumstances can be dangerous (loperamide, tincture of opium, diphenoxylate with atropine). Bismuth subsalicylate preparations may reduce stool volume but are not critical to recovery and are generally not recommended especially in young children due to the salicylate component and potential risk of Reye syndrome. Oral immunoglobulin or specific antiviral agents have occasionally been useful in limiting duration of disease in immunocompromised patients.
Most children are infected with rotavirus more than once, with the first infection being the most severe. Some protective immunity is imparted by the first infection. Prevention of infection occurs primarily by good hygiene and prevention of fecal-oral contamination. As treatment for rotavirus is nonspecific, prevention of illness is critical. The American Academy of Pediatrics issued guidelines in January 2007 recommending the routine use of bovine-based pentavalent rotavirus vaccine to be given orally to infants at 2, 4, and possibly 6 months of age, depending on which vaccine is used. Prevention is the key, and two rotavirus vaccines are commercially available, which are administered in multiple doses typically from 2 to 6 months of age.
2. Other Viral Infections Causing Acute Diarrhea
Other viral pathogens causing diarrhea in children can be identified in stool by electron microscopy, viral culture, or enzyme-linked immunoassay. Depending on the geographic norovirus and enteric adenoviruses are the next most common viral pathogens in infants. The symptoms of enteric adenovirus infection are similar to those of rotavirus, but infection is not seasonal and the incubation period more prolonged (8–10 days) with more prolonged duration of illness of typically 8–10 days, but up to 2 weeks.
Norovirus is now thought to be the leading source of community acquired diarrhea, and is highly contagious. Recent estimates suggest it is responsible for up to 800 deaths, 71,000 hospitalizations, 400,000 emergency department visits, 1.9 million outpatient visits, and 21 million morbidities annually. Norovirus is a small RNA virus that mainly causes vomiting but can also cause diarrhea in older children and adults, usually in common source outbreaks. The duration of symptoms is short, usually 24–48 hours. Other potentially pathogenic viruses include astroviruses, corona-like viruses, and other small round viruses. There is no FDA-approved assay for norovirus.
Cytomegalovirus rarely causes diarrhea in immunocompetent children but may cause erosive enteritis or colitis in immunocompromised hosts. Cytomegalovirus enteritis is particularly common after solid-organ and bone marrow transplant and in the late stages of human immunodeficiency virus (HIV) infection, but can be seen in patients taking immunosuppressive medication.
Probiotics may be effective in treating acute viral gastroenteritis in healthy children with potential reduction in duration and frequency of the illness. A diversity of opinions exist that range from the Center for Disease Control that states “not recommended” to that from the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition that “strongly” recommends use. Probiotics should be used with caution, however, in immunocompromised or seriously ill children, in particular those with a central venous catheter.
DT: Rotavirus overview. Pediatric Infect Dis J 2009 Mar;28(Suppl 3):S50–S53
et al: An update on management of severe acute infectious gastroenteritis in children. Expert Rev Anti Infect Ther 2010 Jun;8(6):671–682
et al: 2017 Infectious Diseases Society of America clinical practice guidelines for the diagnosis and management of infectious diarrhea. Clin Infect Dis 2017 Nov 29 ;65(12):e45–e80
et al: The pros, cons, and many unknowns of probiotics. Nat Med 2019;25(5): 716–729
Bowel habits are variable, making the specific diagnosis of chronic diarrhea difficult. Some healthy infants may have five to eight stools daily. A gradual or sudden increase in the number and volume of stools to more than 15 g/kg/day combined with an increase in fluidity should raise a suspicion that an organic cause of chronic diarrhea is present. Diarrhea may result from (1) interruption of normal cell transport processes for water, electrolytes, or nutrients; (2) decrease in surface area available for absorption secondary to shortened bowel or mucosal disease; (3) increase in intestinal motility; (4) increase in unabsorbable, osmotically active molecules in the intestinal lumen; (5) increase in intestinal permeability, leading to increased loss of water and electrolytes; and (6) stimulation of enterocyte secretion by toxins or cytokines. The most common entities causing chronic diarrhea are listed as follows. Malabsorption syndromes, which also cause chronic or recurrent diarrhea, are considered separately.
1. Causes of Chronic Diarrhea
Acute and chronic diarrhea is reported in up to 60% of children receiving antibiotics. Only a small fraction of these patients have C difficile–related pseudomembranous enterocolitis. Eradication of normal gut flora and overgrowth of other organisms may cause antibiotic-associated diarrhea. Most antibiotic-associated diarrhea is watery, is not associated with systemic symptoms, and decreases when antibiotic therapy is stopped. Data are mixed regarding the use of probiotics, though some suggest their use may decrease the incidence and severity of this diarrhea by helping to restore intestinal microbial balance.
B. Extraintestinal Infections
Infections of the urinary tract and upper respiratory tract (especially otitis media) are at times associated with diarrhea, though the mechanism is incompletely understood. Antibiotic treatment of the primary infection, toxins released by infecting organisms, and local irritation of the rectum (in patients with bladder infection) may play a role.
Malnutrition is associated with an increased frequency of enteral infections. Decreased bile acid synthesis, decreased pancreatic enzyme output, decreased disaccharidase activity, altered motility, and changes in the intestinal flora all may contribute to diarrhea. In addition, severely malnourished children are at higher risk of enteric infections because of depressed cellular and humoral immune functions. Protein-calorie malnutrition can result in villous atrophy, and represent an important cause of malabsorption.
Relative deficiency of pancreatic amylase in young infants causes osmotic diarrhea after starchy foods. Fruit juices, especially those high in fructose or sorbitol, produce diarrhea because these osmotically active sugars are poorly absorbed. Intestinal irritants (spices and foods high in fiber) and histamine-containing or histamine-releasing foods (eg, citrus fruits, tomatoes, fermented cheeses, red wines, and scombroid fish) may also cause diarrhea.
FODMAPs (Fermentable, Oligo-, Di-, Mono-saccharides And Polyols) are a group of poorly absorbed short-chain carbohydrates that are not uncommonly malabsorbed. Lactose and fructose are classic examples of FODMAPs. Malabsorption of foods higher in FODMAPs can cause symptoms of chronic intermittent diarrhea. It has been implicated as a cause of diarrhea and other symptoms (bloating, gassiness, abdominal pain) in certain individuals with a prior diagnosis of irritable bowel syndrome. Removal of certain FODMAPS from the diet may improve symptoms.
Laxative abuse in association with eating disorders or Munchausen syndrome by proxy can cause unpredictable diarrhea. A high concentration of magnesium in the stool may indicate overuse of milk of magnesia or other magnesium-containing laxatives. Detection of other laxative preparations in the stool or circulation requires sophisticated analysis not available in most laboratories. A high index of suspicion and careful observation may be required to make this diagnosis.
Diarrhea resulting from allergy to dietary proteins is a frequently entertained but rarely proven diagnosis. GI symptoms from cow’s milk protein allergy are more common in infants younger than 12 months.
In contrast to the self-limited cow’s milk protein hypersensitivity of infancy, infants and older children may develop more severe diarrhea caused by a systemic allergic reaction. For instance, food protein–induced enterocolitis syndrome (FPIES) is a life-threatening condition occurring during infancy manifested by large-volume diarrhea, acidosis, and shock as a result of an allergic reaction to common food proteins such as milk and soy. Patients require hospitalization for volume resuscitation and strict avoidance of allergens. Reintroduction of allergens should be performed in a controlled setting by an experienced allergist.
Infants and children may develop an enteropathy secondary to milk protein, resulting in flattening of small bowel villi, steatorrhea, hypoproteinemia, occult blood loss, and chronic diarrhea. Skin testing is not reliable since it detects circulating antibodies, not the T-cell–mediated responses that are likely responsible for food sensitivity reactions. Double-blind oral challenge with the suspected food under careful observation is often necessary to confirm this intestinal protein allergy. Small bowel biopsy findings are nonspecific. The diagnosis is often confirmed by either double-blind oral challenge with the suspected food or dietary elimination of the food followed by disappearance of occult blood in the stool and improvement in other symptoms. Consultation with an allergist is recommended for long-term management of patients with this disease.
Anaphylactic, immunoglobulin E (IgE)–mediated reactions to foods can occur in both young and older children. After ingestion, the patient quickly develops vomiting, then diarrhea, pallor, and hypotension. In these cases, radioallergosorbent test (RAST) and skin testing are positive. Food challenges should be undertaken in a setting in which resuscitation can be performed as there is often a progressively more severe reaction with subsequent ingestions. The close association between ingestion and symptoms usually leaves little doubt about the diagnosis.
F. Chronic Nonspecific Diarrhea
Chronic nonspecific diarrhea, also called toddler’s diarrhea, is the most common cause of loose stools in otherwise thriving children. The typical patient is a healthy, thriving child aged 6–20 months who has three to six loose stools per day during the waking hours. They do not have blood in their stools. They grow normally and may have a family history of functional bowel disease. No organic etiology is found for their diarrhea, with stool tests for blood, white blood cells, fat, parasites, and bacterial pathogens being negative. Diarrhea may worsen with a low-residue, low-fat, or high-carbohydrate diet and during periods of stress and infection. Excessive fruit juice ingestion seems to worsen symptoms. This syndrome resolves spontaneously usually by age 3½ years or after potty training. Possible causes of this diarrhea include abnormalities of bile acid absorption in the terminal ileum, excess intake of osmotically active carbohydrates, and abnormal motor function. A change in dietary fiber (either increasing fiber if deficient or decreasing fiber if excessive), a slight increase in dietary fat, and restriction of osmotically active carbohydrates like fruit juices will often help control symptoms. If these measures fail, loperamide (0.1–0.2 mg/kg/day in two or three divided doses) can be used as needed for symptomatic relief. Cholestyramine has also been used in some cases.
G. Immunologic Causes of Chronic Diarrhea
Chronic diarrhea is common in immune deficiency states, especially immunoglobulin A (IgA) deficiency and T-cell abnormalities. It can be due to an autoimmune enteropathy associated with the immune deficient state or could be due to chronic infection. The infectious causes of the diarrhea include common bacterial, viral, fungal, or parasitic organisms usually considered nonpathogenic (rotavirus, Blastocystis hominis, Candida), or unusual organisms (cytomegalovirus, Cryptosporidium, Isospora belli, Mycobacterium spp., microsporidia).
Between 50% and 60% of patients with common variable immune deficiency have enteropathy characterized by intestinal villous atrophy. Lymphonodular hyperplasia of the small intestine is also prominent. Patients with congenital or Bruton-type agammaglobulinemia usually have diarrhea and abnormal intestinal morphology. Patients with isolated IgA deficiency can have chronic diarrhea, a celiac disease–like picture, lymphoid nodular hyperplasia, and are prone to giardiasis. Patients with isolated defects of cellular immunity, combined cellular and humoral immune incompetence, and HIV infection may have severe chronic diarrhea leading to malnutrition but often the cause cannot be identified. Chronic granulomatous disease may be associated with intestinal symptoms suggestive of chronic IBD. Specific treatments are available for many of the unusual pathogens causing diarrhea in the immunocompromised host. Thus, a vigorous diagnostic search for specific pathogens is warranted in these individuals. In addition, treatment must be directed toward correcting the immunologic defect.
H. Other Causes of Chronic Diarrhea
Most infections of the GI tract are acute and resolve spontaneously or with specific antibiotic therapy. Organisms most prone to cause chronic or recurrent diarrhea in immunocompetent children are Giardia lamblia, Entamoeba histolytica, Salmonella species, and Yersinia. Infection with these organisms requires a small inoculum. Some patients may develop a postinfectious diarrhea, with persistent diarrhea present despite the eradication of the offending organism, either viral or bacterial. Bacterial overgrowth of the small bowel in patients with SBS, those undergoing chemotherapy, or with anatomic abnormalities may experience chronic diarrhea.
Pancreatic insufficiency due to cystic fibrosis or Shwachman-Diamond syndrome may result in chronic diarrhea, typically in conjunction with failure to thrive. Certain tumors of childhood (neuroblastoma, ganglioneuroma, metastatic carcinoid, pancreatic VIPoma, or gastrinoma) may secrete substances such as gastrin and vasoactive intestinal polypeptide (VIP) that promote small intestinal secretion of water and electrolytes. Conditions that result in increased or disordered intestinal motility such as hyperthyroidism or irritable bowel syndrome may also present with diarrhea. Children may present with large-volume, chronic, and intermittent watery diarrhea that does not cease when they discontinue oral feedings.
PH: Acute diarrheal disease in children: epidemiology, prevention, and treatment. Infect Dis Clin North Am 2005 Sep;19(3):585–602
et al: Acute and persistent diarrhea. Pediatr Clin North Am 2009 Dec;56(6):1343–1361
At the first evaluation of a child with GI bleeding history, physical examination, and initial examination are key to identifying the bleeding source. In large-volume, acute GI bleeding the primary focus, however, should center on stabilizing the patient to ensure adequate hemodynamic support.
A number of substances simulate hematochezia or melena (Table 21–5). The presence of blood should be confirmed chemically with guaiac testing. Coughing, tonsillitis, lost teeth, menarche, or epistaxis may cause what appears to be occult or overt GI bleeding. A careful history of the specifics surrounding the bleeding is critical, including the site, volume and color of blood, history of NSAID use, and use of other medications should be ascertained. Inquiry about associated dysphagia, epigastric pain, or retrosternal pain should be made and, if present, suggest GER or a peptic cause of bleeding.
Table 21–5.Identification of sites of gastrointestinal bleeding. ||Download (.pdf) Table 21–5. Identification of sites of gastrointestinal bleeding.
Symptom or Sign
Location of Bleeding Lesion
Effortless bright red blood from the mouth
Nasopharyngeal or oral lesions; tonsillitis; esophageal varices; lacerations of esophageal or gastric mucosa (Mallory-Weiss syndrome)
Vomiting of bright red blood or of “coffee grounds”
Lesion proximal to ligament of Treitz
Lesion proximal to ligament of Treitz, upper small bowel. Blood loss in excess of 50–100 mL/24 h
Bright red or dark red blood in stools
Lesion in the ileum or colon (Massive upper gastrointestinal bleeding may also be associated with bright red blood in stool.)
Streak of blood on outside of a stool
Lesion in the rectal ampulla or anal canal
Other important aspects of the history include foreign-body/caustic ingestion, history of chronic illnesses (especially liver/biliary disease), personal or family history of food allergy/atopy, associated symptoms (pain, vomiting, diarrhea, fever, weight loss), and family history of GI disorders (IBD, CD, liver disease, bleeding/coagulation disorder). In the presence of massive upper GI bleeding in the toddler, a high index of suspicion for button battery injury must be maintained despite the lack of any known history of ingestion. Other, more obscure causes of GI bleeding in children include Dieulafoy syndrome and heterotopic pancreas. Table 21–6 lists more common causes of GI bleeding by age and presentation.
Table 21–6.Differential diagnosis of gastrointestinal bleeding in children by symptoms and age at presentation. ||Download (.pdf) Table 21–6. Differential diagnosis of gastrointestinal bleeding in children by symptoms and age at presentation.
| || |
Child (2–12 y)
Adolescent (> 12 y)
Swallowed maternal blood
Hereditary hemorrhagic telangiectasia
Hereditary hemorrhagic telangiectasia
Melena with pain, obstruction, peritonitis, perforation
Ileal ulcer (isolated)
Crohn disease (ileal ulcer)
Hematochezia with diarrhea, crampy abdominal pain
Granulomatous (Crohn) colitis
Granulomatous (Crohn) colitis
Hematochezia without diarrhea or abdominal pain
Rectal gastric mucosa heterotopia
Solitary rectal ulcer
Solitary rectal ulcer
Colonic arteriovenous malformation
The first objective of the examination is to determine if the child is acutely or chronically ill and initiate supportive measures as needed. Physical signs of portal hypertension, intestinal obstruction, or coagulopathy are particularly important. The nasal passages should be inspected for signs of recent epistaxis, the vagina for menstrual blood, and the anus for fissures and hemorrhoids. Skin examination should assess for hemangiomas, eczema, petechiae, or purpura. Clinical assessment of vital signs and perfusion should be assessed to establish need for transfusion.
Initial laboratory tests should include a complete blood cell count (CBC), prothrombin time (PT), and partial thromboplastin time (PTT), at minimum. In specific cases, it may be prudent to add a liver profile (with suspected variceal bleeding), erythrocyte sedimentation rate (ESR)/CRP (with possible IBD), BUN/creatinine (for possible hemolytic uremic syndrome). A BUN to creatinine ratio of more than 30 has been shown to indicate a 10-fold increase in the risk of upper versus lower GI bleeding. In patients with Henoch-Schonlein Purpura, a neutrophil-to-lymphocyte ratio of > 2.86 was found to be a predictor of subsequent GI bleeding, with sensitivity of 73% and specificity of 68%. Low MCV in association with anemia suggests chronic GI losses and may warrant addition of iron studies. Serial determination of hematocrit is essential to assess ongoing bleeding. Detection of blood in the gastric aspirate confirms a bleeding site proximal to the ligament of Treitz. However, its absence does not rule out the duodenum as the source. Testing the stool for occult blood will help monitor ongoing losses. In a large study of over 600 cases of pediatric upper GI bleeding, only 4% who were found to have significant drop in hemoglobin levels required transfusion or emergent endoscopic or surgical intervention. In this series, having one or more risk factors, including melena, hematochezia, unwell appearance, and/or large amount of fresh blood in the emesis, had a sensitivity of 100% in identifying the significant bleeds. Elevation of fecal calprotectin levels have been associated with bleeding from both IBD and juvenile polyposis.
In infants with acute onset of bloody stools, multiple-view plain x-rays of the abdomen are helpful in assessing for pneumatosis intestinalis or signs of obstruction. Children younger than 2 years with a history and examination suggestive of intussusception should undergo air or water-soluble contrast enema. Painless, large-volume bleeding may prompt performance of a 99Tc-pertectnetate nuclear scan to assess for a Meckel diverticulum. Pretreatment with an H2-receptor antagonist may be helpful in increasing the sensitivity of this study; however, a negative scan does not preclude the diagnosis. CT scan of the abdomen with oral and IV contrast may be indicated to look for structural and inflammatory causes of bleeding. More recently, CT enterography has been proposed as a useful tool in cases of lower GI bleeding in children. Persistent bleeding without a clear source may prompt consideration of a radioisotope-tagged red blood cell (RBC) scan with 99mTc-sulfur colloid, though the bleeding must be active at the time of the study, with a rate of at least 0.1 mL/min. Angiography is generally less sensitive, requiring 1–2 mL/min.
In severe bleeding, the ABCs of resuscitation should be performed. Adequate IV access is critical in these cases. If a hemorrhagic diathesis is detected, vitamin K and additional blood products should be administered to correct any underlying coagulopathy. In severe bleeding, the need for volume replacement is monitored by measurement of central venous pressure. In less severe cases, vital signs, serial hematocrits, and gastric aspirates are sufficient.
In suspected upper GI bleeding, gastric lavage with saline should be performed, but there is no value of lavage in controlling bleeding. After stabilization, EGD may be considered to identify the bleeding site, and performance of endoscopy has been associated with lower readmission rates after an initial GI bleeding event. A large retrospective study of endoscopy performed for upper GI bleeding in children found that a definitive source for bleeding was identified in 57%, with a suspected source in another 30%. Risk factors for a nondiagnostic endoscopy in this series were a history of bleeding of less than 1 month and a delay of greater than 48 hours between presentation and endoscopy. Acid suppression with intravenous H2-antagonists or, preferably PPIs, may be helpful in suspected peptic causes of bleeding. A recent randomized trial of pediatric patients with endoscopically treated bleeding compared continuous esomeprazole therapy for 72 hours to second-look endoscopy and bolus esomeprazole and showed them to have no significant difference in rebleeding rates (4.6% vs 6.3%). Colonoscopy may identify the source of bright red rectal bleeding, but it should be performed emergently only if the bleeding is severe and if abdominal radiographs show no signs of obstruction. Colonoscopy on an unprepped colon is often inadequate for making a diagnosis. Capsule endoscopy may help identify the site of bleeding if colonoscopy and upper endoscopy findings are negative. Push or balloon enteroscopy may be helpful to perform therapeutic interventions, obtain biopsies, or mark small bowel lesions (prior to laparotomy/laparoscopy) identified on capsule endoscopy. Use of balloon enteroscopy in conjunction with capsule endoscopy in children with occult GI bleeding has been found to have a diagnostic yield of 95%.
Persistent vascular bleeding (varices [Figure 21–7], vascular anomalies) may be relieved temporarily using intravenous octreotide (1–4 mcg/kg/h) and may be used for up to 48 hours with careful monitoring of glucose homeostasis. Bleeding from esophageal varices may be stopped by compression with a Sengstaken-Blakemore tube. Endoscopic sclerosis or banding of bleeding varices are both effective, with equivalent success rates (87%–89%) and complication rates (10%–19%) between methods. Use of cyanoacrylate for gastric varices in children has been shown to be safe and effective in small, single-center studies.
Esophageal varices. Serpiginous esophageal varix extending to the esophageal lower esophageal sphincter.
If conservative measures are ineffective in stopping ulcer bleeding, endoscopic therapy with argon plasma coagulation, local injection of epinephrine, electrocautery, or application of hemostatic clips may be employed. Newer, over-the-scope clips have recently been shown to be safe and effective in pediatric patients as young as 4 years of age and as small as 17.4 kg. Though there are no studies yet published in children, use of hemostatic powder shows promise as effective and less technically challenging then other forms of endoscopic hemostasis. As in adults, use of only one modality in nonvariceal bleeding has been shown to increase the risk of rebleeding. If bleeding remains refractory to therapy, emergency surgery may be necessary. Alternatively, endovascular therapy with selective coiling of involved vessels by interventional radiology has been shown to be effective in children with refractory bleeding. A single dose of cyclophosphamide has been shown to be effective in steroid-resistant GIB in Henoch-Schönlein purpura. In some cases, angiography and selective embolization have been used successfully in unidentified and refractory bleeding.
et al: Continuous esomeprazole
infusion versus bolus administration and second look endoscopy for the prevention of rebleeding in children with a peptic ulcer. Rev Esp Enferm Dig 2018;110(6):352–357
H: Heterotopic pancreas: a rare cause of gastrointestinal bleeding in children. Dig Dis Sci 2018;63(5):1363–1365
EM: Neutrophil-to-lymphocyte ratio to predict gastrointestinal bleeding in Henoch: Schönlein purpura. Pediatr Int 2018;60(9):791–795
IJ: Successful endovascular treatment of a 13-month-old child with gastrointestinal bleeding due to Dieulafoy syndrome of duodenum. Radiol Case Rep 2018;13(3):685–688
et al: Treatment of gastrointestinal bleeding with hemostatic powder (TC-325): a multicenter study. Surg Endosc. 2019 [Epub ahead of print]
et al: Gastroduodenal artery coiling to curb upper gastrointestinal bleeding. J Pediatr Surg 2017;52(10):1699–1701
DM: Over the scope clips for treatment of acute nonvariceal gastrointestinal bleeding in children are safe and effective. J Pediatr Gastroenterol Nutr 2018;67(4):458–463
Vomiting is an extremely complex activity that is triggered by stimulation of chemoreceptors and mechanoreceptors in the wall of the GI tract, activated by contraction and distension. The vomiting center, paraventricular nuclei, in the brain controls the emetic response. These nuclei receive afferent input from abdominal splanchnic nerves, the vagus nerve, vestibulolabyrinthine receptors, the cerebral cortex, and chemoreceptor trigger zone (CTZ). Vagal afferents from the gut to brain are stimulated by ingested drugs and toxins, mechanical stretch, inflammation, and local neurotransmitters. Once the vomiting response is triggered, a pattern of somatic muscle action occurs with abdominal, thoracic, and diaphragm muscles contracting against a closed glottis. The resulting increased intra-abdominal pressure reverses the negative pressure of the esophagus and forces gastric contents upward. The vomiting response also alters intestinal motility by generating a retroperistaltic contractile complex that moves intestinal contents toward the esophagus.
Vomiting is the presenting sign of many pediatric conditions. The most common cause of vomiting in childhood is acute viral gastroenteritis. However, obstruction and acute or chronic inflammation of the GI tract are also major causes. CNS inflammation, increased intracranial pressure, or mass effect may cause vomiting. Metabolic derangements associated with inborn errors of metabolism, sepsis, and drug intoxication can stimulate either the CTZ or the brain directly to promote vomiting.
Control of vomiting with medication is rarely necessary in acute gastroenteritis, but it may relieve nausea and vomiting and decrease the need for intravenous fluids and/or hospitalization. Antihistamines and anticholinergics are appropriate for motion sickness because of their labyrinthine effects. 5-HT3–receptor antagonists (ondansetron, granisetron) are useful for vomiting associated with surgery and chemotherapy. Benzodiazepines, corticosteroids, and substituted benzamides are also used in chemotherapy-induced vomiting. Butyrophenones (droperidol, haloperidol) are powerful drugs that block the D2 receptor in the CTZ and are used for intractable vomiting in acute gastritis, chemotherapy, and after surgery. Phenothiazines are helpful in chemotherapy, cyclic vomiting, and acute GI infection but are not recommended for outpatient use because of extrapyramidal side effects.
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
DA: Anti-emetics for acute gastroenteritis in children. Curr Opin Pediatr 2009 Jun;21(3);294–298
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 (tear or laceration of the mucous membrane at the gastroesophageal junction) may occur. Patients experience abdominal pain, anorexia, and, occasionally, diarrhea. Autonomic symptoms, such as pallor, sweating, temperature instability, and lethargy, are common and give the patient a very ill appearance. The episodes end suddenly, often after a period of sleep. In some children, dehydration, electrolyte imbalance, and shock may occur. Between episodes, the child is completely healthy.
The cause of CVS is unknown; however, a relationship to migraine headaches has long been recognized. Family history is positive for migraine in 50%–70% of cases, and many patients develop migraine headaches as adults. Research suggests that abnormalities of neurotransmitters and hormones provoke CVS. About one-quarter of patients have typical migraine symptoms during episodes: premonitory sensation, headache, photophobia, and phonophobia. Identifiable triggers are similar to migraines and include infection, positive or negative emotional stress, diet (chocolate, cheese, monosodium glutamate), menses, sleep deprivation, or motion sickness.
Conditions that mimic CVS include drug toxicity, increased intracranial pressure, seizures, brain tumor, Chiari malformation, recurrent sinusitis, choledochal cyst, gallstones, recurrent small-bowel obstruction, IBD, familial pancreatitis, obstructive uropathy, recurrent urinary infection, diabetes, mitochondrial diseases, disorders of fatty and organic acid metabolism, adrenal insufficiency, and Munchausen syndrome by proxy. Chronic marijuana use has been associated with chronic vomiting (cannabinoid hyperemesis syndrome) and can mimic CVS. Although tests for reflux are often positive in these patients, it is unlikely that reflux and CVS are related.
Avoidance of triggers prevents episodes in some patients. Sleep can also end an episode although some children awaken and resume vomiting. Diphenhydramine or lorazepam is used at the onset of spells in some children to reduce nausea and induce sleep. Early use of antimigraine medications (sumatriptan), antiemetics (ondansetron), or antihistamines can abort spells in some patients. Once a spell is well established, intravenous fluids may be required to end it. With careful supervision, some children with predictable spells can receive intravenous fluids at home. Several approaches usually are tried before an effective therapy is found. Preventing spells with prophylactic propranolol, amitriptyline, antihistamines, or anticonvulsants are effective in some patients with frequent or disabling spells. Some patients require the additions of the mitochondrial-targeted cofactors coenzyme Q10 and L-carnitine to help manage their vomiting episodes.
M: Cannabinoid toxicity in pediatrics. Curr Opin Pediatr 2019 Apr;31(2):256–261
RG: High degree of efficacy in the treatment of cyclic vomiting syndrome with combined co-enzyme Q10, L
-carnitine and amitriptyline
, a case series. BMC Neurol 2011 Aug 16;11:102
T: Cyclic vomiting syndrome in children and adults: what is new in 2018? Curr Gastroenterol Rep 2018 Aug 29;20(10):46
AA: Cannabinoid hyperemesis syndrome: diagnosis, pathophysiology, and treatment—a systematic review. J Med Toxicol 2017 Mar;13(1):71–87
Approximately 2%–4% of all pediatric office visits occur because of unexplained, recurrent abdominal pain. Functional GI disorders have been reported in roughly 10%–30% of children/adolescents and 30%–40% of infants and toddlers. Criteria were published in 2016 in order to incorporate new findings in the literature including new information on gut-brain interactions and microenvironments. The descriptive term “recurrent abdominal pain” has been discarded for the more meaningful terms. Those with pain as a significant component have been termed functional abdominal pain disorder (FAPD) that encompasses several entities: functional dyspepsia (with subtypes of epigastric pain vs postprandial distress), irritable bowel syndrome (characterized by altered form and frequency of stools and improvement with defecation), abdominal migraines, and functional abdominal pain.
Children with functional abdominal pain experience recurrent attacks of abdominal pain or discomfort at least once per week for at least 2 months. Functional abdominal pain used to be lumped into a broad category of abdominal pain without a source and without any red flag signs. Classifications of the abdominal pain depend on the characteristics of the pain such as location of pain, association with bowel habits, and associated symptoms. The pain is usually localized to the periumbilical area but may also be more generalized. The pain occurs primarily during the day but may prevent children from falling asleep at night. It may be associated with pallor, nausea, or vomiting, and also with dramatic reactions such as frantic crying, clutching the abdomen, and doubling over. Parents may become alarmed and take their children into the emergency departments, where the evaluation is negative for an acute abdomen. School attendance may suffer, and enjoyable family events may be disrupted.
Alarm symptoms that would suggest a more severe organic etiology are absent. These include dysphagia, persistent vomiting, GI blood loss, associated rashes, or joint complaints, weight loss, stunting, or fevers.
Functional abdominal pain usually bears little relationship to bowel habits and physical activity. However, some patients have a symptom constellation suggestive of irritable bowel syndrome, including bloating, postprandial pain, lower abdominal discomfort, and erratic stool habits with a sensation of obstipation or incomplete evacuation of stool. A precipitating or stressful situation in the child’s life at the time the pains began can sometimes be elicited. School phobia may be a precipitant.
A careful and thorough physical examination that includes a rectal examination is essential and usually normal. Complaints of abdominal tenderness elicited during palpation may be inconsistent, out of proportion to visible signs of distress, and distractable.
Complete blood count, sedimentation rate, and stool test for occult blood are usually a sufficient evaluation. Extraintestinal sources such as kidney, spleen, and genitourinary tract may require assessment. In the adolescent female patient, ultrasound of the abdomen and pelvis may be helpful to detect gallbladder or ovarian pathology. If the pain is atypical, further testing suggested by symptoms and family history should be done. This may include additional imaging studies or endoscopic analysis. Any concern for lower tract inflammation, and IBD in particular may prompt consideration for the use fecal inflammatory markers such as lactoferrin and calprotectin.
Abdominal pain secondary to disorders causing acute abdomen are listed in Table 21–7. Pinworms, mesenteric lymphadenitis, and chronic appendicitis are improbable causes of recurrent abdominal pain. H pylori infection does not cause recurrent abdominal pain. Lactose intolerance usually causes abdominal distention, gas, and diarrhea with milk ingestion. At times, however, abdominal discomfort may be the only symptom. The incidence of peptic gastritis, esophagitis, duodenitis, and ulcer disease is probably underappreciated. Though esophageal eosinophilia typically presents with dysphagia and primarily esophageal symptoms in adolescents and adults, it can present with abdominal pain in younger children. Abdominal migraine and cyclic vomiting are conditions with an episodic character often associated with headaches or vomiting.
Table 21–7.Differential diagnosis of acute abdomen. ||Download (.pdf) Table 21–7. Differential diagnosis of acute abdomen.
Treatment of FAPD consists of reassurance based on a thorough history and physical examination and a sympathetic, age-appropriate explanation of the nature of functional pain. It is important to acknowledge that the child is experiencing pain. The concept of “visceral hyperalgesia” or increased pain signaling from physiologic stimuli such as gas, acid secretion, or stool is one that parents can understand and helps them respond appropriately to the child’s complaints. Another analogy might be to compare a child’s abdominal pain to usual headaches that another person may experience, in that the workup can be normal even though there is pain. Reassurance without education is rarely helpful. Regular activity should be resumed, especially school attendance. Therapy for psychosocial stressors, including biofeedback therapy, may be necessary. In specific patients, targeted therapy based on symptoms may be helpful. For abdominal migraines, treatments for migraine headaches may also be of benefit.
Numerous dietary modifications have been proposed as treatment for functional disorders, but data is a lacking as to their effectiveness. For instance, restriction of lactose and fructose and low fermentable oligo-di-mono-saccharides and polyols (FODMAP) diets may benefit some patients, whereas a positive impact of fiber, prebiotics, and probiotics on symptoms has not been shown. Biopsychosocial therapy, cognitive behavioral therapy, and hypnosis may offer benefit.
Likewise, pharmacologic studies of pediatric patients with FAPD have been underpowered and yielded inconsistent results. For instance, peppermint oil has shown benefit in reducing frequency and severity of pain, a finding that may be attributed to inhibition of calcium channels and reduction in colonic spasm. In contrast, although studies examining the impact of antispasmotic medications in adults have shown promise, these have yet to be replicated in children. One prospective study and other retrospective studies suggest efficacy for some patients with the use of cyproheptadine. Studies examining the impact of tricyclic antidepressants, calcium channel blockers, serotonin antagonists, melatonin, and antibiotics have been studied in the treatment of FAPDs have shown no significant improvement on symptoms. Interestingly, pooled data from a recent systematic review examining the placebo effect shows improvement in pain scales in 41% and resolution of pain in 17%.
et al: Multidisciplinary treatment reduces pain and increases function in children with functional gastrointestinal disorders. Clin Gastroenterol Hepatol 2019 Apr;17(5):994–996
et al: Childhood functional gastrointestinal disorders: neonate/toddler. Gastroenterology 2016 Feb 15;
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
M: Functional abdominal pain. Curr Gastroenterol Rep 2010 Oct;12(5):391–398
et al: Prevalence of pediatric functional gastrointestinal disorders utilizing the Rome IV criteria. J Pediatr 2018 Apr;195:134–139. doi: 10.1016/j.jpeds.2017.12.012
An acute abdomen is a constellation of findings indicating an intra-abdominal process that may require surgery. When this develops, a high degree of urgency exists to identify an underlying cause. The localized or generalized pain of an acute abdomen intensifies over time and is rarely relieved without definitive treatment. The abdomen may be distended and tense, and bowel sounds are often reduced or absent. Patients appear ill and are reluctant to be examined or moved. The acute abdomen is usually a result of infection of intra-abdominal or pelvic organs, but can also occur with intestinal obstruction, appendicitis intestinal perforation, inflammatory conditions, trauma, and some metabolic disorders. Some of the conditions causing acute abdomen are listed in Table 21–7. Reaching a timely and accurate diagnosis is critical and requires skill in physical diagnosis, recognition of the symptoms of a large number of conditions, and a judicious selection of laboratory and radiologic tests. (Acute appendicitis is discussed earlier in the section Disorders of the Small Intestine.)
Malabsorption of ingested food has many causes (Table 21–8). Shortened length (usually via surgical resection) and mucosal damage (CD) both reduce surface area. Impaired motility interferes with normal propulsive movements and with mixing of food with pancreatic and biliary secretions and permits anaerobic bacterial overgrowth. Bacterial overgrowth may lead to increased carbohydrate fermentation and acidic diarrhea. Bacterial overgrowth may also increase bacterial bile acid deconjugation leading to fat malabsorption as seen in intestinal pseudo-obstruction or postoperative blind loop syndrome. Impaired intestinal lymphatic (congenital lymphangiectasia) or venous drainage also causes malabsorption. Diseases reducing pancreatic exocrine function (cystic fibrosis, Shwachman syndrome) or the production and flow of biliary secretions (biliary atresia) cause nutrient malabsorption. Malabsorption of specific nutrients may also be genetically determined (acrodermatitis enteropathica, disaccharidase deficiency, glucose-galactose malabsorption, and abetalipoproteinemia).
Table 21–8.Malabsorption syndromes. ||Download (.pdf) Table 21–8. Malabsorption syndromes.
Acid hypersecretion (eg, Zollinger-Ellison syndrome)
Exocrine pancreatic insufficiency
Decreased intraluminal bile acids
Chronic parenchymal liver disease
Bile acid loss (short gut, ileal disease)
Bile acid deconjugation by bacterial overgrowth
Short bowel syndrome
Metabolic genetic disease
Diarrhea, vomiting, anorexia, abdominal pain, failure to thrive, and abdominal distention are common. With fat malabsorption, stools are typically bulky, foul, greasy, and pale; in contrast, osmotic diarrhea stools are loose, watery, and acidic. Stool microscopic examination for neutral fat (pancreatic insufficiency as in cystic fibrosis) and fatty acids (as in mucosal injury, liver disease) may be useful.
Fat-soluble vitamin deficiency occurs with long-standing fat malabsorption and is manifested by prolonged PT (vitamin K) and low levels of serum carotene (vitamin A), vitamin E, and 25-hydroxy vitamin D. Loss of serum proteins is suggested by elevated fecal α1-antitrypsin levels. Disaccharide or monosaccharide malabsorption manifests by acidic stool with pH less than 5.5 due to lactic acid and reducing substances. Specific enzyme deficiencies may be evaluated by breath hydrogen test, or specific disaccharidase activity measurement from small intestinal biopsy. Other screening tests suggesting a specific diagnosis include sweat chloride concentration (cystic fibrosis), intestinal mucosal biopsy (celiac disease, lymphangiectasia, IBD), liver and gallbladder function tests, and fecal elastase. Common disorders associated with malabsorption in pediatric patients are detailed below.
1. Protein-Losing Enteropathy
Loss of plasma proteins into the GI tract occurs in association with intestinal inflammation, intestinal graft-versus-host disease, acute and chronic intestinal infections, venous and lymphatic obstruction or malformations, and intestinal malignancy (Table 21–9). Chronic elevation of venous pressure in children with the Fontan procedure and elevated right-sided heart pressures may produce protein-losing enteropathy.
Table 21–9.Disorders associated with protein-losing enteropathy. ||Download (.pdf) Table 21–9. Disorders associated with protein-losing enteropathy.
Giant hypertrophic gastritis (Ménétrier disease), often secondary to cytomegalovirus infection or Helicobacter pylori
Infection: TB, Clostridium difficile, parasite (eg, Giardia), bacteria (eg, Salmonella)
Inflammatory bowel disease
Signs and symptoms are mainly caused by hypoproteinemia or fat malabsorption: edema, ascites, poor weight gain, anemia, lymphopenia, and fat-soluble vitamins (A, D, E, K) and mineral deficiencies. Serum albumin and globulins may be decreased. Fecal α1-antitrypsin is elevated (> 3 mg/g dry weight stool; slightly higher in breast-fed infants). In the presence of intestinal bleeding, fecal α1-antitrypsin measurements are falsely high.
Hypoalbuminemia may be due to increased catabolism, poor protein intake, impaired hepatic protein synthesis, or congenital malformations of lymphatics outside the GI tract, and protein losses in the urine from nephritis and nephrotic syndrome.
Albumin infusion, diuretics, and a high-protein, low-fat diet may control symptoms. Nutritional deficiencies should be corrected, and the underlying cause treated.
2. Celiac Disease (Gluten Enteropathy)
Celiac disease (CD) is an immune-mediated enteropathy triggered by gluten, a protein in wheat, rye, and barley. CD presents any time after gluten is introduced in the diet. Disease frequency approaches 1 in 100. Risk factors include type 1 diabetes (4%–10%), Down syndrome (5%–12%), Turner syndrome (4%–8%), IgA deficiency (2%–8%), autoimmune thyroiditis (8%), and family history of CD (5%–10%). Almost all CD patients express HLA-DQ2 or DQ8 tissue antigens.
1. Gastrointestinal manifestations
In the classic form of CD, GI symptoms begin soon after gluten-containing foods are introduced in the diet, between 6 and 24 months of age. Chronic diarrhea, abdominal distention, irritability, anorexia, vomiting, and poor weight gain are typical. Celiac crisis, with dehydration, hypotension, hypokalemia, and explosive diarrhea, is rare. Older children may have oral ulcers, chronic abdominal pain, vomiting, diarrhea or constipation, and bloating.
2. Nongastrointestinal manifestations
Adolescents with CD may present with delayed puberty or short stature, and females with delayed menarche. CD should be considered in children with unexplained iron-deficiency anemia, decreased bone mineral density, elevated liver function enzymes, arthritis, epilepsy with cerebral calcifications, or intensely pruritic rash typically on the elbows, forearms, and knees suggestive of dermatitis herpetiformis. The benefit of early screening and treatment in asymptomatic individuals is unclear.
1. Serologic and genetic testing
Patients over 2 years old who are suspected of celiac disease should be screened with serum IgA and tissue transglutaminase (TTG) IgA, which is highly sensitive and specific. In children under 2 years old, the deamidated gliadin peptide IgG should also be sent. In IgA deficiency, the deamidated gliadin peptide IgG or the IgG-based versions of the TTG or antiendomysial antibodies should also be sent. Testing for HLA-DQ2 and DQ8 has a high negative predictive value, and family members who test negative are unlikely to ever develop CD.
May have partially digested fat or be acidic.
Can be severe enough to lead to edema.
Low MCV and evidence of iron deficiency is common.
5. Insufficient Hepatitis B surface Ab after immunization
Up to 30%–70% of patients with CD are estimated to be nonresponsive to hepatitis B vaccination before treatment with gluten-free diet.
Characteristic duodenal biopsy findings on light microscopy are oftentimes patchy villous atrophy with increased numbers of intraepithelial lymphocytes.
The differential diagnosis includes food allergy, non-celiac gluten sensitivity, Crohn disease, postinfectious diarrhea, primary lactose intolerance, functional abdominal pain, irritable bowel syndrome, immunodeficiencies, and graft-versus-host disease.
Treatment is strict dietary gluten restriction for life. All sources of wheat, rye, and barley are eliminated. Most, but not all, patients tolerate oats as long as the manufacturer takes precautions to avoid cross-contamination in processing. The intestinal mucosa improves after 6–12 months of treatment while secondary lactose intolerance resolves within a few weeks. Supplemental calories, vitamins, and minerals are indicated only in the acute phase. CD-related antibody titers decrease on a gluten-free diet, but may take 12 months or longer to normalize.
Adherence to gluten-free diet is difficult and difficult to assess, but is associated with regrowth of villi, resolution of symptoms, and normal life. Individuals with poor adherence to gluten-free diet may be at increased risk for fractures, iron deficiency anemia, infertility, and enteropathy-associated T-cell lymphoma.
et al: NASPGHAN clinical report on the diagnosis and treatment of gluten-related disorders. J Pediatr Gastroenterol Nutr 2016;63:156–165
et al: Evidence-informed expert recommendations for the management of celiac disease in children. Pediatrics 2016;138(3):e20153147
3. Carbohydrate Malabsorption
Carbohydrate malabsorption is typically a nonimmune-mediated intolerance to dietary carbohydrates due to a deficiency in an enzyme or transporter, or due to excess consumption overloading a functional transporter. These systems are located on the small bowel epithelial brush border. The non-absorbed molecules cause osmotic diarrhea and are fermented in the gut producing gas. As a result, clinical symptoms include abdominal distention, bloating, flatulence, abdominal discomfort, nausea, and watery diarrhea. Stools will test positive for reducing substances, except for sucrose, which is not a reducing sugar.
et al: Diagnosing and treating intolerance to carbohydrates in children. Nutrients 2016;8:157
A. Disaccharidase Deficiency
Starches and the disaccharides sucrose and lactose are the most important dietary carbohydrates. Dietary disaccharides and the oligosaccharide products of pancreatic amylase action on starch require hydrolysis by intestinal brush border disaccharidases for absorption. Disaccharidase levels are highest in the jejunum and proximal ileum. Characteristics of primary disaccharidase deficiency include permanent disaccharide intolerance, absence of intestinal injury, and frequent positive family history.
All human ethnic groups are lactase-sufficient at birth making congenital lactase deficiency extremely rare. Genetic or familial lactase deficiency appears after 5 years of age. Genetic lactase deficiency develops in virtually all Asians, Alaskan natives, Native Americans, 80% of Africans, 70% of African Americans, and 30%–60% of Caucasian Americans. Transient or secondary lactase deficiency caused by mucosal injury such as an acute viral gastroenteritis is common and resolves within a few weeks. Lactose ingestion in lactase deficient individuals causes variable degrees of diarrhea, abdominal distention, flatus, and abdominal pain. Stools are liquid or frothy and acidic, and may test positive for reducing substances. Diagnostic tests include genetic testing and lactose breath test. Symptoms resolve with dietary avoidance of lactose or with lactase supplementation.
C. Sucrase-Isomaltase Deficiency
This condition is inherited in a rare autosomal recessive fashion and found most commonly in Greenland, Iceland, and among Alaskan natives. Infants may present with abdominal distention, failure to thrive, and watery, acidic diarrhea. Diagnosis is made by oral sucrose breath hydrogen testing (1 g/kg), or by testing a snap frozen intestinal biopsy for enzyme activity. Treatment is avoidance of sucrose and starches rich in amylopectin, or the use of sacrosidase enzyme supplement.
WR: Clinical aspects and treatment of congenital sucrose-isomaltase deficiency. J Pediatr Gastroenterol Nutr 2012;55(Suppl 2):S7–S13
4. Monosaccharide Malabsorption
The most important monosaccharides are fructose, glucose, and galactose.
A. Glucose-Galactose Malabsorption
Glucose-galactose malabsorption is a rare disorder in which the sodium-glucose transport protein is defective. Transport of glucose in the intestinal epithelium and renal tubule is impaired. Diarrhea begins with the first feedings, accompanied by reducing sugar in the stool and acidosis. Glycosuria and aminoaciduria may occur and the glucose tolerance test is abnormal. Small bowel histology appears normal. Diarrhea subsides promptly on withdrawal of glucose and galactose from the diet and is mandatory treatment for the congenital disease. The acquired, transient form of glucose-galactose malabsorption occurs mainly in infants younger than 6 months, usually following acute viral or bacterial enteritis, and may require PN until healing. A carbohydrate-free base formula is used with added fructose. Prognosis is good if diagnosed early. Tolerance for glucose and galactose improves with age.
B. Dietary Fructose Intolerance
Fructose malabsorption occurs when fructose is in excess of glucose, often with consumption of high-fructose corn syrup. Malabsorbed fructose leads to symptoms such as abdominal pain, bloating, flatulence, and diarrhea. Diagnosis is made with a fructose breath hydrogen test.
C. Intestinal Lymphangiectasia
This form of protein-losing enteropathy results from obstruction of intestinal lymphatics and leakage of lymph into the bowel lumen. Congenital lymphangiectasia is associated with abnormalities of the lymphatics in the extremities. Malrotation with volvulus can also cause intestinal lymphangiectasia.
Peripheral edema, diarrhea, abdominal distention, chylous effusions, and repeated infections are common. Laboratory findings include low calcium, magnesium, albumin, immunoglobulin levels, lymphocytopenia, and anemia and elevated fecal α1-antitrypsin. Imaging may show bowel wall edema, and biopsy may reveal dilated lacteals in the villi and lamina propria. If only the lymphatics of the deeper layers of bowel or intestinal mesenteries are involved, laparotomy may be necessary to establish the diagnosis. Capsule endoscopy shows diagnostic brightness secondary to the fat-filled lacteals.
Causes of protein losing enteropathy should be considered.
A high-protein diet (6–7 g/kg/day may be needed) enriched with medium-chain triglycerides as a fat source usually allows for adequate nutrition and growth. Vitamin and calcium supplements should be given. Parenteral nutritional supplementation may be needed temporarily. Surgery may be curative if the lesion is localized to a small area of the bowel or in cases of constrictive pericarditis or obstructing tumors. IV albumin and immune globulin may be needed but usually not chronically. The serum albumin may not normalize. The prognosis is not favorable, although remission may occur with age. Malignant degeneration of the abnormal lymphatics may occur, and intestinal B-cell lymphoma may develop.
5. Cow’s Milk Protein Intolerance
Milk protein intolerance refers to nonallergic food sensitivity and is more common in males than females and in young infants with a family history of atopy. The estimated prevalence is 0.5%–1.0%. Symptoms may occur while an infant is still exclusively breast-fed. The most commonly heard history reports a healthy, well appearing infant, who when fed formula or breast milk with cow’s milk protein, develops flecks of blood in the stool or loose mucoid, blood streaked stools. A family history of atopy is common but skin testing is not reliable or indicated since this is not thought to be an IgE-mediated disease. Removal of cow’s milk protein is the treatment. Maternal avoidance of milk protein will usually suffice if breast-fed. If formula-fed, substituting a protein hydrolysate formula for cow’s milk–based formula is indicated. Allergic colitis in young infants is self-limited, usually disappearing by 8–12 months of age. Since no long-term consequences of this problem have been identified, when symptoms are mild and the infant is thriving, no treatment may be needed. Histology, not required for diagnosis, shows mild lymphonodular hyperplasia, mucosal edema, and eosinophilia on rectal biopsy.
In older children, milk protein sensitivity may induce eosinophilic gastroenteritis with protein-losing enteropathy, iron deficiency, hypoalbuminemia, and hypogammaglobulinemia. A celiac-like syndrome with villous atrophy, malabsorption, hypoalbuminemia, occult blood in the stool, and anemia can occur.
et al: Food allergy in childhood. Pediatric Allergy Immunol 2015;26(8):711–720
6. Pancreatic Insufficiency
The most common cause of pancreatic exocrine insufficiency in childhood is cystic fibrosis. Decreased secretion of pancreatic digestive enzymes is caused by obstruction of the exocrine ducts by thick secretions, which destroys pancreatic acinar cells. Other conditions associated with exocrine pancreatic insufficiency are discussed in Chapter 22.
7. Other Genetic Disorders Causing Malabsorption
Abetalipoproteinemia is a rare autosomal recessive condition in which the secretion of triglyceride-rich lipoproteins from the small intestine (chylomicrons) and liver (very low-density lipoproteins) is limited or absent. Profound steatosis of intestinal enterocytes (and hepatocytes) and severe fat malabsorption occur. Deficiencies of fat-soluble vitamins develop with neurologic complications of vitamin E deficiency and atypical retinitis pigmentosa. Serum cholesterol level is very low, and red cell membrane lipids are abnormal, causing acanthosis of red blood cells, two findings that may be the key to diagnosis.
B. Acrodermatitis Enteropathica
Acrodermatitis enteropathica is an autosomal recessive condition in which the intestine has a selective inability to absorb zinc. The condition usually becomes obvious at the time of weaning from breast-feeding and is characterized by rash on the extremities, rashes around the body orifices, eczema, profound failure to thrive, steatorrhea, diarrhea, and immune deficiency. Zinc supplementation by mouth results in rapid improvement.
INFLAMMATORY BOWEL DISEASE
IBD, a chronic relapsing inflammatory disease, is most commonly differentiated into Crohn disease (CrD) and ulcerative colitis (UC). The etiology is multifactorial, involving a complex interaction of environmental and genetic factors leading to maladaptive immune responses to flora in the GI tract. With 5%–30% of patients identifying a family member with IBD, and a 10–20 relative risk of a sibling developing IBD, a genetic association is certain in most. Very early onset IBD, before age 2, is more likely to be monogenic and severe.
Inflammation causes abdominal pain, diarrhea, bloody stools, fever, anorexia, fatigue, and weight loss. CrD may also present as a stricturing process with abdominal pain and intestinal obstruction, or as a penetrating/fistulizing form with abscess, perianal disease, or symptoms similar to acute appendicitis. UC usually presents with abdominal pain and bloody diarrhea.
CrD can affect any part of the GI tract from lips to anus. Childhood CrD most often affects the terminal ileum and colon. UC is limited to the colon, and in children it usually involves the entire colon (pancolitis). The younger the age at onset, the more severe the course is likely to be.
Extraintestinal manifestations are common in both forms of IBD and may precede the intestinal complaints. These include uveitis, recurrent oral aphthous ulcers, arthritis, growth and pubertal delay, liver involvement (typically primary sclerosing cholangitis), rash (erythema nodosa and pyoderma gangrenosum), and iron deficiency anemia.
Diagnosis is based on symptoms, relapsing course, radiographic, endoscopic, and histologic findings, and exclusion of other disorders. No single test is diagnostic. Patients often have low hemoglobin, iron, and serum albumin levels, and elevated ESR and CRP and fecal calprotectin. IBD-related serum antibodies are frequently present; antibodies to Saccharomyces cerevisiae (ASCA) in 60% of CrD, and perinuclear antineutrophil cytoplasmic antibodies (pANCAs) in 70% of UC. These, and other IBD-related antibodies, may be helpful in differentiating CrD from UC, but they are neither sensitive nor specific enough to be diagnostic. Abdominal imaging with CT, magnetic resonance enterography, US, and video capsule may reveal small bowel disease and exclude other etiologies. Findings include thickening of the bowel wall, stricturing, mucosal ulceration, enteric fistulas, and mucosal and mural edema.
Upper endoscopy and ileocolonoscopy are the most useful diagnostic modalities, revealing severity and extent of upper intestinal, ileal, and colonic involvement. Granulomas are found in 25%–50% of CrD cases. Deep linear ulcers, white exudate (Figure 21–8), aphthous lesions (Figure 21–9), patchy involvement, and perianal disease suggest CrD. Superficial and continuous involvement of the colon sparing the upper GI tract are most consistent with UC. Both forms of IBD may have mild gastritis.
Ulcerative colitis. White exudate is present overlying an abnormal colonic mucosa that has lost its typical vascular pattern.
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 or other vasculitides, CD, or hypopituitarism. The acute onset of ileocolitis may be mistaken for intestinal obstruction, appendicitis, lymphoma, infectious diarrhea. Malabsorption symptoms suggest CD, peptic ulcer, Giardia, food protein allergy, anorexia nervosa, or growth failure from endocrine causes. Perianal disease may suggest child abuse. Crampy diarrhea and blood in the stool can also occur with infection such as Shigella, Salmonella, Yersinia, Campylobacter, E histolytica, enteroinvasive E coli (E coli O157), Aeromonas hydrophila, C difficile, and, if immunocompromised, CMV. Mild IBD mimics irritable bowel syndrome, or lactose intolerance. Consider Behçet disease if there are deep intestinal ulcers, oral aphthous ulcerations along with at least two of the following: genital ulcers, synovitis, posterior uveitis, meningoencephalitis, and pustular vasculitis. Chronic granulomatous disease and sarcoidosis also cause granulomas.
Nutritional complications include failure to thrive, short stature, decreased bone mineralization, and specific nutrient deficiencies, including iron, calcium, zinc, vitamin B12, and vitamin D. Prolonged corticosteroid therapy may impact growth and bone mineral density. Intestinal obstruction, fistulae, abdominal abscess, perianal disease, pyoderma gangrenosum, arthritis, and amyloidosis occur. Crohn colitis increases risk for colon adenocarcinoma.
Even with the typical presentation of UC, up to 35% will develop CrD. Arthritis, uveitis, pyoderma gangrenosum, and malnutrition can occur. Growth failure and delayed puberty are less common than in CrD, while liver disease (chronic active hepatitis, sclerosing cholangitis) is more common. Adenocarcinoma of the colon occurs with an incidence of 1%–2% per year after the first 7–8 years of disease in patients with pancolitis and is significantly higher in patients with UC and sclerosing cholangitis.
Therapy for pediatric IBD involves induction of remission, maintenance of remission, and addressing nutritional deficiencies to promote normal growth and development. Treatment includes diet, anti-inflammatory, immunomodulatory, antidiarrheal, antibiotic, and biological options. No medical therapy is uniformly effective in all patients. In severe CrD, growth hormone may be needed to attain full height potential.
Enteral nutrition with liquid formula providing more than 85% of caloric needs is an effective therapy for induction and maintenance for CrD and promotes linear growth. Diet therapies are less effective in UC. Ensuring adequate nutrition for replenishing deficits and promoting normal growth (including pubertal growth) can be challenging. In addition to total calories, micronutrient, calcium, and vitamin deficiencies should be replenished. Restrictive or bland diets are counterproductive because they usually result in poor intake. A high-protein, high-carbohydrate diet with normal amounts of fat is recommended. A diet with decreased fiber may reduce symptoms during active colitis or partial intestinal obstruction; however, once the colitis is controlled, increased fiber may benefit mucosal health via bacterial production of fatty acids. Low-lactose diet or lactase replacement may be needed temporarily for small bowel CrD. Ileal disease may require antibiotics to treat bacterial overgrowth and extra fat-soluble vitamins due to increased losses. In severe CrD, supplemental calories from formulas taken orally or by NG tube promote catch-up growth.
2. Aminosalicylates (ASA)
Multiple preparations of 5-ASA derivatives are available and used to induce and maintain remission in mild CrD and UC. Common preparations including 5-ASA products such as sulfasalazine (50 mg/kg/day), or balsalazide (0.75–2.5 g PO tid) or mesalamine products (adult dose range 2.4–4.8 g/day), are available in tablets, granules, and delayed release formulations targeting specific locations in the GI tract. Side effects include skin rash; nausea; headache and abdominal pain; hair loss; diarrhea; and rarely nephritis, pericarditis, serum sickness, hemolytic anemia, aplastic anemia, and pancreatitis. Sulfasalazine, in which sulfa delivers the 5-ASA, may cause sulfa-related side effects including photosensitivity and rash.
Patients with moderate to severe CrD and UC generally respond quickly to corticosteroids. Methylprednisolone (1 mg/kg/day) may be given intravenously when disease is severe. For moderate disease, prednisone (1 mg/kg/day, orally in one to two divided doses), or budesonide in preparations targeting the ileocecal area or colon may quickly improve symptoms but should be tapered over 4–8 weeks. Budesonide, due to “single pass” liver clearance, may have less side effects than prednisone. Steroid dependence is an indication for escalating therapy. Corticosteroid enemas and foams are useful topical agents for distal proctitis or left-sided colitis. While on systemic corticosteroids, consideration should be given to calcium and vitamin D supplementation as well as acid suppression to prevent gastritis.
4. Immunomodulators: azathioprine (AZA), 6-mercaptopurine (6MP), and methotrexate (MTX)
If patients experience moderate to severe or are steroid-dependent, immunomodulators may be used as effective agents to maintain remission and reduce corticosteroids use. AZA (2–3 mg/kg/day PO) or 6MP (1–2 mg/kg/day PO) provides effective maintenance therapy for moderate to severe CrD. The optimal dose of AZA or 6MP depends on the enzyme thiopurine methylene transferase (TPMT), which should be measured before starting therapy. For individuals deficient in TPMT, MTX should be used; for intermediate enzyme activity, dose is reduced by 50%. In cases when adherence may be an issue, or when dose adjustments may be necessary, AZA or 6MP metabolites may be measured. Maximum therapeutic efficacy may not be seen for 2–3 months after beginning treatment. Side effects include pancreatitis, hepatotoxicity, and bone marrow suppression.
MTX is effective in CrD but not UC, and with onset of action within 2–3 weeks. Weekly oral or intramuscular dosage ranges from 15 mg/m2 up to 25 mg. The most common side effect is nausea, managed with folate 1 mg a day, while serious adverse events include bone marrow, liver, lung, and kidney toxicities. MTX is well known to cause fetal death and deformities.
Metronidazole (15–30 mg/kg/day in three divided doses) and ciprofloxacin treat perianal CrD and bacterial overgrowth. Peripheral neuropathy may occur with prolonged use of metronidazole.
Antibody against tumor necrosis factor-α (TNFα) is used for moderate to severe CrD and UC, and for fistulizing or penetrating disease. Formulations are available for IV (infliximab) or intramuscular (adalimumab) administration. Disease recurrence is usually within 12 months of stopping therapy. New biologicals include vedolizumab, an alpha4/beta7 anti-integrin, and ustekinumab, an anti IL12/23 agent. Use of biologics is associated with risk for infusion reactions, injection site reactions, and increased risk for opportunistic infections and for malignancy. Rarely, hepatosplenic T-cell lymphoma is associated with anti-TNF agents and concomitant AZA/6MP.
Cyclosporine or tacrolimus may be used as a “bridge” to more definitive therapy (such as colectomy for UC). Probiotics and prebiotics are frequently used but with very limited data on efficacy. Tofactinib, an oral JAK inhibitor, has recently received approval for adults with UC.
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.
Ileocecal resection is the most common surgery but recurrence is expected. Indications for surgery in CrD include stricture, obstruction, uncontrollable bleeding, perforation, abscess, fistula, and failure of medical management. Up to 50% of patients with CrD eventually require a surgical procedure.
Total colectomy is curative and is recommended for patients with steroid dependence or steroid resistance, uncontrolled hemorrhage, toxic megacolon, high-grade dysplasia, or malignant tumors; elective colectomy may be chosen for prevention of colorectal cancer after 7–8 years of disease. A J-pouch provides better continence, but pouchitis develops in up to 25% of patients, manifested by diarrhea and cramping, and is treated with metronidazole or ciprofloxacin. Liver disease associated with IBD is not improved by colectomy.
et al: Surgical management of Crohn disease in children: guidelines from the Paediatric IBD Porto Group of ESPGHAN. J Pediatr Gastroenterol Nutr 2017;64(5):818.
et al: ESPGHAN revised porto criteria for the diagnosis of inflammatory bowel disease in children and adolescents. J Pediatr Gastroenterol Nutr 2014;58(6):795
et al: Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn’s disease. J Crohns Colitis 2014;8(10):1179
et al: Management of paediatric ulcerative colitis, part 1: ambulatory care—an evidence-based guideline from European Crohn’s and Colitis Organization and European Society of Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2018;67(2):257.
et al: Management of paediatric ulcerative colitis, part 2: acute severe colitis—an evidence-based consensus guideline from the European Crohn’s and Colitis Organization and the European Society of Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2018;67(2):292