Pediatrics in Review-2012-Zella. Chronic Diarrhea

DOI: 10.1542/pir.33-5-2072012;33;207Pediatrics in Review

Garrett C. Zella and Esther J. IsraelChronic Diarrhea in Children

http://pedsinreview.aappublications.org/content/33/5/207located on the World Wide Web at:

The online version of this article, along with updated information and services, is

Pediatrics. All rights reserved. Print ISSN: 0191-9601. Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2012 by the American Academy of published, and trademarked by the American Academy of Pediatrics, 141 Northwest Pointpublication, it has been published continuously since 1979. Pediatrics in Review is owned, Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly

at UNIV OF CHICAGO on May 3, 2013http://pedsinreview.aappublications.org/Downloaded from

Chronic Diarrhea in ChildrenGarrett C. Zella, MD,*

Esther J. Israel, MD*

Author Disclosure

Drs Zella and Israel

have disclosed no

financial relationships

relevant to this article.

This commentary does

contain a discussion of

an unapproved/

investigative use of

a commercial product/

device.

Educational Gap

It is estimated that diarrheal illnesses are responsible for w2 to 4 million childhood

deaths worldwide each year, representing 13.2% of all childhood deaths worldwide.

Objectives After completing this article, readers should be able to:

1. Understand the pathophysiologic mechanisms involved in chronic diarrhea.

2. Know how to evaluate a child who has chronic diarrhea, including appropriate

elements of history, physical examination, stool analysis, and blood testing.

3. Be familiar with the many disorders that cause chronic diarrhea, both with and

without failure to thrive.

4. Know the therapies for the many causes of chronic diarrhea.

DefinitionsChronic diarrhea is a common complaint in pediatric medicine and can pose a complexsituation for practitioners and families. This complaint is both a symptom and a sign.(1) Although patients or their parents often assess the presence of diarrhea by reportingstool consistency and frequency, one can more scientically dene diarrhea as stool vol-ume >10 g/kg per day in infants and toddlers, and >200 g/day in older children. (2)However, diarrhea should not be dened solely by stool weight. Some adolescents andadults may have up to 300 g of formed stool per day without any complaints. (3) Theduration of symptoms necessary to dene diarrhea as chronic also is not denitive.Most authors agree that 14 days of symptoms meets criteria, although others use a cut-off of 4 weeks. (4) An additional term, persistent diarrhea, acknowledges diarrhealasting more than 14 days but implies a more abrupt onset compared with chronic di-arrhea. Regardless of the specic term or number of days of symptoms, it should beunderstood that this denition should allow for the usual resolution of most causesof acute diarrhea.

EpidemiologyIt is estimated that diarrheal illnesses are responsible for w2 to 4 million childhooddeaths worldwide each year. (5)(6) In 2002, the World Health Organization estimated

that 13.2% of all childhood deaths worldwide were causedby diarrheal diseases, 50% of which were chronic diarrhealillnesses. (7) Large-scale studies indicate that the preva-lence of chronic diarrheal illnesses worldwide ranges from3% to 20%, and the incidence is w3.2 episodes per child-year. (4)(8) Estimates in the United States are substan-tially lower at 0.18 episodes per child-year in children ages6 months to 3 years. (9) In the United States, onlyw25%of cases present for medical care, and fewer than 1%of children are hospitalized for diarrheal diseases. (10)The rotavirus vaccine may decrease hospitalizations byup to 66% in developing countries, because a substantialnumber of these hospitalizations are for rotavirus-associateddiarrhea. (11)

Abbreviations

CCD: congenital chloride diarrheaCF: cystic brosisCNSD: chronic nonspecic diarrheaCSD: congenital sodium diarrheaIBD: inammatory bowel diseaseIBS: irritable bowel syndromeIDI: intractable diarrhea of infancyTTG IgA: tissue transglutaminase immune globulin AZES: Zollinger-Ellison syndrome

*Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Boston, MA.

Article gastrointestinal disorders

Pediatrics in Review Vol.33 No.5 May 2012 207


Pathophysiology

The many causes of chronic diarrhea can be divided intofour principle pathophysiologic mechanisms: osmotic, se-cretory, dysmotility associated, and inammatory. Often,a single disorder will involve multiple overlapping mech-anisms. Regardless of the cause, water in the intestinal lu-men is incompletely absorbed either because net waterabsorption is decreased or because water is being heldwithin the lumen by an osmotic gradient. Reduction innet water absorption by as little as 1% may be sufcientto cause diarrhea. (12)

Osmotic diarrhea is caused by a failure to absorb a lu-minal solute, resulting in secretion of uids and net waterretention across an osmotic gradient. This outcome canresult from either congenital or acquired disease and isbest exemplied by the common disorder of lactose mal-absorption. (13) Other carbohydrates may be malab-sorbed, either because of dissacharidase deciencies orbecause the absorptive capacity of the intestine for thatsugar may be overwhelmed by excessive consumption,eg, fructose and sorbitol. (14) Such excessive intakemay be seen in young children drinking fruit juices. Dis-sacharidase deciencies, such as lactase deciency, arerarely congenital but more often are a result of gutmucosal injury secondary to some process later in in-fancy, such as an enteritis. (2) Pure osmotic diarrheashould cease when the offending dietary nutrients areremoved. (1)

Secretory diarrhea occurs when there is a net secretionof electrolyte and uid from the intestine without com-pensatory absorption. Endogenous substances, oftencalled secretagogues, induce uid and electrolyte secre-tion into the lumen even in the absence of an osmoticgradient. Children with a pure secretory diarrhea willtherefore continue to experience diarrhea even whilefasting. Typically, secretagogues affect ion transport inthe large and small bowel both by inhibiting sodiumand chloride absorption and by stimulating chloride se-cretion via cystic brosis (CF) transmembrane regulatoractivation. Examples of secretory diarrhea include multiplecongenital diarrheal disorders associated with identiedgenetic mutations that affect gut epithelial ion transport.(1) Congenital chloride diarrhea (CCD) is one suchdisorder.

Chronic diarrhea associated with intestinal dysmotilitytypically occurs in the setting of intact absorptive abilities.Intestinal transit time is decreased, the time allowed forabsorption is minimized, and uid is retained withinthe lumen. High-amplitude propagated contractions playa key role in motility disorders of the gut and have been

found to be more frequent in patients with diarrhea-predominant irritable bowel syndrome (IBS). (15) Al-though diarrhea-predominant IBS may be diagnosedin older adolescents, toddlers commonly present withchronic nonspecic diarrhea (CNSD). Changes in smallintestinal motility also have been implicated in causingCNSD. (16)

Inammatory diarrhea may encompass all of the path-ophysiologic mechanisms. Inammation with resultantinjury to the intestine may lead to malabsorption of die-tary macronutrients which, in turn, creates a luminal os-motic gradient. Additionally, particular infectious agentsmay induce secretion of uid into the lumen, and bloodin the gut may alter intestinal motility. Diseases such asinammatory bowel disease (IBD) and celiac disease ex-emplify this inammatory mechanism. (13)

Evaluation of Chronic DiarrheaHistory and Physical Examination

A careful history of the characteristics of the diarrhea isimportant in assessing the severity of the illness and in for-mulating a differential diagnosis. Stool frequency, vol-ume, and appearance; the presence of blood or mucus;and the relationship to feeding or dietary intake shouldbe documented. Also important is the presence or absenceof abdominal pain, weight loss, rash, fatigue, vomiting,joint aches, or oral ulcers, among other extraintestinalsymptoms. A 3-day diary of stool pattern, dietary in-take, and associated symptoms can be helpful. One shouldinquire also about recent travel, exposure to new watersources, family history, and sick contacts.

Physical examination should include plotting ofweight, height, and head circumference on a standardizedgrowth chart. Signs of nutrient deciencies should besought, such as perianal dermatitis in zinc deciency andleg deformity in vitamin D deciency. The abdomenmay reveal distension in malabsorption syndromes or smallbowel bacterial overgrowth or may be exquisitely tender inan inammatory state. Examination of the rectum is im-portant also and may reveal perianal disease in IBD, guaiacpositive stool in many disease states, or loss of surroundingsubcutaneous tissue in celiac disease and other states ofmalnutrition.

Examination of Stool and BloodLaboratory examination should begin with microbiologicstudies for bacteria and parasites in the stool. Infectionwith bacteria such as Yersinia, Escherichia coli, and Sal-monella may develop into chronic illness and can be de-tected by routine stool culture. Additionally, some stool

gastrointestinal disorders chronic diarrhea

208 Pediatrics in Review Vol.33 No.5 May 2012


cultures may include testing for diarrhea-causingAeromonas and Plesiomonas. Clostridium difcile toxinassay should be performed, especially in the setting ofrecent antibiotic use. Antigen detection for Giardia andCryptosporidium are more sensitive and specic than rou-tine microscopy-based ova and parasite examinationsand therefore may be helpful if these infections are sus-pected. (17)

Analysis of the stool for electrolyte content and osmo-larity may be helpful in distinguishing an osmotic froma secretory diarrhea. If there is a difference betweenthe stool osmolarity and twice the sum of the concen-trations of sodium and potassium in the stool of>50mOsm, the diarrhea is osmotic in nature. If thisosmotic gap is 30 g/day in infants and >50 g/day inschool-age children) and a coefcient of fat malabsorp-tion of >5% is considered abnormal past infancy. Thenormal percentage can be up to 15% during infancy.

Blood tests should include routine complete bloodcell count to evaluate for anemia and thrombocytosis,suggesting blood loss and inammation, respectively.Evaluation of red blood cell characteristics may suggestvitamin B12 or folate deciency in malnutrition. Whiteblood cell count and differential and immunoglobulinanalysis screen for immune disorders. Erythrocyte sedi-mentation rate and C-reactive protein support inamma-tion but are nonspecic. Elevated tissue transglutaminaseimmune globulin A (TTG IgA) antibody is sensitive andspecic for celiac disease, but a low total serum IgA levelmay result in a false-negative test. Measurements of albu-min and prealbumin may be obtained to reect low die-tary protein intake. (13) Levels of the fat soluble vitaminsA, 25-OH vitamin D, vitamin E, and vitamin K (reectedby prothrombin time) may be measured if fat malabsorp-tion is suspected.

Additional TestingThe value of radiologic studies in the context of chronicdiarrhea is limited. Abdominal radiographs may show con-stipation or dilated small bowel loops. Computed tomog-raphy and MRI may be useful in IBD to show bowel wallthickening suggestive of mucosal inammation. Breath hy-drogen analysis, or breath testing, can be used to ex-amine for carbohydrate malabsorption. If not absorbed,lactose, sucrose, or lactulose given at the onset of testingreaches colonic bacteria, producing hydrogen that is mea-sured in the breath. Endoscopy may be useful to reveal du-odenal villous blunting and intraepithelial lymphocytes inceliac disease or evidence of ileal or colonic inammationin infectious colitis or IBD. Small bowel biopsy during en-doscopy also may reveal evidence of duodenitis in parasiticinfections. However, stool testing for parasites is much lessinvasive and is more sensitive and specic than endoscopy.

Differential DiagnosisIt may be helpful to separate the wide differential diagno-sis of pediatric chronic diarrhea into those illnesses thatresult in poor weight gain and those in which weight typ-ically is maintained. The Table presents the features of themain causes of chronic diarrhea.

Chronic Diarrhea Without Failure to ThriveChronic Nonspecific Diarrhea of Childhood orInfancy

CNSD is the most common form of persistent diarrhea inthe rst 3 years after birth. (18) The typical time of onsetmay range from 1 to 3 years of age and can last from in-fancy until age 5 years. Patients with CNSD usually passstool that is different in both consistency and frequencyfrom that of other children. Affected children may pass 4to 10 loose bowel movements per day without blood ormucus. Specic to CNSD is the pattern that these pa-tients pass stools only during waking hours, typically be-ginning with a large formed or semiformed stool afterawakening. As the day progresses, stools become morewatery and smaller in volume. Transit time of enteral con-tents may be especially short, and parents frequently describeundigested food remnants in the stool. By denition, chil-dren with CNSD maintain their weights and heights. Al-though some affected children describe mild abdominaldiscomfort, most typically appear healthy and maintaina normal appetite and activity level. (19)(20)

Potential pathophysiologic mechanisms for CNSD in-clude increased intestinal motility and osmotic effects ofintraluminal solutes (eg, carbohydrates). (16) The role ofingested carbohydrates in CNSD has been emphasized in




Table. Causes of Chronic Diarrhea

Without Failure to Thrive Major Clinical Features Major Laboratory and Imaging Findings

CNSD Daytime nonbloody, nonmucousy stools Normal laboratory and imaging resultsNormal growthOccurs in the first few years after birth

Infectious colitis Possible blood and/or mucus in stoolPossible fever and/or abdominal painExposure to undercooked meatContaminated waterOccurs at any age

Positive stool culture, ova and parasiteexamination, or stool antigen test

Lactose malabsorption Abdominal discomfort, bloating,flatulence

Elevated breath hydrogen concentrationafter lactose ingestion

Nonbloody stoolsOccurs beyond infancy

Small bowel bacterialovergrowth

Abdominal discomfortIncreased risk if ileocecal valve

removedOccurs at any age

Elevated fasting breath hydrogenconcentration (>20 ppm)

Elevated early and late breath hydrogenconcentration

After lactulose ingestionIBS Alternating constipation with diarrhea Normal laboratory and imaging results

Abdominal pain relieved by defecationAbsence of weight loss, bloody stool,

fever, or anemiaTypically diagnosed in adolescence

or later

With Failure to ThriveIDI Infectious colitis ruled out Enteropathy by histology

Higher risk in malnourished orimmunodeficient patients

In need of prompt nutritional supportAllergic enteropathy Most commonly in response to cow or

soy milkGrowth failure is in sharp contrast to

well infant with allergic colitisStool may be guaiac positive

May have hypoalbuminemia and anemiaElectrolyte abnormalities from diarrhea/

vomitingSerum IgE may be elevated

Celiac disease Up to 1/100 prevalenceSevere cases have abdominal distensionMyriad of presenting features

Elevated TTG IgA, antiendomysial IgAantibodies

May be IgA deficient*Histologic villous blunting and

intraepithelialLymphocytes

IBD Bloody stool more common in colitisEnteritis may cause nonbloody stoolStooling urgency, abdominal pain,

fatigue

Elevated erythrocyte sedimentation rate,thrombocytosis

Iron-deficiency anemiaHypoalbuminemia

Immunodeficiency state(various diseases)

Recurrent infectionsYoung age, typically in infancy

Abnormal immunoglobulins (eg, low IgG,low IgA, high IgM)

LymphopeniaLow antigen titers to previous

immunizationsCongenital secretory diarrhea(Chronic chloride and chronicsodium diarrhea)

Maternal polyhydramniosSevere secretory diarrhea at birthSevere dehydration

CCD: hypochloremia and metabolicalkalosis

CSD: hyponatremia and metabolicacidosis

Continued




light of a typical toddlers affection for fruit juices. Exces-sive intake of fruit juices, particularly those containingsorbitol or fructose (eg, apple, pear, cherry, and prunejuices), may contribute to the stool osmotic load, thuscausing or worsening diarrhea. (21)(22)

Reassurance is the cornerstone of therapy for CNSD.Parents should be reassured that their child is growing welland is healthy. Although no precise treatment for CNSDhas been established, dietary intervention may be prudent.Fruit juice intake should beminimized or changed to typesof juice with low sucrose and fructose loads. Beyond therestriction of fruit juice, possible helpful changes may beto liberalize fat to encourage normal caloric intake and toslow intestinal transit time, not to restrict ber, and to assureadequate but not overhydration. (21)

Infectious ColitisAlthough many infectious causes of diarrhea result in anacute presentation and short course, other pathogenicbacteria and parasites may cause chronic diarrhea. Virusesrarely cause diarrhea lasting more than 14 days and moretypically range from 2 days (eg, Norwalk-like virus) to 11days (enteric adenoviruses) in duration. (6) Rotavirusmay cause diarrhea lasting up to 20 days. (11)

Salmonella is one of the most common causes oflaboratory-conrmed cases of food-borne intestinal disease

reported to the Centers for Disease Control and Preven-tion each year. (23) The infection usually is contractedfrom exposure to food of animal origin related to poultry,eggs, beef, and dairy products. Nontyphoidal Salmonellaorganisms typically cause gastroenteritis with diarrhea,abdominal cramping, and fever. Salmonella organisms typ-ically are detected in routine stool culture for up to 5 weeksbut may be excreted in stool for >1 year in 5% of patients.(24) Antibiotic therapy for uncomplicated nontyphoidalserotypes is not indicated because it does not shortenthe disease duration and may prolong the duration of ex-cretion of bacteria in the stool. (25) Antibiotics are appro-priate, however, for treating children younger than 3months of age or those with immunosuppressive diseases,given the increased risk for invasive disease (bacteremia, os-teomyelitis, abscess, meningitis) in these populations. (23)

Yersinia enterocolitica and Y pseudotuberculosis causechronic diarrhea less commonly than Salmonella in childrenin the United States. Infection typically occurs via expo-sure to food products, specically pork (a major Yersiniareservoir) and dairy products but may occur with inges-tion of other foods contaminated by these products. Di-arrheal stool may contain blood, mucus, and leukocytes,reecting mucosal inammation. Symptoms may mirrorappendicitis or ileal Crohn disease because Yersinia mayaffect the terminal ileum. Often the organism needs to

Table. (Continued)

With Failure to ThriveTufting enteropathy Intractable watery diarrhea Electrolyte abnormalities

Severe growth failure Small bowel villous atrophy and crypthyperplasia without inflammation

Microvillous inclusiondisease

Diarrhea within first week afterbirth

Small bowel villous atrophy but no crypthyperplasia or inflammation

No history of polyhydramniosAutoimmune enteropathy Secretory diarrhea

May coexist with otherendocrinopathies

May have positive antienterocyte,antigoblet cell, or anticolonocyteserum antibodies

Neuroendocrine tumors Secretory diarrhea VIPoma: elevated serum VIPZES: elevated fasting serum gastrinCarcinoid: elevated urine 5-

hydroxyindoleacetic acidElevated prostaglandin E2

Hirschsprung disease Delayed passage of meconium Abnormal barium enemaDistended abdomen Absent ganglion cells on rectal biopsyExplosive stool with rectal

examinationCF Malabsorption of carbohydrate/

fat/proteinDecreased fecal elastaseElevated fasting breath hydrogen if

small bowel bacterial overgrowth present

IgEimmune globulin E; VIPvasoactive intestinal polypeptide-secreting tumor.* Leads to false-negative IgA-based antibody tests: TTG IgG may be useful in this setting.




be sought specically by laboratory personnel because itmay not be part of each institutions routine stool culture.The efcacy of antibiotics in treating uncomplicatedYersinia infection has not been established. (26)

Other bacterial causes of chronic diarrhea includeEscherichia coli, Campylobacter, Aeromonas, and Ple-siomonas. Enteropathogenic E coli is a leading causeof chronic diarrhea in developing countries, sometimes as-sociated with fever, abdominal pain, and vomiting. (27)Enteropathogenic E coli is one type of E coli disease inwhich antibiotic therapy has been shown to reduce mor-bidity and mortality in uncomplicated diarrheal disease.(28) Persistent bloody diarrhea with abdominal painshould raise suspicion for enterohemorrhagic E coli, par-ticularly because enterohemorrhagic E coli may result inhemolytic-uremic syndrome, a potentially dangerouscomplication.Campylobacter often originates from poultryand may cause diarrhea for only 4 to 5 days, but relapsesare common. Both E coli and Campylobacter can be iso-lated by routine stool culture.

Aeromonas, long considered a normal commensal or-ganism, has been shown recently to cause secretory diar-rhea with up to 20 watery stools per day. Symptoms arepersistent in approximately one-third of patients. Antibi-otics do not seem to be helpful in uncomplicated Cam-pylobacter and Aeromonas illnesses. Pleisomonas can befound in sh, shellsh, cats, and dogs; also causes secre-tory diarrhea; and has a course that may be shortened byantibiotic therapy. (29)

The protozoa Giardia intestinalis and Cryptosporid-ium may affect immunocompetent as well as immunode-cient children and adolescents. Both infections mayaffect the duodenum and upper small bowel, leading tomild villous blunting, dissacharidase deciency, and resul-tant osmotic and secretory diarrhea. Malabsorption of fat,protein, and carbohydrates may occur, worsening diar-rhea. Both infections are linked to contaminated waterand may be associated with childcare centers, exposureto wild animals, swimming in water parks or pools,or recent travel to developing countries. Symptomaticgiardiasis should be treated, even in immunocompetentchildren, with tinidazole, metronidazole, or nitazoxanideas possible agents. Cryptosporidium infection generallydoes not need to be treated unless the patient is immu-nocompromised. However, nitazoxanide has been ap-proved for treating immunocompetent children withdiarrhea associated with Cryptosporidium. (30)

Disaccharide IntoleranceLactose malabsorption is, by far, the most common typeof disaccharide intolerance. Approximately 70% of the

worlds adult population has primary acquired lactase de-ciency, resulting in lactose intolerance. Age of onsetvaries among populations, with one-fth of Hispanic,Asian, and African American children becoming lactoseintolerant before age 5 years. White children typicallydo not lose lactase function until after age 5 years, andoften much later, during later teenage years or beyond.(31) Molecular studies have elucidated differences inmessenger RNA expression among races that mightexplain population-based variations in lactase activity.(32) Congenital lactase deciency is exceedingly rareand only a handful of cases have been published inthe literature.

Secondary lactase deciency results from small intesti-nal mucosal injury when lactase enzyme is lost from thetips of the villi. Causes include rotaviral infection, para-sitic infection, celiac disease, Crohn disease, and otherenteropathies. Many studies question the clinical signif-icance of secondary lactase deciency in diarrheal illnessesexcept in children who are

during adolescence. Without any one specic pathophys-iologic cause identied, IBS is considered a functionaldisorder dened by symptom criteria. (35)(36) TheRome III criteria dene IBS as abdominal pain or dis-comfort at least 3 days per month in the last 3 monthsassociated with two or more of the following features:improvement with defecation, onset associated witha change in frequency of stooling, and onset associatedwith change in the form of the stool. This strict denitionmay be used to dene the syndrome precisely but typi-cally is more useful in research rather than in everydayclinical medicine. The history often suggests the diag-nosis, with abdominal pain often relieved with defeca-tion. These patients do not have rectal bleeding,anemia, weight loss, or fever. It should be determinedthat celiac disease is not present. Treatment is oftenchallenging. Antispasmodic agents, tricyclic antide-pressants, and selective serotonin-reuptake inhibitorsmay improve symptoms. Some probiotics have beenuseful in adult and pediatric IBS, but results are notconsistent. (37)

Chronic Diarrhea With Failure to ThriveIntractable Diarrhea of Infancy

Persistent diarrhea after an acute episode of presumedinfectious diarrhea is known as intractable diarrhea of in-fancy (IDI), postenteritis or postgastroenteritis diarrhea,postenteritis enteropathy, or slick gut. This disorder isunique compared with CNSD because in IDI there isweight loss associated with malabsorption and histologicevidence of enteropathy. (38) IDI remains an importantcause of morbidity and mortality in developing countrieswhere children may be at nutritional risk. Children at par-ticular risk include those who are young, who suffer mal-nutrition, or who have an altered immune state. (39)Osmotic diarrhea with increased uid requirements sec-ondary to carbohydrate malabsorption is common. With-out nutritional support, patients may become severely ill.

IDI should be suspected in any infant with persistentdiarrhea after an acute gastroenteritis. Other causes ofchronic diarrhea should be sought but not at the expenseof promptly supporting caloric needs. (6) Small bowel bi-opsy may reveal patchy villous atrophy and inammatoryinltrates in epithelial and lamina propria layers. Cautionshould be exercised in obtaining biopsies because malnu-trition increases the risks associated with endoscopy.Breastfeeding should continue unless lactose malabsorp-tion is strongly suspected.

To prevent IDI, guidelines for managing acute gastro-enteritis should be followed, which recommend avoiding

formula dilution and promoting early feeding that re-duces intestinal permeability and illness duration and im-proves nutritional outcomes. (40) Dietary protein andfat are important in recovery, but simple carbohydratesshould be minimized. The BRAT diet (bananas, rice, ap-plesauce, toast) in the management of diarrhea is unnec-essary and nutritionally suboptimal. Refeeding syndromeis a risk for severely malnourished patients. Intravenoushydration may be necessary in treating IDI. Toleranceof enteral feeds and resolution of diarrhea typically occurwithin 2 to 3 weeks.

Allergic EnteropathyAllergic enteropathy, or eosinophilic enteropathy, associ-ated with failure to thrive, vomiting, and diarrhea, shouldbe distinguished from allergic colitis occurring in other-wise healthy and thriving infants. As in allergic colitis, al-lergic enteropathy is induced by food proteins withthe most common being cow milk and soy proteins.In allergic enteropathy, however, there is small intestinalmucosal damage resulting in malabsorption of protein,carbohydrate, and fat. Protein malabsorption may leadto hypoalbuminemia and diffuse swelling. Profuse vom-iting and diarrhea may lead to severe dehydration, leth-argy, and hypotension, mimicking sepsis in a younginfant. Serum IgE levels may or may not be elevated.Protein hydrolysate or amino acid-based elemental for-mulas are necessary if breastfeeding on a restricted diet isnot possible. Once the inciting dietary protein is re-moved, the enteropathy will resolve.

Celiac DiseaseCeliac disease is an immune-mediated enteropathy thatoccurs in the setting of gluten ingestion in a geneticallysusceptible individual. With its prevalence in adultsand children approaching 1% worldwide, celiac diseasehas become a more commonly diagnosed disorder. (41)However, the classic presentation of celiac disease inchildren with the triad of failure to thrive, diarrhea,and abdominal distension is being seen less frequently.(42) Because of family screening, more sensitive andeasily accessible testing, and the recognition of thewide variety of presenting symptoms, identication ofpatients presenting with atypical symptoms is on therise. (43)

Diagnosis should begin with establishing the presenceof antiendomysial IgA antibodies, which have near 100%specicity, or employing newer and less expensive tech-niques for measuring enzyme-linked immunosorbentassay-based anti-TTG IgA antibodies. Diagnosis is con-rmed by particular histologic ndings in the duodenum,




including villous blunting and prominent intraepitheliallymphocytosis. Current treatment is with a diet free ofwheat, rye, and barley. New potential therapies are beingsought, including the use of gliadin-digesting recombi-nant enzymes.

Inflammatory Bowel DiseaseChildren and adolescents suffering from diarrhea, with orwithout weight loss, must be evaluated for IBD. Approx-imately 50% to 80% of children with Crohn disease willpresent with diarrhea, among other symptoms. In Crohndisease, stool may contain microscopic blood but maynot be grossly bloody, especially in the absence of signif-icant left-sided colonic disease. Diarrhea is more commonin colonic disease and may be absent altogether in cases ofisolated small bowel inammation. In ulcerative colitis,diarrhea is a more consistent presenting feature, often in-sidious in its development but eventually developinghematochezia. Nocturnal diarrhea with urgency may bea sign of left-sided colonic inammation in either Crohndisease or ulcerative colitis. Diarrhea associated with IBDtypically improves with therapy as mucosal inammationresolves.

Immunodeficiency StatesChildren with primary immunodeciency states oftenpresent with chronic diarrhea. (44) X-linked agamma-globulinemia may result in diarrhea secondary to chronicrotaviral infections or recurrent giardiasis. IgA deciencymay lead to recurrent giardiasis and bacterial overgrowth,and is associated with a 10- to 20-fold increased incidenceof celiac disease. (45) Chronic diarrhea is common alsoin hyper-IgM and human immunodeciency virus syn-dromes and may be caused by infection withCryptosporid-ium parvum in these diseases. Children with commonvariable immunodeency often present with diarrheaand signicant malabsorption along with severe recur-rent life-threatening infections during the rst monthsafter birth. Intractable diarrhea with neonatal insulin-dependent diabetes should raise suspicion for the syn-drome of immune dysregulation, polyendocrinopathy,and enteropathy (autoimmune), X-linked (IPEX syn-drome). Glycogen storage disease type 1B and chronicgranulomatous disease may present very similarly toCrohn disease, likely related to defective intestinal mu-cosal immunity. (46)

Congenital Secretory DiarrheaTwo very rare causes of secretory diarrhea in early infancyare CCD and congenital sodium diarrhea (CSD). Fewerthan 15 patients with CSD and w250 with CCD have

been reported in the literature. (47) Both diseases presentbefore birth with polyhydramnios resulting from in uterodiarrhea. At birth, high-volume secretory diarrhea con-tinues despite bowel rest and may cause life-threateningdehydration and electrolyte disturbances. CCD causes se-vere hypochloremia and a unique metabolic alkalosis,whereas CSD causes hyponatremia with alkaline stoolsresulting in metabolic acidosis. Stool electrolytes oftenaid in the diagnosis, and genetic testing can identify defec-tive chloride transport genes in some patients with CCD.Aggressive uid and electrolyte replacement is the main-stay of therapy for both diseases.

Tufting EnteropathyTufting enteropathy, also known as intestinal epithelialdysplasia, presents in the rst few months after birth withgrowth failure and intractable watery diarrhea. (48) Sig-nicant electrolyte abnormalities may occur even beforethe severity of illness is recognized by caretakers. His-tology of the small bowel reveals a unique picture ofvillous atrophy and crypt hyperplasia without signi-cant inammation. Closely packed enterocytes appearto create focal epithelial tufts. A recent genomicstudy of children born with tufting enteropathy re-vealed mutations in the epithelial cell adhesion mole-cule EpCAM. (49) Affected infants typically becomedependent on parenteral nutrition to allow normalgrowth and development. Small bowel transplant is po-tentially curative, but the associated morbidity and mor-tality are high.

Microvillous Inclusion DiseaseAnother rare cause of chronic secretory diarrhea in theneonatal period is microvillous inclusion disease, present-ing with diarrhea so watery that it may be mistaken forurine. (48) Microvillous inclusion disease is the secondmost common cause of severe, protracted diarrhea inthe rst week after birth, after infectious causes are ex-cluded. Contrary to what occurs in CCD and CSD, poly-hydramnios typically is not seen. Histology reveals smallbowel villous atrophy but without inammation or ex-pected crypt hyperplasia. Villin substance can be seenby immunostaining in affected cell cytoplasm, creatingthe microvillous inclusions. Aggressive intravenous re-hydration and electrolyte replacement are necessary tomaintain life during infancy, followed by lifelong paren-teral nutrition in most cases.

Autoimmune EnteropathyChildren with autoimmune enteropathy usually developsecretory diarrhea after the rst 8 weeks after birth.




Another autoimmune disease, such as insulin-dependentdiabetes, may be present in the setting of chronic diar-rhea and poor growth, which should raise suspicion forIPEX syndrome. (48) However, autoimmune enterop-athy may exist without extraintestinal manifestations.Diagnosis is made by documenting antienterocyte,anticolonocyte, or antigoblet cell antibodies in theblood, although the number of centers that performthis test is limited and the specicity of the test is un-clear. Treatment is difcult but may be accomplishedwith immunosuppressive agents such as corticoste-roids, 6-mercaptopurine, tacrolimus, and iniximab.(50)

Neuroendocrine TumorsNeuroendocrine tumors affecting the gastrointestinaltract in children are rare. These tumors produce symp-toms by the systemic effect of their secretory products.The neuroendocrine tumors produce secretory diarrheaand include vasoactive intestinal polypeptide-secretingtumor, or VIPoma; Zollinger-Ellison syndrome (ZES);tumors secreting prostaglandin E2; and carcinoid syn-drome. VIP stimulates cyclic adenosine monophosphateactivity, eventually resulting in intestinal secretion, similarto the effects of the cholera toxin. Therefore, the classicpresentation of VIPoma is with profuse watery diarrhea(usually >20 cc/kg per day), hypokalemia, and achlor-hydria (WDHA syndrome). ZES causes diarrhea becauseof high intestinal gastrin levels. Carcinoid tumorsmay secrete serotonin, bradykinin, and histamine, alsoleading to gastric acid hypersecretion and diarrhea.Once secretory diarrhea is established, the evaluationmay include measuring the concentrations of serumVIP, fasting gastrin, and prostaglandin E2 levels,along with 24-hour urine 5-hydroxyindoleacetic acidfor carcinoid tumor. Most VIPomas in children areganglioneuromas or ganglioneuroblastomas, whichcan be identied radiographically. Operative resectionis imperative but not always curative if the tumor hasmetastasized. (51)

Hirschsprung DiseaseDiarrhea is present in approximately one-third of neo-nates born with Hirschsprung disease. (52) The diarrheausually is a consequence of enterocolitis that occurs in thesetting of bacterial stasis in the lumen. (53) Children maypresent with fever, diarrhea, and abdominal distension.Some children may appear acutely ill with explosive diar-rhea, vomiting, rectal bleeding, and lethargy, whereasothers may present with only loose stools and perianal

excoriation. Hirschsprung disease should be suspectedin any infant who does not pass meconium within the rst24 hours, which is the case in 94% of affected infants butin only 10% of healthy infants. Older infants may havepoor growth, a distended abdomen, and explosive pas-sage of stool with rectal examination. Older childrenwith Hirschsprung disease usually do not have the fe-cal soiling and stool withholding behaviors that arecommon in functional constipation. Enterocolitis rep-resents the most signicant source of morbidity andmortality in Hirschsprung disease and deserves im-mediate treatment with intravenous antibiotics andsupportive care.

Cystic FibrosisDiarrhea occurs in CF most commonly as a result of pan-creatic insufciency. Approximately 90% of patients withCF have pancreatic insufciency. (54) Loss of exocrinepancreatic function leads to malabsorption of carbohy-drates, fat, and protein because of dysfunctional amylases,lipases, and proteases, respectively. Such malabsorptionleads to poor growth in addition to chronic diarrhea andpossible steatorrhea. Patients with CF also have an in-creased incidence of small bowel bacterial overgrowth,possibly secondary to altered motility and thickened se-cretions, among other complex factors. (55) Fecal elas-tase can be used as a predictor of pancreatic exocrinefunction, with low levels indicating possible pancreaticinsufciency. Pancreatic enzyme replacement therapymay improve malabsorptive diarrhea in patients withCF.

Factitious DiarrheaWhen inconsistencies arise among a patients history,physical signs, and laboratory ndings, the practitionershould consider the possibility of a factitious disorder.Many cases of factitious diarrhea induced by either thepatient or patients parents have been reported in the lit-erature. (56)(57) Although laxative ingestion is the mostcommon cause of factitious diarrhea, the ingestion of os-motic agents or even feces may induce diarrhea. Patientsalso may dilute stool to create the appearance of diarrhea.Munchausen by proxy syndrome (factitious disorder byproxy per Diagnostic and Statistical Manual criteria), inwhich the caregiver creates the childs illness, often in-cludes factitious diarrhea induced with stimulant laxativesor even by syrup of ipecac poisoning. Such cases usuallyrequire hospital admission with careful observation aftera full evaluation for organic causes of chronic diarrhea hasbeen completed.




References1. Binder HJ. Causes of chronic diarrhea. N Engl J Med. 2006;355(3):2362392. Vanderhoof JA. Chronic diarrhea. Pediatr Rev. 1998;19(12):4184223. Wenzl HH, Fine KD, Schiller LR, Fordtran JS. Determinants ofdecreased fecal consistency in patients with diarrhea. Gastroenter-ology. 1995;108(6):172917384. Fine KD, Schiller LR. AGA technical review on the evaluationand management of chronic diarrhea. Gastroenterology. 1999;116(6):146414865. Black RE, Morris SS, Bryce J. Where and why are 10 millionchildren dying every year? Lancet. 2003;361(9376):222622346. Keating JP. Chronic diarrhea. Pediatr Rev. 2005;26(1):5147. Abba K, Sineld R, Hart CA, Garner P. Pathogens associatedwith persistent diarrhoea in children in low and middle incomecountries: systematic review. BMC Infect Dis. 2009;9:888. Kosek M, Bern C, Guerrant RL. The global burden of diarrhoealdisease, as estimated from studies published between 1992 and2000. Bull World Health Organ. 2003;81(3):1972049. Vernacchio L, Vezina RM, Mitchell AA, Lesko SM, Plaut AG,Acheson DW. Characteristics of persistent diarrhea in a community-based cohort of young US children. J Pediatr Gastroenterol Nutr.2006;43(1):525810. Malek MA, Curns AT, Holman RC, et al. Diarrhea- androtavirus-associated hospitalizations among children less than 5years of age: United States, 1997 and 2000. Pediatrics. 2006;117(6):1887189211. Valencia-Mendoza A, Bertozzi SM, Gutierrez JP, Itzler R.Cost-effectiveness of introducing a rotavirus vaccine in developingcountries: the case of Mexico. BMC Infect Dis. 2008;8:10312. Schiller LR. Chronic diarrhea. Gastroenterology. 2004;127(1):28729313. Israel E. Chronic diarrheal disease. In: Kleinman RE, ed.Pediatric Nutrition Handbook. 6th ed. Elk Grove Village, IL:American Academy of Pediatrics; 2009:637649

14. Gibson PR, Newnham E, Barrett JS, Shepherd SJ, Muir JG.Review article: fructose malabsorption and the bigger picture.Aliment Pharmacol Ther. 2007;25(4):34936315. Spiller R. Role of motility in chronic diarrhoea. Neurogas-troenterol Motil. 2006;18(12):1045105516. Fenton TR, Harries JT, Milla PJ. Disordered small intestinalmotility: a rational basis for toddlers diarrhoea. Gut. 1983;24(10):89790317. Bruijnesteijn van Coppenraet LE, Wallinga JA, Ruijs GJ, BruinsMJ, Verweij JJ. Parasitological diagnosis combining an internallycontrolled real-time PCR assay for the detection of four protozoa instool samples with a testing algorithm for microscopy. Clin Micro-biol Infect. 2009;15(9):86987418. Cohen SA, Hendricks KM, Eastham EJ, Mathis RK, WalkerWA. Chronic nonspecic diarrhea: a complication of dietary fatrestriction. Am J Dis Child. 1979;133(5):49049219. Kneepkens CM, Hoekstra JH. Chronic nonspecic diarrhea ofchildhood: pathophysiology and management. Pediatr Clin NorthAm. 1996;43(2):37539020. Kleinman RE. Chronic nonspecic diarrhea of childhood.Nestle Nutr Workshop Ser Pediatr Program. 2005;56:7379, discus-sion 798421. Hoekstra JH, van den Aker JH, Hartemink R, Kneepkens CM.Fruit juice malabsorption: not only fructose. Acta Paediatr. 1995;84(11):1241124422. Moukarzel AA, Lesicka H, Ament ME. Irritable bowelsyndrome and nonspecic diarrhea in infancy and childhoodrelationship with juice carbohydrate malabsorption. Clin Pediatr(Phila). 2002;41(3):14515023. American Academy of Pediatrics. Salmonella infections. In:Pickering LK, Baker CJ, Kimberlin DW, Long SS, eds. Red Book2009 Report of the Committee on Infectious Diseases. 28th ed. ElkGrove Village, IL: American Academy of Pediatrics; 2009:58458924. Buchwald DS, Blaser MJ. A review of human salmonellosis: II.Duration of excretion following infection with nontyphi Salmonella.Rev Infect Dis. 1984;6(3):34535625. Barber DA, Miller GY, McNamara PE. Models of antimicrobialresistance and foodborne illness: examining assumptions andpractical applications. J Food Prot. 2003;66(4):70070926. American Academy of Pediatrics. Yersinia enterocolitica andYersinia pseudotuberculosis infections. In: Pickering LK, Baker CJ,Kimberlin DW, Long SS, eds. Red Book 2009 Report of the Committeeon Infectious Diseases. 28th ed. Elk Grove Village, IL: AmericanAcademy of Pediatrics; 2009:73373527. Fagundes-Neto U, Scaletsky IC. The gut at war: theconsequences of enteropathogenic Escherichia coli infection asa factor of diarrhea and malnutrition. Sao Paulo Med J. 2000;118(1):212928. Nelson JD. Duration of neomycin for enteropathogenic Escher-ichia coli diarrheal disease: a comparative study of 113 cases. Pediatrics.1971;48(2):24825829. Kain KC, Kelly MT. Clinical features, epidemiology, andtreatment of Plesiomonas shigelloides diarrhea. J Clin Microbiol.1989;27(5):998100130. American Academy of Pediatrics. Cryptosporidiosis. In: Pick-ering LK, Baker CJ, Kimberlin DW, Long SS, eds. Red Book 2009Report of the Committee on Infectious Diseases. 28th ed. Elk GroveVillage, IL: American Academy of Pediatrics; 2009:27227331. Heyman MB; Committee on Nutrition. Lactose intolerance ininfants, children, and adolescents. Pediatrics. 2006;118(3):12791286

Summary

The differential diagnosis for chronic diarrhea inchildren is broad. Pediatric clinicians can narrow thesepossible diagnoses beginning with a detailed historyand physical examination.

Particular attention should be paid to growthmeasurements to distinguish between chronicdiarrhea with and without associated growth failure.

Understanding the four basic pathophysiologicmechanisms of diarrhea also may aid in makinga diagnosis. The four categories are osmotic, secretory,dysmotility associated, and inflammatory.

Although specific therapies vary for each disease, theimportance of maintaining nutrition demandsparticular emphasis. Whatever the cause of thediarrhea, each patient requires adequate caloric intaketo allow healing of the initial insult, or at least tosupport the child while pursuing diagnostic andtherapeutic interventions.




32. Wang Y, Harvey CB, Hollox EJ, et al. The geneticallyprogrammed down-regulation of lactase in children. Gastroenterol-ogy. 1998;114(6):1230123633. Sandhu BK, Isolauri E, Walker-Smith JA, et al. A multicentrestudy on behalf of the European Society of Paediatric Gastroenter-ology and Nutrition Working Group on Acute Diarrhoea. Earlyfeeding in childhood gastroenteritis. J Pediatr Gastroenterol Nutr.1997;24(5):52252734. Lauritano EC, Gabrielli M, Lupascu A, et al. Rifaximin dose-nding study for the treatment of small intestinal bacterial over-growth. Aliment Pharmacol Ther. 2005;22(1):313535. Mayer EA. Clinical practice. Irritable bowel syndrome. N EnglJ Med. 2008;358(16):1692169936. . Rome Foundation. Rome III diagnostic criteria. Available at:http://www.romecriteria.org/assets/pdf/19_RomeIII_apA_885-898.pdf. Accessed October 12, 201137. Kligler B, Hanaway P, Cohrssen A. Probiotics in children.Pediatr Clin North Am. 2007;54(6):949967, xi38. Guarino A, De Marco G. Persistent diarrhea. In: Kleinman RE,Sanderson IR, Goulet O, Sherman PM, Mieli-Vergani G, ShneiderBL, eds. Walkers Pediatric Gastrointestinal Disease: Pathology,Diagnosis, Management. 5th ed. Hamilton, Ontario: BC DeckerInc; 2008:26527439. Bhutta ZA, Hendricks KM. Nutritional management ofpersistent diarrhea in childhood: a perspective from the developingworld. J Pediatr Gastroenterol Nutr. 1996;22(1):173740. King CK, Glass R, Bresee JS, Duggan C; Centers for DiseaseControl and Prevention. Managing acute gastroenteritis amongchildren: oral rehydration, maintenance, and nutritional therapy.MMWR Recomm Rep. 2003;52(RR-16):11641. Green PH, Cellier C. Celiac disease. N Engl J Med. 2007;357(17):1731174342. Fasano A. Clinical presentation of celiac disease in the pediatricpopulation. Gastroenterology. 2005;128(4 suppl 1):S68S7343. Garampazzi A, Rapa A,Mura S, et al. Clinical pattern of celiac diseaseis still changing. J Pediatr Gastroenterol Nutr. 2007;45(5):61161444. Goulet O, Seidman EG. Primary immunodeciency diseases.In: Walker WA, ed. Pediatric Gastrointestinal Disease. 4th ed.Hamilton, Ontario: BC Decker Inc; 2004:707733

45. Meini A, Pillan NM, Villanacci V, Monafo V, Ugazio AG,Plebani A. Prevalence and diagnosis of celiac disease in IgA-decientchildren. Ann Allergy Asthma Immunol. 1996;77(4):33333646. Schppi MG, Klein NJ, Lindley KJ, et al. The nature of colitisin chronic granulomatous disease. J Pediatr Gastroenterol Nutr.2003;36(5):62363147. Martin MG, Wright EM. Congenital intestinal transportdefects. In: Walker WA, ed. Pediatric Gastrointestinal Disease. 4thed. Hamilton, Ontario: BC Decker Inc; 2004:91191448. Sherman PM, Mitchell DJ, Cutz E. Neonatal enteropathies:dening the causes of protracted diarrhea of infancy. J PediatrGastroenterol Nutr. 2004;38(1):162649. Sivagnanam M, Mueller JL, Lee H, et al. Identication ofEpCAM as the gene for congenital tufting enteropathy. Gastroen-terology. 2008;135(2):42943750. Akram S, Murray JA, Pardi DS, et al. Adult autoimmuneenteropathy: Mayo Clinic Rochester experience. Clin GastroenterolHepatol. 2007;5(11):12821290, quiz 124551. Goday PS, Cohen MB. Secretory tumors. In: Walker WA, ed.Pediatric Gastrointestinal Disease. 4th ed. Hamilton, Ontario: BCDecker Inc; 2004:1055106452. Imseis E, Gariepy CE. Hirschsprungs disease. In: KleinmanRE, ed. Pediatric Gastrointestinal Disease. 5th ed. Hamilton,Ontario: BD Decker Inc; 2008:68369253. Murphy F, Puri P. New insights into the pathogenesis ofHirschsprungs associated enterocolitis. Pediatr Surg Int. 2005;21(10):77377954. Borowitz D, Baker SS, Duffy L, et al. Use of fecal elastase-1 toclassify pancreatic status in patients with cystic brosis. J Pediatr.2004;145(3):32232655. Fridge JL, Conrad C, Gerson L, Castillo RO, Cox K. Riskfactors for small bowel bacterial overgrowth in cystic brosis.J Pediatr Gastroenterol Nutr. 2007;44(2):21221856. Phillips S, Donaldson L, Geisler K, Pera A, Kochar R. Stoolcomposition in factitial diarrhea: a 6-year experience with stoolanalysis. Ann Intern Med. 1995;123(2):9710057. Katz SL, McGee P, Geist R, Durie P. Factitious diarrhea:a case of watery deception. J Pediatr Gastroenterol Nutr. 2001;33(5):607609

PIR QuizThis quiz is available online at http://www.pedsinreview.aappublications.org. NOTE: Since January 2012, learners cantake Pediatrics in Review quizzes and claim credit online only. No paper answer form will be printed in the journal.

New Minimum Performance Level RequirementsPer the 2010 revision of the American Medical Association (AMA) Physicians Recognition Award (PRA) and credit system,a minimum performance level must be established on enduring material and journal-based CME activities that are certified for AMAPRA Category 1 CreditTM. In order to successfully complete 2012 Pediatrics in Review articles for AMA PRA Category 1 CreditTM,learners must demonstrate a minimum performance level of 60% or higher on this assessment, which measures achievement of theeducational purpose and/or objectives of this activity.

Starting with 2012 Pediatrics in Review, AMA PRA Category 1 CreditTM can be claimed only if 60% or more of the questions areanswered correctly. If you score less than 60% on the assessment, you will be given additional opportunities to answer questionsuntil an overall 60% or greater score is achieved.




1. A 2-year-old girl has had daily diarrhea for the past 3 months. She has a soft but formed stool in the morningand then has seven to eight episodes of increasingly soft-to-watery stools. Her parents at times see undigestedfood in her stools. She does not have loose stools at night. She eats a regular diet, drinks milk, water, and juice.She is growing well. She has not had blood or mucus in her stools and does not complain of abdominal pain. Herparents ask what is the next step in the evaluation and management of her diarrhea. Your best response is torecommend which of the following?

A. Bowel rest with restricted caloric intake for 2 weeks.B. Eliminating juice intake.C. Hydrogen breath testing.D. Initiating treatment with artificial lactase enzymes.E. Obtaining stool cultures.

2. A 14-year-old girl has abdominal pain approximately weekly. During these episodes, she has multiple bowelmovements that are looser than her usual stools. She relates that she feels better after she has a bowelmovement. She has had no fever, rectal bleeding, or mucus in her stool. She has not lost weight. Her physicalexamination is normal. The best next step in the evaluation of her abdominal pain is

A. Endoscopy.B. Upper gastrointestinal series with small bowel follow-through.C. Stool electrolyte content and osmolarity.D. Tissue transglutaminase immune globulin A test.E. 72-hour stool collection for measurement of fecal fat.

3. An 8-month-old girl is seen for daily loose stools for 4 weeks. Her older siblings also had diarrhea butrecuperated after 10 days of illness. The infant has lost weight and is hospitalized for further evaluation.The diet you are most likely to recommend for this infant is

A. Bowel rest with parenteral nutrition.B. BRAT diet (bananas, rice, applesauce, toast).C. Breastfeeding or regular formula.D. Oral rehydration fluids only.E. Restricted protein and fat intake.

4. A 5-month-old boy has been hospitalized for pneumonia. He has had diarrhea for 3 months, with frequentwatery stools daily. He is losing weight. On physical examination, he is afebrile, thin, and listless. Theevaluation you are most likely to initiate includes

A. Enteral transit time study.B. Hydrogen breath testing.C. Immunoglobulin levels.D. Lactulose testing.E. 3-day dietary history.

5. A 3-month-old infant boy has emesis and diarrhea and is losing weight. His formula was changed to a soy-based product and after rehydration he is admitted to the hospital for further evaluation. The diet you are mostlikely to request for this infant is

A. Bowel rest with parenteral nutrition.B. Cows milk-based formula with artificial lactase enzyme.C. Diluted soy formula.D. Oral rehydration solution.E. Protein hydrolysate or amino acid-based elemental formula.




DOI: 10.1542/pir.33-5-2072012;33;207Pediatrics in Review

Garrett C. Zella and Esther J. IsraelChronic Diarrhea in Children

ServicesUpdated Information &

http://pedsinreview.aappublications.org/content/33/5/207including high resolution figures, can be found at:

References

http://pedsinreview.aappublications.org/content/33/5/207#BIBLat: This article cites 47 articles, 8 of which you can access for free

Subspecialty Collections

stinal_disordershttp://pedsinreview.aappublications.org/cgi/collection/gastrointeGastrointestinal Disordersevelopmenthttp://pedsinreview.aappublications.org/cgi/collection/growth_dGrowth and Development_diseaseshttp://pedsinreview.aappublications.org/cgi/collection/infectiousInfectious Diseasesfollowing collection(s): This article, along with others on similar topics, appears in the

Permissions & Licensing

/site/misc/Permissions.xhtmltables) or in its entirety can be found online at: Information about reproducing this article in parts (figures,

Reprints/site/misc/reprints.xhtmlInformation about ordering reprints can be found online:


Pediatrics in Review-2012-Zella. Chronic Diarrhea

Documents

Transcript of Pediatrics in Review-2012-Zella. Chronic Diarrhea