aspectos prácticos de los trastornos funcionales digestivos · – se mantiene la clasificación...

AspectosprácticosdelostrastornosfuncionalesdigestivosRafaelGaleraMartínez

Índice

• ConceptodeTrastornoGIFuncional(TGIF)

• GeneralidadesabordajedelpacienteconTGIF

• CriteriosRomaIV

– Trastornosfuncionalesdigestivosen<5años

– Trastornosfuncionalesdigestivosenniñosyadolescentes

¿QuésonlosTGIF?

• ConjuntosíntomasGIcrónicosorecurrentes

• Noexplicadosporanomalíasestructuralesobioquímicas(nomarcadoresbiológicos)

• Parasuidentificaciónsolopodemosutilizarsíntomas

TGIF:fisiopatología• Modelobiopsicosocial:interaccióncomplejaentrefactores

ambientales,psicológicos,psicosociales,vulnerabilidadgenética, quejuntoconexperienciastempranasenlavida,configuraríanlahabilidaddelSNCydigestivoparaadaptarsealoscambiosfisiológicosodeestrés.

• Unafunciónintestinalalterada implicaríaalteracionesenelprocesamientocentraldelasseñalesdedolordelsistemadigestivo,conunahipersensibilidadvisceraly/odisregulacióninmunemucosaymicrobiana.

• Disfunciónejecerebro-intestino (comunicaciónbidireccional)

Oudenhove LV.Gastroentrology 2016;150:1355-1367

TGIF:fisiopatología

behavior experience more severe stomachaches and moreschool absences than other children6 (Figure 2). Inaddition, when parents were asked to show positive orsympathetic responses to their children’s pain in alaboratory, the frequency of pain complaints was higherthan when parents are instructed to ignore them.7 Finally, alarge randomized clinical trial of children with functionalabdominal pain found that cognitive-behavioral treatment(CBT) targeting coping strategies, as well as parents’ andchildren’s beliefs about, and responses to, children’s paincomplaints, induced greater baseline to follow-updecreases in pain and GI symptoms compared with aneducational intervention controlling for time andattention,8 and that this effect was mediated by changes inparents’ cognitions about their child’s pain.9

There is also a strong association between parentalpsychological status, particularly anxiety, depression, andsomatization, and children’s abdominal symptoms.4,10,11

This association could be occurring through modeling—children observing and learning to display the behaviorsthey observe, in this case, possibly heightened attention to,or catastrophizing about, somatic sensations. However, theeffect of parental traits on children’s symptoms could alsooccur through reinforcement. Parents with certain traits orbeliefs, such as excessive worry about pain, might paymore attention to, and thereby reward, somatic complaints.

Parents’ catastrophizing cognitions about their own painpredicted responses to their children’s abdominal pain thatencouraged illness behavior, which in turn predicted childfunctional disability.12

Figure 1. Biopsychosocial Model of IBS. Genetic and environmental factors, such as early life experiences, trauma, and sociallearning, influence both the brain and the gut, which in turn interact bidirectionally via the autonomic nervous system and theHPA axis. The integrated effects of altered physiology and the person’s psychosocial status will determine the illnessexperience and ultimately the clinical outcome. Furthermore, the outcomes will in turn affect the severity of the disorder. Theimplication is that psychosocial factors are essential to the understanding of IBS pathophysiology and the formulation of aneffective treatment plan. Figure adapted from Drossman et al,109 with permission.

Figure 2. Associations between maternal reinforcement andparental IBS, and illness behavior. In addition to increasedreported severity, children whose mothers strongly reinforceillness behavior also experience more school absences thanother children. Figure adapted from Levy et al,6 withpermission.

1356 Van Oudenhove et al Gastroenterology Vol. 150, No. 6

BIOPSYCHOSOCIALASPECTS

Oudenhove LV.Gastroentrology 2016;150:1355-1367

imaging improved our understanding of the interactionsbetween the brain and gut, and this led to the concept of thebrain–gut axis. The term neurogastroenterology wasmentioned in Rome II in 1999 with the basic science andphysiology chapters17,18 as a means to reflect this emergingfield of research. In effect, neurogastroenterology reflectsthe structural and physiological components of the bio-psychosocial model, and the latter represents the clinicalresearch and application. The use of neurogastroenterologyas a research domain provides a level of legitimacy togut–brain research as never seen before.3 Over the past 2decades, the term has been used by numerous researchsocieties, as well as journals and book publications.

Gastrointestinal Symptoms, Syndromes,and Diagnostic Criteria

The preceding history sets the stage for understandingthe place of functional gastrointestinal symptoms and syn-dromes within gastroenterology, and it provides the basisfor the development of diagnostic criteria and the work ofthe Rome Foundation.

Concepts of Gastrointestinal Disease, Motility, andFunctional GI Disorders. Table 1 identifies the majorclinical domains seen in gastroenterology.

1. The organic (structural) disorders (eg, esophagitis,inflammatory bowel disease) are classified in terms oforgan morphology and the criterion for a disease ispathology at a macro- or microlevel.

2. A motility disorder (eg, gastroparesis, intestinalpseudo-obstruction), is classified in terms of organfunction and specifically altered motility. Althoughdysmotility relates to abnormal visceral muscle ac-tivity (ie, slow bowel transit, delayed gastricemptying), a motility disorder is presumed to bepersistent or recurrent dysmotility recognized as aclinical entity, and variably associated with symp-toms. We also recognize that dysmotility may comeand go with repeated physiological testing.

3. A functional GI disorder (eg, IBS, functional dyspepsia)relates to the patient’s interpretation and reporting of

an illness experience, and it is classified primarily interms of symptoms. A symptom is a noticeable expe-riential change in the body or its parts that is reportedby the patient as being different from normal and mayor may not be interpreted as meaningful. However, asyndrome relates to the association of several clini-cally recognizable symptoms or signs that occurtogether to define a clinical entity. A functional GIdisorder is a syndrome based on symptoms thatcluster together and are diagnosed by Rome criteria.

Notably, there is overlap across these 3 domains. Anorganic disorder such as ulcerative colitis, identified by gutpathology, may be associated with a motility disturbanceand usually is associated with symptoms of pain and diar-rhea, but neither the motility disturbance nor the symptomsare necessary for the diagnosis. A motility disorder such asgastroparesis is identified by a persistent motility distur-bance (eg, delayed gastric emptying). It may occur fromaltered gut neuronal morphology and often has symptomsof nausea and vomiting, but patients do not necessarily havesymptoms that correlate with the disturbed motility.19

However, it is the motility finding that characterizes thedisorder. Similarly, a functional GI disorder such as IBS orfunctional dyspepsia may have pathologic findings of in-flammatory cells in the lamina propria of the gut or eosin-ophils in the duodenum, respectively, as well as disturbedmotility, but histopathology is not necessary for defining afunctional GI disorder. The caveat is that although FGIDcriteria primarily are symptom-based, there are exceptions,such as with the anorectal disorders, in which physiologicalfindings are part of the criteria. Furthermore, identificationof biological substrates may help in terms of subclassifi-cation and treatment.

History of Rome Criteria for Diagnosis ofFGIDs and of the Rome Foundation

Pre-Rome: working team publications leading toclassification of FGIDs. This history began in Rome 30years agowhenAldo Torsoli, Professor of Gastroenterology atthe University of Rome, was engaged in developing WorkingTeams for the International Gastroenterology meetings (held

Table 1.Major Clinical Domains in Gastroenterology

OrganicGI disorder

Motilitydisorder

FunctionalGI disorder

Primary domain Organ morphology Organ function Illness experienceCriterion Pathology (disease) Altered motility SymptomsMeasurement Histology Motility Motility

Pathology Visceral sensitivity Visceral sensitivityEndoscopy Symptom criteria (Rome)Radiology Psychosocial

Examples Esophagitis Diffuse esophageal spasm Esophageal chest painPeptic ulcer Gastroparesis Functional dyspepsiaIBD Pseudo-obstruction IBSColon cancer Colonic inertia Functional constipation

IBD, inflammatory bowel disease.

1266 Douglas A. Drossman Gastroenterology Vol. 150, No. 6

FUNCTIONALGIOVERVIEW

Drossman DA.Gastroentrology 2016;150:1262-79..

GeneralidadesenelabordajedelpacienteconTGIF

Competenciatécnica(CriteriosRomaIV)

+

Algomás…

CriteriosdiagnósticosRoma• CriteriosRomaI(1994):21TGIFenadultos

– “The Functional GastrointestinalDisorders:Diagnosis,Patho- physiology,andTreatment”AldoTorsoli – W.Grant Thompsonetal

• CriteriosRomaII(1999-2000):1ªclasificaciónpediátrica– Basadaensíntomas(tantoadultoscomopediatría)– 4trastornosprincipales:vómitos,dolorabdominal,diarreafuncionalytrastornos

defecación

• CriteriosRomaIII(2006):Modelopsicosocial– Másinclusivos.Semantienelaclasificaciónporsíntomas.Eneladultolaclasificaciónse

basayaenelórganoafecto– 2categoríaspediátricassegúnedad:neonato/niñopequeñovs.Escolar/adolescente

• CriteriosRomaIV(2016):Modelobiopsicosocial– Trastornosdelainteraccióncerebro-intestino– Semantienelaclasificaciónporsíntomasyladivisiónendostramosdeedad


Table 1.Functional Gastrointestinal Disorders

A. Esophageal Disorders

A1. Functional chest pain A4. GlobusA2. Functional heartburn A5. Functional dysphagiaA3. Reflux hypersensitivity

B. Gastroduodenal Disorders

B1. Functional dyspepsia B3. Nausea and vomiting disordersB1a. Postprandial distress syndrome (PDS) B3a. Chronic nausea vomiting syndrome (CNVS)B1b. Epigastric pain syndrome (EPS) B3b. Cyclic vomiting syndrome (CVS)

B2. Belching disorders B3c. Cannabinoid hyperemesis syndrome (CHS)B2a. Excessive supragastric belching B4. Rumination syndromeB2b. Excessive gastric belching

C. Bowel Disorders

C1. Irritable bowel syndrome (IBS) C2. Functional constipationIBS with predominant constipation (IBS-C) C3. Functional diarrheaIBS with predominant diarrhea (IBS-D) C4. Functional abdominal bloating/distensionIBS with mixed bowel habits (IBS-M) C5. Unspecified functional bowel disorderIBS unclassified (IBS-U) C6. Opioid-induced constipation

D. Centrally Mediated Disorders of Gastrointestinal Pain

D1. Centrally mediated abdominal pain syndrome (CAPS)D2. Narcotic bowel syndrome (NBS)/

Opioid-induced GI hyperalgesia

E. Gallbladder and Sphincter of Oddi (SO) Disorders

E1. Biliary painE1a. Functional gallbladder disorderE1b. Functional biliary SO disorder

E2. Functional pancreatic SO disorder

F. Anorectal Disorders

F1. Fecal incontinence F2c. Proctalgia fugaxF2. Functional anorectal pain F3. Functional defecation disorders

F2a. Levator ani syndrome F3a. Inadequate defecatory propulsionF2b. Unspecified functional anorectal pain F3b. Dyssynergic defecation

G. Childhood Functional GI Disorders: Neonate/Toddler

G1. Infant regurgitation G5. Functional diarrheaG2. Rumination syndrome G6. Infant dyscheziaG3. Cyclic vomiting syndrome (CVS) G7. Functional constipationG4. Infant colic

H. Childhood Functional GI Disorders: Child/Adolescent

H1. Functional nausea and vomiting disorders H2a1. Postprandial distress syndromeH1a. Cyclic vomiting syndrome (CVS) H2a2. Epigastric pain syndromeH1b. Functional nausea and functional vomiting H2b. Irritable bowel syndrome (IBS)

H2c. Abdominal migraineH1b1. Functional nausea H2d. Functional abdominal pain ‒ NOSH1b2. Functional vomiting H3. Functional defecation disorders

H1c. Rumination syndrome H3a. Functional constipationH1d. Aerophagia H3b. Nonretentive fecal incontinence

H2. Functional abdominal pain disordersH2a. Functional dyspepsia

1258 Drossman and Hasler Gastroenterology Vol. 150, No. 6

33TGIFenadultos

17TGIFenniños

Algomás…

12pasosenabordajedelpacienteconTGIF1. Improve patient satisfaction andengage with the patient.

– Perception ofthe doctor’s humaneness– Technical competence– Relevant medicalinformation– Engagement relies on nonverbal communication

2. Obtain the history through anondirective,nonjudg-mental,patient-centered interview.– Activelistening,using questions based on the patient’s thoughts,

feeling andexperiences rather than apreset agendaofquestions.

3. Determinethe immediate reason for the patient’s visit (eg,What ledyou tosee meatthis time?)


12pasosenabordajedelpacienteconTGIF

4. Conduct acareful physical examination andcost-efficientinvestigation

5. Determinewhat the patient understands ofthe illness andhis or her concerns

6. Elicit the patient’s understanding ofthe symptoms (illnessschema)andprovide athorough explanation

7. Identify andrespond realistically tothe patient’sexpectations for improvement


12pasosenabordajedelpacienteconTGIF8. When possible,provide alinkbetween stressors and

symptoms that areconsistent with the patient’s beliefs

9. Setconsistent limits

10. Involve the patient inthe treatment

11. Make recommendations consistent with patient interests

12. Help establish an ongoing relationship with you or inassociation with aprimary care provider


CriteriosDiagnósticosRomaIV

Neonatosypre-escolares(G)

TGIF:neonatosypre-escolares(G)

G1.Regurgitacionesdellactante

G2.Sd.Rumiacióndellactante

G3.Sd.Vómitoscíclicos

G4.Cólicodellactante

G5. Diarreafuncional

G6.Disqueciadel lactante

G7. Estreñimientofuncional

Benninga MA, Nurko S et al.Gastroentrology 2016;150:1443-1455.

referred as gastroesophageal reflux.2 When the reflux ishigh enough to be visualized it is called regurgitation.Regurgitation of stomach contents into the esophagus,mouth, and/or nose is common in infants and is withinthe expected range of behaviors in healthy infants. In-fant regurgitation is the most common FGID in the firstyear of life.3 Recognition of infant regurgitation avoidsunnecessary doctor visits and unnecessary in-vestigations and therapy for gastroesophageal refluxdisease (GERD).2 Infant regurgitation is distinguishedfrom vomiting, which is defined by a central nervoussystem reflex involving both autonomic and skeletalmuscles in which gastric contents are forcefullyexpelled through the mouth because of coordinatedmovements of the small bowel, stomach, esophagus,and diaphragm. Regurgitation is also different fromrumination, in which previously swallowed food isreturned to the pharynx and mouth, chewed, andswallowed again. When the regurgitation of gastriccontents causes complications or contributes to tissuedamage or inflammation (eg, esophagitis, obstructiveapnea, reactive airway disease, pulmonary aspiration,feeding and swallowing difficulties, or failure to thrive),it is called GERD.2

G1. Diagnostic Criteria for Infant Regurgitation

Must include both of the following in otherwise healthyinfants 3 weeks to 12 months of age:

1. Regurgitation 2 or more times per day for 3 ormore weeks

2. No retching, hematemesis, aspiration, apnea,failure to thrive, feeding or swallowing difficulties,or abnormal posturing

Rationale for change in diagnostic criteria. Thereare minor changes from Rome III. Recently, a position paperby the North American Society of Pediatric GastroenterologyHepatology and Nutrition (NASPGHAN) and the EuropeanSociety of Pediatric Gastroenterology Hepatology andNutrition added “bothersome symptoms” as one criterion todifferentiate infant regurgitation from GERD.3 The challengewith that definition is that quantitative methods to define“troublesome” are missing. Infants cannot communicate ifthey are bothered. Variations in clinician and parent in-terpretations of troublesome have resulted in unnecessaryevaluation and treatment of many infants with regurgita-tion, not GERD. There is a lack of correlation betweencrying, irritability, and GER.4 GER is not a common cause ofunexplained crying, irritability, or distressed behavior inotherwise healthy infants.2 Therefore, we have elected toleave “troublesome” symptoms out of the criteria.

Clinical evaluation. Daily regurgitation is more com-mon in young infants than in older infants and children, andis found in higher rates in neonates.5 A recent study of 1447mothers throughout the United States showed a prevalenceof infant regurgitation of 26% using Rome III criteria.3

Regurgitation occurs more than once a day in 41%!67%of healthy 4-month-old infants.2,6

Table 1.G. Functional Gastrointestinal Disorders in Neonatesand Toddlers

G1. Infant regurgitationG2. Infant rumination syndromeG3. Cyclic vomiting syndromeG4. Infant colicG5. Functional diarrheaG6. Infant dyscheziaG7. Functional constipation

Figure 1. Age of presen-tation of FGIDs in pediatricpatients. The bars showeach diagnosis. Symp-toms might begin earlier,as there is a time require-ment to fulfill diagnosticcriteria. IBS, irritable bowelsyndrome; FD, functionaldyspepsia.

1444 Benninga and Nurko et al Gastroenterology Vol. 150, No. 6

NEONATE/TODDLER

EdadpresentaciónTDF


Fisiopatologíadolorfuncional

assessment in infants and toddlers is important for theclinician addressing functional pain in children. The modelthat most individuals use to understand pain is that of acutepain in which the pain functions as a signal of anatomic orbiochemical pathology. The underlying assumption is that ifthe pathology is addressed, the pain will dissipate. Thismodel is simplistic because it does not account for thevarious elements that contribute to the interpretation andresponse to nociceptive information. The acute pain modelis inappropriate in addressing functional pain, in which thepain does not serve a warning function, but is itself theillness (Figure 2).

Development of Nociceptive and Pain PathwaysData from neonatal animals and human infants suggest

that preterm infants have nociceptive systems in place atbirth.86 Cutaneous innervation is already present at 8 weeksof gestational age, afferent synapses to the spinal cord by 10weeks, and lamination in the spinal cord by 15 weeks. By 20weeks, there is reflex motor withdrawal to a noxious stim-ulus. Thalamo-cortical projections are present by 24 weeksand somatosensory evoked potentials after cutaneousstimulation are present by 29 weeks gestational age. Noci-ceptive circuitry is functional by 30 weeks gestation. Recentwork measuring cortical hemodynamic activity in thesomatosensory cortex suggests that by 24 weeks, the impactof a noxious stimulus is identifiable in the brain.87 Infantshave a lower pain threshold that increases with age and, as aresult, they may respond to routine handling, such as diaperchanges, similarly to invasive procedures. Additionally, theylack descending inhibitory control, a key element in modu-lating the pain experience, and therefore lack the ability toput the pain experience in perspective. It appears, therefore,that not only are preterm and term infants capable of

cortical level pain processing, but they may experiencepainful stimuli differently and more intensely then others.88

The fact that infants experience pain is evident in theirimmediate response to noxious stimuli. Preterm and terminfants display measurable physiologic responses, such asincreased heart rate, respiratory rate, blood pressure, anddecreased oxygen saturation. They produce cortisol andstress hormones in response to pain. They also displaydistinct behavioral responses to noxious stimuli, such asspecific facial expressions and patterns of movement.89

Another important consideration is the long-term impactof pain in the newborn and its relationship to the subse-quent development of altered pain perception, particularlyas it relates to functional abdominal pain. Infants and tod-dlers exposed to painful events, such as early surgery, maybe predisposed to visceral hyperalgesia.90,91 There are anumber of studies that have examined the impact of earlypainful procedures/neonatal intensive care unit admissionon the subsequent development of chronic abdominal pain.It appears that pyloric stenosis or allergic colitis may pre-dispose infants to development of chronic abdominal pain.92

In addition to physical trauma, Barreau et al,93

attempting to identify the impact of emotional trauma,demonstrated that neonatal maternal deprivation in rodentstriggered changes in the colonic epithelial barrier andmucosal immunity.

Pain Assessment in Infants and ToddlersIn adults and older children who are intellectually

intact, self-report of pain is the gold standard. Typically, anumeric rating scale in which pain can be quantified isused.94 This addresses pain intensity only, and not thequality of the pain, but is often the cornerstone of clinicalpain care. For children aged between 3 and 8 years,

Figure 2. Proposed path-ophysiology of functionalpain. From von Baeyer andChampion,95 adapted withpermission.

1452 Benninga and Nurko et al Gastroenterology Vol. 150, No. 6

NEONATE/TODDLER




• Nocomunicaciónverbal/inexactitudsíntomas

• Dependemosdelrelatoparental+impresiónclínica

• Abordarlossíntomasdelniño+preocupaciónfamiliar– Elplanterapéuticodebeatendertantoaniñocomofamilia

• Evitarpruebasytratamientosinnecesarios


• Tienequecumplirlos2siguientes,enunniñosanode3semanasa12mesesdeedad:

1. 2omásregurgitaciones/díadurante≥3semanas

2. Ausenciadenauseas,hematemesis,aspiración,apnea,fallodemedro,dificultadesparaalimentaciónodegluciónoposturasanormales


CasoclínicoLactantede3mesesderivadoaconsultaporbocanadasdesdeelnacimiento.Lospadresestánmuypreocupados“porqueechamucho”.Adecuadodesarrollopondo-estatural,noirritabilidad

1. SolicitamosTEGparadescartaranomalíaanatómica

2. Iniciamostratamientoconranitidina

3. Explicamosalafamilialabenignidaddelcuadroyausenciadesignosdealarma

4. PlanteamospautarfórmulaAR

5. 3y4soncorrectas


• 41-67%enlactantessanosde4meses

• Resoluciónespontánea90%enprimeros12meses

• Noprecisaexploracionescomplementarias (salvootrasospechaDx)– Datosdealarma:fallodemedro,hematemesis,sangreocultaenheces,anemia,rechazodetomasodificultadesdeglutorias,obligaadescartarERGE.

– Descartaranomalíaanatómicadigestivasuperiorsi:inicioenperiodoneonatalprecoz,vómitosbiliosos,deshidrataciónuotrascomplicacionessugestivas.



• EDUCACIÓNALOSPADRES,CONSEJOYORIENTACIÓN

• Espesarlafórmulaconcereales:reducenelnúmerodebocanadasperonomejoranelIR(GRA).

• Reducirelvolumendelastomas/incrementaraportecalóricodelafórmula

• EnsayoterapéuticoconHIDROLIZADOdurante2-4semanas(GRB).

• Elevacióncabeceradelacama,DECÚBITOLATERALIZQUIERDO. Norecomendadoelusodealmohadas.

Vandenplas Y et at. JPGN 2009;49:498-547.


• Debecumplirtodos lossiguientes:1. Inicioyfindesíntomasantesdelos5meses

2. Episodiosrecurrentesyprolongados dellanto,quejaoirritabilidad,referidosporloscuidadores,queocurrensincausaaparenteynopuedenserprevenidosniresueltosporlosmismos

3. Sinevidenciadefallodemedro,fiebreoenfermedad


CasoclínicoPadresdesesperadosqueacudenanuestraconsultaporquesuhijode2,5mesespresentacrisisdellantodesdehacemesymedio,casitodaslastardes,durante1-2horasyduermemal.Alimentación:f.Inicio.Exploraciónnormal.Orina:tirareactivanegativa.

1. Explicaríalaprobablebenignidaddelcuadroycarácterautolimitado

2. Realizarensayoterapéuticocondietaexentadelechedevaca2semanas

3. Sinoesefectivoplantearíarealizarensayoconprobiótico

4. 1y2soncorrectas

5. 1,2y3soncorrectas


• ≥90%“notcuringthecolic”

• EDUCACIÓNALOSPADRES,CONSEJOYORIENTACIÓN

• EncasossugerentesdeAPLV(historiafamiliar,eccema,diarrea,vómitos...)ocursoprolongadoointenso:ensayotemporal2semanascondietaexentaenPLV

• NOutilizarbloqueadoresdelasecreciónácida

• Ciertaevidenciadelautilidaddealgunosprobióticos,especialmenteLactobacillusreuteriDSM17938


Probióticosencólicodellactante

Copyright 2013 American Medical Association. All rights reserved.

an α-lactalbumin–enriched formula.29 None of the other 5 preven-tion trials found a significant difference between the probiotic andcontrol groups.

Of the 5 management trials for infant colic, 3 trials30-32 re-ported a significant reduction in median daily crying time in the pro-biotic compared with the placebo group30-32 and were sufficientlyhomogenous to meta-analyze (see later). The Dupont et al trial25

could not be included in the meta-analysis because of its dichoto-mized outcome; although it found no difference between groups inthe number of infants with a reduction of daily crying time of morethan 25% at 2 weeks, irritability and agitation without crying de-creased more in the probiotic than the control group. The Mentulaet al trial18 reported no difference in crying duration between the 2groups at 2 weeks; it could not be included in the meta-analysis be-

cause of the vastly different intervention (a combination of differ-ent probiotics), dosing of intervention, mode of intervention deliv-ery (capsules), unclear measure of crying outcomes used, and smallsample size (n = 9).18

The 3 trials included in the meta-analysis30-32 examined the ef-fectiveness of the probiotic L reuteri in the management of colic interm infants. All 209 infants were breastfed only, and in 2 trials, moth-ers were also on dairy-free diets.30,31 All used the same dose ofL reuteri at 109 colony-forming units per day, in the form of 5 dropsper day; the controls received a placebo in 2 trials and simethiconein the third. All 3 trials reported the median daily crying time at 21days of intervention as the primary outcome.

Figure 1 shows results of the meta-analysis. Supplementationwith L reuteri in breastfed term infants with colic reduced the daily

Figure 1. Meta-analyses of Treatment Trials Using a Random-Effects Model

–100 0 10050Median Difference IV, Random, 95% CI

–50

Favors probiotic Favors controlMedian

Difference SESource, Year Weight, %Median Difference

IV, Random, 95% CI

Savino et al,30 2007Savino et al,31 2010Szajewska et al,32 2013

–80–55–53

8.9323.98

9.69

43.714.941.4

–80.00–55.00–53.00

(–97.50 to –62.50)(–102.00 to –8.00)(–71.99 to –34.01)

Total (95% CI) 100.0 –65.10 (–85.82 to –44.38)Heterogeneity: τ2 = 176.00; χ2

2 = 4.46 (P = .11); l2 = 55%Test for overall effect: z = 6.16 (P < .001)

Probiotic

Mean SD Total

Control

Mean SD TotalSource, Year Weight, %Mean Difference

IV, Random, 95% CI


81.7111.2

75.6

38.08335.01

9.91

412540

171.6167

128.4

84.24261.18

10.64

422140

39.93.3

56.8

–89.90–55.80–52.80

(–117.92 to –61.88)(–228.21 to 116.61)(–57.31 to –48.29)

Total (95% CI) 106 103 100.0 –67.72 (–99.79 to –35.64)Heterogeneity: τ2 = 466.33; χ2


A

B

–100 0 10050Mean Difference IV, Random, 95% CI

–50

Favors experimental Favors control

A, Meta-analysis of treatment trials using median difference as the primary outcome, with a random-effects model. B, Meta-analysis of treatment trials using meandifference as the primary outcome, with a random-effects model. IV indicates inverse variance.

Figure 2. Meta-analyses of Treatment Trials Using a Fixed-Effects Model

–100 0 10050Median Difference IV, Fixed, 95% CI

–50

Favors probiotic Favors controlMedian

Difference SESource, Year Weight, %Median DifferenceIV, Fixed, 95% CI


–80–55–53

8.9323.98

9.69

50.37.0

42.7

–80.00–55.00–53.00

(–97.50 to –62.50)(–102.00 to –8.00)(–71.99 to –34.01)

Total (95% CI) 100.0 –66.72 (–79.13 to –54.31)Heterogeneity: χ2


Probiotic

Mean SD Total

Control

Mean SD TotalSource, Year Weight, %Mean DifferenceIV, Fixed, 95% CI


81.7111.2

75.6

38.08335.01

9.91

412540

171.6167128.4

84.24261.18

10.64

422140

2.50.1

97.4

–89.90–55.80–52.80

(–117.92 to –61.88)(–228.21 to 116.61)(–57.31 to –48.29)

Total (95% CI) 106 103 100.0 –53.74 (–58.18 to –49.29)Heterogeneity: χ2


A

B

–100 0 10050Mean Difference IV, Fixed, 95% CI

–50

Favors experimental Favors control

A, Meta-analysis of treatment trials using median difference as the primary outcome, with a fixed-effects model. B, Meta-analysis of treatment trials using meandifference as the primary outcome, with a fixed-effects model. IV indicates inverse variance.

Probiotics and Excessive Infant Crying Review Clinical Review & Education

jamapediatrics.com JAMA Pediatrics December 2013 Volume 167, Number 12 1155


Downloaded From: http://jamanetwork.com/pdfaccess.ashx?url=/data/journals/peds/929424/ by a Biblioteca Virtual del SSPA User on 04/19/2017


Probiotics to Prevent or Treat Excessive Infant CryingSystematic Review and Meta-analysisValerie Sung, MPH; Sarsha Collett, MPH; Tanyth de Gooyer, PhD; Harriet Hiscock, MD; Mimi Tang, PhD;Melissa Wake, MD

IMPORTANCE Excessive infant crying is common, distressing, but without proven effectiveprevention or management options. Probiotics may be a promising solution.

OBJECTIVE To examine whether probiotics are effective in the prevention/management ofcrying (“colic”) in infants 3 months or younger.

DATA SOURCES A systematic search of MEDLINE, EMBASE, and the Cochrane Library,supplemented by the metaRegister of Controlled Trials.

STUDY SELECTION Studies that randomized infants 3 months or younger to oral probiotics vsplacebo or no or standard treatment with the outcome of infant crying, measured as theduration or number of episodes of infant crying/distress or diagnosis of “infant colic.” Twelveof the 1180 initially identified studies were selected.

DATA EXTRACTION AND SYNTHESIS This review/meta-analysis was conducted according toguidelines from the Cochrane Handbook for Systematic Reviews of Interventions, withreporting following the Preferred Reporting Items for Systematic Reviews and Meta-analysesguidelines. Data were independently extracted by 3 of us.

MAIN OUTCOME(S) AND MEASURE(S) Infant crying, measured as the duration or number ofepisodes of infant crying/distress, or diagnosis of “infant colic.”

RESULTS Of the 12 trials (1825 infants) reviewed, 6 suggested probiotics reduced crying, and6 did not. Three of the 5 management trials concluded probiotics effectively treat colic inbreastfed babies; 1 suggested possible effectiveness in formula-fed babies with colic, and 1suggested ineffectiveness in breastfed babies with colic. Meta-analysis of 3 small trials ofbreastfed infants with colic found that Lactobacillus reuteri markedly reduced crying time at21 days (median difference, −65 minutes/d; 95% CI, −86 to −44). However, all trials hadpotential biases. Meanwhile, of 7 prevention trials, 2 suggested possible benefits.Considerable variability in the study populations, study type, delivery mode/dose of probioticsupplementation, and outcomes precluded meta-analysis.

CONCLUSIONS AND RELEVANCE Although L reuteri may be effective as treatment for crying inexclusively breastfed infants with colic, there is still insufficient evidence to support probioticuse to manage colic, especially in formula-fed infants, or to prevent infant crying. Resultsfrom larger rigorously designed studies applicable to all crying infants will help draw moredefinitive conclusions.

JAMA Pediatr. 2013;167(12):1150-1157. doi:10.1001/jamapediatrics.2013.2572Published online October 7, 2013.

Supplemental content atjamapediatrics.com

Author Affiliations: Department ofPaediatrics, The University ofMelbourne, Parkville, Australia (Sung,Hiscock, Tang, Wake); MurdochChildrens Research Institute,Parkville, Australia (Sung, Hiscock,Tang, Wake); Centre for CommunityChild Health, Royal Children’sHospital, Parkville, Australia (Sung,Hiscock, Wake); Department ofEpidemiology and PreventiveMedicine, Monash University,Melbourne, Australia (Collett,de Gooyer); Department of Allergyand Immunology, Royal Children’sHospital, Parkville, Australia (Tang).

Corresponding Author: ValerieSung, MPH, Centre for CommunityChild Health, Royal Children’sHospital, Flemington Road, Parkville,Victoria 3052, Australia([email protected]).

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G5.Diarreafuncional

• Debecumplirtodos lossiguientes:1. 4omásdeposicionesnoformadasdiarias

indoloras

2. Duraciónmayorde4semanas

3. Inicioentre6y60mesesdeedad

4. Ausenciadefallodemedrosilaingestacalóricaesadecuada


G5.Diarreafuncional• Noafectaciónactividadniestadogeneral

• Buenestadonutricionalyvelocidadcrecimiento

• Deposicionestípicas:contienenmocoy/orestosdealimentossindigerir,amenudosonmenossólidasalolargodeldía

• Factoresnutricionalesacorregir:sobrealimentación,excesivoconsumodeazúcaressimples(fructosa,sorbitol),comozumos,bajaingestadegrasa...

• Factorescausantesoexacerbantes posibles:infeccionesentéricas,laxantes,antibióticos


G6.Disqueciadellactante

• Enlactante<9mesesdeedaddebecumplir:

1. Almenos10minutosdeesfuerzoyllantoantes

deladefecación,exitosaono,dehecesblandas

2. Sinotrosproblemasdesalud


Niñosyadolescentes(H)

TGIF:niñosyadolescentes(H)

• Lafrase“noexisteevidenciadeenfermedadorgánica”deloscriteriosRomaIII,hasidosustituidapor“despuésdelaapropiadaevaluaciónmédicalossíntomasnopuedenseratribuidosaotracondiciónmedica”.

• QuedaacriteriomédicolanecesidaddepruebascomplementariasparaapoyareldiagnósticodeTGIF.

TGIF:niñosyadolescentes(H)H1.Nauseasyvómitosfuncionales

H1a.Sd. VómitoscíclicosH1b.Nauseas funcionalesyvómitosfuncionalesH1c.Sd.RumiaciónH1d. Aerofagia

H2.Ttnos.dolorabdominal funcionalH2a. DispepsiafuncionalH2b. Sd.IntestinoirritableH2c.Migraña abdominalH2d. Dolorabdominalfuncional- NOS

H3.Desórdenes funcionalesdeladefecaciónH3a. EstreñimientofuncionalH3b.Incontinenciafuncionalnoretentiva

Hyams JS,DiLorenzoCetal.Gastroenterology 2016;150:1456-1468.

H1.NauseasyvómitosfuncionalesH1.Nauseasyvómitosfuncionales

H1a.Sd. VómitoscíclicosH1b.Nauseas funcionalesyvómitosfuncionalesH1c.Sd.RumiaciónH1d. Aerofagia

H2.Ttnos. dedolorabdominal funcionalH2a. DispepsiafuncionalH2b. Sd.IntestinoirritableH2c.Migraña abdominalH2d. Dolorabdominalfuncional- NOS


H1a.Sd.Vómitoscíclicos• Debecumplirtodoslossiguientes:

1. 2omásepisodiosdenauseasintensaseincoerciblesyvómitosparoxísticos,quedurandehorasadías,dentrodeunperiodode6meses

2. Losepisodiossonestereotipadosencadapaciente

3. Losepisodiosestánseparadosporsemanasomesesconretornoalasituaciónbasal

4. Trasevaluaciónmédicaapropiada,nopuedenatribuirseaotracondición


H1a.Sd.Vómitoscíclicos• Edadescolar(3,5- 7años)• Asocianmáspatologíafuncional: SII(67%),migrañas(21%)

• Niñosconepisodiosdevómitoscíclicos

– 90%delosquecumplencriteriosclínicos=patologíafuncional

– 10%otrascausasSUBYACENTES

LiBUetal.JPediatr Gastroenterol Nutr 2008;47:379–393.

-Vómitos biliosos

-Dolor abdominal severo o decaimiento

-Hematemesis

DESENCADENANTES

-Ayuno

-Enfermedad intercurrente

-Comida con alto contenido proteico

Exploración neurológica anormal

Sin hallazgos sugestivos de otra patología

DURANTE ATAQUE

- ALT/GGT

- Amilasa, Lipasa

EN CUALQUIER MOMENTO

- ECO ABD-PELVICA

- Amilasa, Lipasa

- EDA

DURANTE ATAQUE, ANTES DE TTO IV:

-Glucosa, electrolitos, Ph

-Amonio, Láctico

-C. Cetonicos en orina

-Aa en plasma y orina

VALORAR: Carnitina

TAC/RMN CRANEAL

PROBABLE CVS

PRUEBASCOMPLENTARIAS

NORMALES

-Electrolitos (Na+, K+, Cl+, HCO3-), glucemia, Urea y Creatinina.

-RX ABDOMINAL

CRITERIOS DIAGNOSTICOS SVC

PROFILAXISenMENORESde5AÑOS

ANTIHISTAMINICOS:• CIPROHEPTADINA (de elección):

– 0,25-0,5 mg/kg/día en 2 ó 3 dosis– EFECTOS 2os: aumento apetito, ganancia peso, sueño

β-BLOQUEANTES:

• PROPANOLOL (2ª elección):– 0,25 – 1 mg/kg/día, en 2 ó 3 dosis– MONITORIZACIÓN: FC > 60 lpm– EFECTOS 2os: letragia, reducen tolerancia al ejercicio– CONTRAINDICACIONES: asma, diabetes, enfermedad cardiaca,

depresión– RETIRADA: en 1 ó 2 semanas


ANTIDEPRESIVOS TRICICLICOS:• AMITRIPTILINA (de elección):

– Inicio 0,25-0,5 mg/kg, incrementando semanalmente 5-10 mg, hasta 1-1,5 mg/kg.

– MONITORIZACIÓN: ECG y QTc antes de comenzar y 1 sm. después– EFECTOS 2os: estreñimiento, sedación, arritmia, cambios de

comportamiento (sobre todo en niños pequeños)

β-BLOQUEANTES:• PROPANOLOL (2ª elección): ver arriba.

ALTERNATIVAS:• FENOBARBITAL 2 mg/kg• L-CARNITINA 50-100 mg/kg/día, en 2 ó 3 dosis (max 3g/día)

PROFILAXISenMAYORESde5AÑOS


H1b.Nauseasyvómitosfuncionales• Todosloscriterios≥2meses:• H1b1.NÁUSEASFUNCIONALES

1. Nauseainsidiosacomosíntomapredominante,porlomenos2vecesalasemana,ygeneralmentenorelacionadasconlascomidas

2. Sinasociaciónconsistenteconvómitos



H1b.Nauseasyvómitosfuncionales• Todosloscriterios≥2meses:• H1b2.VÓMITOSFUNCIONALES

1. Enpromedio,unoomásepisodiossemanalesdevómitos

2. Ausenciadevómitosauto-inducidosocriteriosparaunTCAorumiación



H1.NauseasyvómitosfuncionalesH1a.Sd. VómitoscíclicosH1b.Nauseas funcionalesyvómitosfuncionalesH1c.Sd.RumiaciónH1d. Aerofagia

H2.Ttnos.dedolorabdominal funcionalH2a. DispepsiafuncionalH2b. Sd.IntestinoirritableH2c.Migraña abdominalH2d. Dolorabdominalfuncional- NOS


H2.Trastornosdedolorabdominalfuncional

• Puedehabersolapamiento enelmismopaciente

• Relevanciadelosdatosdealarmapotencial

• Objetivoprincipalterapéutico:recuperacióndelaactividadhabitualnormaldelniño,másqueladesaparicióndeldolor

• Laaceptacióndelpapelpredominantedeloscomponentesbiopsicosocialesdeldolorporlafamilia,ydelniñosegúnsuedad,seasociafuertementeconunpronósticofavorable

H2.Trastornosdedolorabdominalfuncional


CasoclínicoPacientede8añosqueconsultapordolorabdominalperiumbilical,enrelaciónconlascomidas.Buendesarrollopondero-estatural.Estudioetiológico,incluyendoEDA,negativo.Eldiagnósticomásprobablesería:

1. Dolorabdominalrecurrente

2. Dolorabdominalfuncional

3. Síndromedeintestinoirritable

4. Dispepsiafuncional

5. Migrañaabdominal

H2a.Dispepsiafuncional

1. Debecumplirunoomásdelossiguientes,almenos4días/mes,durantealmenos2meses:– Plenitudpost-prandial– Saciedadprecoz– Dolorepigástricooacideznoasociadoscondefecación



H2a.Dispepsiafuncional:2subtipos

• Síndromedistréspost-pandrial:– Incluyeplenitudpost-pandrialysaciedadprecozmolestosqueimpidenterminarunacomidahabitual

– Apoyaneldiagnostico:hinchazónabdomensuperior,náuseapost-pandrialoeructosexcesivos

• Síndromededolorepigástrico:– Doloroacidezepigástricosqueinterfierenenlaactividadnormalyquenosealiviaconladefecaciónolaexpulsióndegases

– Apoyaneldiagnóstico:dolorquemanteperosincomponenteretroesternalydolorqueseinduceosealiviaconlaingestióndecomida,peroquetambiénpuedeocurrirenayunas

H2a.Dispepsiafuncional

• Hipótesis:anomalíasacomodacióngástrica,hipersensibilidadintestinal,inflamaciónbajo-grado,predisposicióngenética

• En24%niñosFDcomosecuelaGEbacteriana• ¿Papelendoscopiadigestivaalta?• Evitar:cafeína,especias,alimentosmuygrasos,tabaco,alcoholyfármacosgastrolesivos

• Pruebaterapéutica:– Antiácidos4semanas(IBP)– Procinéticossipredominanáusea,hinchazón,saciedadprecoz


Dispepsiafuncional:ciproheptadina

Figure 1.Response to cyproheptadine according to presenting symptom.

Rodriguez et al. Page 11

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NIH

-PA

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uthor Manuscript

NIH

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Author M

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Rodriguez L..JPediatr.2013;163:261–267.

• Estudioretrospectivo80niñostratadosconciproheptadina (0,04– 0,62mg/kg/día)

H2b.Sd.IntestinoIrritable• Debecumplirtodos lossiguientes:

1. Dolorabdominalalmenos4díaspormesasociadoconunoomásdelossiguientes,almenos≥2meses:• Relacionadoconladefecación• Cambiosenlafrecuenciadedefecación• Cambiosenlaformaoaparienciadelasdeposiciones

2. Enniñosconestreñimiento,eldolornoseresuelveconlaresolucióndelmismo



disease or H pylori infection, children older than 10 years ofage, when symptoms persist for >6 months, and if symp-toms are severe enough to affect activities of daily living,including sleep.31 The Rome IV pediatric committee doesnot believe there is compelling evidence to require an EGDin order to make a diagnosis of FD, but recognizes that localpractice patterns and social considerations may influencethe decision. See Table 2 for alarm features suggestingfurther diagnostic testing.

Treatment. There are no adequately sized, double-blind, placebo-controlled pediatric studies of FD treatment.Foods aggravating symptoms (eg, caffeine containing, spicy,fatty) and nonsteroidal anti-inflammatory agents should beavoided. Psychological factors that can contribute to theseverity of the problem should be addressed. Acid blockadewith histamine receptor antagonists and proton pump in-hibitors can be offered for pain predominant symptoms.32 Ifcure of FD is defined as complete symptomatic relief after 4weeks of treatment, omeprazole is superior to ranitidine,famotidine, and cimetidine.33 Although convincing data arelacking, low-dose tricyclic antidepressant therapy withagents such as amitriptyline and imipramine is oftenconsidered in difficult cases. Nausea, bloating, and earlysatiety are more difficult to treat, and prokinetics such ascisapride and domperidone can be offered where available.A retrospective, open-label study suggested that cyprohep-tadine is safe and effective for treating dyspeptic symptomsin children.11 Gastric electrical stimulation seems to be apromising option for pediatric patients with FD refractory tomedical treatment.34

H2b. Irritable Bowel SyndromeEpidemiology. School-based studies in Colombia and

Sri Lanka found a prevalence of IBS of 4.9% and 5.4%,respectively.4,35 IBS prevalence in children across theUnited States based on parental report ranges from 1.2% to2.9%.13,36

H2b. Diagnostic Criteriaa for Irritable Bowel Syndrome

Must include all of the following:

1. Abdominal pain at least 4 days per month asso-ciated with one or more of the following:

a. Related to defecation

b. A change in frequency of stool

c. A change in form (appearance) of stool

2. In children with constipation, the pain does notresolve with resolution of the constipation (chil-dren in whom the pain resolves have functionalconstipation, not irritable bowel syndrome)

3. After appropriate evaluation, the symptomscannot be fully explained by another medicalcondition

aCriteria fulfilled for at least 2 months before diagnosis.

Pediatric IBS can be divided into subtypes analogous toadults reflecting the predominant stool pattern (IBS withconstipation, IBS with diarrhea, IBS with constipation anddiarrhea, and unspecified IBS).37

Rationale for changes in diagnostic criteria. Theterm discomfort was removed from Rome III criteria, as it isnot clear whether the distinction between pain anddiscomfort is quantitative or qualitative. The difference be-tween functional constipation and IBS with constipation hasbeen clarified. As many as 75% of children with constipationreport pain,38 and studies have shown IBS patients oftenreceive a diagnosis of functional constipation.39 The com-mittee recommends that patients with constipation andabdominal pain initially be treated for constipation only. Ifabdominal pain resolves with constipation treatment, the

Figure 1. Pathophysiologyof functional abdominalpain disorders. Visceralhyperalgesia leading todisability is shown as thefinal outcome of sensi-tizing medical factors thatare superimposed on abackground of geneticpredisposition and earlylife events.

May 2016 FGIDs in Children and Adolescents 1461

CHILD/AD

OLES

CENT

H2b.Sd.IntestinoIrritable• Signosdealarma!!!

• Calprotectinafecal:utilidadcomomarcadordescreeninginflamaciónintestinal

• Tratamiento:aunquedeevidenciaescasa,con:– Probióticos(LGG*)

– Aceitedementa(antiespasmódiconatural)

– Dietasbajasenmonosacáridos,disacáridos,oligosacáridosypoliolesfermentables(FODMAPs)

– Terapiasconductuales


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Gut Microbes 5:2, 165–175; March/April 2014; © 2014 Landes BioscienceRESEARCH PAPER

Introduction

Childhood irritable bowel syndrome (IBS) is a common functional gastrointestinal (GI) disorder, affecting up to 19% of school-aged children.1 As in adults, childhood IBS is believed to be multifactorial, with different factors (e.g., diet, visceral hyperalgesia, and gut microbiome composition) potentially playing more of a role in one individual with IBS as compared with another.2 We recently reported that as a group, children with IBS have a different gut microbiome composition as compared with healthy controls.3 Whether these differences impact the success of treatments or interventions is unknown.

In adults with IBS, multisubstrate carbohydrate elimination diets, which are believed to decrease gut microbial fermentation, have demonstrated efficacy in reducing GI symptoms.4-6 These include limiting overall carbohydrate intake and/or limiting intake of specific carbohydrates believed to be poorly digested, fermentable, and osmotic (low fermentable substrate diet, LFSD).4-6 Proposed mechanisms for efficacy have included decreased microbial hydrogen production7 and decreased stool

output, resulting in improved stool form primarily in adults with IBS-diarrhea predominant.8 However, not all those given an LFSD benefit. To date, identifying the subpopulation in which these dietary interventions will be most successful has not been accomplished.9

To our knowledge, a comprehensive LFSD has not been formally investigated in children with IBS. We hypothesized that, similar to adults with IBS, an LFSD would be effective in children. Therefore, we undertook a pilot study to evaluate the potential efficacy of such a diet in reducing abdominal pain frequency in children with IBS. In addition, we sought to examine microbial factors that might be related to whether the diet improves IBS symptoms and thereby gain insight into potential baseline factors that may help predict a successful response to an LFSD.

Results

Twelve children with pediatric Rome III-defined IBS were enrolled in a pilot study, of whom eight completed the study

*Correspondence to: Bruno P Chumpitazi; Email: [email protected]: 12/05/2013; Revised: 12/21/2013; Accepted: 01/20/2014; Published Online: 01/27/2014http://dx.doi.org/10.4161/gmic.27923

Gut microbiota influences low fermentable substrate diet efficacy in children

with irritable bowel syndromeBruno P Chumpitazi1,2,*, Emily B Hollister3,4, Numan Oezguen3,4, Cynthia M Tsai1,2, Ann R McMeans5, Ruth A Luna3,4,

Tor C Savidge3,4, James Versalovic1,3,4, and Robert J Shulman1,2,5

1Department of Pediatrics; Baylor College of Medicine; Houston, TX USA; 2Section of Pediatric Gastroenterology, Hepatology, and Nutrition; Texas Children’s Hospital; Houston, TX USA; 3Department of Pathology and Immunology; Baylor College of Medicine; Houston, TX USA; 4Texas Children’s Microbiome Center;

Department of Pathology; Texas Children’s Hospital; Houston, TX USA; 5Children’s Nutrition Research Center; Houston, TX USA

Keywords: pediatric, abdominal pain, irritable bowel syndrome, FODMAPs, microbiome, metabolites

We sought to determine whether a low fermentable substrate diet (LFSD) decreases abdominal pain frequency in children with irritable bowel syndrome (IBS) and to identify potential microbial factors related to diet efficacy. Pain symptoms, stooling characteristics, breath hydrogen and methane, whole intestinal transit time, stool microbiome, and metabolite composition were collected and/or documented in eight children with IBS at baseline and during one week of an LFSD intervention. Pain frequency (P < 0.05), pain severity (P < 0.05), and pain-related interference with activities (P < 0.05) decreased in the subjects while on the LFSD. Responders vs. non-responders: four children (50%) were identified as responders (>50% decrease in abdominal pain frequency while on the LFSD). There were no differences between responders and non-responders with respect to hydrogen production, methane production, stooling characteristics, or gut transit time. Responders were characterized by increased pre-LFSD abundance of bacterial taxa belonging to the genera Sporobacter (P < 0.05) and Subdoligranulum (P < 0.02) and decreased abundance of taxa belonging to Bacteroides (P < 0.05) relative to non-responders. In parallel, stool metabolites differed between responders and non-responders and were associated with differences in microbiome composition. These pilot study results suggest that an LFSD may be effective in decreasing GI symptoms in children with IBS. Microbial factors such as gut microbiome composition and stool metabolites while on the diet may relate to LFSD efficacy.

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the average number of OTUs (Table S2). Neither OTU richness nor related α-diversity metrics (e.g., Shannon H’ and Simpson 1/D) differed from baseline to LFSD periods (Table S2).

Baseline stool communities were composed, in large part, of taxa belonging to the Bacteroidaceae, Ruminococcaceae, Lachnospiraceae, and related orders. Within the entire cohort, the distribution of these taxa did not change significantly after exposure to the LFSD; however, overall trends toward increased abundances of members of the Clostridiales and decreased abundance of Bacteroidetes were observed following the LFSD intervention (Fig. 2).

In contrast to the comparison of baseline vs. LFSD periods for the entire cohort, there was significantly greater OTU richness and diversity at baseline within the stool communities of responders compared with non-responders (Table S3). Among responders, LEfSe analysis identified significantly increased abundances of OTUs belonging to the family Ruminococcaceae (Fig. 3A). Specifically, these included members of the genera Sporobacter and Subdoligranulum. Non-responders were characterized by significantly increased abundance of two OTUs belonging to the class Bacteroidales and an OTU representing members of the family Ruminococcaceae (Fig. 3A). Furthermore, the baseline microbiomes of responders and non-responders were fairly well separated by OTU composition as seen on principal components analysis (Fig. 3B). This was even more striking when using only those children with IBS-C (Fig. 3C). Responder microbial communities were enriched in OTUs resembling Phascolarctobacterium faecium when we limited our analysis to IBS-C subjects only.

Differences between responders and non-responders in community composition were also detected following the LFSD

intervention (Fig. 4). The responder community was found to be enriched in OTUs resembling Subdoligranulum, members of the Prevotellaceae, and unclassified Coriobacteriaceae. Notably, it was also depleted in Dialister, a genus belonging to the family Veillonellaceae. In contrast, the non-responder community was enriched with an Acetivibrio cellulolyticus-like OTU (OTU 914, unclassified Ruminococcaceae) and multiple Bacteroides- and Dialister-like OTUs. On average, Bacteroides accounted for 21% of the non-responder communities, whereas Bacteroides only accounted for 10% of the sequences recovered from the responder communities. Likewise, at the genus-level, Dialister accounted for nearly 5% of non-responder communities, but only 0.15% of the sequences recovered from responders.

To identify microbial-metabolite changes associated with responders to the LFSD, a tripartite network analysis was performed to identify fecal metabolites that correlated with microbiome differences between responders and non-responders

Table 1. Pain characteristics and stooling frequency during baseline and low fermentable substrate diet (LFSD) periods

Symptom Baseline LFSD P value

Pain episodes/week 11.5 ± 6.3* 6.3 ± 6.8 0.02

Mean pain throughout the week 1.8 ± 1.1 0.8 ± 0.7 0.02

Maximum pain severity of worst episode 5.8 ± 2.5 3.9 ± 2.9 0.04

Number of pain episodes interfering with activity 9.9 ± 7.9 6.3 ± 7.2 0.05

Number of bowel movements 5.8 ± 2.6 3.5 ± 2.4 0.11

*Mean ± SD

Figure 2. The gut microbiome (family-level) at baseline and during the low fermentable substrate diet by relative abundance. LFSD, low fermentable substrate diet.

GRUPOSDEALIMENTOS

ALIMENTOSCONELEVADOCONTENIDOENFODMAPs ALIMENTOSCONBAJOCONTENIDOENFODMAPs

Lácteos • Lechedevaca,cabra,oveja• Yogures• Helados• Quesofresco,quesostiernos

• Lechedevacasinlactosa• Lechedearroz• Yoguressinlactosa• Sorbetes,heladosdehielo• Quesocurado

Frutas • Manzana,pera• Melocotón,nectarina,albaricoque• Cerezas,sandía,granada• Paraguayo,mango,caqui• Chirimoya,ciruelas• Pasas,frutossecos,higos,dátiles• Frutasenalmíbaroenlatadasensujugo• Zumosdefrutas

• Plátano,naranja,mandarina,limón,lima,pomelo• Uva,kiwi,melón• Fresas,frambuesas,moras• Arándano

Verdurasyhortalizas

• Brócoli,coliflor,colesdebruselas• Puerro,ajo,cebolla,guisantes• Alcachofa,espárragos,remolacha,col,hinojo• Aguacate,ajo,batata• Champiñones,setas

• Maíz,lechuga,tomate,pepino,zanahoria• Acelgas,espinacas,judíasverdes,apio• Calabacín,calabaza,berenjena,pimiento,rábano• Patata

Cereales • Alimentoselaboradosabasedetrigoycenteno(sisecomenengrandescantidades,comopan,pasta,galletas,cuscús,crackers,…)

• Alimentosfabricadosabasedemaíz,arroz• Pandeespelta• Avena,mijo,quinoa

Legumbres • Lentejas,garbanzos,judíasblancas,alubias

Edulcorantes • Edulcorantesqueterminenen–ol(isomaltitol,sorbitol,xilitol,manitol,E968,E953,E966,E965,E421,E420,E967)

• Miel

• Glucosa• Edulcorantesartificialesnoacabadosen–ol(E950,

E951,E952,E960,E959,E961,E954,E962,E955,E957)

Proteínas • Carne,pescado,huevos.

¿Tienealgúnpapelladietasingluten?

Juliette MTMet.Pediatrics 2015;Aziz Ietal.Clin Gastroenterology andHepatology 2016,doi:10.1016/j.cgh.2015.12.031.

relative risk (RRs) along with 95%confidence intervals (CIs). Forcontinuous outcomes, the meandifferences (MDs) with 95% CIs werereported. Heterogeneity wasquantified by using x2 tests and theI2 statistic, which can be interpretedas the percentage of the totalvariation between studies that isattributable to heterogeneity ratherthan chance. A value of 0% indicatesno observed heterogeneity, whereaslarger values show increasingheterogeneity. If heterogeneity wasnot revealed, results of the fixed effectmodel are presented. If there wassubstantial heterogeneity (.50%),the random effect model was used.

RESULTS

A total of 568 potentially relevantarticles and abstracts were identified(Fig 1). After removal of duplicates(n = 316) and screening of abstracts(n = 210), 42 full-text articles wereassessed for eligibility. Twenty-ninearticles were excluded because of thefollowing: adult study population (n = 6),irrelevant outcome measures, such asimprovement in rectal sensitivity orgastrointestinal symptoms without

abdominal pain (n = 2), no systematicreview or RCT (n = 15), or inclusiononly of trials that were alreadyincluded by another systematicreview (n = 6). Thirteen articlesremained for analysis: 7 systematicreviews11,12,15,16,18,22,23 (including18 RCTs) and 6 RCTs.24–29 Twoincluded trials concerned follow-upstudies,26,30 which will be discussedby using their original studies.31,32

Two systematic reviews11,12 includedstudies with ,10 patients pertreatment arm, and these studieswere therefore excluded.33–35

Data of 1390 children aged 3 to18 years were included for analysis.Sample sizes ranged from 21 to 200,and follow-up varied from 2 weeks to5 years. Four trials investigated fibersupplements compared withplacebo,24,36–38 and 2 trials studieda lactose-free diet.39,40 Four trialsinvestigated probiotics,27,41–43 and3 trials compared HT versus standardcare or a wait-list.25,32,44 Seven studiescompared CBT with standard care,physiotherapy, fiber supplements,biofeedback, and/or parentalsupport.28,31,45–49 One trial comparedyoga with a wait-list,50 and 1 trialevaluated written self-disclosure(WSD) in addition to standard care.29

No studies were included on lifestyleadvice or prebiotics. A range ofdifferent outcomes were measured, andeven if the same outcome wasmeasured, different measurementinstruments were used. All trialsmeasured abdominal pain as theprimary or secondary outcome.

Nine studies reporteddisability or schoolabsenteeism.25,31,32,38,42,44,47,49,50

Four studies assessed quality oflife,25,28,29,44 and 8 studies assessedadverse effects.24,25,37,38,41–44 Dataof 3 studies were pooled to performa meta-analysis of the efficacy of fibersupplements,36–38 and 3 studieswere used to perform a meta-analysison probiotics.41–43 Table 1 presentsthe characteristics of the includedstudies.

Methodologic Quality

The overall quality of evidence wasvery low to moderate. TheSupplemental Appendix displays theGRADE evidence profiles.

Concealment of allocation wasunclear in 6 studies.36,44–46,48,49 Dueto the nature of HT, CBT, WSD, andyoga, blinding was not possiblefor the caregiver orpatient.25,28,29,31,32,44–50 Dropout wasconsiderable in 4 studies36,40,41,47

or vaguely described in 3others.31,46,50 Two studies excludedpatients due to poor compliance.40,41

The method of randomization wasunclear in 3 studies.27,31,50 Alfvén andLindstrom48 provided no informationon outcome blinding or treatmentduration. Six trials did not presentresults with absolute numbers andwere therefore not included in themeta-analysis.27,39,40,44,47,48 Analysesfor follow-up were uncontrolledfor baseline differences by Levy et al.31

Because participants were recruitedthrough physician referral and flyers,these patients were therefore seriouslymotivated, which can cause bias.

Dietary Interventions

No studies were included evaluatinggluten-, histamine-, and carbonicacid–free diets or fluid intake.

Fiber Supplements

Two systematic reviews15,16

including 3 RCTs36–38 and 1 RCT24

evaluated the efficacy of fibersupplements compared with placebofor RAP. A systematic review byHuertas-Ceballos et al15 included2 RCTs, involving 92 children aged3 to 15 years.36,37 Children receivedfiber supplements for 6 weeks. Noinformation was available regardingdaily fiber intake before and/orduring intervention weeks.Information about abdominal painwas collected through the use ofdiaries, but the authors did not clarifyhow these diaries were analyzed. Thesystematic review by Horvath et al16

included a third trial with 90 children

FIGURE 1Flow chart showing results of the litera-ture search and study inclusion.

524 RUTTEN et alby guest on April 21, 2017Downloaded from

Nonpharmacologic Treatment ofFunctional Abdominal Pain Disorders:A Systematic ReviewJuliette M.T.M. Rutten, MDa*, Judith J. Korterink, MDa*, Leonie M.A.J. Venmans, PhDb, Marc A. Benninga, MD, PhDa,Merit M. Tabbers, MD, PhDa

abstract BACKGROUND AND OBJECTIVE: Various nonpharmacologic treatments are available for pediatricabdominal pain–related functional gastrointestinal disorders (AP-FGIDs). Data on efficacy andsafety are scarce. The goal of this study was to summarize the evidence regardingnonpharmacologic interventions for pediatric AP-FGIDs: lifestyle interventions, dietaryinterventions, behavioral interventions, prebiotics and probiotics, and alternative medicine.

METHODS: Searches were conducted of the Medline and Cochrane Library databases. Systematicreviews and randomized controlled trials (RCTs) concerning nonpharmacologic therapies inchildren (aged 3–18 years) with AP-FGIDs were included, and data were extracted on participants,interventions, and outcomes. The quality of evidence was assessed by using the GRADE approach.

RESULTS: Twenty-four RCTs were found that included 1390 children. Significant improvement ofabdominal pain was reported after hypnotherapy compared with standard care/wait-listapproaches and after cognitive behavioral therapy compared with a variety of controltreatments/wait-list approaches. Written self-disclosure improved pain frequency at the6-month follow-up only. Compared with placebo, Lactobacillus rhamnosus GG (LGG) andVSL#3 were associated with significantly more treatment responders (LGG relative risk: 1.31[95% confidence interval: 1.08 to 1.59]; VSL#3: P , .05). Guar gum significantly improvedirritable bowel syndrome symptom frequency; however, no effect was found for other fibersupplements (relative risk: 1.17 [95% confidence interval: 0.75 to 1.81]) or a lactose-free diet.Functional disability was not significantly decreased after yoga compared with a wait-listapproach. No studies were found concerning lifestyle interventions; gluten-, histamine-, orcarbonic acid–free diets; fluid intake; or prebiotics. No serious adverse effects were reported.The quality of evidence was found to be very low to moderate.

CONCLUSIONS: Although high-quality studies are lacking, some evidence shows efficacy ofhypnotherapy, cognitive behavioral therapy, and probiotics (LGG and VSL#3) in pediatricAP-FGIDs. Data on fiber supplements are inconclusive.

aDepartment of Pediatric Gastroenterology and Nutrition, Emma’s Children’s Hospital, Academic Medical Center, Amsterdam, Netherlands; and bPediatric Association of the Netherlands,Utrecht, Netherlands

Drs Rutten and Korterink participated in the design of the study, judged the eligibility and validity of the studies, and drafted the initial manuscript; Dr Venmansparticipated in the design of the study, performed the literature search, and judged the eligibility and validity of the studies; Dr Benninga participated in the design ofthe study and critically reviewed and revised the manuscript; Dr Tabbers participated in the design of the study, performed the literature search, judged the eligibilityand validity of the studies, and critically reviewed the manuscript; and all authors approved the final manuscript as submitted.

*Drs Rutten and Korterink contributed equally.

www.pediatrics.org/cgi/doi/10.1542/peds.2014-2123

DOI: 10.1542/peds.2014-2123

Accepted for publication Nov 25, 2014

REVIEW ARTICLE PEDIATRICS Volume 135, number 3, March 2015by guest on April 21, 2017Downloaded from

MANUSCRIP

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ACCEPTED

ACCEPTED MANUSCRIPT

Figure 3: Change in IBS-symptom severity score and subcomponents during a six-week GFD; according to HLA-DQ status

¿Niños? ¿Adultos?

H2c.Migrañaabdominal• Debecumplirtodos,almenos2vecesen6meses:

1. Episodiosparoxísticosdedolorabdominalperiumbilical,enlíneamediaodifuso,deduración≥1hora,siendoelsíntomamásimportante

2. Separadosporsemanasameses3. Doloresincapacitanteeinterfiereconactividad4. Síntomasypatronesestereotipados5. Dolorasociadocondosomás:anorexia,nausea,

vómitos,dolordecabeza,fotofobiaypalidez6. Trasevaluaciónmédicaapropiada,nopueden

atribuirseaotracondiciónHyams JS,DiLorenzoCetal.Gastroenterology 2016;150:1456-1468.

H2d.Dolorabdominal– NOS• Debecumplirtodos,almenos4veces/mesdurantealmenos2mesespreviosaldiagnóstico:1. Dolorabdominalepisódicoocontinuoqueno

ocurresolamenteduranteeventosfisiológicos(p.ej.comer,menstruación)

2. CriteriosinsuficientesparaSII,DFoMA



treatment of children with FAP.72 Clinicians, patients, andparents should be aware of a black box warning issued bythe US Food and Drug Administration for an increased riskof suicidal ideation in adolescents. Hypnotherapy73 andcognitive behavioral therapy74 have provided short- andlong-term benefit in these patients.

H3. Functional Defecation DisordersH3a. Functional Constipation

Epidemiology. A systematic review reported a meanand median prevalence in children of 14% and 12%,respectively.75 The wide range in reported prevalence maybe due to the use of different FC criteria and cultural in-fluences. Peak incidence of constipation occurs at the time oftoilet training with no sex differences.76 Childhood FC isdistributed equally among different social classes with norelationship to family size, ordinal position of the child inthe family, or parental age. Boys with constipation hadhigher rates of fecal incontinence than girls.

H3a. Diagnostic Criteria for Functional Constipation

Must include 2 or more of the following occurring atleast once per week for a minimum of 1 month withinsufficient criteria for a diagnosis of irritable bowelsyndrome:

1. 2 or fewer defecations in the toilet per week in achild of a developmental age of at least 4 years

2. At least 1 episode of fecal incontinence per week

3. History of retentive posturing or excessive voli-tional stool retention

4. History of painful or hard bowel movements

5. Presence of a large fecal mass in the rectum

6. History of large diameter stools that can obstructthe toilet

After appropriate evaluation, the symptoms cannot befully explained by another medical condition.

Justification for change in diagnostic criteria. Theonly change is the decrease from 2 months to 1 month inthe duration of symptoms needed to fulfill the criteria inorder to harmonize with the European and the NorthAmerican Societies for Pediatric Gastroenterology, Hep-atology and Nutrition constipation guidelines, which sug-gested that the 2-month interval listed in the Rome IIIcriteria for older children may unduly delay treatment insome children. The shorter interval is now similar to thetime needed to fulfill the definition of FC in the neonate/toddler group.

Pathophysiology. Because FC is equally common inboth sexes and children with diverse socioeconomic back-grounds, dietary practices, and cultural influences,75 thetriggering event is most likely the universal instinct toavoid defecation because of pain or social reasons (eg,

Figure 2. The appraisal of any pain episode experienced by a child may have significant impact on the child’s ability to copeeffectively and accommodate to the pain, and consequently his or her normal function and development. In the presence ofrisk factors or when protective factors are less effective, the child may develop a maladaptive response leading to a state ofchronic pain. From Walker et al,90 adapted with permission.

1464 Hyams et al Gastroenterology Vol. 150, No. 6

CHILD/ADOLESCENT

H2d.Dolorabdominalfuncional– NOS

• Asociaciónconeventosestresantes• Síntomassomáticosextraintestinalesfrecuentes• Signosdealarma!!!• Evaluacióndiagnósticalimitadaparareafirmaciónparental

• Tratamiento:aunquedeevidenciaescasa,con:

– Amitriptiplina,citalopram– Terapiasconductuales– Hipnosis


12pasosenabordajedelpacienteconTGIF1. Improve patient satisfaction andengage with the patient.

2. Obtain the history through anondirective,patient-centered interview.3. Determinethe immediate reason for the patient’s visit

4. Conduct acareful physical examination andcost-efficient investigation.

5. Determinewhat the patient understands ofthe illness andhis or her concerns6. Elicit the patient’s understanding ofthe symptoms (illness schema)andprovide athorough

explanation7. Identify andrespond realistically tothe patient’s expectations

8. Trytoprovide alinkbetween stressors andsymptoms that areconsistent with the patient’sbeliefs

9. Setconsistent limits

10. Involve the patient inthe treatment

11. Make recommendations consistent with patient interests

12. Help establish an ongoing relationship with you or inassociation with aprimary careprovider


aspectos prácticos de los trastornos funcionales digestivos · – se mantiene la clasificación...

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