Dolor abdominal infantil
18- Mayo - 2017
Dolor abdominal infantil desde Roma a la Sala de examen
Donna K. Zeiter, Pediatric Clinics North Amercian Junio 2017
Traducción Dr Gerardo Flores Henríquez Pediatra Puerto Montt Chile
El dolor abdominal crónico sigue siendo uno de los problemas más comunes observados por los pediatras y gastroenterólogos pediátricos. En todo el mundo, el síndrome del intestino irritable (IBS) parece afectar al 11% de la población y el 30% de ellos se presentan para recibir atención médica.1 En un estudio comunitario de 1996, el 13% de los estudiantes de secundaria y el 17% de estudiantes high school experimentaron dolor semanalmente.2 Un estudio más reciente utilizó cuestionarios en línea y los criterios de ROMA III. En este estudio, los padres de niños que viven en Estados Unidos entre las edades de 4 años y 18 años se les pidió que informe sobre los síntomas gastrointestinales3; 23,1% de los niños calificaron para al menos 1 FGID.3 (functional gastrointestinal disorders (FGIDs) ).
FGIDs representan aproximadamente el
50% de las consultas de gastroenterología pediátrica.4
El
dolor abdominal continúa siendo un frustrante síntoma de presentación,
poniendo presión sobre el actual entorno de atención médica de ritmo
acelerado. El diagnóstico y el tratamiento de un niño con dolor abdominal
requieren tiempo para escuchar, aconsejar y educar; tiempo que es difícil de
encontrar en la práctica actual. Una gran mayoría de los pacientes que se
presentan para la evaluación del dolor abdominal no tienen enfermedad
orgánica en el sentido clásico y caen en una categoría funcional.
Muchos clínicos todavía creen que los niños con dolor abdominal crónico
están ansiosos o estresados. Según un estudio de la Academia Americana de
Pediatría y la Sociedad Norteamericana de Gastroenterología Pediátrica,
Hepatología y Nutrición, el 16% de los 300 pediatras encuestados pensaron
que el dolor abdominal funcional era un diagnóstico de descarte. Sólo el 11%
de estos pediatras pensaron que el dolor abdominal funcional era un
diagnóstico específico basado en criterios claros.5 Cualquiera de estas
preconcepciones tiene un impacto en la relación médico-paciente y
potencialmente afecta la futura interacción terapéutica.
Los FGID tienen un impacto significativo sobre las afectados. Las FGIDs causas dificultades significativas con comorbilidades a largo plazo, incluyendo ansiedad por depresión, trastornos psiquiátricos durante toda la vida, fobia social y síntomas somáticos.4
La distinción entre enfermedad orgánica y enfermedad no orgánica (FGID) es falsa. La investigación continúa apoyando la comprensión de que estos trastornos están relacionados con alteraciones en el sistema nervioso entérico (ENS) y en la modulación entre la ENS y el SNC, alteraciones que tienen una etiología orgánica a través de la modulación de neurotransmisores, receptores y vías de procesamiento celular Involucrados en el sistema nervioso.
El dolor abdominal se entiende mejor en el marco del modelo biopsicosocial de la enfermedad. El modelo biopsicosocial enfatiza la naturaleza multifactorial del dolor abdominal, incluyendo componentes genéticos, ambientales, sociales y psicológicos. Los planes de tratamiento necesitan desarrollarse y adaptarse con el tiempo y ser extremadamente individualizados. A medida que aumenta la comprensión de la fisiopatología de las FGIDs, habrá un repertorio más amplio de terapias a partir de las cuales seleccionar. Este artículo revisa la comprensión actual del FGIDS relacionado con el dolor y la etiología, fisiopatología y modalidades de tratamiento disponibles.
Etiología
Las posibles causas del dolor abdominal en los niños son numerosas y van desde trastornos benignos a urgencias quirúrgicas que amenazan la vida. El dolor abdominal puede surgir de trastornos en múltiples sistemas de órganos, incluyendo los sistemas pulmonar, gastrointestinal, urológico y ginecológico. Mecanismos infecciosos, neoplásicos, metabólicos y anatómicos pueden conducir al síntoma de presentación de dolor abdominal (Tabla 1) Los pacientes y las familias están ansiosos. A los clínicos les preocupa que equivoquen un diagnóstico. Estas preocupaciones a menudo conducen a numerosas referencias y a exámenes potencialmente invasivos.
Tabla 1.- Potenciales causas de dolor abdominal en el paciente pediátrico
IBS funcional (sindrome de intestino irritable)
FD (funcional dispepsia)
Functional abdominal pain
Functional constipation
Cyclic vomiting syndrome
Migraña abdominal
Gynecologic
Ovarian cyst
Ovarian torsion
Testicular torsion
Pulmonology
Pneumonia
Infectious
Viral
Enterovirus, adenovirus
Bacterial
Salmonella, Shigella, Campylobacter, Yersinia, E coli
Parasites
Giardia, Entamoeba histolytica
Intestinal
Reflujo Gastroesofágico (esofagitis)
Gastritis
Ulcera (duodenal / péptica)
Cholelithiasis, cholecystitis, choledochal cyst
Pancreatitis (acute, chronic), pseudoquiste pancreático
Hepatitis
Enfermedad Inflamatoria intestinal (Crohn / ulcerative colitis)
Enfermedad Eosinofílica (esophagitis, gastroenteritis)
Carbohydrate malabsorption (lactose intolerance)
Metabólica
Diabetes mellitis
Neoplasia
Porfiria tumores
Estructural / quirúrgica
Malrotation
Intussusception
Pólipo
Cuerpo extraño
Divertículo de Meckel
Vólvulo
Trauma
Urológica
Urinary tract infection
Nephrolithiasis
Urinary pelvic junction obstruction
Afortunadamente, hay varios síntomas de alarma que ayudan a los profesionales a diferenciar a los niños con enfermedades orgánicas, que requieren mayor investigación de aquellos con FGID ( Box 1) .5 Sin estos síntomas, es poco probable que las pruebas extensas descubran otros trastornos.
Box 1.- Signos de advertencia que sugieren un mayor riesgo de enfermedad orgánica en niños con dolor abdominal crónico
Involuntary weight loss
Deceleration of linear growth
Gastrointestinal blood loss
Significant vomiting (bilious emesis, protracted vomiting)
Dysphagia
Odynophagia
Chronic severe diarrhea
Night time stooling
Pain awakening the child at night
Persistent right upper or right lower quadrant pain
Unexplained fever
Abnormal physical findings (clubbing, localized tenderness, mass, hepatomegaly, esplenomegaly, perianal abnormalities, erythema nodosum)
Abnormal laboratory testing (elevated C-reactive protein/erythrocyte sedimentation rate, occult blood in stool)
Family history of inflammatory bowel disease
Evaluación
La evaluación de un paciente con dolor abdominal comienza con una historia y un examen físico detallado. Los pacientes a menudo describen sus síntomas usando "diagnósticos", tales como "He estado teniendo problemas con reflujo". Los clínicos deben centrarse específicamente en cada síntoma.
¿ Cuánto tiempo ha estado ocurriendo el dolor ?
¿ Se ha mejorado o empeorado el dolor o se ha mantenido estable?
¿ Cuál es la localización del dolor ?
¿ Es el dolor asociado con las comidas o el sueño?
¿ Existen desencadenantes específicos que empeoren o alivien el dolor ?
La historia y el examen físico deben incluir siempre una revisión de los síntomas de alarma, lo cual puede guiar al clínico a realizar pruebas más específicas (ver Cuadro 1). Sin embargo, el juicio clínico debe utilizarse en esta evaluación y estos síntomas de alarma deben ser vistos en el contexto de toda la historia.6 Por último, la evaluación del funcionamiento del paciente, aunque a menudo no indica el diagnóstico definitivo, proporciona pistas dado que el niño copia las estrategias de los padres.
Como mínimo, los estudios de laboratorio básicos deben incluir un recuento completo de células sanguíneas y un análisis de orina. Dependiendo de la historia, puede estar indicado un panel metabólico completo, amilasa, lipasa, velocidad de sedimentación de eritrocitos, proteína C reactiva o prueba de función tiroidea.
En el escenario clínico apropiado, el
profesional debe evaluar causas infecciosas, como Giardia y otras
enfermedades parasitarias, bacterianas y virales.
Muchos pacientes con IBS (sindrome de intestino irritable ) presentan
diarrea. En los niños, esto puede aumentar la preocupación por la enfermedad
inflamatoria intestinal. La calprotectina fecal se ha convertido en un test
de detección de la inflamación de mucosa que si tiene valores inferiores a
50 mg / g de heces sugiere que la inflamación es poco probable.7
Aunque controvertido, el screening de
enfermedad celíaca se recomienda en el actual Roma IV. En un estudio de
cohortes prospectivo, la prevalencia de la enfermedad celíaca fue 4 veces
mayor en los pacientes con IBS en comparación con la población general.8
La malabsorción de carbohidratos puede causar dolor abdominal, hinchazón y
diarrea, síntomas que imitan el IBS (sindrome de intestino irritable) . La
deficiencia de disacaridasa más común es la deficiencia de lactasa primaria.
Antes de pruebas más formales, un breve período de dieta con
eliminación de lactosa debe ser considerado en pacientes con síntomas
compatibles. Se pueden enviar biopsias endoscópicas para determinar la
actividad disacaridásica medida. La prueba de aliento (Breath testing)
es una prueba más funcional y es útil para determinar la malabsorción del
disacárido testeado.
Los pacientes pueden ser deficientes en enzimas o malabsorber carbohidratos; sin embargo, estas anormalidades no necesariamente se correlacionan con la intolerancia y los síntomas.
Los estudios radiológicos de rutina tienen un rendimiento mínimo en pacientes con dolor abdominal y sin síntomas de alarma. Las radiografías abdominales pueden ayudar a definir una neumonía, demostrar aire libre y ayudar a evaluar el aire intestinal o la carga de heces.
Los estudios han indicado que sin
síntomas de alarma la ecografía tiene poca utilidad para diferenciar a un
paciente con enfermedad orgánica de causas funcionales. Un estudio demostró
que la ecografía abdominal / pélvica en pacientes con dolor abdominal y sin
síntomas de alarma sólo detectó anomalías en el 1% .9 Estudios
recientes sobre los riesgos de cáncer en niños que reciben TAC han llevado a
limitar su uso como una herramienta de investigación para el dolor abdominal
.10
Las pruebas más invasivas, como la Endoscopia, siguen siendo controvertidas.
La endoscopia en pacientes con dolor abdominal crónico puede encontrar
anormalidades en 25% al 56% de las veces ; sin embargo, la presencia de
inflamación puede no predecir la resolución exitosa del problema.11
Hay poca evidencia de que una endoscopia normal en pacientes sin síntomas de
alarma proporcione beneficios en el manejo de niños con dolor abdominal.11
Un estudio reciente demostró que una endoscopia negativa no afecta la
persistencia, la frecuencia o la intensidad del dolor abdominal.12
Una endoscopia negativa no condujo a una mejoría en el absentismo escolar o
la interrupción del funcionamiento diario.12
Afortunadamente, existen sistemas de clasificación, como ROMA IV , para ayudar a los médicos a hacer un diagnóstico de FGIDs (desórdenes gastrointestinales funcionales) de una manera proactiva y no por exclusión.
Roma IV
Approximately 25 years ago, an international group of clinical practitioners and researchers met to establish a classification system for FGIDs, which would help in the diagnosis, the standardization of research, and dissemination of information on these common but poorly understood disorders. The symptoms-based classification was selected because it was thought the most relevant to clinical practice and less tied to a single pathophysiologic mechanism (ie, motility).13
The process of consensus was used to revise these criteria in 1999, 2006, and most recently 2016 with the publication of Rome IV.14
Rome IV now divides pediatric FGIDs into 3 forms6:
Nausea and vomiting disorders
Abdominal pain disorders
Defecation disorders
Pediatric FGIDs are outlined in chapters 15 and 16 ofRome IV.6,15 Boxes 2 and 3 outline those disorders. These criteria include all symptoms of FGIDs, not just the complaint of abdominal pain. For the purposes of this article, however, functional abdominal pain, IBS, and functional dyspepsia (FD) are reviewed.
Box 2.- Childhood FGIDs, Neonate / toddler10
Infant regurgitation
Rumination syndrome
Cyclic vomiting syndrome
Infant colic
Functional diarrhea
Infant dyschezia
Functional constipation
Data from Nurko S, Benninga M, Faure C, et al. Childhood functional gastrointestinal disorders, neonate/toddler. In: Drossman D, Chang L, Chey W, et al, editors. ROME IV, functional gastrointestinal disorders, disorders of gut-brain interaction. Raleigh (NC): The Rome Foundation;2016. p. 1237–96.
Box 3.- Childhood functional gastrointestinal disorders: child/adolescent
Functional nausea and vomiting disorders
Cyclic vomiting syndrome
Functional nausea and functional vomiting
Functional nausea
Functional vomiting
Ruminations syndrome
Aerophagia
FAPDs
FD
Postprandial distress syndrome
Epigastric pain syndrome
IBS
Abdominal migraine
FAP-NOS
Functional defecation disorders
Functional constipation
Nonretentive fecal incontinence
Data from DiLorenzo C, Hyams J, Saps M, et al. Childhood functional gastrointestinal disorders, child/adolescent. In: Drossman D, Chang L, Chey W, et al, editors. ROME IV, functional gastrointestinal disorders, disorders of gut-brain interaction. Raleigh (NC): The Rome Foundation; 2016. p. 1297–371.
FUNCTIONAL ABDOMINAL PAIN DISORDERS (FAPDs) IN CHILDREN AND ADOLESCENTS
In Rome IV, the committee reevaluated the terminology used in describing pain-based FGIDs. The term, functional abdominal pain, was not specific enough a descriptor for either clinical or research purposes. The terminology has been changed to FAPDs, which is inclusive of FD, IBS, functional abdominal pain–not otherwise specified (FAPNOS), and abdominal migraine.6 Each of these disorders has been carefully defined by the committee. The last phrase of each definition was altered to ensure that FAPD did not become a diagnosis of exclusion and mandates an appropriate, selective evaluation.
FD is defined as :
Bothersome symptoms at least 4 times a month for at least 2 months, which include
Postprandial fullness
Early satiation
Epigastric pain or burning not associated with stooling
After appropriate evaluation, symptoms that cannot be fully explained by another medical condition
IBS is defined as :
Abdominal pain at least 4 days per month over at least 2 months associated with 1 or more of the following:
Related to defecation
A change in stool frequency
A change in stool form
In children with abdominal pain and constipation, the pain does not resolve with resolution of the constipation and, after appropriate evaluation, the symptoms cannot be fully explained by another medical condition.
IBS has been divided into 4 subtypes based on the Bristol Stool Form Scale6:
IBS-C — constipation predominate
IBS-D — diarrhea predominate
IBS-M — mixed stool types
IBS-U — unsubtyped
Subtyping of IBS has been important in directing therapy. Many current therapies are being targeted to treat and approved for use with specific subtypes.6
FAP-NOS is defined as abdominal pain occurring at least 4 times a month and all of the following:
Episodic or continuous abdominal pain that does not occur solely during physiologic events
Insufficient criteria for IBS, functional dyspepsia, or abdominal migraine—after appropriate evaluation, the symptoms cannot be fully explained by another medical condition.6
Fisiopatología
FGIDs are the result of a complex interplay of factors that affect the individual and combine to produce disease. This paradigm is the biopsychosocial conceptual model.
This model defines FGIDs as gastrointestinal symptoms resulting from a combination of :
Early life events, which may include :
Genetics
Environmental factors (trauma, infections, parental behaviors)
Psychosocial factors
Life stress
Personality traits
Psychological state
Coping
Social support
Physiologic factors
Motility disturbance
Visceral hypersensitivity
Altered CNS processing
Altered mucosal and immune function
Altered gut microbiota13
Early Life Events
Early life pain or stress seems able to lead to chronic abdominal pain later in life through the development of visceral hypersensitivity. The abdominal pain may be the result of :
Increased sensitization of central neurons
Sensitization of primary sensory neurons
Impaired stress response through alterations in the hypothalamic-pituitaryadrenal axis (HPA) axis altered descending inhibition of sensory stimulation16
The development of CNS changes has been studied in neonatal rats16 as well as human infants. Exposure to colonic irritation in neonatal rats results in permanent alteration in spinal neurons, which leads to visceral hypersensitivity, a decreased pain threshold, when they become adults.16 Also in rats, somatic pain experienced in the neonatal period can increase sensitization of spinal neurons and lead to visceral hypersensitivity in adult rats.16 Infants with prior surgical history have been shown to have increased need for anesthesia during procedures as well as higher pain control postoperatively.17
The sensory neurons of the ENS also seem to have a lower sensory threshold and increased signaling to the CNS in individuals with FAPD. Animal studies have shown that colonic irritation sensitizes the sensory neuron in the lumbosacral region, leading to increased signaling in response to colorectal distension.18
Stress seems to be 1 trigger for FGIDs in children. Animal studies have demonstrated the development of visceral hypersensitivity after stress events.16 Stress events have also been shown to increase corticotropin-releasing factor (CRF) expression in the periventricular nucleus, locus coeruleus, and amygdala of adult rats.19 This action alters the set point of the CRF system and may affect an organism’s response to stress and pain later in life.
Pain signals sent by the ENS undergo processing in the spinal cord by inhibitory or excitatory neurons from the CNS. Studies evaluating the effect of fentanyl in response to rectal stimulation demonstrate an improved response in patients with IBS compared with controls. This suggests an alteration in the pain modulatory opioid system.16
Genética
The clustering of FGIDs in families suggest a possible genetic cause of chronic abdominal pain, although this finding could be explained by common environmental factors. Twin studies have not been consistent; however, several studies from the United States, Australia, and Norway have shown increasing concordance for IBS in twins.20
Evidence supporting the role of early life events in the etiology of FGIDs has led to research into candidate genes. Studies have identified numerous genes and gene products, which may lead to altered visceral sensitivity and pain processing, including; a2-adrenergic receptors, serotonin receptors, serotonin and norepinephrine transporters, interleukin (IL)-10, tumor necrosis factor (TNF)-a, TNF superfamily member 15, G proteins (involved in intracellular signaling and ion channels [SCN5A]).21
Using genome-wide association studies and data from the Screening Across the Lifespan Twin Study, a locus on 7p22.1 consistently showed increase genetic risk for IBS.22 This area maps to 2 genes, KDEL receptor 2 gene (KDELR2) expressed in all tissues and glutamate receptor-ionotropic-delta 2 interacting protein (GRID2IP) localized expression in the brain. KELR2 seems to play a role in vesicle trafficking and transport to the endoplasmic reticulum. The gene seems more highly expressed in the rectum of patients with IBS. GRID2IP encodes a protein, delphilin, which plays a role in glutamatergic neurotransmission.22
Factores psicosociales
Studies have demonstrated an increase rate of stress, anxiety, and depression in patients with FGIDs.6 There do not seem to be any differences in psychosocial profiles among patients with different abdominal pain–based FGIDs.23 Children with FAP have a decreased quality of life, frequent school avoidance, school absences, and social difficulties.24 These pain syndromes are not short lived. In 25% to 45% of patients, these pain symptoms persist for 5 years.24 Children with extraintestinal somatic symptoms, such as dizziness, back pain, headache, and depression, are more likely to have FGIDs, which extend into young adulthood.25 It is important to know, however, that 50% of children with FGIDs have no emotional, behavioral, or social functioning problems.26
Each individual approaches stress differently. This approach depends on how a child perceives an event and the available coping strategies. Children who feel threatened by a pain event and use passive coping strategies do not have as good an outcome. Children who are more accepting of the pain and have accommodating coping strategies tend to have better function.27 In addition to individual strategies, a child’s social network provides potential support for coping with chronic abdominal pain, in both positive and negative ways. Families and friends can facilitate wellness or promote disability.
Physiologic Factors
The network of communication between the gut and the brain includes the CNS (brain and spinal cord), the autonomic nervous system, the ENS, and the HPA axis.28 Sensations from the gastrointestinal tract are the result of signaling from mechanoreceptors located in the afferent terminal of spinal afferent nerves. These nerves have cell bodies in the vagal nodose ganglia and dorsal root spinal ganglia. The signals are then sent via vagal sensory afferents to the brainstem via the nodose ganglia and nucleus tractus solitarius. Serotonin is an important neurotransmitter in pain signaling, mainly through the 5-HT3 receptor.29 Increased secretion of serotonin or decreased uptake of serotonin leads to increased pain signaling.29 In patients with visceral hypersensitivity, afferent sensory receptors seem to have a lower threshold for stimulation. These receptors continue to send pain signals after the stimulus has already passed.30 This increased sensitivity may be triggered by intestinal inflammation related to inflammatory bowel disease, allergy, or infection.
The role of pain signal processing in the cerebral cortex has been investigated in humans using both functional MRI and PET. These imaging studies have demonstrated that pain signaling from the secondary somatosensory cortex projects to the limbic and paralimbic regions. These are areas of the brain that are important in an individual’s mood, motivation, and cognition, all important components in the experience of visceral pain.29 Functional MRI has demonstrated that patients with IBS have increased activation of the midcingulate cortex in response to rectal distention.31 The cingulate cortex is believed an integrative center for emotional experience and pain information.29
The HPA axis is vital in coordinating the organism’s response to stress. The HPA is part of the limbic system of the brain that is involved with memory and emotional response. Stress activates release of CRF from the hypothalamus, which then stimulates secretion of corticotropin from the pituitary. Corticotropin then stimulates the secretion of cortisol from the adrenal glands. Both neural and hormonal mechanisms allow the brain to influence many cell functions in the intestine, including immune cells, epithelial cells, neurons, smooth muscle cells, interstitial cells of Cajal, and enterochromaffin cells.28
Inflamación
There is evidence to suggest that an imbalance in proinflammatory and antiinflammatory cytokines may play a role in the development of IBS.6 Children with IBS seem to have a lower secretion of an anti-inflammatory cytokine (IL-10), which suggests altered immune regulation in this disease process. These changes are subtle and may be induced by prior infections.6
Microbioma
Studies have demonstrated differences in the microbiome of children with IBS. These children have a higher proportion of Proteobacteria than healthy children.32 There seems to be bidirectional influence between the gut microbiome and the gut-brain axis via neural, endocrine, immune, and humoral mechanisms.28 In the CNS, studies using germ-free mice have demonstrated that the microbiome can effect stress reactivity as well as modulate the serotonergic system.28,33 In these same germ-free mice, addition of probiotics has led to changes in gut-brain axis mRNAexpression in the brain, reduced stress-induced release of cortisol, and reduced anxiety and depression behaviors.28
Peripherally, the microbiome may interact with the GBA by modulating afferent sensory nerves, producing molecules that act as local neurotransmitters, and through the production of short chain fatty acids, which can stimulate the sympathetic nervous system.28 The CNS also interacts in direct ways with the gut microbiome. For reasons not fully understood, bacteria in the colon contain binding sites for enteric neurotransmitters, the same neurotransmitters used in signaling by the ENS and CNS. The CNS directly controls the environment in which the microbiome resides by modulating intestinal motility; the secretion of acid, bicarbonate, and mucus; intestinal fluid handling and the mucosal immune system. These studies point to the microbiome as a compelling area of research and possible therapeutic target in the treatment of FGIDs.
Tratamiento de los desórdenes gastrointestinales funcionales relacionados con dolor
The development of a treatment plan for the patient with FGIDs is an individualized process. Therapeutic outcomes depend on a plan that directs treatment to many aspects of the disorder.
The arms of therapy include :
Dietary therapy
Pharmacologic therapy
Psychosocial support
Complementary /alternative interventions34
Simple reassurance in the setting of a strong clinical therapeutic relationship can be helpful in enabling children with FD to resume normal activity. Placebo response rates in patients with FGIDs range from 20% to 60%.35
Terapia dietética
If FGIDs are understood as the result of visceral hypersensitivity, foods that increase abdominal distention, and therefore pain signaling, may complicate symptoms. Recently, studies have evaluated food triggers and have suggested a role of nonabsorbable carbohydrates, nonceliac gluten sensitivity, and food chemical sensitivity.36 More specifically, fermentable oligosaccharides, disaccharides andmonosaccharides, and polyols (FODMAPs) are a group of poorly digestible carbohydrates that seem to participate in causing symptoms.36 These carbohydrates include fructose, lactose, sorbitol, fructo-oligosaccharides, gluco- oligosaccharides, and mannitol.
FODMAPs are believed to lead to symptoms through several mechanisms, including increase osmotic load and intestinal distention, altered intestinal motility, direct injury to colonic epithelium with increased permeability, and interaction with the intestinal microbiome and the varied metabolism of those organisms.36
There are few current tables of FODMAPs in foods and no validated FODMAP cutoff levels to help determine whether a food is truly high FODMAP. Recommendations are to attempt to keep FODMAPs below 3 g a day, however, to benefit IBS patients.36 On a strict restriction, studies out of Australia have demonstrated a 74% response rate with durability linked directly to dietary compliance.37
Probióticos
Intestinal bacteria play a complex role in multiple processes, including effects on bowel motility, pain signaling, immune response, nutrient processing. Manipulationof this microbiome is a potential therapeutic target In a recent meta-analysis of placebo-controlled randomized studies,38 Lactobacillus rhamnosus GG, Lactobacillus reuteri DSM 17938, and VSL#3 were all shown to increase treatment success with abdominal pain type FGIDs, especially in those patients with IBS. LGG and L reuteri DSM 17938 significantly decreases the intensity of the pain. The data for VSL#3 demonstrated that the intensity of pain and bloating was significantly lower than placebo; however, pain frequency was unchanged.38
More research is needed to determine the exact strain, dosage, or combination that is the most effective.
Farmacoterapia
Medications for the treatment of FGIDs target multiple points along the pain transmission pathway — from the peripheral receptor, the spinal cord, and also the cortex. Controlled trials in pediatrics continue to be rare.
Antibióticos
With the understanding that the microbiome plays an important role in the etiology of FGIDs, the use of antibiotics in therapy seems a logical step. TARGET-1 and TARGET- 2 were 2 double-blind, placebo-controlled studies comparing rifaximin to placebo in the treatment of IBS without constipation.39 These 2 large-scale trials, enrolling 1260 patients, demonstrated that a 14-day course of rifaximin, at a dose of 550 mg 3 times a day for 14 days, was superior to placebo in improving IBS symptoms with no increased risk of side effects.39 The Food and Drug Administration–approved rifaximin for treatment of IBS-D in May 2015.
Antiespasmódicos
Although commonly used in treating patients with pain FGIDs, the anticholinergic hyoscyamine (Levsin) has not been studied in a controlled fashion.40 Dicyclomine (Bentyl) has been studied in IBS-C and was found to improve overall IBS symptoms.40
Antidepresivos
Antidepressants affect both the central and peripheral nervous system through multiple pathways, including anticholinergic effects, leading to decreased gastrointestinal transit, improved sleep, treatment of comorbid depression, and analgesia through receptor binding throughout the pain transmission pathway.41 In a pediatric study, citalopram improved function and decreased pain in 84% of patients with FGIDs.42
Serotonina
Serotonin is a critical neurotransmitter in the pain pathway and is an attractive target for potential therapy. Two serotonin type 3 compounds have been developed and studied in adults, alosetron and cilansetron. Complications with these medications, including severe constipation and ischemic colitis, have restricted their use.41 Tegaserod, a serotonin type 4 antagonist, is used in constipation predominate IBS.
Soporte psicosocial
One of the most important aspects of therapy in these patients is the development of a supportive doctor-patient relationship in which the patient is an active participant in developing to plan of care. Drossman,13 in Rome IV, outlines 12 steps to enhance this relationship.
These steps include :
Learning to engage the patient in the visit
Being nonjudgmental and patient centered while taking the history
Determining the immediate need for the patient visit
Conducting a careful physical examination and cost-efficient investigation
Determining patients’ understanding of their illness and focus on their concerns
Eliciting patient understanding of symptoms and provide education
Responding to patient expectations
Associating stress and symptoms in a way that is consistent with patient beliefs
Setting limits
Involving the patient in treatment
Making recommendations consistent with patient interests
Establishing an ongoing relationship13
Cognitive Behavioral Therapy
Psychological therapies are effective in the treatment of FGIDs and include parent training, family support, psychotherapy/cognitive behavioral therapy (CBT), relaxation, distraction, hypnotherapy, and biofeedback.43
Multiple studies have demonstrated that psychological therapy, such as hypnotherapy and CBT, are effective in the treatment of FGIDs.44,45 Family therapy and parent training help address acceptance of a rehabilitation approach to therapy. These interventions are also helpful in changing behaviors in the family that may promote disability or catastrophizing; ongoing behavioral plans should promote independence and functioning.
CBT is a psychotherapeutic approach focused on changing unhelpful cognitions, assumptions, beliefs, and behaviors.43 During this therapy, patients learn a more biopsychosocial framework of disease. They may keep a diary of symptoms and events to help identify triggers or outcomes that can be targeted for intervention. Patients learn to question their thoughts, assumptions and beliefs that may not be helpful and formulate a new approach.43 Hypnotherapy helps patients focus away from the pain, alter sensory experience, decrease stress, promote relaxation, and provide a way to reconsider painful stimuli. In patients with FGIDs, there are gut-specific techniques that may be used.43
Complementary Medicine
Complementary medicine techniques may include acupuncture, Ayurveda medicine, chiropractic, homeopathy, and mind-body medicine. Modalities include herbal supplementation, massage therapy, acupuncture, and hypnotherapy.46
Peppermint oil is a common and studied herbal often used in patients with FGIDs. In 1 study in children, there was a 76% improvement in symptoms compared with a 19% placebo response.47 Ginger has been shown helpful in patients with nausea and seems to have a prokinetic function.46
The use of massage therapy remains controversial. The underlying theory is that massage may reduce visceral hypersensitivity and alter gastrointestinal tone and motility. Although promising, more studies are needed to confirm its efficacy. Acupuncture has been shown to effect acid secretion, gastrointestinal motility, and visceral pain in animals. Studies at this time, however, have not demonstrated efficacy for FGIDs.
Gut-directed hypnotherapy has been shown effective in both adults and children in the management of FGIDs. One study demonstrated that hypnotherapy was superior to standard medical therapy. Most interestingly, at 1-year follow-up, symptoms were successfully treated in 85% of the cases.
Dispepsia funcional
Although FAP-NOS and IBS refer to more generalized abdominal pain, functional dyspepsia (FD) refers to symptoms that seem to refer to the gastroduodenal region. These symptoms may include abdominal bloating, epigastric pain, early satiety, belching, epigastric burning, nausea, and vomiting. In Rome IV, FD in children has been divided into 2 subtypes, postprandial distress syndrome and epigastric pain syndrome.6,48 There is some controversy around this separation. A recent study demonstrated that in a significantnumberofpatients, noclinical distinctionwaspossible and43%of children switched subtypes, suggesting a common pathophysiology.49 In another study, however, 29%of patients fit into the postprandial distress syndrome, 24%met criteria for epigastric pain syndrome, 26%met criteria for both, and 21%did not fulfill either diagnosis.50 The clinical distinction, when present,may provide an alternative to overuse of empiric acid-blocking therapy as well as alternatives to immediate endoscopy or subspecialty referral.51
FD is defined as symptoms occurring at least 4 times a month for at least 2 months, including :
1. Postprandial fullness
2. Early satiety
3. Epigastric pain or burning not associated with stooling
4. After appropriate evaluation, symptoms that cannot be fully explained by another medical condition6
Postprandial distress syndrome is defined as bothersome postprandial fullness or early satiation that prevents finishing a meal. These sensations may include upper abdominal bloating, postprandial nausea, or excessive belching.6
Epigastric pain syndrome includes pain or burning located in epigastrium, a burning quality pain that may be induced or relieved by ingestion of a meal.6 The major pathophysiologic mechanisms of other FGIDs are also thought to lead to FD, including motility abnormalities, abnormalities of accommodation, and visceral hypersensitivity.51
A direct link between motor abnormalities and resultant symptoms is not firmly established.52 Changes in gastric motor patterns may be the result of abnormalities of the vasovagal reflex, the intrinsic inhibitory innervation, or altered smooth muscle.51 Approximately two-thirds of adults with FD have abnormal gastroduodenal motility, leading to postprandial fullness, nausea, and vomiting.51
Gastric accommodation is a motor event in which the gastric fundus seems to relax in an attempt to accept an incoming meal, without increasing gastric pressure. In patients with abnormal gastric accommodation, the food bolus seems to localize to the distal stomach. Abnormal gastric accommodation has been demonstrated in 40% of adult patient with FD, leading to early satiety or postprandial pain.51 Visceral hypersensitivity may occur at many levels in the upper gastrointestinal tract.
Adults with FD have increased sensitivity to acid within the duodenum, leading to nausea in a subset of patients. Adults with FD have also been found more sensitive to gastric balloon distention, with increased brain signaling.52
Recent studies in adults have also demonstrated a link between prior infections, such as Salmonella, Eshcherichia coli 0157, Campylobacter jejuni, Giardia lamblia, and norovirus, and the development of FD.53
Work-up of Functional Dyspepsia
In the upper tract, alarm symptoms include vomiting, dysphagia, odynophagia, weight loss, hematemesis, and abnormal laboratory studies, such as anemia. In
the setting of alarm symptoms, endoscopy is the most sensitive and specific test for the evaluation of other inflammatory causes of upper gastrointestinal symptoms.
Gastric emptying scans may also be helpful in demonstrating motor dysfunction and delayed gastric emptying. Anatomic studies, such as an upper gastrointestinal radiograph, help define normal anatomy and evaluate for malrotation, hiatal hernia, rings, or webs. Upper gastrointestinal radiography does not establish the diagnosis of gastroesophageal reflux disease in any meaningful way.
Endoscopy continues to be controversial in pediatric FD. Adult Rome criteria have required an esophagogastroduodenoscopy; in pediatrics, esophagogastroduodenoscopy is not a requirement in the diagnosis of FD.6 In a study from Hong Kong, 80 consecutive children with FD were evaluated.54 Alarm symptoms included gastrointestinal blood loss, dysphagia, vomiting and right upper quadrant pain, nocturnal pain, family history of peptic ulcer disease, and weight loss. Endoscopic mucosal abnormalities were noted in 3 of 9 patients with alarm symptoms and 2 of 71 children without alarm symptoms.54 If no alarm symptoms are present, a therapeutic trial of acid blockade, prokinetic agents, or other motility agents, such as cyproheptadine, may lead to symptomatic improvement.
Terapia
There are few randomized studies on the treatment of FD, especially in children. Acid suppression was shown helpful in a study comparing cimetidine, ranitidine, famotidine, and omeprazole in the treatment of children with FD. This study demonstrated a 53.8% symptom relief with omeprazole after 4 weeks of therapy, 44.4% for famotidine. 55 The study supported the use of proton pump inhibitors over H2-receptor antagonists in the treatment of FD.
There are few data in children supporting the use of prokinetics in children for the treatment of FD. Pharmacotherapy has focused on agents that stimulate gastric emptying by targeting serotonin receptors (serotonin type 2 antagonists and serotonin type 4 agonists), dopamine, and motilin receptors.51 Unfortunately, most of these agents, such as cisapride, domperidone, and reglan, are either ineffective or carry significant cardiac or neurologic risk.
Cyproheptadine, an antagonist of serotonin, histamine H1, and muscarinic receptors, seems to improve gastric accommodation and has been shown to improve symptoms in children with FD. In a retrospective, open-label study, there was a 55% improvement in dyspeptic symptoms in pediatric patients.56 There was also a 30% incidence of side effects; however, all were mild and self-limited. Only 2 of 80 children stopped therapy.56
As in the treatment of other FGIDs, antidepressant medications, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may also be helpful in treating FD. These medications may act by improving gut motility or modulations of visceral hypersensitivity.51
Abdominal pain continues to be a common and concerning symptom in children. Abdominal pain leads to frequent physician visits and often extensive testing. Rome IV has helped to define FGIDs, and promote education and research into these disorders. A fascinating, intricate web of neurologic signaling, hormonal signaling, commensal organisms, stress, anxiety, social support, and genetics seems involved in the ultimate manifestation of FGIDs. Further research is needed to more specifically define this interplay and effects. Therapeutic interventions need to address these multiple pathophysiologic mechanisms in the setting of individual experience of disease.