Differential diagnosis of recurrent abdominal pain: new considerations

RAP is a common and challenging clinical presentation in general pediatrics and pediatric gastroenterology. The differential diagnosis is extensive and growing but dominated by functional disorders for which there are new diagnostic criteria despite the lack of specific confirmatory laboratory markers. Because FRAP, dyspepsia, and IBS are common and defined by clinical criteria, it is now prudent to initiate empiric therapy for suspected functional disorders while performing limited laboratory screening to exclude organic disorders. Using this approach, one is no longer bound to undertake extensive testing in all children with undifferentiated RAP. Alarm symptoms help identify children at greater risk for a specific underlying organic cause to their symptoms and can narrow the focus for diagnostic evaluation. Because of altered family dynamics, interaction with psychological comorbidities, and the child's disabled status, the role of the psychologist is critical in many cases. IBS is the most common single diagnosis in undifferentiated RAP and can be readily identified using the current Rome II criteria. The clinical patterns in children--pain plus altered bowel habits--help differentiate patients into diarrhea-predominant and constipation-predominant subtypes. Although the pathophysiology of IBS is unknown, specific approaches to identify and reduce triggers, pharmacologically reduce bowel spasm, and attenuate neural-pain processing are now commonly used and effective strategies.     

New insights in the etiology and pathophysiology of irritable bowel syndrome: contribution of neonatal stress models

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders, characterized by abdominal pain and disturbed defecation that cannot be explained by structural abnormalities. Although IBS symptoms (visceral pain, increased gut permeability, motility alterations) are clearly established, the etiology of this pathology is loosely understood. Nevertheless, clinical studies have reported that some early abuse (physical and psychological) is often associated with IBS development. Thus, loss and separation in the family during childhood may contribute to the IBS development. The recent development of animal models has pointed out the importance of early traumatic experiences in favoring the occurrence of IBS in adult life. Among these different models, neonatal maternal deprivation (NMD), neonatal colonic irritation (inflammatory stimuli), and neonatal colonic pain (rectal distension) have been described to mimic some cardinal features of IBS. The purpose of this review is 3-fold. First, to present the different neonatal stress models. Second, to review the literature on the influence of these early traumatic experiences on the gastrointestinal tract disturbances observed in adult life. Finally, we will also present the mediators and mechanisms involved in gut dysfunction triggered by NMD and probably in IBS.     

维生素D在儿童肠易激综合征中的作用

肠易激综合征（IBS）是一种儿童常见的功能性胃肠病,临床表现以反复腹痛伴排便频率或大便性状的改变为特征。多项研究表明,IBS患儿维生素D水平显著低于健康人群,且补充维生素D能明显改善IBS患儿的临床症状和生活质量,提示维生素D可能对IBS有治疗作用。该综述主要讨论维生素D与儿童IBS的关系,并就其可能的作用机制进行阐述。     

Irritables Kolon bei Kindern

Irritable bowel syndrome (IBS) represents the most prevalent manifestation of functional gastrointestinal disorders in children and adolescents. It is characterized by recurrent abdominal pain or discomfort without evidence for organic disorders associated with defecation or alterations in stool frequency or stool form (diarrhea or constipation). The etiology of irritable bowel syndrome is multifactorial and complex. Genetic and familial factors together with stressful early life events and gastrointestinal infections may lead to mucosal inflammation, disturbances of intestinal motility and permeability. The diagnostic process consists of careful history and physical examination and simple investigations. Invasive procedures should be avoided whenever possible. Treatment of children and adolescents with IBS should be based on the biopsychosocial model of functional gastrointestinal disorders. Development of a positive relationship between pediatrician, child and parents is part of the therapeutic process. Cognitive-behavioral training as part of a multidisciplinary psychosocial intervention is recommended. Pharmacotherapy (probiotics, peppermint oil and macrogol) should be given only in selected cases.     

Investigation and management of coeliac disease.

Coeliac disease (CD) is common in children with an estimated prevalence of approximately 1:100. The clinical presentation has altered over the last decade, with most children manifesting non-specific or mild symptoms. The accuracy of serological testing has improved dramatically with targeted assessment of children with conditions known to be associated with CD leading to the detection of asymptomatic cases. The diagnosis of CD still requires upper gastrointestinal endoscopy and small bowel biopsy, and management requires a life-long gluten-free diet to avoid long-term complications.     

Investigation and management of coeliac disease

Coeliac disease (CD) is common in children with an estimated prevalence of approximately 1:100. The clinical presentation has altered over the last decade, with most children manifesting non-specific or mild symptoms. The accuracy of serological testing has improved dramatically with targeted assessment of children with conditions known to be associated with CD leading to the detection of asymptomatic cases. The diagnosis of CD still requires upper gastrointestinal endoscopy and small bowel biopsy, and management requires a life-long gluten-free diet to avoid long-term complications.     

Cow’s milk-induced gastrointestinal disorders: From infancy to adulthood

Milk is related to many gastrointestinal disorders from the cradle to the grave due to the many milk ingredients that can trigger gastrointestinal discomfort and disorders. Cow’s milk protein allergy (CMPA) is the most common food allergy, especially in infancy and childhood, which may persist into adulthood. There are three main types of CMPA; immunoglobulin E (IgE)-mediated CMPA, non-IgE-mediated CMPA, and mixed type. CMPA appears before the first birthday in almost all cases. Symptoms may start even during the neonatal period and can be severe enough to simulate neonatal sepsis. CMPA (often non-IgE mediated) can present with symptoms of gastroesophageal reflux, eosinophilic esophagitis, hemorrhagic gastritis, food protein-induced protein-losing enteropathy, and food protein-induced enterocolitis syndrome. Most CMPAs are benign and outgrown during childhood. CMPA is not as common in adults as in children, but when present, it is usually severe with a protracted course. Lactose intolerance is a prevalent condition characterized by the development of many symptoms related to the consumption of foods containing lactose. Lactose intolerance has four typical types: Developmental, congenital, primary, and secondary. Lactose intolerance and CMPA may be the underlying pathophysiologic mechanisms for many functional gastrointestinal disorders in children and adults. They are also common in inflammatory bowel diseases. Milk consumption may have preventive or promoter effects on cancer development. Milk may also become a source of microbial infection in humans, causing a wide array of diseases, and may help increase the prevalence of antimicrobial resistance. This editorial summarizes the common milk-related disorders and their symptoms from childhood to adulthood.     

Cow’s milk-induced gastrointestinal disorders: From infancy to adulthood

Milk is related to many gastrointestinal disorders from the cradle to the grave due to the many milk ingredients that can trigger gastrointestinal discomfort and disorders. Cow’s milk protein allergy (CMPA) is the most common food allergy, especially in infancy and childhood, which may persist into adulthood. There are three main types of CMPA; immunoglobulin E (IgE)-mediated CMPA, non-IgE-mediated CMPA, and mixed type. CMPA appears before the first birthday in almost all cases. Symptoms may start even during the neonatal period and can be severe enough to simulate neonatal sepsis. CMPA (often non-IgE mediated) can present with symptoms of gastroesophageal reflux, eosinophilic esophagitis, hemorrhagic gastritis, food protein-induced protein-losing enteropathy, and food protein-induced enterocolitis syndrome. Most CMPAs are benign and outgrown during childhood. CMPA is not as common in adults as in children, but when present, it is usually severe with a protracted course. Lactose intolerance is a prevalent condition characterized by the development of many symptoms related to the consumption of foods containing lactose. Lactose intolerance has four typical types: Developmental, congenital, primary, and secondary. Lactose intolerance and CMPA may be the underlying pathophysiologic mechanisms for many functional gastrointestinal disorders in children and adults. They are also common in inflammatory bowel diseases. Milk consumption may have preventive or promoter effects on cancer development. Milk may also become a source of microbial infection in humans, causing a wide array of diseases, and may help increase the prevalence of antimicrobial resistance. This editorial summarizes the common milk-related disorders and their symptoms from childhood to adulthood.     

Autism medical comorbidities

Medical comorbidities are more common in children with autism spectrum disorders (ASD) than in the general population. Some genetic disorders are more common in children with ASD such as Fragile X syndrome, Down syndrome, Duchenne muscular dystrophy, neurofibromatosis type I, and tuberous sclerosis complex. Children with autism are also more prone to a variety of neurological disorders, including epilepsy, macrocephaly, hydrocephalus, cerebral palsy, migraine/headaches, and congenital abnormalities of the nervous system. Besides, sleep disorders are a significant problem in individuals with autism, occurring in about 80% of them. Gastrointestinal (GI) disorders are significantly more common in children with ASD; they occur in 46% to 84% of them. The most common GI problems observed in children with ASD are chronic constipation, chronic diarrhoea, gastroesophageal reflux and/or disease, nausea and/or vomiting, flatulence, chronic bloating, abdominal discomfort, ulcers, colitis, inflammatory bowel disease, food intolerance, and/or failure to thrive. Several categories of inborn-errors of metabolism have been observed in some patients with autism including mitochondrial disorders, disorders of creatine metabolism, selected amino acid disorders, disorders of folate or B12 metabolism, and selected lysosomal storage disorders. A significant proportion of children with ASD have evidence of persistent neuroinflammation, altered inflammatory responses, and immune abnormalities. Anti-brain antibodies may play an important pathoplastic mechanism in autism. Allergic disorders are significantly more common in individuals with ASD from all age groups. They influence the development and severity of symptoms. They could cause problematic behaviours in at least a significant subset of affected children. Therefore, it is important to consider the child with autism as a whole and not overlook possible symptoms as part of autism. The physician should rule out the presence of a medical condition before moving on to other interventions or therapies. Children who enjoy good health have a better chance of learning. This can apply to all children including those with autism.     

‘Rapid transit’ constipation in children: a possible genesis for irritable bowel syndrome

Children with chronic idiopathic constipation (CIC) often end up at the surgeon when medical treatments have failed. This opinion piece discusses a recently described pattern of CIC called ‘Rapid transit constipation (RTC)’ first identified in 2011 as part of surgical workup. RTC was identified using a nuclear medicine gastrointestinal transit study (NMGIT or nuclear transit study) to determine the site of slowing within the bowel and to inform surgical treatment. Unexpectedly, we found that RTC occured in 29% of 1000 transit studies in a retrospective audit. Irritable bowel syndrome (IBS) occurs in 7–21% of the population, with a higher prevalence in young children and with constipation type dominating in the young. While 60% improve with time, 40% continue with symptoms. First-line therapy for IBS in adults is a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols which reduces symptoms in > 70% of patients. In children with functional gastrointestinal disorders, fructose intolerance occurs in 35–55%. Reducing fructose produced significant improvement in 77–82% of intolerant patients. In children with RTC and a positive breath test upon fructose challenge, we found that exclusion of fructose significantly improved constipation, abdominal pain, stool consistency and decreased laxative use. We hypothesise that positive breath tests and improvement of pain and bowel frequency with sugar exclusion diets in RTC suggest these children have IBS-C. These observations raise the possibility that many children with CIC could be treated by reducing fructose early in their diet and this might prevent the development of IBS in later life.     

Characterization of irritable bowel syndrome and constipation in children with allergic diseases

Allergy is believed to play a role in the pathogenesis of irritable bowel syndrome (IBS) and constipation. We investigated whether allergic patients are more prone to constipation or IBS. In a multicenter study, two groups of outpatient children aged 3–13 years were included. In group 1, children with allergic symptoms were enrolled. Group 2 consisted of nonallergic children. In both groups, the assessment of IBS and constipation was carried out using a questionnaire based on the Rome criteria for functional gastrointestinal disorders. All children were examined and underwent skin prick tests (SPT) to foods and aeroallergens. The allergic group (n = 196) and controls (n = 127) were comparable with respect to sex, age, and anthropometric parameters. IBS was found in 6.6% of the allergic children and in 6.3% of the controls (p = 0.581). The frequency of constipation was similar in the two groups. In allergic children, positive SPTs to food and self-reported reactions to food were associated with IBS. Our results show that evaluation of constipation comorbidity is not required in allergic children. In allergic children with positive SPT to foods attention may be paid to IBS symptoms.     

Health-related quality of life in pediatric patients with irritable bowel syndrome: a comparative analysis

The primary aim of the study was to investigate the generic health-related quality of life (HRQOL) of pediatric patients meeting Rome II criteria for irritable bowel syndrome (IBS) in comparison to healthy children. The secondary aim was to compare pediatric patients with IBS to pediatric patients with Rome II criteria diagnosed functional abdominal pain (FAP) and patients with diagnosed organic gastrointestinal (GI) disorders. The study also investigated the associations between GI symptoms with generic HRQOL and evaluated group differences in school days missed and days sick in bed and needing care. HRQOL was measured with the PedsQLtrade mark 4.0 Generic Core Scales (Physical, Emotional, Social, and School Functioning). The PedsQLtrade mark was administered in outpatient pediatric gastroenterology clinics in California, Texas, and New Jersey. A total of 287 families (280 child self-report, 286 parent proxy-report) with children diagnosed with IBS (n = 123), FAP (n = 82), or organic GI disorders (n = 82) participated. Pediatric patients with IBS demonstrated significantly lower Physical, Emotional, Social, and School Functioning in comparison to healthy children, and comparable HRQOL to patients with FAP and organic GI diagnoses. GI symptoms were significantly associated with generic HRQOL. Patients with IBS demonstrated a significantly greater number of days missed from school, days sick in bed/too ill to play, and days needing someone to care for them than healthy children, but significantly fewer days than patients with FAP and organic GI disorders. Pediatric patients with IBS demonstrated impaired HRQOL in dimensions measuring Physical, Emotional, Social, and School Functioning. These findings suggest the need for targeted interventions to address these dimensions of impaired HRQOL.     

Visceral hyperalgesia in children with functional abdominal pain.

OBJECTIVE: Our purpose was to evaluate visceral sensitivity and psychologic profiles in children with functional gastrointestinal disorders. STUDY DESIGN: We measured visceral perception in the stomach and in the rectum by using an electronic barostat. Psychologic questionnaires were completed. Ten children with recurrent abdominal pain (RAP)(8 female, mean age 11.3 +/- 0.8 years), 10 children with irritable bowel syndrome (IBS) (8 female, mean age 13.0 +/- 0.9 years), and 15 control children (8 female, mean age 12.7 +/- 1.2 years) completed the study. RESULTS: Thresholds for visceral perception in the rectum were decreased in patients with IBS (P <.001 vs control patients) and in patients with RAP (P <.05 vs control patients). Children with IBS had lower thresholds than children with RAP (P <.01). In contrast, thresholds for perception were decreased in the stomach of children with RAP (P <.005 vs control patients) but not in children with IBS. There were elevated anxiety scores in 45% of patients. Duration of symptoms was associated with higher scores of anxiety (P <.001) and depression (P <.02). CONCLUSIONS: Hyperalgesia was demonstrated in children with RAP and IBS; sites of hyperalgesia appear to be associated with different symptom phenotypes; anxiety was common, and there was an association between the duration of symptoms and increased scores for both anxiety and depression.     

Challenges in management of irritable bowel syndrome in children

Irritable bowel syndrome (IBS) is a common cause of recurrent abdominal pain (RAP) in children and can be a debilitating experience for both child and family. Organic causes of RAP symptoms such as celiac and inflammatory bowel diseases should be excluded before a diagnosis of IBS is made. Treatment consists of dietary manipulation, drugs, and stress management. Newer therapies may offer better control of symptoms with minimal side-effects. This article discusses the challenges faced by pediatricians in managing IBS and reviews management in the context of children from the Indian subcontinent.     

Serotonin, inflammation, and IBS: fitting the jigsaw together?

Unexplained diarrhoea is a frequent indication for gastroenterologic referral, and after full investigation the most common final diagnosis is irritable bowel syndrome (IBS). Some patients with IBS describe an acute onset of symptoms following infective gastroenteritis. Postinfective IBS affects 7% to 31% of individuals infected, and appears to be a nonspecific response to injury which has been reported following Salmonella-, Campylobacter-, and Shigella-related IBS. The strongest risk factor for developing postinfective IBS is severity of the initial diarrhoea illness, but toxigenicity of the infected bacteria, age <60 years, and female sex also are important risk factors. Adverse life events, hypochondriasis, and depression are also important, as is increased enteroendocrine cell and lymphocyte numbers in rectal biopsies. Postinfective IBS and IBS with diarrhoea without an infectious onset both show increased postprandial release of serotonin, whilst constipated patients show a depressed release. Several studies suggest impairment of the serotonin transporter in IBS, which in animal studies has been shown to occur following a range of inflammatory insults. Clinical conditions with an inflammatory basis, such as coeliac and Crohn disease, also are characterised by excess postprandial serotonin release. Several studies report evidence of low-grade inflammation in IBS with diarrhoea. However, reliable markers of low-grade inflammation that may predict response to serotonin antagonists or other anti-inflammatory agents remain a goal for future research.     

Approach to a Child with Functional Abdominal Pain

Functional abdominal pain (FAP) is one of the most common functional gastrointestinal disorders (FGIDs) of childhood. Only a minority of patients with FAP seek medical attention, often presenting to the primary care physician while symptoms are still evolving. The bio-psychosocial model of treatment not only aims to alleviate the illness symptoms but also identifies and remedies the psychological comorbidities and social factors that contribute to illness behavior. Many patients with a mild illness can be managed in the primary care setting. However those with chronic, severe, frequently relapsing, and disabling illness usually are referred to a pediatric gastroenterologist. One of the reason for referral is to exclude organic disorders such as peptic ulcer disease, celiac disease or inflammatory bowel disease which can present with chronic abdominal pain. Recent data suggest that psychological therapy is very effective in alleviating symptoms, a subset of patients may require dietary modification and medications as an adjunct to psychological treatment.     

The use of Lactobacillus GG in irritable bowel syndrome in children: a double-blind randomized control trial

OBJECTIVE: To determine whether oral administration of the probiotic Lactobacillus GG under randomized, double-blinded, placebo-controlled conditions would improve symptoms of irritable bowel syndrome (IBS) in children. STUDY DESIGN: Fifty children fulfilling the Rome II criteria for IBS were given Lactobacillus GG or placebo for 6 weeks. Response to therapy was recorded and collected on a weekly basis using the Gastrointestinal Symptom Rating Scale (GSRS). RESULTS: Lactobacillus GG was not superior to placebo in relieving abdominal pain (40.0% response rate in the placebo group vs 44.0% in the Lactobacillus GG group; P=.774). There was no difference in the other gastrointestinal symptoms, except for a lower incidence of perceived abdominal distention (P=.02 favoring Lactobacillus GG). CONCLUSIONS: Lactobacillus GG was not superior to placebo in the treatment of abdominal pain in children with IBS but may help relieve such symptoms as perceived abdominal distention.     

The use of dietary fiber in the management of simple, childhood, idiopathic, recurrent, abdominal pain. Results in a prospective, double-blind, randomized, controlled trial

Recurrent abdominal pain (RAP) affects 10% to 18% of school-age children and is caused by obvious organic pathology in fewer than 10% of cases. Two recent studies do not support previous beliefs that most RAP is psychogenic. Studies have shown disorders of bowel motility in children with RAP similar to those of adult irritable bowel syndrome (IBS); controlled trials of additional dietary fiber in adult IBS have shown beneficial results. We did a randomized, double-blind, placebo-controlled study in 52 children with RAP and demonstrated a clinically and statistically significant decrease in pain attacks (at least 50% fewer) in almost twice as many children who were given additional fiber as placebo. Compliance was excellent in both groups and side effects were few. Although the cause of RAP is poorly understood, it is hypothesized that the beneficial effect of added fiber is due to its effect on shortening transit time, as in IBS.     

Brain-gut axis: from basic understanding to treatment of IBS and related disorders

The present review describes advances in understanding the mechanisms and provide an update of present and promising therapy directed at the gut or the brain in the treatment of irritable bowel syndrome (IBS). The diagnosis of IBS typically is based on identification of symptoms, such as the Rome III criteria for IBS in adults and children. The criteria are similar in children and adults. The focus of the present review is the bowel dysfunction associated with IBS.     

Modifications of intestinal permeability during food provocation procedures in pediatric irritable bowel syndrome

An intestinal permeability test analyzing the differential urinary elimination of lactulose and mannitol orally ingested at the same dosage was carried out first in fasting condition, then combined with specific food ingestion, in 17 children with clinical symptoms of irritable bowel syndrome (IBS). Foods were selected based on a suggestive clinical history or on a positive radioallergosorbent or prick test. Comparison of the results with those of a control population reported in a previous study showed that in nine IBS patients, specific food ingestion was associated with a modification of intestinal permeability. The nine children all had a personal and/or familial history of allergy and/or raised total IgE. The symptoms disappeared in the nine patients after food exclusion either alone (seven patients) or together with further treatment by cromolyn (two patients). We conclude that, at least in some children, symptoms of IBS may be related to food hypersensitivity.