Irritable Bowel Syndrome

Rome IV. Diagnostic criteria a for irritable bowel syndrome

Must include all of the following

1. Abdominal pain at least 4 days per month over at least 2 months associated 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 not resolve with resolution of the constipation (children in whom the pain resolves have functional constipation, not IBS)

3. After appropriate evaluation, the symptoms cannot be fully explained by another medical condition

aCriteria fulfilled for at least 2 months prior to diagnosis

From Hyams JS, DiLorenzo C, Saps M, Shulman R, Staiano A, van Tilburg M. Functional disorders: Children and adolescents. Gastroenterology. 2016 Feb 15. pii: S0016-5085(16)00181-5, with permission

In addition to clinical criteria for the diagnosis of IBS, the Rome IV working groups have furthermore delineated 4 pediatric-IBS subtypes analogous to adults based on stool form: IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), mixed IBS (IBS-M), and un-subtyped IBS (IBS-U) [70, 71]. Studies suggest that IBS-C is the most prevalent subtype (45 %), followed by IBS-D (26 %) with up to 24 % of children with IBS changing subtype within 1 year of diagnosis [2]. Subclassification may help practitioners select more targeted therapies in clinical practice, with the caveat that symptoms may change over time and classification may not be firm. Recent data suggest that the Bristol Stool Form Scale (BSFS ), which is frequently used to aid in subclassification, may not be able to accurately identify different stool types in children 6–17 years of age even if made more child friendly [72]. The modified pediatric BSFS, which reduces stool categories from 7 to 5, has been shown to have higher inter- and intra-rater reliability in children, in addition to being reliable and valid in younger children ages 6 and 7 even if the descriptors were read to them [73, 74]. Additional supporting symptoms not required to make the diagnosis of IBS but commonly observed include abnormal stool frequency, straining, urgency, gas bloat, passage of mucus, and sensation of incomplete evacuation. IBS has also been associated with other gastrointestinal, somatic, and psychological symptoms including upper gastrointestinal complaints (e.g., dyspepsia), fibromyalgia, headache, backache, genitourinary symptoms, anxiety, depression, and poor school performance [75].

Clinical Evaluation

If the practitioner highly suspects IBS based on gastrointestinal complaints that meet Rome IV criteria (Table 37.1), and the patient exhibits no alarm signs as listed in Table 37.2, specificity for IBS is high, the diagnostic yield of further testing is generally low, and no further testing is required. Functional constipation should be differentiated from IBS-C based on a careful history and physical examination and if present, should be treated appropriately. Similarly, excessive fructose and sorbitol intake may mimic IBS-D. Unnecessary testing performed to obtain negative results increase the fear that a diagnosis is being missed and therefore should be avoided [76]. Screening for giardia should be considered in children from endemic areas [77]. It is unclear whether the prevalence of celiac disease is higher in children with IBS; a study from Italy reported a prevalence of 4 % in children with IBS compared to 1 % in the general population, whereas other studies show no increased risk [78]. There are data however, suggesting that screening for celiac disease in patients presenting with IBS symptoms may be cost effective [79, 80]. A differential diagnosis for conditions that may present similarly to IBS is provided in Table 37.3. Alarm signs may not differentiate organic disease from functional disorders, but evidence suggests that the greater the number of alarm signs present, the higher the likelihood of organic disease [8184]. The presence of hematochezia, anemia, and weight loss in the same patient was shown to be highly predictive of Crohn’s disease [81]. If any red flags are raised, initial laboratory tests to consider that are focused, relatively inexpensive, and readily available include a complete blood count, erythrocyte sedimentation rate, C-reactive protein, serum aminotransferases and albumin, urinalysis, and celiac serologies. Fecal calprotectin is being frequently utilized as a noninvasive screen for intestinal mucosal inflammation and may be superior to C-reactive protein [85]. Normal fecal calprotectin levels make inflammatory bowel disease unlikely [86]. The need for other diagnostic testing such as abdominal imaging, breath tests, and endoscopy will depend on the clinical judgment of the practitioner.

Table 37.2
Alarm features in children and adolescents with abdominal pain and abnormal stool pattern

• Gastrointestinal bleeding

• Perirectal disease

• Fever

• Arthritis

• Persistent vomiting

• Persistent right upper or right lower quadrant pain

• Dysphagia

• Involuntary weight loss

• Nocturnal symptoms

• Family history of inflammatory bowel disease, celiac disease, and peptic ulcer disease

• Growth failure/pubertal delay

From Rasquin A, Di Lorenzo C, Forbes D, et al. Childhood functional gastrointestinal disorders: Child/adolescent. Gastroenterology. 2006;130(5):1527–1537, with permission

Table 37.3
Differential diagnosis of chronic abdominal pain and abnormal stool pattern

Celiac disease

Carbohydrate malabsorption

Inflammatory bowel disease

Lymphocytic/collagenous colitis

Small intestinal bacterial overgrowth


Iatrogenic (e.g., medications)


There are many approaches to the treatment of IBS involving medications, dietary manipulations, and behavioral and physical therapies. An effective treatment plan is often multifaceted and should be individually tailored and symptom directed. It must be noted that data in the pediatric literature to support the evidence-based use of any particular treatment strategy for IBS are sparse. Most therapeutic strategies are empiric and/or are extrapolated from adult studies or from studies of recurrent abdominal pain rather than irritable bowel syndrome specifically as defined by Rome criteria.

The cornerstone of successful treatment of IBS is an effective physician–patient–family relationship based on validation of pain complaints, education, and ongoing support and reassurance for the patient and family members. Realistic goals of therapy are not necessarily to eliminate symptoms, but rather to optimize patient function, quality of life, school attendance, and extracurricular participation through a biopsychosocial approach. These goals may be achieved by alleviating symptoms using appropriately selected pharmacologic and non-pharmacologic approaches, while at the same time identifying and addressing psychological comorbidities and social factors that contribute to illness behavior. In order to set realistic expectations, goals of treatment should be made clear with the patient and family from the start. Pharmaceutical and non-pharmaceutical approaches for the treatment of IBS are shown in Table 37.4.

Table 37.4
Therapeutic approaches to irritable bowel syndrome


 • Antispasmodics

 • Antidepressants

 • Probiotics

 • Antibiotics

 • Melatonin

 • Chloride channel agonists

 • 5-HT targets (investigational in children)

 • Guanylate cyclase receptor agonists (investigational in children)

 • Eluxadoline (pediatric data lacking)

 • Miscellaneous agents (loperamide, laxatives, antacids)


 • Limiting possible “triggers”

 • Increased fiber

Behavioral approaches

 • Cognitive behavioral therapy

  – Psychotherapy

  – Hypnotherapy

  – Guided imagery

Physical therapies

 • Massage

 • Acupuncture

 • Reflexology

 • Yoga


Antispasmodic s

Anticholinergic medications such as dicyclomine and hyoscyamine may produce symptom relief through inhibition of smooth muscle contraction. Despite their common use in clinical practice, pediatric studies are lacking and adult studies have not found clear efficacy [87, 88]. Anticholinergic side effects may include constipation, dry mouth, and urinary retention. Evidence has also been conflicting for the use of peppermint oil whose active ingredient, menthol, is thought to produce smooth muscle relaxation in the ileum and colon via calcium channel blocker properties. While less rigorous and/or smaller studies have yielded positive results for its use in the treatment of IBS [8992], including one pediatric-specific study [93], other larger studies do not show efficacy [94]. However, despite a dearth of convincing evidence, peppermint oil is becoming more commonplace for the treatment of IBS likely secondary to its relatively favorable side effect profile and role as a “natural” remedy. Possible side effects of peppermint oil include rectal and esophageal burning.


The mechanism of action of antidepressant medications for the treatment of IBS is not fully understood; it is likely complex, involving multiple targets on the brain–gut axis. Studies have suggested that benefit in IBS may be due to a combination of their psychotropic, neuromodulatory, and analgesic properties [9598]. In the adult literature, there is strong evidence showing the benefit of tricyclic antidepressants (TCA) on IBS symptoms, particularly for IBS-D [99101]. In pediatrics, the data are limited and somewhat conflicting. One recent trial of amitriptyline for the treatment of IBS in teenagers showed overall improvement [102], whereas another recent study in a pediatric population demonstrated that amitriptyline and placebo offer similar benefit [103]. In the adult literature, there is a limited body of evidence for the use of selective serotonin reuptake inhibitors (SSRIs) in the treatment of IBS particularly for IBS-C [95, 101, 104, 105]. However, there are no large studies for the use of SSRIs in children with IBS. In neither adult nor pediatric literature are there head-to-head trials comparing SSRIs and TCAs for use in IBS. In children with severe symptoms, especially associated with low mood, flat affect, antidepressants such as low dose amitriptyline may be necessary. Side effects for TCAs and SSRIs include fatigue, dizziness, headaches, cardiac dysrhythmias, and worsening depression. Constipation may be a side effect of TCAs, and diarrhea may be a side effect of SSRIs. Therefore, TCAs may be considered for use in IBS-D and SSRIs for IBS-C. Due to the potential side effect of cardiac dysrhythmias with TCAs and SSRIs, a baseline EKG should be considered prior to initiating therapy and dose increments. Patients on antidepressant medications must be monitored carefully for signs of depression and suicidal ideations (see Chap. 6).


Evidence suggests that enteric flora is a regulator of mucosal inflammation and immunity, and derangements of enteric flora may contribute to IBS symptoms. [45, 46] Probiotics, which are live microorganisms capable of inducing a beneficial effect in the host, are postulated to alleviate IBS symptoms via restoration of the normal enteric flora and downregulation of mucosal inflammation. Various strains of probiotics have been studied in adults with IBS yielding mixed results. Some trials have shown benefit for the use of certain Bifidobacterium, Saccharomyces, and Lactobacillus strains and VSL #3 and mixed strains of probiotics in IBS-D [61, 106111], while others report negative results [112116]. Pediatric-specific studies are becoming available but the results are conflicting. While some studies of children with IBS found a modest benefit for the use of Lactobacillus GG in IBS [117, 118], a different pediatric study found that Lactobacillus GG was not superior to placebo [119]. Later, a recent meta-analysis of these studies found lactobacillus rhamnosus GG to be effective in IBS [120]. Another crossover trial evaluating VSL#3 was found the probiotics to be safe and more effective than placebo in ameliorating symptoms and improving the quality of life in children affected by IBS [121]. Thus, even though the role of probiotics for the treatment of IBS in pediatrics remains uncertain due to heterogeneous data, there seems to be a benefit for the use of Lactobacillus rhamnosus GG and VSL#3 in children with the IBS-D phenotype. In addition, the lack of quality control/quality assurance with respect to the type and number of live organisms found in the myriad probiotic products sold over the counter poses an additional challenge for their therapeutic use.


With some evidence suggesting that small intestinal bacterial overgrowth (SIBO) may play a role in IBS [60], the use of antibiotics for the treatment has been investigated. Several small, short-term studies have demonstrated symptomatic improvement in adult patients with IBS treated with a course of metronidazole [122] or the nonabsorbable antibiotics rifaximin [123126]. Two large, identically designed randomized controlled trials demonstrated efficacy of rifaximin when compared to placebo in adults with IBS-D and its benefits persisted for up to 10 weeks following cessation of treatment [127, 128]. The most common side effects reported were nausea and increase in alanine aminotransferase (ALT). Based on the results from these studies, the U.S. Food and Drug Administration (FDA) recently approved rifaximin for the treatment of IBS-D in adults. Although similar trials in the pediatric population are lacking, a prospective study of children with IBS who also had an abnormal breath test at enrollment reported improvement in abdominal pain after a 1 week course of rifaximin only in those who had a negative lactulose breath test after treatment [63]. Large, well-designed pediatric trials are necessary to establish a definitive role for antibiotics in the treatment of IBS in children.


Melatonin is a sleep-promoting hormone primarily secreted by the brain. It has more recently been shown to be produced in the gastrointestinal tract as well, and although the mechanism remains unclear, recent investigation suggests that melatonin secretion and metabolism may be involved in the pathogenesis of IBS [129131]. A recent randomized controlled study found improvements in pain scores and stooling patterns to correlate with higher early morning salivary melatonin levels in males with the use of VSL#3 [132]. Other studies have shown that administration of exogenous melatonin may have a beneficial role in IBS independent of its effect on sleep [133135]. Melatonin is a relatively safe drug that may play a role in the management of IBS due to its antinociceptive effect [136].

Chloride Channel Agonists

Lubiprostone, a bicyclic fatty acid prostaglandin E2 derivative, stimulates type 2 chloride channels in the intestine to increase fluid secretion and transit thereby improving symptoms of constipation. Lubiprostone has been US FDA approved for the treatment of adults with chronic idiopathic constipation since January 2006 and for the treatment of IBS-C in adult females since April 2008. A 2009 combined analysis of 2 phase 3, randomized, placebo-controlled studies demonstrated a higher response rate for lubiprostone compared with placebo in predominantly adult females with IBS-C [137]. An extension study of patients who had completed the abovementioned trials reported significant improvements in symptoms at 52 weeks of treatment [138]. Reported side effects of lubiprostone are diarrhea, nausea, headache, and abdominal distension. Pediatric data for lubiprostone are limited and mostly available in abstract form.

5-Hydroxytryptamine (5-HT) Targets

5-HT (serotonin) is a neurotransmitter found in the gut thought to mediate gastrointestinal sensorimotor function. Recent research investigating the role of 5-HT in the pathophysiology of IBS has shown altered 5-HT signaling in the digestive mucosa [23]. As such, alosetron, a 5-HT3 receptor antagonist, and tegaserod, a 5-HT4 partial agonist, have been shown to be effective in the treatment of adults with IBS-D and IBS-C, respectively [139141]. Alosetron appears to decrease visceral sensation, prolong and reduce postprandial motility, increase colonic compliance, and enhance small bowel water and salt absorption slowing down transit time [142]. Tegaserod may increase gastrointestinal motility and alter visceral sensitivity. Alosetron, released in the year 2000, and tegaserod, released in 2002, were subsequently withdrawn from the market shortly thereafter secondary to an association with ischemic colitis and serious adverse cardiovascular events, respectively. In the United States currently, alosetron is available for the treatment of IBS-D through restricted marketing. Ramosetron, a novel 5-HT3 antagonist was shown to provide global relief of IBS-D symptoms more frequently and effectively than with placebo in four adult randomized controlled trials [143146]. Even though there was no reported incidence of ischemic colitis or severe constipation, long-term data on the safety profile of ramosetron is currently lacking. Prucalopride, a newer 5-HT4 agonist, is also being studied in adults, mostly for chronic constipation [147]. Pediatric data on 5-HT targets is currently lacking.

Guanylate Cyclase Receptor Agonists

Linaclotide is a peptide agonist of guanylate cyclase-C, the receptors for which are located on the luminal aspect of the enterocytes [147]. In animal studies, linaclotide has been found to stimulate intestinal fluid secretion and transit and decrease visceral hypersensitivity [148]. Several large phase IIB and III trials have shown potential benefit for constipation and IBS-C and linaclotide recently was approved by the US FDA for these indications [149151]. A head-to-head comparison using placebo-controlled model inputs found linaclotide to have higher treatment response rates and lower per-patient costs compared to lubiprostone [152]. Safety and efficacy of linaclotide have not been established in patients younger than 18 years and a black box warning exists for its use in children 6 and younger.


Eluxadolin e, a mixed μ-opioid receptor agonist, δ-opioid receptor antagonist, and a k-opioid agonist, was recently US FDA approved for the management of IBS-D in adults. The safety and efficacy of Eluxadoline was established in two double-blind, placebo-controlled clinical trials in which the drug was more effective in reducing abdominal pain and improving stool consistency than placebo over 26 weeks of treatment [153, 154]. The most common side effects in patients in the treatment arm were constipation, nausea, and abdominal pain, whereas serious side effects included sphincter of Oddi spasm and pancreatitis. Pediatric data are currently lacking.

Other symptom-targeted agents that are often used in patients with IBS include loperamide for the treatment of associated diarrhea and various laxatives (e.g., polyethylene glycol 3350) for the treatment of constipation. Antacids, promotility agents (e.g., metoclopramide, erythromycin), and antiemetics are used to target nausea and dyspepsia.

Dietary Approaches


Dietary supplementation with fiber is often used as a first-line approach in patients with IBS-C, particularly in the primary care setting, but its use is controversial [155]. Fiber is postulated to shorten intestinal transit time, thereby alleviating constipation and decreasing intracolonic pressure. Adult studies have shown that fiber may improve both constipation and diarrhea associated with IBS but not pain alone, and this was reflected in a recent randomized, double-blinded pediatric pilot study on guar gum [156159]. Psyllium may reduce pain frequency in children with IBS. On the contrary, evidence suggests that insoluble fiber, in particular, may actually worsen pain in IBS due to increased gas bloat [158]. Therefore, limited data on the use of fiber in recurrent abdominal pain in children do not suggest clear benefit [160, 161].

Elimination Diet

Many patients perceive their IBS to be triggered by food [162, 163] and often want to discuss the role of food in their condition. As mentioned earlier, composition of the diet can induce symptoms in IBS. A diet eliminating fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) has been shown to be of benefit in adults, especially in the IBS-D subtype [164]. Various meta-analyses, systemic reviews, and randomized control trials in adults support the use of a low FODMAP diet [165167]. Furthermore, dietitian-led FODMAP group education was found to be clinically and cost effective [168]. In a pilot double-blind crossover trial, children with IBS who were placed on a low FODMAP diet had improvements in both pain frequency and severity in addition to lesser pain-related interference with activities. Stool microbiota and metabolites differed between responders and nonresponders, suggesting the role of diet in the pathogenesis of IBS [169]. Although the FODMAP-restricted diet may be effective in short-term management of selected patients with IBS, pediatric data on long-term consequences are lacking. Other commonly identified dietary offenders are milk, wheat, eggs, and coffee. Given the difficulty for patients in maintaining elimination diets and the risk of imbalanced nutrition particularly in the pediatric population, further studies are needed to validate dietary elimination as a treatment for IBS.

Oral serum-derived bovine immunoglobulin/protein isolate (SBI) was recently evaluated as nutritional therapy for adults with IBS-D in a randomized, double-blind, placebo-controlled trial [170]. A dose of 5–10 g/day was well tolerated and resulted in improvements in both symptom days and daily symptom scores. Additional studies with larger numbers of subjects are needed to validate these findings. Pediatric studies evaluating SBI in IBS-D are ongoing.

There have been several recent studies linking IBS with higher food-specific IgG levels [171, 172] and positive skin prick testing [173], suggesting a potential role for directed food elimination in the treatment of IBS. However, this association is currently weak, and further investigation is therefore needed.

Psychological Therapies

Techniques used by therapists may include psychotherapy, guided imagery, progressive muscle relaxation, and gut-directed hypnotherapy, with the aim of developing symptom coping skills. Two pediatric-focused systemic reviews of psychological interventions (including cognitive behavioral therapy) concluded that such therapies were slightly superior to usual care [174, 175]. Since then, several pediatric studies have shown the effectiveness of cognitive behavioral therapy for treatment of functional gastrointestinal disorders, including IBS, with evidence of long-term efficacy, although one trial showed no benefit [176180]. Gut-directed hypnotherapy was found to be beneficial in two randomized control trials [181, 182]. Treating coexisting anxiety and depression may be of additional benefit [183] (see Chap. 6).

Physical Therapies

Although massage therapy, acupuncture, yoga exercises, and reflexology have been proposed as potential treatments for IBS, there is only limited evidence to support their use.


Irritable bowel syndrome (IBS) is a commonly encountered pediatric functional gastrointestinal disorder with varying clinical presentations. Multiple mechanisms likely contribute to its development and may include visceral hypersensitivity, altered gastrointestinal microbiota, mucosal immune activation, psychiatric disorders and cerebral activation, and altered gastrointestinal motility. The recently refined pediatric Rome (IV) criteria are more inclusive than adult criteria with respect to duration of symptoms and aid in diagnosis while avoiding exhaustive, low-yield medical testing. Although a myriad of therapeutic options are available for the treatment of IBS including medications, dietary manipulations, and behavioral and physical therapies, convincing evidence-based pediatric data to support any particular treatment modality is sparse. An effective management strategy is often multifaceted and should be individually tailored and symptom directed. Previous studies have demonstrated a particularly high placebo rate for the treatment of IBS [184], suggesting that with a strong physician–patient–family relationship, patients will improve regardless of the treatment approach. Future research in IBS will continue to focus on the pathophysiology of this disorder and on the discovery of more targeted therapies. Lastly, pediatric trials investigating the safety and effectiveness of therapies approved in adult IBS are warranted.



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Aug 29, 2017 | Posted by in GASTROENTEROLOGY | Comments Off on Irritable Bowel Syndrome

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