Materials for practical classes for 4-years student
Irritable Bowel Syndrome
Background
Irritable bowel syndrome (IBS) is defined as chronic or recurrent abdominal pain, altered bowel habits, and bloating, with the absence of structural or biochemical abnormalities to explain these symptoms. IBS is part of a broader group of disorders known as functional gastrointestinal disorders. It is the most common gastrointestinal diagnosis among gastroenterology practices in the United States and is one of the top 10 reasons for visits to primary care physicians. IBS is recognized in children, and many patients trace the onset of their symptoms to childhood. Children who have a history of recurrent abdominal pain are at increased risk of IBS during adolescence and young adulthood.
Pathophysiology
IBS has no identifiable cause, and laboratory testing is unrevealing. Over the last 5 decades, the understanding of IBS has evolved from a disorder of motor activities in the upper and lower gastrointestinal tracts to a more integrated understanding of visceral hypersensitivity and brain-gut interaction.
Gastrointestinal motility abnormalities
Studies evaluating the motor response of the colon to meals, pain, and stress suggest a difference between control subjects and patients with IBS. Pretreatment with anticholinergic medication in IBS was demonstrated to reduce meal-stimulated pain and diarrhea. The finding of an abnormal, 3-cycle-per-minute, slow-wave activity in the colon of patients with IBS was not confirmed by other studies and was noted in some individuals without IBS.
Abnormal small-bowel motility has also been reported by some investigators. Intestinal transit has been demonstrated to be delayed in patients with constipation-predominant IBS. In contrast, the transit was accelerated in patients with diarrhea-predominant IBS. Clustered contractions in the duodenum and jejunum and prolonged propagated contractions in the ileum were noted more frequently in patients with IBS. Small-bowel motility studies have demonstrated more abnormal findings in patients with IBS in conscious states than during sleep, suggesting that the condition may result in part from CNS input.
Nongastrointestinal smooth-muscle abnormalities
Bladder dysfunction was identified in 50% of patients with IBS and in only 13% of control subjects. One study found patients with IBS to have a higher incidence of orthostatic hypotension. A clinical study demonstrated a greater reduction of forced expiratory volumes in 1 second (FEV1) induced by methacholine in patients with IBS than in control subjects.
Visceral hypersensitivity
Most patients with functional disorders appear to have inappropriate perception of physiologic events and altered reflex responses in different gut regions. Patients with IBS undergoing balloon distension studies of the colorectum demonstrated awareness of distension and pain at pressures and volumes that were significantly lower than in control subjects. The development of chronic hyperalgesia within the gastrointestinal tract can be explained by the development of hyperexcitability of neurons in the dorsal horn in response to peripheral tissue irritation or to descending influences from the brain stem. Multiple factors are proposed to alter neuroreceptors and afferent spinal neuron functions. These factors include genetic, inflammatory, local nerve mechanical irritation, motility, and psychological factors.
Brain-gut interaction
The brain-gut axis is a bidirectional pathway that links higher cortical centers with visceral afferent sensation and intestinal motor function. Regulation of these connections occurs via numerous neurotransmitters found in the brain and gut, including cholecystokinin, vasoactive intestinal peptide, substance P, 5-hydroxytryptamine (5-HT), and many others. These transmitters act at different sites in the brain and gut and lead to varied effects on gastrointestinal motility, pain control, emotional behavior, and immunity. The 5-HT receptors are implicated in the mechanisms controlling gastrointestinal functions.
Dysregulation of the brain-gut system is becoming an acceptable theory to explain the functional gastrointestinal disorders. Furthermore, several studies have hypothesized that specific 5-HT receptor antagonists may be beneficial in IBS. Recently, a number of newer noninvasive imaging techniques (eg, positron emission tomography, functional MRI) have been applied to assess brain-gut interactions in healthy patients and in those with IBS.
Psychosocial factors in irritable bowel syndrome
Numerous studies have found an increased prevalence of abnormal psychiatric disorders, including anxiety, major depression, personality disorders, and hysteria, in adult patients with IBS, especially patients referred to medical facilities. These psychological disturbances are not believed to cause or induce the symptoms of IBS, but they are thought to influence the patient's perception of the symptoms and affect the clinical outcome. Stressful events are known to affect gastrointestinal functions and may lead to exacerbation of symptoms in patients with IBS. In addition, antidepressant or antipsychotic therapy is helpful in some patients with IBS. A recent meta-analysis has confirmed the relative efficacy of antidepressant medications in irritable bowel syndrome, particularly in predominantly diarrheic patients experiencing severe pain. Recent studies have reported an increased frequency of prior sexual or physical abuse in patients with IBS and other functional gastrointestinal disorders.
Dietary factors
Some studies have proposed that carbohydrate intolerance may produce significant symptoms in patients with IBS. Ingestion of lactose, sorbitol, or fructose is associated with increased gastrointestinal symptoms. Likewise, a food allergy may play a minor role in triggering or exacerbating symptoms in some patients with IBS.
Gastrointestinal infection and irritable bowel syndrome
Some investigations found a correlation between the development of IBS and a prior severe gastrointestinal infection, especially in patients with higher scores for anxiety. Symptoms compatible with IBS will affect 10-15% of patients after acute infectious gastroenteritis. Recent studies have demonstrated low-grade lymphocytic infiltration in the intestinal mucosa, increased permeability, and increases in inflammatory components including enterochromaffin and mast cells.
Some studies have shown that small intestinal bacterial overgrowth is common in subjects with IBS. A double-blind placebo-controlled study by Pimentel et al (2003) showed that normalization of lactulose breath testing with neomycin correlated with symptom improvement in patients with IBS.
Frequency
United States
Symptoms consistent with IBS are present in 10-20% of adolescents and adults. Less than one third of patients seek medical advice. In the pediatric population, IBS symptoms are reported in 14% of high school students and 6% of middle school students. One third of patients with IBS trace their symptoms to childhood.
International
Prevalence in developing countries is probably lower than in Western countries, but this may be explained by a combination of reduced availability of medical care and different cultural approaches to illness.
Mortality/Morbidity
IBS is not a life-threatening condition, but it can have a serious impact on a patient's daily activities and quality of life. Greater impairments in quality of life are reported in patients with IBS who sought medical care compared to those who did not consult their physicians for IBS symptoms. It is a major cause of absenteeism at the workplace and at school. Abdominal pain in patients with IBS is responsible for significant school absences in 4-5% of middle and high school students.
Race
IBS is not well characterized outside Western countries. According to reported studies, the disease prevalence is lower in Hispanic and Asian populations than in Caucasian populations, and whites are more likely to have IBS than blacks.
Sex
Women are 2-3 times more likely than men to have IBS.
In pediatric patients, both sexes are affected equally.
Age
IBS is a disorder of young people. One half of patients experience symptom onset when younger than 35 years, and 40% of patients are aged 35-50 years when symptoms begin.
IBS is recognized in children. Symptoms consistent with IBS are reported in 16% of students aged 11-17 years.
IBS is not described in preschool-aged and younger children because the diagnosis depends on the child's ability to report detailed symptoms.
Clinical
History
IBS has a broad range of symptoms; the most common are abdominal pain and altered bowel movements. Although symptoms may vary among patients, a pattern usually develops for each patient. The presence of characteristic symptoms in an otherwise healthy individual is sufficient to make a diagnosis of IBS in most individuals.
The characteristics of abdominal pain vary between patients and even within an individual patient.
The pain can be dull, achy, colicky, or sharp.
Pain can occur anywhere in the abdomen but is commonly located in the hypogastric or periumbilical regions.
The pain has no specific pattern but may be aggravated by stress and food and partially relieved after defecation.
Altered bowel habits include constipation, diarrhea, or alternating constipation with diarrhea.
Stools usually are of small volume and pasty. Constipation is associated with small, hard, pelletlike stools. Diarrhea characteristically occurs during waking hours and often is precipitated by meals.
Mucus can be a component of the stool in as many as 50% of patients with IBS.
In some patients, defecation is associated with a sense of incomplete evacuation that can lead to repeated trips to the bathroom and prolonged straining.
Symptoms of abdominal distension (ie, bloating, increased belching, flatulence) frequently are reported by patients with IBS. They are less common in children than adults.
Other gastrointestinal symptoms (ie, heartburn, dyspepsia, nausea, vomiting) are reported in 25-50% of adult patients with IBS. Dyspeptic symptoms are present in as many as 30% of pediatric patients with IBS.
Extraintestinal symptoms are also reported. Patients with IBS frequently report dysmenorrhea, urinary frequency, incomplete bladder emptying, back pain, and headache. These complaints are common in adults but rare in children.
Patients may relate a history of inciting events.
Exacerbation of IBS symptoms is sometimes reported to follow stressful experiences, ingestion of specific foods, or consumption of alcohol or caffeine.
Menses may exacerbate IBS symptoms in women.
In children, symptom precipitants include school-related problems, overeating, or eating problems.
The following clinical features should alert the physician to the possibility of a disorder other than IBS:
Frequent awakening by symptoms
Steady progressive course
Fever
Weight loss
Arthritis
Rectal bleeding
Persistent vomiting
The diagnosis of IBS requires the identification of the symptoms characteristic of IBS and the exclusion of other medical conditions with similar clinical presentations. Symptom-based criteria have been established for the diagnosis of IBS, which includes the Manning or, more recently, the Rome criteria. The pediatric working team adopted the Rome II criteria in the adult population because these criteria seemed to apply equally well to children. Rome II criteria apply to children old enough to provide an accurate pain history of at least 12 weeks, which need not to be consecutive, in the preceding 12 months. The history can include the following:
The abdominal discomfort or pain has 2 out of 3 features, ie, (1) relief with defecation, (2) onset associated with a change in frequency of stool, and (3) onset associated with a change in the form of stool.
No structural or metabolic abnormalities exist to explain the symptoms.
Physical
Physical examination findings generally are unremarkable. The patient may appear tense and anxious with sweaty palms. Abdominal tenderness may be present. Tender and palpable sigmoid is found in some patients.
Findings against the diagnosis of IBS include the following:
Abdominal rigidity
Rebound tenderness
Lymphadenopathy
Hepatosplenomegaly
Positive fecal bleeding test result
Causes
IBS has no identifiable cause (see Pathophysiology).
Laboratory Studies
No specific laboratory markers exist for IBS. Patients who have characteristic symptoms and meet the Rome criteria for IBS (see History) do not require a thorough diagnostic evaluation. A more aggressive approach is recommended for individuals with atypical symptoms, those with a rapidly progressive course, or when the index of suspicion for an organic disease is high.
In classic cases, a limited screen for organic disease is reassuring and should consist of the following:
Complete blood count
Erythrocyte sedimentation rate
Stool studies for ova and parasites
Stool cultures and stool Clostridium difficile toxin assay, if clinically indicated
A breath hydrogen test or a trial of dietary lactose restriction to exclude lactose intolerance
The following laboratory tests are indicated in special instances:
Lead level assessment
Celiac serologic tests
Serum immune markers for inflammatory bowel disease
Thyroid function tests
Tests for Helicobacter pylori (ie, serum antibody titers, urea breath test)
Imaging Studies
Plain abdominal radiography is recommended for patients with pain-predominant symptoms. Perform plain abdominal radiography during a pain episode to exclude intermittent obstruction.
Upper gastrointestinal study with small-bowel follow through is a useful study if Crohn disease or celiac sprue is suggested.
Barium enema can be useful for patients in whom Hirschsprung disease or congenital structural anomalies of the colon are suspected. Barium enema is also indicated in older patients (>50 y) because of the increased likelihood of colonic neoplasms.
Gastric scintigraphy is indicated for selected patients to evaluate for gastroparesis.
Abdominal ultrasonography is suggested for patients in whom biliary disease is suspected. It has high sensitivity and specificity for gallstones. It can also detect gallbladder wall thickening.
Other Tests
Gastrointestinal manometry can assist in evaluating patients in whom gastroparesis or intestinal pseudoobstruction is suspected.
Anorectal manometry is useful to screen patients in whom Hirschsprung disease is suspected.
Procedures
Sigmoidoscopy or complete colonoscopy is useful to evaluate for inflammatory conditions such as ulcerative colitis and microscopic colitis.
Upper endoscopy with small-intestinal biopsies is recommended in patients in whom peptic ulcer disease, Helicobacter pylori infection, Crohn disease, celiac disease, or other malabsorption conditions are suspected.
Treatment
Medical Care
IBS is a chronic illness and has no cure. Treatment may be challenging and even frustrating to the physician, the patient, and the patient's family. The most important component of treatment is to establish an effective and therapeutic relationship with the patient and his or her family. Educate the child and parents that IBS is a chronic illness that cannot be cured. At the same time, reassure them that it is not a life-threatening condition and it does not lead to physical impairment. Tell the patient and the family that the symptoms are real and respond to their worries and concerns. Reassurance is more effective if offered after a careful history and physical examination and a conservative diagnostic evaluation.
Most patients have mild symptoms and maintain normal daily activities and regular school attendance. Address the possible dietary and psychosocial triggering factors. Counseling, dietary modifications, and lifestyle changes usually are effective and sufficient for treatment.
A smaller proportion of patients have moderate-to-severe symptoms with some disruption of their activities and school performance. This group of patients may benefit from pharmacotherapy and behavioral treatment. Referral to a psychologist may be required.
Consultations
Consider further evaluation and a referral to a pediatric gastroenterologist if findings from the patient's history, physical examination, or screening laboratory tests are suggestive of organic disease.
Diet
Dietary modification
Some patients with IBS report exacerbation of their symptoms after ingestion of certain foods. Elimination of certain foods, such as sorbitol, fructose, and gas-forming legumes, achieves relief in some patients with IBS, especially those with excess gas. Attempt lactose restriction in patients with documented lactose malabsorption.
Foods associated with increased flatulence include onions, beans, celery, carrots, prunes, bananas, raisins, brussel sprouts, wheat germ, and bagels.
Fiber supplements
A high-fiber diet or supplement is useful in patients with constipation-predominant IBS. Several studies have demonstrated that fiber enhances water-retentive properties of stool, increases stool weight, and accelerates colonic transit.
In general, dietary fibers are less soluble and more effective as bulking agents, whereas synthetic fibers are more soluble and increase water retention.
The recommended daily intake of fiber (in grams) for children is estimated by adding 5 to their age in years.
Medication
Pharmacotherapy is recommended for patients with moderate-to-severe symptoms that cause disruptions in activity. Treatment is symptomatic and is directed at the most predominant symptom (eg, dietary fiber supplementation and stool softeners for constipation, antidiarrheals for diarrhea, smooth muscle relaxants for pain). A better understanding of the pathophysiology of IBS and the role of neurotransmitters and receptors involved in the gastrointestinal sensory and motor functions have provided opportunities for the development of newer therapeutic agents. The role of serotonin in the pathophysiology of IBS has drawn much attention, and agonists and antagonists at 5-hydroxytryptamine (5-HT) receptors have been approved for the treatment of subgroups of patients with IBS.
Antispasmodic and anticholinergic agents
These are the most frequently used medications (ie, hyoscyamine, dicyclomine) in the United States for the treatment of pain episodes in patients with IBS. Results from adult studies on the efficacy of these medications have provided conflicting data. The meta-analysis of the use of smooth muscle relaxants (eg, cimetropium, otilonium bromide, pinaverium, mebeverine, trimebutine) by Poynard et al showed efficacy over placebo in IBS. These drugs have calcium channel–blocking properties or antimuscarinic activities. No pediatric data exist with which to evaluate their efficacy or adverse effects.
Hyoscyamine (Levsin, Levbid)
Blocks action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and CNS, which in turn has antispasmodic effects.
Adult
Levsin: 0.125-0.25 mg (1-2 tab) PO/SL q4h prn; not to exceed 12 tab per d
Levbid: 0.375-0.75 mg PO bid
Pediatric
<2 years: 0.125-mg/mL gtt; repeat q4h PO prn
The following is an approximate dosage guide:
2.3 kg (5 lb): 3 gtt; not to exceed 18 gtt per d
3.4 kg (7.5 lb): 4 gtt; not to exceed 24 gtt per d
5 kg (11 lb): 5 gtt; not to exceed 30 gtt per d
7 kg (15 lb): 6 gtt; not to exceed 36 gtt per d
10 kg (22 lb): 8 gtt; not to exceed 48 gtt per d
15 kg (33 lb): 11 gtt; not to exceed 66 gtt per d
2-12 years: Use 1.25-5 mL of elixir (0.03125-0.125 mg) PO q4h prn; not to exceed 30 mL/d
The following is an approximate dosage guide:
10 kg (22 lb): 1.25 mL
20 kg (44 lb): 2.5 mL
40 kg (88 lb): 3.75 mL
50 kg (110 lb): 5 mL
>12 years: Administer as in adults
Dicyclomine (Bentyl)
Treats GI motility disturbances. Blocks action of acetylcholine at parasympathetic sites in secretory glands, smooth muscle, and CNS.
Reports show that administration of dicyclomine syrup in infants has been followed by serious respiratory symptoms, seizures, syncope, pulse rate fluctuations, and coma. Death has been reported.
20-40 mg PO qid; discontinue if not effective within 2 wk or if 80 mg qd is associated with adverse effects
Pediatric
<6 months: Contraindicated
>6 months to 2 years: 5-10 mg PO tid/qid 15 min ac; not to exceed 40 mg/d
>2 years to 12 years: 10 mg PO tid
>12 years: Administer as in adults
Antidiarrheal agents
These agents are used to treat diarrhea adjunctly with rehydration therapy to correct fluid and electrolyte depletion. They are usually helpful when diarrhea is the predominant symptom. Studies of the opiate agent loperamide show that it improves stool consistency, decreases stool frequency, and reduces abdominal pain. Cholestyramine acts by binding bile acids and can be helpful in some patients with IBS. Alosetron and tegaserod are 5-HT4 receptor partial agonists that bind with high affinity at human 5-HT4 receptors. The activation of 5-HT4 receptors in the gastrointestinal tract stimulates the peristaltic reflex and intestinal secretion and inhibits visceral sensitivity. In vivo studies showed that tegaserod enhanced basal motor activity and normalized impaired motility throughout the gastrointestinal tract. In addition, studies demonstrated that tegaserod moderated visceral sensitivity during colorectal distension in animals.
Tegaserod was temporarily withdrawn from the US market in March 2007; however, as of July 27, 2007, restricted use of tegaserod is now permitted via a treatment IND protocol. The treatment IND allows tegaserod treatment of irritable bowel syndrome (IBS) with constipation or chronic idiopathic constipation (CIC) in women younger than 55 years who meet specific guidelines. Its use is further restricted to those in critical need who have no known or preexisting heart disease.
Earlier this year, tegaserod marketing was suspended because of a meta-analysis of safety data pooled from 29 clinical trials that involved more than 18,000 patients. The results showed an excess number of serious cardiovascular adverse events, including angina, myocardial infarction, and stroke, in those taking tegaserod compared with placebo. In each study, patients were assigned at random to either tegaserod or placebo. Tegaserod was taken by 11,614 patients, and placebo was taken by 7,031 patients. The average age of patients in these studies was 43 years, and most patients (ie, 88%) were women. Serious and life-threatening cardiovascular adverse effects occurred in 13 patients (0.1%) treated with tegaserod; among these, 4 patients had a heart attack (1 died), 6 had unstable angina, and 3 had a stroke. Among the patients taking placebo, only 1 (0.01%) had symptoms suggesting the beginning of a stroke that went away without complication.
For more information, see the FDA MedWatch Product Safety Alert.
Loperamide (Imodium)
Synthetic opioid; does not have central nervous action in therapeutic doses. Acts by slowing intestinal motility and enhancing water and electrolyte absorption. Reduces diarrhea and pain in patients with diarrhea-predominant IBS.
Adult
2-12 mg/d PO divided bid/tid; necessary doses differ greatly between individuals
Pediatric
<2 years: Not recommended
>2 years: 0.08-0.24 mg/kg/d PO divided bid/tid; not to exceed 2 mg/dose
Cholestyramine (Prevalite, Questran)
Binds endogenous bile acids and can improve diarrhea in patients with unexplained diarrhea or idiopathic bile acid malabsorption.
Adult
3-4 g PO bid/qid mixed with fluid or food
Pediatric
240 mg/kg/d PO divided tid ac as slurry in water, juice, or milk
Antidepressant drugs
A number of studies have shown that TCAs (ie, imipramine, amitriptyline) can be useful in the treatment of IBS in some patients. In addition to their antidepressant effects, TCAs have neuromodulatory and analgesic properties, which can be achieved at lower doses than those required for treatment of depression. Because of their inhibitory effect on gut motor function, TCAs may benefit patients with IBS with predominant diarrhea or pain. TCAs particularly benefit patients with IBS who have well-defined depression or panic attacks.
Amitriptyline (Elavil)
Inhibits reuptake of serotonin and/or norepinephrine at presynaptic neuronal membrane, which increases concentration in CNS.
Adult
10-50 mg/d PO qhs; administered at lower doses than required for depression
Pediatric
0.2-0.4 mg/kg/d PO qhs
Laxatives and stool softeners
Can be useful in patients with constipation-predominant IBS. Osmotic laxatives (eg, magnesium hydroxide, lactulose, sorbitol) or stool lubricants (eg, mineral oil) are usually required for long-term therapy for children with moderate-to-severe constipation. Long-term studies have shown that these medications are safe and equally effective. Stimulant laxatives may be necessary intermittently and for short periods, but avoid prolonged use.
Mineral oil (Milkinol)
An emollient laxative that does not appear to have any pharmacologic action on the GI tract. Acts by lubrication. When taken for 2-3 d, penetrates and softens stool and may interfere with absorption of water. Generally is well tolerated and without major adverse effects. Onset of action is approximately 6-8 h. Indigestible; limited absorption.
Prognosis
IBS is a chronic disorder that cannot be cured and usually persists in a waxing and waning fashion. Many children and adolescents who are diagnosed with IBS continue to experience symptoms into adulthood, and many adult patients with IBS trace their symptoms to childhood. The intensity of pain for a particular patient may vary with time, but the nature of symptoms usually remains unchanged.
The quality of life for many patients with IBS can be enhanced with ongoing education, reassurance, psychosocial support, and appropriate pharmacotherapy when indicated.