| Irritable Bowel Syndrome | ||
 |
||
|
BRIEF CLINICAL UPDATEIrritable Bowel SyndromeAngela Ruman, M.D.Introduction Irritable bowel syndrome (IBS) is the most common functional disorder of the gastrointestinal tract. It is a common clinical problem encountered by primary care physicians and gastroenterologists. Epidemiological studies indicate a high prevalence in the general population: 14-24% of women and 5-19% of men.1 Its prevalence in the elderly population is similar to that of young adults although the elderly may be given the diagnosis of uncomplicated diverticular disease, which is similar in presentation to IBS. IBS may account for up to 12% of visits to primary care physicians and 28% of visits to gastroen-terologists.2 Patients with IBS have poorer quality of life and higher health care utilization than persons without the disorder.3 Based on the large portion of the population affected, the societal costs of the disease are large. IBS results in 2.4-3.5 million physician visits and 2.2 million medication prescriptions annually in the United States.4 The diagnosis and treatment of IBS and its associated problems account for billions of health care dollars. The scope of this article will be to discuss the current diagnostic criteria for IBS, to address a cost-effective approach to diagnose and treat IBS and to discuss current treatment options and innovations in treatment. Diagnosis No structural, biochemical or physiologic diagnostic marker exists for IBS. The diagnosis is made using symptom based criteria. In an attempt to develop standardized diagnostic criteria for clinical practice and research in IBS, international working teams developed the ROME I diagnostic criteria in 1990.5 In 1999 those criteria were revised and simplified, resulting in the ROME II criteria.(Table 1) Investigators have begun to evaluate the sensitivity, specificity and congruence of the ROME II criteria with the ROME I criteria. One study suggested that the ROME II criteria may provide equal efficacy in identifying patients with IBS while being simpler to use.6 The predictive value of the criteria decrease with increasing age of the patient and is less useful in predicting IBS in men.7 Combining use of these criteria with a complete history and physical exam increases diagnostic accuracy enabling a conservative workup to be performed.8 A meticulous history is essential, with the physician cognizant of stress factors, dietary particulars (lactose intolerance, use of offending agents like caffeine, sorbitol gum, etc.), previous diagnostic and treatment approaches, additional accompanying disorders and awareness of any warning signals suggestive of organic disease. In IBS patients, the physical exam should be unremarkable except for possible mild discomfort on deep palpation of the abdomen or mild abdominal distension. Other positive findings on physical exam necessitate a search for an organic pathology. Attempts at limiting diagnostic testing are impor-tant.9 A complete blood count to evaluate for anemia, and an erythrocyte sedimentation rate to assess for Table 1 .Diagnostic Criteria for IBS
malignancy and inflammatory bowel disease should be obtained. Depending on the age of the patient, duration of symptoms and specific complaints, thyroid function tests and chemistries may be supplementary tests. For patients with diarrhea, stool studies can be obtained to look for infectious etiologies and malabsorption syndromes. In patients over 40 years of age a colonoscopy may be indicated to evaluate for structural lesions. Treatment Significant advances in the treatment of IBS have been made over the last few years. Various investigators have increased our understanding of the enteric nervous system and the importance of neurotransmitters present in the gut. These findings have lead to an explosion in research to develop specific agents that can positively affect neurotransmitter function in the treatment of IBS symptoms. The hallmark of the treatment of IBS is the establishment of a therapeutic physician-patient relationship. Patient education is also important. Patients need information about their disorder and reassurance that their symptoms are real but not life threatening. Diet education is essential, and patients should learn which foods trigger their symptoms. Pharmacotherapy should be considered a second-line treatment for patients with a poor response to a first-line treatment regimen. A critique of randomized, controlled trials published in 1988 found no convincing evidence to support the efficacy of any medication used for the treatment of IBS and highlighted methodological flaws in the treatment trials.10 A recent meta-analysis that was limited to smooth muscle relaxants found five agents to be efficacious, although none of these has been approved for use in the United States. Over the past decade additional studies have been done with conflicting conclusions as to the efficacy of pharmacological treatment of IBS. One study conducted a systematic review of the published literature on pharmacological treatment of IBS to provide evidence-based guidance for clini-cians.1 This systematic review found that a great number of trials focused on smooth muscle relaxants and bulking agents for the treatment of IBS. The evidence supports the efficacy of smooth muscle relaxants in patients whose predominant symptom is abdominal pain. The efficacy of bulking agents has not been clearly established. Fewer trials studied loperamide and psychotropic agents. The corresponding data suggested that loperamide is effective for diarrhea while the evidence for use of psychotropic agents is inconclusive. Smooth Muscle Agents Only smooth muscle agents consistently decreased abdominal pain, the most frequent and disabling symptom of IBS.1 Dicyclomine is widely used in the United States and has been associated with decreased abdominal pain and improvement in constipation. However, most treated patients experienced anti-cholin-ergic side effects. There are four smooth muscle relaxants that are used in Europe for the treatment of IBS which are selective anti-muscarinic agents. These agents are cimetropium, pinaverum, otilonium, and trimebutine. They are efficacious without the anti-cholinergic side effects. None of these agents is currently approved for the treatment of IBS in the United States. Bulking Agents Although bulking agents are widely prescribed for the treatment of IBS, the evidence does not support a clear benefit. Psyllium, bran and methylcellulose are commonly used and while they may be associated with improvement in global status and constipation the evidence is insufficient.1 Antidepressants Tricyclic antidepressants are often used in the treatment of IBS. They have been found to be most useful in diarrhea predominant IBS and for patients with co-morbid depressive and anxiety disorders. The neuromodulatory and analgesic properties of antidepressants are recognized to work independently of their psychotropic effects. The systematic review of all randomized, controlled trials on pharmacological treatment of IBS found that in patients without definite psychiatric disorders, the benefit of antidepressants was unclear.1 Selective serotonin reuptake inhibitors have not been evaluated for use in IBS. Peripheral Opioid Mediators Loperamide is effective for IBS in which diarrhea is the predominant symptom. Trimebutine, available in Europe, binds to mu, kappa and delta opiate receptors, decreasing post-prandial colonic activity, colonic transit time and abdominal pain in constipated patients with IBS.2 Fedotozine, a kappa receptor agonist, normalizes visceral hypersensitivity in IBS. The Role of Serotonin The 5-HT3 and 5-HT4 receptor sites are distributed on the enteric neurons of the human gastrointestinal tract. The 5-HT3 receptors are non-selective cation channels. Activation of these channels and the resulting neuronal depolarization affect the regulation of visceral pain, colonic transit and gastrointestinal secretions, processes that relate to the pathophysiology of IBS.11 The newest medication to be approved for the treatment of IBS was alosetron, a 5-HT3-receptor antagonist. Alosetron inhibits activation of these nonselective cation channels, which results in modulation of the enteric nervous system. It has been shown to reduce stool frequency in patients with diarrhea predominant IBS, and it decreases abdominal pain and rectal urgency. The FDA approved alosetron in February 2000. However, it was withdrawn in November 2000 from the market after reports of serious adverse events. Since the drug\'s approval, 49 cases of ischemic colitis and 21 cases of severe constipation were reported to the FDA. Five reports of death were attributed to alosetron. Subsequently, alosetron was voluntarily withdrawn from the market due to the increased risk of patients developing ischemic colitis and severe constipation possibly requiring surgical interven-tion.12 5HT-4 agonists are also being studied for the treatment of IBS. These agonists have promotility effects on the gastrointestinal tract and studies are ongoing to evaluate their effectiveness in treatment of constipation predominant IBS. Prucolopride and tegaserod are 5HT-4 receptor agonists that are currently being studied.2 Conclusion IBS is a common clinical entity that can impose a significant economic burden on the health care system. The primary care physician can play a pivotal role in diagnosing and managing this condition. Patients with IBS need an integrated, individualized approach to treatment. A strong physician-patient relationship is the foundation. Patient education, reassurance and judicious dietary modification remain central to treatment. As advances in the pathophysiology of IBS become known, newer pharmacological treatments have become available with promising results. Pharmacological treatments are not without side effects as noted by the recent side effect profile on alosetron and should be targeted at major symptoms. Patients should be carefully monitored for adverse effects. REFERENCES
|
![](\"/images/19RUMAN%20Ibs1.jpg\")
