EVALUATION OF IBS
A diagnosis of IBS is usually suspected on the basis of the patient’s history and physical examination, without additional tests. Confirmation of the diagnosis of IBS requires the confident exclusion of organic disease in a manner dictated by an individual patient’s presenting features and characteristics. In many instances (eg, in young patients with no alarm features), a secure diagnosis can be made on clinical grounds alone.
There is a lack of robust evidence and prospective studies regarding the appropriate use of radiologic imaging in patients with IBS-like symptoms.5
In clinical research, the Rome III criteria are those most commonly used to make a diagnosis of IBS. However, is should be noted, firstly, that these are due to be updated in 2016 and that a systematic review (2012) of the diagnostic criteria for IBS demonstrated low validity and utilization of the Rome III criteria, and suggested that the Manning criteria were more widely validated and may be more clinically applicable.6
In clinical practice, whether in the setting of primary or specialist care, clinicians usually base a diagnosis of IBS on their evaluation of the whole patient (often over time) and consider a multiplicity of features that support the diagnosis (apart from pain and discomfort associated with defecation, or change in stool frequency or form). This approach includes a history of symptoms regarded as common in IBS and generally supportive of its diagnosis, as described above combined with the presence of behavioral features considered helpful in recognizing IBS in general practice, such as the presence of symptoms for >6 months, and their aggravation by stress or meals. A pattern of frequent consultations for nongastrointestinal symptoms, a history of previous medically unexplained symptoms, or an association with anxiety and/or depression may also raise suspicion for IBS. It must also be remembered that noncolonic complaints, such as dyspepsia (reported in 42% to 87%), nausea, and heartburn often accompany IBS.
Nongastrointestinal symptoms, including lethargy, fatigue, backache and other muscle and joint pains, fibromyalgia, headache, urinary symptoms (eg, nocturia, frequency and urgency of micturition, incomplete bladder emptying), dyspareunia, insomnia, and a low tolerance to medications in general may also be evident.
Additional Tests or Investigations
In the majority of cases of IBS, no additional tests or investigations are required. An effort to keep investigations to a minimum is recommended in straightforward cases of IBS, and especially in younger individuals.
Additional tests or investigations should be considered if symptoms begin after the age of 50, if warning signs (red flags), as listed above, are present, or if any abnormalities are detected on physical exam.
The following tests (although commonly performed) are indicated only if supported by the clinical history and where locally relevant: FBC, serum biochemistry, thyroid function tests, and stool testing for occult blood and ova and parasites
Additional tests or investigations may also be considered if the patient has persistent symptoms or is anxious despite treatment, a major qualitative change in chronic symptoms has occurred, or a new coexisting condition should be considered.
Adult-onset BAM is now recognized as an important cause of an IBS-D-type presentation. A recent review study7 found evidence that >25% of patients with IBS-D have BAM. Etiologic factors that appear to contribute to the onset and persistence of chronic diarrhea symptoms are alterations in the enterohepatic circulation, accelerated intestinal transit, an increase in the bile acid pool, and low levels of fibroblast growth factor-19.8 Diagnostic tools that help in diagnosing BAM and differentiating it from IBS-D are assays of fecal bile acid concentration, 23-seleno-25-homo-taurocholic acid (SeHCAT) testing, and high-performance liquid chromatography for serum 7-α-OH-4-cholesten-3-one (C4)—in addition to the use of therapeutic trials (with the bile acid sequestering agents cholestyramine and colesevelam), and heightened awareness of the likelihood of BAM.9
The main symptoms and signs of celiac disease are chronic diarrhea, failure to thrive (in children), and fatigue. It is estimated to affect approximately 1% of all Indo-European wheat-eating populations. It must be emphasized that nowadays many with celiac disease do not have classic features and present with “IBS-type” symptoms, including bloating and constipation, along with iron deficiency. A low threshold for investigation should therefore be maintained in high-prevalence (>1%) regions.10
The main symptoms are bloating, flatulence, and diarrhea acutely related to consumption of milk and dairy products. Although genetic testing can now detect lactase deficiency, this is not necessarily predictive of intolerance, which is best tested using the lactose hydrogen breath test. Indeed, a substantial proportion of individuals who lack lactase can tolerate oral lactose despite bacterial fermentation.
In countries with a high prevalence of lactase deficiency, inappropriately labeling IBS patients as lactose intolerant should be avoided, unless they are consuming substantial amounts of milk and/or milk products, as this could deprive the community of a cheap nutritious source of protein and nutrition in countries such as India. In all parts of the world, the prevalence of lactose malabsorption on breath tests has been consistently similar between IBS and non-IBS subjects.
IBD (Crohn’s Disease, Ulcerative Colitis)
There are very significant variations in prevalence worldwide. In a high-prevalence area, IBD, should be considered if diarrhea has persisted for >2 weeks or if rectal bleeding is reported and/or an inflammatory mass, weight loss, perianal disease, or fever is detected. In areas in which it is endemic, intestinal tuberculosis should also be considered, as its presentation may be similar to that of IBD.
Colorectal carcinoma should be considered in older patients who develop IBS-type symptoms for the first time later in life and/or in the presence of hematochezia or unintended weight loss. An obstructive-type pain may be a feature of the left-sided lesions, whereas anemia or iron deficiency is common with the right-sided lesions
Microcytic (Lymphocytic and Collagenous) Colitis
This disorder accounts for 20% of unexplained diarrhea in patients over the age of 70, is typically painless, and is most common in middle-aged females (M:F=1:15). Diagnosis is based on the pathologic examination of colonic biopsies
Acute or Chronic Diarrhea Due to Protozoa or Bacteria
Here the principal symptom is an acute onset of diarrhea and the diagnosis is confirmed by stool examination or duodenal biopsy.
A review11 on the role of intestinal protozoa in IBS concluded that there was “a possible role for protozoan parasites, such as Blastocystis hominis and Dientamoeba fragilis” in the etiology of IBS. D. fragilis is known to cause IBS-like symptoms and has a propensity to cause chronic infections. It can be detected using nested polymerase chain reaction,12 where available, or alternatively using microscopy. The role of B. hominis as an etiological agent in IBS remains unclear, due to contradictory reports and the controversial nature of B. hominis as a human pathogen. The role of B. hominis may be genotype related.13 Although Entamoeba histolytica infections occur predominantly in developing regions of the world, the clinical diagnosis of amebiasis is often difficult, as symptoms in patients with IBS may closely mimic those in patients with nondysenteric amebic colitis. Clinical manifestations of Giardia intestinalis infection also vary from asymptomatic carriage to acute and chronic diarrhea with abdominal pain.
Although stool testing for Giardia and Amoeba is recommended in India, self-medication with imidazoles is common, rendering the results difficult to interpret. It is essential that all patients with IBS in relevant areas should undergo parasitological investigations to rule out the presence of protozoan parasites. It is equally important that these tests are appropriately interpreted and that overtreatment is avoided.
SIBO is rare unless the patient has a primary or secondary motility disorder, has been operated on (in particular with ileocecal resection or bariatric surgery), or has impaired immunity (such as immunoglobulin A deficiency). The classic features of SIBO are those of maldigestion and malabsorption. Some of the symptoms of SIBO (bloating, diarrhea) overlap with those of IBS, which has led to the suggestion that SIBO is related to IBS. However, it is generally believed that SIBO is not a common cause of IBS-like symptoms.
Tropical sprue should be considered in returning travelers with persistent diarrhea. The symptoms and histologic findings of tropical sprue may resemble those of celiac disease. A diagnosis of celiac disease is unlikely in the absence of antiendomysium or antitissue transglutaminase antibodies, but conversely their absence increases the likelihood of tropical sprue.14
The relationship between IBS and so-called “painful diverticular disease” is unclear; is painful diverticular disease no more than IBS in a patient who has diverticula? In diverticulitis, the classic symptoms and/or findings are episodic and acute to subacute during an episode, featuring left-sided abdominal pain, fever, and the presence of a tender inflammatory mass in the left lower quadrant. However, it is now evident that afflicted patients may have more chronic symptoms in between discrete episodes/attacks, and that left-sided and bilateral, but not right-sided diverticular disease, may increase the risk for IBS.15
Endometriosis will be suggested by the presence of cyclical lower abdominal pain and the detection of enlarged ovaries or nodules dorsal to the cervix on digital vaginal examination.
Pelvic Inflammatory Disease
Here the main symptoms and/or findings include: chronic lower abdominal pain, fever and upward pressure pain or adnexal tenderness, and swollen adnexa on digital vaginal examination.
In women over the age of 40, ovarian cancer should be considered in the differential diagnosis. In 1 survey, the following symptoms were more common among women with ovarian cancer: increased abdominal girth, bloating, urinary urgency, and pelvic pain. The combination of bloating, increased abdominal girth, and urinary symptoms was found in 43% of women with ovarian cancer, but in only 8% of a control population.
Enterocolitis Associated With Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
This may account for diarrhea in elderly patients who are receiving treatment from neurologists and rheumatologists.
Comorbidity With Other Diseases
Patients with overlap syndromes tend to have more severe IBS. Thus, fibromyalgia has been reported in up to 20% to 50% of IBS patients and IBS is common in several other chronic pain disorders, such as chronic fatigue syndrome (51%), temporomandibular joint syndrome (64%), chronic pelvic pain (50%), as well as nonulcer dyspepsia and so-called gall-bladder and biliary dyskinesia
In a meta-analysis, the prevalence of biopsy-proven celiac disease was found to be >4 times higher in patients who met the diagnostic criteria for IBS than in control individuals without IBS.16
There is a significantly higher prevalence of chronic idiopathic constipation in patients with IBS. Distinguishing between IBS-C and chronic idiopathic constipation may be difficult in clinical practice; several recent studies have called into question the appropriateness and feasibility of creating what appears to be an artificial division between these 2 functional gastrointestinal disorders.17
The prevalence of gastroesophageal reflux-type symptoms in patients with IBS is 4 times higher than in those without IBS. There is an overlap between the 2 conditions in up to 25% of individuals. It is recommended that when physicians encounter patients with symptoms of IBS, they should routinely screen for coexistent gastroesophageal reflux symptoms.18
Symptoms compatible with IBS have been reported to be significantly higher in patients with IBD in comparison with non-IBD controls, even among those thought to be in remission. IBS-type symptoms were also found to be significantly more common in patients with Crohn’s disease than in those with ulcerative colitis (UC), and in those with active disease.19 Of course, a diagnosis of IBS would not be appropriate in a patient with active IBD.
MANAGEMENT OF IBS
Given that there is no general agreement on the cause of IBS, it comes as no surprise that no single treatment is currently regarded throughout the world as being universally applicable to the management of all IBS patients.
Given also the common association between IBS symptoms and such factors as diet, stress, and psychological factors, attention should be given to adopting measures that may alleviate, if not eliminate, such precipitants. Dietary differences between different countries and ethnic groups would be expected to have a significant influence on the prevalence of symptoms of IBS, but little information is available.
Recent data on disturbances in the intestinal flora (microbiota) in IBS have spurred interest in novel approaches: probiotics, prebiotics, and antibiotics. Recent meta-analyses confirm a role for probiotics in IBS, but also make it clear that the effects of probiotics in IBS, as elsewhere, are highly strain specific. Variability and the formulation of specific strains vary dramatically around the world. Issues of quality control also continue to complicate recommendations in this area.
IBS patients commonly have recourse to a variety of alternative/complementary therapies throughout the world. In India (in Ayurvedic medicine) and China, for example, herbal remedies are widely available and commonly used for IBS. However, their efficacy is difficult to assess, as the concentrations of active ingredients vary considerably depending on the extraction process. Few “alternative” therapies have been subjected to the rigors of a randomized trial in IBS.
Nonpharmacological factors are often ignored, but are of paramount importance in the management of IBS. The physician-patient relationship is critical and should include attention to several aspects, both during the initial assessment and in the subsequent follow-up. These include identifying and exploring the patient’s concerns. A positive patient-physician relationship should be established, with the patient’s symptoms and distress being accepted as real and appreciating the impact of symptoms. Time should be taken to explore the patient’s anxieties related to symptoms and possible diagnoses, with the aim being to eliminate unnecessary worries and in so doing to identify and helping to resolve stressful factors. Attempts should be made to reduce avoidance behavior. Patients may avoid activities that they fear are causing the symptoms, but avoidance behavior has a negative influence on the prognosis. General guidance on diet and activity should be provided.
Diet 20 and Dietary Supplements
A fiber-rich diet or a bulk-former (eg, psyllium) combined with sufficient intake of fluids would seem to be a logical approach in IBS, but the general status of fiber in IBS is not straightforward.20 Insoluble fibers may exacerbate symptoms and provide little relief—adverse events and bloating, distension, flatulence, and cramping, in particular, may limit the use of insoluble fiber, especially if increases in fiber intake are not introduced gradually. Soluble fibers such as psyllium (ispaghula), in contrast, provide relief in IBS.21 Diets low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) reduce abdominal pain and bloating, and improve the stool pattern,21 but long-term outcomes and the safety of low-FODMAP diets remain to be demonstrated. It is also still unclear whether the low-FODMAP intervention diet is beneficial to all IBS patients.21 Although they are widely used, especially in North America and Europe, the status of wheat-free or gluten-free diets in IBS is uncertain. Some probiotics provide global relief of symptoms in IBS, and others alleviate individual symptoms such as bloating and flatulence.20,22 However, the duration of these benefits and the nature of the most effective species are not clear.23 The efficacy of probiotics is difficult to interpret, as different strains, doses, formulations, and methods of delivery have been used in various studies.21 Furthermore, most randomized controlled studies of probiotics in IBS have been of short duration, have not used an appropriate study design, and have not adequately reported adverse events.22 There is at present insufficient evidence for a general recommendation of prebiotics or synbiotics in patients with IBS.20 A recent consensus statement provides guidance on the use of specific probiotics in the management of IBS.24
A variety of agents are used throughout the world for the treatment of individual symptoms in IBS. These include antispasmodics for pain, laxatives, fiber, bulking agents, the chloride-channel agonist lubiprostone, and the guanylate cyclase agonist linaclotide for constipation, fiber, bulking agents, antidiarrheals, the poorly absorbable antibiotic rifaximin and eluxadoline, a mu-opioid receptor agonist, and delta-opioid receptor antagonist for diarrhea.
Overall Symptoms—First-Line Therapy
Certain antispasmodics (otilonium, hyoscine, cimetropium, pinaverium, dicyclomine, and mebeverine) provide symptomatic short-term relief in IBS. Adverse events are more common with antispasmodics than with a placebo.20 Peppermint oil is superior to placebo in improving IBS symptoms.20,25 The risk of adverse events is no greater with peppermint oil than with a placebo.20
Overall Symptoms—Second-Line Therapy
TCAs and SSRIs are effective for symptom relief in IBS.20,21,26 Adverse effects are common, with drowsiness and dizziness the most common,26 and may limit patient tolerance.20 TCAs are associated with significant adverse effects in treating IBS-D and should be avoided in IBS-C; clinicians should expect 1 adverse effect for every 3 patients who benefit from therapy.27 SSRIs may be considered in resistant IBS-C, although it is not currently recommended that SSRIs should be routinely prescribed for IBS in patients without comorbid psychiatric conditions, because of conflicting and limited data regarding efficacy, safety, and long-term outcomes.28 Rifaximin is effective in reducing overall symptoms in IBS-D.20,29 Rifaximin may be considered as a second-line therapy.21 Older patients and women were found to have higher response rates.29 Rifaximin is well tolerated,30 but its efficacy and safety have not been established beyond 16 weeks.29 However, retreatment efficacy and safety has been recently reported.31 It has also been reported that 846 patients benefit for each adverse effect.27
Alosetron is useful for second-line therapy of IBS-D.20,21 However, it has been associated with an increased risk of ischemic colitis and may cause severe constipation.21 Clinicians should expect 1 adverse effect for every 3 patients who benefit from therapy.27 Lubiprostone is safe and effective for treatment of IBS-C.20,27 Nausea has been the major side effect limiting use. Linaclotide is safe and effective for treatment of IBS-C.20,32,33 Diarrhea is the major adverse effect of linaclotide; further studies are needed to evaluate its long-term efficacy and safety.33
However, there is insufficient evidence to recommend loperamide for use in IBS20; mixed 5-HT4 agonists/5-HT3 antagonists are no more effective than placebo at improving symptoms of IBS-C20 and renzapride and cisapride have no benefit in IBS.34 Although there is no evidence that polyethylene glycol (PEG) improves overall symptoms in patients with IBS, it may relieve constipation.20
Ondansetron was found to improve urgency, diarrhea, and bloating in IBS-D, but did not provide any benefits in relation to pain. Ramosetron, where available, should also be considered as second-line therapy in IBS-D; it has also been shown to be effective in IBS-D and seems to be devoid of serious adverse effects such as severe constipation and ischemic colitis.21
If an analgesic is required, paracetamol is preferable to NSAIDs. Opiates are to be avoided at all costs, as dependence and addiction are a significant risk in such a chronic condition. NSAIDs and opiates also have undesirable side effects on the gastrointestinal tract. The probiotic strain Bifidobacterium infantis 35624 has been shown to reduce pain, bloating, and defecatory difficulty and normalize stool habit in IBS, regardless of predominant bowel habit, but is currently available only in the United States, Canada, the United Kingdom, and Ireland.
The probiotic strain B. lactis DN-173010 has been shown to accelerate gastrointestinal transit and to increase stool frequency among IBS patients with constipation. Although osmotic laxatives are often useful, few have been formally tested. Lubiprostone and linaclotide have been approved for the treatment of IBS-C.21
Although it is an effective agent for the treatment of diarrhea, because of the lack of effects on pain, the cardinal symptom of IBS, there is insufficient evidence to recommend loperamide for use in IBS.20 Alosetron is indicated only for women with severe IBS-D with symptoms lasting >6 months and no response to antidiarrheal agents. Eluxadoline and rifaximin have recently been approved in the United States for IBS-D; it is difficult, at this early stage, to define their position in IBS management.
Specific Symptoms—Bloating and Distension
Diets that produce less gas, such as the low-FODMAP diet, may be helpful in some patients. There is no evidence to support the use of activated charcoal–containing products, “antiflatulents,” simethicone, and other agents in IBS. Some specific probiotic strains, such as B. lactis DN-173010 and the probiotic cocktail VSL#3, have clinical trial evidence of efficacy for bloating, distension, and flatulence. Others, such as B. infantis 35624, reduce bloating as well as the other cardinal symptoms of IBS. Antibiotic treatment with rifaximin has been shown to reduce bloating in some IBS patients. Older patients and women have been found to have higher response rates.29 Rifaximin has been shown to be effective on retreating patients who have relapsed after a first effective treatment.31
Apart from the general approaches described above for governing the conduct of the doctor-patient relationship in IBS, more formal psychological interventions may be contemplated in certain circumstances and depending on the availability of appropriate resources and expertise. Such approaches may include:
Cognitive behavioral therapy, in group or individual sessions, has shown excellent results, but its limited availability and labor-intensive nature limit routine use.21,26 Behavioral techniques are aimed at modifying dysfunctional behaviors through and include: relaxation techniques, contingency management (by rewarding healthy behavior), and assertion training. Gut-directed hypnosis should be recommended for patients with IBS refractory to conventional (drug) treatment.35 It has a high level of safety and tolerability, and there is evidence of sustained efficacy, in contrast to drug therapy.35 It should be offered by licensed hypnotherapists with specialist training in the technique.35 Group treatment is more time efficient than individual sessions and at least as effective.35 Daily practice by patients, supported by audiorecordings, boosts efficacy; training and experiences should regularly be discussed with patients.35 However, there is limited evidence from randomized controlled trials (RCTs). Future RCTs are needed that use strict diagnostic criteria, have follow-up periods of at least 1 year, and include newly diagnosed and treatment-resistant patients.36 The limited availability and labor-intensive nature of hypnotherapy limits routine use.21
The American College of Gastroenterology (ACG) Task Force37 concluded that psychological therapies, including cognitive therapy, dynamic psychotherapy, and hypnotherapy, but not relaxation therapy, are more effective than usual care in relieving global symptoms of IBS. However, Ford et al20 found that the quality of evidence was very low and that the results were only slightly superior to usual care or waiting-list control. With the exception of a single study, these therapies have not been shown to be superior to placebo. The sustainability of their effect is questionable.
With regard to herbal therapies and acupuncture, the ACG Task Force concluded that the available RCTs, mostly testing unique Chinese herbal mixtures, seemed to show a benefit. It was not possible to combine these studies into a meaningful meta-analysis, however, and overall, any benefit of Chinese herbal therapy in IBS continues to be potentially confounded by the variable components used and their purity. Also, there are significant concerns about toxicity, especially liver failure, with the use of any Chinese herbal mixture. A systematic review of trials of acupuncture was inconclusive due to heterogenous outcomes. Further research is needed before any recommendations on acupuncture or herbal therapy can be made.
For most patients with IBS, symptoms are likely to persist, but not worsen. Symptoms will deteriorate in a smaller proportion, and some patients will recover completely.
Factors that may negatively affect the prognosis include: avoidance behavior related to IBS symptoms, anxiety about certain medical conditions, impaired function as a result of symptoms, a long history of symptoms, chronic ongoing life stress, and psychiatric comorbidity. In contrast, the physician can positively affect treatment outcome by acknowledging the disorder, educating the patient about IBS and reassuring them.
In mild cases, there is generally no medical need for follow-up consultations in the long term, unless symptoms persist and/or are accompanied by considerable inconvenience or dysfunction, diarrhea, or constipation do not respond to therapy or warning signs emerge.
One should beware of possibility that an eating disorder might develop. Many patients with IBS try some form of dietary manipulation and this can lead to nutritionally inadequate diets or ingestion of abnormal amounts of fruit, caffeine, dairy products, and dietary fiber. The tendency for eating disorders to develop is more common in female IBS patients.
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