IBS Fact : Evidence-based management of irritable bowel syndrome

Other causes of IBS-like symptoms and their identification

 

Colorectal cancer

A primary concern of many new IBS patients is their potential risk of developing colorectal cancer. Indeed, studies indicate that patients with a presumptive diagnosis of IBS are 5-7 times more likely to be diagnosed with a colorectal cancer after a detailed examination than those without abdominal complaints. Here, three red flags – unintended weight loss, family history of colon cancer and onset of symptoms after age 50 – have reasonably high predictive value of between 4 and 6%. In contrast, blood in stools has a predictive value of only 2.4 %. Indeed, small amounts of bright red blood usually originate from a haemorrhoid or small tear (fissure) in the anal passage. Rarely, it could be due to another condition that requires treatment, although large amounts of red blood or black, tarry coloured stool does call for urgent medical attention. Although patients with symptoms of IBS seem to have a higher chance of being diagnosed with colorectal cancer than people without abdominal complaint, this association is not causative, i.e. IBS does not predispose for colorectal cancer. Instead, the association is merely caused by overlapping symptoms of IBS and colorectal cancer. Thus, in a fraction of patients with an initial presumptive diagnosis of IBS, and particularly in those with red flags, colorectal cancer may be the underlying cause, which is usually diagnosed following a more detailed endoscopic examination. Fortunately, for the large majority of people with IBS symptoms, including 83.8 % of those with red flags, detailed diagnostic examination reveal no other pathologies, and the diagnosis of IBS can be made with high amount of certainty.

 

Irritable bowel disease (IBD)

Because their names sound a lot alike, it is easy to confuse irritable bowel syndrome with inflammatory bowel disease (commonly called IBD). However these are two different conditions with different underlining pathological mechanisms and treatment strategies. The name IBD encompasses several diseases but its two main forms are Crohn’s disease and ulcerative colitis. Both refer to a long-lasting inflammation of the lining of the digestive tract. In Crohn’s disease, the inflammation affects different areas of the digestive tract, such as the large or small intestine or both, and often spreads deep into affected tissues. Ulcerative colitis is usually limited to the colon and rectum. IBD patients experience symptoms similar to those in IBS. Among these, diarrhoea and anaemia are very common. Others include abdominal pain, fatigue, weight loss, vomiting, constipation, urgency to evacuate, bloating, and passage of mucous and rectal bleeding. Some patients suffer from continuous disease activity while others experience episodes of active disease (flares) of different severity and frequency interspersed with periods of remission. Similar to IBS, the underlying causative mechanisms of IBD are multifactorial and largely unknown. However, in contrast to IBS, IBD is a structural disease, which means that the physical damage causing the symptoms can be clearly identified in most cases. Doctors can pinpoint the inflamed intestinal tissue by endoscopic examination of the intestinal mucosa and by microscopical assessment of collected tissue samples (biopsies). This is a fundamental difference when compared to IBS, which lacks clearly observable structural changes and is therefore referred to as a functional disease (i.e. diagnosis is based on disturbed function). Consequently, endoscopy, X-ray, or biopsies can be used to make a positive diagnosis of IBD while excluding IBS in the majority of patients. Because of the similarity in symptoms, a group of patients with actual IBD might, however, be initially suspected to suffer from IBS. Indeed this seems to be the case for a small fraction of patients, particularly those in a state of temporal remission in which inflammation has subsided and can no longer be observed by endoscopy. According to studies, approximately 1% of patients with a tentative diagnosis of IBS turn out to suffer from IBD. In addition, some data suggests that true IBD patients have a higher risk of developing IBS in the long term compared to the general population. In a study following IBD patients during 15 years, 1.8% of them developed IBS, in contrast to 0.5% in the general population over the same 15 year period. Thus, in a small number of cases, patients with IBD may be diagnosed equivocally with IBS or they may develop IBS in addition to IBD. However, in the large majority of cases, a clear differentiation between IBD and IBS can be readily made by colonoscopy combined with biopsy. Laboratory testing for inflammatory proteins such as calprotein in faeces may also be useful as it allows identification of ongoing inflammation suggesting IBD. Such assays for inflammatory proteins may be particularly useful to diagnose IBD during periods of remission, during which inflammation of the intestinal tract may not yet, or no longer be visible by endoscopy. Red flags that seem to have some predictive value pointing toward IBD are blood in stools and recent antibiotic use. Use of antibiotics seems an unusual factor to predict a condition. It is, however, based on the observation that future IBD patients seem to have a relatively higher use of antibiotics even prior to the diagnosis of their condition. The cause for this association has not been identified. Some studies suggest that frequent use of antibiotics actually predisposes for development of IBD, particularly in young children, by affecting the intestinal flora and the development of the immune system. Other studies oppose this view and suggest that the frequent use of antibiotics merely reflects the need for treatment of abdominal symptoms caused by IBD even before a definitive diagnosis has been made. Thus, the cause-effect relationship between IBD and antibiotics remains to be clarified. Other red flags that might suggest IBD are fever, weight loss, night-time diarrhoea, and first-degree relatives with IBD. Extra-intestinal symptoms such as inflammation in the skin, joints, or eyes are also common in IBD patients. However, it should be noted that IBD is much less frequent than IBD, and the red flags are certainly not to be considered as hard evidence for one or the other condition.

 

Lactose intolerance

Lactose is a natural sugar present in milk and milk products. Its digestion requires an enzyme called lactase, which is produced in the small intestine. Due to genetic differences, some persons lose the ability to produce this enzyme in sufficient amounts to properly digest the dairy products containing this lactase. Prevalence of lactase deficiency varies enormously geographically. It is most prevalent in Asian and African countries with a frequency as high as 95%. In Northern Europe, prevalence is only about 5%. In lactose intolerant persons, the consumed lactose remains undigested and passes into the colon. Here some of it is fermented by colonic bacteria, which produces large amounts of hydrogen and methane gas. The undigested lactose also attracts water molecules, which prevents them from being properly absorbed into the bloodstream. Together, the excessive gas and retained water result in symptoms such as diarrhoea, cramping, bloating and flatulence. The threshold for lactose intolerance, i.e., the amount that can be ingested without symptoms, varies widely among individuals. In addition, symptoms may occur sometime after the ingestion. Therefore, one may not connect the symptoms to dietary factors or even mistakenly attribute it to IBS. Diagnosis of lactose intolerance is most commonly performed by the lactose hydrogen breath test. This test measures the amount of hydrogen produced in your breath following the consumption of lactose. If the lactose is not digested by your body, it will be fermented by bacteria, leading to production hydrogen which can then be detected in your breath. The lactose hydrogen breath test usually involves taking a specified amount of lactose orally and measuring breath hydrogen levels over the following 3 – 6 h. Other lactose intolerance tests include blood sugar measurements after ingesting lactose, and measurements of stool acidity. Using the above diagnostic tests, studies revealed that lactose malabsorption affects about 24 – 45% of patients with IBS, which is considerably higher than the 4.7 – 5.7% found among non-IBS sufferers. Studies on dietary exclusion support these findings, showing that 19% – 44% of IBS patients improve their symptoms following a lactose-free diet. This indicates a considerable overlap between IBS and lactose intolerance, although the exact cause-effect relationship is still a subject of scientific debate. One possible explanation for the high incidence of lactose intolerance among IBS patients is misdiagnosis of IBS, i.e, patients mistakenly diagnosed with IBS while in fact suffering from lactose intolerance only. Although this might apply to some presumed IBS sufferers, many of them experience only a partial improvement of symptoms after omitting lactose. Thus, despite dietary changes, these persons continue to experience some degree of abdominal complaints suggesting IBS as an independent underlying condition. A second explanation is that true IBS sufferers are much more sensitive to certain dietary components such as lactose. In these persons even a low-grade intolerance that would go unnoticed in healthy persons, and which might be in fact even undetectable by lactose breath testing, produces significant abdominal complaints. This is supported by studies showing that as many as 62% of IBS sufferers who actually test negative for lactose intolerance do experience much improvement of symptoms following a lactose-free diet. This is further complicated by the fact that some persons might be intolerant to milk proteins instead of lactose. These individuals would also experience an improvement of their abdominal complaints despite negative lactose breath test. Interestingly, some persons testing positive for lactose intolerance do not experience symptoms after consumption of significant amounts of milk, presumably due to an adaptation of their intestinal flora to compensate for the lack of lactose digesting enzymes. In summary, dietary intervention, and to a lesser extent, diagnostic tests such as the lactulose breath test might provide important clues to the diagnosis of IBS and to determine whether lactose is a contributing factor relevant for the severity of symptoms. Prolonged exclusion of dairy-containing products should be done with care and preferably under professional assistance as it may remove an important source of nutrients such as calcium and vitamin D. A possible alternative may be the use of commercially available lactose digesting enzymes (see here). These can be ingested to compensate for the lacking endogenous enzymes, improving thereby the digestion of lactose-containing foods. Although such supplementation seems a promising strategy, its efficacy has not been studied in detail and should be considered from a critical perspective. Finally, although lactose intolerance is a common condition and can be mistaken for IBS, other dietary components such as proteins, fats, and carbohydrates, and in particular fibres, may also cause food intolerances and contribute to IBS-like symptoms. Here, proper testing and effective dietary intervention may reveal misdiagnosis of IBS in some persons, and reduce the severity and frequency of true IBS symptoms in others.

 

Coeliac disease:

Celiac disease is a chronic inflammation of the small intestine caused by an immune reaction to dietary gluten, a protein contained in wheat, barley, and rye. Upon ingestion, gluten provokes an immune response that attacks the body’s own intestinal tissue. Hence, celiac disease is not an allergy but an autoimmune disease. Celiac disease has a strong genetic component, affecting almost exclusively those with genetic susceptibility. The inflammatory response results in damage of the intestinal lining causing abdominal complaints and malabsorption of nutrients. Celiac disease occurs in about 1% of the population worldwide. Symptoms can include diarrhoea, fatty stools, weight loss, bloating, flatulence and abdominal pain. Extra-intestinal symptoms such as anaemia, osteoporosis, and skin disorders are also common. However, many individuals with celiac disease may have no symptoms at all. Diagnosis of celiac disease consists of several steps and should be performed by a gastroenterologist. The first step consists of serologic (blood) testing for elevated autoantibodies while on a gluten-containing diet. Here, the two most effective tests are the IgA anti-transglutaminase antibody test (TTG) and the IgA anti-endomysial antibody test (EMA). Positive results for one of these antibodies indicate a high likelihood of CD, with each test having greater than 90% sensitivity. However, approximately 3% of patients with celiac disease have a deficiency in total IgA. Thus, despite suffering from celiac disease, they may present falsely negative blood test results. In such patients, measuring total IgA levels may be performed in addition to the above blood tests. In patients testing positive for either TTG or EMA, the next step in the diagnosis consists of an endoscopic collection of tissue samples (biopsy) from the small bowel to assess tissue damage, again while on a gluten-containing diet. Together, the positive blood tests and intestinal tissue damage confirmed by biopsy indicate celiac disease with 99% specificity. The diagnosis of coeliac disease is then definitively confirmed by an improvement of symptoms and a decrease of specific antibodies after introducing a gluten-free diet. Guidelines for diagnosing celiac disease are continuously being updated, and with the improving accuracy of blood tests and the development of new disease markers, invasive endoscopic biopsies can be expected to become less important. As mentioned above, genetic predisposition plays an important role in celiac disease. In fact, celiac disease does not develop unless a person carries either the so called HLA-DQ2 or HLA-DQ8 gene variant, also known as an allele. However, these gene variants are also very common among the general population (30 – 40%) and do not cause celiac disease in most persons. Thus, although HLA-DQ2 or HLA-DQ8 is necessary for the development of the disease, it is not sufficient. Testing for the presence of HLA-DQ2 or DQ8 may be, however, useful in persons with a family history of celiac disease or those in whom diagnosis is uncertain. Here, negative results for both genes practically exclude the diagnosis of celiac disease (<1% likelihood of the disease being present), while positive results only indicate a relative risk of 36 -53% and will still require further workup. The above screening methods will also identify patients with wheat allergy or a, so called, non-celiac gluten sensitivity. In such patients, symptoms improve considerably when on a gluten free diet despite negative blood test and genetic screening for celiac disease. Currently, no curative treatment exists for celiac disease, and the only option available is a strict life-long gluten free diet. Such diets require significant education, motivation, and follow-up and should be initiated only after a definitive diagnosis has been made. This is particularly important since avoidance of gluten during celiac disease screening may cause false negative results. Because of similar symptoms, celiac disease may be mistakenly diagnosed as IBS. Indeed, studies have shown a 4.5% prevalence of celiac disease in patients clinically diagnosed with IBS. Other studies have concluded that celiac disease, as diagnosed by serologic testing and biopsy, is four times more prevalent among patients with a clinical presentation of IBS than in non-IBS populations. Because of this overlap, patients with IBS symptoms should consider celiac screening. This applies in particular to those with diarrhoea and anaemia and to first-degree relatives of confirmed celiac disease sufferers.

 

Other conditions with IBS-like symptoms

Less frequent disorders that may also be mistakenly attributed to IBS include various food allergies and intolerances, parasitic infections, thyroid and pancreatic diseases, diverticulitis, gallstones and diseases of the female reproductive organs. In addition, IBS is relatively more frequently accompanied by disorders such as fibromyalgia, depression, somatisation and anxiety. This further adds to the complexity of IBS and stresses the need of thorough diagnosis and treatment by a professional gastroenterologist. Although the so called red flags may point toward a more serious pathology and should prompt further examination, their sensitivity and selectivity is quite poor. Accordingly, the great majority of patients presenting one or more of these red flags does not suffer from other conditions than IBS. Here, again, a professional gastroenterologist should be consulted to resolve any doubts.

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Diagnostic examinations in IBS

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