Medication and non-drug therapy options are available for irritable bowel syndrome. However, typical symptoms must first be recognized and alarm signs correctly interpreted. A long-term doctor-patient relationship is central to this condition.
Irritable bowel syndrome (IBS) is a condition in which the colon is irritated. Irritable Bowel Syndrome [IBS]) is a functional bowel disease that is one of the most common gastrointestinal disorders with a prevalence of 5-15%. It occurs primarily around the third decade of life [1,2]. In Western countries, women are affected twice as often as men; conversely, in Asia, men are more likely than women to have this disease [3]. Irritable bowel syndrome leads to a significant reduction in quality of life and is one of the most common causes of absenteeism from work [4]. Approximately 40% of consultations with gastroenterologists or 2% of all visits to primary care physicians are due to irritable bowel symptoms.
Pathogenesis and course
The pathogenesis of irritable bowel syndrome is not yet fully understood. Altered gastrointestinal motility is described. In addition, visceral hypersensitivity is thought to occur, in the sense of increased pain perception [5–7]. In addition, it has been demonstrated that after a gastrointestinal infection, there is an increased risk for the development of what is then termed postinfectious irritable bowel syndrome. For example, the risk of developing functional bowel disorders after traveler’s diarrhea is increased three- to fourfold [8]. It is worth mentioning the role of the gut microbiome, the alteration of which is considered to favor the development of IBS [9].
Psychosocial predispositions such as anxiety or sleep disorders or a genetic predisposition also favor the development of irritable bowel syndrome [10,11]. In summary, the pathogenesis of irritable colon should be understood as multifactorial. It includes not only somatic but also psychosomatic factors.
Data on the natural history of this disease is still limited. More than 5% of affected patients continue to experience recurrent symptoms seven years after diagnosis, and only about 10% of patients report complete regression of symptoms [12]. However, the disease does not lead to a reduction in life expectancy, which is why the prognosis is described as good despite the protracted symptoms.
Clinic
In irritable bowel syndrome, intermittent abdominal pain of varying intensity and frequency is at the forefront of symptoms [13]. Complaints typically occur in association with defecation in terms of altered stool frequency and consistency [14]. Affected patients are classified into four subtypes depending on the predominant stool consistency. Thus, a distinction is made between diarrhea-predominant (IBS-D), obstipation-predominant (IBS-C), or irritable bowel syndrome with variable stool consistency (IBS-M). In the latter, flatulence and abdominal pain are often at the forefront of symptoms. The fourth IBS subtype describes “unclassified” IBS patients (IBS-U) who meet IBS criteria (Rome IV, Table 1) but cannot be classified into any of the other subclasses [14].
Patients often additionally report abdominal bloating, mucus discharge, as well as the sensation of incomplete emptying. For diagnostic purposes, these complaints are considered supportive, but they do not necessarily have to be present [15].
The symptoms often lead to numerous laboratory chemical and bacteriological as well as instrumental examinations, without any underlying organic disease being detected.
Diagnostics
The diagnosis of irritable bowel syndrome should be made as early as possible and with the least possible expenditure of equipment and money.
The step-by-step diagnosis is based first on a detailed anamnesis with recognition of the typical clinical symptoms and identification of the so-called alarm signs (Tab. 2) and then on a careful clinical examination. Any abnormalities or alarm signs must subsequently be clarified further [16].
The next diagnostic step involves performing a basic laboratory (blood count with ESR/CRP, clinical chemistry, TSH), which is typically unremarkable. In addition, especially in IBS-D patients, sprue serology should be determined (antigliadin and antiendomysium antibodies as well as antibodies against tissue transglutaminase [IgG, IgA] and determination of total IgA to exclude false negative findings due to IgA deficiency). The exclusion or diagnosis of celiac disease is relevant because it can present with virtually the same symptoms as IBS [17]. However, celiac disease is also a very important differential diagnosis because IBS patients are approximately five times more likely to be pre-tested for a diagnosis of sprue than the normal population [18].
In IBS-D patients, additional stool tests for bacteria, parasites (lamblia!) and leukocytes as well as calprotectin should be performed, especially if there is a positive travel history. Calprotectin plays an important differential diagnostic role in differentiating inflammatory bowel disease from functional bowel disease [19,20]. However, it is not possible to distinguish between infectious and non-infectious inflammation using calprotectin. In addition, calprotectin may be elevated in tumors, gastrointestinal bleeding, diverticulitis, and liver cirrhosis.
If food intolerances are suspected, the patient should be registered for a food exposure test. If lactose intolerance is clinically suspected, an H2 breath test or a lactase gene test is indicated, and an omission test may additionally be attempted, avoiding aimless diets. If there is evidence of an intolerance, it makes sense to link the patient to nutritional counseling, especially to avoid malnutrition.
Apparatus-based diagnostics usually include abdominal ultrasonography, but this usually does not reveal serious pathologic findings, although gallstones are detected in approximately 5% of patients. In women, a gynecologic examination with endovaginal ultrasound is also recommended to rule out endometriosis, adnexitis, ovarian cancer, and ovarian cysts [17].
Gastroscopy is recommended especially in patients with alarm signs or predominant irritable bowel syndrome (IBS-D type). Duodenal biopsies should be performed to exclude sprue or Whipple’s disease. In addition, the collection of duodenal juice may be useful to exclude SIBO (“small intestinal bacterial overgrowth”).
Similarly, in patients with IBS-D or alarm signs, ileo-colonoscopy is part of the diagnostic workup to rule out important differential diagnoses (such as microscopic colitis, infectious colitis, diverticulitis, inflammatory bowel disease). In IBS patients over 50 years of age, ileo-colonoscopy is indicated even in the absence of diarrhea, if only for polyp screening or early cancer detection. However, in the sense of “reassurance,” one-time endoscopic examinations can be undertaken in symptomatic patients to convincingly convey the harmlessness of the distressing symptoms.
Non-drug therapy
General measures: The first pillar of therapy for IBS patients consists of establishing a stable, long-term doctor-patient relationship and taking seriously the complaints that are subjectively perceived as extremely distressing. Clear and comprehensive diagnostic communication plays a central role. Patients must be educated that this disease is harmless and not associated with any reduction in life expectancy. Repeated and unnecessary diagnostic testing as an expression of doubt that another underlying disease has been overlooked should be avoided.
Lifestyle adjustment is recommended. Thus, it has been shown that an increase in physical activity is associated with a significant decrease in IBS symptoms [21]. Individual trigger factors of symptomatology (e.g., stress, nicotine, lack of sleep) should be identified and probatorily eliminated.
Nutrition: IBS patients can additionally benefit from a change in diet. The so-called low-FODMAP diet (reduced intake of fermentable oligo-, di- and monosaccharides as well as polyols) is often recommended. FODMAPs include fructose, lactose, and sugar alcohols such as sorbitol and xylitol. These substances are osmotically active in the intestinal lumen and are fermented by bacteria, which can lead to flatulence and exacerbation of symptoms.
However, numerous studies yielded controversial results, so it is currently unclear whether a complex low-FODMAP diet is truly superior to typical general dietary recommendations for IBS (such as avoiding beans, eating regular meals, eating slowly, avoiding carbonated beverages, etc.).
Probationary dietary changes can be made at any time, but these always carry the risk of malnutrition and should therefore be included in professional nutritional counseling.
Stool regulants: A high-fiber diet plays an important role in the therapy of IBS patients of any subtype. Dietary fiber has a regulating effect on stool consistency. However, several studies could only show a beneficial effect for soluble dietary fibers, e.g. for psyllium husks (Psyillium/Ispaghula). In contrast, water-insoluble fiber (such as bran) had no benefit compared with placebo and was even responsible for exacerbation of symptoms in some cases [17,19].
Probiotics: In the development of irritable bowel syndrome, alterations in the gut microbiome play a pathogenetically important role. Therefore, attempts can be made to influence the microbiome in terms of health benefits through the use of probiotics. The preparations consist of single bacterial strains or mixtures of Lactobacilli, Bifidobacteria or Saccharomyces strains considered beneficial. They are usually administered in the form of fermented milk or yogurt. However, it remains unclear which of the numerous preparations should be used in which patients and IBS subtypes. Failure to respond to probationary therapy with a probiotic may result in a change of preparation [21].
Drug therapy
In the case of inadequate response despite exhaustion of non-drug therapies, various drug therapy principles are used based on the predominant symptomatology or IBS subtype. Due to the overall weak evidence for the efficacy of medication in IBS as well as the large placebo effect, drug therapy has a probationary character and must be suspended and switched to an alternative after three months at the latest if there is no response.
Pain therapy: Analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs), metamizole (Novalgin®) or paracetamol do not play a role in the treatment of IBS due to their lack of efficacy for pain in IBS patients. Similarly, opiates are generally not used, partly because of a lack of evidence and partly because of their obstipating effect. An alternative is the use of spasmolytics such as butylscopolamine (Buscopan®), which, in addition to its anticholinergic component, also acts as an opioid agonist and therefore modulates pain [22]. Mebeverine (Duspatalin®) also has an antispasmodic effect, but unlike other spasmolytics, it is not anticholinergic. Another important class of substances for pain modulation are the antidepressants, specifically tricyclic antidepressants such as amitriptyline (tryptizol®) 10 mg/d unretarded (no longer available in Switzerland or only available from international pharmacies), alternatively Saroten if necessary® retard 25 mg, whereby the pain-modulating effect is already achieved at a lower dose than is required for the antidepressant effect. They have a positive effect on IBS symptoms regardless of subtype [23]. Side effects of amitriptyline include urinary retention and constipation, which may be beneficial in IBS-D but problematic in IBS-C.
Phytotherapeutics: Numerous phytotherapeutics and other natural remedies are available for the treatment of functional gastrointestinal disorders. However, their effectiveness has been little studied. An exception is Iberogast®, a mixture of nine different herbal extracts (peppermint, chamomile, lemon balm, caraway, celandine, milk thistle fruit, licorice root, angelica and farmer’s mustard). It showed in several scientifically convincing studies a significant reduction of irritable bowel symptoms and in addition also an improvement of gastric symptoms in functional dyspepsia [24].
Loperamide (Imodium®): Loperamide is frequently used as a stool regulator in patients with diarrhea-type IBS. Its efficacy has been demonstrated in numerous studies; in particular, there is an improvement in stool consistency and a regurgitation of stool frequency [4]. However, there is no evidence that loperamide leads to a decrease in global IBS symptoms [21]. Because of the better dosage, the application as syrup can be considered, which, in contrast to other dosage forms, is not subject to compulsory health insurance in Switzerland.
Linaclotide (Constella®): For several years, linaclotide has been available as a drug specifically for the treatment of moderate to severe IBS-C. The substance acts on the luminal surface of the intestinal epithelium and has a prosecretory effect (chloride, bicarbonate), leading to an acceleration of the colonic transit time. In addition, there is a pain modulating effect through inhibition of afferent visceral nerve fibers [4,25,26]. About one week after the start of therapy, an improvement of the symptoms can be expected. If the medication is discontinued after three months of continuous treatment, no rebound effect is observed. As the drug is still relatively new on the market, no long-term side effect data are currently available. A common side effect is secretory watery diarrhea, which occurs in less than one-fifth of patients and is responsible for discontinuation of therapy in up to 4%.
Eluxadoline (Viberzi®): This promising new compound is used specifically for the treatment of diarrhea-predominant irritable bowel syndrome. It is a combined μ- and κ-opioid receptor agonist and a δ-opioid receptor antagonist that acts on intestinal motility. In the studies conducted to date, significant regredience of abdominal pain and improvement in stool consistency have been achieved. The drug is currently already approved in the USA [27]. Adverse effects are mainly nausea and constipation. However, according to new FDA recommendations, the drug should not be given to cholecystectomized patients because of an increased risk of pancreatitis due to sphincter Oddi spasm. In Switzerland, the preparation is currently not (yet) registered.
Other therapies
Despite exhausted general measures and drug therapy principles, it happens that patients respond inadequately to treatment and are still significantly limited in their quality of life. In these cases, referral to a psychologist or psychotherapist should also be evaluated. Various psychotherapeutic procedures (including psychosomatic-cognitive procedures such as mindfulness therapy [28] or hypnotherapy) are available and have shown therapeutic benefit in IBS with varying response rates. The effect is probably due to a reduction in psychological stress and a reduction in somatization [29]. The importance of other procedures such as acupuncture in the treatment of IBS remains unclear [30].
Conclusion
Irritable bowel syndrome is a common gastrointestinal disorder, which is prognostically harmless, but due to the symptoms is often very stressful for patients and leads to a significant reduction in quality of life. A detailed medical history, meaningful and targeted diagnostics, and the establishment of a good doctor-patient relationship with adequate symptom-oriented therapy are the building blocks of successful treatment.
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