Irritable bowel syndrome (IBS)

The significant chapter of psychosomatics consists of gastrointerstinal diseases. A new science has been generated – neurogastroenterology.

The Rome criteria have been using as the gold stand­ard for diagnostics and classification of functional gastrointestinal disorders (FGID) over 20 years.

The brain-gut axis represents a classical model of internals and central nervous system cooperation while IBS is a clinical manifestation of the disco- operation. The concept of “brain-gutaxis” was sug­gested in purpose of explanation of different poly­peptides (calcitonin-gene releasing peptide (CGRp), neurotensin, bombesin).

Irritable bowel syndrome (IBS) is a complex of functional disorders that last at least 3 days per month for 3 consecutive months associated with abdominal pain and sense of dis­comfort improving after defecation and change in stool consistency. The total clinical duration should be at least 6 months.

Symptoms of Irritable bowel syndrome

The special IBS symptoms include stool frequency less than 3 per week or more 3 per day, fast, lumpy, liquid or porridge-like stool, defecation tendency, rec­tal urgency, feeling of incomplete bowel emptying, defecation release of mucus and tympany.

The clinical variants of IBS are: diarrhea-prevalent, constipation-prevalent, mixed variant, un-subtyped, postinfectious. The defining parameter is a stool form.

The urgency of the issue: it affects 20% of popu­lation; IBS patients makes up to 12% of visits to primary care doctors and 28% of all visits to gastro­enterologists and a substantial percentage of visits to primary care doctors (in USA 2.5-3.5 million visits yearly); the medical bill for IBS may be as much as 20-25 billion $ annually in USA . The IRS patients visiting a doctor are only a tip of the iceberg, 71­80% of patients seek no medical advice (“nonconculters”, “nonpatients”).

Diagnosis mistakes: IRS misinterpretation as col­lecting condition, wrong diagnosis (chronic spastic colitis, chronic pelvic pain, chronic appendicitis, disbacteriosis and others). There are more 18 syn­onyms for IBS (mucocolitis, intestinal asthma, ab­dominal migraine).

IRS is a biophysycosocial disease.

• Emotional stress: 50% of IBS patients associatethe onset with stress, 1/3 point to the episodes ofphysical or sexual abuse in past history, anxio-depressive disorders and phobias occur more fre­quent in IBS patients.
• Intestinal Dysmotility due to the influence of dif­ferent factors (stress, feeding) is the main reasonfor abdominal pain in IBS patients.
• Visceral hypersensitivity. The lesser extent of bow­el stretching can cause to abdominal pain in IBSpatients because of the altered alertness of centralnervous system; the rectal dilatation activated notlimbic structure as in norm but the prefrontal zoneresponsible for depressive reactions.

In terms of above mentioned many doctors attach great importance to so-called “enteral nervous system” (EnS) presented in gut wall with neurons and intermuscular plexus, receptors combining in a complex network through neurotransmitters, bio­amines connection, in particular, serotonin .

The clinical features of IBS abdominal pain are: lo­calization in ileac region, increasing after food and during menses in women, improvement after def­ecation of passage of flatus, no night awakening.

The clinical features of IBS diarrhea are: absence in the night, start in the morning after breakfast (“morning rush syndrome”), stool frequency 2-4 per day, short intervals between defecations, total fae­ces weight less than 200g per day.

“Extrabowel IBS symptoms” are: headache in the form of migraine, sense of lump by swallowing, in­hale dissatisfaction, impossibility to sleep on the left side, vasospastic reactions, frequent urination, gynaecological disorders.

The key IBS features: onset at a young age, rela­tion of intestinal disorders with neuropsychic fac­tors, high frequency of anxious and hypohondriac reactions, a gap between complaint diversity and objective findings, lack of progression, absence of alarm symptoms.

Alarm IBS symptoms are: onset at an old age, fever, blood admixtures in the excrement, intestinal dis­orders interrupt night sleep, unmotivated weight loss, anemia, leucocitosis, elevated ESR.

The main problem for current IBS diagnosis is a possible overdiagnosis of the disease.

The overdiagnosis reasons:

• Ignorance of the mismatching clinical symptoms and course of disease to Rome criteria III;
• alarm symptoms leave out of account by diagno­sis (“red banners”);
• unreasonable expansion the frame of IBS (IBS in case of Chronic Inflammatory Bowel Diseases -CIBD , bowel diverticulosis) ;
• lack of preliminary laboratory and instrumental examination before diagnosis.

There are two approaches to IBS diagnosis:

1. The compliance of complaints to Rome criteria III and lack of alarm symptoms;
2. IBS diagnosis – diagnosis of exclusion (careful examination of a patient (including colonofiberscopy) and exception organic diseases).

It should be noticed that in patients with diarrhea variant of IBS antibodies to gliadinare identified more often (by several times) than in population, and clinical manifestation in 28% patients with mi­croscopic colitis (lymphocytic, collagenous) com­pletely fulfill Rome criteria for diarrhea variant.

In many patients with ulcerous colitis and Crohn’s disease symptoms are similar to those in case of IBS, so IBS diagnosis can be settled only after the exclusion of specific intestinal diseases and chron­ic inflammatory diseases.

The probability of organic pathology in patients with clinical findings fulfilling Rome Criteria for IBS and with no alarm symptoms is 14%.

In many cases the disease of IBS often combines with dolichosygmoid increasing the obsti­pation-prevalent IBS severity.

It should be noticed that in some patients with postinfectious IBS Faecal Calprotectin (FC) typical for CIBD can be identified. FC identification is rea­sonable not only as a marker of CIBD aggravation or remission, treatment efficiency but for differen­tial diagnosis with functional disorders, first of all IBS. Some studies of ulcerative colitis and Crohn’s disease are performing where Faecal Calprotectin is identified every 3 months for the purpose dynamics monitoring of this parameter during the treatment.

Treatment of Irritable bowel syndrome

The IBS management includes:

1. General arrangements
2. Drug therapy
3. Psychotherapy and psycopharmacotherapy

The most important for the successful manage­ment in patients with IBS is a correct patient – physician relationship.

The key question of IBS drug therapy include:

• Choice of an “adequate” drug
• Optimum duration for drug administration (ex juvantibus)
• Assessment of efficiency
• Decision about drug change or treatment contin­uation

It must be taken into consideration that more than drugs possess a potential hepatotoxicity, 10%of acute hepatic failure is a result of drug admin­istration.

What is a clinical study mission?

The metaanalysis showed the antispastic drug effi­ciency by IBS (53-61%), placebo efficiency – 31-41% (NNT=2.5-5.0) : mebeverine, pinaverium bromide, otilonium bromide.

IBS diarrhea treatment: opioid receptor agonists (loperamide), cholestiramine, tripotassiumdicitra- tobismuthate, 5-HT3receptor antagonists (alosetron); unresorbing antibiotic rifaximin.

Obstipation-prevalent IBS pharmacotherapy: psilium (Plantago ovata), lactulose, promotility agents M- andK-opioid receptoragonists (trimebutine)), 5-HT4-receptor agonists (tegaserod, prucaloprid). Lubiproston and Linaclotide are still being studied .

Concerning about the drug safety changed for the last few years.

The metoclopramide administration can cause tar­dive dyskinesia prolonging after drug cancel. More than 60% of drug withdrawal from pharmaceutical market over the last 16 years have been made be­cause their influence to OT-intervalsize and inducing dangerous arrhythmias (in particular cisapride).

The psychotherapy includes selective serotonin reuptake inhibitor (SSRI) and tricyclic antidepres­sant administering. However the compliance to these drugs is quite low in IBS patients.

The current idea about IBS pathogenesis include carried infections (postinfectious IBS), proinflammatory cytokines elevation, Faecal Calprotectin (FC). In 25% patients the IBS-Like disease with proinflammatory cytokines expression developed after an acute infectious enteritis (including salmonellesis) .Taking into account the new branches of IBS pathogenesis other drug application will be exam­ined (sodiumcromoglycate, 5-ASA-mesaLazine, glucocorticosteroid-budesonide).

Concerning probiotics – the published data are contradictory (efficiency often is overestimated, at best moderate). However the clinical improvement as the response to Bifidobacterinfantis application in case of associated damage of IL -10, Il -12 was mentioned.

Evidence-based assessment is complicated due to the great variety, significant differences of probiot­ics dose and duration application.

“It can be possible that IBS represents no single dis­ease, but a group of some pathogenic-different dis­eases that should be identified in the future.”

Many studies are still being performed and the ob­jectives of the Rome criteria fund remain the same decoding the complexity of functional gastroe­sophageal reflux in the future, that may be reflect­ed in the Rome criteria IV .