Irritable bowel syndrome overview

# Overview
Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by abdominal pain and alteration of bowel habits. IBS is caused by the complex interaction of various factors such as intrinsic gastrointestinal factors, CNS dysregulation, psychosocial factors, genetic and environmental factors. Intrinsic gastrointestinal factors include motor abnormalities, visceral hypersensitivity, immune activation, and mucosal inflammation, altered gut microbiota and abnormal serotonin pathways. A definite cause of irritable bowel syndrome (IBS) has not yet been established. However, an interplay of several factors contribute to the development of IBS such as emotional disturbances, stress, adverse early life events, history of inflammatory bowel disease, and acute gastrointestinal infections. Irritable bowel syndrome (IBS) may be classified according to Rome IV criteria into four sub types/groups: IBS with predominant constipation, IBS with predominant diarrhea, IBS with mixed bowel habits, and unclassified IBS. In addition, IBS occurring secondary to GI infections is known as post infectious-IBS or PI-IBS. Irritable bowel syndrome must be differentiated from other diseases that cause diarrhea, constipation, and abdominal pain, such as celiac disease, inflammatory bowel disease (Crohn's disease and ulcerative colitis), thyroid disease (hyper or hypothyroidism), strictures due to ischemia, diverticulitis or ischemia, among others. The diagnosis of IBS depends on the recognition of gastrointestinal symptoms that wax and wane and are exacerbated by psycho-social stress. Therefore, the diagnosis of IBS is based primarily on clinical symptoms and elimination of other organic gastrointestinal diseases. This is due to lack of definitive radiologic or laboratory diagnostic tests in IBS. There are no strict guidelines for the treatment of IBS and the therapy is mostly symptom-based. All IBS patients are required to adapt a diet low in fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs). A psychiatric referral and regular exercise are very helpful for all IBS patients. Pharmacological therapy is adjunctive and only preferred in patients where symptoms of IBS are moderate-severe in intensity and markedly impair the quality of life. Pharmacological therapy administered to patients is based on the predominant symptom, with diarrhea-predominant, constipation-predominant, and pain-predominant subtypes having their own different regimens. New therapies such as herbal medications, tight-junction modulators, mast cell stabilizers, acupuncture, and mind body therapy currently have an uncertain role in the treatment of IBS.

# Historical Perspective
Irritable Bowel syndrome(IBS) was first mentioned in the Rocky Mountain Medical Journal in 1950.  IBS was described as a psychosomatic disorder, not explained by any biochemical or structural abnormalities. Apley and Nash conducted a famous study on 1000 children in Bristol, United Kingdom and were the first to describe Recurrent Abdominal Pain (RAP) as the predominant feature of IBS. In 1978, the first diagnostic criteria i.e. the Manning criteria was described. It did not specify any required duration for the symptoms of IBS. The subsequent criteria saw a reduction in the required duration of symptoms to facilitate early diagnosis and treatment. In Rome in 1995, an international group of gastroenterologists defined the diagnostic criteria for IBS and this was published in 1999 under the title of the Rome II criteria. This criteria underwent modification and was described as the Rome III criteria. Since June 2016, the criteria being followed is the Rome IV criteria.

# Classification
Irritable bowel syndrome (IBS) may be classified according to Rome IV criteria into four sub types/groups: IBS with predominant constipation , IBS with predominant diarrhea, IBS with mixed bowel habits,and IBS unclassified. In addition, IBS occurring subsequent to GI infections is known as Post infectious-IBS or PI-IBS. The rationale behind these different sub types is to maintain consistency of patient selection. This increases understanding of pathophysiological mechanisms, aids in effective diagnosis, treatment and patient recruitment for clinical trials.

# Pathophysiology
IBS is caused by the complex interaction of various factors such as intrinsic gastrointestinal factors, CNS dysregulation and psychosocial factors, genetic and environmental factors. Intrinsic gastrointestinal factors include motor abnormalities, visceral hypersensitivity, immune activation and mucosal inflammation, altered gut microbiota and abnormal serotonin pathways. Visceral hypersensitivity is a decreased threshold for the perception of visceral stimuli that affects spinal excitability brain stem and cortical modulation, activation of specific gastrointestinal mediators and recruitment of peripheral silent nociceptors. Immune activation and mucosal inflammation involves an interaction of lymphocytes, mast cells and proinflammatory cytokines. Environmental factors encompass dietary changes and infections. Psychosocial factors such as stress, anxiety and depression directly shape adult connectivity in the executive control network consisting of structures such as the insula, anterior cingulate cortex and the thalamus. Semipermanent/permanent changes in complex neural circuits lead to central pain amplification and contribute to abdominal pain in IBS patients. The dorsolateral prefrontal cortex activity (responsible for vigilance and alertness of the human brain) and the mid-cingulate cortex (engaged in attention pathways and responses) is reduced in IBS patients,  which may lead to alterations in the subjective sensations of pain. Genetic factors also play a role in IBS. It has high twin concordance and familial aggregation. It is associated with Single nucleotide polymorphisms (SNPs) in genes involved in immune activation, neuropeptide hormone function, oxidative stress, nociception, permeability of the GI tract, host-microbiota interaction, inflammation, and TNF activity.

# Causes
There is no definite cause that has been established for irritable bowel syndrome (IBS). However, an interplay of several factors contribute to the development of IBS such as emotional disturbances, stress, adverse early life events, history of inflammatory bowel disease, and acute gastrointestinal infections. Less common causes of IBS include genetics and hormonal changes.

# Differentiating IBS from Other Diseases
Irritable bowel syndrome must be differentiated from other diseases that cause diarrhea, constipation, and abdominal pain, such as Celiac disease, Inflammatory bowel disease(Crohn's disease and Ulcerative colitis) Thyroid disease (Hyper or Hypothyroidism), strictures due to ischemia, diverticulitis or ischemia, among others.
The differential diagnosis for Irritable bowel syndrome can be listed based on predominant symptoms, such as constipation predominant, diarrhea predominant and pain predominant diseases.

# Epidemiology and Demographics
IBS is an extremely common disorder in the population. The incidence of IBS is approximately 200 per 100,000 individuals worldwide. The prevalence of IBS is approximately 11,200 per 100,000 individuals worldwide. The prevalence of IBS varies with geographical and demographic distribution. Females are more commonly affected by IBS than males. The female to male ratio is approximately 1.5-3.  The prevalence of IBS in USA and Europe is 10,000-20,000 per 100,000 individuals. In USA and Australia, 1 in every 10 people fulfill the Rome criteria for IBS. In Asia, Africa and South America, IBS is becoming increasingly prevalent as a disease of urbanization and industrialization. This is due to increased access to health care, higher stress levels and differing dietary choices.

# Risk Factors
Common risk factors in the development of IBS include stress, anxiety, depression, history of IBD and acute gastrointestinal infections.

# Screening
There is insufficient evidence to recommend routine screening for Irritable Bowel Syndrome.

# Natural History, Complications, and Prognosis
The symptoms of IBS usually develop in the second decade of life, and start with symptoms such as abdominal pain, diarrhea and constipation. IBS may develop after exposure to early life adverse events, sexual abuse, anxiety, depression and stressors. Psychological conditions may also develop as complications of the disease. If left untreated, patients with IBS may progress to develop malnutrition (resulting from food intolerance), impacted bowel, and poor quality of life. Common complications of IBS include dehydration, hemorrhoids and fatigue. Prognosis is good, as IBS does not lead to life threatening complications or shorten lifespan of an individual.  IBS patients tend to have long symptom free intervals interspersed with periods of severe symptoms. Although Irritable bowel syndrome may be a life-long condition, symptoms can often be improved or relieved through treatment.

# Diagnosis
As per the Rome IV criteria, the diagnosis of IBS is made when at least two of the following diagnostic criteria are met in association with abdominal pain for  1 day per week, in the previous 3 months with an onset of 6 months : Change in stool consistency, pain related to defecation and absence of warning signs such as unintentional loss of weight, age 50 years, recent change in bowel habit, hematochezia or melena i.e. evidence of overt gastrointestinal bleeding.
The definition of IBS according to Rome IV, is recurrent abdominal pain associated with a change in frequency and/or form of the stool. It considers IBS as a disorder of gutbrain interaction as opposed to being a functional disorder of the GI tract. The term abdominal discomfort mentioned in Rome  III, has been removed in Rome IV to counter ambiguity. In addition to this, the frequency of abdominal pain has been changed from at least 3 days a month in the preceding 3 months (Rome III) to at least one day per week in the preceding 3 months (Rome IV).  The phrase improvement of abdominal pain with defecation in Rome III has been changed toabdominal pain related to defecation in Rome  IV, as some IBS patients may report worsening of pain following defecation. Experts state that physicians should limit evaluation to Rome criteria fulfillment, if no alarm symptoms are present.

## History and Symptoms
The diagnosis of IBS relies on recognition of gastrointestinal symptoms that wax and wane for and are exacerbated by psycho social stress. Diagnosis of IBS is based on on clinical symptoms and elimination of other organic gastrointestinal diseases. This is due to lack of definitive radio logic or laboratory diagnostic tests in IBS.The hallmark of IBS is abdominal pain. A positive history of stress, anxiety, depression, panic disorders, gastrointestinal disorders such as IBD and acute GI infection predispose individuals to IBS. The most common symptoms of IBS include presence of abdominal pain and alteration of bowel habits. Less common symptoms of IBS include flatulence and upper GI symptoms such as heartburn, nausea, dyspepsia and vomiting.

## Physical Examination
Patients with IBS usually appear normal on physical exam. Physical examination of patients with IBS may elicit abdominal tenderness in some patients. A digital rectal examination must be performed in all patients to rule out rectal growths, blood in stool and evaluate for dyssynergic defecation (where paradoxical contraction of the rectal sphincter occurs on straining, leading to constipation).  Physical findings such as fever, abdominal mass, hepatosplenomegaly, lymph node enlargement, weight loss, peritoneal signs and ascites are absent in IBS and help rule out organic causes.

## Laboratory Findings
The diagnosis of IBS is based on clinical symptoms and elimination of other organic gastrointestinal diseases. This is due to lack of definitive radiologic or laboratory diagnostic tests in IBS. If the history and physical exam are suggestive of IBS in the absence of alarm features, complete blood count, occult blood test, complete metabolic panel and ESR are usually normal. Additional tests may be costly and harmful in young patients with typical IBS symptoms, in the absence of alarm features. To determine the aggressiveness of the diagnostic evaluation, the American Gastroenterological Association has defined certain factors that must be considered such as degree of psychosocial impairment, age and sex of the patient, family history of colorectal cancer etc. In patients that require aggressive diagnostic evaluation, additional diseases such as Celiac disease, IBD, Clostridium difficile infection, Giardiasis, lactase deficiency, bile salt malabsorption and colon cancer should be ruled out.

## Electrocardiogram
There are no ECG findings associated with IBS.

## X-ray
There are no x-ray findings associated with IBS. However, an x-ray may be helpful in the ruling out obstruction, stool retention and aerophagia during a pain episode. In  IBS patients presenting with dyspepsia, upper GI radiographs help rule out other causes. Small bowel barium radiography helps in the diagnosis of ileal and jejunal Crohn's disease and diverticulae.

## CT scan
There are no CT scan findings associated with IBS.

## MRI
There are no MRI findings associated with IBS.

## USG
There are no ultrasound findings associated with IBS.  IBS patients presenting with with postprandial right upper quadrant pain, must undergo an ultra sonogram of the gallbladder to rule out pain due to cholecystitis. Postmenopausal women presenting with constipation, abdominal distension and pain localized to the lower abdomen should undergo  trans vaginal and trans abdominal ultrasonography to rule out ovarian cancer.

## Other Imaging Findings
75SeHCAT testing may be helpful in the diagnosis of IBS patients with bile acid diarrhea. The 75SeHCAT test measures the whole-body retention of 75Se-homocholyltaurine, a bile acid radiolabeled with the gamma-emitting isotope selenium-75. Retention of the isotope is measured by gamma-camera scanning performed a week after administration.

## Other Diagnostic Studies
In young patients with symptoms of classic IBS, additional invasive investigations such as endoscopy are not required and increase patient dissatisfaction. However, endoscopic evaluation is performed in difficult cases of IBS where history is unclear but the physical examination is suggestive of the diagnosis. All IBS patients with alarm features must undergo endoscopic evaluation. Moreover, colonoscopy must be considered in patients aged more than 50 years as part of routine colon cancer screening. Sigmoid colon biopsies and duodenal biopsies are required for exclusion of microscopic colitis, Crohn's disease, and celiac disease. Anorectal manometry is a diagnostic technique used to rule out obstructive defecation (pelvic-floor dyssynergia).

# Treatment

## Medical Therapy
IBS is heterogeneous in its presentation. There are no strict guidelines for the treatment of IBS and therapy is mostly symptom-based. All IBS patients are required to adopt a diet low in  fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs). A psychiatric referral and regular exercise are considered necessary in all IBS patients. Pharmacological therapy is adjunctive and only preferred in patients where symptoms of IBS are moderate-severe in intensity and markedly impair the quality of life. Pharmacological therapy administered to patients is based on the predominant symptom with diarrhea-predominant, constipation-predominant and pain-predominant subtypes having their own different regimens. New therapies such as herbal medicines, tight-junction modulators, mast cell stabilizers, acupuncture, and mind body therapy currently have an uncertain role in the treatment of IBS.

## Surgery
Surgical intervention is not recommended for the management of IBS.

## Primary Prevention
Effective measures for the primary prevention of IBS include early and effective treatment of stress, anxiety, depression and panic disorders. Early counseling for victims of physical or sexual abuse and avoidance of certain foods such as fatty food, wheat, carbonated drinks, sorbitol and alcohol in those with food sensitivities helps in the primary prevention of IBS.

## Secondary Prevention
There are no established measures for the secondary prevention of IBS.