Irritable Bowel Syndrome

Epidemiology and Pathophysiology

Epidemiology

• The onset of symptoms usually begins in adolescence and young adulthood. Approximately 50% of patients report symptoms before the age of 35.
• 60%–70% of cases are women.
• Prevalence in North America is 10%–15%.

Pathophysiology

Although no specific organic cause has been identified, there are several possible pathogenic mechanisms.

• Abnormal motility: 
  • ↑ Frequency of luminal contractions in the intestines
  • Irregularity of luminal contractions
  • ↑ Transit → irritable bowel syndrome (IBS) with constipation
  • ↑ Motor response to cholecystokinin and meals → IBS with diarrhea
• Visceral hyperalgesia: 
  • Hypothesized to be due to ↑ receptor stimulation in the gut wall
  • ↑ Sensitivity to abdominal and rectal distension 
  • ↑ Sensitivity to bloating and gas
• Intestinal inflammation:
  • ↑ Lymphocytes and mast cells have been noted in the bowel → possible ↑ release of mediators that stimulate the enteric nervous system
• Post-infectious changes:
  • ↑ T cells and enteroendocrine cells → ↑ serotonin levels → ↑ gastrointestinal (GI) motility and sensitivity
  • Antibiotic use may also play a role.
• Psychosocial abnormalities:
  •  > 50% of IBS patients have underlying depression, anxiety, or somatization disorders. 
  • Stress → may ↑ corticotropin-releasing factor activity (mediator of the stress response) → ↑ abdominal pain and colonic motility → ↑ IBS symptoms
• Other factors that are being investigated:
  • Altered fecal flora or small intestinal bacterial overgrowth
  • Food allergies, mala

Clinical Presentation

Classification

Irritable bowel syndrome is classified based on the clinical presentation.

• IBS with diarrhea: 
  • Loose or watery stools 
  • Frequent bowel movements (> 3/day)
  • Fecal urgency +/- incontinence
• IBS with constipation: 
  • Hard or lumpy stools 
  • Infrequent bowel movements (< 3/week) 
  • Straining during defecation 
• IBS with mixed bowel habits: presents with both diarrhea and constipation
• Unclassified IBS: insufficient abnormality in the stool consistency or frequency to meet criteria for the other types

Other signs and symptoms

• Chronic abdominal pain 
  • Intermittent, crampy, and frequently in the lower abdomen 
  • Associated with altered bowel habits
  • May improve or worsen with defecation
  • Abdominal tenderness is commonly present in the lower abdomen.
• Abdominal distension or bloating
• Mucousy stools
• Extraintestinal symptoms:
  • Somatic symptoms (e.g. generalized pain, fatigue)
  • Dyspareunia
  • Increased urinary frequency and urgency
• Alarm features that suggest an alternative diagnosis and warrant further investigations:
  • Weight loss or anorexia
  • Fever
  • Nocturnal diarrhea
  • Anemia
  • Severe constipation or diarrhea
  • Progressive symptoms
  • Acute onset of disease, or onset in older patients 

Diagnosis

Criteria for diagnosis

Irritable bowel syndrome is a diagnosis of exclusion, but the Rome IV criteria help provide a standardized diagnosis:

• Recurrent abdominal pain that lasts at least 1 day per week during the previous 3 months
• Is associated with ≥ 2 of the following:
  • Pain related to defecation
  • Change in stool frequency

Tests to rule out organic disease

Work-up will be guided by the patient’s clinical presentation.

• Laboratory tests
  • Complete blood count → screen for iron deficiency anemia → malignancy, celiac disease
  • Fecal calprotectin or fecal lactoferrin → screen for inflammatory bowel disease (IBD)
  • Immunoglobulin A (IgA) tissue transglutaminase → screen for celiac disease
  • Thyroid-stimulating hormone → hyperthyroidism or hypothyroidism
  • Stool ova and parasite → test for Giardia
  • Stool culture → test for other infectious causes
• Abdominal radiograph 
  • Performed in patients with constipation
  • Rules out stool impaction
  • Determines the severity of constipation
• Colonoscopy with biopsy 
  • All patients should have age-appropriate cancer screening. 
  • Use is based on the patient’s presentation to exclude malignancy, IBD, and microscopic colitis.

Management

General measures

• Reassurance, education, and support
• Involve the patient in the treatment process.
• Encourage physical activity.

Dietary modifications

• Most patients can follow a normal diet.
• May exclude gas-producing foods (e.g., beans, brussel sprouts)
• Low-FODMAP (fermentable oligo-, di-, mono-saccharides and polyols) diet
• Dietary or supplemental fiber
• Avoid alcohol and caffeine.
• Maintain proper hydration.

Pharmacologic agents, based on symptoms

• Diarrhea
  • Antidiarrheal agents (loperamide, exuladoline)
  • Bile acid sequestrants (cholestyramine)
  • 5HT-3 receptor antagonists (ondansetron, alosetron, cilansetron)
• Constipation
  • Osmotic laxatives (polyethylene glycol)
  • Chloride channel activators (lubiprostone)
  • Guanylate cyclase-C agonists (linaclotide)
  • 5-HT4 receptor agonists (tegaserod)
• Abdominal pain and bloating
  • Antispasmodic agents (hyoscyamine, dicyclomine, peppermint oil)
  • Tricyclic antide

Differential Diagnosis

• Celiac disease: an immunologically mediated disease resulting in mucosal inflammation and villous atrophy in the small bowel due to gluten. Symptoms include abdominal bloating and foul-smelling diarrhea. Patients may also have nutritional deficiencies and weight loss due to malabsorption, which is not found in IBS. The diagnosis is established with serologic markers and small bowel biopsy. Treatment requires a strict, gluten-free diet.
• Inflammatory bowel disease: includes Crohn’s disease and ulcerative colitis. The disease is characterized by chronic inflammation of the GI tract due to a cell-mediated immune response to the GI mucosa. Symptoms include diarrhea, abdominal pain, weight loss, and extraintestinal manifestations, which help differentiate IBD from IBS. Diagnosis includes imaging, endoscopy and biopsy. Treatment involves steroids, aminosalicylates, immunomodulators, and biologic agents.
• Microscopic colitis: a chronic inflammatory disease of the colon, which can be categorized as collagenous or lymphocytic colitis. Patients tend to be middle-aged. Symptoms include chronic, watery diarrhea, abdominal pain, and bloating. A colonoscopy will appear normal, but inflammatory cells, cryptitis, or a subepithelial collagen band will be seen on biopsy, differentiating microscopic colitis from IBS. Treatment includes trigger avoidance, glucocorticoids, and symptom management.
• Small intestinal bacterial overgrowth: defined as excessive bacteria growing in the small intestine, and can result due to alteration in the intestinal anatomy or motility. Symptoms can range from mildly symptomatic to chronic diarrhea, weight loss, and malabsorption. Bacterial cultures and breath tests can distinguish this condition from IBS. Treatment includes antibiotics and correction of nutritional deficiencies.
• Lactose intolerance: an intolerance to lactose-containing foods due to lactase deficiency. Symptoms include crampy abdominal pain, bloating, nausea, and diarrhea. Diagnosis is based on the association with lactose-containing foods and a lactose hydrogen breath test, which will differentiate the condition from IBS. Management includes restriction of dietary lactose and enzyme replacement.
• Giardiasis: an intestinal infection due to Giardia duodenalis. Patients may be asymptomatic or have watery, foul-smelling diarrhea; abdominal cramping; and distension. Weight loss and evidence of malabsorption may be present and will differentiate this condition from IBS. Stool studies for Giardia will establish the diagnosis, and treatment includes metronidazole, tinidazole, or nitazoxanide.