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Irritable Bowel Syndrome

Chapter 338 | Disorders of the Gastrointestinal System · Part 10 – Gastrointestinal Disorders · Chapter 338


Key Clinical Points

  1. IBS is a functional gastrointestinal disorder characterized by abdominal pain and altered bowel habits without structural abnormalities.
  2. Diagnosis is based on Rome IV criteria: recurrent abdominal pain (≥1 day/week for 3 months) associated with ≥2 of: relation to defecation, change in stool frequency, or change in stool form.
  3. Alarm features (age >40 at onset, weight loss, nocturnal symptoms, rectal bleeding, anemia) require investigation to rule out organic disease.
  4. Core pathophysiology includes visceral hypersensitivity, central neural dysregulation, and gut-brain interaction.
  5. Postinfectious IBS occurs in >10% of patients with infectious enteritis (4-fold higher risk than non-infected individuals).
  6. Low FODMAP diet improves symptoms in 50–80% of patients, primarily addressing pain and bloating.
  7. Rifaximin (550 mg TID for 2 weeks) is effective for IBS-D with bloating and gas.
  8. Secretagogues (Linaclotide, Lubiprostone) are used for IBS-C; Eluxadoline is used for IBS-D.
  9. Gut dysbiosis in IBS involves decreased Bifidobacterium/Faecalibacterium and increased Enterobacteriaceae/Lactobacillaceae/Bacteroides.
  10. Up to 25% of patients with IBS-D may have underlying bile acid malabsorption.

1. DEFINITION & OVERVIEW

Definition: Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by abdominal pain or discomfort and altered bowel habits in the absence of detectable structural abnormalities. • Clinical Characteristics: ◦ No specific diagnostic markers exist; diagnosis is based on clinical presentation. ◦ Symptoms fluctuate over time and often overlap with other functional disorders (fibromyalgia, headache, backache, and genitourinary symptoms). ◦ Significant impact on quality of life and high direct/indirect healthcare costs. • Rome IV Diagnostic Criteria: ◦ Requirement: Symptoms for ≥3 months, with onset at least 6 months prior to diagnosis. ◦ Core Criteria: Recurrent abdominal pain (average ≥1 day per week in the last 3 months) associated with ≥2 of the following: → Related to defecation → Associated with a change in frequency of stool → Associated with a change in form (appearance) of stool


2. EPIDEMIOLOGY

Prevalence: Approximately 10% of adults and adolescents worldwide. ◦ Most patients present before age 45. • Gender Distribution: ◦ Women are diagnosed 2–3 times more often than men. ◦ Women comprise 80% of the population with severe IBS. • Comorbidities: High prevalence in other functional GI disorders (e.g., noncardiac chest pain, esophageal hypersensitivity).


3. ETIOLOGY & PATHOPHYSIOLOGY

Multifactorial Nature: Involves genetic susceptibility and environmental insults.

3.1 GI Motor Abnormalities: ◦ No consistent abnormalities in unstimulated conditions. ◦ Prominent under stimulated conditions (e.g., post-prandial). ◦ IBS-D: Increased motility index and peak amplitude of high-amplitude propagating contractions (HAPCs) → rapid colonic transit → abdominal pain.

3.2 Visceral Hypersensitivity: ◦ Exaggerated sensory responses to visceral stimulation. ◦ Food intolerance perception is ≥2x more common than in the general population. ◦ Lower thresholds for first sensation of gas, discomfort, and pain (especially with lipids). ◦ Selection: Afferent pathway disturbances are specific to visceral innervation; somatic pathways are spared.

3.3 Central Neural Dysregulation: ◦ Evidence from functional brain imaging (MRI). ◦ Mid-cingulate cortex: Greater activation in response to distal colonic stimulation → increased perception of unpleasantness. ◦ Prefrontal lobe: Shows hypervigilance of visceral pain.

3.4 Abnormal Psychological Features: ◦ Present in up to 80% of patients. ◦ Stress alters sensory thresholds. ◦ History of sexual or physical abuse associated with higher distress and worse outcomes (linked to activation of posterior/middle dorsal cingulate cortex).

3.5 Postinfectious IBS: ◦ >10% of patients with infectious enteritis develop IBS (4-fold risk compared to non-infected individuals). ◦ Higher risk in females, younger patients, and those with severe/prolonged infections (parasitic/bacterial gt viral).

3.6 Immune Activation & Mucosal Inflammation: ◦ Low-grade mucosal inflammation; activated lymphocytes, mast cells, and proinflammatory cytokines (IL-6, IL-1β, TNF). ◦ Mast cell activation mediates barrier dysfunction.

3.7 Altered Intestinal Permeability: ◦ "Leaky gut" primarily in IBS-D and postinfectious IBS. ◦ Reduced expression of tight junction proteins → increased passage of macromolecules/bacteria.

3.8 Altered Gut Flora: ◦ 4x higher odds of small-intestinal bacterial overgrowth (SIBO) based on breath tests. ◦ Lower diversity in IBS patients. ◦ Decreased: Bifidobacterium, Faecalibacterium. ◦ Increased: Enterobacteriaceae, Lactobacillaceae, Bacteroides.

3.9 Abnormal Serotonin Pathways: ◦ Increased enterochromaffin cells in IBS-D. ◦ TPH1 polymorphism associated with IBS subtypes. ◦ SERT downregulation due to gram--negative gut dysbiosis → abnormal mucosal serotonin levels.

3.10 Bile Acids: ◦ Up to 25% of patients with IBS-D have idiopathic bile acid diarrhea. ◦ Mechanism: Reduced synthesis of FGF-19 by ileal mucosa or genetic variation → increased colonic bile acid → accelerated transit, increased permeability, and visceral hypersensitivity.


4. CLINICAL FEATURES

Abdominal Pain: ◦ Essential for diagnosis. ◦ Variable intensity/location; often episodic/crampy or constant ache. ◦ Exacerbated by eating/stress; improved by flatus/stool passage. ◦ Females: Worsening during premenstrual/menstrual phases.

Altered Bowel Habits: ◦ Most consistent clinical feature. ◦ Subtypes: IBS-C (constipation), IBS-D (diarrhea), IBS-M (mixed). ◦ IBS-C: Hard stools, infrequent (<3/week), incomplete evacuation, straining. ◦ IBS-D: Small volumes of loose stools (<200 mL), urgency, mucus, incontinence.

Gas and Flatulence: ◦ Patients report bloating/distention; however, gas volume is often normal. ◦ Mechanism: Impaired transit → intolerance of gas loads → reflux of gas from distal to proximal intestine (belching).

Upper GI Symptoms: ◦ 25–50% experience dyspepsia, heartburn, nausea, vomiting. ◦ High overlap between dyspepsia and IBS.


5. DIFFERENTIAL DIAGNOSIS

Epigastric/Periumbilical Pain: → Differentiate from: Biliary tract disease, peptic ulcer, intestinal ischemia, carcinoma (stomach/pancreas). • Lower Abdominal Pain: → Differentiate from: Diverticular disease, IBD (UC/Crohn's), colon cancer. • Postprandial Symptoms (Nausea/Vomiting): → Differentiate from: Gastroparesis, partial intestinal obstruction. • Diarrhea-specific: → Rule out: Lactase deficiency, malabsorption, celiac sprue, hyperthyroidism, IBD, infectious diarrhea. • Constipation-specific: → Rule out: Drug effects (anticholinergic, antihypertensive), hypothyroidism/hypoparathyroidism, acute intermittent porphyria, lead poisoning. • Infectious: → Giardia lamblia or other parasites.


6. INVESTIGATIONS & DIAGNOSIS

  1. Clinical Evaluation: Perform thorough history and physical exam to identify typical features (recurring pain, no progression, absence of systemic symptoms) and rule out organic disease.
  2. Routine Laboratory Testing: • CBC, fecal calprotectin (or lactoferrin), and/or CRP in IBS-D patients even without alarm features → rule out IBD.
  3. Serologic Testing: Perform celiac serology if prevalence of celiac disease is ≥1% in the population.
  4. Stool Examination: Test for ova and parasites if in endemic regions or history suggests exposure to untreated water.
  5. Specific Symptom-Driven Tests: • For diarrhea/gas: Hydrogen breath test (lactase deficiency) or 3-week lactose-free diet. • For excessive gas/bloating: Glucose hydrogen breath test (rule out SIBO).
  6. Imaging/Endoscopy: • If dyspepsia present: Upper GI radiographs or esophagogastroduodenoscopy. • If postprandial RUQ pain: Ultrasound of the gallbladder.
  7. Alarm Features (Require Colonoscopy): • Age >40 at onset. • Weight loss. • Nocturnal symptoms. • Rectal bleeding. • Anemia. • Persistent diarrhea after 48-h fast. • Steatorrheal stools.
  8. Laboratory Findings Arguing Against IBS: → Evidence of anemia, elevated sedimentation rate, leukocytes/blood in stool, or stool volume >200–300 mL/d.

7. MANAGEMENT & TREATMENT

  1. Education and Counseling: • Reassurance regarding functional nature. • Identification of personal triggers.
  2. Lifestyle Modifications: • Stress management. • Exercise (recommended for all patients).
  3. Dietary Management: • Elimination of identified food precipitants. • Low FODMAP diet: Reduces global symptoms in 50–80% of patients (improves pain and bloating). Common sources include apples, wheat, lactose, etc.
  4. Pharmacotherapy:Stool-Bulking Agents: → Psyllium husk, Methylcellulose, Calcium polycarbophil. • Antidiarrheal Agents: → Loperamide: 2–4 mg when necessary (max 12 g/d). → Diphenoxylate and atropine sulfate (Lomotil): 1–2 tabs as needed or daily. → Eluxadoline: 100 mg bid (approved for IBS-D). → Alosetrona: 0.5–1 mg bid (severe IBS, women). → Linaclotide: (for IBS-C). → Lubiprostone: (for IBS-C). → Other options: Cholestyramine, Lactulose, 70% sorbitol, Polyethylene glycol 3350, Magnesium hydroxide, Plecanatide, Tenapanor. • Antispasmodics: → Smooth-muscle relaxants: qd to qid ac. • Neuromodulators: → Tricyclic antidepressants (TCAs): Start 25–50 mg hs, then adjust (effective for IBS-D by slowing transit and modulating visceral afferent neural function). • Antimicrobials: → Rifaximin: 550 mg TID for 2 weeks (for IBS-D with bloating/gas). • Probiotics: → Used to modulate gut flora.

8. PROGNOSIS & COMPLICATIONS

Prognosis: ◦ Generally good; no progression of disease. ◦ Malnutrition is extremely rare. ◦ Sleep deprivation is uncommon as pain is typically only during waking hours. • Complications: ◦ Impact on quality of life and productivity. ◦ Potential for overlap with other functional disorders (fibromyalgia, etc.).


9. SPECIAL CONSIDERATIONS

Pediatric/Adolescent: → Symptoms often begin before age 45; similar management principles apply. • Postinfective Patients: → Higher risk in females and younger patients; may require more aggressive investigation of underlying triggers.


10. KEY PEARLS & CLINICAL TRAPS

Rome IV is the gold standard for diagnosis based on pain + 2 features (defecation, frequency, form). • Alarm features are the primary trigger to escalate to invasive testing (colonoscopy/endoscopy). • Visceral hypersensitivity is a core mechanism; patients have lower thresholds for pain than healthy controls. • Rifaximin is specifically indicated for IBS-D with gas/bloating. • Low FODMAP diet is highly effective but should not lead to nutritionally deficient diets. • Bile acid malabsorption is a common underlying cause in a subset of IBS-D patients.


Reference Tables

TABLE 338-1 Rome IV Diagnostic Criteria for Irritable Bowel Syndrome a Recurrent abdominal pain, on average, at least 1…

Harrison's 22e, p.2571

  • Recurrent abdominal pain, on average, at least 1 day per week in the last
    3 months, associated with ≥2 of the following criteria:
    1. Related to defecation
    2. Associated with a change in frequency of stool
    3. Associated with a change in form (appearance) of stool

TABLE 338-2 Some Common Food Sources of FODMAPs

Harrison's 22e, p.2576

FOOD TYPE FREE FRUCTOSE LACTOSE FRUCTANS GALACTO-
OLIGOSACCHARIDES
POLYOLS
Fruits Apple, cherry, mango,
pear, watermelon
Peach, persimmon, watermelon Apple, apricot, pear, avocado,
blackberries, cherry, nectarine,
plum, prune
Asparagus, artichokes,
sugar snap peas
Artichokes, beetroot, Brussels
sprout, chicory, fennel, garlic,
leek, onion, peas
Grains and cereals Wheat, rye, barley
Pistachios
Milk and milk products Milk, yogurt, ice cream,
custard, soft cheeses
Legumes, lentils, chickpeas Legumes, chickpeas,
lentils
Other Honey, high-fructose
corn syrup
Chicory drinks
Inulin, FOS

TABLE 338-4 Possible Drugs for a Dominant Symptom in

Harrison's 22e, p.2577

SYMPTOM DRUG DOSE
Diarrhea Loperamide 2–4 mg when necessary/maximum
12 g/d
Diphenoxylate
hydrochloride and
atropine sulfate (Lomotil)
1–2 tabs as needed or daily (can be
taken up to 4 times daily)
Cholestyramine resin 4 g with meals, can be started qd
and increased to tid
Eluxadoline 100 mg bid
Alosetrona 0.5–1 mg bid (for severe IBS,
women)
Psyllium husk
Methylcellulose
Calcium polycarbophil
Lactulose syrup
70% sorbitol
Polyethylene glycol 3350
Lubiprostone
Magnesium hydroxide
Linaclotide
Plecanatide
Tenapanor
Abdominal pain Smooth-muscle relaxant qd to qid ac
Tricyclic antidepressants Start 25–50 mg hs, then adjust
Low FODMAP diet
Low FODMAP diet
Probiotics
Rifaximin

TABLE 338-3 Spectrum of Severity in IBS Clinical Features Prevalence Correlations with gut physiology Symptoms constant…

Harrison's 22e, p.2577

MILD MODERATE SEVERE
Clinical Features
Prevalence 70% 25% 5%
+++ ++
Symptoms constant 0 + +++
0 +
Health care issues + ++ +++
Primary Specialty