Irritable Bowel Syndrome

Aka: Irritable Bowel Syndrome, Diarrhea Dominant Irritable Bowel Syndrome, Irritable Bowel Syndrome with Diarrhea, Pain Dominant Irritable Bowel Syndrome, Constipation Dominant Irritable Bowel Syndrome, Irritable Bowel Syndrome with Constipation, Irritable Bowel Syndrome with Alternating Bowel Habits

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II. Epidemiology

  1. Prevalence
    1. Overall in U.S.: 5-10%
    2. Lifetime Prevalence: 10-22%
  2. Slightly more common in women (1.5 fold increased risk over men)
  3. Prevalence for elderly same as for young (however, peak time of diagnosis at 20-39 years old)
  4. Most common condition seen by Gastroenterologists

III. Pathophysiology

  1. Organic factors
    1. Gastrointestinal Hypersensitivity
    2. Altered motility
    3. Neurohormonal factors
    4. Mucosal barrier dysfunction
  2. Provoked by psychosocial risk factors
    1. Prior physical or sexual abuse significantly increases risk
  3. Severe Gastroenteritis episode may be associated (Odds Ratio 5.9)
    1. Antibiotics (Rifaximin, Neomycin) have reduced symptoms in some cases
  4. Familial association
    1. Risk increases 3 fold with Family History of Irritable Bowel Syndrome

IV. Associated Conditions

  1. Gastroesophageal Reflux Disease
  2. Dysphagia
  3. Globus Hystericus
  4. Fatigue
  5. Non-cardiac Chest Pain
  6. Urologic dysfunction
  7. Gynecologic disease (e.g. Chronic Pelvic Pain)
  8. Fibromyalgia
  9. Chronic Fatigue Syndrome
  10. Temperomandibular joint syndrome
  11. Food Allergy
  12. Low-fiber diet

V. Risk Factors: Psychosocial

  1. Anxiety Disorder
  2. Major Depression
  3. Somatization Disorder
  4. Sexual abuse or physical abuse
  5. Stressful life events
  6. Substance Abuse

VI. Types

  1. Alternating Diarrhea and Constipation
  2. Nervous Diarrhea
  3. Predominant Constipation
  4. Upper Abdominal Bloating and discomfort

VII. Symptoms

  1. Altered bowel habits
    1. Diarrhea
    2. Constipation
    3. Scybalous stools (hard, pellet-like stools)
    4. Mucus per Rectum (40% of cases)
    5. Incomplete evacuation Sensation (69% of cases)
  2. Recurrent and Chronic Abdominal Pain (73% of cases)
    1. Upper abdominal discomfort after eating
    2. Left Lower Quadrant Abdominal Pain
    3. Right Lower Quadrant Abdominal Pain
    4. Abdominal Pain relieved with Defecation (52% of cases)
  3. Gaseousness
    1. Excessive Flatulence or Eructation
    2. Normal patients experience about 13 farts per day
    3. Abdominal Distention (32% of cases)
  4. Nausea or Vomiting
  5. References
    1. Ford (2008) JAMA 300(15): 1793-805 [PubMed]

VIII. Exam

  1. Obtain a full set of Vital Signs including weight for comparison with historical weights
  2. Perform a general exam evaluating for undiagnosed systemic disease
  3. Perform a complete abdominal exam including genitourinary exam and Rectal Exam

IX. Diagnosis: Rome IV Criteria

  1. Abdominal symptoms persistent or recurrent for 6 months or more
    1. Symptoms occur at least one day per week for at least 3 months
    2. Abdominal Pain, bloating or discomfort
  2. Two or more below
    1. Related to Defecation (Straining, stool urgency, incomplete evacuation, pain relieved with stooling)
    2. Change in frequency of stool
    3. Change in appearance, form or consistency of stool
  3. Other symptoms supporting Irritable Bowel Syndrome diagnosis
    1. Abnormal stool frequency (>3/day or <3/week)
    2. Abnormal stool form (loose or watery, or hard and lumpy)
    3. Abnormal stool passage (urgency, straining, incomplete emptying)
    4. Mucus in stool
    5. Abdominal Distention or bloating (exclude red flag causes)
  4. Subtype classification
    1. Diarrhea predominant
      1. More than 25% of stools are Bristol Stool Scale 6-7 (Mushy or liquid stools) and less than 25% are type 1-2
    2. Constipation predominant
      1. More than 25% of stools are Bristol Stool Scale 1-2 (Hard or lumpy stool) and less than 25% are type 6-7
    3. Mixed
      1. More than 25% of stools are Bristol Stool Scale 6-7 (Mushy or liquid stools)
      2. More than 25% of stools are Bristol Stool Scale 1-2 (Hard or lumpy stool)
  5. Changes from Rome III Criteria
    1. Altered stool passage criteria removed (Straining, stool urgency, incomplete evacuation)
    2. Rome IV requires weekly symptoms (previously monthly symptoms with Rome III)
  6. References
    1. Lacy (2016) Gastroenterology 150(6): 1393-407 [PubMed]

X. Diagnosis: Manning Criteria

  1. Onset of pain linked to more frequent Bowel Movements
  2. Looser stools associated with onset of pain
  3. Pain relieved by stool passage
  4. Noticeable Abdominal Bloating
  5. Sensation of incomplete evacuation more than 25% of the time
  6. Diarrhea with mucus more than 25% of the time

XI. Red Flags: Symptoms and signs suggestive of other diagnosis

  1. Red Flag Symptoms
    1. Nighttime Diarrhea
    2. Nocturnal Stool Incontinence
    3. Nocturnal awakening due to abdominal discomfort
    4. Abdominal Pain that interferes with normal sleep
    5. Diarrhea without pain suggests alternative diagnosis
    6. Severe large volume Diarrhea (esp. bloody, nocturnal, or unrelated to eating)
    7. Tenesmus
  2. Red Flag Signs
    1. Visible or occult blood in stool
    2. Unintentional Weight Loss
    3. Recurrent Fever
    4. Abdominal mass
    5. Jaundice
    6. Lymphadenopathy
  3. Red Flag Risk Factors
    1. Family History of Colon Cancer
    2. Family History of Inflammatory Bowel Disease
    3. Family History or other risk factors for Ovarian Cancer
    4. Older patients with new onset after age 55 years old
  4. Red Flag Laboratory abnormality
    1. Leukocytosis
    2. Anemia
    3. Increased Erythrocyte Sedimentation Rate (ESR) or C-Reactive Protein

XII. Differential Diagnosis

  1. Colonic Adenocarcinoma (Colon Cancer)
  2. Inflammatory Bowel Disease
    1. Ulcerative Colitis
    2. Crohn's Disease
  3. Abdominal Angina (Ischemic Colitis or Mesenteric Ischemia)
  4. Pseudo-obstruction (Diabetes Mellitus, Scleroderma)
  5. Intermittent Sigmoid Volvulus
  6. Endocrine causes
    1. Hypothyroidism or Hyperthyroidism
    2. Diabetes Mellitus
    3. Addison's Disease
    4. Electrolyte abnormalities associated with Constipation (Hypokalemia, Hypomagnesemia)
  7. Malabsorption
    1. Celiac Sprue (strongly consider if Diarrhea with red flags)
    2. Lactose Intolerance
    3. Pancreatic insufficiency
  8. Infectious Causes
    1. Giardiasis
    2. Clostridium difficile (Pseudomembranous colitis)
    3. Toxic Megacolon or Bacterial overgrowth syndrome
  9. Genitourinary Causes
    1. Endometriosis
  10. Other Functional Gastrointestinal Disorders
    1. Dyssynergic Defecation (Pelvic Floor Dysfunction)
    2. Functional Abdominal Bloating
    3. Functional Diarrhea
  11. Psychiatric illness (provocative)
    1. Major Depression
    2. Somatization
    3. Anxiety Disorder or Panic Disorder
  12. Medications
    1. Opioids (Opioid Induced Constipation)
    2. See Medication Causes of Diarrhea
    3. See Medication Causes of Constipation

XIII. Evaluation

  1. General
    1. Avoid a piecemeal work-up
      1. Perform a complete evaluation, based on presenting symptoms, the first time
      2. Avoid over-investigation and exhaustive testing
    2. Irritable bowel is no longer diagnosis of exclusion
      1. Diagnostic criteria above are sufficient to treat
      2. Lab and imaging are typically low yield in cases otherwise suggestive of Irritable Bowel Syndrome
        1. Fewer than 5% of Irritable Bowel Syndrome patients receive an alternative diagnosis
        2. El Serag (2004) Alminent Pharmacol Ther 19(8): 861-70 [PubMed]
    3. Indications for full evaluation and Gastroenterology
      1. Red flags present (see above) or
      2. Onset over age 50-55 years
  2. Careful History
    1. History of Gastrointestinal Symptoms
    2. Family History of gastrointestinal disease
    3. Marital History
    4. Sexual Abuse (strong correlation)
  3. Reasonable exam
    1. Thorough abdominal examination
    2. Also focus on possible endocrine causes
  4. Look for Food Intolerance (consider diet diary)
    1. Lactose Intolerance
    2. Sorbitol
    3. Wheat (Gluten Sensitive Enteropathy)

XIV. Labs: Initial, based on predominant symptom

  1. Constipation Dominant
    1. Complete Blood Count (CBC)
    2. Serum Electrolytes or Chemistry panel (chem8) including Serum Calcium
    3. Thyroid Stimulating Hormone (TSH)
    4. Digital Rectal Exam for rectal mass, impaction
    5. Other tests to consider
      1. Anorectal manometry (dyssynergic Defecation)
      2. Colon transit study (slow transit Constipation)
  2. Diarrhea Dominant
    1. See Chronic Diarrhea
    2. See Chronic Watery Diarrhea
    3. Distinguish from non-allergic food intolerance (e.g. Lactose), Bile Acid Malabsorption
    4. Distinguish from chronic Functional Diarrhea (>25% loose stools without pain or bloating)
    5. Evaluation in absence of negative red flags
      1. Complete Blood Count (CBC)
      2. Celiac Sprue testing (esp. if signs of Iron Deficiency)
        1. IgA Tissue Transglutaminase AND
        2. Total IgA (with reflex if low to IgG Gliadin)
    6. Other tests to consider if indicated by history (previously recommended as part of standard default protocol)
      1. Fecal Calprotectin
      2. Stool GiardiaAntigen
      3. Stool Ova and Parasites
      4. Fecal Leukocytes
      5. Stool 48 hour collection for bile acid (evaluation for bile acid Diarrhea)
      6. Serum Electrolytes or chemistry panel
      7. Thyroid Stimulating Hormone (TSH)
      8. Erythrocyte Sedimentation Rate (ESR) or C-Reactive Protein (C-RP)
      9. Colonoscopy with biopsy (see below)
  3. Pain Dominant
    1. Complete Blood Count (CBC)
  4. Reference
    1. Fass (2001) Arch Intern Med 161:2081-8 [PubMed]

XV. Diagnostics

  1. Colonoscopy of Flexible Sigmoidoscopy
    1. More uncomfortable in Irritable Bowel Syndrome
    2. Not absolutely indicated if remainder of evaluation suggests Irritable Bowel Syndrome
      1. Consider if red flags, age over 50 years or Microscopic Colitis risk
  2. Consider additional studies as indicated (to evaluate differential diagnosis)
    1. CT Abdomen with contrast
    2. Right upper quadrant Ultrasound
    3. Upper GI Study
    4. Barium Enema

XVI. Management: General Measures

  1. See the patient frequently
    1. Maintain a strong doctor-patient relationship
    2. Offer frequent reassurance of Irritable Bowel Syndrome as a benign condition
    3. Identify and treat emotional stressors
    4. Answer patients questions in unhurried environment
    5. Patient should keep a journal of symptoms combined with dietary intake and other triggers
  2. Do not downplay symptoms as psychiatric
    1. Irritable Bowel is a real functional bowel problem
    2. Explain physiology and absence of serious illness
  3. Reduce stressors
    1. Teach Relaxation Techniques
    2. Teach coping mechanisms for chronic illness
  4. Regular Daily Exercise
  5. Consider Probiotics (weak evidence)
    1. May improve bloating, Flatulence, pain and Constipation
    2. Bifidobacterium infantis (Align)
    3. Bifidobacterium bifidum MIMBb75
      1. Decreases overall irritable bowel symptoms
      2. Guglielmetti (2011) Aliment Pharmacol Ther 33(10): 1123-32 [PubMed]
  6. General Diet recommendations
    1. Get adequate fluid intake (>64 ounces/day)
    2. Bulk agents
      1. See Fiber Supplementation
      2. Gradually increase to 25-30 g daily (and ensure adequate hydration)
        1. Risk of gas, bloating, distention, Flatulence if started too quickly with high dosing
        2. Side effects more likely with dyssynergic Defecation
        3. Side effects are more common with insoluble fiber
      3. Soluble Fiber Sources (absorbs water)
        1. Psyillium (Metamucil)
        2. Oat bran
      4. Insoluble Fiber Sources
        1. Methylcellulose (Citrucel)
        2. High fiber-bran, wheat brain
    3. Avoid FODMAPs (Fementable Oligo- di and mono saccharides and polyols)
      1. See FODMAP
      2. FODMAP avoidance may reduce pain, bloating, distention and overall bowel-related symptoms
        1. Considered a first-line intervention, and appears more effective than antispasmodics
        2. Black (2022) Gut 71(6): 1117-26 [PubMed]
        3. Carbone (2022) Gut 71(11): 2226-32 [PubMed]
      3. Avoid fructose (e.g. apples, pears, high fructose corn syrup)
      4. Avoid Fructans (fructooligosaccharides, inulins, levans - e.g. high fiber bars)
      5. Avoid Lactose (consider challenge with quart of skim milk)
      6. Avoid Polyols (sugar Alcohols: Sorbitol, xylitol, Mannitol, malitol
      7. Avoid Galactooligosaccharides (e.g. brussel sprouts, onions)
    4. Consider avoiding other provocative agents
      1. Consider Elimination Diet (although no evidence to support this)
        1. True food intolerance is a rare cause of symptoms
        2. FODMAPS restriction has much higher yielf
      2. Avoid Caffeine
      3. Avoid Alcohol
      4. Avoid Legumes and other gas producing foods (see FODMAPS above)
      5. Avoid Artificial Sweeteners and carbonated beverages (see Polyols above)
      6. Avoid Fatty meals
      7. Corn, wheat and citrus may also exacerbate Irritable Bowel Syndrome
      8. Some fiber can also exacerbate symptoms
  7. Avoid Provocative or addictive medications
    1. See Medication Causes of Diarrhea
    2. See Medication Causes of Constipation
    3. Avoid Stimulant Laxatives (except brief use)
      1. Correctol
      2. Dulcolax
      3. Cascara
    4. Avoid Sedatives or Tranquilizers (Benzodiazepines)
    5. Avoid Opioids
    6. Avoid Anticholinergic Medications such as Antihistamines (Constipation dominant IBS)
    7. Other medications that may contribute to Irritable Bowel Syndrome symptoms
      1. Antibiotics
      2. Calcium Channel Blockers
      3. Metformin
      4. Magnesium containing Antacids

XVII. Management: Diarrhea Dominant Irritable Bowel Syndrome

  1. General measures (see above)
    1. Consider eliminating lactose, Caffeine from diet
    2. Exclude Gluten Sensitive Enteropathy as cause
    3. Fiber supplementation
    4. Probiotics
    5. Consider dietician Consultation
    6. Avoid provocative medications
      1. See Medication Causes of Diarrhea
  2. Rifaximin (Xifaxan)
    1. Small improvements in symptoms (NNT 10) at a high cost ($1300 for a 14 day course)
    2. Relapse by 6 months is common (requiring another dose)
  3. Eluxadoline (Viberzi)
    1. Schedule IV OpioidAgonist similar to Imodium, but taken daily at $1400/month
    2. Marginal efficacy (NNT 11) for decreased Diarrhea and Abdominal Pain at 6 months
    3. Risk of serious Pancreatitis (deaths have occurred) due to sphincter of odi spasm
      1. Contraindicated in prior Cholecystectomy, prior Pancreatitis or >3 Alcohol drinks per day
    4. (2016) Presc Lett 23(6):32
    5. (2017) Presc Lett 24(5):27
  4. Alosetron (Lotronex)
    1. Like Ondansetron, also a Serotonin (5-HT3) receptor Antagonist that reduces rapid transit and stool urgency
    2. Risk of Constipation and Ischemic Colitis
      1. Iatrogenic deaths have occured
      2. Black box warning: Signed Informed Consent needed
    3. FDA controlled prescriptions only for women with IBS with Diarrhea
      1. Requires special Informed Consent and must be part of a prescriber program
    4. Dose: 0.5 mg orally twice daily (may advance to 1 mg twice daily after 4 weeks if tolerated)
  5. Cholestyramine 4 grams at bedtime to 6 times daily
    1. Limited evidence
    2. Consider empiric trial (bile acid Diarrhea)
  6. Loperamide (Imodium) 2-4 mg up to four times daily
    1. Before meals and as needed in stressful social situations
    2. Lomotil could be used, but has not been studied in IBS.
  7. Ondansetron (Zofran)
    1. Ondansetron 4 mg up to three times daily (typically once daily or less)
    2. Serotonin (5-HT3) receptor Antagonist
    3. Reduces rapid transit and stool urgency and frequency
  8. Amitriptyline (Elavil)
    1. Amitriptyline 10 mg titrated to 30-50 mg at bedtime (increasing dose by 10 mg per 1-2 weeks)
    2. Consider for pain and Diarrhea (Anticholinergic effects may reduce stooling)
  9. Peppermint
    1. Enteric coated Peppermint Oil (e.g. Pepogest)
    2. Pittler (1998) Am J Gastroenterol 93:1131-5 [PubMed]

XVIII. Management: Pain Dominant Irritable Bowel Syndrome

  1. General measures (see above)
    1. Exercise
    2. Cognitive Behavioral Therapy
    3. Pain management
  2. Chronic Pain
    1. Tricyclic Antidepressants
      1. Amitriptyline (Elavil) 25 mg orally at bedtime
      2. Desipramine (Norpramin) 50 mg orally three times daily
      3. SNRI agents (e.g. Venlafaxine, Duloxetine) may be considered, but have not been definitively studied in IBS
    2. Tegaserod (Zelnorm)
      1. Withdrawn from market in 2007 due to Cardiovascular Risks (but still available for limited use)
      2. Nyhlin (2004) Scand J Gastroenterol 39:119-26 [PubMed]
    3. SSRI medications do not appear to be effective in reducing IBS symptoms including pain
      1. Tabas (2004) Am J Gastroenterol 99:914-20 [PubMed]
  3. Post-prandial pain: Anticholinergic
    1. Avoid chronic, frequent use
    2. Trial for 2 weeks and stop if no effect
    3. Antispasmodics
      1. Dicyclomine (Bentyl) 10-20 mg, 15-30 min before meal, up to 4 times daily
      2. Hyoscamine XR (Levbid) 0.375 to 0.75 mg twice daily (up to 1.5 g/day)
      3. Hyoscyamine (Levsin) 0.125 to 0.25 mg, 15-30 min before meal, up to every 4 hours (max 1.5 mg/day)
    4. Peppermint Oil (see reference below)
      1. Enteric coated Peppermint Oil (e.g. Pepogest)

XIX. Management: Constipation Dominant Irritable Bowel Syndrome

  1. General measures (see above)
    1. Exercise
    2. Use gastro-colic response
      1. Wake-up, eat breakfast and anticipate stool in AM
    3. Avoid provocative medications
      1. See Medication Causes of Constipation
  2. First line: Bulk agents (e.g. Fiber, Psyllium, bran)
    1. Titrate to 20-30 grams per day
    2. Risk of bloating initially (requires adequate hydration)
    3. Evidence to support is lacking, but remains a central tool in IBS management
  3. Second line (use at bedtime for AM stool)
    1. Improves stool frequency, but may not alter Abdominal Pain or bloating
    2. Osmotic agents
      1. Polyethylene Glycol (Miralax) 1 capful in 8 ounces at bedtime (preferred)
      2. Lactulose 1-2 teaspoons at bedtime
      3. Milk of Magnesia 1-2 tablespoons at bedtime
    3. Consider Stimulant Laxatives if osmotic agents fail
      1. Senna or Cascara
      2. Bisacodyl
  4. Third line (typically by gastrointestinal specialist referral)
    1. Prescription agents that increase gastrointestinal transit and intestinal fluid
      1. Expensive (even generic Amitiza is $300 per month)
    2. Linzess (Linaclotide)
      1. Guanylate cyclase-c Agonist
      2. May improve stool frequency, consistency, Abdominal Pain and straining, but risk of Diarrhea
      3. Expensive ($7 per pill) for minimal efficacy (NNT 5-8) for decreased pain
      4. (2012) Prescr Lett 19(12): 68-9
    3. Trulance (Plecanatide)
      1. Guanylate cyclase-c Agonist similar to Linzess (Linaclotide)
    4. Ibsrela (Tenapanor)
      1. Sodium/Hydrogen Exchanger 3 Inhibitor (NHE3 Inhibitor)
      2. Taken 50 mg orally twice daily immediately before first meal of day and then again in the evening
      3. Expensive ($1500/month in 2022 for twice daily dosing; other third line agents are $300 to $500/month)
      4. Increases intestinal fluid with similar efficacy as Lubiprostone and Linaclotide
      5. Risk of Diarrhea (16% of cases) which may be severe (2.5% of cases)
      6. (2022) Presc Lett 29(6): 36
      7. Curtis (2022) Am Fam Physician 105(6): 656-8 [PubMed]
  5. Restricted Use agent (emergency use only due to risk)
    1. Tegaserod (Zelnorm): 5-HT4 Agonist
      1. Cardiovascular event risk prompted removal from U.S. market in 2007
      2. Dose: 6 mg bid 30 minutes before meals
  6. Other agents potentially useful
    1. Amitiza (Lubiprostone)
      1. Acts at intestinal chloride channels to increase intestinal fluid secretion and Small Intestine stool transit
      2. Drossman (2009) Aliment Pharmacol Ther 29(3): 329-41 [PubMed]
    2. Loxiglumide (Cholecystokinin-A receptor Antagonist)
    3. Guar-Gum
      1. Parisi (2002) Dig Dis Sci 47:1696-704 [PubMed]
    4. Peppermint
      1. Enteric coated Peppermint Oil (e.g. Pepogest)
      2. Pittler (1998) Am J Gastroenterol 93:1131-5 [PubMed]

XX. Management: Other specific symptoms or comorbidities

  1. Excessive Flatus (gas)
    1. See General dietary recommendations (including FODMAP avoidance) as above
    2. Simethicone 40 to 125 mg up to qid
    3. Beta-galactosidase (Beano)
  2. Comorbid Mood Disorders
    1. Major Depression
      1. SSRI Medications or other Antidepressants
    2. Anxiety
      1. See Anxiety Management

XXI. Resources

  1. International Foundation for Functional GI Disorders
    1. http://www.iffgd.org
  2. American College of Gastroenterology
    1. http://www.ACG.GI.org

XXII. References

  1. (2015) Presc Lett 22(5):29
  2. Burgers (2020) Am Fam Physician 101(8): 472-80 [PubMed]
  3. Camilleri (2000) Gastroenterology 120:652-68 [PubMed]
  4. Camilleri (1999) Am J Med 107(5A):27F-32S [PubMed]
  5. Chang (2006) Curr Treat Options Gastroenterol 9(4):314-23 [PubMed]
  6. Drossman (1999) Am J Med 107(5A):41S-50S [PubMed]
  7. Hammer (1999) Am J Med 107(5A):5S-11S [PubMed]
  8. Heymann-Monnikes (2000) Am J Gastroenterol 95:981-4 [PubMed]
  9. Holten (2003) Am Fam Physician 67(10):2157-62 [PubMed]
  10. Jailwala (2000) Ann Intern Med 133:136-47 [PubMed]
  11. Mertz (2003) N Engl J Med 349:2136-46 [PubMed]
  12. Naliboff (1999) Curr Rev Pain 3:144-52 [PubMed]
  13. Ringel (2001) Annu Rev Med 52:319-38 [PubMed]
  14. Viera (2002) Am Fam Physician 66:1867-80 [PubMed]
  15. Weinberg (2014) Gastroenterology 147(5):1146-8 +PMID:25224526 [PubMed]
  16. Wilkins (2012) Am Fam Physician 86(5): 419-26 [PubMed]
  17. Wilkinson (2021) Am Fam Physician 103(12): 727-36 [PubMed]

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