Diarrhea Predominant Irritable Bowel Syndrome Jon P Walker, MD MS Division of Gastroenterology, Hepatology, & Nutrition Department of Internal Medicine The Ohio State University Wexner Medical Center

No financial disclosures.

Objective • Understand the diagnostic criteria for D-IBS • Understand the multiple factors contributing to the condition • Understand the important of doctor-patient relationship in successful therapy • Understand the role for dietary regulation • Understand the medication options • Understand the role for probiotics/antibiotics

Epidemiology • Epidemiologic factor difficult to ascertain (approx 5-20%) • Difficult disease to clearly diagnose • Physician and Patients more or less willing to make the diagnosis • Cultural factors may effect reporting of symptoms

• Young/Middle age Patients • Symptoms reported back to childhood

• Predominance in women • 4:1 • Western countries; Opposite in Asia • Underlying psychiatric/psychologic condition

Challenging Medical Condition • 40% report symptom severe enough: • • • • • •

Miss work Curtail social life Cancel appointments Stop traveling Home confinement Avoid sexual intercourse

J Psychosom Res 1990 34: 483

Challenging Medical Conditions • Difficult to diagnose • Leads to further worry/doubt • Frequent doctors visits: test & procedures • Surgeries • Estimated health care cost: $8 billion/year

Gastroenterology; 1995 109: 1736

IBS Rome III Criteria • Recurrent abdominal pain or discomfort at least 3 days/months at least 3 months associated with 2 or more of the following: • Improvement with defecation • Onset associated with a change in frequency of stools • Onset associated with a change in consistency of stools Note: In the absence of red flag symptoms!

Clinical Features: Supporting the Diagnosis • Rome Criteria • Long history relapsing/remitting course (childhood) • Exacerbations triggered by life events/stressors • Variability of symptoms (location, nature, severity) • Associated with symptoms of other organ systems… • Coexistence of anxiety or depression • Distress out of proportion to nature of the symptoms • Exacerbations with eating • Conviction that symptoms are caused by “popular” concerns

IBS Symptoms Extraintestinal symptoms

Other Associated GI symptoms: • Heartburn • Dyspepsia • Loss of appetite • Bloating

• • • • • • • • • • •

Fatigue Dyspnea Back pain Headache Dizziness Urinary frequency Arthritis Palpitations Anxiety/panic attacks Sexual dysfunction Depression

Clinical Features: Supporting the Diagnosis • Rome Criteria • Long history relapsing/remitting course (childhood) • Exacerbations triggered by life events/stressors • Variability of symptoms (location, nature, severity) • Associated with symptoms of other organ systems… • Coexistence of anxiety or depression • Distress out of proportion to nature of the symptoms • Exacerbations with eating • Conviction that symptoms are caused by “popular” concerns

Rule Out Typical Organic Disease • Celiac • Microscopic colitis • IBD (Crohn’s, UC) • Cancer (Right colon cancer; VIPoma) • Food allergy • SBBO • Infection • Pancreatic insufficiency

Rule out underlying organic disease • Celiac markers +/- upper endoscopy with small bowel biopsies • Colonoscopy with right/left colon biopsies • Stool culture • CBC, chemistries, CRP, ESR • Fecal fat • +/- CT abdomen

IBS

J Neurogastroenterol Motil. 2011 Oct;17(4):349-359

IBS Physiologic Scenario

J Neurogastroenterol Motil. 2010 Oct;16(4):363-373.

Physician/Patient Interaction

Most important aspect of care: • Establish healthy relationship with the patient • Need to know you think this is real • Need to know its not just “in their head” • Need to know you are interested in helping their symptoms, not just proving that this is not organic then being done. • Need reassurance • Chance at improved symptoms deminished if patient does not “buy into the treatment”.

Physician-Patient Interaction • 262 patients • 3 arms • Wait-list (28) • Sham acupuncture (44) • Sham acupuncture with strong interaction (62)

• Patient with placebo and strong interaction did best • BMJ. 2008;336(7651):999.

Diet

Role for Diet • Romanian study: 193 patients • 19.1% met criteria for IBS • IBS subjects ate more canned meat, processed meat, legumes, whole cereals, sweets, and fruit compotes

• Swedish study: 197 patients w/ IBS completed survey • 84% reported symptoms associated w/ ≥1 food • 70% carbs: dairy, legumes, apple, flour, plums

Chirila J Gastrointestinal Liver dis Dec 21 357 2012 Bohn Am J Gastroenterol 108 634 2013

Dietary Considerations • 46 patients • 17 completed study • Received 3 x 45 min dietician counseling sessions • IBS questionnaire before and 3 months after

Molecular Medicine Reports 8(3) 2013; 845

Lactose and Fiber • Lactose • Not more prevalent in IBS patients • May exacerbate IBS symptoms • Worth a try! • No benefit of lactose breath test

• Psyllium based fiber • Long history of use for IBS-D • 13 RCT : Not efficacious • May actually cause worsened: • • • •

Abdominal pain Bloating Global symptoms NICE Guidelines actually suggest decreasing fiber to 12g/day. BMJ 2008: 336.

Gluten Sensitivity • Non-celiac gluten hypersensitivity may contribute to symptoms • Am J Gastro 2011 : • 34 patients • No endoscopic or genetic (HLA-DQ2 or DQ8) evidence of celiac disease. • Received gluten free diet or placebo • Gluten diet patient more likely to report inadequate symptoms control (68 vs 40%)

Am J Gastroenterol 2011; 106:508–514

Low Carbohydrate Diet Daily Stool Frequency

• 17 patient enrolled; 13 completed the study • 2 week standard diet; followed by 4 week VLCD • 77% reported adequate relief for at 2 weeks during the 4week VLCD • Decreased stool frequency: 2.6 to 1.4 (p Intracerebral & Peripheral Gastrointestinal Effects • Intraperitoneal CRF increased colonic transit and gut permeability (blocked by 5-HT3 inhibitor) • Post-infectious IBS Biopsies: EC hyperplasia with increased serotonin availability -> Increased sensitivity to gut distension (blocked by 5-HT3 inhibitor)

5-HT3 Inhibitor • Alosetron • Constipation/Ischemic colitis/bowel perforation • Restricted prescribing program • Women with severe, refractory IBS-D for >6 months

• Ondansetron • Limited data • May be beneficial and safe

5-HT3 Inhibitor: Alosetron • 705 women with severe IBS • RCT Placebo, 0.5mg QD, 1mg QD, 1mg BID • IBSQOL, Treatment satisfaction, Lost workplace productivity, Daily activities • Measured at baseline and after 12 weeks.

Aliment Pharmacol Therap 2012 Sep;36(5):437-48

5-HT3 Inhibitor: Alosetron

Loss of workplace productivity

Treatment satisfaction Aliment Pharmacol Ther. 2012 Sep;36(5):437-48

5-HT3 Inhibitor: Alosetron • 705 women with severe IBS • RCT Placebo, 0.5mg QD, 1mg QD, 1mg BID • IBSQOL, Treatment satisfaction, Lost workplace productivity, Daily activities • Measured at baseline and after 12 weeks. • One case ischemic colitis • Most common side-effect: constipation

Aliment Pharmacol Ther. 2012 Sep;36(5):437-48

Ondansetron • Few studies investigating its use • Small studies indicate potential for use in chronic diarrhea • Increase stool bulk • No significant side effects reported • Possible alternative to Alosetron

5HT3 Inhibitor: Ondansetron • NEJM 2013 (N Engl J Med 2013; 368:1947-1948) • Report of 6 patients with diarrhea secondary to metastatic neuroendocrine tumor • All with significant benefit with ondansetron 8mg x 2 doses.

Psychosocial therapy

Psychosocial therapy • Hypnosis, Biofeedback, Psychotherapy • Motivated patients • Metaanalysis 2009: 1278 adults w/ IBS • 50% reduction in symptoms • RR for persisting symptoms 0.66 (95% CI, 0.57-0.79) • NNT 4 • Supported by ACG Task Force on IBS Gut 2009; 58: 367

Summary • Rule out organic disease (limited workup) • Evaluate for presence of stressors • Carefully evaluate role of diet in symptoms: Think about FODMAPs or Gluten Free • Multiple options for therapy: will likely require multifocal therapy • Consider TCA as 1st line agent in depression w/ strong IBS symptoms.

• No easy answer: patients need to understand • Establishing rapport imperative!!!

Gastroenterology

Patient

Psychology/ Psychiatry

PCP

The End

Narcotics • May be beneficial for short term use in suspected organic etiology • Must avoid for long-term use • Patients must understand long term ramifications • Fight the urge for short-term positive reinforcement • Narcotic bowel syndrome

Narcotic Bowel Syndrome • Chronic or recurrent abdominal pain • Narcotics relieve bowel pain but then tachyphylaxis occurs • Pain worsens when narcotic effect wears off • Shorter pain free episodes result in increasing narcotic doses • Increase doses further alters motility and aggravate pain • Can occur in functional disease, organic disease, or healthy patients

Clin Gastro Hep 2007; 5:1126

Narcotic Bowel Syndrome

Narcotic Bowel Syndrome

IBS – Role of Immunity

J Neurogastroenterol Motil. 2011 Oct;17(4):349-359

IBS Diarrhea

Intest Res. 2010 Dec;8(2):95-105.

Augmentation Therapy • Use more than one treatment to enhance benefit • Can use lower doses and minimize side effects • Helpful when one treatment not successful or with side effects • Use with referactory disorders • Examples • Add antidepressant to peripheral GI agent • Add SSRI to TCA • Combine antidepressant and psychologic treatment Am J Gastro; 2009; 104; 2897