Diarrhoea: A Running Commentary

Diane O’Meara Physician Associate

Digestive Diseases Centre Objectives

• Discuss common and sort-of-common causes of (chronic) diarrhoea • Review the standard tests done in GP setting for evaluation of diarrhoea • Discuss what happens after a patient is referred to gastroenterology for investigation of diarrhoea A Few Causes, in no particular order • Medication • Microscopic • Infectious • Bile acid diarrhoea • Coeliac • Small bowel bacterial • IBD overgrowth • Bowel cancer • Pancreatic insufficiency • Diverticular • Lactose malabsorption • Overflow • IBS Definition

• A condition in which stool is – more liquid than usual and – is passed more frequently than usual (three or more in a day) • Patients may use a variety of terms – Clotted cream – Liquidy – Fluffy – Wet wind Classification Possible Investigations GP

• Standard stool culture – Salmonella, Shigella, Campylobacter, E coli 0157 – C difficile • Ova and Parasites, Giardia and Cryptosporidium • Bloods – FBC, B12, folate, studies – Thyroid function – tTG IgA (coeliac) – CRP (IBD) – CA-125 (ovarian cancer) • FIT (if age appropriate) – Measure of occult blood- neoplasm/polyp? • Faecal – Measure of - (IBD?) Parasitic Infection and Chronic Diarrhoea • Recommended to send 3 samples for O&P, 2 days apart • Immunocompromised • Travellers – ‘other than to Western Europe, North America, Australia or New Zealand’ (NICE) Note travel history

• On request form for the lab • Where • When (up to 2 years?) • Household contacts travelled?? UHL • Immune-mediated (immune system attacking the small bowel) • Precipitated by exposure to dietary gluten Coeliac Disease

• 0.7% prevalence in Europe • Diarrhoea may be present in 43-85% of patients • Other signs and symptoms may include abdominal pain, constipation, weight loss, iron/vitamin deficiencies, fatigue, infertility Interactive • A 25 year old woman is seen in the GP surgery for a history of abdominal bloating and diarrhoea. Her brother had similar symptoms and was diagnosed with coeliac and is much better on a gluten free diet. Which is the most appropriate screening test for coeliac disease? – A. Duodenal biopsy – B. Endomysial – C. HLA-DQ2 and HLA-DQ8 – D. Total IgA – E. tTG IgA Interactive • A 25 year old woman is seen in the GP surgery for a history of abdominal bloating and diarrhoea. Her brother had similar symptoms and was diagnosed with coeliac and is much better on a gluten free diet. Which is the most appropriate screening test for coeliac disease? – A. Duodenal biopsy – B. Endomysial antibody – C. HLA-DQ2 and HLA-DQ8 – D. Total IgA – E. tTG IgA Coeliac Disease

• tTG IgA (tissue transglutaminase) – Screening test – Lab should check total IgA levels – Must be done on a gluten-containing diet • Endomysial antibody – More expensive – More specific (fewer false positives) than tTG IgA – Less sensitive (more false negatives) than tTG IgA – Must be done on a gluten-containing diet • HLA-DQ2 (85-90%) and HLA-DQ8 (5-10%) – Must carry to have coeliac – Low sensitivity- 40% of population carries it (don’t have to have coeliac if you carry it) – Can be used in patients on a gluten free diet Interactive • Her tTG IgA is 40 U/mL (0-4). What is the next appropriate step? – A. Gluten challenge with 2 pieces of bread a day and recheck tTG IgA in eight weeks to measure change. – B. Keep on current diet and refer to Gastroenterology for OGD with duodenal biopsy. – C. Initiate gluten-free diet and refer to Gastroenterology for OGD with duodenal biopsy. – D. Initiate gluten-free diet and recheck tTG IgA in eight weeks. – E. Metronidazole 500mg bd for 10 days. Interactive • Her tTG IgA is 40 U/mL (0-4). What is the next appropriate step? – A. Gluten challenge with 2 pieces of bread a day and recheck tTG IgA in eight weeks to measure change. – B. Keep on current diet and refer to Gastroenterology for OGD with duodenal biopsy. – C. Initiate gluten-free diet and refer to Gastroenterology for OGD with duodenal biopsy. – D. Initiate gluten-free diet and recheck tTG IgA in eight weeks. – E. Metronidazole 500mg bd for 10 days. Coeliac Disease

• Patients with positive tTG IgA must be referred to Gastro for Oesophagogastroduodenoscopy (OGD) with duodenal biopsy. – Gold standard – This is needed to make the diagnosis – Must be done on a gluten-containing diet Coeliac Disease

Upper endoscope: used for OGD Endoscopic findings

Normal duodenal villi Endoscopic findings

• Villous atrophy

• Histologic findings: Photo credit Sherif Shabana Intraepithelial lymphocytes, (Friends of Endoscopy Facebook Group) crypt hyperplasia Coeliac disease • Treatment: – Lifelong gluten free diet (dietician) • coeliac.org.uk • Monitor tTG IgA (should return to normal on a 100% gluten free diet) • Other bloods- FBC, haematinics, Vitamin D, , TFTs, LFTs • First degree relatives should be offered screening (FCP) • Measure of intestinal inflammation • Protein (dimer of calcium binding proteins) • High concentration in cytoplasm • Resistant to degradation- easy to measure in faeces • Typically used in Inflammatory Bowel Disease (colitis more than small bowel disease) FCP • Results – <30 normal – Up 200 not sure, need to consider other factors – 200 to 1800 not sure, warrants investigation – >1800 strongly considering IBD (or infection) Interactive • A 19 year old man is referred to Gastro outpatients for a six month history of loose stool. He opens his bowels 8 times a day with occasional blood. He has lost approximately one stone (6kg) over this period of time. He complains of joint pains. Faecal calprotectin is >1800. Which is the next most appropriate step? – A. – B. CT Thorax, abdomen, pelvis – C. OGD with duodenal biopsy – D. Rheumatology referral – E. Soluble fibre (psyllium husk) Interactive • A 19 year old man is referred to Gastro outpatients for a six month history of loose stool. He opens his bowels 8 times a day with occasional blood. He has lost approximately one stone (6kg) over this period of time. He complains of joint pains. Faecal calprotectin is >1800. Which is the next most appropriate step? – A. Colonoscopy – B. CT Thorax, abdomen, pelvis – C. OGD with duodenal biopsy – D. Rheumatology referral – E. Soluble fibre (psyllium husk) Colonoscopy Inflammatory Bowel Disease

• Ulcerative Proctitis Inflammatory Bowel Disease • Autoimmune disease • Crohn’s Colitis UK website • Crohn’s disease • Treatment – Small bowel – 5 ASAs – Colon • Mesalasine, Pentasa, – Fistulising Salofalk, Asacol, Octasa • Sulfasalazine (joint • problems) – Proctitis – Immunomodulators – Left/right sided • 6MP, Azathioprine – Pancolitis – Biologics • Infliximab, Adalimumab, • Diagnosed Vedolizumab, – Colonoscopy Ustekinemab, Golimumab – Capsule endoscopy – Steroids • Prednisolone, Budesonide Interactive • A 54 year old man goes to the GP surgery with a 6 week history of loose stool. Prior to this he had a normal bowel habit. He has lost one stone (6kg). Investigations are sent and stool cultures are negative, tTg IgA is <1, thyroid function tests are normal, FBC is normal, FIT is elevated at 300 ng/mL (<10). Which is the next most appropriate test? – A. Colonoscopy on 2WW – B. Faecal calprotectin – C. Flexible sigmoidoscopy on 2WW – D. Referral to dietician – E. Iron studies Interactive • A 54 year old man goes to the GP surgery with a 6 week history of loose stool. Prior to this he had a normal bowel habit. He has lost one stone (6kg). Investigations are sent and stool cultures are negative, tTg IgA is <1, thyroid function tests are normal, FBC is normal, FIT is elevated at 300 ng/mL (<10). Which is the next most appropriate test? – A. Colonoscopy on 2WW – B. Faecal calprotectin – C. Flexible sigmoidoscopy on 2WW – D. Referral to dietician – E. Iron studies Colonoscopy Obstructive diarrhoea CT Colonography

https://radiopaedia.org/articles/computed-tomographic-ct- Case courtesy of Dr Dalia Ibrahim, Radiopaedia.org, rID: 28747 colonography Dr Dan J Bell◉ and Dr Dalia Ibrahim et al. FIT (faecal immunochemical test)

• Newer test specific for human blood in stool (as opposed to blood from foods eaten) • Rolled out in 2018 • One sample instead of three samples of two • BCSP ages 60 to 74 every other year • May use for over age 50 with unexplained pain/weight loss FIT • Who will have a positive FIT? – Neoplasm – Polyp – Colitis (IBD, ischaemic) – Haemorrhoids • How does diarrhoea fit in? – Obstructive neoplasm – IBD/colitis Interactive • A 30 year old man goes to gastro outpatients for follow up. He has had several normal investigations for diarrhoea including a colonoscopy. He reports feeling better for a few weeks after the colonoscopy but his diarrhoea has returned. He is embarrassed because he is now having accidents. He has been on increasing doses of loperamide, currently taking 16mg a day. Which is the best recommendation? – A. Add macrogol – B. Discontinue loperamide and start macrogol – C. Haemorrhoid suppositories – D. Increase loperamide to 32mg daily – E. Trial a gluten free diet Interactive • A 30 year old man goes to gastro outpatients for follow up. He has had several normal investigations for diarrhoea including a colonoscopy. He reports feeling better for a few weeks after the colonoscopy but his diarrhoea has returned. He is embarrassed because he is now having accidents. He has been on increasing doses of loperamide, currently taking 16mg a day. Which is the best recommendation? – A. Add macrogol – B. Discontinue loperamide and start macrogol – C. Haemorrhoid suppositories – D. Increase loperamide to 32mg daily – E. Trial a gluten free diet Overflow diarrhoea

• Not uncommon • Constipation problem • May have alternating constipation and diarrhoea • Patients often report improvement in diarrhoea after undergoing bowel prep for colonoscopy • Treatment is fibre/laxatives/getting bowels moving Diverticular Disease

• Diverticula: – Outpouchings of bowel wall • Diverticulitis – An infection of the diverticula • Diverticular Bleed – Results from an exposed vessel at a diverticular edge Diverticula on colonoscopy and barium enema

Case courtesy of Dr Jeremy Jones, Radiopaedia.org, rID: 6197 Diverticular Disease

• Over time the bowel wall can become thickened and create a bottle neck effect resulting in alternating diarrhoea and constipation • Treatment – Laxatives Interactive

• A 63 year old woman is seen in gastro outpatients for an 8 month history of diarrhoea opening her bowels 6 times a day without blood. She has been taking lisinopril for a few years but no other regular medications. She denies weight loss. Stool culture, tTG IgA, thyroid function tests are normal and she is up to date with bowel cancer screening. What is the next step? – A. Trial of gluten free diet – B. Colonoscopy with biopsies – C. Laxatives daily – D. Loperamide as needed – E. Food diary Interactive

• A 63 year old woman is seen in gastro outpatients for an 8 month history of diarrhoea opening her bowels 6 times a day without blood. She has been taking lisinopril for a few years but no other regular medications. She denies weight loss. Stool culture, tTG IgA, thyroid function tests are normal and she is up to date with bowel cancer screening. What is the next step? – A. Trial of gluten free diet – B. Colonoscopy with biopsies – C. Laxatives daily – D. Loperamide as needed – E. Food diary Microscopic Colitis • Inflammatory disease of the colon (not UC or Crohn’s) • Endoscopically normal bowel (looks fine) • Histologic changes (biopsies show disease) • Middle aged, more often female • Two types (depending on layer of bowel affected) – Collagenous colitis – Lymphocytic colitis Colonoscopy with biopsies Microscopic Colitis Histology Collagenous Colitis Lymphocytic Colitis Thickened collagen layer Increased intraepithelial lymphocytes (commons.wikimedia.org) (commons.wikimedia.org)

Normal Colonic mucosa (commons.wikimedia.org) Microscopic Colitis Treatment

• Discontinue offending medications High likelihood Intermediate likelihood

Proton Pump Inhibitors Lisinopril H2 Blockers/Ranitidine Statins • Loperamide NSAIDs Aspirin Smoking? • Budesonide SSRIs/Sertraline – 9mg qd x 30d – 6mg qd x 30d – 3mg qd x 30d – Sometimes this is enough, sometimes this is long term Interactive • A 45 year old woman is seen in Gastro outpatients in follow up for chronic diarrhoea. She has had a normal colonoscopy including biopsies. She mentions that her bowel habit hasn’t been the same since she had her gallbladder out 5 years ago. Which is the most appropriate investigation? – A. SeHCAT test – B. FIT – C. Faecal calprotectin – D. tTG IgA – E. Stool culture Interactive • A 45 year old woman is seen in Gastro outpatients in follow up for chronic diarrhoea. She has had a normal colonoscopy including biopsies. She mentions that her bowel habit hasn’t been the same since she had her gallbladder out 5 years ago. Which is the most appropriate investigation? – A. SeHCAT test – B. FIT – C. Faecal calprotectin – D. tTG IgA – E. Stool culture Bile acid diarrhoea (BAD)

• Normally bile acids secreted by the liver, aid with digestion and are reabsorbed in the terminal ileum and recirculated • With bile acid diarrhoea bile acids are not properly reabsorbed and end up in the colon resulting in diarrhoea Bile acid diarrhoea (BAD)

• The colon gets grumpy when it’s exposed to bile acid! • Factors: ileal resection, active small bowel Crohn’s, cholecystectomy, ? Bile acid diarrhoea (BAD)

• Investigations:

– SeHCAT (23-seleno-25-homotaurocholic acid, selenium homocholic acid taurine) • Radioactive bile acid analogue tablet administered • 3 hours later nuclear medicine scan (gamma camera) • 7 days later repeat scan • % retained (<15% suggests BAD) – Fasting Serum C4 test – Trial of bile acid sequestrants (not rec by BSG) – https://gut.bmj.com/content/gutjnl/67/8/1380.full.pdf Bile acid diarrhoea (BAD)

• Treatment – Bile acid sequestrants: • Bind bile acids and prevent their reabsorbtion • Used for hypercholesterolaemia (promotes liver to convert cholesterol into bile acids) • Colestyramine, Colesevelam, Colestipol – Must separate these medications from other medications (absorption) Interactive • A 63 year old man is seen in Gastro outpatients for follow up of a many year history of diarrhoea. He has had normal stool tests, bloods, colonoscopy and SeHCAT. He describes ongoing loose stools that are hard to flush away. He has a long history of heavy alcohol use but has decreased his intake to 4 units per week over the past year. Which would be the most appropriate test? – A. Blood alcohol level – B. Faecal elastase – C. Amylase – D. Endomysial antibody – E. FIT Interactive • A 63 year old man is seen in Gastro outpatients for follow up of a many year history of diarrhoea. He has had normal stool tests, bloods, colonoscopy and SeHCAT. He describes ongoing loose stools that are hard to flush away. He has a long history of heavy alcohol use but has decreased his intake to 4 units per week over the past year. Which would be the most appropriate test? – A. Blood alcohol level – B. Faecal elastase – C. Amylase – D. Endomysial antibody – E. FIT Pancreatic exocrine insufficiency • Impaired secretion of pancreatic which results in maldigestion of fat, diarrhoea • Often 10-15 y after a diagnosis of chronic pancreatitis • Testing – Faecal elastase will be low- normal 200-500ug/g – May consider pancreatic imaging/MRI • pancreatic cancer • Treatment – Pancreatic enzymes with meals Small Bowel Bacterial Overgrowth SBBO • Small bowel normally has less bacterial colonisation than the colon • Overgrowth may cause various symptoms including bloating and diarrhoea • Conditions that can predispose – Diabetes – Small bowel diverticula – Anatomic alterations – Small Bowel Bacterial Overgrowth SBBO • Testing- no agreed upon test – Glucose, lactulose, hydrogen breath tests • low (sometimes extremely low) sensitivity and specificity – Urinary indicans (UHL) – Duodenal aspirate • lack of standardisation of bacterial counts, sampling error and need for OGD Small Bowel Bacterial Overgrowth SBBO • Treatment- antibiotics – BSG recommends empirical trial of antibiotics if suspecting SBBO – Co-amoxiclav, Cipro, Rifaxamin? – Probiotics? – May require multiple courses in intervals Lactose intolerance

• Lactose maldigestion • Testing: – Lactose hydrogen breath test if available (BSG) – Withdrawal of dietary lactose (BSG) – ‘Home lactose challenge’ IBS-D • Consider maldigestion of fermentable oligo-, di- mono- sacchrides and polyols (FODMAPs) • Not absorbed in the small bowel become fermented in the colon – Fructose (glucose transporter) – Fructans (found in wheat- may be wheat intolerant non-coeliac patients) – Sorbitol, non-absorbed sugar alcohols, artificial sweetners • Patients may notice correlation with certain foods High FODMAPs foods (avoid)

• Sweeteners – Fructose, high fructose corn syrup, sorbitol, mannitol, xylitol, isomalt • Dairy – Milk from cows, goats, sheep. Ice cream, yogurts, soft cheeses. • Cereals – Wheat and rye in large amounts- biscuits, bread, pasta, crackers, cake • Vegetables – Artichoke, asparagus, broccoli, beetroot, cauliflower, garlic, green peas, leek, onion, green peppers • Fruits – Tinned fruit in natural juice, apple, mango, pear, apricot, avocado, apricot, cherry, blackberry, plum, peach, watermelon • Legumes – Baked beans, kidney beans, lentils, chickpeas, soy beans (tofu okay though) IBS • IBS recommendations – https://www.bda.uk.com/foodfacts/IBSfoodfacts.pdf – try not to skip any meals, eat late at night, eat large meals – limit alcohol intake to no more than two units per day and have at least two alcohol free days a week – limit intake of caffeine-containing drinks- three cups a day – reduce intake of fizzy drinks IBS… and everyone else

• Avoid processed foods and limit rich and fatty foods • Take regular exercise • Take time to reduce stress Any Questions?

Thank you!