Updated BSG guidelines for investigation of

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Updated BSG guidelines for investigation of

  1. 1. Investigation of chronic diarrhoea British Society of Gastroenterology Guidelines 2 nd Edition 2003 <ul><ul><ul><ul><ul><li>Dr. P.D. Thomas </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Consultant Gastroenterologist </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Taunton and Somerset Hospital </li></ul></ul></ul></ul></ul>
  2. 2. Outline  <ul><li>Definitions </li></ul><ul><li>Initial assessment </li></ul><ul><li>Factitious diarrhoea </li></ul><ul><li>Functional bowel problems </li></ul><ul><li>Colonic investigations </li></ul><ul><li>Small bowel investigations </li></ul><ul><li>Investigation of fat and carbohydrate malabsorption </li></ul><ul><li>Investigation of malabsorption due to pancreatic insufficiency </li></ul><ul><li>Specific conditions small bowel bacterial overgrowth, bile salt malabsorption, hormone secreting tumours </li></ul>
  3. 3. Mechanisms <ul><li>Intestinal secretions and food- 7l per day </li></ul><ul><li>5L absorbed in small intestine </li></ul><ul><li>1.5-2L absorbed by colon </li></ul><ul><li>Stool 100-200mL water </li></ul><ul><li>10% decrease in fluid absorbed by colon will double stool volume </li></ul><ul><li>Considerable reserve capacity of colon to absorb increased ileal effluent </li></ul>
  4. 5. Approaches to the classification of diarrhoea <ul><li>Mechanistic Osmotic - eg carbohydrate/ fat malabsorption Secretory- mucosal disease, defects of ion absorption, stimulant laxatives Gut hormone Deranged motility - post vagtomy, IBS carcinoid </li></ul>
  5. 6. <ul><li>Distinguishing osmotic from secretory diarrhoea - fasting - osmotic diarrhoea should stop - osmotic gap low stool osmolality <290 mosmol/kg suggests contamination with hypotonic fluid 290-2x (Na and K conc) Osmotic gap >125mosmol/kg osmotic diarrhoea <50 in secretory diarrhoea </li></ul>
  6. 7. <ul><li>Anatomical …... </li></ul>
  7. 8. Causes of diarrhoea <ul><li>Colonic </li></ul><ul><li>Colonic neoplasia Endocrine </li></ul><ul><li>Ulcerative and Crohn's colitis Hyperthyroidism </li></ul><ul><li>Microscopic colitis Diabetes </li></ul><ul><li>Small bowel Hypoparathyroidism </li></ul><ul><li>Coeliac disease Addison's disease </li></ul><ul><li>Crohn's disease Hormone secreting tumours (VIPoma, Other small bowel enteropathies, gastrinoma, carcinoid) </li></ul><ul><ul><ul><li>(e.g. Whipples disease, tropical sprue, amyloid, </li></ul></ul></ul><ul><ul><ul><li>intestinal lymphangiectasia ) </li></ul></ul></ul><ul><ul><ul><li>Bile Acid malabsorption </li></ul></ul></ul><ul><ul><ul><li>Disaccharidase deficiency </li></ul></ul></ul><ul><li>Small bowel bacterial overgrowth </li></ul><ul><li>Mesenteric ischaemia </li></ul><ul><li>Radiation enteritis  Other </li></ul><ul><li>Lymphoma Factitious diarrhoea </li></ul><ul><li>Giardiasis Surgical' causes (e.g. small bowel Pancreatic resections) </li></ul><ul><li>Chronic pancreatitis Autonomic neuropathy </li></ul><ul><li> Pancreatic carcinoma Drugs </li></ul><ul><li>Cystic fibrosis Alcohol </li></ul>
  8. 9. Definitions <ul><li>>200g stool/24 hours </li></ul><ul><li>More than three loose stools/day </li></ul><ul><li>Chronic > 4 weeks </li></ul><ul><li>Layman’s definition </li></ul>
  9. 10. Initial assessment <ul><li>Organic vs functional <3 months, continuous, nocturnal, alarm symptoms </li></ul><ul><li>Malabsorptive or colonic/inflammatory </li></ul><ul><li>Specific Drugs, family history, surgery, systemic disease, alcohol, infective </li></ul>
  10. 11. Initial investigations <ul><li>Blood tests FBC, UE, LFT, B12, folate, fe studies, ESR, CRP, TFT </li></ul><ul><li>Serological tests for coeliac disease Prevalence of 1:200 in asymptomatic western pops. IgA anti-endomysium antibodies anti-tissue transglutaminase antibodies </li></ul>
  11. 12. Stool tests <ul><li>Stool microscopy culture Protozoal eg Giardia, amobae, cryptosporidia </li></ul><ul><li>Non specific Stool osmolality stool fat </li></ul><ul><li>Specific stool elastase other.. </li></ul>
  12. 13. <ul><li>Stool markers of intestinal inflammation e.g. lactoferrin </li></ul><ul><li>Stool calprotectin cytosolic protein in monocytes, neutrophils stable for 1 week at RT </li></ul><ul><li>Use of surrogate markers of inflammtion and Rome criteria to distinguish organic from non-organic disease Tibble et al Gastroenetrology 2002 </li></ul>
  13. 14. <ul><li>N=602 all patients underwent invasive imaging Ix Rome criteria, Intestinal permeability </li></ul><ul><li>Results 263 organic disease, 339 IBS Sensitivity specificity stool calprotectin 89 79 intestinal permeability 63 87 Rome criteria 85 71 </li></ul>
  14. 15. Factitious diarrhoea <ul><li>4% of patients attending district gastroenterology clinic </li></ul><ul><li>20-33% attending tertiary referral centres </li></ul><ul><li>Association with medical training/eating disorder </li></ul><ul><li>In patient assessment/monitoring - stool collections - 24-48 hour fast </li></ul><ul><li>‘ Laxative screen’ - anthraquinones, biascodyl, phenolphthaleins, oils, Mg, PO 4 . </li></ul>
  15. 16. Case 1 <ul><li>50 year old female </li></ul><ul><li>6 months watery diarrhoea up 6 x day </li></ul><ul><li>Normal baseline investigations including TFT, coeliac serology </li></ul><ul><li>Normal flexible sigmoidoscopy with bx 2 years ago Next investigation? </li></ul>
  16. 17. Microscopic colitis <ul><li>Lymphocytic or collagenous colitis </li></ul><ul><li>Rectosigmoid biopsies alone may miss up to 40% of cases (Offner1999) </li></ul>
  17. 18. Frequency Age Malignancy
  18. 19. Overlap between functional and organic disease <ul><li>Irritable Bowel syndrome Rome criteria (II) > 3 months abdominal pain or discomfort with 2 or more - altered stool frequency - altered stool consistency - relieved by defecation bloating or distention or mucous supportive </li></ul>
  19. 21. Discriminant factors <ul><li>>45 </li></ul><ul><li>Family history </li></ul><ul><li><45 </li></ul><ul><li>Female sex </li></ul><ul><li>Other ‘functional’ Sx </li></ul>Irritable bowel Colonic pathology
  20. 22. Chronic diarrhoea in patients <45yrs <ul><li>Flexible sigmoidoscopy Fine et al 2000 800 patients studied Microscopic colitis 10% >Crohn’s >UC 99.7% of pathology accessible with FS </li></ul>
  21. 23. Chronic diarrhoea in patients >45yrs Rationale for total colonic examination <ul><li>Neoplasia 37% asymptomatic individuals have adenomas 8% adenomas>1cm (Lieberman 2000) Prevalence in symptomatic? </li></ul><ul><li>Higher prevalence of proximal non-neoplastic pathology e.g microscopic colitis, IBD 7-31% </li></ul><ul><li>Colonoscopy or barium enema and flexi sigmoidoscopy </li></ul>
  22. 24. Case 2 <ul><li>40 year old male </li></ul><ul><li>Loose offensive stools 4x/day ? ½ stone weight loss 1 year </li></ul><ul><li>FBC, LFT, CRP etc normal </li></ul><ul><li>IgA Antiendomysial antibodies negative </li></ul><ul><li>Flexible sigmoidoscopy normal </li></ul>
  23. 25. <ul><li>Selective IgA deficiency 0.14% population 2.6% coeliac disease </li></ul><ul><li>IgG antiendomysium Ab or IgG anti-tTG Ab are suitable alternative serological tests </li></ul><ul><li>Check IgA levels </li></ul>
  24. 26. Endoscopic distal duodenal biopsies <ul><li>Little information on diagnostic yield </li></ul><ul><li>Serological tests have replaced D2 biopsies as the initial investigation for coeliac disease </li></ul><ul><li>Coeliac disease is (by far) the most common small bowel enteropathy in western european populations BUT other small bowel enteropathies should be considered. ‘D2 biopsies where small bowel malabsorption is clinically suspected’ </li></ul>
  25. 27. Case 3 <ul><li>55 year old male </li></ul><ul><li>RIF pain and diarrhoea </li></ul><ul><li>Tenderness RIF </li></ul><ul><li>Baseline Ix NAD except CRP 32 </li></ul><ul><li>Colonoscopy incomplete (histology normal) Next step? </li></ul>
  26. 28. Terminal ileal disease How to assess?
  27. 29. Small bowel imaging <ul><li>Barium follow through Enteroclysis -yield low, equivalent role -small bowel malabsorption suspected (distal duodenal histology normal) Structural abnormalities </li></ul>
  28. 30. Small bowel imaging (2) <ul><li>Tc- HMPAO labelled white cell scanning </li></ul><ul><li>Enteroscopy diagnostic yield up to 31% ( 20% if gastroscopically accessible lesions excluded) </li></ul>
  29. 31. Small bowel imaging (3) <ul><li>Capsule endoscopy? Established role in the investigation of iron deficiency anaemia ? Suspected small bowel malabsorption or diarrhoea of unknown cause </li></ul><ul><li>Superior to small bowel barium XR 70% vs 40% diagnostic yield </li></ul>
  30. 32. Capsule Endoscopy: Detection of inflammatory lesions in the small intestine Thickened infiltrated folds (Jejunum) Villous erosion Linear ulcerations Apthous ulcerations (ileum)
  31. 33. Capsule endoscopic diagnosis of Crohn’s Disease Jejunal Crohn's Disease
  32. 34. CELIAC DISEASE
  33. 35. INVESTIGATION OF CHRONIC DIARRHOEA Basic investigations FBC, LFT, Ca, B12, Folate, Fe status, TFT Coeliac serology History suggestive of organic diarrhoea Abnormal basic investigations Symptoms suggestive of functional disease Age <45,normal basic investigations irritable bowel syndrome History or findings c/w malabsorption History or findings c/w colonic disease or small bowel inflammatory disease 'Difficult diarrhoea' Suspicion of laxative abuse persistent symptoms despite negative Ix High volume diarrhoea Small Bowel D2 biopsy Barium follow through Pancreatic Enteropathy Review histology ?Enteroscopy Or capsule endoscopy Flexible sigmoidoscopy if <45 Complement with barium enema if >45 Colonoscopy preferred if >45 Terminal ileal disease excluded? Barium follow through 99mTc-HMPAO 75SeHCAT
  34. 36. Malabsorption and ‘difficult diarrhoea’
  35. 37. ‘‘ Malabsorption’’ <ul><li>Malabsorption - mucosal disease </li></ul><ul><li>carbohydrate>fat </li></ul><ul><li>Maldigestion - pancreatic disease </li></ul><ul><li>fat> carbohydrate </li></ul><ul><li>(protein quantification difficult) </li></ul>
  36. 38. Tests related to fat malabsorption (1) <ul><li>Stool tests </li></ul><ul><li>3 day faecal fat (poorly reproducible) patients with steatorrhoea reduce fat intake no assessment of completeness of collection no quality control </li></ul><ul><li>faecal fat concentration (not widely available) </li></ul><ul><li>Stool steatocrit and Sudan III (semi-quantitative) all are non-specific </li></ul>
  37. 39. Tests of fat malabsorption (2) <ul><li>Breath tests </li></ul><ul><li>14 C-triolein </li></ul><ul><li>13 C-hiolein Lembke 1996 8-12 hr , 30 min breath samples sensitivity 92% in severe, 46% in mild/mod pancreatic insufficiency </li></ul><ul><li>13 C- mixed chain triglyceride </li></ul><ul><li>Only sensitive if moderate or severe steatorrhoea </li></ul>
  38. 40. Tests related to carbohydrate malabsorption <ul><li>D-xylose - used in assessment of mucosal disease for 30 years - High sensitivity (98%) and specificity (95%) reported (although controvercial) - 5 hour urine collection and/or 1 hour serum sample </li></ul><ul><li>D-xylose breath test </li></ul><ul><li> Both have been largely replaced by endoscopic distal duodenal biopsies </li></ul>
  39. 41. Chronic pancreatitis <ul><li>Usually obvious </li></ul><ul><li>Previous episodes of pancreatitis </li></ul><ul><li>History of XS alcohol </li></ul><ul><li>Weight loss </li></ul><ul><li>Steatorrhoea </li></ul><ul><li>Coincident diabetes? </li></ul>
  40. 42. Investigation of pancreatic malabsorption: Imaging <ul><li>USS 50-60% sensitive </li></ul><ul><li>CT 74-90% sensitive </li></ul><ul><li>ERCP ‘Gold standard’ </li></ul><ul><li>MRI ?equivalent to ERCP </li></ul>
  41. 43. Investigation of pancreatic malabsorption <ul><li>Invasive </li></ul><ul><li>Pancreatic function tests - Secretin/cholecystokinin stimulation - ‘Lundh’ test Sensitivity 90% </li></ul><ul><li>ERCP secretin-cholecystokinin ERCP 26/30 abnormal 21/30 </li></ul>
  42. 44. Investigation of pancreatic malabsorption <ul><li>Non-invasive (1) </li></ul><ul><li>(all tests related to fat malabsorption) </li></ul><ul><li>(Serum enzymes) </li></ul><ul><li>Faecal tests - chymotrypsin (Sens 80% Spec 84%) - lipase (sensitivity 46%) - elastase mild moderate severe sensitivity 63 100 100% (Loser 1996) 40 33 82% (Lankisch 1998) </li></ul>
  43. 45. Investigation of pancreatic malabsorption <ul><li>Non-invasive (2) </li></ul><ul><li>‘ Tubeless’ oral pancreatic function tests </li></ul><ul><li>NBTP/PABA - N-benzoyl-L-tyrosyl-p-aminobenzoic acid - hydrolysed by chymotrypsin - 6 hour urine collection - Sensitivity 64-83% Specificity 89% </li></ul><ul><li>Fluorescein dilaurate (Pancreolauryl) test - Pancreatic esterase - 10 hour urine collection - variable sensitivities reported </li></ul>
  44. 46. Investigation of pancreatic malabsorption (summary) <ul><li>Faecal elastase is the non-invasive investigation of choice </li></ul><ul><li>May complement with Urine test such as pancreolauryl or NBTP-PABA but - specificity influenced by small bowel disease - technically more demanding </li></ul>
  45. 47. Miscellaneous causes and ‘difficult diarrhoea’ <ul><li>Small bowel bacterial overgrowth </li></ul><ul><li>Bile acid malabsorption </li></ul><ul><li>Hormone secreting tumours </li></ul>
  46. 48. Small bowel bacterial overgrowth <ul><li>Underdiagnosed -few data on prevalence - Up to 50% of patients with gastrojejeunostomy - Resection of ileo-caecal valve eg pouch patients - 14% asymptomatic elderly by glucose HBT </li></ul><ul><li>Small bowel aspirate and culture - ‘Gold standard’ >10^6 cfu/mL - Culture of anaerobes difficult - May overestimate -contamination and ‘normal’ small bowel colonisation by bacteria. </li></ul>
  47. 49. Investigation of small bowel bacterial overgrowth <ul><li>Breath tests - 14 C-cholylglycine - now abandoned - Hydrogen breath tests (glucose or lactulose) Sensitivity: 17 - 68% Specificity: 70-83% - 14 C-D xylose – not available in UK Proximally absorbed No reliance on H 2 production </li></ul>
  48. 50. Bile acid malabsorption <ul><li>Causes terminal ileal disease, surgical resection primary defect, post cholecystectomy rapid transport </li></ul><ul><li>75Se homotaurocholate (75SeHCAT) synthetic analogue of taurocholic acid retained fraction assessed by gamma camera 7 days after oral administration <15% suggest BAM </li></ul><ul><li>7alphahydroxy-4-cholestone-3-one </li></ul><ul><li>Therapeutic trial of cholestyramine </li></ul>
  49. 51. Hormone secreting tumours <ul><li>Rare! Incidence approx. 1 per million </li></ul><ul><li>VIPoma, gastrinoma, carcinoid, somatostatinoma </li></ul><ul><li>Large volumes (>1 litre) of watery diarrhoea </li></ul><ul><li>VIPoma 90% are pancreatic, large tumours Diarrhoea primary symptom (100%) Can be episodic. Secretory diarrhoea Fasting VIP level >170pg/mL </li></ul>
  50. 52. Summary
  51. 53. Conclusions <ul><li>Baseline investigations (primary care) </li></ul><ul><li>lower GI endoscopy with biopsy </li></ul><ul><li>Consider factitious diarrhoea </li></ul><ul><li>Small bowel malabsorption - Distal duodenal biopsies - small bowel imaging </li></ul><ul><li>Pancreatic insufficiency - faecal elastase, Pancreolauryl test, pancreatic imaging </li></ul><ul><li>Other – SB bacterial overgrowth, BAM etc In 1/3 patients no diagnosis made: ‘chronic idiopathic diarrhoea’ </li></ul>

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