IBS. TomSult Sult, MD Patrick Hanaway, MD. Post Webinar Sept 21, 2011

Transcription

1 Case Studies Differentiating IBD from IBS TomSult Sult, MD Patrick Hanaway, MD ApplyingFunctional Medicine inclinical Practice Post Webinar Sept 21, 2011

2 Tom Sult, MD Patrick Hanaway, MD

3 Inside the Presentation If you have a technical issue, type your question in this box and select send to : Host, then click send If you have a question or comment for the Presenters, type it here and then click send In full screen mode, click the? icon to ask a question

4 Case Studies Differentiating IBD from IBS Patrick Hanaway, MD Patrick Hanaway, MD Tom Sult, MD

5 IS IT?: Irritable Bowel Syndrome (IBS) OR Inflammatory Bowel Disease (IBD) OR Celiac Disease

6 The BIG Picture Many conditions start with imbalances in Digestion & Absorption Inflammation & Immune dys-regulation Gut microbiology (bacteria, parasites, fungus) An excellent starting point for clinicians interested in getting to the root and IBS and GI symptoms, found in nearly 80% of all patients seen!

7 Management of IBS Digestion/ Absorption Inflammation/ Immune/ Infection Gut Bacterial Flora/ Dysbiosis Intestinal Permeability enteric Nervous System

8 IBS Epidemiology Up to 20% of population Females > males Younger > older 3.6 million visits/ year Sociocultural factors affect M.D. visits 12% primary care practice, 28% GI practice >3x work loss, M.D. visits Drossman DA et al. Gastroenterology 1997;112:2137b

9 Irritable Bowel Syndrome ROME III Criteria For at least 3 months, with onset at least 6 months previously, of recurrent abdominal pain or discomfort* >2d/month associated with 2 or more of the following symptoms: Improvement with defecation; and/ or Onset associated with a change in frequency of stool; and/or Onset associated with a change in form (appearance) of stool * Discomfort means an uncomfortable sensation not described as pain.

10 Cash BD, Chey WD. Gastroenterol Clin North Am. 2005;34:

11 Case Study Irritable Bowel Syndrome Challenges in Diagnosis Diagnosis of Exclusion Physicians rule out Inflammatory Bowel Disease (Crohns Disease, Ulcerative Colitis) and categorize all other conditions as IBS Challenges in Treatment IBS can actually be many different things, including: bacterial infection, food allergy, parasitic infection, pancreatic insufficiency, i dysbiosis. i One particular treatment will not work for all situations.

12 IBS Case #1 32 yo Male, recently returned from traveling in Asia. Had occasional abdominal discomfort before traveling, now present 2-4x/ month over 3 months. DIG Digestion/ Absorption Hypochlorhydria y Food Intolerance Villous Atrophy Pancreatic Insufficiency Small Intestinal Bowel Overgrowth (SIBO)

13 IBS Case #1 32 yo Male, recently returned from traveling in Asia. Had occasional abdominal discomfort before traveling, now present 2-4x/ month over 3 months. DIG Immune Regulation/ Inflammation Food Sensitivity y(g (IgG) and Allergy (IgE) Neutrophilic inflammation (Infection, IBD, CA) Eosinophilic Inflammation Infection (bacterial, viral, parasitic) Gluten Sensitive Enteropathy (Celiac)

14 IBS Case #1 32 yo Male, recently returned from traveling in Asia. Had occasional abdominal discomfort before traveling, now present 2-4x/ month over 3 months. DIG Gut Microflora Dysbiosis Beneficial bacteria Other bacteria Infection SIBO Candidiasis

15 Management of IBS Digestion/ Absorption Inflammation/ Immune/ Infection Gut Bacterial Flora/ Dysbiosis Intestinal Permeability enteric Nervous System

16 Conclusions There is no single IBS When we observe the relationships between: Digestion & Absorption Immune/ Inflammation Gut Microflora... we move beyond symptom suppression to a level of personalized diagnosis and treatment.

17 Maldigestion Inadequate mastication Hypochlorhydria Pancreatic insufficiency* Bile insufficiency* Villous atrophy brush border enzyme destruction*

18 IBS Evaluation

19 Pancreatic Elastase Proteolytic enzyme secreted exclusively by the human pancreas Reflects overall enzyme production (amylase, lipase and protease) Simple, non-invasive marker for evaluating exocrine pancreatic function 1,2 Sensitivity = % Specificity = 93-98% Stein J, et al. Clin Chem 1996 Feb;42(2):222 6 Loser C, Mollgaard A, Folsch UR. Gut 1996;39(4):580 6.

20 Pancreatic Elastase Treatment > 350 μg/g Normal pancreatic function μg/g Declining pancreatic function Consider supplement with pancreatic enzymes μg/g Moderate pancreatic insufficiency Supplement with broad array of pancreatic enzymes <100 μg/g Severe pancreatic insufficiency Supplement with broad array of pancreatic enzymes

21 IBS Evaluation

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23 Calprotectin Predominately found in extra lysosomal cytosol of the neutrophil Accounts for ~ 60% of the cytosolic protein Inhibitory effect on zinc dependent enzymes Bacteriostatic activity Dale I, et al. Am J Clin Pathol 1985;84:24 34 Brun JG, et al. Scand J Immuno, 1994;40:

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25 Calprotectin Elevated in: Inflammatory Bowel Disease Post-Infectious Irritable Bowel Syndrome Cancer of the GI Certain GI infections NSAID enteropathy Food allergy Chronic Pancreatitis Poullis A et al. J Gastroenterol Hepatol 2003;18:

26 Interpreting Calprotectin: Know when it s SERIOUS < 50 μg/g No significant inflammation μg/g Indicates some GI inflammation: IBD, infection, polyps, neoplasia, NSAIDS > 120 μg/g Significant inflammation; referral may be indicated to determine pathology > 250 μg/g Active disease present; predicts imminent relapse in treated patients Tibble J, Teahon K, Thjodleifsson B, et al. Gut 2000;47:

27 Colonoscopies Deemed Unnecessary For Most IBS Patients 3/17/2010 American Journal of Gastroenterology, "people with irritable bowel syndrome (IBS) are not at increased risk for polyps, colon cancer or inflammatory bowel diseases, such as Crohn's disease and, in most cases, don't require a colonoscopy." Lead investigator Dr. William D. Chey, of the University of Michigan, said, unless there is a family history of colorectal cancer or the patient has alarming symptoms such as unexplained weight loss or anemia, or bleeding from the gastrointestinal tract," there is no need for the procedure.

28 Eosinophilic Protein X

29 Eosinophil Protein X (EPX) Released in eosinophil degranulation Sensitive marker of GI inflammation Levels correlate well with clinical course and can predict relapse in IBD Superior to lactoferrin and siga Stable in transport up to 7 days Less intra-individual variability Much more sensitive marker for low-level inflammation 3,4

30 Celiac vs. Gluten Sensitivity

31 Am J Gastro March, ac 2011 IBS Rome III Celiac negative Randomized Trial +/ gluten

32 Am J Gastro March, 2011 Symptoms worsened No change in Ab: ttg IgA AGA IgA AGA IgG No change hs-crp No change L/M ratio

33 The Gut Flora Our intestinal flora has a massive amount of influence the on our metabolism! 10x the number of cells 100x the genomic material Metabolic activity > liver 3# of body mass THE HIDDEN ORGAN!

34 Metabolic Functions of Bacteria Mucous production Short Chain Fatty Acids Metabolism Pi Primary Bile Acid Deconjugation Vitamin absorption Fats, TG, Cholesterol regulation Undigested dietary fiber breakdown Gas production Fermentation ti Production of Phenols Breakdown of oligo-saccharides Detoxification

35 Microbiota At birth - digestive tract of humans is sterile. Colonised by microbes within the first few days of life At first, predominantly bifidobacteria (breast fed infants) With the introduction of other foods, a diverse microbial population develops in the gastrointestinal tract. As adults, of all the cells in a human body, the overwhelming majority are non-human.

36 Bacteroides, Lactobacillus, Clostridium, Fusobacterium, Bifidobacterium, Eubacterium, Peptococcus, Peptostreptococcus, Escherichia, and Veillonella. Bacterial count 100,000/ml /ml >400 different microbial species

37 Bacteroides, Lactobacillus, Clostridium, Fusobacterium, Bifidobacterium, Eubacterium, Peptococcus, Peptostreptococcus, Escherichia,, and Veillonella. Bacterial count 100,000/ml /ml >400 different microbial species

38 Dysbiosis CDSA 2.0 < 6+

39 Dysbiosis CDSA 2.0 > 12+

40 Treating Dysbiosis Stool culture Microbiology Additional Bacteria: LOW to MODERATE Additional Bacteria: EXCESSIVE Beneficial Bacteria: No need Treat with anti- ADEQUATE to treat microbial herbs Beneficial Bacteria: Treat with ProBiotics Treat with Probiotics INSUFFICIENT billion cfu qd billion cfu qd + antibiotics If patient is ILL add ~50 billion cfu qd & advance to antibiotics more quickly

41 Probiotics: History

42 Common Parasites A recent Genova study revealed 23.5 % of submitted clinical samples tested positive for at least one parasite (3,223/ 13,857) Blastocystis hominis (12.5%) Dientamoeba fragilis (3.8%) Entamoeba spp. (3.4%) Endolimax nana (2.2%) Giardia lamblia (0.7%)

43 Conclusions There is no single IBS When we observe the relationships between: Digestion & Absorption Immune/ Inflammation Gut Microflora... we move beyond symptom suppression to a level of personalized diagnosis and treatment.

44 IBS Case #2 24 yo Female with intermittent recurrent abdominal pain/ discomfort x5 years. Also with depression and fatigue. Currently being treated with tri-cyclic anti-depressants. DIG Digestion/ Absorption food not completely digested, exocrine pancreatic function decreased Immune Regulation/ Inflammation serum ttg +, DGP +, and confirmed with endomysial IgA + Gut Microflora normal

45 IBS Case #2 24 yo Female, newly diagnosed with Celiac disease & pancreatic insufficiency i TREATMENT Remove Gluten Replace enzymes 10x USP Pancreatin, take before each meal Repair gut lining L-Glutamine 1000mg TID, increasing to 3000mg TID for 4 weeks.

46 IBS Case #2 24 yo Female, newly diagnosed with Celiac disease & pancreatic insufficiency TREATMENT Pancreatic supplementation until villous atropy (2 o celiac disease) resolves Repair of leaky gut Totally, gluten-free diet lifetime! 6 & 12 weeks Symptoms significantly improved Intermittent dietary 1 year Screen for auto-immune diseases

47 IBS Case #3 48yo Female with a history of depression and intermittent abdominal pain with cramping over the past 6 months. DIG Digestion/ Absorption no problems Immune Regulation/ Inflammation significant elevation in neutrophilic markers of inflammation, Calprotectin = 378! Gut Microflora no alterations in bacteria, no parasites present, no C. difficile

48 IBS Case #3 48yo Female with a history of depression and dintermittent itt tabdominal pain with cramping over the past 6 months. TREATMENT Referred for colonoscopy must determine source of significantly elevated inflammation: Inflammatory Bowel Disease ColoRectal Carcinoma

49 IBS Case #3 48yo Female with a history of depression and intermittent abdominal pain with cramping over the past 6 months. TREATMENT Referred for colonoscopy FOLLOW-UP Ulcerative Colitis noted on colonoscopy 5-ASA begun, attempt to spare steroids Hi-dose probiotics to induce remission i

50 Historical 31% Tx 13% Tx 3% Referral 25% Tx 47% Tx 19% Tx

51 The BIG Picture Many conditions start with imbalances in Digestion & Absorption Inflammation & Immune dys-regulation Calprotectin need for referral? Celiac Disease and non-cd gluten sensitivity Gut microbiology (bacteria, parasites, fungus) An excellent starting gpoint for clinicians interested in getting to the root and IBS and GI symptoms, found in nearly 80% of all patients seen!

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53 Next Two Webinars with Drs. Hanaway and Sult: Wednesday, September 28 th, 4 pm: Systemic disease and increased intestinal permeability-eczema and the 5R program Wednesday, October 5. th, 4 pm: Case Evaluations The last webinar will be a discussion of cases that participants submit. Cases must be submitted to Dan Lukaczer ([email protected]) in electronic form using the template no later than Monday, October 3 rd. The template can be found under Dr. Sult s presentation on the CD or on the Course Materials page