update in gi: what’s new and useful - scripps

Update in GI: WhatUpdate in GI: What’’s s New and UsefulNew and Useful

Walter J. Coyle, MD, FACP,FACGWalter J. Coyle, MD, FACP,FACG

October 2012October 2012

DisclosuresDisclosures

I have no disclosures related to this talkI have no disclosures related to this talk

Specifically, I have no interests in any probiotic Specifically, I have no interests in any probiotic or preor pre--biotic brandsbiotic brands

Movement of the TalkMovement of the Talk

Eosinophilic esophagitis: What is it and how do Eosinophilic esophagitis: What is it and how do I treat it?I treat it?

GERD: WhatGERD: What’’s New?s New?

Celiac Sprue: The epidemicCeliac Sprue: The epidemic

CRC screening: Follow the guidelinesCRC screening: Follow the guidelines

WhatWhat’’s new?s new?

Movement of the Talk Part IIMovement of the Talk Part II

Stool Transplants: The New RageStool Transplants: The New Rage

Rosacea and SIBO: New evidenceRosacea and SIBO: New evidence

Chronic nausea: a new linkChronic nausea: a new link

The Human Microbiome: Hot topicThe Human Microbiome: Hot topic

Pro and Pre biotics: a rational approachPro and Pre biotics: a rational approach

C. difficileC. difficile: It will not go away!: It will not go away!

ConclusionsConclusions

Question Number 1Question Number 1

27 year old male 27 year old male presents with presents with intermittent solid food intermittent solid food dysphagia for years. He dysphagia for years. He has had 2 food has had 2 food impactions. He had impactions. He had childhood asthma. childhood asthma. The most likely The most likely diagnosis is?diagnosis is?

A.A.

Peptic stricturePeptic stricture

B.B.

SchatzkiSchatzki’’s rings ring

C.C.

Eosinophilic esophagitisEosinophilic esophagitis

D.D.

Adenocarcinoma of the Adenocarcinoma of the distal esophagusdistal esophagus

E.E.

AchalasiaAchalasia

Eosinophilic EsophagitisEosinophilic Esophagitis

Common, may be increasingCommon, may be increasing

Higher in males, younger pts with h/o atopyHigher in males, younger pts with h/o atopy

Strong association with food and aeroallergensStrong association with food and aeroallergens

THE ALLERGIC ESOPHAGUSTHE ALLERGIC ESOPHAGUS

Adults: present with dysphagia, atypical GERD Adults: present with dysphagia, atypical GERD symptoms: Usually have years of symptomssymptoms: Usually have years of symptoms

Children: Failure to thrive, nausea or vomiting.Children: Failure to thrive, nausea or vomiting.


Linear FurrowsLinear Furrows

RingsRings

Diagnosis: Biopsy Diagnosis: Biopsy at endoscopyat endoscopy


Eos. AbscessesEos. Abscesses

Long, often Long, often complex stricturescomplex strictures

Careful dilationCareful dilation


Mucosal tear after Mucosal tear after scope passagescope passage

Try medical Try medical treatment firsttreatment first

Eosinophilic Esophagitis:Eosinophilic Esophagitis: TreatmentTreatment

PPIs have shown efficacy in up to 50% of ptsPPIs have shown efficacy in up to 50% of pts

Topical steroids useful but recent PC/Rand Topical steroids useful but recent PC/Rand studies have shown less efficacy then open label studies have shown less efficacy then open label studiesstudies

Fluticosone or budesonide: Swallowed (not inhaled)Fluticosone or budesonide: Swallowed (not inhaled)

Allergy consultation: May be helpful in finding Allergy consultation: May be helpful in finding food or aeroallergen that is main culpritfood or aeroallergen that is main culprit

Am J Gastroenterol 2010; 105:747–756

GERD: WhatGERD: What’’s Hots Hot

Visceral Adiposity Increases the Risk Visceral Adiposity Increases the Risk of GERDof GERD

Courtesy of Brian Jacobson

Subcutaneous adiposity Visceral adiposity

Presenter

Presentation Notes

Studies have correlated gerd with visceral adiposity – that is fat in the intraperitoneal cavity – not subcutaneous fat.

ObesityObesity--Separation of the LES and Separation of the LES and Diaphragmatic CrusDiaphragmatic Crus

Pandolfino JE, et al. Pandolfino JE, et al. GastroenterologyGastroenterology 2006; 6392006; 639--349349

InspirationInspiration

ObeseObeseNormalNormal

LESLES

Crural Crural DiaphragmDiaphragm

Intragastric Intragastric PressurePressure

Intragastric Intragastric PressurePressure

HRM

Visceral Adiposity

separation

Presenter

Presentation Notes

Looked intragastric pressure in normals vs. obese individuals

GERD and BMI: WomenGERD and BMI: Women

N Engl J Med 2006;354:2340-2348.

An increase in BMI of 3.5 was associated with increased risk of frequent GERD symptoms, even in women with normal baseline weight

P<0.001 Multivariate odds in women with at least weekly GERD symptoms (n=2306) or no symptoms (n=3904)0

0.51

1.52

2.53

3.54

Od

ds

Rat

io

<20 20 22 25 27 30 ≥35

Obesity as a Risk Factor: Obesity as a Risk Factor: BarrettBarrett’’s Esophaguss Esophagus

Obesity Odds Ratio 95% CI

With GERD Symptoms 34.4 6.3-188.0

Without GERD Symptoms 0.7 0.2-2.4

Risk of Barrett’s Esophagus in Obesity with GERD Symptoms

n = 167 with histologically confirmed Barrett’s esophagus

Smith KJ, et al. Cancer Epidemiol Biomarkers Prev. 2005;14:2481-2486.

n = 2602

Hvid-Jensen et al., NEJM 2011;365(15):1375-1385

Lower Incidence of EAC with Larger Studies

Wani et al Clin Gastroenterol Hep. 2011; 9:200-220

GERDGERD

PPIs are no longer viewed as innocuous medsPPIs are no longer viewed as innocuous meds

Malabsorption of nutrientsMalabsorption of nutrients

Iron, calcium, Vitamin B12Iron, calcium, Vitamin B12

Increase risk for fracturesIncrease risk for fractures

Increase risk for infections including Increase risk for infections including Clostridium Clostridium difficiledifficile

Interaction with clopidogrel (less an issue now)Interaction with clopidogrel (less an issue now)

PPI use and Hip fracturePPI use and Hip fracture

CaseCase--control study of patients older than 50 control study of patients older than 50 years in a large UK databaseyears in a large UK database

PPI users had a 4 /1000 risk for hip fx vs 1.8 /1000 in nonPPI users had a 4 /1000 risk for hip fx vs 1.8 /1000 in non-- users of acid related medsusers of acid related meds

Absolute risk still lowAbsolute risk still low

Seven case control or cohort trials have shown Seven case control or cohort trials have shown a small absolute increased risk of fracturesa small absolute increased risk of fractures

Recent metaRecent meta--analysis (DDW abs only) showed a analysis (DDW abs only) showed a slight increase in hip fx with PPI therapyslight increase in hip fx with PPI therapy

JAMA 2006;296:2947-29Calcif Tissue Int. 2008;83:251-259

Long term PPI useLong term PPI use

AGA now recommends Calcium / Vit D in long AGA now recommends Calcium / Vit D in long term users at risk for osteoporosisterm users at risk for osteoporosis

No guidelines for monitoring B12 or ironNo guidelines for monitoring B12 or iron

Be aware, check when clinically indicatedBe aware, check when clinically indicated

Be aware of meds that absorb better with acidBe aware of meds that absorb better with acid

Digoxin, amoxicillin, ketoconazole, iron, calciumDigoxin, amoxicillin, ketoconazole, iron, calcium

Organic (heme derived) iron now availableOrganic (heme derived) iron now available

PPIs and InfectionsPPIs and Infections

Studies have linked acid suppresion meds Studies have linked acid suppresion meds including PPIs with including PPIs with C. difficile C. difficile infectioninfection

Higher recurrence of C diff if on PPI at time of RxHigher recurrence of C diff if on PPI at time of Rx

May increase risk for hospital acquired May increase risk for hospital acquired pneumoniapneumonia

Am J Gastro 2007;102:2047-56 CMAJ 2004;171:33-38JAMA. 2004;292:1955-60 Ann Intern Med. 2008;149:391-98Arch Intern Med 2010;170:772-8

Arch Intern Med. 2010;170(9):772-778

42% more likely to recur if on PPIs

PPIs: WaltPPIs: Walt’’s Recss Recs

Right drug, right disease, right patientRight drug, right disease, right patient

If your patient needs the PPI for PUD, GI bleeding, If your patient needs the PPI for PUD, GI bleeding, BarrettBarrett’’s esophagus, then use the PPIs esophagus, then use the PPI

Lowest dose that worksLowest dose that works

Use Calcium and Vit D in long term usersUse Calcium and Vit D in long term users

If it is symptomatic GERD only, other optionsIf it is symptomatic GERD only, other options

Lifestyle changes, H2 blockers, antacidsLifestyle changes, H2 blockers, antacids

Informed consent to patient until final dataInformed consent to patient until final data

NB. More GI bleeding in Cogent study in nonNB. More GI bleeding in Cogent study in non--PPI PPI usersusers

Celiac Disease: WhatCeliac Disease: What’’s New!s New!

Common gene: DQ2 and DQ8: Up to 25%Common gene: DQ2 and DQ8: Up to 25%

ONLY predisposes one to CeliacONLY predisposes one to Celiac

Actual disease in 1% in US: Iceberg analogyActual disease in 1% in US: Iceberg analogy

Gluten enteropathy VS Gluten intoleranceGluten enteropathy VS Gluten intolerance

Gluten avoidance is in vogue!!!Gluten avoidance is in vogue!!!

Diagnosis: Gold standard remains SB biopsyDiagnosis: Gold standard remains SB biopsy

Serology: Tissue Transglutaminase and Serology: Tissue Transglutaminase and Endomysial antibody excellent sens/specificityEndomysial antibody excellent sens/specificity

ALWAYS check serum IgA (IgA deficiency)ALWAYS check serum IgA (IgA deficiency)

Celiac BurdenCeliac Burden

Varying Forms of Celiac DiseaseVarying Forms of Celiac Disease

••

Classical celiac disease of childhoodClassical celiac disease of childhood

••

Late onset, nonLate onset, non--specific GI symptomsspecific GI symptoms

••

Dermatitis herpetiformisDermatitis herpetiformis

••

ExtraExtra--intestinal presentations (many)intestinal presentations (many)

••

Associated conditions (many)Associated conditions (many)

••

Silent or asymptomatic celiac disease Silent or asymptomatic celiac disease (relatives)(relatives)

••

Latent or potential celiac diseaseLatent or potential celiac disease

Dermatitis HerpetiformisDermatitis Herpetiformis

••

Pruritic papulovesicular lesionsPruritic papulovesicular lesions

IgA deposits at dermalIgA deposits at dermal--epidermal junctionepidermal junction

••

Almost all have abnormal intestinal biopsiesAlmost all have abnormal intestinal biopsies

Few have GI symptomsFew have GI symptoms

••

Treatment directed against skin doesnTreatment directed against skin doesn’’t help gut lesions t help gut lesions (e.g., dapsone)(e.g., dapsone)

••

Gluten free diet helps both gut and skinGluten free diet helps both gut and skin

Associated Autoimmune Associated Autoimmune Conditions Conditions

••

Diabetes mellitus Diabetes mellitus --

Type IType I

~ ~ 3 to 8 % have celiac disease3 to 8 % have celiac disease

••

Autoimmune thyroid disease Autoimmune thyroid disease (~5%)(~5%)

••

AddisonAddison’’s diseases disease

••

Alopecia areataAlopecia areata

••

SjogrenSjogren’’s syndromes syndrome

••

OthersOthers

Associated Hepatobiliary Associated Hepatobiliary Conditions Conditions

••

Primary sclerosing cholangitisPrimary sclerosing cholangitis

••

Autoimmune cholangitisAutoimmune cholangitis

••

Primary biliary cirrhosisPrimary biliary cirrhosis

••

Elevated transaminasesElevated transaminases

((up to 5 X normal)up to 5 X normal)

Nonspecific histologic changesNonspecific histologic changes

Normalize on GFD within a year in 75Normalize on GFD within a year in 75--95%95%

Evaluation of unexplained elevated AST, Evaluation of unexplained elevated AST, ALT includes testing for celiac diseaseALT includes testing for celiac disease

Rubio-Tapa, A, et al, Hepatology, 46, 1650, 2007

Changing Picture of DiseaseChanging Picture of Disease

••

Classical form less prevalent nowClassical form less prevalent now

••

Average age of diagnosis in 5Average age of diagnosis in 5thth

decadedecade

••

Many are overweight Many are overweight

••

Seroprevalence M=F, diagnosis M<FSeroprevalence M=F, diagnosis M<F

••

Other presentations are being increasingly Other presentations are being increasingly recognized: recognized:

AnemiaAnemia

OsteoporosisOsteoporosis

Obstetrical problemsObstetrical problems

Neuropsychiatric manifestationsNeuropsychiatric manifestations

Related autoimmune conditionsRelated autoimmune conditions

Celiac Issues and DilemmaCeliac Issues and Dilemma

Pt presents for Celiac testing on gluten free dietPt presents for Celiac testing on gluten free diet

Pt has negative serology (maybe even normal SB Pt has negative serology (maybe even normal SB biopsy) and insists they have celiacbiopsy) and insists they have celiac

Role for genetic testingRole for genetic testing

Gluten intolerance vs Gluten enteropathyGluten intolerance vs Gluten enteropathy

Health Maintenance:Health Maintenance:

Bone healthBone health

Liver diseaseLiver disease

Vitamin and mineral deficienciesVitamin and mineral deficienciesAm J Gastroenterol advance online pub, 1 March 2011

Gluten Causes Gastrointestinal Symptoms in Subjects Without Celiac Disease: A Double-Blind

Randomized Placebo-Controlled Trial

Jessica R. Biesiekierski , B Appl Sci 1 , Evan D. Newnham , MD, FRACP 1 , Peter M. Irving , MD, MRCP 1 , Jacqueline S. Barrett ,PhD, BSc, MND 1 , Melissa Haines

, MD 1 , James D. Doecke , BSc, PhD 2 , Susan J. Shepherd , B Appl Sci, PhD 1 , Jane G. Muir ,PhD, PGrad Dip(Dietetics) 1 and Peter R. Gibson , MD, FRACP 1

Am J Gastroenterol advance online publication, 11 January 2011; doi: 10.1038/ajg.2010.487

Results

Am J Gastroenterol advance online publication, 11 January 2011; doi: 10.1038/ajg.2010.487

Results

Discussion

No prior randomized controlled trials demonstrating that the entity of “gluten intolerance”

does actually exist

This study supports the existence of non-celiac gluten sensitivity based on the following symptoms:

Bloating

Dissatisfaction with stool consistency

Abdominal pain

Tiredness

Gluten: The new bad boyGluten: The new bad boy

Future studies

Gluten may have the following deleterious effects in non-celiac patients:

Increase fermentation, and thus, distension

Increase cholinergic activation, and thus, increased smooth muscle contractility

Increase enteric NS stimulation by gluten digestion creating neurally active peptides

Symptoms may not be related to gliadin proteins of gluten

Carbohydrates –

fructans (in wheat)

Novak Djokavic claims his energy improved on gluten-

free diet and coincided with his winning streak

“A gluten-free diet can have implications far beyond the physical, especially in tennis, which taxes the mind like few other sports.”

Colon Cancer ScreeningColon Cancer Screening

Review of the GuidelinesReview of the Guidelines

WhatWhat’’s new?s new?

How are we doing?How are we doing?


What is the lifetime What is the lifetime risk for colon risk for colon cancer in the cancer in the United States?United States?

A.A.

2%2%B.B.

4%4%

C.C.

6%6%D.D.

8%8%

E.E.

10%10%

Colon CancerColon Cancer

Second most common cause of cancer deathSecond most common cause of cancer death

Prototypical disease for screeningPrototypical disease for screening

Intermediate probability of diseaseIntermediate probability of disease

Significant impact on public healthSignificant impact on public health

Well defined, modifiable disease progressionWell defined, modifiable disease progression

USPSTFUSPSTF ACS ACRACS ACR

USMSTFCCUSMSTFCC

ACGACG

AgeAge 5050--7575 5050 50/45 AfAm50/45 AfAm

ColonoscopyColonoscopy 10 yrs10 yrs 10 yrs10 yrs 10yrs10yrs

Flex SigFlex Sig 5 yrs5 yrs 55--10 yrs10 yrs

FS/FOBTFS/FOBT 5 yrs/ 3 yrs5 yrs/ 3 yrs

DCBEDCBE 5 yrs5 yrs

CT CT ColonographyColonography

Insuff EvidInsuff Evid 5 yrs5 yrs 5 yrs5 yrs

FOBTFOBT YearlyYearly YearlyYearly YearlyYearly

FITFIT YearlyYearly YearlyYearly Pt refusesPt refuses

Stool DNAStool DNA ??

Current Guidelines

Colo FSig FOBT FIT DCBE CTC sDNA

USPSTF2008

Q10yr;Age 50-75

Q5yr;Age 50-75

Annually;Age 50-75

Annually;Age 50-75

NM Insufficient evidence

Insufficient evidence

ACS-MSTF 2008

Q10yr;Age ≥

50Q5yr;Age ≥

50Annually; Age ≥

50Annually; Age ≥

50Q5yr;Age ≥

50Q5yr;Age ≥

50Age ≥

50; interval uncertain

ACG 2009 ACS/MSTF Q5-10yr;Age ≥

50Annually; Age ≥

50Annually; Age ≥

50NM Q5yr;

Age ≥

50Q3 yr; Age ≥

50

AAFP 2010 USPSTF USPSTF USPSTF NM NM USPSTF USPSTF

NCCN 2010 ACS/MSTF ACS/MST

FACS/MSTF ACS/MSTF NM ACS/MSTF Not first-line;

Uncertaininterval

Kaiser Avg risk adults

Avg risk adults

Avg risk adults

Avg risk adults

NR NR NR

Aetna ACS/MSTF ACS/MST

FACS/MSTF ACS/MSTF ACS/MSTF Exper. and

Investigat.Exper. andInvestigat.

United ACS/MSTF ACS/MST

FACS/MSTF ACS/MSTF ACS/MSTF NM Exper. and

Investigat.

Recent Evidence: Colonoscopy Reduces Recent Evidence: Colonoscopy Reduces MortalityMortality

National Polyp Study (2012)National Polyp Study (2012)

Removal of adenomas resulted in 53% lower risk of Removal of adenomas resulted in 53% lower risk of CRC related death within 10 years (up to 23 years)CRC related death within 10 years (up to 23 years)

Canadian studiesCanadian studies

CRC related deaths decreased with gastroenterologist CRC related deaths decreased with gastroenterologist performed colonoscopy complete to cecum (even performed colonoscopy complete to cecum (even right sided)right sided)

German studyGerman study

Diminished CRC incidence after colonoscopyDiminished CRC incidence after colonoscopy

Zauber AG et al. NEJM 2012

FITFIT

Antibody tests for the globin productAntibody tests for the globin product

Test performance can be modified/adjustedTest performance can be modified/adjusted

Better compliance than FOBTBetter compliance than FOBT

Easier (brush stool in toilet water) Easier (brush stool in toilet water)

Not impacted by dietNot impacted by diet

One, two, or three samples requiredOne, two, or three samples required

Any positive test = colonoscopyAny positive test = colonoscopy

Cannot make a class recommendationCannot make a class recommendation

Individual tests vary considerably; similar sensitivity to Individual tests vary considerably; similar sensitivity to HS FOBT and better specificityHS FOBT and better specificity

N ENGL J MED 2012; 366:697-706

Colonoscopy versus FIT in Colorectal- Cancer Screening

26,703 colo invites; 26,599 FIT invites

Male and females, randomized, prospective

24.6% had colo vs 34.2% had FIT (P<.001)

CRC: 30 pts (.1%) vs 33 (.1%)

Adenomas: 514 (1.9%) vs 234 (.9%) P<.001

FIT test may compare well to colo for cancer detection. Poor for detection of polyps.

N ENGL J MED 2012; 366:697-706

Average Risk Screening: Average Risk Screening: RecommendationsRecommendations

Stool cards(yearly); FIT??

Flexiblesigmoidoscopy(every 3–5 years)

Colonoscopy(every 10 years)

Barium enema(every 5 years)

OR

OR

AND

FUTURE?Stool DNACT colonographyCapsule Colonoscopy

≥50 years old

Preferred: ACG and MSGITFPreferred: ACG and MSGITF

Option: USPSTF, ACS, AGAOption: USPSTF, ACS, AGA

New Recommendations for New Recommendations for AfricanAfrican--AmericansAmericans

Younger mean age at diagnosis (60Younger mean age at diagnosis (60––66 years)66 years)

Higher incidence ratesHigher incidence rates

Higher mortality ratesHigher mortality rates

More proximal distribution of cancers and adenomasMore proximal distribution of cancers and adenomas

Recent American College of Gastroenterology Recent American College of Gastroenterology recommendations to beginrecommendations to begin

averageaverage--risk screening at risk screening at

age 45age 45

http://seer.cancer.gov/csr/1975http://seer.cancer.gov/csr/1975--2000. Access February 23, 2006. Agrawal S, et al. 2000. Access February 23, 2006. Agrawal S, et al. Am J Gastroenterol.Am J Gastroenterol. 2005;100:5152005;100:515––523. Ghafoor A, et al. 523. Ghafoor A, et al. CA Cancer J Clin.CA Cancer J Clin.

2002;52:3262002;52:326––341.341.

Screening Compliance is LowScreening Compliance is Low

Cancer Prevention and Early Detection, Fact s and Figures 2008

Stool Transplants:Stool Transplants: Everyone is doing it!Everyone is doing it!

Stool Transplants: How ToStool Transplants: How To

Stool transplants: Stool transplants: ““preparedprepared””

feces by feces by

NGT or enema or colonoscopyNGT or enema or colonoscopy

Usually family member; 30Usually family member; 30--50 g fresh 50 g fresh stoolstool

Stool homogenized for deliveryStool homogenized for delivery

No infectious complications to dateNo infectious complications to date

Screen for Hepatitis, HIV, etcScreen for Hepatitis, HIV, etc……

7373--100% response reported in C Diff100% response reported in C Diff

Gastro 2006;130 Clin Infect Dis 2003;36

Stool Transplant: EvidenceStool Transplant: Evidence

2003 case series of refractory 2003 case series of refractory C diffC diff patients patients Stool via NG from healthy family memberStool via NG from healthy family member

15 of 18 became recurrence15 of 18 became recurrence--freefree

2009 case series of refractory 2009 case series of refractory C diff C diff patientspatients 11 of 15 became recurrence11 of 15 became recurrence--freefree

2010 case series of refractory C diff patients2010 case series of refractory C diff patientsStool via colonoscopyStool via colonoscopy

12 of 12 with immediate and sustained response12 of 12 with immediate and sustained response

Clin Infect Dis 2003;36: 540-544 QJM 2009;102:781-784 Yoon, J of Clin Gastro 2010, 44:562-66

Colonoscopy Stool TransplantsColonoscopy Stool Transplants

Coming to your neighborhood soonComing to your neighborhood soon……..

Stool transplants done here.

Donations accepted.

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2010;8:471–473

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2011;9:1044–1049

Fecal Transplant WorkgroupFecal Transplant Workgroup

Good review and provides Good review and provides ““cookbookcookbook””

recipe for performing fecal transplantrecipe for performing fecal transplant

CoyleCoyle’’s Corollarys Corollary

It is better to be a stool donor

than a recipient.

Stool donor cards will be made available after this

lecture.

Stool Donor Card

Share your stool; stop C diff

Clinical Gastro Hep 2008; 759-764

MethodsMethods

Prosp. study; 113 pts with rosacea 60 controlsProsp. study; 113 pts with rosacea 60 controls

Derm Assessment by two docsDerm Assessment by two docs

7 point scale7 point scale

All subjects completed global scoreAll subjects completed global score

Baseline labs, Urease BT, H2 Breath testsBaseline labs, Urease BT, H2 Breath tests

Lactulose BT: 1Lactulose BT: 1stst, + test if double peak seen, + test if double peak seen

Glucose BT: 2Glucose BT: 2ndnd

(1 wk later), + test single peak(1 wk later), + test single peak

Hp + pts, treated then reHp + pts, treated then re--tested by H2 BTtested by H2 BT

If both Hp + and SIBO+: rx SIBO 1stIf both Hp + and SIBO+: rx SIBO 1st

Results: SIBO pos and neg ptsResults: SIBO pos and neg pts

Clinical Gastro Hep 2008; 759-764

Rosacea and the MicrobiomeRosacea and the Microbiome

DiscussionDiscussion

SIBO common in Rosacea ptsSIBO common in Rosacea pts

Esp those with papulopustulesEsp those with papulopustules

Rx of SIBO results in dramatic improvement of rashRx of SIBO results in dramatic improvement of rash

78% resolved/17% improved (95% total)78% resolved/17% improved (95% total)

Affect is sustained (9 months); relapse can be reAffect is sustained (9 months); relapse can be re--treatedtreated

Hypothesis: SIBO increases intest absorption of Hypothesis: SIBO increases intest absorption of bacterial products, esp endotoxin, proinflam cytokinesbacterial products, esp endotoxin, proinflam cytokines

SIBO more important then colonic bacteria (SIBO SIBO more important then colonic bacteria (SIBO neg rosacea pts did not respond as well)neg rosacea pts did not respond as well)

Question number 4.Question number 4. What is the cause of discoloration?What is the cause of discoloration?

A.A.

Strep toxic shock Strep toxic shock syndromesyndrome

B.B.

Gray Turner sign from Gray Turner sign from pancreatitispancreatitis

C.C.

Cannabinoid Cannabinoid hyperemesis syndromehyperemesis syndrome

D.D.

HeparinHeparin--induced induced cutaneous hemorrhagecutaneous hemorrhage

Cannabinoid Hyperemesis Cannabinoid Hyperemesis SyndromeSyndrome

First reported in AustraliaFirst reported in Australia

Chronic, heavy marijuana useChronic, heavy marijuana use

More common in malesMore common in males

Recurrent episodes of abdominal pain and Recurrent episodes of abdominal pain and vomitingvomiting

Compulsive hot bathing and showers for relief Compulsive hot bathing and showers for relief of symptomsof symptoms

Rx: Rx: Quit the Weed!Quit the Weed!

Singh E, Coyle W. Am J Gastro 2008;103:1048-49

Mayo Clin Proc. 2012;87(2):114-119

The Microbiome and The Microbiome and ProbioticsProbiotics

The Human MicrobiomeThe Human Microbiome

Definitions: Definitions:

Microbiome: Aggregate of all gut speciesMicrobiome: Aggregate of all gut species

Microbiota: Individual bacterial species in the biomeMicrobiota: Individual bacterial species in the biome

Over 100 trillion organisms (10Over 100 trillion organisms (101414))

Passengers in the mobile colonic petri dishPassengers in the mobile colonic petri dish

Over 500 species identified so far (70 divisions)Over 500 species identified so far (70 divisions)

90% of the cells in our body our microbial!90% of the cells in our body our microbial!

100 fold more genes in our gut then in us100 fold more genes in our gut then in us

Our flora are an integral part of our genetic Our flora are an integral part of our genetic landscape and evolutionlandscape and evolution

The Microbiome: WhoThe Microbiome: Who’’s there?s there?

Early gut colonization has four phasesEarly gut colonization has four phases

Phase 1: Sterile gut Phase 1: Sterile gut

Phase 2: Initial acquisition: vagina, feces, hospitalPhase 2: Initial acquisition: vagina, feces, hospital

Phase 3: Breast feeding or bottlePhase 3: Breast feeding or bottle--feeding (different)feeding (different)

Breast fed more bifidobacteria (up to 90% of flora)Breast fed more bifidobacteria (up to 90% of flora)

Bottle fed more diverse; more Bottle fed more diverse; more BacteroidesBacteroides

, and , and Clostridial speciesClostridial species

Phase 4: Start of solids; move to adult flora Phase 4: Start of solids; move to adult flora

Bifidobacteria remain key flora into adulthoodBifidobacteria remain key flora into adulthood

Ley, Peterson, Gordon. Cell 2006 ;124:837Ley, et al. PNAS. 2005, 102: 11070 Edwards, et al. Br J Nutr. 2002

CC--Section and Gut FloraSection and Gut Flora

Danish Registry:CDanish Registry:C--section vs NVD in 2.1 mil Danessection vs NVD in 2.1 mil Danes

32 million person years of follow32 million person years of follow--upup

1.29 RR for IBD (most notable < age 14)1.29 RR for IBD (most notable < age 14)

Scottish study on rising incidence of IBDScottish study on rising incidence of IBD

CC--section associated with increased risk of IBD section associated with increased risk of IBD

1.26 RR (boys only)1.26 RR (boys only)

More UC than CDMore UC than CD

Bager, et al. Inflam Bowel disease, 2012;18:857-62Andersen et al. Inflam Bowel disease, 2012;18:999-1005

Breastfeeding and IBDBreastfeeding and IBD

Systemic review: Found 8 articles relatedSystemic review: Found 8 articles related

Children who are breast fed protected from IBDChildren who are breast fed protected from IBD

Decreased risk for IBD (OR .69, CI .51Decreased risk for IBD (OR .69, CI .51--.94, P=02) .94, P=02)

Only protective in early yearsOnly protective in early years

Is it microbiome or some factor in breast milk?Is it microbiome or some factor in breast milk?

Barclay et al. J Pediatrics, 2009;155:421-426

The Human Gut Flora

DiBiase, et al. Mayo Clin Proc 2008;83:460-469

Microbes and Humans

Dethlefsen Nature 2007; 449:812-818

International J of Obesity; 2012: 1-8

Studied 11,532 children in Avon, UK (91Studied 11,532 children in Avon, UK (91--93)93)

Mapped antibiotic use (<6m,6Mapped antibiotic use (<6m,6--14m,1514m,15--23m)23m)

Body mass documented at 6wks, 10m, 20m, Body mass documented at 6wks, 10m, 20m, 38m and 7 yrs38m and 7 yrs

Multivariate analysis: role of tob, motherMultivariate analysis: role of tob, mother’’s BMI, s BMI, other medications, etcother medications, etc……

Blaser, et al. Nature 2012

Antibiotics in children and obesityAntibiotics in children and obesity

Proposed Mechanisms in Obesity

DiBiase, et al. Mayo Clin Proc 2008;83:460-469

Gut Flora and MetabolismGut Flora and Metabolism

Microbial genomes enhance our metabolic activityMicrobial genomes enhance our metabolic activity

May indirectly or directly effect our metabolismMay indirectly or directly effect our metabolism

The colon is very active metabolicallyThe colon is very active metabolically

2020--70 gms of carbos and 570 gms of carbos and 5--20 gms of protein/day20 gms of protein/day

Over 100 kcal per day!Over 100 kcal per day!

Mass of colonic microbiome = single kidneyMass of colonic microbiome = single kidney

Metabolically as active as the liverMetabolically as active as the liver

Hooper, et al. Annu Rev Nutr, 2002

ProbioticsProbiotics

Definition: Live microorganisms which when Definition: Live microorganisms which when ingested in adequate amounts confer a health ingested in adequate amounts confer a health benefit on the host. benefit on the host.

Majority of probiotics are Gram +, lactic acid Majority of probiotics are Gram +, lactic acid producers (ie. Firmacutes)producers (ie. Firmacutes)

Bifidobacterial species and Bifidobacterial species and LactobacillusLactobacillus speciesspecies

Survive transit through stomach and duodenumSurvive transit through stomach and duodenum

Others include: nonOthers include: non--pathogenic streptococci, pathogenic streptococci, enterococci, enterococci, E coliE coli Nissle 1917, Nissle 1917, Saccharomyces Saccharomyces boulardiiboulardii (yeast)(yeast)

Fooks, et al. Int Dairy J, 1999 Sheil, et al. In Gastrointestinal Microbiology, 2006


Which probiotic Which probiotic has been shown to has been shown to decrease mucosal decrease mucosal ILIL--6 levels?6 levels?

A.A.

Lactobacillis acidopholusLactobacillis acidopholusB.B.

Bifidobacter infantisBifidobacter infantis

C.C.

Saccharomyces boulardiiSaccharomyces boulardiiD.D.

Lactobacillus rhamnosus Lactobacillus rhamnosus GGGG


VSL #3VSL #3

4 lactobacilli4 lactobacilli

L. plantarum, casei, L. plantarum, casei, acidopholus, delbrueckii acidopholus, delbrueckii sppspp

3 bidifobacteria3 bidifobacteria

B. infantis, breve, longumB. infantis, breve, longum

1 streptococcus1 streptococcus

Streptococcus salivarius ssp. Streptococcus salivarius ssp. thermophilusthermophilus

Rand, PC studies have shown efficacy in pouchitis and IBSSome efficacy in mild/mod UC in new study


12 different species12 different species

Mostly Lactobacillus and Mostly Lactobacillus and Bidifobacter speciesBidifobacter species

Clinical data with these Clinical data with these combinations lackingcombinations lacking


Digestive AdvantageDigestive Advantage

Ganeden BCGaneden BC3030

Bacillus coagulansBacillus coagulans

ErythritolErythritol

CelluloseCellulose

Other minor ingredients Other minor ingredients

Some data for IBSSome data for IBS

Mostly bloatingMostly bloating

Postgrad Med, Vol. 121, Issue 2, March 2009


Bifidobacterium infantisBifidobacterium infantis 35624 aka Bifantis 35624 aka Bifantis

““PatentedPatented””

strain of strain of probiotic in Alignprobiotic in Align

Decreased symptoms in Decreased symptoms in two large trials in two large trials in subjects with IBS*subjects with IBS*

*Whorwell P, et al. Am J Gastro 2006; 101O’Mahoney L, et al. Gastro 2005;128


Saccharomyces Saccharomyces boulardiiboulardii

Other minor ingredientsOther minor ingredients

Shown in Rand / PC Shown in Rand / PC trials to help prevent trials to help prevent recurrent recurrent C. difficileC. difficile

infectioninfection

Decreases antibiotic Decreases antibiotic associated diarrheaassociated diarrhea

Am J Gastroenterol. 2006 Apr;101(4):812-22McFarland, et al. JAMA 1994;271:1913-8

Probiotics: E. coli Nissle 1917Probiotics: E. coli Nissle 1917

Discovered in 1917 Discovered in 1917 by Professor Alfred by Professor Alfred NissleNissle

Well studiedWell studied

Some data for use in Some data for use in IBD, IBS, and Ab IBD, IBS, and Ab associated diarrheaassociated diarrhea

Excellent safety Excellent safety profileprofile

Probiotics in Food (Actimel)Probiotics in Food (Actimel)

L. caseiL. casei

ImmunitasImmunitas™™

Claim it is scientifically Claim it is scientifically proven to be effectiveproven to be effective

““Each bottle contains Each bottle contains 10 billion live10 billion live””

bacteria bacteria

““that survive and that survive and remain active in theremain active in the

digestive tract.digestive tract.””

Probiotics in Food (Activia)Probiotics in Food (Activia)

Contains Contains Bifidus regularisBifidus regularis

Bifidobacterium animusBifidobacterium animus

Scientific trials show Scientific trials show increased transit time in increased transit time in adults and womenadults and women

““Helps with slow transit in Helps with slow transit in women and the elderlywomen and the elderly””

Bioscience and Microflora, 2001;20:43-48,Aliment Pharn Ther 2002;16:587-93

Probiotics for Immune SystemProbiotics for Immune System

Lactobacillus rhamnosusLactobacillus rhamnosus

GG (ATCC GG (ATCC 53103)53103)

Patented by Gorbach and GoldinPatented by Gorbach and Goldin

Various studies have shown it to Various studies have shown it to be better than placebo for diarrheal be better than placebo for diarrheal illnessesillnesses

Proven to survive the stomach, Proven to survive the stomach, produces lactic acid and binds to produces lactic acid and binds to human colonocyteshuman colonocytes

BMJ 2007; 335 : 340-345

Probiotics and prebiotics in maintenance of Probiotics and prebiotics in maintenance of remission in Crohnremission in Crohn’’s diseases disease

Study Groups Relapse Rate (%)

n Intervention Comparator Dur Intervention Comparator p

Guslandi (2000)

32 S. Bouliardii +

Mesalamine

Mesalamine 6 6 38 0.04

Campieri (2000)

40 VSL #3 Mesalamine 12 20 40 NR

Prantera (2002)

45 LGG Placebo 12 17 11 0.3

Schultz (2004)

11 LGG Placebo 6 60 67 NS

Bousvaro s (2005)

75 LGG Placebo 24 31 17 0.18

Marleau (2006)

98 L. johnsonii Placebo 6 49 64 0.15

Van Gossum (2007)

70 L. johnsonii Placebo 3 15 14 0.91

Chermes h (2007)

30 Synbiotic 2000

Placebo 24 25 20 NS

Clostridium difficileClostridium difficile

Clostridium difficile Clostridium difficile and altered and altered microbiotamicrobiota

Confirmed BI NAP1 strainConfirmed BI NAP1 strain

Gerding, et al. GASTRO 2009;136:1913–1924

Metronidazole failuresMetronidazole failures

Leffler and Lamont in GASTRO 2009;136:1899–1912

New New C Difficile C Difficile Rx GuidelinesRx Guidelines

Infect Control Hosp Epidemiol 2010; 31(5):431-455

Burden Of CDI in USBurden Of CDI in US

Gerding, et al. GASTRO 2009; 136:1913–1924

TreatmentTreatment

DC offending antibiotic (s) if possibleDC offending antibiotic (s) if possible

Avoid antiperistaltic agents (incl narcs)Avoid antiperistaltic agents (incl narcs)

Supportive care (hydrate, electrolytes)Supportive care (hydrate, electrolytes)

Antimicrobial therapy:Antimicrobial therapy:

Oral metronidazole: 250 mg qid or 500 mg TID Oral metronidazole: 250 mg qid or 500 mg TID for 10 days; low cost, effectivefor 10 days; low cost, effective

Oral Vancomycin: 125Oral Vancomycin: 125--250 mg QID for 10 days250 mg QID for 10 days

High costHigh costAnn Intern Med 2006;145

Gastro 2009; 136:1913–1924

Recurrence: Probiotic Treatment Recurrence: Probiotic Treatment of of C difficileC difficile


Saccharomyces boulardii: 500 mg bid for 4Saccharomyces boulardii: 500 mg bid for 4--6 wks6 wks

Best evidence of all probioticsBest evidence of all probiotics

Several DB / PC trials show good efficacySeveral DB / PC trials show good efficacy

Lactobacilli: 1 g qid for 4Lactobacilli: 1 g qid for 4--6 weeks6 weeks

Evidence not as convincingEvidence not as convincing

PO nontoxicogenic C Diff: experimentalPO nontoxicogenic C Diff: experimental

Effective but only case reports to dateEffective but only case reports to date

Gastro 2006;130 Ann Intern Med 2006; 145 Am J Gastroenterol 2006; 101:812–822.

FidaxomicinFidaxomicin

Macrocyclic antibioticMacrocyclic antibiotic

Cure: 88.2% vs 85.8% vancomycinCure: 88.2% vs 85.8% vancomycin

Recurrence Rate: 15.4 % vs 25.3 % Recurrence Rate: 15.4 % vs 25.3 %

FDA approved.FDA approved.


NEJM 2011;364:422-431


FDA approved May 2011FDA approved May 2011

Macrolide Ab: Aka Macrolide Ab: Aka DificidDificid

Dose: 200 mg BID for 10 daysDose: 200 mg BID for 10 days

Estimated cost: $2800 for full courseEstimated cost: $2800 for full course

WaltWalt’’s Recs Rec: : Not first line, too expensiveNot first line, too expensive

Save for recurrent Save for recurrent C. difficileC. difficile

infectionsinfections

Probiotics and DiarrheaProbiotics and Diarrhea

135 hospitalized pts given antibiotics135 hospitalized pts given antibiotics

DB, PC, Rand trialDB, PC, Rand trial

Probiotic Yogurt (Actimel) or PC BIDProbiotic Yogurt (Actimel) or PC BID

Diarrhea: 34% PC vs 12% active (NNT:5)Diarrhea: 34% PC vs 12% active (NNT:5)

C DiffC Diff: Less often in Rx arm (NNT: 6): Less often in Rx arm (NNT: 6)

First rand trial to show prevention of First rand trial to show prevention of C diff C diff with with probioticsprobiotics

Hickson M, et al. BMJ, 2007:335-80

Probiotics and PancreatitisProbiotics and Pancreatitis Not all good news!Not all good news!

296 hospitalized pts with acute pancreatitis given 296 hospitalized pts with acute pancreatitis given probioticsprobiotics

DB, PC, Rand trial; Given in tube feedingsDB, PC, Rand trial; Given in tube feedings

Probiotic : Ecologic 642 (Probiotic : Ecologic 642 (L. acidophilus, casei, L. acidophilus, casei, salivarius, lactis and B. bifidum, lactissalivarius, lactis and B. bifidum, lactis.).)

Morbidity: No difference in infectionsMorbidity: No difference in infections

Mortality: 24 (16%) vs 9 (6%) in PCMortality: 24 (16%) vs 9 (6%) in PC

9 pts in Rx arm developed ischemic bowel9 pts in Rx arm developed ischemic bowel

Besselink M,

Gooszen H, et al Lancet 2008:371:651-659

PrebioticsPrebiotics


Ingested substances that selectively stimulate the Ingested substances that selectively stimulate the proliferation and/or activity of desirable proliferation and/or activity of desirable bacterial populations present in the host bacterial populations present in the host intestinal tract.intestinal tract.

Usually target bifidobacteria and lactobacilliUsually target bifidobacteria and lactobacilli

Bifidogenic or bifidus factors explored in the 50sBifidogenic or bifidus factors explored in the 50s

Usually are nonUsually are non--digestible oligosaccharides digestible oligosaccharides (NDOs)(NDOs)

Lactulose, galactoLactulose, galacto--oligosaccharides, lactosucroseoligosaccharides, lactosucrose……

Crittenden and Playne. In Gastrointestinal Microbiology, 2006, pg 285-314.


Inulin: plant polymers Inulin: plant polymers mainly comprising mainly comprising fructose units, use have a fructose units, use have a terminal glucoseterminal glucose

Indigestable fiberIndigestable fiber

Gut flora produce H2, Gut flora produce H2, CO2, methane gas from CO2, methane gas from inulininulin


Inulin: plant polymers mainly Inulin: plant polymers mainly comprising fructose units, comprising fructose units, use have a terminal glucoseuse have a terminal glucose

Indigestable fiberIndigestable fiber

Gut flora produce H2, CO2, Gut flora produce H2, CO2, methane gas from inulinmethane gas from inulin

““Breakfast of FlatulanceBreakfast of Flatulance””


Feed your flora!!!


Is is possible to design a food, sugar, protein, or Is is possible to design a food, sugar, protein, or fat that would alter your gut flora to promote fat that would alter your gut flora to promote weight loss?weight loss?

More likely possibility is to give a prebiotic that More likely possibility is to give a prebiotic that decreases your decreases your ““Energy HarvestEnergy Harvest””

of colonic of colonic

bacteriabacteria

ie. lose weight by making your gut flora less efficient ie. lose weight by making your gut flora less efficient at digesting your left over food at digesting your left over food

Designing Probiotics: The Future?Designing Probiotics: The Future?

GASTROENTEROLOGY 2009;136:2015–2031

ConclusionsConclusions

Future studies must focus on the mechanisms of Future studies must focus on the mechanisms of influence of our gut flora.influence of our gut flora.

Studies must be placebo controlled and high Studies must be placebo controlled and high quality.quality.

Truly need translational science to work at the Truly need translational science to work at the levels of the petri dish, genomics, and clinical levels of the petri dish, genomics, and clinical outcomes.outcomes.

Much more to come!Much more to come!

GI Update: SummaryGI Update: Summary

Longstanding dysphagia: Think EoELongstanding dysphagia: Think EoE

PPIs: Use them thoughtfullyPPIs: Use them thoughtfully

Be smart about Celiac disease: Know the testsBe smart about Celiac disease: Know the tests

Colon cancer screening: DO IT!Colon cancer screening: DO IT!

Colonoscopy saves livesColonoscopy saves lives

New role for FIT testingNew role for FIT testing

GI Update: SummaryGI Update: Summary

Stool transplants: Not ready for prime timeStool transplants: Not ready for prime time

Think SIBO with RosaceaThink SIBO with Rosacea

Pot and vomiting: Ask about hot bathsPot and vomiting: Ask about hot baths

Microbiome: research will explodeMicrobiome: research will explode

C. difficileC. difficile: the pest is here to stay: the pest is here to stay

QuestionsQuestions

Break TimeBreak Time

THE CALLTHE CALL

First Rule: Never go to “check”

a puppy out

The Visit

Review of Bloodline

Rule two: Never believe that parents have anything to do with the pup

Rule Three: Never bring the puppy home

The InfectionThe Infection

The DecisionThe Decision

Probiotics and Probiotics and C. DifficileC. Difficile

124 Adults with 124 Adults with C difficile C difficile (Rand, PC)(Rand, PC)

64 164 1stst

episode, 60 recurrent CDADepisode, 60 recurrent CDAD

Standard Ab with Standard Ab with S. boulardii S. boulardii or PBO or PBO

Outcome: Recurrence of CDADOutcome: Recurrence of CDAD

11stst

Episode: 19.3% vs 24.2% (P=.86)Episode: 19.3% vs 24.2% (P=.86)

Rec CDAD: 34.6% vs 64.7% (P=.04)Rec CDAD: 34.6% vs 64.7% (P=.04)

S. boulardii S. boulardii reduces risk for recurrence in subjects reduces risk for recurrence in subjects with recurrent with recurrent C difficileC difficile

McFarland, et al. JAMA 1994;271:1913-8

PPIs and ClopidogrelPPIs and Clopidogrel

Most PPIs are metabolized partly via CYP 2C19Most PPIs are metabolized partly via CYP 2C19

CYP 2C19 critical for activation of clopidogrelCYP 2C19 critical for activation of clopidogrel

Very mixed data whether PPIs decrease efficacy Very mixed data whether PPIs decrease efficacy of clopidogrel: ie. of clopidogrel: ie. Concern is stent patencyConcern is stent patency

Prompted FDA warningPrompted FDA warning

The only Rand/PC controlled studyThe only Rand/PC controlled study

Showed no effect from PPIs on stent occlusionShowed no effect from PPIs on stent occlusion

Study stopped due to funding shortageStudy stopped due to funding shortage

COGENT TRIALCOGENT TRIAL

N Engl J Med 2010;363:1909-17

-3761 subjects-CV Event Rate:

4.9% vs 5.7%

COGENT TRIALCOGENT TRIAL

N Engl J Med 2010;363:1909-17

-3761 subjects-GI event rate:1.1% vs 2.9%

COGENT TrialCOGENT Trial

End point Placebo, n PPI, n p

All CV events 67 69 NS

MI 37 36 NS

Revascularization 67 69 NS

GI events 67 38 0.007

COGENT event ratesCOGENT event rates

Bhatt D. TCT 2009; Sept 24, 2009; San Francisco, CA.

PPIs and clopidogrelPPIs and clopidogrel

US Food and Drug Administration: Drug Safety Information Nov 2009

N Engl J Med 2010;363:1909-17.

Inflammatory Bowel DiseaseInflammatory Bowel Disease

Newer ConceptsNewer Concepts

TreatmentTreatment

Top down VS Step upTop down VS Step up

IMMUNE RESPONSE

GENETICSUSCEPTIBILITY

ENVIRONMENTALTRIGGERS & MODIFIERS

Current Model:Current Model: Pathogenesis of CrohnPathogenesis of Crohn’’s s

Disease and UCDisease and UC

Bickston SJ, et al. Curr Gastroenterol Rep. 2003;5:518.Bickston SJ, et al. Curr Gastroenterol Rep. 2003;5:518.

Environment and IBDEnvironment and IBD

Geographic distributionGeographic distribution

Increase incidence in emigrants to NorthIncrease incidence in emigrants to North

SmokingSmoking

Germ free animals do not get IBDGerm free animals do not get IBD

Influence of the microbiomeInfluence of the microbiome

? Infectious (? Infectious (M. paratuberculosis, E.coliM. paratuberculosis, E.coli, , Measles) Measles) ––

Antibody testing Antibody testing

Diet and Diversion of fecal streamDiet and Diversion of fecal stream

Environmental TriggersEnvironmental TriggersInflammatory

Bowel Disease

Infections

NSAIDsNSAIDs

StressStressSmokingSmoking

DietDiet

AntibioticsAntibiotics

IBDIBD

Normal Intestine vs. Normal Intestine vs. Intestine With IBDIntestine With IBD

Normal bowel: controlled inflammationNormal bowel: controlled inflammation

Normally: inflammationIs down-regulatedNormally: inflammationIs down-regulated

IBD: failure todown-regulate inflammation

IBD: failure todown-regulate inflammation

Chronic uncontrolledinflammation = IBDChronic uncontrolledinflammation = IBD

Environmentaltriggers (medicationsinfections, diet?)

Environmentaltriggers (medicationsinfections, diet?)

Inflamed bowelInflamed bowel

Normal bowel:controlled inflammation

Normal bowel:controlled inflammation

Management Goals in IBDManagement Goals in IBD

Define disease extent and severity and type

Evaluate for extra-intestinal disease and complications

Induction of clinical remission–

Short term side effects balanced vs. disease severity

Maintenance of remission–

Medical vs. Surgical

–

STEROID SPARING************************

Education and improvement of quality of life

“Step up”

vs “Top down therapy”

Therapeutic Options in IBDTherapeutic Options in IBD

Crohn’s Disease–

5-Aminosalicylates

–

Antibiotics–

Corticosteroids

–

6-MP/AZA–

Methotrexate

–

Biologics (TNFs)–

Tacrolimus

–

Probiotics?–

Surgery

Ulcerative Colitis–

5-Aminosalicylates

–

Corticosteroids

–

6-MP/AZA

–

Cyclosporine

–

Biologics (only infliximab to date)

–

Probiotics?

–

Surgery

Top down vs Step up RxTop down vs Step up Rx

Should we use TNFs earlierShould we use TNFs earlier

Summary for IBDSummary for IBD

Pathogenesis remains obscure stillPathogenesis remains obscure still

Role of Role of MicrobiomeMicrobiome

keykey

Serology has limited role in diagnosisSerology has limited role in diagnosis

Helpful in borderline casesHelpful in borderline cases

Treatment options have increasedTreatment options have increased

Individualized therapy bestIndividualized therapy best

Top down appropriate for some patientsTop down appropriate for some patients


Which of the following Which of the following extraextra--intestinal intestinal manifestations of IBD manifestations of IBD does not respond to does not respond to treatment of the IBD???treatment of the IBD???

A.A.

Primary Primary sclerosingsclerosing

cholangitischolangitisB.B.

ErythemaErythema

nodosumnodosum

C.C.

SacroileitisSacroileitis

D.D.

Acute arthritisAcute arthritis

E.E.

A and CA and C

F.F.

B and DB and D

update in gi: what’s new and useful - scripps

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