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Chronic Diarrhea

Christina Surawicz, MD, MACGProfessor of Medicine

University of Washington

Annual ACG Postgraduate CourseOct 30, 2011Oct. 30, 2011

Diagnostic Approach to Chronic Diarrhea

●Bloody

●Fatty

●Watery

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Diarrhea with Blood → Coli s Infection IBD Ischemia Ischemia Some drugsNSAIDS Isotretinoin

SCAD – Segmental Colitis Associated with Di ti l DiDiverticular Disease

Radiation Diversion colitis

Infection Uncommon

Stool Culture O + PSalmonella ∙ ParasitesCampylobacter • AmebaYersinia • TrichurisAeromonasPlesiomonas C. difficile (recurrent)

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Chronic Bloody Diarrhea: Work – up

Colonoscopy/biopsy= helpful to

distinguish IBD vs. infection

Colorectal Biopsy

IBD Infectionh b l lArchitecture Abnormal Normal

Inflammation Acute & Chronic Acute

Basal inflammation Yes None

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Normal Colon

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Chronic Bloody Diarrhea

History + exam History + exam

Stool cultures, O + P, in some

Colonoscopy and colorectal biopsy -py p ymainstay of diagnosis

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Steatorrhea – Clinical Clues Dietary history – intake compared to others

W i ht l Weight loss Stools –Not always diarrhea, may be bulkyHard to flushOily droplets floating on toilet

( )water (unhydrolyzed TG)

Steatorrhea – Vitamin Malabsorption

Fat soluble vitamins D A K EFat soluble vitamins D A K E

D - OsteomalaciaA - Night blindnessK - Easy bruisabilityK Easy bruisability

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Fecal Fat Analysis Qualitative I start with this I start with thisCan be subjective - variable lab personnelNormal is less than 20 drops/ hpf

Quantitative – 24 hr on 100 gm fat dietW i hWeight < 200 – 300 gm

Fat < 7 gm / 24 hr

Stool Fat Tests – Caveats High carbohydrate diet – increases stool weight

to 300 – 400 gms3 4 g Voluminous stools will raise fat excretion (up to

14 g/24 hour) Correct for fat intake - low fat diets False positives - Olestra, Brazil nuts Panc biliary source Panc – biliary source

> 9.5 gm / 100 gm stool∙ A guide – not 100%

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Steatorrhea

Luminal Mucosal

Pancreatic insufficiency ∙ Celiac sprue Bile salt deficiency ∙ Crohn’s disease Bacterial overgrowthBacterial overgrowth

Luminal - Pancreatic Insufficiency∙Direct function test: secretin test is a

research toolresearch tool

∙ Indirect tests ∙Serum trypsin∙Fecal chymotrypsin∙Fecal elastase

∙All have poor sensitivity/specificity

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Fecal Elastase 1 (FE1) 6% of pancreatic enzymes Abnormal: < 200 μg/gram stoolAbnormal: < 200 μg/gram stool But abnormal in many other conditionsCeliac disease IBD IBS

HIVHIV Diabetes

(Leeds et al, Nature Rev Gastro Hep 2011)

Pancreatic Insufficiency

Empiric trial of enzymes – reasonableEmpiric trial of enzymes reasonable• High dose – monitor wt gain or fecal fat• If respond, image pancreas

Another option is to rule out mucosal disease Another option is to rule out mucosal disease first

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Luminal - Bile Salt Deficiency

● Secondary- Cirrhosis, including PSC and PBC- Ileal disease or resection

< 100 cm - watery diarrhea> 100 cm - fatty diarrhea

● Primary- Primary bile salt deficiency, ususally

a watery diarrhea

Luminal - Small Intestinal Bacterial Overgrowth (SIBO)

Structural causes SI diverticulosis SI diverticulosis Stricture Surgical diversions

Dysmotility Scleroderma Intestinal pseudo-obstruction

Others ? Diabetes IBS Acid suppression

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SIBO Diagnosis• Clue:

• High folate - bacteria produceg p• Low B12 – bacteria consume

• SB aspirate – difficult to get accurate specimen

• Breath tests – not great

• Therapeutic trial of antibiotic – probably best

Mucosal - Celiac Disease

• Diarrhea • Infertilit and• Diarrhea • Infertility and recurrent fetal loss

• Weight Loss • Microscopic colitis

• Iron deficiency • Abnormal liver enzymesy y

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Celiac Diagnosis Antibody tests - On gluten

- IgA tTG or EmA and Serum IgA (2-3 % of sprue patients are IgA deficient) - tTG preferred- Not antigliadin ab

Small bowel biopsy +Response to therapy

Genotype-HLADQ2, DQ8Rules out if negativeCan use if mild sx, neg serology and borderline biopsy

Malabsorption - think about… Parasites Giardia Cryptosporidia Cyclospora

Post gastric surgery

Chronic mesenteric ischemia

Radiation

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Malabsorption - Uncommon Small Intestinal Diseases

CausesCollagenous sprueCollagenous sprueWhipple’s diseaseEosinophilic enteritis LymphomaAmyloid

Diagnosis DiagnosisRadiologic imagingCapsule studyDBE for biopsy

Watery Diarrhea If Not Bloody and

Not Steatorrhea,

It’s Watery . . .

All the rest

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Watery Diarrhea – Medical History

Diabetes, other diseases Surgery – gall bladder, stomach, intestineg y g , , Family history Celiac IBD

Sexual history Infections HIV

Travel History – Traveler’s diarrhea High risk areas

Watery Diarrhea – History • Medications

% f ll d id ff i ll• 7% of all drug side effects especially “new” ones

• Antimicrobials• PPIs (lansoprazole)• NSAIDS, 5-ASAs

SSRIs• SSRIs• Psycholeptics• Allopurinol

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Watery Diarrhea - Diet

AlcoholDairyNutritional supplementsOTC drugsHerbals Fructose and sorbitol – osmotic diarrhea

Watery Diarrhea -Diabetes

Visceral autonomic neuropathyVisceral autonomic neuropathy Bacterial overgrowth Celiac sprue Pancreatic insufficiency Unabsorbed CHO (Sugarless g

sweets)

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Watery Diarrhea - Post Cholecystectomy Diarrhea

Incidence 20%Incidence 20% Can be delayed Rarely severe Low bile acid absorption in TI at night Rx – bile acid bindersRx bile acid binders

Watery Diarrhea - Mucosal Disease

Colon ColonCrohn’sMicroscopic colitisColon cancer

Small bowel diseases Small bowel diseases Previously Mentioned

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Watery Diarrhea – Initial Evaluation

History + Exam

Initial labsCBCChemistries (total protein, albumin)Thyroid tests

C li lCeliac serologyESR/CRP Stool FOBT

Watery Diarrhea - Infections

Stool culture low yield

If only several months, considerParasitesAmebaGiardiaCryptosporidia, Cyclospora Blastocystis hominis (?)Candida (?)

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Watery Diarrhea – Infections (Cont’d)

Stool culture low yieldy

Bacteria SalmonellaAeromonas Plesimonas PlesimonasC. difficile (recurrent)

Watery Diarrhea – Evaluation

Colonoscopy + biopsyColonoscopy + biopsyCrohn’s

Microscopic colitis

Colon cancer

EGD + duodenal biopsy

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Chronic Diarrhea – Yield of Biopsy at Colonoscopy

Series vary: 10—20%Series vary: 10 20%Most commonly:

IBDMicroscopic ColitisPseudomelanosis coliPseudomelanosis coliSpirochetosis

Probably Shouldn’t Biopsy Normal Cecum

Cecal and rectal biopsy in 85 healthy adultsCecal and rectal biopsy in 85 healthy adults

Cecal biopsies had increased microscopic inflammation, abnormal architecture and cryptitis compared to rectal biopsies

Paski et al, Amer J Gastroenterol 2007

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When to Biopsy TI

Chronic diarrhea and right lower quadrantChronic diarrhea and right lower quadrant pain are the best indications to biopsy normal TI

Still yield low 1 – 2 %

Factitious Diarrhea

Surreptitous laxatives

Eating disorders

Secondary gain

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Watery Diarrhea

If work-up negative so far,Consider other stool tests

Fecal fatLaxative screen

O tiOsmotic gap

Stool Osmotic Gap

Normal 290 - 2 (Na+K)

Secretory < 50Osmotic > 125Contamination > 375

Lab will not do test on solid stool, so can use to confirm diarrhea

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Secretory DiarrheaContinues with fast

∙ Hormonal:Hormonal: ZE - GastrinVIP - VIPCarcinoid - 5HIAA (24 hr urine)Medullary Ca - CalcitoninThyroidThyroid

∙ Idiopathic secretory diarrhea

Idiopathic Secretory DiarrheaOften sudden onset

Up to 20 pound weight loss, then stablep p g ,Lasts 2 years

1. EpidemicContaminated food or water“Brainerd” diarrhea (Minnesota)( )

2. SporadicTravel to local lakes or otherNo one else sick

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Other Diagnostic Tests Abdominal CT / SB x-rays

Capsule

Enteroscopy/double balloon enteroscopy

When I am stumped . . . I Take More History

Diarrhea onset

After Infectious gastroenteritisPI – IBS

After GI tract surgeryAfter GI tract surgeryPost-cholecystectomyPost anti reflux surgery

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When I am stumped . . . ITake More History

Family history

Example: Celiac disease in 65 yo with sent for evaluation of recurrent C. difficile

When I am stumped . . . I MayRedo an Important Study

Pancreatic insufficiency – a womanPancreatic insufficiency a woman with steatorrhea and poor response to enzymes, had a normal CT + EUS

A repeat CT showed pancreatic atrophyA repeat CT showed pancreatic atrophy

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When I am stumped . . . I MayOrder a Special Study

A woman with protein losing enteropathyA woman with protein losing enteropathy,

Extensive evaluation negative except diffuse edema of small intestine

? Sli ht ↑ i hil i d d l b ? Slight ↑ eosinophils in duodenal bx

DBE → eosinophilic enteritis

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When I am stumped . . .Empiric Trials

Cholestyramine

Pancreatic enzymes

A ibi iAntibiotics

Antimotility agents

Case – 63 y o Woman

6 months watery diarrheaOnset after trip to MissouriLarge volume, 6 – 7/day even fastingNo abdominal painPrerenal azotemia twiceIV fluid dependentu d depe de t20 lb wt loss, now stableSounds secretory

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Normal w/u

Stool culture, O + P,Celiac antibodiesEGD + BxColon + BxAbdominal CT scan

Her 24 HR Stool980 gm – on a “good” day

f t (d d b hi h l )12 gm fat (dragged by high volume)Laxative screen normalNa 119, K 17 Osmotic gap 290 -2 (119 + 17) = 3

l l t d i b tt th dcalculated is better than measured osmsThus, secretory diarrhea

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Secretory Diarrhea

- Infection – R/O’d

- Mucosal – R/O’d

- Iatrogenic – R/O’d

- Hormonal ?

Evaluation

• VIP – nl VIP level

• ZE – nl gastrin off PPI

• Carcinoid – nl 24 hr urine 5HIAA

• Medullary Carcinoma Thyroid – nlcalcitonin

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Evaluation

G d l i tGradual improvement over 3 mos

Dx: Sporadic Idiopathic secretory diarrhea

Summary1. History, + stool characteristics & initial labs

will guide w/ug2. Reasonable w/u will diagnose most

Check Diet/medsExclude infectionEndoscopy and Biopsy

– upper & lower3. If normal further w/u to include therapeutic

trials4. Uncommon causes are uncommon

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