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Approach to the Patient with Chronic Diarrhea and A Few Interesting IBS Cases
Christina Surawicz, MD, MACGProfessor of Medicine
University of Washington
McCall, IdahoJanuary 2014
Alarm Symptoms
• Weight loss “Beware the diet that works”
• Blood in stool
• Nocturnal diarrhea
• Anemia
Diagnostic Approach to Chronic Diarrhea
● BLOODY – gross or occult
● Fatty
● Watery
Diarrhea with Blood → Colitis
InfectionIBDIschemiaSome drugs
NSAIDSIsotretinoin
SCAD – Segmental Colitis Associated with Diverticular Disease
RadiationDiversion colitis
Work – upChronic Bloody Diarrhea
Stool culture for enteric pathogens, Yersinia, Aeromonas, Plesiomonas, C. difficile
Stool O + P – Ameba, Trichuris
Stool WBC, lactoferrin--nonspecific
Colonoscopy/biopsy= helpful to distinguish IBD vs. infection
Colonoscopic AppearancesInfections – often patchy
Ulcerative Colitis – typical
Crohn’s - segmental
Ischemia – Rectal sparing Location, location, location
Can be multifocal
Chronic Bloody Diarrhea
History + exam
Stool cultures, O + P, in some
Colonoscopy and colorectal biopsy - mainstay of diagnosis
Colonoscopy in Any Diarrhea Work Up
Age > 50 years old
Family history colon cancer at an early age (<60)
Infection Uncommon Stool Culture O + P• Salmonella • Ameba• Campylobacter • Trichuris• Yersinia • Aeromonas • Plesiomonas• C. difficile
Chronic Bloody Diarrhea: Work – up
Colonoscopy/biopsy - mainstays of diagnosis
Helpful to distinguish IBD vs. infection
Colonic Biopsy can Diagnose Specific Infections
PseudomembranesC. difficileSTEC
Viral InclusionsCMVHSV
ParasitesAmebaShistosomiasis
Tuberculosis
Diagnostic Approach to Chronic Diarrhea
● Bloody – gross or occult
● FATTY
● Watery
Steatorrhea – Clinical Clues
Dietary history – Intake compared to others
Weight lossStools – Not always diarrhea, may
be bulkyHard to flushOily droplets floating on
toilet water (unhydrolyzed TG)
Steatorrhea – Vitamin Malabsorption
Fat soluble vitamins D A K E
Osteomalacia DNight blindness AEasy bruisability KVitamin E
Fecal Fat Analysis
Qualitative – Can be subjective Variable lab personnel Nl is less than 20 drops/ hpf
Quantitative – 24 hr on 100 gm fat diet
Weight < 200 – 300 gm
Fat < 7 gm / 24 hr
Stool Fat Tests – Caveats
1. High carbohydrate diet – increases stool weight to 300 – 400 gms
2. Voluminous stools will raise fat excretion (up to 14 g/24 hour)
3. Correct for fat intake - low fat diets
4. False positives; Olestra, Brazil nuts
Steatorrhea
Mucosal Luminal
CELIAC SPRUE • PANCREATIC INSUFFICIENCY
CROHN’S • Bile salt deficiencyIleitis/ • Bacterial overgrowth Ileal resection • SIBOShort bowel syndrome
Celiac Disease – Not Just Diarrhea
Weight Loss Infertility
Abdominal distension Recurrent fetal loss
Abnormal LFTs – enzymes Microscopic colitis
Iron deficiency
Celiac Diagnosis Antibody tests - On gluten
* IgA tTG and Serum IgA (2-3 % of sprue patients are IgA deficient)
- EmA antibody – second line- Not antigliadin ab (unless deaminated)
Small bowel biopsy + response to therapy High suspicion – biopsy even if
serology negative Genotype-HLADQ2, DQ8
- Rules out if negativeRubio-Tapia et al. Guidelines, AM J Gastroentrol, Feb 2013
You have a patient on a gluten free diet who is convinced she has celiac disease. She does not want a gluten challenge. Which of the following applies to her?
A. Order HLA DQ2,8 – if positive it will confirm she has celiac disease
B. Order HLA DQ2,8- if negative it will rule out celiac disease
C. Order serology as it will help even on a gluten free diet
D. Screen her siblings for celiac disease
Answer BHLA DQ2,8- if negative it does rule
out celiac but does not everyone who is positive has celiac disease
The serology will be negative if on a true gluten free diet, and screening siblings is only helpful if you have a true case
Gluten and IBS34 patients with IBS
NonceliacDouble blind RCT – 6 weeks
Gluten free muffins & bread vs. PlaceboResults
Symptoms better
Gluten free group 68%
Placebo 40%
Biesierkierski et al, Am J Gastroenterol 2011; 106:508-14
Symptoms Worse within 1 Week
OverallBloatingPainFatigueSatisfaction with stool
consistency
GFD in IBS-DNon celiac patients
RCT of GFD
Reduced stool frequency
(Vazquez-Roque et al, Gastroenterol. 2013)
Bottom Line
Non-celiac glutenSensitivity probably exists
We need to know more
Malabsorption - think about…
Post gastric surgery or anti-reflux surgery - history
Chronic mesenteric ischemia - history
Drugs, including HAART - history
Radiation - history
Malabsorption - think about…
Parasites – stool tests Giardia
Cryptosporidia
Cyclospora
Next Steps in Evaluation
• Radiologic imaging- cross sectionalCT Abdomen and pelvis and CT Enterography
• Capsule study
• Enteroscopy or DBE for biopsy
Uncommon Small Intestinal Diseases• Collagenous sprue
• Whipple’s disease
• Eosinophilic enteritis
• Lymphoma
• Amyloid
Luminal - Pancreatic Insufficiency
∙ Direct function test: secretin test, research tool
∙ Indirect tests ∙Serum amylase/lipase∙Serum trypsin∙Fecal chymotrypsin ∙Fecal elastase
ALL HAVE POOR SENSITIVITY/SPECIFICITY
Fecal Elastase 1 6% of pancreatic enzymesAbnormal: < 200 μg/gram stoolBut abnormal in many other
conditionsCeliac diseaseIBDIBSHIV Diabetes
(Leeds et al, Nature Rev Gastro Hep 2011)
Pancreatic Insufficiency
Empiric trial of enzymes – reasonable
• High dose – monitor wt gain or fecal fat
• If respond, image pancreas
Another option is to rule out mucosal disease first
Bile Acid DiarrheaBile acids cause colonic salt and water
secretion and increased colon motility
Secondary bile acid malabsorptionIleal resection or disease (Crohn’s)< 100 cm – watery> 100 cm - malabsorption
Primary bile acid malabsorption? (misnomer)
Luminal - Small Intestinal Bacterial Overgrowth (SIBO)• Structural causes • SI diverticulosis• Stricture• Surgical diversions
• Dysmotility• Scleroderma • Intestinal pseudo-obstruction
• Others ?• Diabetes• IBS • Acid suppression
SIBO Diagnosis• Clue: high folate, low B12
Bacteria produce/consume
• SB aspirate
• Breath tests – not great
• Therapeutic trial – probably bestAntibiotics
Watery DiarrheaIf Not Bloody and
Not fatty
It’s WATERY . . .
All the rest
Watery Diarrhea –HistorySurgery – gall bladder, stomach, intestine
Family historyCeliacIBD
Sexual historyInfectionsHIV
Travel History – Traveler’s diarrheaHigh risk areas
Watery Diarrhea – History • Medications - 7% of all drug side effects
especially “new” ones
• Antimicrobials• PPIs (lansoprazole)• NSAIDS, 5-ASAs• SSRIs• Psycholeptics• Allopurinol• Metformin• Angiotensin ARBs
Watery Diarrhea - Diet
AlcoholDairyNutritional supplements, herbals,
OTC drugsHerbalsFructose and sorbitol – osmotic
diarrhea
Watery Diarrhea -Diabetes
• Visceral autonomic neuropathy- Often nocturnal
• Bacterial overgrowth• Celiac disease • Pancreatic insufficiency• Unabsorbed CHO (Sugarless
sweets)
Watery Diarrhea - Post Cholecystectomy Diarrhea
Incidence 20%
Can be delayed
Rarely severe
Rx – bile acid binders
Watery Diarrhea – Initial Labs• CBC• Chemistries (total protein, albumin)• Thyroid tests• Celiac serology• ESR/CRP • Stool FOBT
Watery Diarrhea - Infections
• Ameba• Giardia• Cryptosporidia • Cyclospora• Blastocystis hominis (?)• Candida (?)
• Yersinia• Salmonella• Aeromonas• Plesiomonas
• C. difficile (recurrent)
Stool exam low yield
Watery Diarrhea - Mucosal Disease
Colonoscopy + biopsyCrohn’s Microscopic colitisColon cancerLarge rectal villous adenoma
Small bowel diseases - EGD + duodenal biopsy
Previously Mentioned
Chronic Diarrhea – Yield of Biopsy at Colonoscopy
Series vary: 10—20%
Most commonly:IBDMicroscopic ColitisPseudomelanosis coliSpirochetosis
Pseudomelanosis coli
Surreptitious laxatives
Factitious Diarrhea
Microscopic Colitis—Collagenous and Lymphocytic
Typically: Chronic watery diarrheaColon bx diagnosticOther w/ u – negative
Histology: increased lamina propria lymphocytes, intraepithelial lymphocytes, increased collagen band in CC, not LC
Collagenous Colitis
Lymphocytic Colitis
Watery Diarrhea
If work-up negative so far,
Consider other stool testsFecal FatLaxative screenOsmotic gap
Consider small bowel evaluation
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
Secretory Diarrhea
Continues with fast● Hormonal: ZE - Gastrin VIP - VIP Carcinoid - 5HIAA Medullary Ca - Calcitonin
Thyroid
● Idiopathic secretory diarrhea
Idiopathic Secretory Diarrhea
Often sudden onsetUp to 20 pound weight loss, then stableLasts 2 years
1. EpidemicContaminated food or water“Brainerd” Minnesota
2. SporadicTravel to local lakes or otherNo one else sick
Previously healthy, likely infectiousEpidemic – BrainerdSporadic – travel, lakes, no one else
sickAbrupt onset, 20 lb wt loss then stableResolves over 2 yrs
Idiopathic Secretory Diarrhea
When I am stumped . . . I Take More History
• Diarrhea onset After Infectious gastroenteritis
PI – IBSAfter GI tract surgery
Post-cholecystectomyPost anti reflux surgery
Sugarless chewing gum10 packs/day
When I am stumped . . . I Take More History
• Family history
Example: Celiac disease in 65 yo with sent for evaluation of recurrent C. difficile
When I am stumped . . . I MayOrder a Special Study
A woman with protein losing enteropathy,
Extensive evaluation negative except diffuse edema of small intestine
? Slight ↑ eosinophils in duodenal bx
When I am stumped . . .Empiric Trials Cholestyramine
Pancreatic enzymes
Antibiotics
Antimotility agents
Dx of Obscure Diarrheas at Referral Center
Fecal incontinenceFunctional, IBS HistoryIatrogenic – drugs,
surgery, radiation
Surreptious laxatives Colon + bxMicroscopic colitis
Schiller, Sleisinger & Fordtran, GI & Liver Dis, 2002
Dx of Obscure Diarrheas at Referral Center – Cont’d
SB bacterial overgrowthPanc insufficiency Hx + Therapeutic
trialCHO malabsorption
Peptide secreting tumors Assays + Scans
Chr idiop secr diarrhea
Schiller, Sleisinger & Fordtran, GI & Liver Dis, 2002
Empiric TrialsLoperamide Adsorbents, bulk, Bismuth
subsalicylate
Bacterial overgrowth - Metronidazole or Quinolone
Bile salt MalabsorptionCholestyramine
Therapeutic TrialsUnexplained steatorrhea – pancreatic
enzymes or conjugated bile acidUnexplained idiopathic
Bile acid resinsOpiates helpful in some
Opium tincture 2 – 20 drops QIDOthers
OctreotideClonidineProbiotics
Chronic Diarrhea - Summary
1. History, + stool characteristics & initial labs will guide w/u
2. 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