Investigation of chronic diarrhoeaBritish Society of Gastroenterology

Guidelines 2nd Edition 2003

Dr. P.D. ThomasConsultant Gastroenterologist

Taunton and Somerset Hospital

Outline● Definitions● Initial assessment ● Factitious diarrhoea● Functional bowel problems● Colonic investigations● Small bowel investigations

● Investigation of fat and carbohydrate malabsorption● Investigation of malabsorption due to pancreatic

insufficiency● Specific conditions

small bowel bacterial overgrowth, bile salt malabsorption, hormone secreting tumours

Mechanisms

• Intestinal secretions and food- 7l per day• 5L absorbed in small intestine• 1.5-2L absorbed by colon• Stool 100-200mL water• 10% decrease in fluid absorbed by colon will

double stool volume• Considerable reserve capacity of colon to absorb

increased ileal effluent

Approaches to the classification of diarrhoea

• MechanisticOsmotic - eg carbohydrate/ fat malabsorptionSecretory- mucosal disease, defects of ion

absorption, stimulant laxativesGut hormone

Deranged motility - post vagtomy, IBS carcinoid

• Distinguishing osmotic from secretorydiarrhoea

- fasting - osmotic diarrhoea should stop

- osmotic gaplow stool osmolality <290 mosmol/kg

suggests contamination with hypotonic fluid290-2x (Na and K conc)Osmotic gap >125mosmol/kg osmotic diarrhoea

<50 in secretory diarrhoea

• Anatomical …...

Causes of diarrhoeaColonic

Colonic neoplasia EndocrineUlcerative and Crohn's colitis HyperthyroidismMicroscopic colitis Diabetes

Small bowel HypoparathyroidismCoeliac disease Addison's diseaseCrohn's disease Hormone secreting tumours (VIPoma, Other small bowel enteropathies, gastrinoma, carcinoid)(e.g. Whipples disease, tropical sprue, amyloid, intestinal lymphangiectasia )

Bile Acid malabsorptionDisaccharidase deficiencySmall bowel bacterial overgrowthMesenteric ischaemiaRadiation enteritis OtherLymphoma Factitious diarrhoeaGiardiasis Surgical' causes (e.g. small bowel

Pancreatic resections)Chronic pancreatitis Autonomic neuropathy Pancreatic carcinoma DrugsCystic fibrosis Alcohol

Definitions

● >200g stool/24 hours

● More than three loose stools/day

● Chronic > 4 weeks

● Layman’s definition

Initial assessment

• Organic vs functional<3 months, continuous, nocturnal, alarm symptoms

• Malabsorptive or colonic/inflammatory

• SpecificDrugs, family history, surgery, systemic disease,

alcohol, infective

Initial investigations

• Blood testsFBC, UE, LFT, B12, folate, fe studies, ESR, CRP, TFT

• Serological tests for coeliac diseasePrevalence of 1:200 in asymptomatic western pops. IgA anti-endomysium antibodies

anti-tissue transglutaminase antibodies

Stool tests

• Stool microscopy cultureProtozoal eg Giardia, amobae, cryptosporidia

• Non specificStool osmolalitystool fat

• Specificstool elastaseother..

• Stool markers of intestinal inflammatione.g. lactoferrin

• Stool calprotectincytosolic protein in monocytes, neutrophilsstable for 1 week at RT

• Use of surrogate markers of inflammtion and Rome criteria to distinguish organic from non-organic disease Tibble et al Gastroenetrology 2002

• N=602 all patients underwent invasive imaging Ix

Rome criteria, Intestinal permeability• Results

263 organic disease, 339 IBS Sensitivity

specificitystool calprotectin 89 79intestinal permeability 63 87Rome criteria 85 71

Factitious diarrhoea

● 4% of patients attending district gastroenterology clinic

● 20-33% attending tertiary referral centres● Association with medical training/eating disorder● In patient assessment/monitoring

- stool collections- 24-48 hour fast

● ‘Laxative screen’ - anthraquinones, biascodyl,phenolphthaleins, oils, Mg, PO4.

Case 1

• 50 year old female• 6 months watery diarrhoea up 6 x day• Normal baseline investigations including TFT,

coeliac serology• Normal flexible sigmoidoscopy with bx 2 years

ago

Next investigation?

Microscopic colitis

• Lymphocytic or collagenous colitis

• Rectosigmoid biopsies alone may miss up to 40% of cases (Offner1999)

C o l o n i c S m a l l b o w e l P a n c r e a t i c

C h r o n i c d i a r r h o e a

FrequencyAgeMalignancy

Overlap between functional and organic disease

• Irritable Bowel syndromeRome 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

Discriminant factors

• >45• Family history

• <45• Female sex• Other ‘functional’ Sx

Irritable bowel Colonic pathology

Chronic diarrhoea in patients <45yrs

• Flexible sigmoidoscopy Fine et al 2000

800 patients studied Microscopic colitis 10% >Crohn’s >UC 99.7% of pathology accessible with FS

Chronic diarrhoea in patients >45yrsRationale for total colonic examination

• Neoplasia 37% asymptomatic

individuals have adenomas 8% adenomas>1cm(Lieberman 2000) Prevalence in symptomatic?

• Higher prevalence of proximal non-neoplastic pathology

e.g microscopic colitis, IBD7-31%

• Colonoscopy or barium enema and flexi sigmoidoscopy

Case 2

• 40 year old male• Loose offensive stools 4x/day

? ½ stone weight loss 1 year• FBC, LFT, CRP etc normal• IgA Antiendomysial antibodies negative • Flexible sigmoidoscopy normal

• Selective IgA deficiency 0.14% population2.6% coeliac disease

• IgG antiendomysium Abor IgG anti-tTG Ab are suitable alternative serological tests

• Check IgA levels

Endoscopic distal duodenal biopsies

• Little information on diagnostic yield• Serological tests have replaced D2 biopsies as the

initial investigation for coeliac disease • Coeliac disease is (by far) the most common

small bowel enteropathy in western europeanpopulations BUT other small bowel

enteropathies should be considered. ‘D2

biopsies where small bowel malabsorption is clinically suspected’

Case 3

• 55 year old male• RIF pain and diarrhoea• Tenderness RIF• Baseline Ix NAD except CRP 32• Colonoscopy incomplete (histology normal)

Next step?

Terminal ileal diseaseHow to assess?

Small bowel imaging

• Barium follow through Enteroclysis

-yield low, equivalent role -small bowel

malabsorption suspected (distal duodenal histology normal)Structural abnormalities

Small bowel imaging (2)

• Tc- HMPAO labelled white cell scanning

• Enteroscopydiagnostic yield up to 31% ( 20% if

gastroscopically accessible lesionsexcluded)

Small bowel imaging (3)

• Capsule endoscopy?Established role in the investigation of

iron deficiency anaemia? Suspected small bowel malabsorption

or diarrhoea of unknown cause

• Superior to small bowel barium XR70% vs 40% diagnostic yield

Capsule Endoscopy:Detection of inflammatory lesions

in the small intestine

Thickened infiltrated folds (Jejunum) Villous erosion

Linear ulcerationsApthous ulcerations (ileum)

Capsule endoscopic diagnosis of Crohn’s Disease

Jejunal Crohn's Disease

CELIAC DISEASE

INVESTIGATION OF CHRONIC DIARRHOEA

Basic investigationsFBC, LFT, Ca, B12, Folate, Fe status, TFT

Coeliac serology

History suggestive of organicdiarrhoea

Abnormal basic investigations

Symptoms suggestive of functionaldisease

Age <45,normal basic investigationsirritable bowel syndrome

History or findings c/w malabsorptionHistory or findings c/w colonic

disease or small bowel inflammatorydisease

'Difficult diarrhoea'Suspicion of laxative abuse

persistent symptoms despite negative IxHigh volume diarrhoea

Small BowelD2 biopsy

Barium follow throughPancreatic

EnteropathyReview histology?Enteroscopy

Or capsule endoscopy

Flexible sigmoidoscopy if <45Complement with barium enema if >45

Colonoscopy preferred if >45

Terminal ileal disease excluded?Barium follow through

99mTc-HMPAO75SeHCAT

Malabsorption and ‘difficult diarrhoea’

‘‘Malabsorption’’

Malabsorption - mucosal disease

carbohydrate>fat

Maldigestion - pancreatic disease

fat> carbohydrate

(protein quantification difficult)

Tests related to fat malabsorption (1)

Stool tests● 3 day faecal fat (poorly reproducible)

patients with steatorrhoea reduce fat intakeno assessment of completeness of collectionno quality control

● faecal fat concentration (not widely available)● Stool steatocrit and Sudan III (semi-quantitative)

all are non-specific

Tests of fat malabsorption (2)

Breath tests● 14C-triolein ● 13C-hiolein Lembke 1996

8-12 hr , 30 min breath samplessensitivity 92% in severe, 46% in mild/mod

pancreatic insufficiency● 13C- mixed chain triglyceride● Only sensitive if moderate or severe steatorrhoea

Tests related to carbohydrate malabsorption

● 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

● D-xylose breath test

Both have been largely replaced by endoscopic distal duodenal biopsies

Chronic pancreatitis

• Usually obvious• Previous episodes of

pancreatitis• History of XS alcohol• Weight loss• Steatorrhoea• Coincident diabetes?

Investigation of pancreatic malabsorption: Imaging

• USS50-60% sensitive

• CT74-90% sensitive

• ERCP ‘Gold standard’

• MRI?equivalent to ERCP

Investigation of pancreatic malabsorption

Invasive ● Pancreatic function tests

- Secretin/cholecystokinin stimulation- ‘Lundh’ test

Sensitivity 90%● ERCP

secretin-cholecystokinin ERCP26/30 abnormal 21/30

Investigation of pancreatic malabsorption

Non-invasive (1)● (all tests related to fat malabsorption)● (Serum enzymes)● 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)

Investigation of pancreatic malabsorption

Non-invasive (2)‘Tubeless’ oral pancreatic function tests● NBTP/PABA

- N-benzoyl-L-tyrosyl-p-aminobenzoic acid - hydrolysed by chymotrypsin- 6 hour urine collection- Sensitivity 64-83% Specificity 89%

● Fluorescein dilaurate (Pancreolauryl) test- Pancreatic esterase- 10 hour urine collection- variable sensitivities reported

Investigation of pancreatic malabsorption (summary)

• Faecal elastase is the non-invasive investigationof choice

• May complement with Urine test such as pancreolauryl or NBTP-PABA but - specificity influenced by small bowel disease - technically more demanding

Miscellaneous causes and ‘difficult diarrhoea’

• Small bowel bacterial overgrowth• Bile acid malabsorption• Hormone secreting tumours

Small bowel bacterial overgrowth

● 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

● 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.

Investigation of small bowel bacterial overgrowth

● Breath tests- 14C-cholylglycine - now abandoned- Hydrogen breath tests (glucose or lactulose)

Sensitivity: 17 - 68%Specificity: 70-83%

- 14C-D xylose – not available in UKProximally absorbedNo reliance on H2 production

Bile acid malabsorption

• Causesterminal ileal disease, surgical resection primary defect, post cholecystectomyrapid transport

• 75Se homotaurocholate (75SeHCAT)synthetic analogue of taurocholic acidretained fraction assessed by gamma camera 7 days after oral administration<15% suggest BAM

• 7alphahydroxy-4-cholestone-3-one• Therapeutic trial of cholestyramine

Hormone secreting tumours

• Rare! Incidence approx. 1 per million

• VIPoma, gastrinoma, carcinoid, somatostatinoma• Large volumes (>1 litre) of watery diarrhoea• VIPoma

90% are pancreatic, large tumoursDiarrhoea primary symptom (100%)Can be episodic. Secretory diarrhoeaFasting VIP level >170pg/mL

Summary I N V E S T I G A T I O N O F C H R O N I C D I A R R H O E A

E n t e r o p a t h yR e v i e w h i s t o l o g y

? E n t e r o s c o p y

B a c t e r i a l o v e r g r o w t hG l u c o s e h y d r o g e n b r e a t h t e s tJ e j e u n a l a s p i r a t e a n d c u l t u r e

S m a l l B o w e lD 2 b i o p s y

B a r i u m f o l l o w t h r o u g h

F u r t h e r s t r u c t u r a l t e s t sE R C P o r M R C P

P a n c r e a t i cC T p a n c r e a s

f a e c a l e l a s t a s e o r c h y m o t r y p s i nP a n c r e o l a u r y l t e s t

H i s t o r y o r f i n d i n g s c / w m a l a b s o r p t i o n

T e r m i n a l i l e a l d i s e a s e e x c l u d e d ?B a r i u m f o l l o w t h r o u g h

9 9 m T c - H M P A O7 5 S e H C A T

F l e x i b l e s i g m o i d o s c o p y i f < 4 5C o m p l e m e n t w i t h b a r i u m e n e m a i f > 4 5

C o l o n o s c o p y p r e f e r r e d i f > 4 5

H i s t o r y o r f i n d i n g s c / w c o l o n i cd i s e a s e

G u t h o r m o n e sS e r u m g a s t r i n , V I P

U r i n a r y 5 H I A A

C o n s i d e r i n - p a t i e n t a s s e s s m e n t2 4 - 7 2 h r s s t o o l w e i g h t s

S t o o l o s m o l a l i t y / o s m o t i c g a pL a x a t i v e s c r e e n

' D i f f i c u l t d i a r r h o e a 'S u s p i c i o n o f l a x a t i v e a b u s e

p e r s i s t e n t s y m p t o m s d e s p i t e n e g a t i v e I xH i g h v o l u m e d i a r r h o e a

H i s t o r y s u g g e s t i v e o f o r g a n i cd i a r r h o e a

A b n o r m a l b a s i c i n v e s t i g a t i o n s

S y m p t o m s s u g g e s t i v e o f f u n c t i o n a ld i s e a s e

A g e < 4 5 , n o r m a l b a s i c i n v e s t i g a t i o n si r r i t a b l e b o w e l s y n d r o m e

B a s i c i n v e s t i g a t i o n sF B C , L F T , C a , B 1 2 , F o l a t e , F e s t a t u s , T F T

C o e l i a c s e r o l o g y

Conclusions● Baseline investigations (primary care)● lower GI endoscopy with biopsy● Consider factitious diarrhoea● Small bowel malabsorption

- Distal duodenal biopsies- small bowel imaging

● Pancreatic insufficiency- faecal elastase, Pancreolauryl test, pancreatic imaging

● Other – SB bacterial overgrowth, BAM etc

In 1/3 patients no diagnosis made:‘chronic idiopathic diarrhoea’