Transcript Investigation of chronic diarrhoea

Investigation of chronic diarrhoea
British Society of Gastroenterology
Guidelines 2nd Edition 2003
Dr. P.D. Thomas
Consultant Gastroenterologist
Taunton and Somerset Hospital
Outline
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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
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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
• Mechanistic
Osmotic - eg carbohydrate/ fat malabsorption
Secretory- mucosal disease, defects of ion
absorption, stimulant laxatives
Gut hormone
Deranged motility - post vagtomy, IBS
carcinoid
• Distinguishing osmotic from secretory
diarrhoea
- fasting - osmotic diarrhoea should stop
- osmotic gap
low stool osmolality <290 mosmol/kg
suggests contamination with hypotonic fluid
290-2x (Na and K conc)
Osmotic gap >125mosmol/kg osmotic diarrhoea
<50 in secretory diarrhoea
• Anatomical …...
Causes of diarrhoea
Colonic
Colonic neoplasia
Ulcerative and Crohn's colitis
Microscopic colitis
Small bowel
Coeliac disease
Crohn's disease
Other small bowel enteropathies,
Endocrine
Hyperthyroidism
Diabetes
Hypoparathyroidism
Addison's disease
Hormone secreting tumours (VIPoma,
gastrinoma, carcinoid)
(e.g. Whipples disease, tropical sprue, amyloid,
intestinal lymphangiectasia )
Bile Acid malabsorption
Disaccharidase deficiency
Small bowel bacterial overgrowth
Mesenteric ischaemia
Radiation enteritis
Lymphoma
Giardiasis
Pancreatic
Chronic pancreatitis
Pancreatic carcinoma
Cystic fibrosis
Other
Factitious diarrhoea
Surgical' causes (e.g.
resections)
Autonomic neuropathy
Drugs
Alcohol
small
bowel
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
• Specific
Drugs, family history, surgery, systemic disease,
alcohol, infective
Initial investigations
• Blood tests
FBC, UE, LFT, B12, folate, fe studies, ESR,
CRP, TFT
• Serological tests for coeliac disease
Prevalence of 1:200 in asymptomatic western
pops. IgA anti-endomysium antibodies
anti-tissue transglutaminase antibodies
Stool tests
• Stool microscopy culture
Protozoal eg Giardia, amobae, cryptosporidia
• Non specific
Stool osmolality
stool fat
• Specific
stool elastase
other..
• Stool markers of intestinal inflammation
e.g. lactoferrin
• Stool calprotectin
cytosolic protein in monocytes, neutrophils
stable for 1 week at RT
• Use of surrogate markers of inflammtion and
Rome criteria to distinguish organic from nonorganic 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
specificity
stool calprotectin
89
79
intestinal permeability 63
87
Rome criteria
85
71
Factitious diarrhoea
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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)
Chronic diarrhoea
Colonic
Small bowel
Pancreatic
Frequency
Age
Malignancy
Overlap between functional and organic
disease
• Irritable Bowel syndrome
Rome 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
• Female sex
• Other ‘functional’ Sx
Irritable bowel
• >45
• Family history
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 >45yrs
Rationale 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, IBD
7-31%
• 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% population
2.6% coeliac disease
• IgG antiendomysium Ab
or 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 european
populations BUT other small bowel
enteropathies should be considered.
‘D2 biopsies where small bowel malabsorption is
clinically suspected’
Case 3
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55 year old male
RIF pain and diarrhoea
Tenderness RIF
Baseline Ix NAD except CRP 32
Colonoscopy incomplete (histology normal)
Next step?
Terminal ileal disease
How 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
• Enteroscopy
diagnostic yield up to 31% ( 20% if
gastroscopically accessible lesions
excluded)
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 XR
70% vs 40% diagnostic yield
Capsule Endoscopy:
Detection of inflammatory lesions
in the small intestine
Villous erosion
Apthous ulcerations (ileum)
Thickened infiltrated folds (Jejunum)
Linear ulcerations
Capsule endoscopic diagnosis of
Crohn’s Disease
Jejunal Crohn's Disease
CELIAC DISEASE
INVESTIGATION OF CHRONIC DIARRHOEA
Basic investigations
FBC, LFT, Ca, B12, Folate, Fe status, TFT
Coeliac serology
History suggestive of organic
diarrhoea
Abnormal basic investigations
History or findings c/w malabsorption
Small Bowel
D2 biopsy
Barium follow through
Enteropathy
Review histology
?Enteroscopy
Or capsule endoscopy
Pancreatic
Symptoms suggestive of functional
disease
Age <45,normal basic investigations
irritable bowel syndrome
History or findings c/w colonic
disease or small bowel inflammatory
disease
Flexible sigmoidoscopy if <45
Complement with barium enema if >45
Colonoscopy preferred if >45
Terminal ileal disease excluded?
Barium follow through
99mTc-HMPAO
75SeHCAT
'Difficult diarrhoea'
Suspicion of laxative abuse
persistent symptoms despite negative Ix
High volume diarrhoea
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
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(poorly reproducible)
patients with steatorrhoea reduce fat intake
no assessment of completeness of collection
no quality control
faecal fat concentration (not widely available)
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Stool steatocrit and Sudan III (semi-quantitative)
all are non-specific
Tests of fat malabsorption (2)
Breath tests
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14C-triolein
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13C-hiolein
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Lembke 1996
8-12 hr , 30 min breath samples
sensitivity 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
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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
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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
• USS
50-60% sensitive
• CT
74-90% sensitive
• ERCP
‘Gold standard’
• MRI
?equivalent to ERCP
Investigation of pancreatic malabsorption
Invasive
 Pancreatic function tests
- Secretin/cholecystokinin stimulation
- ‘Lundh’ test
Sensitivity 90%
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ERCP
secretin-cholecystokinin
26/30 abnormal
ERCP
21/30
Investigation of pancreatic malabsorption
Non-invasive (1)
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(all tests related to fat malabsorption)
(Serum enzymes)
Faecal tests
- chymotrypsin (Sens 80% Spec 84%)
- lipase (sensitivity 46%)
- elastase
mild
sensitivity 63
40
moderate severe
100
100%
33
82%
(Loser 1996)
(Lankisch 1998)
Investigation of pancreatic malabsorption
Non-invasive (2)
‘Tubeless’ oral pancreatic function tests
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NBTP/PABA
- N-benzoyl-L-tyrosyl-p-aminobenzoic acid
- hydrolysed by chymotrypsin
- 6 hour urine collection
- Sensitivity 64-83% Specificity 89%
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Fluorescein dilaurate (Pancreolauryl) test
- Pancreatic esterase
- 10 hour urine collection
- variable sensitivities reported
Investigation of pancreatic
malabsorption (summary)
• Faecal elastase is the non-invasive investigation
of 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
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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
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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
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Breath tests
- 14C-cholylglycine - now abandoned
- Hydrogen breath tests (glucose or lactulose)
Sensitivity: 17 - 68%
Specificity: 70-83%
- 14C-D xylose – not available in UK
Proximally absorbed
No reliance on H2 production
Bile acid malabsorption
• Causes
terminal ileal disease, surgical resection
primary defect, post cholecystectomy
rapid transport
• 75Se homotaurocholate (75SeHCAT)
synthetic analogue of taurocholic acid
retained 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 tumours
Diarrhoea primary symptom (100%)
Can be episodic. Secretory diarrhoea
Fasting VIP level >170pg/mL
Summary
INVESTIGATION OF CHRONIC DIARRHOEA
Basic investigations
FBC, LFT, Ca, B12, Folate, Fe status, TFT
Coeliac serology
History suggestive of organic
diarrhoea
Abnormal basic investigations
History or findings c/w malabsorption
Small Bowel
D2 biopsy
Barium follow through
Enteropathy
Review histology
?Enteroscopy
Bacterial overgrowth
Glucose hydrogen breath test
Jejeunal aspirate and culture
Symptoms suggestive of functional
disease
Age <45,normal basic investigations
irritable bowel syndrome
History or findings c/w colonic
disease
'Difficult diarrhoea'
Suspicion of laxative abuse
persistent symptoms despite negative Ix
High volume diarrhoea
Pancreatic
CT pancreas
faecal elastase or chymotrypsin
Pancreolauryl test
Flexible sigmoidoscopy if <45
Complement with barium enema if >45
Colonoscopy preferred if >45
Consider in-patient assessment
24-72 hrs stool weights
Stool osmolality/osmotic gap
Laxative screen
Further structural tests
ERCP or MRCP
Terminal ileal disease excluded?
Barium follow through
99mTc-HMPAO
75SeHCAT
Gut hormones
Serum gastrin, VIP
Urinary 5HIAA
Conclusions
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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’