Transcript Recent developments in coeliac disease

To the ileum …….
and beyond
Dr. Matt W. Johnson BSc MBBS MRCP (??MD!!)
Consultant Gastroenterologist
1909 Royal Military Asylum
1733 – Hyde Park
1976 - Tooting
St. George’s Hospital
Achievements
• First Class BSc Degree
• Medical Sciences with Physiology
• Physiology research project: Effects of alpha and beta sympathetic
adrenoreceptors on mucus content and quantity.
• MBBS
(University of London)
• Eating in every one of the 28 Indian restaurants
from Tooting Broadway to Tooting Bec
HO + SHO Posts
MEDICAL SHO POSTS
• St. Helier Hospital,
• Hemel Hempstead Hospital,
• Royal Free Hospital,
• St. Thomas’ Hospital,
• Lewisham Hospital,
• Lewisham Hospital,
• Guy’s Hospital,
Gastro and GIM
Gastro, Haem and GIM
Specialist Liver Unit and GIM
Cardiology
Endocrine and GIM
Care of the Elderly
Accident and Emergency
PRE REGISTRATION HOUSE OFFICER
• Mayday Hospital,
General Surgery and ENT
• St. George’s Hospital,
GIM and Care of the Elderly
St. Thomas’s Hospital
South East Thames SpR Rotation
QUEEN ELIZABETH THE QUEEN MOTHER (MARGATE) HOSPITAL
• Dr. A. Piotrowicz, Dr. K. Hills
DARENT VALLEY HOSPITAL
• Dr. W. Melia, Dr. R. Ede, Dr. P. Mairs
KINGS COLLEGE HOSPITAL - LIVER UNIT
General Hepatopancreatobiliary / Liver ITU / Transplant Medicine
• Dr. J. O’Grady, Dr. M. Heneghan, Dr. J. Devlin, Dr. P. Harrison,
• Dr. V. Aluvihare, Dr. K. Agarwal, Dr. E. Sizer, Dr. W. Bernal.
• Dr. G. Auzinger, Dr. J. Wendon.
St. MARK’S and St. THOMAS’S HOSPITAL
• Research Fellowship, Specialist Surgical Gastroenterology
• Prof R.J. Nicholls, Prof P.J. Ciclitira and Prof A. Forbes
St. THOMAS’ and GUYS’ NHS TRUST
• Sir R. Thompson, Prof P.J. Ciclitira, Dr. J. Meenan,
• Dr. J. Sanderson, Dr. T. Wong, Dr. M. Wilkinson, Dr. R.Ede
BROMLEY NHS TRUST
• Dr. J. Hunt, Dr. A. Jenkins, Dr. M. Asante
ROYAL SURREY COUNTY HOSPITAL
• Dr. M. Smith
FRIMLEY PARK HOSPITAL - LAS
• Col. Fabricius, Col. Ineson
Specialty Areas of Interest
• Inflammatory Bowel Disease – including
tertiary referral clinics at St. Mark’s and St.
Thomas’s hospitals.
• Surgical Gastroenterology - National Referral
Unit for ileoanal pouches, faecal incontinence,
complex anorectal fistula disease at St. Mark’s
• Small bowel pathology + Coeliac disease
tertiary referral clinics for complicated and nonresponsive cases.
• Hepatology (General hepatopancreatobiliary
medicine, Hepatitis clinics, Liver ITU, pre/post liver
transplant medicine)
17 Publications
2009
Coeliac disease in the elderly. Nat Clin Pract Gastroenterol Hepatol. 2008 Dec; 5(12): 697-706
Bacterial community diversity in cultures derived from healthy and inflamed ileal pouches after restorative proctocolectomy. IBD. 2009 Nov
The bacteriology of pouchitis: A molecular phylogenetic analysis. GUT. 2009. Dec
The prevalence of osteoporosis and osteopenia in ileal pouch patients post-restorative proctocolectomy. IBD. 2009. Sept
Prolonged toxic megacolon secondary to Salmonella. [Submitted to Diseases of the Colon and Rectum]
2008
Coeliac disease in the older patient: Are we ageist in our practice. [Awaiting publication in Gastroenterolgy CME Journal]
The medical management of patients with an ileal pouch anal anastomosis after restorative proctocolectomy. EJoGH.
Faecal M2-pyruvate kinase; a novel, non-invasive marker of ileal pouch inflammation. EJoGH
2007
Faecal calprotectin: A non-invasive diagnostic tool and marker of severity in pouchitis. Eur J Gastroentero Hepatol. 2008 March; 20(3): 174-179
2006
Hyperbaric oxygen as a treatment for malabsorption in a radiation damaged short bowel. June 2006; 18(6):685-688
Risk of dysplasia and adenocarcinoma following restorative procto-colectomy for ulcerative colitis. Colorectal Disease. CDI-00256-2005.R1. 03/05/06
2005
Use of fecal lactoferrin to diagnose irritable pouch syndrome: A word of caution. Gastroenterology. 2004. 127(5):1647-8
Presentation, diagnosis and management of inflammatory bowel disease in older people. CME Geriatric Medicine, 2005; 7(3): 149-153
The pathogenesis of coeliac disease. Molecular Aspects of Medicine, Dec 2005: 26 (6); 421-458
2004
11th International Symposium on Coeliac Disease: A report. Gastroenterology Today. Summer 2004; 14 (2): 46-7
Clinical toxicity of HMW glutenin subunits of wheat to patients with celiac disease.
Proceedings of the 19th Meeting of the Working Group on the prolamin analysis and toxicity, 2004; III Symposium: 147-9
2002
Malaria: The dilemmas of malarial diagnostics. J R Army Med Corps 2002; 148: 122-126
Research Fellowship
• St. Marks’ and St. Thomas’ Hospital
• The Bacterial Pathogenesis of Pouchitis
and Development of Novel Probiotic
Therapies
• Prof PJ. Ciclitira, Prof RJ. Nicholls and Prof
A. Forbes
• MD – Awaiting Examination
Aims
• IBD Centre of Excellence
• SBCE
• HRM
• EUS
Luminology
To the ileum …and beyond
Oesophagus
High Resolution Manometry
• Spatiotemoral plots derived from >36
closely spaced pressure sensors
• Reveals complex functional anatomy
• Increased our understanding of
dysmotility
• Looks beautiful
Normal
Achalasia
Mid-oesophageal submucosal Ca
Herniation of Lap Wrap
Stomach
Management of Dyspepsia
BSG Guidelines 1996
Updated 2002
By
Matt Johnson
St. Thomas’s and East Surrey
Dyspepsia Introduction
• Prevalence = 23 – 41% in UK
• 4% of GP consultations
• 10% of these are referred to hospital
• 2% of entire adult population receive
either an OGD or a barium meal each year
Rationing of Endoscopy
• Morbidity = 1:1,000 (Haemorrhage)
• Death = 1:10,000 (Perforation)
• OGD is recommended in all patients >55y
– with new onset uncomplicated dyspepsia
– for > 1/12 duration
• < 55y with “alarm symptoms”
D
C
Alarm Symptoms
• These include dyspeptic patients with:
– Unintentional weight loss
– GI Bleeding
– Previous gastric surgery
– Epigastric mass
– Previous gastric ulcer
– Unexplained Fe deficiency
– Dysphagia or Odynophagia
– Persistent continous vomiting
– Suspicious barium meal
Investigation of dyspepsia
in patients <55 years
NICE guidelines www.nice.org CG17
Test and treat Helicobacter
Empirical PPI therapy
Reduce role of endoscopy in the <55 yrs
Manage uninvestigated reflux as dyspepsia
Alarm symptoms via TWW
February
2008
Surrey and Sussex Healthcare
NHS Trust
Investigation of dyspepsia in
patients <55 years
724 endoscopies performed
54% normal
13% major abnormalities
33% minor abnormalities
42% recommended PPI therapy
8.1% helicobacter eradication resulting
1 oesophageal cancer discovered (aged 52) *
Investigation of dyspepsia in
patients <55 years
Conclusions:
Three weeks out of year spend endoscoping this group
Findings in line with other studies
Very low prevalence of cancer in this group
Minimal evidence of change in management
Iron Deficiency Anaemia
Causes of Fe deficiency Anaemia
• Occult GI Blood Loss
– Aspirin/NSAID use
10–
15%
– Colonic carcinoma
5–10%
– Gastric carcinoma
5%
– Gastric ulceration
5%
– Angiodysplasia
5%
– Oesophagitis
2–4%
– Oesophageal Ca
1–2%
– GAVE (ectasia)
1–2%
– Small bowel tumours 1–2%
– Ampullary Ca.
<1%
– Ancylomasta duodenale <1%
• Malabsorption
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Coeliac disease
Gastrectomy
H. pylori colonisation
Gut resection
Bacterial overgrowth
4–6%
<5%
<5%
<1%
<1%
• Non-GI blood loss
– Menstruation
30%
– Blood donation
– Haematuria
– Epistaxis
20–
5%
1%
<1%
Iron Deficiency Anaemia
• Haemoglobin
<12 or <13 nmg/L
• MCV
<76
• Ferritin
<15nmg/L
• Coeliac serology
• TFT
• Sickle cell and Thalassaemia screen
• Non-vegetarian
• No menorrhoea
•Small
Bowel
Matt Johnson + David Dewar
Professor Paul Ciclitira
St Thomas’s Hospital, London
Prevalence of coeliac disease
• Sweden
• Ireland
• England
• Europe
• N America
• Australia
1:67 antibody positive
1:100
1:150
1:300
1:300
1:300
DERMATITIS HERPETIFORMIS
Associations
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Dermatitis herpetiformis
IgA deficiency
SBBO
Hyposplenism
Microcytic colitis
Autoimmune conditions
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Thyroid disease
Type 1 diabetes
Addison’s
Sjogrens syndrome
2-3%
8% of NRCD
?80%
5%
25%
AD and age at diagnosis:
Group
A1 – age<2yrs
A2 – age 2-10yrs
A3 – age>10yrs
Prevalence AD
5.1%
17%
23.6%
• Prevalence of autoimmune disease is
related to duration of gluten exposure
Ventura A (1999) Gastroenterology 117:297-303
Osteoporosis
• 47% women < 50% men on GFD have
osteopenia / osteoporosisa
• Improvement 1 year post treatmentb
aMcFarlane
(1995) Gut 36:710-14
bValdimarsson (1996) Gut 38:322-7
Mortality
• Almost all mortality in CD is due to malignancy
• >50% due to EATCL
• Other tumours = mouth, oesophagus, sb,lb
• Mortality 1.9-3.4x control population
• Holmes et al : 2x control pop1
• Mortality normal after 5 yrs on GFD2
GK et al (1976) Gut 17(8): 612-9
2Holmes GK et al (1989) Gut 30(3): 333-8
1Holmes
Ulcerative jejunitis
• Rare (6th decade) pre-malignant state
• Related to Enteropathy-associated T cell
lymphoma (EATL)
• T Cell receptor PCR monoclonality
– UCL – Prof. Isaacson
– Atypical gTcell receptor abnormalities
• Steroids, nutritional support, close observation
Treatment of coeliac disease
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Gluten-free diet
Avoidance of wheat, rye and barley
Oats (probably OK)
Dietician
Codex Alimentarius
Coeliac societies handbook
• BUT NOT CORNFLAKES
Using Serology to Monitor Patients
• IgA gliadin and TTG normalise on a strict
GFD after 3-6/12
• Must have pre-treatment levels
• IgG gliadin can be used but takes longer
to normalise
• IgA endomyseal is costly and more
difficult to quantify
Dewar D, Johnson MW,
Ciclitira PJ, GUT 2005
Small Bowel
• UGI tract
• LGI tract
• Sb
0.8m
1m
5.6m
95% absorption capacity
Capsule Endoscope
A small disposable capsule about the
size of a jelly bean.
Has own light source and video
camera.
Suitable for adults and older children.
Transmits data to recorder worn at
waist.
Patient swallows capsule with glass of
water after a simple overnight fast.
Carries on with normal activities and
returns data recorder after 8 hours.
BSG Indications for SBCE
Guidelines April 2008
1)
2)
3)
4)
Obscure gastrointestinal bleeding
Suspected sb Crohn’s disease
Assessment of Coeliac disease
Screening for Polyps / FAP
• Suspected small bowel malignancy
• Evaluation of side-effects of NSAIDs
Dartford SBCE Service
A review of the first 37 small bowel capsule enteroscopies performed at Darent Valley Hospital.
Stomach
• Gastritis (5)
• Erosions (6)
• Angiectasia (4)
• Polyps (1)
Small bowel
• NSAID induced enteropathy (9)
• Angiodysplasia (2)
• Coeliac disease (7)
- UCH pre-malignant ulcerative jejunitis
• Gastrointestinal stromal tumours (GISTs) (2)
- 2x St. Mark’ for D-balloon enteroscopy
• Crohn’s disease (5)
• Juvenile polyposis (1)
- GOS
• Bacterial overgrowth secondary to small bowel diverticulae (1)
• Parasitic infestation (1)
• Multiple cystic lymphangiectasia (1)
Coeliac Disease
Using SBCE in Crohn’s
• 10-30%
• 66%
• 20%
sb only
ileocaecal disease
colonic
• Wireless capsule endoscopy and Crohn’s
disease. P Swain
• Gut: March 2005 vol 54 no 3
Suspected Crohn’s
Obscure Intestinal
Bleeding
5% of all UGI haemorrhages
Benefits
Safe, well tolerated, able to view entire small bowel, clarity of image + Share
images; patient preference;
Reduced diagnostic cost and utilization
If bleeding source identified = Less need for transfusions
Reduced treatment cost and utilization
Small bowel malignancies
Prior to SBCE sb tumours = 1 - 2% of all GI malignancies
Now it is thought to compromise 5%
PillCam™ Trial = incidence of small bowel tumors among
1,235 patients – 6% - 9% (Corbin, Bailey, Keuchel)
60% of SBTs are malignant
- adenocarcinomas, carcinomas, melanomas,
lymphomas and sarcomas
40% of SBTs are benign
GISTs, hemangiomas, hamartomas, and adenomas
Small Bowel malignancies
Often diagnosed late or incidentally at laparotomy
Malignant tumors of small bowel (poor prognosis)
Metastases - 45% - 75%
Unresectable - 20% - 50%
80% of SBTs undergoing SBCE present with obscure GI
bleeding/anemia
Improved outcome of earlier diagnosed tumors in the small bowel
On average patients with SBTs who present for SBCEs have already
undergone detected SBTs after patients had undergone an average of
4.6 negative endoscopic procedures
PillCam™ Trial (Corbin, Bailey, Keuchel)
Final points
• Safe + Well tolerated
• Cost-effective in economic analysis.
• This is now standard practice throughout UK
• Watford, Stevenage, Wellen Garden City, Cambridge,
?Aylesbury
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Presently the paediatricians refer to GOS
Adult medicine is under-referring St.Mark’s
External referral = £800-1200
Cost of service = £13,000
Cost of capsule = £340
Colon
Operative Picture
Complications
• Obstruction
• Bleeding
• Inflammation “itis”
– Fistula
– Sepsis
– Perforation
• May co-exist with IBD
Specimen showing blood in diverticulae
Criteria for Toxic Megacolon
• 1) Radiographic evidence
(Jalan
et al)
– Total or segmental non-obstructive colonic dilatation of > 6cm
• 2) 3 or more of:
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Fever > 38 C
PR > 120 / min
Neutrophils > 10.5
Hb <12.5
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Dehydration
Hypotension
Electrolyte imbalance
Altered consciousness
• 3) At least 1 of:
Probiotics are sooo outdated
• Prebiotics = “functional foods”
• Inulin / Fructo-oligosaccharides / Lactulose
Transgalacto-oilgosaccharides
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Chicory (boiled root = 90% inulin)
Jerusalem artichoke
Onion
Leek
Garlic
Asparagus
Banana
(cereals eg. Oatmeal)