matt johnson + david dewar professor paul ciclitira st thomas’ hospital, london

Download Matt Johnson + David Dewar Professor Paul Ciclitira St Thomas’ Hospital, London

Post on 18-Dec-2015

215 views

Category:

Documents

1 download

Embed Size (px)

TRANSCRIPT

  • Slide 1
  • Matt Johnson + David Dewar Professor Paul Ciclitira St Thomas Hospital, London
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Mortality Almost all mortality in CD is due to malignancy Almost all mortality in CD is due to malignancy >50% due to EATCL >50% due to EATCL Other tumours = mouth, oesophagus, sb Other tumours = mouth, oesophagus, sb Mortality 1.9-3.4x control population Mortality 1.9-3.4x control population Holmes et al : 2x control pop 1 Holmes et al : 2x control pop 1 Mortality normal after 5 yrs on GFD 2 Mortality normal after 5 yrs on GFD 2 1 Holmes GK et al (1976) Gut 17(8): 612-9 2 Holmes GK et al (1989) Gut 30(3): 333-8
  • Slide 6
  • Prevalence of coeliac disease Sweden1:67 antibody positive Sweden1:67 antibody positive Ireland1:100 Ireland1:100 England 1:150 England 1:150 Europe 1:300 Europe 1:300 N America 1:300 N America 1:300 Australia1:300 Australia1:300
  • Slide 7
  • Cereal Taxonomy FamilyGRAMINEAE Subfamily FESUCOIDEAE PANICOIDEAE Tribe TRITICEAE AVENEAE ORYZEAE TRIPSACEAE Subtribe TRITICINAE GenusTRITICUM SECALE HORDEUMAVENA ORYZA ZEA Species WHEAT RYE BARLEY OATS RICE MAIZE
  • Slide 8
  • Are oats safe in coeliac disease? Pure oat products are probably safe: Janatuinen et al 2002 Gut. (Finland) 5 year follow up of oat and non-oat eating coeliacs 5 year follow up of oat and non-oat eating coeliacs No clinical, serological and histological differences at 5 years. No clinical, serological and histological differences at 5 years. UK oat products may have contamination (harvesting, milling, food preparation) UK oat products may have contamination (harvesting, milling, food preparation) Gluten free = Food industry standards 200 ppm Gluten free = Food industry standards 200 ppm
  • Slide 9
  • Slide 10
  • Slide 11
  • Slide 12
  • Tissue transglutaminase Auto-antigen target of anti-endomyseal antibodies Auto-antigen target of anti-endomyseal antibodies Intracellular, released during inflammation Intracellular, released during inflammation Cross links matrix proteins, stabilising connective tissue during inflammation. Cross links matrix proteins, stabilising connective tissue during inflammation. Deamidates specific glutamine residues. Deamidates specific glutamine residues. Creation of neo-epitopes with gluten Creation of neo-epitopes with gluten
  • Slide 13
  • Slide 14
  • Slide 15
  • Slide 16
  • Slide 17
  • Slide 18
  • Slide 19
  • TAKE THAT VILLUSES
  • Slide 20
  • Pathology the coeliac lesion Villus atrophy Villus atrophy Crypt hyperplasia Crypt hyperplasia Loss of enterocyte height Loss of enterocyte height Lamina propria infiltration Lamina propria infiltration Increased intra-epithelial lymphocytes Increased intra-epithelial lymphocytes Increased mitotic activity Increased mitotic activity
  • Slide 21
  • Intra-epithelial lymphocytes
  • Slide 22
  • NORMAL SMALL INTESTINE COELIAC DISEASE
  • Slide 23
  • Clinical categories of coeliacs Coeliac disease Coeliac disease Undiagnosed coeliac disease Undiagnosed coeliac disease Silent coeliac disease Silent coeliac disease Latent coeliac disease Latent coeliac disease
  • Slide 24
  • Clinical features in adults Lethargy Tired all the time Lethargy Tired all the time Anaemia (Fe, folate, B12 and mixed) Anaemia (Fe, folate, B12 and mixed) Abdominal pain Abdominal pain Non-specific abdominal symptoms Non-specific abdominal symptoms Diarrhoea Diarrhoea Weight loss Weight loss Osteoporosis Osteoporosis Sub-fertility Sub-fertility
  • Slide 25
  • Associations Dermatitis herpetiformis Dermatitis herpetiformis IgA deficiency IgA deficiency SBBO SBBO Hyposplenism Hyposplenism Autoimmune conditions Autoimmune conditions Thyroid disease Type 1 diabetes Addisons Sjogrens syndrome
  • Slide 26
  • AD and age at diagnosis: GroupPrevalence AD A1 age10yrs23.6% Prevalence of autoimmune disease is related to duration of gluten exposure Prevalence of autoimmune disease is related to duration of gluten exposure Ventura A (1999) Gastroenterology 117:297-303
  • Slide 27
  • Osteoporosis 47% women < 50% men on GFD have osteopenia / osteoporosis a 47% women < 50% men on GFD have osteopenia / osteoporosis a Improvement 1 year post treatment b Improvement 1 year post treatment b a McFarlane (1995) Gut 36:710-14 b Valdimarsson (1996) Gut 38:322-7
  • Slide 28
  • DERMATITIS HERPETIFORMIS
  • Slide 29
  • Dermatitis Herpetiformis 2 -3% 2 -3% IgA deposition at the basement membrane IgA deposition at the basement membrane Rx Rx 1) GFD = 6-12/12 1) GFD = 6-12/12 2) Dapsone 2) Dapsone
  • Slide 30
  • SBBO 8% of non-responsive coeliac patients 8% of non-responsive coeliac patients Symptoms Symptoms Diarrhoea > Pain > Weight loss > Bloating > Flatulence > Nausea > Steatorrhoea Nutritional deficiencies Vit D (tetany) > Vit A (night blindness) > Cobalamin (neuropathy) > Vit B12 (macrocytosis) Vit D (tetany) > Vit A (night blindness) > Cobalamin (neuropathy) > Vit B12 (macrocytosis) Ix = H2 Lactose / Glucose breath test Ix = H2 Lactose / Glucose breath test Rx = 7-10/7 course of Rx = 7-10/7 course of Co-amoxiclav + Metronidazole Cephalexin + Co-trimoxazole Gentamicin + Metronidazole
  • Slide 31
  • Hyposplenism ? 80% of coeliac patients have evidence of hyposplenism {Vasquez 1991} ? 80% of coeliac patients have evidence of hyposplenism {Vasquez 1991} Features Features Howell Jolly bodies, target cells, thrombocytopenia Mx Mx Meningococcal, Pneumococcal + HIB vaccinations Prophylactic antibiotics 10g per day, 2/52) Repeat challenge (>10g per day, 2/52) ESPGAN guidelines ESPGAN guidelines">
  • Diagnosis Serology Serology D2 Bx (3 biopsies with jumbo forceps) D2 Bx (3 biopsies with jumbo forceps) Repeat biopsy on gluten-free diet Repeat biopsy on gluten-free diet Repeat challenge (>10g per day, 2/52) Repeat challenge (>10g per day, 2/52) ESPGAN guidelines ESPGAN guidelines
  • Slide 37
  • Coeliac antibodies Anti-reticulin, anti-gliadin, anti-jejunal Anti-reticulin, anti-gliadin, anti-jejunal Anti-endomysial Anti-endomysial Anti-tissue transglutaminase Anti-tissue transglutaminase
  • Slide 38
  • Serological screening tests SensitivitySpecificity IgA Anti-Gliadin 83%82% IgA Anti Endomysium 90%99% IgA Anti tissue transglutaminase (Human Umbilical cord) 93%95%
  • Slide 39
  • Developments in serological tests IgA deficiency occurs in 2-3% of coeliacs IgA deficiency occurs in 2-3% of coeliacs Coeliacs disease occurs in 8% of IgA deficients Serology Ix Serology Ix IgG1 subgroup testing more specific than IgG Combine both IgA and IgG1 EMA/tTG testing 10-15% are symptomatic 10-15% are symptomatic Recurrent sinopulmonary infections AI associations Anaphylactic Transfusion Reactions GI Disorders (failure to clear large proteins from GI mucosal barrier
  • Slide 40
  • Using Serology to Monitor Patients IgA gliadin and TTG normalise on a strict GFD after 3-6/12 IgA gliadin and TTG normalise on a strict GFD after 3-6/12 Must have pre-treatment levels Must have pre-treatment levels IgG gliadin can be used but takes longer to normalise IgG gliadin can be used but takes longer to normalise IgA endomyseal is costly and more difficult to quantify IgA endomyseal is costly and more difficult to quantify
  • Slide 41
  • Screening Relatives Fraser J: GUT; 2004 1 st Degree relatives = 5%-15% 1 st Degree relatives = 5%-15% 2 nd Degree relatives no increased prevalence 11.4% of these would be missed using IgA EMA in isolation and so an algorithm has been devised Coeliac disease can occur in antibody negative individuals and that biopsy is recommended if there is a high index of suspicion.
  • Slide 42
  • Algorithm for Screening 1 Relatives
  • Slide 43
  • Treatment of coeliac disease Gluten-free diet Gluten-free diet Avoidance of wheat, rye and barley Avoidance of wheat, rye and barley Oats (probably OK) Oats (probably OK) Dietician Dietician Codex Alimentarius Codex Alimentarius Coeliac societies handbook Coeliac societies handbook
  • Slide 44
  • Treatment of coeliac disease Gluten-free diet Gluten-free diet Avoidance of wheat, rye and barley Avoidance of wheat, rye and barley Oats (probably OK) Oats (probably OK) Dietician Dietician Codex Alimentarius Codex Alimentarius Coeliac societies handbook Coeliac societies handbook BUT NOT CORNFLAKES BUT NOT CORNFLAKES
  • Slide 45
  • Efficacy of Gluten-free diet 70% respond symptomatically 70% respond symptomatically 30%refractory 30%refractorynon-compliant inadvertent intake another diagnosis
  • Slide 46
  • Dewar D, Johnson MW, Ciclitira PJ, GUT 2005
  • Slide 47
  • Gluten-free diet failure Check diagnosis correct Check diagnosis correct Consider second diagnosis Consider second diagnosis pancreatic insufficiency Check Compliance Check Compliance inadvertent/intentional Refractory sprue Refractory sprue REPEAT DUODENAL BIOPSY REPEAT DUODENAL BIOPSY
  • Slide 48
  • Pitfalls Ins