Coeliac Flashcards
1
Q
Provide a summary of coeliac disease
A
- Autoimmune disease
- characterised by small intestinal enteropathy and both gastrointestinal and extra-
gastrointestinal symptoms - Triggered by chronic gluten exposure
- Water soluble and insoluble proteins found in wheat, rye and barley
- Can present at any age
- Association with other autoimmune diseases
- Only effective treatment is a gluten-free diet
2
Q
Describe the epidemiology of coeliac
A
- Estimated prevalence in Australia 1.2 % (men) and 1.9% (women)
- Europe and US - up to 2% in adults
- Increasing global incidence
- North Africa (0.5%)
- Middle East (1%)
- India (up to 1.4%)
- China
- ? related to increased introduction of wheat
- World-wide increase in autoimmune diseases (3-4% annual increase in type I DM over past three
decades)
3
Q
Describe the pathogenesis of coeliac
A
- Usually responds to strict exclusion of gluten
- Requires a specific genetic background (HLA DQ2 or HLA DQ8)
- Patients have circulating IgA autoantibodies to tissue transglutaminase (tTG) a ubiquitous enzyme that
catalyses deamination from a glutamine to lysine residue - increases afffinity for HLA - 30-50% amino acids in gluten are glutamine
- A 33 amino acid peptide from alpha-2 gliadin, the main fraction of gluten binds to HLA class II DQ2 > DQ8
- These class II antigens loaded with peptide stimulate antigen-specific CD4 T cells and trigger an
inflammatory response and antibodies directed against tTG - Only 1/50 of those who are HLA DQ2 or DQ8 positive develop coeliac disease with other genetic and/or
environmental factors contributing to development of the disease - A number of non-HLA genes identified as conferring predisposition to coeliac disease
- Diarrhoea related to villous atrophy i.e. flattening in the
small intestine resulting in mucosal
malabsorption (steatorrhoea) and lactase
deficiency, fluid hypersecretion from crypt
epithelia secondary to crypt hyperplasia
4
Q
Distinguish between types of coeliac
A
- Classical coeliac disease
- Diarrhoea, steatorrhoea, weight loss or growth failure
- Non-classical coeliac disease
- Present without signs of malabsorption
- Symptomatic coeliac disease
- Gastrointestinal or extra-intestinal symptoms secondary to gluten intake
- Refractory coeliac disease
- Persistent or recurrent malabsorption symptoms and villous atrophy on small bowel biopsy despite a strict gluten free diet for 12 months
- Gluten-related disorders
- Coeliac disease, gluten ataxia, dermatitis herpetiformis
- Non-coeliac gluten sensitivity
- Symptoms precipitated by eating gluten where coeliac disease and wheat allergy have been excluded
5
Q
List some GI manifestations of coelaic
A
- Vomiting
- Abdominal bloating
- Abdominal pain
- Variable bowel habit (both loose bowel motions and constipation)
- Iron deficiency anaemia
6
Q
List some non GI manifestations
A
- Lethargy, weakness
- Altered bowel habit
- Failure to thrive
- Recurrent or persistent iron deficiency anaemia
- Dental enamel defects
- Low vitamin D
- Delayed puberty and infertility
- Aphthous ulcers
- Raised transaminases
- Dermatitis herpetiformis
7
Q
When shoul dserology be performed?
A
- Persistent, unexplained abdominal or gastrointestinal symptoms
- Growth failure
- Prolonged fatigue
- Unexpected weight loss
- Severe or persistent mouth ulcers
- Unexplained iron, vitamin B12 or folate deficiency
- At diagnosis for type I DM and autoimmune thyroid disease
- Irritable bowel syndrome in adults
- First degree relatives of people with coeliac disease
8
Q
Whens hould serology be considered?
A
- Osteopenia or osteomalacia
- Unexplained neurological symptoms (ataxia or peripheral neuropathy)
- Unexplained sub fertility or recurrent miscarriage
- Persistently raised transaminases with unknown cause
- Dental enamel defects
- Trisomy 21
- Gonadal dysgenesis (Turner syndrome)
9
Q
List some associated conditions
A
- Type I diabetes mellitus (> 8%)
- Selective IgA deficiency (~1.7 - 7.7%)
- Trisomy 21 (5-12%)
- Turner’s syndrome (4-8%)
- Autoimmune thyroid disease (~15%)
- Autoimmune liver disease (~12%)
- Dermatitis herpetiformis (75%)
- Relatives of individual with coeliac disease
- First degree relative (~10%) HLA matched sibling (~30-40%), monozygotic twin (~ 70%
10
Q
Describe dermatitis herpetiformis
A
- Intensely pruritic blistering rash
- Extensor surfaces of arms and
knees, buttocks - Occurs in ~ 10 % individuals
with coeliac disease - Reducing incidence over time ( in
contrast to coeliac disease)
11
Q
What are the consequences of a msised diagnosis?
A
- Persistent gastrointestinal symptoms
- Osteopenia and osteoporosis (risk of pathological fractures)
- Impaired growth and both macro and micronutrient malnutrition
- Delayed puberty, infertility and increased risk of miscarriage
- Increased risk of small bowel malignancy
- T cell lymphoma and other gastrointestinal cancers
- non-Hodgkin lymphoma (2-4 x increased risk)
- Increased risk of renal, ocular and vascular complications in patient with type I diabetes mellitus and
coeliac disease - Hyposplenism (increased risk of infections with encapsulated organisms)
12
Q
Describe serology
A
- Firstly confirm that the patient is consuming a normal, gluten-containing diet
- Serum IgA levels and tissue transglutaminase IgA antibodies or
- tissue transglutaminase IgA antibodies and deaminated gliadin peptide IgG
(DGP - IgG) - IgA endomyseal antibodies (performed in limited laboratories)
- Where tTG-IgA and/or DGP IgG positive refer for confirmatory small intestinal
biopsy
13
Q
Describe genotying
A
- HLA DQ2 and HLA DQ8 found in 99% of patients with coeliac disease
- 40-50% of the Australian community so most people with these genes will not
develop coeliac disease - Main use of HLA DQ2/DQ8 genotyping to exclude a diagnosis of coeliac
disease
14
Q
Describe histology and pathology
A
- Macroscopic clues on endoscopy
- loss of folds, modularity, fissuring
- Multiple biopsies of the duodenum required
- duodenal bulb and second part of the duodenum
- Biopsies need to be performed while the individual is on a gluten-containing diet
- Histological diagnosis based on the classification of Marsh, Marsh modified or Corazza
classification - Important to correlate clinical presentation, serology and histopathology.
- Similar features can be seen in setting of primary antibody deficiency, medications, infection
-
* Increased HLA Class II and
cytokine expression precedes
abnormal histology
* Intraepithelial lymphocytes
* Crypt hyperplasia
* Villous atrophy
* Patchy involvement so multiple
biopsies required
15
Q
Describe management
A
- Life-long gluten-free diet
- Beware hidden sources, avoid milk (lactose) initially for 4 weeks, oats for 3 months
- Patient education and motivation required
- Dietitian involvement
- NIHCE recommends
- annual review of medical and dietary progress
- BMD scan in pts at risk for osteoporosis or > 55 years
- pneumococcal vaccine for newly diagnosed adult patients
- Symptomatic improvement within days to weeks
- Coeliac serology often used as a surrogate for mucosal healing
- Results usually return to normal values by 12 months on a gluten-free diet
- Better correlation in children with resolution of mucosal inflammation
- Adults have slower resolution and mucosal recover may be incomplete
- Persistently raised tTG antibodies should assess for adherence to a gluten-
free diet, accidental gluten contamination
16
Q
1.
DEscribe refractory disease
A
- Primary if no response to a gluten-free diet at 12 months
- Secondary if initial response followed by relapse
- Consider biopsy if diagnosis in doubt or symptoms despite a gluten- free diet
- Where persistent evidence for enteropathy
- small bowel imaging where abdominal pain, fever, anaemia, unexplained weight loss or
gastrointestinal blood loss to exclude coeliac-related malignancies or other conditions - thyroid function tests
- pancreatic insufficiency
- secondary lactose intolerance
- ~ 5% will have refractory symptoms despite a stringent gluten-free diet
- Diarrhoea, weight loss, malabsorption, gastrointestinal blood loss, ulcerative
jejunitis (refractory spur) - Type I
- normal intraepithelial lymphocyte phenotype
- Type II
- clonal expansion of abnormal intraepithelial lymphocytes
- associated with high risk of enteropathy associated T cell lymphoma
17
Q
Describe management of refractory disease
A
- Strict gluten-free diet
- Nutritional support - may require TPN
- Immunosuppressive therapy
- corticosteroids
- other corticosteroid sparing agents
18
Q
List some new therapes
A
- Anti-interleukin 15 therapy: Blocking intestinal epithelial permeability (reduce passage through tight
junctions) - Peptidase supplements to inactivate immunogenic gluten peptides in the
gastrointestinal tract prior to reaching the small intestine - Gluten tolerization, targeting gluten-specific T cells and/or APCs to modify the response to
gluten
19
Q
What are some differentials?
A
- non-coeliac gluten sensitivity
- wheat allergy
