Lecture 6: Coeliac disease Flashcards
What is coeliac disease?
A common digestive condition
Inflammation of the mucosa of the upper small bowel
Improves when glute is withdrawn
Immune-mediated enteropathy
Define enteropathy?
Disease to the small intestine
What cna coeliac disaese patients will not be able to digest?
Gluten
What is gluten?
Gluten is a dietary protein
Subtype of prolamin (a group of plant storage proteins)
What are 3 grains contain gluten?
Rye
Wheat
Barley
Why do some people have coeliac disease but not everyone?
People have a genetic predisposition for coeliac
Positive for HLA DQ2/8
How common is coeliac disease?
Prevalence around 1% in the general population
High prevalence compared to other immune diseases
Many as silent i.e. as asymptomatic
Describe the progression of coeliac disease?
3 stages
- Latent coeliac disease where there is normal mucosa
- Silent coeliac disease where there is manfiestations of mucosal lesion (but no symptoms are present)
- Coeliac disease present with symptoms
What is the purpose of gluten?
means “glue” in latin
Gives dough its viscoelastric properties
Which compoent of wheat flour is mainly made up for gluten?
The protein component of wheat is made of 90% gluten
Why does gluten cause digestive problems?
Gliadin (component of gluten) peptides cannot be digested by proteases.
Gliadin peptides pass through the epithelium and are deaminated by tissue transglutaminase (TTG)
Gliadin peptides bind to antigen-presenting cells, which interact with CD4+ T cells via HL2 class molecules DQ2 or DQ8.
These T cells produce pro-inflammatory cytokines causing the inflammation.
T cells interact with B cells, which creates anti-TTG antibodies (which attacks the TTG)
What are the two main components of gluten?
Gliadin and Glutenin
What is the significance of HLA DQ 2/8 for coeliac disease?
HLA DQ2/8 gene.
HLA DQ2/8 is needed for the dendritic cells (which has uptake the Gliadin) to expose it to T cells.
Being positive for HLA DQ2/8 does not mean you will have coeliac disease but you require it to have it i.e. you cannot have coeliac disease without it
Can you be born with coeliac disease?
No
Requires exposure to gluten as it is the trigger i.e. once no gluten in diet, symptoms disappear.
Born with genetic disposition but needs to be a trigger
What triggers coeliac disease?
Gluten
What are the signs and symptoms of coeliac disease?
Diarrhoae or loose stools
Dyspepsia i.e. indigestion
Vomiting
Any GI symptom
Dermatitis herpetiformis (itchy rash)
Short stature due to malnutrition
Anxiety and depression
Multiple others
How do we test for coeliac disease?
Patient must be on a gluten diet
Serology for endomysial or anti-TTG
Duodenal biopsy
Human leucocyte antigen
Imaging of small bowel: MRI to show buldging
At what age is coeliac disease most prevalence?
Can occur at any age
Peak period of diagnosis is in the 5th decade
What is the limitations of the serology tests for coeliac disease?
These tests uses IgA class antibodies.
IgA deficiency is far more common in coeliac disease patients. Hence, these tests will be a false negative for these patients
What is the visible signs of coeliac disease on a endoscope?
Loss of villi present
Crypt hyperplasia
What does the inflammation associated with coeliac disease do chronically?
It causes the loss of villi and crypt hyperplasia.
Therefore, significant decrease in surface area
What happens with a coeliac disease patient sticks to a gluten free diet ?
Symptoms should disappear
After 2-3 years, the damage done to the mucosa of the small bowel should be healed
What is the diagnostic algorithm for coeliac disease?
Test for 3 parameters: TTG, biopsy and HLA DQ2/8
Needs HLA to be positive (negative it is not coeliac disease)
Biopsy negative: could be because of a low quality specimen OR because it is the latent coeliac (no changes have occured yet)
TTG negative: could be because of IgA deficiency
What is the management of coeliac disease?
Gluten-free diet. Removing rye, barley and wheat.
Nutritional assessment
Vaccinate for penumococcus and meningococcus
DEXA scan
Why is DEXA scan important for patients with coeliac disease?
Coeliac patients are at higher risk of osteoporosis.
It may be due to the low BMI or calcium/vitamin D deficiency.
Why is vaccination for pneumococcus and meningococcus important for patients with coeliac disease?
These patients are at higher risk of septicemia
What else can go wrong with coeliac disease?
Increase risk of sepsis
Increase risk of osteoporosis
Increase risk of cancer
Why should a coeliac patient go gluten-free even if they are asymptomatic?
Risk of malnutrition and malabsorption
Higher risk of cancer
Relieve future symptoms from occuring
What could be the reasons for coeliac patients to still have symptoms?
Still ingesting gluten
Other conditions present alongside coeliace.g. lactose intolerance.
Refractory coeliac disease
What is refractory coeliac disease?
Rare and life threatening
Persistent or recurrent malabsorption symptoms and villous atrophy despite adherence to a gluten-free diet
What are the two type of refractory coeliac disease and define each
Primary and secondary
Primary/ type 1: when a diagnosis of coeliac disease is confirmed and provide treatment but the treatment does not work. i.e. treatment has never worked
Secondary/ type 2: when a patient has been diagnosed with coeliac disease for a long time (years) but then suddently treatment no longer worked.
Type 2 is more dangerous
Why is secondary/type 2 refractory coeliac disease more dangerous?
It is a precursor for enteropathy associated T-cell lymphoma
What are the treatment options for enteropathy associated T-cell lymphoma?
High dose chemotherapy + stem cell transplant
What is the prognosis of enteropathy associated T-cell lymphoma (EATL)?
Poor prognosis
28% 2 year survival
11-20%: 5 years
What are the two types of enteropathy associated T-cell lymphoma? What are their connection with coeliac
Type 1 and 2
Type 1: Strongly associated with coeliac and HLA DQ2
Type 2: Less frequently associated with coeliac
Name a system used to classify coeliac disease?
Marsh classification
