89-92. Coeliac disease Flashcards
What is coeliac disease? What are the features of the disease?
Gluten sensitive enteropathy
Small intestinal villous atrophy that resolves when gluten is withdrawn from the diet
Inappropriate T cell response in genetically susceptible individuals
What is the most toxic moiety of gliadin (present in wheat)?
alpha-gliadin
What is the gene which genetically predisposes people to coeliac disease?
HLA-DQ2 (95%)
The rest are HLA-DQ8
What causes coeliac disease?
Infection with adenovirus 12 in genetically susceptible individuals
Peptide on alpha-gliadin is similar to that within the Eb1 portion of the virus
This leads to cross reactivity with alpha-gliadin and development of coeliac disease
How does alpha-gliadin produce an inflammatory response in coeliac patients?
Digestion of alpha-gliadin produces a stable peptide, which is absorbed intact to the lamina propria
Exposure to TTG (an autoantibody) from damaged epithelium leads to deamination of glutamine residues
This enables bonding to HLA-DQ2 and the activation of pro-inflammatory T cell responses
What are the 7 main presentations associated with coeliac disease?
- Symptomatic (may be provoked by infection, pregnancy or surgery)
- diarrhoea, bloating, flatulence, abdominal discomfort - Chronic or recurrent iron deficiency anaemia (50% of coeliacs present with this)
- Nutritional deficiency (i.e. vit B12, folate)
- Reduced fertility/amenorrhoea
- Osteoporosis
- Unexplained raised AST/ALT
- Neurological/psychiatric symptoms
How many litres of fluid does the small intestine absorb daily?
6 litres
What is the surface area of the small intestine?
200m^2
What are the pathological changes of the small intestine in coeliac disease?
Mucosal inflammation - can vary based on severity & extent
Mild proximal disease typically occurs
Mucosal damage may be patchy
Loss of villous height
- villi may be completely flat or short and broad (sub total villous atrophy)
No change in total mucosal thickness as crypts become elongated (hypertrophy)
Increased plasma cells and intraepithelial lymphocytes (IELs)
Describe the clinical features related to the small bowel in coeliac disease
Diarrhoea - steatorrhoea, watery and high volume, rarely bloody
Weight loss
Malabsorption
abnormal pain/vomiting
What are the indicators of small bowel disease?
Malabsorption/electrolyte imbalances
- folate
- vit D/ calcium —–> osteoporosis
- Vit K/ coagulopathy
- magnesium
- vit B12
Chronic/recurrent IDA
What 80% of iron is incorporated into red cell haemoglobin?
80%
How many mg of iron is required daily for the rate of renewal of RBCs?
20mg
What is the RDA of iron, including pregnant women?
8-18mg
27 in pregnancy
How many mg of iron is lost per day and what causes this loss?
1mg lost through sloughing of cells from skin and mucosal surfaces, including the lining of the GI tract
In menstruation, this increases to 2mg per day
Where is iron absorption most predominant?
Duodenum and proximal jejunum
Why is more iron absorbed in the duodenum and upper jejunum than other areas?
At physiological pH, iron is rapidly oxidised from the ferrous iron into insoluble ferric iron
Gastric acid lowers the pH, and when present in the duodenum this increases the solubility of iron for enhanced uptake
What enhances uptake of iron?
Vitamin C and citric acid
What inhibits the uptake of iron?
Phytates and tannins (tea)
What are tested in serology for the diagnosis of coeliac disease?
IgA tTG (tissue transglutaminase antibody) IgA EMA (antiendomysial Ab)
TTG more sensitive in adults, with EMA more specific
What can be used to monitor patient compliance?
Seroconversion (the length of time it takes for an antibody to develop) with gluten free diet
What may appear on endoscopy of a patient with coeliac disease?
Scalloping of the folds Insufficient amount of folds Music pattern "cracked mud" Prominent submucosal blood vessels Nodular pattern to the mucosa
May also appear NORMAL
How are biopsies used to diagnose coeliac disease?
Taken from distal duodenum
Minimum of 4 biopsies
Biopsies from duodenal bulb may improve diagnosis
Must be on gluten rich diet
If there is villous atrophy with no coeliac serology, what do you check for?
IgA selective deficiency (in 2-5%)
What are rarer causes of villous atrophy without coeliac serology?
Giardiasis (parasitic disease) - most common parasite infection in humans CVID (common variable immune deficiency) Radiation enteritis Crohn's disease lymphoma Whipple's disease Tropical Sprue HIV enteropathy Chronic ischaemia NSAIDs
What are the coeliac related diseases?
Dermatitis herpetiformis
T1DM - NICE advise to screen all patients
Thyrotoxicosis (hyperthyroidism)
Addison’s disease (not enough cortisol)
What are features of dermatitis herpetiformis?
Itchy rash on exterior surfaces
90% villous atrophy
Gluten sensitive/dapsone
What foods should coeliacs avoid and what foods can they eat?
Avoid: wheat, barley, rhye
Can eat: Oats*, rice and maize
Should continue to eat dairy to avoid hypolactasia (50%)
*Debate as to whether or not coeliacs can eat oats
What % show symptomatic improvement within 2-52 weeks?
70%
How long does it take to show improvement in histology?
3-12 months
What are the 4 main complications of coeliac disease?
Osteoporosis
Malignancy
Recurrent coeliac disease
Infection
What may cause infection in coeliacs?
Functional hyposplenism - defective immune responses to: Encapsulated organisms Pneumococcal Haemophilus influenzae Meningococcus Vaccinations
What % of coeliacs develop osteoporosis and why?
25%
Low BMI
Calcium and vitamin D deficiency
(consider DEXA at diagnosis and supplementation)
What is refractory coeliac disease?
Recurrent malabsorptive symptoms and villous atrophy despite strict adherence to a gluten free diet for at least 6-12 months in the absence of other causes of non-responsive treated coeliac disease and overt malignancy.
What are the outcomes and treatment for patients with refractory coeliac disease 1 (RCD1) - villous atrophy with normal immunophenotype?
96% 5 year survival rate
Treated with steroids/azathiopine (over 75% response)
What are the outcomes for RCD2 - villous atrophy with abnormal immunophenotype?
58% 5 year survival rate
60-80% progression onto EATL (enteropathy associated T cell lymphoma) at 5 years
What are the clinical features of EATL, the treatment and survival rate?
Weight loss, night sweats, itch, overt/occult GI bleeding, venous thromboembolism
Often advanced and incurable
Chemotherapy and autologous stem cell Tx
Poor response, 8-20% 5 year survival
What are the main features of small bowel adenocarcinoma?
Rare -13% coeliac, 7% Crohns 58% survival at 30 months Male more than female 55% present with obstruction Mean time from symptoms to diagnosis - 14 months
