Coeliac Disease and IBD Flashcards
Coeliac disease is an —— small intestine enteropathy triggered by exposure to dietary —— in genetically predisposed individuals, leading to malabsorption.
- immune-mediated
- gluten
Gluten, specifically gliadin is a protein found in
wheat, barley and rye
oats can be contaminated
What % of the population have coeliac disease?
1%
Coeliac disease:
- which gender affected more
- occurs at what age?
- F>M
- occurs at any age
Coeliac disease has a higher prevalence among 1st degree relatives of patients with what disease and ———
- among 1st degree relatives of patients with Crohn’s
disease and a greater concordance in monozygotic
(identical) twins
Which countries is coeliac disease most prevalent?
Western Europe and USA
especially in patients of Irish and Scandinavian descent
Ceoliac Disease: Presentation:
- diarrhoea
- steatorrhea (fatty floating stools)
- weight loss
- anaemia
- vague abdominal pain
Clinical signs:
- anaemia signs: glossitis (B12 and iron deficiency,
mouth ulcers, dermatitis herpetiformis (rash)
- 1/3 individuals asymptomatic
Coeliac disease vs normal bowel endoscopy
What is shown below?
- dermatitis herpetiformis (itchy, vesicular rash on
extensor surfaces)
Pathogenesis of Coeliac Disease:
- the gluten by product gliadin, complexes with tissue
transglutaminase (tTG) in the gut binding as an
antigen (deaminated gliadin) to HLA-DQ2 on T cells,
creating an immune response that results in anti-tTG
IgA, anti-endomysial and antigliadin antibodies in the
blood and inflammation through Natural Killer cells - tTG cross-reacts with epidermal Tg, hence dermatitis
herpetiformis
Pathogenesis of Coeliac Disease
Coeliac Disease Histopathology:
Coeliac Disease: Diagnosis:
- Serology:
- anti-endomysial
- IgA anti-tissue transglutaminase (IgG anti tTG in
patients with IgA deficiency) - anti-gliadin antibodies
- Endoscopy with biopsy:
- histology of the small bowel shows raised
intraepithelial lymphocytes, crypt hyperplasia and
villous atrophy
Coeliac Disease: Treatment:
- Gluten free diet (oats are fine)
- vaccination against pneuomococcus (30% have
reduced splenic function, more likely to get severe
infections) - osteoporosis screening and prevention (1g Ca daily)
- iron, B12, folate supplementation
- monitor for other autoimmune disease (Graves
disease (thyroiditis) and autoimmune hepatitis) - annual blood monitoring
Inflammatory Bowel Disease:
- Crohn’s disease
- Ulcerative colitis
Crohn’s disease:
- what type of ulceration
- which parts of the GI tract affected
- patchy, transmural ulceration
- affecting the bowel anywhere from mouth to anus
Ulcerative Colitis:
- what type of ulceration
- which parts of the GI tract affected
- continous, mucosal ulceration
- only affects the colon
What does the endoscopy show?
Cohn’s Disease
Deep ulcers
Patchy inflammation
What does the endoscopy show?
Ulcerative colitis
continuous inflammation
Histological features of Crohn’s disease:
- transmural inflammation (all layers can be affected)
- granulomas are seen
- may have crypt disturbances
Histological features of Ulcerative Colitis:
- mucosal inflammation
- crypt abscesses
- NO GRANULOMAS
What is the histological key feature that differs Crohn’s and ulcerative colitis?
Granulomas only present in Crohn’s
What are granulomas?
- aggregations of macrophages around foreign
substances to be eliminated
Differences between CD and UC:
Crohn’s disease mostly affects what age group?
younger adults/children
Crohn’s disease and smoking**
strong predisposition to smokers
What three structures are seen in Crohn’s disease?**
- fistulas
- strictures
- perianal disease
Crohn’s disease is a penetrating disease where**
inflammation tracks across the bowel wall to adjacent bowel or organs and can cause localised abscess formation
Epidemiology of CD:
- high prevalence in which countries
- high prevalence in pts of which origins
- what type of presentation (age wise)
- western world
- Ashkenzai Jews
- bimodal presentation in teens-20s and 60-70
What causes CD?
- unknown exact cause
- genetic, infectious, environmental, dietary, smoking,
NSAIDs, psychological factors - defects in mucosal barriers, which allow entry of
pathogens and other antigens
What are the genetics of CD?
- strong evidence for genetic predisposition
- first degree relatives have 13-18% increased risk
- 50% concordance in monozygotic (identical) twins**
- no classical mendelian inheritance but polygenic
- NOD2 (nucleotide binding domain on Chromosome
16 is the most known varient for predisposition for
CD**
Crohn’s Disease:
- aim is to prevent excessive surgery and short bowel
syndrome - 50% of patients with CD will need surgery and 70% of
those will need a 2nd operation within 5 years of the
first - surgery may be the only treatment for drainage of
abscesses or treatment of fibrostenotic strictures
(where there is little inflammation but symptoms of
bowel obstruction) - thiopurines, then if worsening biologics second line
defence - corticosteroids for inflammation
Crohn’s disease presentation:
- diarrhoea
- abdominal pain
- weight loss
- lethargy
- peri-anal disease
Crohn’s Investigations:
- inflammatory markers
- anaemia
- increased faecal calprotein (qFIT)
- low B12
- low vit D
- colonscopy
Crohn’s Treatment:
- corticosteroid to reduce inflammation
- thiopurines to maintain remission
- biologics second line
- always check TPMT, if no TPMT then severe side
effect of bone marrow suppression - thioguanine nucleotides are the active metabolites of
thipourines which incorporate the sulphur mostly into
the backbone of DNA, preventing unwinding
Ulcerative colitis affects:
- females
- non-smokers***
- bimodal age distribution; 20s and 60s
- genetics definitely implicated
- concordance between monozygotic twins high
- NSAIDs can cause flares
Ulcerative Colitis:
- although only colon is affected, risk of Toxic
Megacolon (dilatation of colon) followed by colonic
perforation if inflammation is very severe - 1/3 will go into remission, 1/3 will have some
symptoms, 1/3 will go on to more extensive disease - the location of disease is a risk factor
Ulcerative Colitis: Presentation:
- bloody diarrhoea
- urgency
- tensemus (cramping rectal pain)
- abdominal pain lower left quadrant
Ulcerative Colitis: Diagnosis:
- colonscopy + biopsy but balanced with risk of bowel
perforation
Treatment of UC:
- mesalazine
- mesalazine+thiopurine+corticosteroid
- biologics
Mesalazines
- 5-ASAs; 5-aminosalicylic acids
- pH dependent capsules affects where in the intestine
and colon they are released
Thiopurines:
- azathioprine, mercaptopurine
- takes 6 weeks to act
- metabolism is under the influence of an enzyme called thiopurine methyl transferase TPMT
TPMT checks
- thiopurine methyl transferase
- metabolises thiopurines
- if not present may result in prevention of DNA
unwinding and bone marrow suppression
Anti-TNF agents; Biologics:
- block bodys natural response to tumour necrosis factor
- infliximab
- given acutely for patient in whom steroids are not working
- 60%
Treatment of Acute CD:
- nil by mouth
- IV antibiotics if there are abdominal absesses***
- modulen (liquid diet)
- IV hydrocortisone (corticosteroid)
- biologics such as infliximab
Treatment of Acute UC:
- IV hydrocortisone (corticosteroid)**
- low molecular weight heparin
- early surgical review
- infliximab for patients who fail steroids
Steroids are not long term. Just for flares.
True or False?
True
Case 1:
- 28 male
- 6 week history of blood diarrhoea
- mild abdo pain relieved by defecation
- weight loss (significant and unintentional)
- grandmother had Crohn’s
- gave up smoking 8 weeks ago
Bloods:
- CRP: high
- Hb: low
- Platelts: high
- MCV: low
superficial inflammation
- ulcerative colitis
- steroids
- blood thinner to prevent clot
- mesalazines
- thiopurines
Case:
- 75 F
- 1 year history of diarrhoea
- no abdo pain
- significant unintentional weight loss
- known hypothyroidism
Bloods:
- CRP: low
- Hb: low
- Platelts: high
- MCV: low
coeliac disease
gluten free diet
