Coeliac Disease & IBD

Question 1

Coeliac disease definition

Answer 1

Gluten sensitive enteropathy or coeliac sprue

leading to malabsorption with cessation of symptoms on gluten-free diet

Question 2

Gluten definition

Answer 2

A protein compound of wheat, rye and barley which is left behind after washing off the starch

Gluten consists of gliadin and glutenins

Question 3

Genetic abnormalities in Coeliac Disease

Answer 3

Associated with HLA – DQ2 and HLA - DQ8 in 95% and 5% of the patients respectively

The genes are located on Chr 6p21

Question 4

High coeliac disease prevalence in patients with

Answer 4

Down’s syndrome, Type I diabetes mellitus, auto-immune hepatitis and thyroid gland abnormalities

Abnormal liver function tests

Question 5

Process

Answer 5

Gluten + Small bowel mucosa

Tissue transglutaminase
↓ 
diamidates glutamine in gliadin
↓
Negatively charged protein
↓
IL – 15
↓
Natural killer cells + 
Intraepithelial T lymphocytes
↓
	Tissue destruction + villous atrophy

Question 6

Hallmarks of coeliac disease [6]

Answer 6

Malabsorption of nutrients
Short stature; failure to thrive in children
Diarrhoea : smelly & bulky stool, rich in fat (steatorrhoea)
Weight loss and fatigue
Anaemia – folate and Fe deficiency
Osteopenia and osteoporosis – calcium and Vitamin D deficiency

Question 7

Classification of Coeliac Disease

Answer 7

Classical – Malabsorption symptoms
Non-classical including symptoms outside the gastro-intestinal tract:

constipation, bloating alternate bowel habits
→ constipation/diarrhoea
Heartburn, nausea, vomiting and dyspepsia

Recurrent miscarriage/infertility
Sub-clinical – Detected with blood tests

Question 8

Coeliac disease investigations

Answer 8

FBC, U & Es, LFTs
Deamidated gliadin peptide IgA & IgG
Endomysial IgA
Tissue transglutaminase IgA

HLA D2 & HLA DQ8 in children with positive TTGA and symptoms to avoid biopsies

Question 9

Tissue transglutaminase IgA

Answer 9

98% sensitive, 96% specific

Question 10

Endomysial IgA

Answer 10

100% specificity,

90% sensitivity

Question 11

Macroscopic features of coeliac disease

Answer 11

Villous atrophy (VA)
Crypt hyperplasia
Increase in lymphocytes in the lamina propria/chronic inflammation
Increase in intraepithelial lymphocytes (IEL)
Recovery of villous abnormality on gluten-free diet

Question 12

Coeliac disease complications

Answer 12

Enteropathy associated T-cell lymphoma

High risk of adenocarcinoma

Dermatitis hepetiformis – very itchy skin condition
Infertility and miscarriage

Refractory coeliac disease despite strict adherence to gluten free diet

Question 13

Crohn’s disease definition

Answer 13

An idiopathic, chronic inflammatory bowel disease often complicated by fibrosis and obstructive symptoms a

Affect any part of the GIT from mouth to anus

Question 14

Potential CD genetics

Answer 14

NOD2 (nucleotide binding domain) also known as IBD1 gene on Chr16 encodes a protein that binds to intercellular bacterial peptoglycans, activates nuclear factor kappa B (NF-KB) and inhibits normal immune response to luminal microbes leading to uncontrolled inflammation

Question 15

Hint that CD could be infectious

Answer 15

Because granulomas are present in 60 -65% of patients, mycobacterium para-tuberculosis was extensively investigated as a possible cause but never proven

Other infectious organisms implicated – measles virus, pseudomonas, listeria, but never proven

Question 16

CD environmental factors

Answer 16

Improved hygiene hypothesis
Migration to high risk population
Cigarette smoking

Question 17

CD clinical features

Answer 17

Chronic, indolent course punctuated by periods of remission and relapses
Abdominal pain, relieved by opening bowels
Prolonged non-bloody diarrhoea
Blood may be present if the colon is involved
Loss of weight, low grade fever

Question 18

CD morphological features

Answer 18

Fat wrapping of the serosa - noted during surgery
Typically segmental morphology→normal bowel separated by abnormal bowel = skip lesions
Ulceration with a cobblestone pattern
Strictures due to fibrosis

Question 19

Microscopic appearance of CD

Answer 19

Transmural or full thickness inflammation of the bowel wall
Mixed acute and chronic inflammation i.e. polymorphs and lymphocytes
Preserved crypt architecture
Mucosal ulceration
Fissuring ulcers (deep crevices)
Granulomas ( collection of macrophages) present in 60 - 65%
Fibrosis of the wall

Question 20

UC

Answer 20

A chronic inflammatory bowel disease which only affects the large bowel from the rectum to the caecum. Unlike CD, the inflammatory process is confined to the mucosa and sub-mucosa except in severe cases.

Question 21

UC causes

Answer 21

High incidence of UC in first degree relatives and high concordance in twins
HLA-B27 identified in most patients with UC, but not thought to be an aetiological factor

NSAIDs exacerbates UC
Antioxidants Vitamins A & E are found in low levels in UC

Question 22

UC clinical features

Answer 22

Intermittent attacks of bloody diarrhoea 
Mucoid diarrhoea
Abdominal pain
Low grade fever
Loss of weight

Question 23

UC macroscopic features

Answer 23

Affects the large bowel from rectum to the caecum
Can affect the rectum only (proctitis), left sided bowel only ( splenic flexure to rectum) or whole large bowel = total colitis
Despite the term ‘ulcerative’ there are no ulcers on endoscopic examination in early disease
Diffuse mucosal involvement which appears haemorrhagic
With chronicity, the mucosa becomes flat with shortening of the bowel

Question 24

Microscopic features of UC

Answer 24

Inflammation confined to the mucosa (black bar)
Diffuse mixed acute & chronic inflammation
Crypt architecture distortion
In quiescent (inactive) UC, the mucosa may be atrophic with little or few inflammatory cells in the lamina propria