Coeliac Disease & Inflammatory Bowel Disease

Question 1

What is coeliac disease?

Answer 1

An auto-immune mediated disease of the small intestine triggered by the ingestion of gluten in genetically predisposed individuals leading to malabsorption with cessation of symptoms on gluten free diet

Question 2

What is coeliac disease otherwise known as?

Answer 2

Gluten sensitive enteropathy or coeliac sprue

Question 3

What is found in gluten?

Answer 3

Gluten consists of gliadin and glutenins

Question 4

What is gluten?

Answer 4

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

Question 5

What are the genetic abnormalities of coeliac disease?

Answer 5

Associated with HLA – DQ2 and HLA - DQ8 in 95% and 5% of the patients respectively
The genes are located on Chr 6p21
Other coeliac disease genes are under investigation
Coeliac disease has a strong hereditary predisposition affecting 10% of first degree relatives

Question 6

Who gets coeliac disease?

Answer 6

Most prevalent in Western Europe and United States especially in patients of Irish and Scandinavian descent
Increasing incidence in Africa and Asia
A lot of patients in the community have undiagnosed coeliac disease - requires a high index of suspicion
High prevalence of coeliac disease in patients with Down’s syndrome, Type I diabetes mellitus, auto-immune hepatitis and thyroid gland abnormalities
Can present with abnormal liver function tests due to auto-immune hepatitis

Question 7

How does gluten cause coeliac disease?

Answer 7

Gluten in Wheat	     + 	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 8

How does coeliac disease present?

Answer 8

Hallmark of coeliac disease is the 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 9

Name the 3 types of classified coeliac disease

Answer 9

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 10

What are the investigations for coeliac disease?

Answer 10

General investigations: FBC, U & Es, LFTs

Serology for diagnosis of coeliac disease

• Tissue transglutaminase IgA (TTGA); 98% sensitive, 96% specific
• Endomysial IgA – connective tissue covering the smooth muscle fibres; 100% specificity, 90% sensitivity
• Deamidated gliadin peptide IgA & IgG (new)
• For monitoring compliance to gluten free diet
• Sero-negative coeliac disease reported in 6.4-9% of patients

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

Question 11

How do routine coeliac disease tests work?

Answer 11

They are tissue damage tests
When the small bowel is exposed to gluten there is overreaction of the immune system to produce  antibodies to the  proteins involved in tissue damage i.e. antibodies to :
Tissue transglutaminase 
Endomysium
Deamidated  gliadin peptide

Question 12

What are the microscopic features of coeliac disease?

Answer 12

At least four biopsies to be sampled from the duodenum at upper GIT endoscopy as changes can be patchy
On microscopy there is:
-Villous atrophy (VA)- finger like pattern becomes flat
-Crypt hyperplasia
-Increase in lymphocytes in the lamina propria/chronic inflammation- induced by IL-15
-Increase in intraepithelial lymphocytes (IEL)- induced by IL-15
-Recovery of villous abnormality on gluten-free diet

Question 13

What are the complications of coeliac disease?

Answer 13

Enteropathy associated T-cell lymphoma
High risk of adenocarcinoma of small bowel and other organs – large bowel, oesophagus, pancreas
May be associated with dermatitis hepetiformis – very itchy skin condition
Infertility and miscarriage
Refractory coeliac disease despite strict adherence to gluten free diet
Gluten free diet may reduce risk of complications

Question 14

What constitutes as inflammatory bowel disease?

Answer 14

Crohn’s Disease (CD)
Ulcerative Colitis (UC)
Diverticular disease
Ischaemic colitis
Drug-induced colitis – NSAIDs
Infective colitis
CD & UC = collectively idiopathic inflammatory disease (IBD)

Question 15

What is crohn’s disease?

Answer 15

An idiopathic, chronic inflammatory bowel disease often complicated by fibrosis and obstructive symptoms and can affect any part of the GIT from mouth to anus

Question 16

What is the epidemiology of crohn’s disease

Answer 16

High prevalence in the Western world with increased incidence in patients of Jewish origin
Increasing incidence in Africa, South America and Asia
Bimodal presentation with peaks in the teens-20s and 60-70 year age groups

Question 17

What causes crohn’s disease?

Answer 17

The exact cause is unknown
Genetic, infectious, immunologic, environmental, dietary, vascular, smoking, NSAIDs and psychological factors – all have been implicated
Defects in mucosal barriers

Question 18

What are the genetics of crohn’s disease?

Answer 18

Strong scientific evidence for genetic predisposition to CD
First degree relatives have 13-18% increased risk of developing CD with a 50% concordance in monozygotic twins
No classical Mendelian inheritance but polygenic

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 19

Is there a possible infectious cause of crohn’s disease?

Answer 19

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 20

Describe the improved hygiene hypothesis implicated in crohn’s disease

Answer 20

Improved hygiene in susceptible individuals reduces enteric infections and this reduces the ability of the GIT mucosa to develop regulatory processes that would normally limit immune response to pathogens which cause self-limiting infections i.e. because of the good hygiene, the mucosa is not immunised to microbes and when exposed to whatever pathogen that causes CD there is exaggerated immune response resulting in mucosal damage.

Question 21

Describe some other environmental factors that are implicated in crohn’s disease

Answer 21

Migration from a low risk population to high risk population increases the risk of developing CD
Cigarette smoking doubles the risk of developing CD (NB – smoking protective in UC)

Question 22

What are the clinical features of crohn’s disease?

Answer 22

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 23

What is the distribution of crohn’s disease?

Answer 23

Any part of GIT from mouth to anus
Small bowel alone – 40%
Large bowel alone – 30%
Small and large bowel – 30%

Question 24

What are the morphological features of crohn’s disease?

Answer 24

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 25

What are the microscopic appearances of crohn's disease?

Answer 25

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 26

What are the complications of crohn's disease?

Answer 26

Intra-abdominal abscesses Deep ulcers lead to fistula = communication between two mucosal surfaces (e.g. colo-vesical fistula leads to pneumaturia) Sinus tract = blind ended tract ends in a “cul de sac” Obstruction due to adhesions Obstruction due strictures caused by increased fibrosis Perianal fistula and sinuses Risk of adenocarcinoma, but not as high as in UC

Question 27

What is ulcerative colitis?

Answer 27

UC is 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 28

What is the epidemiology of ulcerative colitis?

Answer 28

More common in Western countries with higher prevalence in patients of Jewish descent Less frequent in Africa, Asia and South America Can arise at any age but rare before the age of 10 Peaks between 20-25 years with a smaller peak in 55-65 year age groups

Question 29

What causes ulcerative colitis?

Answer 29

As with CD the cause of UC is unknown Similar to CD multiple factors are implicated Genetics not as well defined as in CD -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 Similar to CD no specific infective agent has been identified Environmental factors? Smoking is protective in UC; cessation of smoking may trigger UC or activate disease in remission NSAIDs exacerbates UC Antioxidants Vitamins A & E are found in low levels in UC

Question 30

What are the clinical features of ulcerative colitis?

Answer 30

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

Question 31

What are the macroscopic features of ulcerative colitis?

Answer 31

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 32

What are the microscopic features of ulcerative colitis?

Answer 32

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

Question 33

What are the complications of ulcerative colitis?

Answer 33

``` Complications invariably lead to surgery Refractory to medical treatment Toxic megacolon = bowel grossly dilated and hemorrhagic Patient very ill Bloody diarrhoea Abdominal distention Electrolyte imbalance with hypoproteinaemia Refractory bleeding Dysplasia or adenocarcinoma UC at an early age Total unremitting UC After 8-10 years of UC Patient requires annual screening colonoscopy ```

Question 34

What are the extra-intestinal manifestations of ulcerative colitis and crohn's disease?

Answer 34

Ocular - uveitis, iritis, episcleritis Cutaneous - erythema nodosum, pyoderma gangrenosum Arthropathies - ankylosing spondylitis and others Hepatic - screlosing cholangitis

Question 35

What investigations are carried out during crohn's disease and ulcerative colitis?

Answer 35

``` FBC U & Es LFTs Inflammatory markers – C reactive protein (CRP) Endoscopy and biopsies Radiological imaging Barium studies MRI USS CT Scan ```

Question 36

Why is it important to distinguish between ulcerative colitis and crohn's disease?

Answer 36

A patient may have a pouch after surgery in UC but not in CD because of risk of recurrence A pouch is created from the small bowel as stool reservoir following surgical removal of the large bowel.