Coeliac Disease and Inflammatory Bowel Disease

Question 1

What is Coeliac Disease

Answer 1

• Gluten sensitive enteropathy or coeliac sprue
• 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
• Gluten is a protein compound of wheat, rye and barley which is left behind after washing off the starch
• Gluten consists of gliadin and glutenins

Question 2

Genetic Abnormalities of Coeliac Disease

Answer 2

• 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 3

Incidence of Coeliac Disease

Answer 3

• Mostly in Western Europe and USA, especially of Irish or 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
• Bimodal presentation in childhood and late thirties
• Approximately 20% of patients with coeliac disease are older than 60years

Question 4

How does gluten cause coeliac disease

Answer 4

Gluten in wheat + small bowel mucosa
-> tissue transglutaminase -> dominates glutamine in gliadin -> negatively charged protein -> IL-15 -> natural killer cells and intraepithelial T lymphocytes -> tissue destruction + villous atrophy
Inflammation and flat lining in the small bowel villi

Question 5

Symptoms of coeliac disease

Answer 5

• Flat mucosa does not absorb nutrients and leads to symptoms
• May be asymptomatic (detected by blood test)

Question 6

Classical Presentation of coeliac d

Answer 6

Diarrhoea 45 – 85% of patients - smelly & bulky stool, rich in fat (steatorrhoea)
Flatulence 28% of patients
Borborygmus 35 – 72% of patients
Weight loss 45% of patients 
In children failure to thrive
Weakness & fatigue 78 – 80% of patients 
Severe abdominal pain 34 – 64% of patients
Irritable bowel syndrome like symptoms

Question 7

Atypical Presentation of coeliac d

Answer 7

Anaemia 10 – 15% of people
Osteopenia and osteoporosis
Muscle weakness, pins and needles, loss of balance, fits 8 – 14% of people
Itchy skin conditions such as dermatitis herpetiformis 10 – 20% of people
Lack of periods, delayed periods in teenagers, infertility in women and impotence and infertility in men
Bleeding disorders due to Vitamin K deficiency
Emaciation, pot belly, muscle wasting, osteoporosis

Question 8

Routine Investigations for coeliac d

Answer 8

FBC, U&Es, LFTs
Serology for diagnosis
o Tissue transglutaminase IgA (TTGA); 98% sensitive, 96% specific
o Endomysial IgA – connective tissue covering the smooth muscle fibres; 100% specificity,
o 90% sensitivity
o Deamidated gliadin peptide IgA & IgG (new)
o For monitoring compliance to gluten free diet
o Sero-negative coeliac disease reported in 6.4-9% of patients.
HLA DQ2 & HLA DQ8 in children with positive TTGA and symptoms to avoid biopsies
Duodenal biopsies

Question 9

How do the tests for coeliac d work?

Answer 9

Assess tissue damage
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 10

Microscopic features of Coeliac disease

Answer 10

4 biopsies at least should be sampled at upper GIT endoscopy
There is: Villous atrophy (VA), Crypt hyperplasia, Increase in lymphocytes in the lamina propria/chronic inflammation, Increase in intraepithelial lymphocytes (IEL), Recovery of villous atrophy on gluten-free diet

Question 11

Complications of coeliac disease

Answer 11

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 12

What constitutes inflammatory bowel disease

Answer 12

Crohn’s Disease (CD)
Ulcerative Colitis (UC)
Diverticular disease
Ischaemic colitis
Drug-induced colitis – NSAIDs
Infective colitis
CD & UC = collectively known as idiopathic inflammatory disease (IBD)
Important to distinguish CD from UC – different complications and different surgical procedures

Question 13

What is Crohn’s Disease

Answer 13

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
Epidemiology: 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-olds§

Question 14

Causes of Crohn’s

Answer 14

Genetic, infectious, immunologic, environmental, dietary, vascular, smoking, NSAIDs and psychological factors – all have been implicated
Defects in mucosal barriers which allow pathogens and other antigens to induce an unregulated inflammatory reaction
Infectious cause? - 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 include measles virus, pseudomonas, listeria
Improved hygiene hypothesis - GIT mucosa unable to develop regulatory processes that would limit immune response to pathogens which cause self-limiting infections
Smoking doubles risk

Question 15

Genetics of Crohn’s

Answer 15

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 gene also CARD15 on Chr16 encodes a protein associated with to uncontrolled inflammatory response to luminal contents and microbes

Question 16

Clinical Features of CD

Answer 16

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 17

Distribution of CD

Answer 17

Small bowel alone – 40%
Large bowel alone – 30%
Small and large bowel – 30%

Question 18

Morphological features of CD

Answer 18

Fat wrapping of the serosa i.e. there is fat deposition on the anterior surface which is usually fat-free
Involves the bowel in a segmental manner where normal bowel is separated by abnormal bowel to give rise to skip lesions
Ulceration of the mucosa to give rise a cobblestone pattern
Strictures due to fibrosis

Question 19

Microscopic appearances 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

Complications of CD

Answer 20

Intra-abdominal abscesses
Deep ulcers lead to fistula = communication between two mucosal surfaces (e.g. colo-vesical fistula leads to pneumaturia/gas in the urine)
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 21

What is Ulcerative Colitis and epidemiology

Answer 21

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
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 olds

Question 22

Causes of UC

Answer 22

As with CD the cause of UC is unknown
Similar to CD multiple factors are implicated
Genetic predisposition 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
What about environmental factors?
oSmoking is protective in UC; cessation of smoking may trigger UC or activate disease in remission
oNSAIDs exacerbates UC
oAntioxidants Vitamins A & E are found in low levels in UC

Question 23

Clinical features of UC

Answer 23

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

Question 24

Macroscopic features of UC

Answer 24

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 25

Microscopic features of UC

Answer 25

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 26

Complications of UC

Answer 26

Usually lead to surgery
Refractory to medical treatment
Toxic megacolon = bowel grossly dilated
oPatient very ill, Bloody diarrhoea, Abdominal distention, Electrolyte imbalance with hypoproteinaemia.
Refractory bleeding
Dysplasia or adenocarcinoma in patients at risk:
oUC at an early age
oTotal unremitting UC.
After 8-10 years of UC patient require annual screening colonoscopy

Question 27

Extra-intestinal manifestations of CD & UC

Answer 27

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

Question 28

Investigations in CD & UC

Answer 28

FBC, U&Es, LFTs, inflammatory markers (CRP)
Faecal calprotectin
Endoscopy and biopsies
Radiological imaging
o Barium studies, MRI, USS, CT scan