Coeliac disease and inflammatory bowel disease Flashcards
What is coeliac disease?
- 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
What is gluten?
•Gluten is a protein compound of wheat, rye and barley which is left behind after washing off the starch
What does gluten consist of?
•Gluten consists of gliadin and glutenins
What are the Genetic Abnormalities of Coeliac Disease ?
- 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
Who gets coeliac disease?
- Most prevalent in Western Europe and USA especially in patients of Irish and Scandinavian descent
- Increasing incidence in Africa and Asia
High prevalence of coeliac disease in patients with Down’s syndrome, Type I diabetes mellitus, auto-immune hepatitis and thyroid gland abnormalities
Why does coeliac disease require a high index of suspision?
•A lot of patients in the community have undiagnosed coeliac disease
What is the most common age of presentation of coeliac?
• Bimodal presentation in childhood and late thirties
•Approximately _____% of patients with coeliac disease are older than 60years
20%
How does gluten cause coeliac disease?
What does this show?
Normal Small Bowel Lining with Finger-like Villi
What does this show?
INFLAMMATION + FLAT LINING
How does coeliac disease cause symptoms?
•Flat mucosa does not absorb nutrients and leads to symptoms of coeliac disease
What are the 3 types of coeliac disease symptoms?
- Asymptomatic coeliac disease - detected by a blood test
- Classical coeliac disease
- Atypical coeliac disease
What are the classical coeliac disease symptoms?
- Diarrhoea 45 – 85% of patients
- Diarrhoea : 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
What is this?
Classic presentation of coeliac disease: steatorhoea – bulky, pale offensive stool
What are the symptoms of atypical coeliac disease?
- 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
What is an atypical presentation of coeliac disease?
- Emaciation
- Pot belly due to gaseous distention
- Muscle wasting
- Osteoporosis
What are the investigations for coeliac disease?
- General investigations: FBC, U & Es, LFTs
- Serology for diagnosis of coeliac disease
- HLA DQ2 & HLA DQ8 in children with positive TTGA and symptoms to avoid biopsies
- Duodenal biopsies
How can serology be used to diagnose 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
How do routine coeliac disease tests work?
- They 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
What are the Microscopic features of Coeliac disease?
- On microscopy 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
How many biopsies should be sampled from the duodenum for coeliac disease?
•At least four biopsies should be sampled from the duodenum at upper GIT endoscopy as changes can be patchy
What does this show?
What does this show?
•Increase in intraepithelial lymphocytes (IEL)
What are the complications of coeliac disease?
- 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
What is the result of a gluten-free diet?
•Gluten free diet may reduce risk of complications
Name the conditions included in inflammatory bowel disease
- Crohn’s Disease (CD)
- Ulcerative Colitis (UC)
- Diverticular disease
- Ischaemic colitis
- Drug-induced colitis – NSAIDs
- Infective colitis
What is idiopathic inflammatory disease?
•CD & UC = collectively known as idiopathic inflammatory disease (IBD)
Why is it important to distinguish CD from UC?
•Important to distinguish CD from UC because of different complications and different surgical procedures
What is Crohns Disease?
- 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
- Described by Crohn Ginzburg in 1932 but not distinguished from UC until 1959
Who is at risk of CD?
- High prevalence in the Western world with increased incidence in patients of Jewish origin
- Increasing incidence in Africa, South America and Asia
What is the most common age of presentation of CD?
•Bimodal presentation with peaks in the teens-20s and 60-70 year olds
What causes CD?
- The exact cause is unknown
- 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
What are the genetics of CD?
- 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
Is there a possible infectious cause of CD?
- 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
What is the improved hygeine hypothesis?
•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.
What are the environmental factors in CD?
- Migration from a low risk population to high risk population increases the risk of developing CD
- Cigarette smoking doubles the risk of developing CD
What are the clinical features of CD?
- 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
What is the distribution of CD thoughout the digestive tract?
- Affects any part of GIT from mouth to anus
- Small bowel alone – 40%
- Large bowel alone – 30%
- Small and large bowel – 30%
What are the morphological features of CD?
- 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
Why can fat wrapping be useful?
Fat wrapping in CD at the time of Surgery can assist the Surgeon to demarcate the extend of the disease is the small bowel
What does this show?
Fat wrapping in CD
What does this show?
What does this show?
Cobblestone Pattern in Colonic CD
What does this show?
Fibrosis and long stricture of terminal ileum
What are the microscopic appearances of CD?
- 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
What does this show and what is the arrow pointing at?
Transmural inflammation in CD
What are the complications of CD?
- 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
What is Ulcerative Colitis (UC)?
•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.
Where is there a high prevalance of UC?
- More common in Western countries with higher prevalence in patients of Jewish descent
- Less frequent in Africa, Asia and South America
What is the most common age of presentation for UC?
- 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
What causes UC?
- 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
- Similar to CD no specific infective agent has been identified
What is the genetic predisposition of UC?
- 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
Which environmental factors link to UC?
- 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
What are the clinical Features of UC?
- Intermittent attacks of bloody diarrhoea
- Mucoid diarrhoea
- Abdominal pain
- Low grade fever
- Loss of weight
What are the macroscopic features of UC?
- 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
What is the distribution of UC in GI tract?
- 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
What does this show?
The mucosa looks red and flat
UC
What are the microscopic features of UC?
- 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
What is the diagnosis?
UC
What does this show?
Crypt architecture distortion in UC
What are the complications of UC?
Complications invariably lead to surgery
- Refractory to medical treatment
- Toxic megacolon = bowel grossly dilated
- Patient very ill
- Bloody diarrhoea
- Abdominal distention
- Electrolyte imbalance with hypoproteinaemia
- Refractory bleeding
- Dysplasia or adenocarcinoma in patients at risk:
- UC at an early age
- Total unremitting UC
When does a UC patient recieve bowel cancer screening?
•After 8-10 years of UC patient require annual screening colonoscopy
What does this show?
Toxic Megacolon: bowel dilated and haemorrhagic
From UC
This patient has had long standing UC
What does this show?
Early cancer in long standing UC
What are the extra-intestinal manifestations of CD & UC?
- Ocular - uveitis, iritis, episcleritis
- Cutaneous - erythema nodosum, pyoderma gangrenosum
- Arthropathies - ankylosing spondylitis
- Hepatic - screlosing cholangitis
What are the investigations in CD & UC?
- FBC
- U & Es
- LFTs
- Inflammatory markers – C reactive protein (CRP)
- Faecal Calprotectin
- Endoscopy and biopsies
- Radiological imaging
- Barium studies
- MRI
- USS
- CT Scan
Complete the table on the differences between UC and CD
Complete the table on the differences between CD and UC
Do CD or UC patients have a pouch after surgery?
- 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.
