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
Gluten consists of gliadin and glutenins
What genes are associated with coeliac disease?
Associated with HLA-DQ2 and HLA-DQ8 in 95% and 5% of the patients respectively
Which chromosome are the genes associated with coeliac disease located on?
Chr 6p21
What percentage approximately are genetically predisposed to coeliac disease
around 10% if first degree relatives
Where is coeliac disease most prevalent?
Most prevalent in western europe and US in patients of irish and scandinavian descent
Increasing incidence in Africa and Asia
What conditions do patients have that coincide with a high incidence of coeliac disease?
Down’s syndrome, Type 1 diabetes mellitus, auto-immune hepatitis and thyroid gland abdnormalities
How can coeliac disease be diagnosed?
Can present with abnormal liver function tests due to auto-immune hepatitis
How does gluten cause coeliac disease?
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
How does the microscopic appearance of the small bowel lining change as a result of coeliac disease?
Normal small bowel lining shows finger-like appearance.
Coeliac disease causes inflammation + flat lining
How does coeliac disease present?
Malabsorption of nutrients
Short stature and failure to thrive in children
Diarrhoea - smelly and bulky stool, rich in fat(steatorrhoea)
Weight loss and fatigue
Anaemia - folate and Fe deficiency
Osteopenia and osteoporosis - calcium and vitamin D deficiency
Classes of coeliac disease
Classical - malabsorption symptoms
Non-classical including symptoms outside the GI tract:
- constipation, bloating alternate bowel habits
- Heartburn, nausea, vomiting and dyspepsia(indigestion)
- Recurrent miscarriage/infertility
Sub-clinical - detected with blood tests
What are general investigations for coeliac disease?
FBC, U and Es(urea and electrolytes, LFTs(liver function tests)
What compounds are measured for in 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 and IgG
- 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 are tissue damage tests
There is overreaction of the immune system to produce antibodies to the proteins involved in tissue damage i.e antbodies to:
- tissue transglutaminase
- Endomysium
- Deamidated gliadin peptide
What are the microscopic features of coeliac disease?
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)
- Crypt hyperplasia
- Increase in lymphocytes in the lamina propria/chronic inflammation
- Increase in intrapeithelial lymphocytes (IEL)
Recovery of villous abnormality on gluten-free diet
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
How can you reduce the risk of complications arising in coeliac’s disease?
Gluten free diet may reduce the risk of complications such as T cell lymphoma
What is crohn’s disease?
An idiopathic, chronic inflammatory bowel disease often complicated by fibrosis and obstructive symptoms and can affect any part of the GIT
Describe the epidemiology of crohn’s disease?
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 teens-20s and 60-70 year age groups
Causes of crohn’s disease
Exact cause is unknown
Genetic, infectious, immunologic, environmental, dietary, vascular, smoking, NSAIDs and psychological factors
Defects in mucosal barriers
What are the genetics of crohn’s disease?
- First degree relatives have 13-18% increased risk of developing crohn’s 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 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
Possible infectious cause of CD
- As 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
What is the improved hygiene 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 responses to pathogens which cause self-limiting infections
This leads to an exaggerated immune response to whatever pathogen that causes crohn’s resulting in mucosal damage as the mucosa is not immunised to microbes
What are the other environmental factors implicated in crohn’s?
- migration from a low risk population to high risk population
- cigarette smoking doubles the risk of developing crohn’s
What effect does smoking have in ulcerative colitis?
Smoking is protective
What are the clinical features of crohn’s disease?
- 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
- Weight loss, low grade fever
What is the distribution of crohn’s disease?
- Any part of GIT from mouth to anus
- Small bowel alone is 40%
- Large bowel alone is 30%
- Small and large bowel is 30%
What are the morphological features of crohn’s disease?
- 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
What are the microscopic appearances of crohn’s disease?
- 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
Complications of crohn’s disease?
- Intra-abdominal abscesses
- Deep ulcers lead to fistula = communication between two mucosal surfaces
- Sinus tract = blind ended tract
- Obstruction due to adhesions
- Obstruction due strictures caused by increased fibrosis
Perianal fistual and sinuses - Risk of adenocarcinoma(but not as high as in UC)
What is ulcerative colitis?
- Ulcerative colitis is a chronic inflammatory bowel disease which only affects the large bowel from the rectum to the caecum
What is the difference in the inflammatory process of ulcerative colitis and crohn’s disease?
The inflammatory process in ulcerative colitis is confined to the mucosa and sub-mucosa except in severe cases
Describe the epidemiology of ulcerative colitis?
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
What causes ulcerative colitis?
- Cause is unknown
- High incidence of ulcerative colitis in first degree relatives and high concordance in twins
- HLA-B27 identified in most patients with ulcerative colitis, but not thought to be an aetiological factor
What environmental factors can cause ulcerative colitis?
- Smoking is protective in ulcerative colitis; cessation of smoking may trigger ulcerative colitis or activate disease in remission
- NSAIDs exacerbates ulcerative colitis
- Antioxidants vitamins A and E are found in low levels in ulcerative colitis
What are the clinical features of ulcerative colitis?
- Intermittent attacks of bloody diarrhoea
- Mucoid diarrhoea
- Abdominal pain
- Low grade fever
- Loss of weight
What are the macroscopic features of ulcerative colitis?
- 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
- No ulcers
- Diffuse mucosal involvement which appears haemorrhagic
- With chronicity, the mucosa becomes flat with shortening of the bowel
What are the microscopic features of ulcerative colitis?
- Inflammation confined to the mucosa
- Diffuse mixed acute and 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 are the complications of ulcerative colitis?
- Rrefractory to medical treatment
- Toxic megacolon = bowel grossly dilated
- Patient very ill
- Bloody diarrhoea
- Abdominal distention
- Electrolyte imbalance with hypoproteinaemia
- Refractory bleeding
- Dysplasia or adenocarcinoma
- UC at an early age
- Total unremitting UC
- 8-10 years of ulcerative colitis
- Patients requires annual screening colonscopy
What are the extra-intestinal manifestations of crohn’s disease and ulcerative colitis?
- Ocular - uveitis, iritis, episcleritis
- Cutaneous - erythema nodosum, pyoderma gangrenosum
- Arthopathies - ankylosing spondylitis and others
- Hepatic - screlosing cholangitis
What are the investigations in crohn’s disease and ulcerative colitis?
- FBC
- U and Es
- LFTs
- Inflammatory markers - C reactive protein
- Endoscopy and biopsies
- Radiological imaging
Barium studies, MRI, USS and CT scan
Differences between crohn’s disease and ulcerative colitis
- Bleeding is occasional in CD and very common in UC
- Obstruction is common in CD and uncommon in UC
- Fistula is common in CD and non-existent in UC
- Weight loss is common in CD and uncommon in UC
- Perinanal disease is common in CD and rare in UC
- Distribution is in entire GIT with skip lesions in CD and only in the large bowel and continuous in UC
- Full thickness, fissuring ulcers, granulomas 60-65%, crypt architecture preserved in CD but mucosa only, no ulcers early stages, no granulomas, crypt architecture distortion
- Skip lesions, fistula abscess and fibrotic strictures in CD and continuous process in UC Radiology
- Cancer risk is increased in CD and is much higher 1% at 10yrs of diag
- Smoking makes CD worse and is protective in UC
