Coeliac Disease & Inflammatory Bowel Disease Flashcards
What is coeliac disease?
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 coeliac disease otherwise known as?
Gluten sensitive enteropathy or coeliac sprue
What is found in gluten?
Gluten consists of gliadin and glutenins
What is gluten?
Gluten is a protein compound of wheat, rye and barley which is left behind after washing off the starch
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 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
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 coeliac disease present?
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
Name the 3 types of classified coeliac disease
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
What are the investigations for coeliac disease?
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
How do routine coeliac disease tests work?
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
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)- 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
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
Gluten free diet may reduce risk of complications
What constitutes as inflammatory bowel disease?
Crohn’s Disease (CD) Ulcerative Colitis (UC) Diverticular disease Ischaemic colitis Drug-induced colitis – NSAIDs Infective colitis CD & UC = collectively idiopathic inflammatory disease (IBD)
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 from mouth to anus
What is 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 the teens-20s and 60-70 year age groups
What causes crohn’s disease?
The exact cause is unknown
Genetic, infectious, immunologic, environmental, dietary, vascular, smoking, NSAIDs and psychological factors – all have been implicated
Defects in mucosal barriers
What are the genetics of crohn’s disease?
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
Is there a possible infectious cause of crohn’s disease?
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
Describe the improved hygiene hypothesis implicated in crohn’s disease
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.
Describe some other environmental factors that are implicated in crohn’s disease
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)
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
Loss of weight, low grade fever
What is the distribution of crohn’s disease?
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 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
What are the complications of crohn’s disease?
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
What is ulcerative colitis?
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.
What is 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?
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
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
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 are the microscopic features of ulcerative colitis?
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 are the complications of ulcerative colitis?
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
What are the extra-intestinal manifestations of ulcerative colitis and crohn’s disease?
Ocular - uveitis, iritis, episcleritis
Cutaneous - erythema nodosum, pyoderma gangrenosum
Arthropathies - ankylosing spondylitis and others
Hepatic - screlosing cholangitis
What investigations are carried out during crohn’s disease and ulcerative colitis?
FBC U & Es LFTs Inflammatory markers – C reactive protein (CRP) Endoscopy and biopsies Radiological imaging Barium studies MRI USS CT Scan
Why is it important to distinguish between ulcerative colitis and crohn’s disease?
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.
