Coeliac disease and inflammatory bowel disease Flashcards
Coeliac disease
Gluten sensitive enteropathy or coeliac sprue
Auto- immune mediated disease of the small intestine triggered by ingestion of gluten
Malabsorption
Gluten
Protein compound of wheat, rye and barley left behind after washing off the starch
Consists of gliadin and glutenins
Genetic abnormalities od coeliac disease
Associated with HLA-DQ2 and HLA-DQ*
Genes located in Chr 6p21
Strong hereditary predisposition affecting ~ 10% first degree relatives
Who gets coeliac disease?
Most prevalent in western europe and united states
Down’s syndrome, type 1 diabetes mellitus, auto- immune hepatitis and thyroid gland abnormalities
How does gluten cause coeliac disease?
Gluten in wheat + small bowel mucosa
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Tissue transglutaminase
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Diamidates glutamine in gliadin
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Negatively charged protein
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IL-15
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Natural killer cells + intraepithelial T lymphocytes
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Tissue destruction + villous atrophy
How does coeliac disease present?
Short stature and failure to thrive in children
Diarrhoea: smelly and bulky stool, rich in fat
Weight loss and fatigue
Anaemia- folate and Fe deficiency
Ostopenia and osteoporosis- calcium and vitamin D deficiency
Classification of coeliac disease
Classical- malabsorption symptoms
Non- classical symptoms outside GI tract
- constipation, bloating alternate bowel habits
- heartburn, nausea, vomiting and dyspepsia
- recurrent miscarriage/ infertility
Investigations for coeliac disease
General: FBC, U and Es, LFTs
Serology:
- tissue transglutaminase
- endomysial IgA- connective tissue covering smooth muscle fibres
- deamidated gliadin peptide IgA and IgG
- sero negative coeliac disease
HLA D2 and HLA DQ8 in children
Duodenal biopsies
Microscopic features of coeliac disease
At least four biopsies sampled from duodenum at upper GIT endoscopy
On microscopy:
- villous atrophy
- crypt hyperplasia
- increase in lymphocytes in the lamina proporia
- increase in intraepithelial lymphocytes
- recovery of villous abnormality on gluten free diet
Complication of coeliac disease
Enteropathy associated T-cell lymphoma
High risk of adenocarcinoma of small bowel and other organs
Associated with dermatitis hepetiformis
Infertility and miscarriage
Refractory coeliac disease despite strict adherence to gluten free diet
What constitutes inflammatory bowel disease?
Crohn’s disease
Ulcerative colitis
Diverticular disease
Ischaemic colitis
Drug induced colitis
Infective colitis
CD and UC
Crohn’s disease
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 of Crohn’s disease
High prevalence in 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 CD?
Exact cause unknown
Genetic, infectious, immunological, environmental, dietary, vascular, smoking, NSAIDs and psychological factors
Defects in mucosal barriers
Genetics of Crohn’s disease
First degree relative have 13-18% increased risk
NOD2 known as IBD1 gene on Chr16 encodes protein that binds to intercellular bacteria peptoglycans
Possible infectious cause of Crohn’s
Granulomas present in 60-65% patients
Mycobacterium para-tuberculosis extensively investigated but never proven
Other infectious organisms- measles virus, pseudomonas, listeria- never proven
Environmental factors implicated in Crohn’s disease
Improved hygiene hypothesis- reduces ability of GIT mucosa to develop regulatory process that would normally limit immune response to pathogens which cause self limiting infectiouns
Migration from low risk population to high risk population
Cigarette smoking doubles risk
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 colon involved
Loss of weight, low grade fever
Morphological features of Crohn’s disease
Fat wrapping around serosa
Typically segmental morphology- normal bowel separated by abnormal bowel
Ulceration with a cobblestone pattern
Strictures due to fibrosis
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
Granulomas present in 60-65%
Fibrosis of the wall
Complications of Crohn’s disease
Intra-abdominal abscesses
Deep ulcers lead to fistula
Sinus tract
Obstruction due to adhesions
Obstruction due to strictures caused by increased fibrosis
Perianal fistula and sinuses
Risk of adnemocarcinoa
Ulcerative colitis
Chronic inflammatory bowel disease only affects large bowel from the rectum to the caecum
Confined to the mucosa and sub-mucosa except in severe cases
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 age 10
Peaks between 20-25 with small peak in 55-65
What causes ulcerative colitis?
Unknown
Genetic not as well defined as in CD
Smoking is protective
NSAIDs exacerbates it
Antioxidants vitamins A and E found in low levels
Clinical features of ulcerative colitis
Intermittent attacks of bloody diarrhoea
Mucoid diarrhoea
Abdominal pain
Low grade fever
Loss of weight
Macroscopic features of ulcerative colitis
Large bowel from rectum to caecum
Affect rectum only, left sided bowel only or whole large bowel
No ulcers on endoscopic examination in early disease
Mucosa becomes flat with shortening of the bowel
Microscopic features of ulcerative colitis
Inflammation confined to mucosa
Diffuse mixed acute and chronic inflammation
Crypt architecture distortion
In quiescent, mucosa may be atrophic with little or few inflammatory cells in the lamina proporia
Complications of ulcerative colitis
Toxic megacolon- bowel grossly dilated
- patient very ill
- bloody diarrhoea
- abdominal distention
- electrolyte imbalance with hypoproteinaemia
Refractory bleeding
Dysplasia or adenocarcinoma
- UC at early age
- total unremitting UC
- after 8-10 years UC
- requires annual screening colonoscopy
Extra-intestinal manifestations of CD and UC
Ocular- uveitis, iritis, episcleritis
Cutaneous- erythema . nodosum, pyoderma gangrenosum
Arthropathies- ankylosing spondylitis and others
Hepatic- screlosing cholangitis
Investigations in CD and UC
FBC
U and E’s
LFTs
Inflammatory markers- C reactive protein
Endoscopy and biopsies
Radiological imaging
- barium studies
- MRI
- USS
- CT scan
