LOWER GI DISEASE- IBD

*2 inflammatory disorders of the GI tract- Crohn’s D and Ulcerative C *Chronic disease that follows unpredictable relapsing and remitting. *10-15% of UC & CD= Difficult to distinguish

Crohn’s Disease: -Affects ANY part of GI M-R -Inflammation extends through all layers of the gut wall -Inflammation = PATCHY in distribution Ulcerative Colitis: -Affects only COLON and RECTUM -Affects ONLY Mucosa and Submucosa -Inflammation is diffuse in Distribution

Common=Industrialised countries, all races and both sex Peak incidence= 10-40yrs, 15% = over 60yrs, Occur any age 1/250 = affected in UK Rapid increase incidence bet 1955-75 (CD)= now stabilised

CD: -5-10 per 100,000 population per year -Prevalence of 50-100 cases per 100,000 population -More common = FEMALES, occurs in younger age + mean age of onset = 26 years!! M:F = 1:1.2 UC: -10-20 per 100,000 population per year - Prevalence of 100-200 cases per 100,000 population - Common = Males, Occurs = Older age, Mean age = 35 years. M:F = 1:2.1

• Causative agent = Unknown -Diet (fat, fast food indigestion, milk, fibre, R carbs) -Smoking (Increase risk of relapse and need for surgery) -Infection (Mycobacterium Paratuberculosis = CD Associated with measles & mumps infection • Enteric Microflora ( IBD patients- Loss of immunological tolerance to intestinal microflora). Manipulated by antibiotics Drugs ( NSAIDs can exacerbate IBD , Antibiotics, Oral contraceptive pill- increase risk of CD, Isotretinoin-acne) Appendectomy: protective effect in UC and UC Stress: can trigger relapse in IBD, Activate inflammatory mediators at enteric nerve ends in guy wall

• Mutations of the gene CARD15/NOD2 located on chromosome 16 – Associated with small intestine CD in white populations • The genes OCTNI on chromosome 5 and DLG5 on chromosome 10 have also been linked to CD • 70% of UC patients – Have anti-neutrophil cytoplasmic antibodies (pANCA) • ? Autoimmune component – Association between IBD, ankylosing spondylitis & histocompatibility antigen HLA-B27

• Ethical factors: – Jews are more prone than non-Jews – IBD incidence is lower in non-white races • Familial factors: – First-degree relatives of those with IBD have up to 20-fold increase in developing the disease – 15-fold greater concordance for IBD in identical twins than non-identical twins

– Disruption of epithelial barrier integrity – Deficits in autophagy – Deficiencies in innate pattern recognition receptors – Problems with lymphocyte differentiation, especially CD

-40% of CD patients are smokers (10% UC) • Smoking may help to prevent the onset of UC – Chemicals affect colon smooth muscle • Alters gut motility & transit time

– Increased activity of effector lymphocytes & proinflammatory cytokines that override normal control mechanisms – Primary failure of regulatory lymphocytes & cytokines – In CD, T cells are resistant to apoptosis after inactivation

One or multiple areas ( affected areas are thickened, oedematous and narrow) -Deep ulcers can appear – Mucous membrane between fissures has a cobblestone appearance – Can progress to deep fissuring ulcers, fibrosis & strictures -Can lead to bowel obstructions, abscesses and guy perforations Usually Terminal ileum & ascending colon Discontinuous

– Non-specific granulomatous inflammation – Inflammation extends throughout all layers of the bowel (transmural) – Inflammatory cells are seen throughout – lymphocytes and plasma cells – Th1-associated Chronic inflammation leads to an increased risk of cancer

• At first presentation: – 40%- rectum (proctitis) – 40% - sigmoid & descending colon (left-sided colitis) – 20% - whole colon • Only the mucosa & submucosa are affected • Continuous, starting in rectum • Formation of crypt abscesses & mucosal ulceration • Mucosa looks red, inflamed & bleeds easily – Purulent & granular with superficial ulceration – Pseudo polyps in severe inflammation

Microscopically: – Inflammatory cells infiltrate the lamina propria & crypts – Th2-associated – Dysplasia can be seen from biopsies * Can progress to carcinomas

IBD – depends on site, extent & severity of active disease

– Diarrhoea – Fever – Abdominal pain – Nausea & vomiting(more common in CD) – Malaise – Lethargy – Weight loss (more common in CD) – Malabsorption – Growth retardation in children

• Tends to be more disabling than UC • Onset can be acute or insidious • Other symptoms can include: – Pain (particularly LRQ) – Anaemia – Palpable masses – Small bowel obstructions – Abscesses – Fistulas – Gut perforation

• Symptoms – Diarrhoea – possibly with blood/mucus • Up to 10-20 liquid stools a day – Abdominal pain (cramps) with fever – Constipation • 50% of UC patients have a relapse each year – Severe attacks can be life-threatening

• Joints and Bones – Arthropathies & Osteopenia • Skin – Erythema nodosum (Tender, hot, red nodules – subside over a few days to leave brown skin discolouration) – Pyoderma gangrenosum (Pustule–develops into an ulcer) • Ocular – Episcleritis (Intense burning & itching of blood vessels involved) – Uveitis ( Headache, burning red eye, blurred vision • Sclerosing Cholangitis – Chronic inflammation of the biliary tree – Leads to progressive fibrosis & biliary strictures

• Quality of life generally lower in CD vs UC, especially because of recurrences after surgery • Increased risk of peritonitis and malignancy • Malnutrition and chronic anaemia common in long-standing CD

• Confirmed by clinical evaluation & a combination of investigations: – Biochemical – Endoscopic – Radiological – Histological – Nuclear medicine based

• Full history including: – Recent travel – Medication – Smoking – Family history • Details of symptoms including: – Stool frequency & consistency – Urgency – Rectal bleeding – Abdominal pain – Fever

Physical signs: – General well-being – Pulse – Blood pressure – Temperature – Weight loss – Abdomen tenderness or distension * Right iliac fossa mass – Anus *Oedematous anal tags, fissures or perianal abscesses

• Blood tests – Anaemia is common – Deficiency of iron and/or folate also occurs – Raised ESR & CRP & a raised WCC – Hypoalbuminaemia – LFTs may be abnormal • Microbiological testing for infectious diarrhoea • Serological tests – Saccharomyces cerevisae antibody usually present in CD – p-ANCA antibody • -ve in CD & +ve in UC