Inflammatory Bowel Disease (IBD) :Inflammatory Bowel Disease (IBD) Dr S Sen SpR Paediatric Gastroenterology Booth Hall hospital


IBD :IBD Definition:- Comprised of two major disorders:- Ulcerative Colitis Crohn's Disease Indeterminate Colitis – has features of both conditions, unclassifiable after investigations into either of the above conditions. These disorders have distinct pathologic and clinical characteristics but their pathogenesis remains poorly understood.


Epidemiology :Epidemiology In the UK:- Incidence of UC: approx 10-20 per 100 000 per year Incidence of Crohn’s: approx 5-10 per 100 000 per year (Carter et al 2004) Incidence of IBD in children <16 yrs: 5.2 per 100 000 per year. In a study of 739 children in Great Britain and Ireland - 442 Crohn`s, 211 UC and 86 indeterminate colitis (Sawczenko & Sandhu 2003)


Epidemiology :Epidemiology In the UK:- Prevalence of UC: 100 – 200 per 100 000 Prevalence of Crohn’s: 50-100 per 100 000 (Carter et al 2004) Combined prevalence: 150-250 per 100 000 in Northern Europe (Baburajan & Parkes 2003) Common in Western developed countries but higher incidence in Ashkenazi Jews. Early studies show that the incidence in Asian immigrants is similar to that of the indigenous population (Bruce and Finlay 1997). In children, there was a significantly greater proportion of children of Asian origin <5 diagnosed with IBD (Sawczenko & Sandhu 2005)


Epidemiology :Epidemiology Peak incidence is between 10-40 years, however can affect any age, 15% being over 60 years at time of diagnosis (Carter et al 2004).


Epidemiology :Epidemiology


Pathophysiology :Pathophysiology It is still unclear what causes IBD, but researchers believe that a number of factors may be involved, such as:- environment diet possibly genetics IBD is thought to result from inappropriate & ongoing activation of the mucosal immune system driven by the presence of normal luminal flora


Pathophysiology :Pathophysiology Current evidence suggests that there is likely to be a genetic defect that affects how the immune system works and how the inflammation is turned on and off in those people with inflammatory bowel disease, in response to an offending agent, like:- bacteria a virus protein in food


Pathophysiology :Pathophysiology The aggregate effect of genetic, environmental and other processes is the sustained activation of mucosal immune responses


Pathophysiology :Pathophysiology


Pathophysiology :Pathophysiology Immune Response & Inflammatory Pathway Both UC and Crohn’s disease are characterized by a production of:- Mucosal IgG, T- and B-cell mucosal lymphocytosis and Macrophage activation during exacerbation of the disease


Ulcerative Colitis :Ulcerative Colitis Characterised by:- diffuse mucosal non-granulomatous inflammation limited to the colon & rectum. Distal UC relates to the rectum (proctitis), rectum & sigmoid colon (proctosigmoiditis). Extensive disease includes left sided colitis & pancolitis 40-50% of patients have disease limited to the rectum and rectosigmoid 30-40% of patients have disease extending beyond the sigmoid 20% of patients have a total colitis


Ulcerative Colitis :Ulcerative Colitis Macroscopic changes:- Mucosa is erythematous, has a granular surface that looks like sandpaper In more severe disease, the mucosa is haemorrhagic, oedematous and ulcerated In fulminant disease, a toxic colitis or a toxic megacolon may develop (wall becomes very thin and mucosa is severely ulcerated)


Ulcerative Colitis :Ulcerative Colitis Colonic Pseudopolyps


Ulcerative Colitis :Ulcerative Colitis The left side of the colon is affected. The image shows confluent superficial ulceration and loss of mucosal architecture.


Ulcerative Colitis :Ulcerative Colitis Microscopic Changes:- Process is limited to the mucosa and submucosa with deeper layer being unaffected Two major histologic features:- - the crypt architecture of the colon is distorted - some patients have basal plasma cells and multiple basal lymphoid aggregates


Ulcerative Colitis :Ulcerative Colitis Clinical features:- bloody diarrhoea frequency tenesmus passage of mucous abdominal cramps. blood and pus in the stools (can be significant) severe attacks - weight loss, fever, nausea, vomiting and anorexia


Ulcerative Colitis :Ulcerative Colitis Double contrast barium enema exam of the colon (lead pipe appearance)


Ulcerative Colitis :Ulcerative Colitis Complications:- Haemorrhage Perforation Stricture Toxic megacolon (transverse colon with a diameter of more than 5-6 cm with loss of haustration) Colorectal cancer risk By 10 years after onset about 5% of patients have developed colorectal cancer; the cumulative incidence is 20-25% at 20 years and 30-40% at 30 years.


Crohn’s Disease :Crohn’s Disease Characterised by:- patchy transmural granulomatous inflammation which may affect any part of the GI tract (mouth to anus). Most commonly affects distal ileum and proximal colon. 30-40% of patients have small bowel disease alone 40-55% of patients have both small and large intestines disease 15-25% of patients have colitis alone In 75% of patients with small intestinal disease the terminal ileum in involved in 90%


Crohn’s Disease :Crohn’s Disease Macroscopic changes:- transmural process segmental with skip areas in the midst of diseased intestine peri-rectal fistulas, fissures, abscesses and anal stenosis in 1/3 of patients cobblestone appearance active disease:- characterised by focal inflammation & formation of fistula tracts thickened bowel wall which becomes narrowed and fibrotic, leading to chronic, recurrent bowel obstruction


Crohn’s Disease :Crohn’s Disease Crohn’s colitis showing deep ulceration


Crohn’s Disease :Crohn’s Disease


Crohn’s Disease :Crohn’s Disease Radiological changes


Crohn’s Disease :Crohn’s Disease Clinical features:- diarrhoea weight loss & anorexia fever malaise abdominal pain apthous ulcers nausea & vomiting palpable mass (ileo-colitis) anorectal lesions – fissures, ulcers, fistulas


Crohn’s Disease :Crohn’s Disease Anorectal disease


Crohn’s Disease :Crohn’s Disease Complications:- intestinal obstruction ulcers fistula anal fissures malnutrition small risk of small bowel cancer


IBD :IBD Extra-intestinal manifestations:- 1/3 of patients Dermatological erythema nodosum, pyogenic gangrenosum Rheumatological arthritis, ankylosing spondylitis, sacroilitis Ocular anterior uveitis, episcleritis, iritis Urological calculi, ureteral obstruction, fistula Osteoporosis 2° to vit D def, Ca malabsorption, malnutrition, steroid use Cardiopulmonary endocarditis, myocarditis, pleuropericarditis, interstitial lung disease


IBD :IBD Iritis


IBD :IBD Erythema Nodosum


IBD :IBD Arthritis


IBD :IBD Investigations:- Laboratory FBC U&E’s LFT’s ESR Orosomucoid/CRP B12/Iron/Ferritin Immunological test


IBD :IBD Imaging CXR/AXR Barium enema Upper GI with small bowel follow through Procedures Endoscopy/Colonoscopy


Management :Management Polymeric Diet- ESPEN currently recommends enteral nutrition as first line therapy in active Crohn’s Disease.


Management :Management Drug Therapy Glucocorticoids effective for induction of remission, not for maintenance side effects 5-aminosalicylates (5-ASA) Sulphasalazine first agent discovered Group now includes: Pentasa (mesalazine), Asacol (mesalazine), Dipentum (olsalazine), Salazopyrin-EN (sulphasalazine) Work locally on the lining of the gut to reduce inflammation S/E - diarrhoea


Side-effects of steroids :Side-effects of steroids - Acne -“Moon” face - Hair growth -Obesity -Purple / red streaks (striae) -Muscle weakness -Depression -Anxiety -“Buffalo” hump Bruising -Bone thinning


Management :Management Immunosuppressant Azathioprine 6-mercaptopurine Methotrexate Interfere with inflammatory pathway Effective Up to 75% of patients brought into remission Slow Optimal effect often not seen until after 12 weeks of treatment Need close monitoring for toxicity Safety Methotrexate not to be used in pregnancy


Management :Management Biological Therapy Infliximab (Remicade) infusion – TNF alpha Ab Chimeric Monoclonal Antibody TNF-α is a key mediator of inflammation Neutralises TNF-α, thus beneficial in treatment of Crohn’s disease Hypersensitivity Allergic reaction at time of infusion – 5% Autoimmune syndromes Lupus like illness – rare and recovers on stopping on therapy Infection Profound immunosuppression occurs Opportunistic infections can occur Tuberculosis high risk Hepatitis B can be reactivated Cancer Recent data suggests that overall cancer rates may be reduced Hepatosplenic T-cell lymphomas – 1 in 20000 patients


Management :Management


Management :Management Total or supplementary parenteral nutrition Surgery


Thank you for Listening :Thank you for Listening


Slide 42:Thank You