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Inflammatory Bowel Diseases

Inflammatory Bowel Diseases. Ulcerative Colitis & Crohns disease. Are chronic inflammatory bowel diseases with protracted relapsing & remitting coarse. The incidence of ( IBD ) vary between population. The incidence of UC is 10/ 100000,while CD is 5-7/100000.

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Inflammatory Bowel Diseases

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  1. Inflammatory Bowel Diseases

  2. Ulcerative Colitis & Crohns disease • Are chronic inflammatory bowel diseases with protracted relapsing & remitting coarse. • The incidence of ( IBD ) vary between population. • The incidence of UC is 10/ 100000,while CD is 5-7/100000. • CD & UC had 2 peaks 1st in young & 2nd in 7th decade.

  3. Factors associated with the development of (IBD) • Genetic: • More common in Jews. • 10% have + ve FH of IBD. • High concordance between identical twins. • Associated with autoimmune thyroiditis & SLE. • Four regions of linkage on chromosomes 16, 12, 6 & 14 (IBD 1-4 ). • HLA-DR 103 associated with sever UC. • UC & CD with HLA-B27 commonly develop ankylosing spondylitis.

  4. Environmental: • UC is more common in non-smokers & ex- smokers. • CD most patients are smokers. • Associated with low residue ,high refined sugar diet. • Appendicectomy protects against UC.

  5. Pathogenesis Of IBD TRIGGER eNTEROCYTES MACROPHAGES tnf IL.1 Stim.cd4 IL8 Fibroblast activation Mast & plasma cell activation ADHESION MOLECULE SYS.SYM. NEUTROPHIL AGREGGATION Fibrosis ACTIVATION OF NEUTROPHILS INFLAMMATION

  6. Common patterns of IBD distribution: • Ulcerative colitis: • 40-50% proctitis or proctosigmoiditis. • 30-40% left sided colitis or extensive colitis . - 20% pan colitis.

  7. Crohns, disease: • 40% Ileal or ileocolonic. • 30-40% small intestinal. • 20% Crohns colitis. - <10% perianal disease (alone).

  8. Histopathology of IBDS • Ulcerative Colitis: -- The inflammatory process is limited to the mucosa .Acute & chronic inflammatory cells infiltrate the lamina propria & crypts ( Cryptitis ).Crypt abscesses are typical. -- Distorted Goblet cell which loss its mucus. -- Dysplasia : increased mitotic rate + nuclear atypia which herald the development of Ca colon.

  9. Crohn,s disease: --The whole wall of the intestine is oedematous & thickened ,There are deep ulcers which appear as linear fissures with normal mucosa between them ( cobblestone). -- Fistulae & ulcers. -- The lesion is patchy ( skip lesion ). -- Chronic inflammatory cell infiltrate the whole layers -- Microgranuloma (aggregate of histeocytes which surrounded by lymphocytes & contain giant cells). -- Aphthus ulcer.

  10. Clinical features of IBDS • Ulcerative Colitis: -- The 1st attack is most severe. -- Characterized by relapse & remission. -- Rarely chronic unremitting coarse.

  11. Precipitating factors for acute relapse: • Gastroenteritis. • Antibiotic. • NSAIDS. • Emotional stress. • Intercurrent infection.

  12. Proctitis: Rectal bleeding & mucous discharge some times with tenesmus ,no constitutional symptoms. • Proctosigmoiditis: bloody diarrhea with mucous ,Small no. of patients with v. active limited disease develop fever, lethargy & abdominal discomfort. • Extensive colitis: bloody diarrhea with passage of mucous, in sever cases anorexia , nausea ,weight loss & abdominal pain ,patient is toxic with fever & tachycardia & signs of peritoneal inflammation.

  13. Disease severity assessment in UC Mild severe • Daily Bowel frequency <4 >6 • Blood in stool +/- +++ • Stool volume <200 >400 • PR <90 >90 • Temperature Normal >37.8 • Sigmoidoscopy Normal or granular Blood in lumen • Abdominal XR Normal Dilated bowel & /or mucosal islands • Hb g/dl Normal <100 • ESR <30 >30 • S.Albumin g/l >35 <30

  14. Crohn ,s disease: • Ileal involvement: Abdominal pain which is associated with watery diarrhea (with out blood & mucous) + weight loss + features of protein & vitamines deficiencies. • Crohn ,s colitis: Like ulcerative colitis. *** Rectal sparing + Perianal disease*** • Small bowel & colonic disease. • Isolated Perianal disease. • Severe oral ulceration.

  15. Differences between UC & CD • 1-UC involve only the colon while CD involve any part of GIT. • 2-UC is continuous while CD is patchy. • 3-Rectum is always involved in UC while rectal sparing in CD. • 4-Histology:UC is superficial while CD affect all intestinal layers. • 5-Pathology:UC there is Cryptitis & Crypt abscess While CD there is granuloma. • 6-Presence of fistulae in CD > UC. • 7-Presence of Perianal lesions in CD > UC. • 8-Clinical presentation: bloody diarrhea in UC while in CD abdominal pain , wt. loss. • 9-UC is more in non/ex-smoker while CD more in smokers. • 10-Surgery is curative in UC & not in CD.

  16. Complications of IBD • Intestinal : • Severe colitis. • Perforation. • Hemorrhage. • Toxic megacolon. • Fistula. • Cancer of the colon.

  17. Extra intestinal: • Seronegative arthritis & Sacroilitis/Ankylosingspondylitis. • Ocular: *Conjunctivitis ,*Iritis ,*Episcleritis. • * Mouth ulcers. • Hepatic. *Fatty liver,Sclerosing cholangitis & cholangiocarcinoma,*Liver abscess & *portal pyemia • Renal.Amyloidosis & Oxalate calculi • Vascular.*DVT,*Mesenteric or *portal vein thrombosis • *Erythemanodosum,*Pyodermagangrenosum..

  18. Differential diagnosis of IBD • D.D of UC & Crohn ,s colitis: • Infective: • Bacterial: Salmonella, Shegella ,Campylobacter pylori • Viral: Herpes simplex proctitis, Cytomegalovirus. • Protozoal: Amoebaiasis.

  19. Non-Infective: • Vascular: Ischemic colitis, Radiation proctitis. • Idiopathic: Collagenous colitis. • Drugs: NSAIDs. • Neoplastic: Colonic carcinoma. • Other: Diverticulitis.

  20. D.D of small bowel CD: • Other causes of right iliac fossa mass. • Caecal carcinoma • Appendicular mass • Infection ( TB , Yesinia ,Actinomycosis ) • Mesenteric adenitis. • Pelvic inflammatory disease. • Lymphoma.

  21. Investigationsof IBDs. • Blood tests: HB,WBC ,ESR, CRP,S.albumin. • Bacteriology: Stool microscopy, culture,clostridiumdifficil toxin. Bl. Culture & serology.

  22. Endoscopy: Indications for endoscopy: • Disease extent . • Stricture ( biopsy ). • Filling defect. • Differentiation between UC & CD. • For follow up: Random biopsies for dysplasia or cancer for UC > 8ys. • Radiolog: --Barium studies.MRI,Plain X-Ray of abdomen,US

  23. Drugs used in treatment of IBDs • Aminosalysilates: (( Mesalasine, Olsalazine , Balsalazide)) Modulate cytokine release from mucosa Delivered to the colon by: 1-PH-dependent ( Asacol ) 2-Time-dependent ( Pentasa ) 3-Bacterial breakdown by colonic bacteria from carrier molecule ( Sulfasalazine, Olsalazine,Balsalized ).

  24. Corticosteroid Prednisolon , Hydrocortisone ,Budesonide. Anti-inflammatory ( topical, oral or I.V) • Thiopurines: Azothiopurine , 6-mercaptopurine Immunomodulation by inducing T-cell apoptosis. Is effective in 6-8ws after starting therapy.

  25. Methotrexate • Anti-inflammatory • SE:Intolerance in 10-18%, nausea , stomatitis, hepatotoxicity & pneumonitis. • Infliximab: • Chimeric anti-TNF monoclonal AB. • Given as I.V infusion 4-8 weekly. • Induce apoptosis of inflammatory cells • Uses: Moderately-severely active CD especially fistulating. Sever active UC. • Anaphylactic reaction after multiple infusions. • Contraindicated in presence of infection.

  26. Ciclosporine • Suppression of T cell expansion. • As rescue therapy to prevent surgery in UC responding poorly to corticosteroid. • No value in CD. SE:-Nephrotoxicity. -Neurotoxicity. -Hirsutism.

  27. Antibiotics Antibacterial. Useful in perianal CD. SE:Peripheral neuropathy in long term metronidazole. • Antidiarrhoeal agents: ( Codeine phosphate , Loperamide , lomotil) Avoided in moderately or severe active UC may precipitate colonic dilatation.

  28. Treatment of IBDs Treatment of Ulcerative Colitis: • Treatment of acute attacks( Induction of remission ). • Prevent relapses (Maintenance ).Sulfasalasine, Aminosalysilate. • Detect carcinoma at early stage. • Select patients for surgery.

  29. Active Proctitis: In mild to moderate disease: Mesalazine enema or suppositories combined with oral mesalazine . Topical corticosteroids are less effective& are used for patients who are intolerant of topical mesalazine. Patients who fail to respond are treated with prednisolone40mg daily.

  30. Active left-sided or extensive ulcerative colitis: • In mildly active cases: High dose Aminosalysilate Topical aminosalicylat & Corticosteroid • Oral prednisolon 40mg for more active disease & if no response to topical therapy. • Sever UC: Admission& managed by physician, surgeon. 1-Clinically: for presence of abd. Pain, Temp. , PR , stool bl.& frequency. 2-Lab. : Hb% , WBC count , Alb. , Electrolytes ,ESR & CRP. 3-Radiologically: For colonic dilatation on plain abd. XR

  31. Medical management of fulminant UC 1-I.V fluid. 2-Transfusion if Hb< 10gm/L. 3-I.V methylprednisolone ( 60mg daily ) or Hydrocortisone. 4-Antiboitic for proven infection. 5-Nutritional support. 6-Subcutanous heparin for prophylaxis of venous thromboembolism. 7-Avoidance of Opiates & Antidiarrhoeal agents. 8-I.V Ciclosporine ( 2mg/kg) or Infliximab ( 5mg/kg ) in stable patient not responding to steroid 3-5 days

  32. Indication for Urgent Colectomy • Colonic dilatation >6cm on plain abdominal X-Ray. • Lab. & Clinical deterioration. • No response after 7-10 days.

  33. Indications for Colectomy • Impaired quality of life. -Loss of occupation or education. -Disruption of family life. • Failure of medical therapy. -Dependence on corticosteroids. -Complications of drug therapy.

  34. Indications for Colectomy • Fulminant colitis. • Disease complications unresponsive to medical therapy. -Arthritis. -PyodermaGangerinosum. • Colon cancer or severe dysplasia.

  35. Maintenance of remission in UC: -Life-long treatment for all patients with extensive disease & distal disease with more than once per year relapse. -Oral Aminosalysilate ( Mesalasine or Balsalazide ) or Salazopyrine ( for patients with arthropathy ). • If no response Thiopurine.

  36. Medical treatment of CD • Active Colitis or Iliocolitis:Like UC ( AS + Steroid ). • Isolated Ileal:Corticosteroid( Budesonide) if no response surgery. Anti-TNF AB (Infliximab) : • I.V infusion 4-8 weekly on 3 occasions induce remission in patients with CD at any site of GIT • For refractory cases to steroid. • Heals enterocutanous fistulae & maintains longer remissions.

  37. Effective in the management of Pyoderma gangerosum & arthritis. • It is contraindicated in presence of infection like TB. • Relapse occur after 12 weeks so combine with Disease modifying drugs like methotrexate or thiopurine. • It cause remarkable mucosal healing---- scaring & stricturing so used with caution in stenosing disease.

  38. Extensive & diffuse iliocolonic: Drug therapy +Nutritional (Prolonged Parantral Nutrition )+Surgical Intervention +Endoscopic Balloon dilatation. Fistulating & Perianal disease: • -Metronidazol or Ciprofloxacin. • -Localize fistula by Ba. radiography , CT , MRI. • -Surgical treatment. • -Corticosteroid & nutritional therapy ( TPN ). • -Thiopurine for chronic disease. • -Infliximab infusion 4-8 weekly.

  39. Maintenance of remission in CD: 1-Smoking cessation. 2-Aminosalysilate have minimal efficacy. 3-Patients with relapse more than once per year: Thiopurine. 4-If patient intolerant to thiopurine or 6-mercaptopurine then use once weekly methotrexate + Folic acid. 5-More severe & aggressive disease: Combined immunomodulating agents + Infliximab.

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