Inflammatory Bowel Disease Lecture Notes PDF

# Inflammatory Bowel Disease ## Introduction - Inflammatory bowel disease (IBD) represents a group of intestinal disorders that cause prolonged inflammation of the digestive tract. - It is a spectrum of chronic idiopathic inflammatory condition. ## Classification - **Ulcerative Colitis:** Ulcerati...

# Inflammatory Bowel Disease ## Introduction - Inflammatory bowel disease (IBD) represents a group of intestinal disorders that cause prolonged inflammation of the digestive tract. - It is a spectrum of chronic idiopathic inflammatory condition. ## Classification - **Ulcerative Colitis:** Ulcerative colitis is a disease that causes mucosal inflammation and sores (ulcers) in the lining of the large intestine (colon). - **Chron's Disease:** Crohn's disease is a chronic, relapsing and remitting inflammatory disease of the gastrointestinal tract, affecting any site from mouth to anus. ## Epidemiology - In the United States, it is currently estimated that about 1 - 1.3 million people suffer from IBD. - Ulcerative colitis is slightly more common in males, while Crohn's disease is more frequent in women. - Diet, oral contraceptives, perinatal and childhood infections, or atypical mycobacterial infections have been suggested, but not proven, to play a role in developing IBD. ## Etiology - **Infectious Agents** - Viruses (Measles) - Bacteria (Mycobacteria) - **Genetics** - **Environmental Factors** - Diet - Smoking - **Psychological Factors** - Stress - Emotional or physical trauma ## Pathophysiology - **ALtered Mucosal Immune Response** - Dietary and bacterial antigens penetrate into the intestinal wall and activates the immune system. - This causes increased production of pro-inflammatory mediators which will lead to inflammation of the mucosal layer. ## Clinical Manifestations - Clinical symptoms are the same in both cases. - Diarrhoea - Abdominal pain, cramping & bloating due to bowel obstruction - Hematochezia: Blood in stool - Low fever - Decreased appetite - Weight loss and anorexia - Fatigue - Arthritis ## Diagnosis - Physical Examination - Endoscopy - Biopsy - Radiology - Blood Test ## Physical Examination - The main features to look for are: oral aphtosis, abdominal tenderness and masses, anal tags, fissure and fistulae, nutritional deficiency. - An important feature in children is growth retardation. ## Endoscopy/Colonoscopy/Sigmoidoscopy - Colonoscopy helps to determine the pattern and severity of colonic and terminal ileum inflammation and allows biopsies to be obtained. - Endoscopic features are aphtous ulcers, deeper ulceration, postinflammatory polyps (which indicate previous severe inflammation), but always accompanied by intervening normal mucosa, which is an important differential feature between CD and UC. ## Biopsy - Rectal and colonic biopsies should be examined to find the nature of the inflammation (ulcerative colitis versus CD), collagenous colitis or microscopic inflammation if macroscopic appearance is normal, and infection. ## Radiology - **Barium Enema** - Barium inserted into rectum - Fluoroscopy used to image bowel - Rarely used due to colonoscopy - Useful for identifying colonic strictures or colonic fistulae - **Barium Small bowel follow-through X-ray** - Barium sulfate suspension drink - Fluoroscopic images of bowel taken over time - Useful for looking for inflammation and narrowing of small bowel ## Blood Test - Anemia may be present due to blood loss (iron deficiency), chronic inflammation or B12 malabsorption (macrocytic). - Hypoalbuminemia suggests severe disease with denutrition. The best markers of inflammation severity are elevation of the C-reactive protein and platelet count. - Anti-saccharomyces cerevisiae antibodies (ASCA) are positive in 50-60% of CD patients while anti-neutrophil polynuclear antibodies (ANCA) are positive in 50-60% of UC patients. ## Crohn's Disease vs Ulcerative Colitis | Feature | Crohn's Disease | Ulcerative Colitis | |---|---|---| | Terminal ileum involvement | Commonly | Seldom | | Colon involvement | Usually | Always | | Rectum involvement | Seldom | Usually | | Involvement around the anus | Common | Seldom | | Bile duct involvement | No increase in rate of primary sclerosing cholangitis | Higher rate | | Distribution of Disease | Patchy areas of inflammation (Skip lesions) | Continuous area of inflammation | | Endoscopy | Deep geographic and serpiginous (snake-like) ulcers | Continuous ulcer | | Depth of inflammation | May be transmural, deep into tissues | Shallow, mucosal | | Fistulae | Common | Seldom | | Stenosis | Common | Seldom | | Autoimmune disease | Widely regarded as an autoimmune disease | No consensus | | Cytokine response | Associated with T17 | Vaguely associated with T2 | | Granulomas on biopsy | May have non-necrotizing non-peri-intestinal crypt granulomas | Non-peri-intestinal crypt granulomas not seen | | Surgical cure | Often returns following removal of affected part | Usually cured by removal of colon | | Smoking | Higher risk for smokers | Lower risk for smokers | ## Goals of Treatment - Maintain or improve quality of life. - Terminate the acute attack and induce clinical remission. - Prevent symptoms during chronic symptomatic periods. - Prevent or reduce complication. - Use the most cost-effective drug treatment. - Avoid surgery if possible. - Replacement of vitamin A, D, K if necessary in case of malabsorption. ## Non-Pharmacological Treatment - To avoid smoking cessation - To reduce alcohol consumption - To avoid the use of NSAIDs - To avoid spicy and fried/oily food - To take fiber rich diet as tolerated that include tender cooked vegetables, canned or cooked fruits, and starches like cooked cereals and whole wheat noodles and tortillas. - To incorporate more omega-3 fatty acids in the diet. These fats may have an anti-inflammatory effect. They are found most probably in fish. ## Inflammatory Bowel Disease: Treatment - **Severe** - Surgery - Biologics (e.g., infliximab) - **Moderate** - Corticosteroids - Immunomodulators: 6-MP, AZA, MTX - **Mild** - Antibiotics - Aminosalicylates ## Pharmacological Treatment The major types of drug therapy used in IBD include - Aminosalicylates - Corticosteroids - Immunosuppressive agents - TNF - Tumor Necrosis Factor Inhibitor - Antimicrobials ## Aminosalicylates / 5-ASA - These agents have anti-inflammatory effects. They are used to maintain remission and to induce remission of mild flares of disease. - Egs., Sulfasalazine, Mesalamine - Sulfasalazine and mesalamine are used to treat mild to moderate disease and to maintain remission induced by corticosteroids. - Sulfasalazine is useful for ileocolonic and colonic disease. - The side effects are hemolytic anemia & pruritic dermatitis. - Pentasa is a recently developed sustained-release preparation (coated with ethylcellulose) that delivers 5-ASA to the distal ileum and colon. ## Corticosteroids - Corticosteroids (I mg/kg/day) are effective in decreasing disease activity and inducing remission in most patients. However, due to undesirable side effects, long-term use of corticosteroids is not recommended. - Oral or parenteral corticosteroids are indicated for the treatment of ambulatory patients with moderate to severe colitis whose symptoms cannot be controlled by aminosalicylates. - The adverse effects include cosmetic effects, suppression of linear growth in children and osteopenia. - Egs., Prednisolone, Budenoside ## Immunosupressive Agents - If it is impossible to taper corticosteroids or frequent relapses occur, immunomodulating therapy should be considered. However, the use of immunomodulators is not approved by the national health insurance scheme. - Azathioprine and 6-mercaptopurine are used due to their steroid-sparing or steroid- reducing effects, since approximately 50% of patients experience adverse effects from corticosteroids. - Due to delayed onset of action, these agents are not used to treat acute colitis. - Cyclosporine and tacrolimus have been used to treat acute steroid-refractory UC when surgery seemed inevitable. ## TNF Inhibitors - Increased production of inflammatory cytokines, especially tumor necrosis factor alpha (TNF-α), has been described in both normal and inflamed mucosa. - These agents prevent the endogenous cytokine from binding to the cell surface receptor and exerting biological activity. These agents adversely affect normal immune responses. - Thalidomide, originally used for its sedative and antiemetic properties, has recently been shown to inhibit TNF-α production by monocytes and other cells. - Infliximab is a chimeric mouse-human monoclonal antibody to TNF. It binds free and membrane-bound TNF and thus prevents the cytokine from binding to its cell surface receptor. ## Antimicrobial Agents - Metronidazole and ciprofloxacin are useful in the treatment of mild to moderate disease, particularly in patients with perianal disease and infectious complications. - Sensory neuropathy, which may be seen with long-term metronidazole use, usually resolves completely or improves after discontinuation of the drug.