Inflammatory Bowel Disease Overview

Inflammatory Bowel Disease (IBD)

• IBD is a group of chronic inflammatory conditions of the intestine
• Associated with mucosal immune activation and inflammation
• Major types include Crohn's disease and Ulcerative colitis
• Not to be confused with Irritable Bowel Syndrome (IBS), which is a less severe and distinct condition
• Occurs in ~1:200 individuals
• 3 major differences between Crohn's disease and Ulcerative colitis:
  • Site of inflammation
  • Occurrence of lesions
  • Depth of inflammation
• Symptoms include: Abdominal pain, Diarrhoea, Rectal bleeding (more common in UC), Weight loss, Anemia
• Consequences can lead to decreased quality of life and increased susceptibility to cancer
• Pathogenesis involves complex interplay of genetic susceptibility, environmental factors, altered microbiome (dysbiosis), epithelial dysfunction, and chronic immune activation
• Treatment aims to induce and maintain remission, and enhance quality of life

Drug Treatment of IBD

• No cure currently exists
• Treatment methods vary based on severity
• Common drugs include:
  • Aminosalicylates
  • Antimicrobials
  • Steroids
  • Immunosuppressants
  • Biologics

Aminosalicylates

• Contain 5-aminosalicylic acid (5-ASA, mesalamine)
• Often the first line treatment for mild-to-moderate UC and CD
• Effective in preventing relapses and maintaining remission
• Administered orally or rectally
• Mechanism of action: Thought to inhibit production of proinflammatory mediators in the mucosa
• 5-ASA is an intestine-specific form of aspirin
• Different formulations enhance delivery to the distal intestine

Antimicrobials

• Luminal bacteria play a crucial role in IBD pathogenesis
• Treatment aims to alter the composition of the intestinal microbiota, decrease bacterial invasions, and treat micro-abscesses and fistulas
• Most commonly used: metronidazole and ciprofloxacin
• More effective in CD than UC, and not useful in flare-ups or maintenance therapy

Glucocorticoids

• Powerful, fast-acting anti-inflammatory drugs, mainstay of treatment for acute flare-ups
• Effective in inducing remission for 90% of UC patients and 60-90% of CD patients
• Long-term use not advised due to side effects
• Examples include prednisolone, methylprednisolone, hydrocortisone, budesonide
• Side effects limit long-term use: Cushing’s syndrome, osteoporosis

Immunosuppressants

• Used when steroids and 5-ASA fail to control inflammation
• Purine analogues inhibit nucleic acid synthesis for long-term maintenance of UC and CD
• Examples include mercaptopurine (6-MP), azathioprine, and methotrexate

Biologics

• Primarily used for severe UC and Crohn's
• Inhibit TNFα, a key pro-inflammatory cytokine
• Examples include:
  • Infliximab: Binds to soluble and transmembrane TNF
  • Adalimumab, Golimumab: Humanized anti-TNF antibodies
  • Etanercept: Decoy receptor, binding TNF
• Side effects and high costs limit usage

Other Treatments

• Faecal transplantation (FMT): Transplanting microbiota from a healthy donor to alter microbial biome
• Insufficient evidence of efficacy for both UC and CD, and for IBS

Diarrhoea

• Defined as ≥ 3 loose or liquid stools per day for 3 days
• Classified as acute (14 days) or chronic
• Causes are varied: Infections, Dietary factors, Motility-related, Inflammatory, Osmotic, Secretory

Constipation

• Characterised by < 3 bowel movements a week, hard, lumpy stools, and straining
• Occurs primarily due to diminished peristaltic action
• Common causes: Insufficient intake of dietary fibre, insufficient H20 intake, Iatrogenic causes (medication)
• 1st line treatment: Lifestyle changes (diet, fluid intake, exercise)
• 2nd line treatment: Laxatives
• Be alert about laxative abuse

Treatment of Diarrhoea

• Main approaches:
  • Treat the symptoms: Oral rehydration therapy (ORT)
  • Treat the causes: Avoidance, Drug therapy (Anti-diarrhoeals, Antibiotics, Absorbant agents, Anti-inflammatories)

Oral Rehydration Therapy (ORT)

• First priority for diarrhoea treatment
• Contains salts and glucose
• Restores electrolyte balance and drives fluid absorption
• Does not cure or prevent diarrhoea
• Maintains hydration while the body expels the pathogen

Treatment for Diarrhoea - Opiates

• Slow down intestinal transit, enabling more fluid absorption
• Example: Loperamide (Imodium)
• Mechanism of action: μ opiate receptor agonists decrease myenteric plexus activity, reducing peristaltic activity
• Contraindications: Blood or mucus in stool, high fever, children < 3 years old, pregnancy, breastfeeding

Treatment for Diarrhoea - Antibiotics

• Used for treating infectious diarrhoea
• Common examples: Rifaximin, ciprofloxacin, azithromycin (bacterial), metronidazole (parasites)
• Use should be limited and only recommended if a specific pathogen is identified as the cause

Treatment for Diarrhoea - Adsorbents

• Bind to luminal toxins, preventing entry into the body and enhancing elimination
• Examples include: Kaolin, Pectin, Activated charcoal, Bismuth subsalicylate (Pepto-Bismol)
• Side effects are rare, but drug interactions must be considered

Inflammatory Bowel Disease (IBD)

• IBD is a group of chronic inflammatory conditions of the intestine associated with mucosal immune activation and inflammation.
• IBD should not be confused with IBS (irritable bowel syndrome), which is a distinct and less severe condition associated with altered motility and fluid transport.

Crohn's Disease versus Ulcerative Colitis

• Site of inflammation: Crohn's disease can occur anywhere in the GI tract, while ulcerative colitis is limited to the colon and rectum.
• Occurrence of lesions: Crohn's disease lesions are patchy and "skip" sections of the intestine, while ulcerative colitis lesions are continuous.
• Depth of Inflammation: Crohn's disease involves transmural inflammation (all layers of the intestinal wall), while ulcerative colitis primarily affects the mucosal layer.

IBD Symptoms and Consequences

• Common symptoms include abdominal pain, diarrhea, rectal bleeding, weight loss, and anemia.
• Chronic fatigue, anxiety, depression, and social withdrawal are common non-GI symptoms associated with decreased quality of life.
• IBD increases the risk of developing cancer.

IBD Pathogenesis

• Genetic susceptibility: Predisposition to IBD is influenced by genetics.
• Environmental factors: Diet, stress, and exposure to certain environmental factors may contribute to IBD development.
• Altered microbiome: Dysbiosis, an imbalance in the gut microbiome, is a significant factor in IBD pathogenesis.
• Epithelial dysfunction: Loss of epithelial barrier function allows bacteria to access the mucosal layer.
• Chronic immune activation: The intestinal immune system becomes chronically activated, leading to inflammation.

IBD Treatment

• Aminosalicylates: First-line treatment for mild-to-moderate UC and CD. They contain 5-aminosalicylic acid (5-ASA, mesalamine), which inhibits production of pro-inflammatory mediators in the mucosa.
• Antibiotics: Used to target bacteria, such as metronidazole and ciprofloxacin, in IBD.
• Glucocorticoids: Powerful and fast-acting anti-inflammatory drugs used to induce remission during acute flare-ups. Prednisolone, methylprednisolone, hydrocortisone, and budesonide are commonly used.
• Immunosuppressants: Used when steroids and 5-ASA fail. Includes azathioprine, mercaptopurine, and methotrexate. These drugs suppress the immune system, reducing inflammation.
• Biologics: For severe UC and Crohn's. They are antibodies that target specific inflammatory proteins, like TNF-alpha, to block their inflammatory effects. Examples include infliximab, adalimumab, golimumab, and etanercept.

Constipation

• Constipation is a common condition characterized by infrequent bowel movements, hard, lumpy stools, and straining during defecation.
• Most often occurs when slow intestinal motility causes stool to harden and dry.
• Can be caused by inadequate dietary fiber intake, low fluid intake, lack of physical activity, and certain medications.
• First-line treatment includes lifestyle changes: Increasing dietary fiber, fluid intake, and physical activity.
• Second-line treatment includes laxatives, classified as bulk-forming, osmotic, and stimulant.

Diarrhoea

• Diarrhoea is frequent passage of loose or liquid stools.
• Can be acute (lasting less than 14 days) or chronic.
• Acute: Infections, dietary factors (spicy, sugary, fatty foods, alcohol, caffeine), and travel are common causes.
• Chronic: Motility disorders, inflammation, osmotic issues (lactose intolerance, gluten sensitivity), and secretory conditions (allergies).
• Treatment: Oral rehydration therapy (ORT), treating underlying causes, and using antidiarrheal agents like:
  • Opiates: Loperamide (Imodium) slows intestinal transit, allowing for fluid absorption.
  • Antibiotics: Used for infectious diarrhoea caused by bacteria, but not typically used for viral or parasitic diarrhoea.
  • Adsorbents: Bind to toxins in the gut, preventing their absorption and aiding in their elimination. Examples include kaolin, pectin, activated charcoal, and bismuth subsalicylate (Pepto-Bismol).

This quiz covers the essentials of Inflammatory Bowel Disease (IBD), including its types, symptoms, pathogenesis, and treatment options. Understand the differences between Crohn's disease and Ulcerative colitis, and how IBD impacts the quality of life. Test your knowledge on the complexities of this chronic condition.