Expected

Learning
a) Inflammatory bowel disease: Crohn’s disease & Ulcerative Colitis
b) Aims of treatment
c) Drug management: mechanisms of action, indications & adverse effects
d) Treatment guidelines
 INTRODUCTION
• Inflammatory bowel disease (IBD):
 Chronic inflammation of all or part of the digestive tract.
 IBD primarily includes Ulcerative Colitis and Crohn’s Disease.
 Painful, debilitating and sometimes leads to life-threatening complications.

• Ulcerative Colitis is an inflammatory bowel disease that causes long-lasting inflammation in

the part of the digestive tract. Symptoms usually develop over time, rather than suddenly.
Ulcerative colitis usually affects only the innermost lining of large intestine (colon) and rectum.
It occurs only through continuous stretches of colon.

• Crohn’s Disease is an inflammatory bowel disease that causes inflammation anywhere along
the lining of digestive tract and often spreads deep into affected tissues. This can lead to
abdominal pain, severe diarrhoea and even malnutrition. The inflammation caused by Crohn's
disease can involve different areas of the digestive tract in different people.


ULCERATIVE COLITIS
Conditions:
- Loose stools with blood and mucus
- Poor absorption of nutrients
- Thickening of colon wall and may form abscess (pus)
- Acute episodes may involve bleeding and perforations
- Chronic stage may have fibrosis and narrowing of colon.
 Subjective Symptoms
• Abdomen cramp and pain
• Nausea
SYMPTOM • Loss of appetite
S OF UC • Irritability

Objective Symptoms
• Bloody diarrhoea with pus and mucus (up to 10-20/days)
• Weight loss
• Vomiting
 TYPES OF UC
• Ulcerative Proctitis - Area closest to the anus (rectum). Rectal bleeding and feeling of urgency
or have frequent, small bowel movements.

• Proctosigmoiditis - Rectum and the lower end of the colon, known as the sigmoid colon.
Bloody diarrhoea, abdominal cramps and pain and an inability.

• Left-sided colitis - Inflammation extends from the rectum up through the sigmoid and
splenic flexure.
Bloody diarrhoea, abdominal cramping and pain on the left side and
unintended weight loss.

• Pancolitis - Affecting more than the left colon and often the entire colon.
Bloody diarrhoea that may be severe, abdominal cramps and pain,
fatigue and significant weight loss.

• Fulminant colitis - This rare, life-threatening form of colitis affects the entire colon and
causes severe pain. Profuse diarrhoea, dehydration and shock.
COMPLICATIONS OF RISK FACTORS OF
UC UC
• Extensive ulceration • Isotretinoin use
• Toxic Megacolon (very dilated colon) • NSAIDs e.g.
• Haemorrhage
- Ibuprofen, Naproxen and Aspirin
• Increased risk of colon cancer • Recent research
• Malabsorption
-Lifestyle and diet
• Bowel obstruction
 DIAGNOSIS OF UC
• H&P - history and physical (examination)
• Stool examination
• Flexible sigmoidoscopy (preferred in patients with severe colitis)
• Colonoscopy (should be avoided in patients with severe colitis
because of the potential to precipitate toxic megacolon)
• Capsule endoscopy
• Balloon endoscopy
• Biopsy
• Barium enema
• Abdominal radiography
• Computerized tomography (CT) scan
• Magnetic resonance imaging (MRI)
 TREATMENT OF UC
• Defining Disease Severity
• MILD – ≤4 stools per day with or without small amounts of blood, no signs of systemic toxicity (eg,
no tachycardia) and a normal C-reactive protein and/or erythrocyte sedimentation rate.
• MODERATE – frequent (4-6 per day) loose, bloody stools, mild anemia not requiring blood
transfusions (hemoglobin >10 g/dL), and abdominal pain that is not severe; no or minimal signs of
systemic toxicity.
• SEVERE – frequent, loose bloody stools (≥6 per day) with severe cramps and evidence of
systemic toxicity as demonstrated by a fever (temperature ≥37.8°C), tachycardia (heart rate ≥90
beats per minute), anemia (hemoglobin <10.0 g/dL), and/or an elevated CRP or ESR; patients may
have weight loss.
• Medical Treatment
• 5 - aminosalicylates (Mesalamine / Sulfasalazine)
• Steroids (Prednisolone)
• Anti-tumor necrosis factor (TNF) agent-based therapy (Infliximab, Adalimumab, Golimumab)
• Immunosuppressant (Azathioprine, Methotrexate)
 CROHN’S DISEASE
Crohn’s Disease - Name from a New York doctor, Burrill Crohn, who
reported a number of cases in 1932.
CROHN’S DISEASE

 Can affect any part of the gastrointestinal (GI) tract from the mouth to the anus.
 Segmental with skip areas.
 Intestine Perirectal fistulas and abscesses are present in one-third of patients.
 Both subjective and objective symptoms are relatively identical to Ulcerative colitis.
 Assessments are identical.
Diagnostic tests are the same except:
1. With Crohn’s will find string sign (segments of stricture separated by
normal bowel)
2. With colonoscopy will find patchy areas of inflammations.
3. Need biopsy for definitive diagnosis.
Signs and symptoms of Crohn's
disease
• Diarrhea
• Abdominal pain & cramping
• Blood in stool
• Ulcers
• Reduced appetite & weight loss
• Fistulas
Severe Crohn's disease may also experience:
• Fever
• Fatigue
• Arthritis
• Eye inflammation
• Skin disorders
• Inflammation of the liver or bile ducts
• Delayed growth or sexual development in children
 TREATMENT
• Defining Disease Severity
• Mild Crohn disease – These patients are typically ambulatory and tolerating an oral diet. They
have <10 percent weight loss and no symptoms of systemic disease such as fever, tachycardia,
abdominal tenderness, and no signs or symptoms of obstruction.

• Moderate to Severe Crohn disease – This group comprises patients who have failed treatment
for mild to moderate disease or those patients with prominent symptoms such as fever, weight
loss, abdominal pain and tenderness, intermittent nausea or vomiting or anemia.

MEDICATIONS
• Steroids (Prednisolone)
• 5-aminosalicylates (Mesalamine / Sulfasalazine)
• Anti-tumor necrosis factor (TNF) agent-based therapy (Infliximab, Adalimumab)
• Immunosuppressant (Azathioprine, Methotrexate)
5-aminosalicylates (5-ASAs)
• Mesalamine (single 5-aminosalicylic acid molecule)
• Sulfasalazine (Sulfapyridine + 5-aminosalicylic acid)
• 5-aminosalicylic acid is the active component of the drug and acts
readily in the colon but absorbed in small intestine.
• Sulfapyridine acts as a carrier molecule which prevents absorption
of 5-aminosalicylic acid in the small intestine.
Contraindications /Cautions
• Mesalamine: Salicylate hypersensitivity
• Sulfapyridine: G6PD deficiency (haemolysis), Undergoes acetylation in
liver, Slow acetylator status ( risk of hepatic and blood disorders)

Adverse Effects - Mesalamine

• Dose-related (10-45%): - Headache, nausea, epigastric pain, diarrhoea
• Idiosyncratic (rare): - Acute pancreatitis; hepatitis; myocarditis; pericarditis;
eosinophilia; fibrosing alveolitis; nephrotic syndrome
• Peripheral neuropathy
• Blood disorders: - Agranulocytosis; aplastic anaemia; leucopenia;
neutropenia, thrombocytopenia; methaemoglobinemia
• Skin reactions: - Lupus like syndrome; Stevens-Johnson syndrome; alopecia
 Adverse Effects - Sulfasalazine

• Hypersensitivity reactions
• Heinz body anaemia (irreversible and the continual elimination of damaged RBC)
• Megaloblastic anaemia
• Oligospermia
• Orange coloured urine
 Corticosteroids
• Prednisolone
• Enter cells where they combine with steroid receptors in cytoplasm

Adverse Effects
• Na retention/ K loss / Ca loss
•  gluconeogenesis
• Redistribution of fat – Cushingoid appearance
• Acute adrenal insufficiency
Thiopurines
• Azathioprine is a pro-drug. Following oral ingestion, it is metabolized into 6-
mercaptopurine and later 6-thioguanine nucleotides, which is a purine
synthesis inhibitor.

Adverse Effects
• Dyspeptic symptoms
• Hepatotoxicity; pancreatitis (<5%)
• Leucopenia (3%) – Bone marrow suppression
- determined by Thiopurine methyltransferase (TPMT) activity
- weekly FBC x 8 weeks
- 3 monthly thereafter
 Indications for Surgery
• In patients with UC:
• Severe attacks that fail to respond to medical therapy.
• Complications of a severe attack
(e.g., perforation, acute dilatation).
• Chronic continuous disease with an impaired quality of life.
• Dysplasia or carcinoma.

• In patients with CD
• Obstruction, severe perianal disease unresponsive to medical therapy, difficult fistulas, major bleeding,
severe disability.
• 30% relapse rate.

Procedures:
• Proctocolectomy with permanent ileostomy
• Colectomy with ileorectal anastomosis
• Strictureplasty
• Resection
 CLINICAL CASES/MCQs
1. A 22-year-old man with ileal Crohn disease presents with worsening right lower quadrant
abdominal pain, constipation, nausea, and vomiting. He reports adherence to infliximab
therapy. Computed tomography shows distal ileal inflammation with a 15 cm long-segment
stricture in the terminal ileum and upstream small bowel dilation.There is no significant clinical
improvement with bowel rest, intravenous fluids, and intravenous methylprednisolone. What is
the most appropriate treatment for this patient?

A. Surgical resection of the terminal ileum stricture

B. Endoscopic dilation of the terminal ileum stricture
C. Add intravenous ciprofloxacin and metronidazole
D. Add monoclonal antibody vedolizumab
2. Which of the following are used for Crohn’s disease EXCEPT

A. Metronidazole
B. Mesalazine
C. Azathioprine
D. Mebendazole

3. Which of the following is associated with an increased risk of colorectal cancer in

patients with ulcerative colitis?

A. Duration of disease
B. Duration and extent of disease
C. Severity of disease
D. Extent of the colon affected by the disease
4. A woman presents with 2 years of abdominal pain, rectal bleeding, unintentional weight loss, and loss
of appetite. A biopsy was performed during colonoscopy procedure. The findings with 2-year duration of
clinical signs and symptoms are suggestive of ulcerative colitis. Which of the following is the major long-
term risk for this patient?

A. Perforation
B. Bowel Obstruction
C. Colon Cancer
D. Diverticulitis
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