Inflammatory Bowel

Disease
• A group of inflammatory conditions of the colon and small
intestine
• Disorders of unknown cause, involving genetic and
immunological influence on the gastrointestinal tract’s
ability to distinguish foreign from self-antigens
• Major types
– Crohn’s disease
– Ulcerative colitis
 Pathophysiology
• Inflammation of the mucosa of the intestinal tract, causing ulceration,
oedema, bleeding and fluid and electrolyte loss
• Cytokines, which are released by macrophages in response to various
antigenic stimuli differentiate lymphocytes into different types of T
cells.
• Helper T cells, type 1 (Th-1), are associated principally with Crohn disease,
whereas Th-2 cells are associated principally with ulcerative colitis.
• The immune response disrupts the intestinal mucosa and leads to a chronic
inflammatory process
 Sign and symptoms
Crohn's disease Ulcerative colitis
Often porridge-like,
Often mucus-like
Defecation sometimes
and with blood
steatorrhea
Tenesmus Less common More common
Indicates severe
Fever Common
disease
Fistulae Common Seldom
Weight loss Often More seldom
Findings in diagnostic workup in Crohn's disease vs. ulcerative colitis
Sign Crohn's disease Ulcerative colitis

Terminal ileum involvement Commonly Seldom

Colon involvement Usually Always

Rectum involvement Seldom Usually
Involvement around
Common Seldom
the anus
No increase in rate of primary
Bile duct involvement Higher rate
sclerosing cholangitis
Patchy areas of inflammation Continuous area of
Distribution of Disease
(Skip lesions) inflammation
Deep geographic and
Endoscopy Continuous ulcer
serpiginous (snake-like) ulcers
May be transmural, deep into
Depth of inflammation Shallow, mucosal
tissues
Stenosis Common Seldom
May have non-necrotizing
Non-peri-intestinal crypt
Granulomas on biopsy non-peri-intestinal crypt
granulomas not seen
granulomas
Extra-intestinal
manifestation
 Complication Prevalence
Scleritis 18%
Anterior uveitis 17%
Gall stones (particularly in Crohn 13-34%
disease)
Inflammatory arthritis 10-35%
Anemia 9-74%
Aphthous stomatitis 4-20%
Osteoporosis 2-20%
Erythema nodosum 2-20%
Source: Larson S, Bendtzen K, Nielsen OH. Extraintestinal
manifestations of inflammatory bowel disease: epidemiology, diagnosis
and management. Ann Med. 2010;42:97-114.
Risk factors in Crohn's disease vs. ulcerative colitis.
Crohn's disease Ulcerative colitis
Smoking Higher risk for smokers Lower risk for smokers
Peak incidence
Usual onset between
Age between
15 and 30 years
15 and 25 years
10–15% of patients with Crohn’s disease have a family history
Family history of the disorder; 5–7% have a family history of ulcerative colitis

Ethnicity Whites, Ashkenazi Jewish descent

Where you live Higher risk in urban or industrial area
NSAIDs Will worsen IBD
Aims of therapy
• Treatment of active disease followed by maintenance of
remission.
• Treatment should successfully suppress active
inflammatory disease medically and attempt to conserve
the small bowel.
• CD: Surgery should be reserved for managing
complications (fistulae and abscesses) as well as treating
obstruction.
• UC: Surgery cures UC
5-ASA
• Mild to moderate Crohn’s disease has a good response to
5-aminosalicylate-containing agents.
• 5-aminosalicylic acid (5-ASA) derivatives (mesalamine,
mesalazine and sulfasalazine) provide anti-inflammatory
actions for connective tissue.
• Aminosalicylates can be targeted to sites along the
gastrointestinal tract.
• Asacol, coated with a pH-sensitive acrylic polymer, releases
5-ASA in the distal ileum and colon at pH of 7.0.
• Sulfasalazine acts as the transport mechanism to carry the
5-ASA component to the colon tract.
• Pentasa is comprised of coated granules that release 5-ASA
in the upper gastrointestinal tract, as well as the ileum and
colon.
• s/e; headache, dyspepsia, malaise, nausea, vomiting and
anorexia
Antibiotics
• Metronidazole comparable to sulfasalazine
• Ciprofloxacin as effective as mesalamine in mild to
moderate

Steroids
•Moderate to severe
•s/e osteoporosis- tx with biphosphonate or calcitonin
 Immunomodulator drugs
• Azathioprine, 6-MP
• alter the immune response by inhibition of natural killer
cell activity and suppression of T-cell function
• s/e: fever, rash, nausea, leukopenia. hepatitis, pancreatitis
• Cyclosporin: potent T cell inhibitor
• Methotrexate

Biological therapy
•Infliximab
•Drawback: Multiple dosing
Management in Crohn's disease vs. ulcerative colitis
Crohn's disease Ulcerative colitis
Mesalamine Less useful More useful
Antibiotics Effective in long-term Generally not useful
Often returns
following Usually cured by
Surgery
removal of affected removal of colon
part
CD
UC
Diet
• Enteral: Simple sugar and amino acids
• TPN- 2-3 weeks in medically refractory patients
• Together with other medical therapy

Maintenance therapy
•5-ASA
•Azathioprine and 6-MP: Shown to be effective after 3-4
months
Surgical therapy
Complication of UC
• Massive haemorrhage
• Fulminant colitis
• Colonic stricture (rare)
• Colon cancer
• Toxic megacolon
• Higher risk of nutrient
deficiency
Complication of CD
• Abscess and fistula
• Obstruction
• Perianal disease
• Colon cancer
Complications of CD
• Bile acid malabsorption
– Secretory diarrhoea- bile acids on colon
– Gallstornes- bile more lithogenic
– Steatorrhoea- vitamin A, D, E, K malabsorption
– Nephrolithiasis- steatorrhoea causes more oxalate
absorption leading to calcium oxalate stones– not uric
acid stones
• Malignancy- colon cancer, small bowel cancer (lymphoma
or adenocarcinoma- very rare)
Complications of Crohn's disease vs. ulcerative colitis
Crohn's disease Ulcerative colitis
Nutrient deficiency Higher risk
Colon cancer risk Slight Considerable
Prognosis
• Most pts managed with current standard medical and
surgical approaches report a good quality of life
• Excellent prognosis for long term
 Pharmaceutical Care Issues
• Monitoring of drug efficacy and toxicity
• Drug dosage form
• Thank you
Case example
• Ms A, is a 26-year-old lady who presents with a
prescription for sulphasalazine 500mg qid. She has
recently been referred to the gastroenterologist following
a 3-month history of abdominal pain, diarrhoea and
several episodes of rectal bleeding. Inpatient
investigation found mild ulcerative colitis extending
through most of the large bowel and most active
proximally.
• Q1. What monitoring should be carried out in patients
starting sulphasalazine for ulcerative colitis?
• Q2. What information about the drug should be provided
to the patient?
• Q3. Why is sulphasalazine often of limited usefulness in
Crohn’s disease?
 Extra-intestinal
manifestation
• Primary sclerosing cholangitis
• Arthritis
• Skin manifestation: erythema
nodosum, pyoderma gangrenosum
• Eye problem: episcleritis, iritis,
uveitis
• Oral aphthae
• Ankylosing spondylitis
 Prevalence of extraintestinal complications
Females 2.2% 3.2%
Iritis/uveitis
Males 1.3% 0.9%
Primary Females 0.3% 1%
sclerosing
cholangitis Males 0.4% 3%

Ankylosing Females 0.7% 0.8%

spondylitis Males 2.7% 1.5%
Pyoderma Females 1.2% 0.8%
gangrenosum Males 1.3% 0.7%
Erythema
Females 1.9% 2%
nodosum