This document discusses inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease. IBD is characterized by chronic inflammation of the gastrointestinal tract. The document covers the etiology, pathophysiology, clinical presentation, complications, and management of both Crohn's disease and ulcerative colitis. Treatment involves the use of aminosalicylates, corticosteroids, immunomodulators, antibiotics, and in some cases surgery. Lifestyle modifications like avoiding certain foods and behaviors are also recommended.

1. Inflammatory Bowel Disease
Dr. Abhimanyu Parashar
Assistant Professor
Dept. Of Pharmacy Practice
MMCP, Mullana, Ambala

2. IBD
It is an idiopathic bowel disease which includes
ulcerative colitis (UC) & crohn’s disease (CD)
UC & CD are chronic, relapsing inflammatory
diseases of the gut may be associated with a
range of extra intestinal manifestations

3. CD or Regional enteritis
It is an idiopathic chronic ulcerative IBD,
characterised by transmural, non-caseating
granulomatous inflammation affecting most
commonly the segment of terminal ileum
and/or colon though any part of the GIT may
be involved

4. Ulcerative Colitis
Idiopathic form of acute & chronic ulcero-inflammatory
colitis affecting chiefly the mucosa & submucosa of
the rectum & descending colon, though it may
involve the entire length of large bowel

5. Etiopathogenesis
1. Infectious mechanisms
2. Immunologic mechanisms
i) humoral factors
ii) cell mediated immunologic factors
iii) immunodeficiency
3. Others
i) psychological factors
ii) genetic factors
iii) racial factors
iv) diet
v) social habits
vi) drugs

6. Infectious mechanisms
Bacterial infections:
mycobacteria
dysentery bacilli
chlamydia
Viral infections:
roatvirus
EB virus
intestinal cytopathic virus
Certain protozoal & fungal infections

7. Immunologic mechanisms
i) Humoral factors
a) the specific anti-colon antibodies to E.coli
causes the lesion, but no correlation b/n the
levels of these antibodies & activity of the
IBD
b) Increased synthesis of Ig G
by the lymphoid cells of diseased bowel,
produce antibody mediated damage
but IBD was observed in
agammaglobulinaemia also

8. c) Circulating immune complexes
produces extra intestinal lesions of IBD but their
role in intestinal lesions of IBD is not established
d) IgE mediated hypersensitivity reaction
leads to excessive histamine release by mast cells
in the bowel wall may cause oedema of bowel
wall in IBD
But administration of antihistamines does not
alter the course of the disease

9. Cell mediated immunologic factors
a) Decreased number of peripheral T cells.
b) presence of T cells sensitized to various
bowel antigens may be cytoyoxic to mucosa
c) Antibody dependent cellular cytotoxicity
(ADCC) may occur by interaction of K cells
with humoral antibodies

10. immunodeficiency
Immunodeficiency of IgA in crohn’s disease has
been suggested more recently as possible
immune mechanism for the lesion

11. Others
Psychological factors:
individuals who are sensitive, dependent on
others & unable to express themselves suffer
from irritable colon
Genetic factors:
certain HLA have also been found to be
associated with IBD

12. Racial factors:
high incidence of IBD have been identified in Jews &
in whites
Diet:
milk, fibres & diet rich in CH provokes IBD
Social habits:
smokers are more prone to develop IBD
Drugs:
women who are on Ocs have increased risk of IBD

13. Pathologic changes - CD
CD may involve any portion of GIT but affects
most commonly 15-25 cms of terminal ileum
which may extend into the caecum &
sometimes into the ascending colon
Transmural inflammatory cell infiltrate:
It consists of chronic inflammatory cells
(lymphocytes, plasma cells & macrophages) –
the classical microscopic feature

14. Non-caseating, sarcoid- like granulomas
Present in all layers of affected bowel & in
regional lymph nodes
Patchy ulceration of mucosa
Which may form deep fissures, accompanied by
inflammatory infiltrates of lymphocytes &
plasma cells
Widening of submucosa due to oedema & foci
of lymphoid aggregates

15. In chronic condition, fibrosis is prominent in all
the layers disrupting muscular layer
Regardless of the site, bowel wall injury is
excessive & intestinal lumen is often narrowed
The mesentery first becomes thickened &
oedematous & then fibrotic
Ulcers tend to be deep & elongated & extend
along the longitudinal axis of the bowel, atleast
into the submucosa

16. The cobblestone appearance of the bowel wall
results from deep mucosal ulceration
intermingled with nodular submucosal
thickening

17. Pathologic changes - UC
The characteristic feature is the continuous
involvement of rectum & colon without any
uninvolved skip areas as seen in CD
The appearance of colon may vary depending
upon the stage & intensity of the disease
because of remissions & exacerbations
Mucosa shows linear & superficial ulcers, usually
not penetrating the muscular layer

18. The intervening intact mucosa may form
inflammatory pseudo polyps
The muscle layer is thickened due to contraction
producing shortening & narrowing of the
affected colon with loss of normal haustral
folds giving garden-hose appearance
Because of remission & exacerbations it is
characterised by alternating active disease
process & resolving colitis

19. Crypt distortion, cryptitis & focal accumulations
of neutrophils forming crypt abscesses
Marked congestion, dilation & hemorrhages
from mucosal capillaries
Superficial mucosal ulcerations, usually not
penetrating into the muscle coat, except in
severe cases & is accompanied by nonspecific
inflammatory cell infiltrate of lymphocytes,
plasma cells, neutrophils, some eosinophils &
mast cells in the lamina propria

20. Goblet cells are markedly diminished in cases of
active disease
Areas of mucosal regeneration & mucodeplition
of lining cells
In long-standing cases, epithilial cytologic atypia
ranging from mild to marked dysplasia & some
times developing into carcinoma in situ &
frank carcinoma

21. Types of UC
• Proctitis - ulcerative colitis affecting only the
rectal mucosa.
• Proctosigmoiditis – It involves rectum and the
colon
• Colitis- It involves other parts of the colon.

22. Complications - CD
Malabsorption
Fistula formation
Stricture formation
Carcinoma
Bleeding
Hypochromic anemia
Systemic complications like, arthritis, iritis, skin
lesions, liver disease, renal stones, gall stones,
weight loss, growth failure

23. Complications of - UC
Toxic megacolon
Perianal fistula
Carcinoma
Stricture formation

24. CLINICAL PRESENTATION
Clinical
presentation
Crohn’s disease Ulcerative colitis
Malaise, fever Common Un common
Abdominal
tenderness
Common May be present
Rectal bleeding Less 100%
Illeal Very common Rare
Granulomas Common Rare
Fistulas Common Rare

26. Management
Goals:
to induce remission in active disease
to maintain remission / prevent relapse

27. CD
Mild to moderate disease
Active CD: oral/parenteral steroids- most
effective & safer than oral aminosalicylates
CD of colon: aminosalicylates
Crohn’s ileitis- mesalazine should be used
as 5 aminosalicylic acid is not released in the
small bowel from sulfasalazine or olsalazine

28. Dose of aminosalicylates required for CD is more
than of UC especially in small bowel disease
Prednisolone/prednisone 20-60 mg PO/D for 8-12
weeks
Or
budesonide CR 9 mg PO/D for 8-12 weeks
Aminosalicylates:
Sulfasalazine 2-4 g PO/d in DD
Mesalazine 3-4.8 g PO/d in DD
Olsalazine 2-3 g PO/d in DD

29. Metronidazole is as effective as sulfasalazine for colonic
disease
Metronidazole 20 mg/kg PO/d in DD
Severe disease:
Hydrocortisone 100 mg IV Q6H or
Hydrocortisone 300-400 mg by CIVIF/d or
Methylprednisolone 60-80 mg IV/d in DD or by CIVIF for
5-10 days
Oral steroids should be substituted when disease
activity has subsided
Prednisolone or prednisone 40-60 mg/d PO
Gradually reducing to zero over 8-12 weeks

30. Chronically active disease:
Patients who do not respond to steroids or
require continuous steroids to control disease
activity
AZT
6-MP
Surgery should be considered if more than 5-10
mg of prednisolone/d is required
AZT 2-2.5 mg/kg PO/d or
6-MP 1-1.5 mg/kg PO/d

31. Newer agents:
Infliximab- monoclonal antibody directed against the
proinflammatory cytokine TNF-alpha
Effective in patients with refractory & acutely or chronically
active disease
Dose: 5 mg/kg IVIF
Maintenance therapy:
AZT & 6-MP effective as prophylactic agents in patients with
frequent relapses & in those who are steroid dependent
AZT 2-2.5 mg/kg/PO/d
6-MP 1-1.5 mg/kg/PO/d

32. Management - UC
Mild disease- topical therapy for proctitis
Moderate/severe/more extensive- oral/IV
Aminosalicylates:
Effective in inducing remission in active colitis/proctitis
Response is dose realted
Sulfasalazine 6g/d
Mesalazine 4g/d
Olsalazine 3g/d
ADRs of s & o are dose related hence should be started
at low doses & titrated to recommended dose

33. Immunosupressive agents:
AZT & 6-MP, effective for both remission induction &
maintenance therapy
Takes 3-6 months to achieve benefit
Significant ADRs
Active proctitis/distal colitis:
I-line:
Topical steroids alone or with oral aminosalicylates
Prednisolone sod.phosphate 20 mg/100ml/d enema
rectally at night or twice daily

34. Hydrocortisone acetate 10% foam rectally/d at night or
twice daily or
Prednisolone 5 mg rectally twice daily
Along with,
Sulfasalazine 2-4 g/PO/d in 3-4 DD
Mesalazine 1-1.5 g/PO/d in 3 DD
Olsalazine 1-1.5 g/PO/d in 2-3 DD
CTE:
5-aminosalicylic acid enemas are superior to topical
steroids
Combination oral & topical 5 AS therapy is more effective
than either therapy alone

35. II-line:
Addition of an oral CS to I-line
Prednisolone or prednisone 20-60 mg/PO/d for
8-12 weeks
Extensive UC:
Mild to moderate disease:
Prednisolone or prednisone 20-60 mg/PO/d for
8-12 weeks and/or
Oral aminosalicylate

36. Severe disease:
More than 6 bloody stools/d
Temp more than 37.5
Pulse more than 100 bpm
Hb less than 100g/l
S.Alb less than 35 g/l
Fluid, electrolyte or blood replacement should
be considered
Early surgical consulatation is essential

37. Hydrocortisone 100 mg IV Q6H or by CIVIF or
Methylprednisolone 60-100 mg IV/d in DD or by
CIVIF
For 5-10 days and should be substituted with
oral steroids
If deteriorating or failure to respond consider
colectomy or IV cyclosporin
Avoid:
Loperamide & other antidiarrhoeals &
anticholinergics in severe disease as it may
leads to toxic megacolon

38. Chronically active disease:
AZT, 6-MP, surgery
AZT 2-2.5 mg/kg PO/d or
6-MP 1-1.5 mg/kg PO/d
ADRs of s&o are dose related hence should be
started at low doses & titrated to
recommended dose
Proctocolectomy, ileal pouch anal anastomosis
may be considered for the traetment of
chronic refractory disease

39. Maintenance therapy:
To reduce the relapse-aminosalicylates or
immunosupressive agents
Sulfasalazine 2-3 g/Po/d in 3-4 DD
Incidence of ADRs increases with increase in
dose
Mesalazine 1-1.5g/PO/d in 3 DD
Olsalazine 1-1.5 g/PO/d in 2-3 DD
ADR: watery diarrhoea (10-15%)

40. Patients responded to topical AMS preparations may
continue to use as maintenance therapy at reduced
doses
Mesalazine 2-4 g in 60 ml enema rectally 2-3 times a
week
A prolonged remission may be achieved with,
AZT 2-2.5 mg/kg/Po/d or
6-MP 1-1.5 mg/kg/PO/d

41. Pouchitis:
In patients who have undergone ileal-pouch
anal anastomosis may develop inflammation
of ileal pouch
Metronidazole 20mg/kg/po/d in DD, probiotic is
also useful

42. Treatment approach for CD

43. Treatment approach for UC

44. DRUGS TreDaOStEment oMpAINtTiEoNAnNCsE
DOSE
SITE OF ACTION
Sulfasalazine 3 – 4 gm/day 2 – 4 g/day colon
Olsalazine 2 – 3 gm/day 1g/day colon
Balsalazide 2 – 6.75 gm/day 2 – 6.75g/day colon
Mesalamine
(DR)
2.4 – 4.8 gm/day 2.4-4.8g/day Distal ileum and
colon
Mesalamine (enema) 1 – 4 g/day 0.8 – 4.8 g/day Rectum and terminal
colon
Mesalamine (SR) 2 – 4 g/day 1.5 – 4 g/day Small bowel and
colon
Mesalamine suppository 1 – 1.5g/day 0.5 – 1
gm/bedtime
Rectum and terminal
colon

45. corticosteroids
DRUGS DOSE
Methylprednisolone (IV) 40 – 60mg/day
Prednisolone ( IV) 60 – 80 mg/day
Hydrocortisone IV 300mg/day
Prednisone( oral) 20 – 60mg/day
Budesonide( oral) 9 mg/day
Hydrocortisone enema 100 – 200 mg/day

46. DRUGS ROUTE REMISSION DOSE MAINTENANCE DOSE
Azathioprine Oral 2–3 mg/kg/day 2–3 mg/kg/day
6-Mercaptopurine Oral 1–1.5 mg/kg/day 1–1.5 mg/kg/day
Cyclosporine IV 2–4 mg/kg/day Not indicated
Oral 4–8 mg/kg/day Not indicated
Tacrolimus IV 0.01 mg/kg/day Not indicated
Oral 0.1–0.2 mg/kg/day Not indicated
Methotrexate IM 25 mg/wk 25 mg/wk
Oral 15–25 mg/wk 15–25 mg/wk
Infliximab IV 5 mg/kg 5–10 mg/kg

47. ANTIMICROBIALS
DRUGS REMISSION DOSE MAINTANANCE
DOSE
Metronidazole
Oral
10–20 mg/kg/day Not indicated
Ciprofloxacin
Oral
1–1.5 g/day Not indicated

48. FOODS TO AVOID
• Alcohol (Mixed Drinks, Beer, Wine)
• Butter, Mayonnaise, Margarine, Oils
• Carbonated Beverages
• Coffee, Tea, Chocolate
• Corn Husks
• Dairy Products (If Lactose Intolerant)
• Fatty Foods (Fried Foods)
• Foods High In Fiber
• Gas-producing Foods (Lentils, Beans, Legumes, Cabbage, Broccoli, Onions)
• Nuts And Seeds (Peanut Butter, Other Nut Butters)
• Raw Fruits
• Raw Vegetables
• Red Meat And Pork
• Spicy Foods
• Whole Grains And Bran