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DR. Daras AL- Wasebi
INFLAMMATORY BOWEL DISEASE (IBD)
◾
IBDs are a group of chronic inflammatory conditions in which the body’s own immune system attacks parts of the
digestive system, with a relapsing & remitting course.
◾
IBD is characterized by times of active disease (flares), when symptoms are present, and times of remission,
when little or no symptoms are present.
INFLAMMATORY BOWEL DISEASES (IBD)
 The two most common inflammatory bowel diseases are Crohn’s disease (CD) and ulcerative colitis
(UC).
 There is no cure for IBD but there are treatments to reduce and control the symptoms of the disease.
PATHOPHYSIOLOGY:
◾ IBD is a polygenic disease; has both environmental & genetic components.
◾ Activation of immune cells by unknown inciting agent (microorganism, dietary component, bact. or self-Ag)→
release of cytokines & inflammatory mediators.
o ↑risk in 1stdegree relatives of pts with IBD (largest independent risk factor)
o HLA-DR2 with UC & a CD-related gene.
o SerumANCA in 70% of UC pts.
o Abs to Saccharomyces cerevisiae (ASCA) in 70% of CD pts.
PATHOPHYSIOLOGY (CONT.….)
o Emotional stress
o Intercurrent infection
o GE
o ABX or NSAIDs
o Cessation of smoking
o In both CDAnd UC the intestinal wall is infiltrated with acute & chronic inflammatory cells but there are
importance differences b/w them in the distribution of lesions & in histological features.
CLINICAL FEATURE OF IBD
 The symptoms of IBD vary from person to person, and may change over time.
 The most common symptoms for CD and UC are frequent and/or urgent bowel movements, diarrhea, bloody
stool, abdominal pain and cramping.
 People with IBD may also report symptoms such as fatigue, lack of appetite and weight loss.
◾ Rectal bleeding; bloody D with mucus (Cardinal symptoms).
◾ 1st attack is the most severe (D/D?) followed by relapses & remissions.
◾ Proctitis: with tenesmus. Constitutional symptoms do not occur.
◾ L.S & pancolitis: abd. cramps.
◾ Severe cases:A, malaise, wt. loss & abd. pain. Pt is toxic, with signs of peritonitis (?). The Truelove–Witts
criteria for acute severe UC:
◾ ≥ 6 bloody stools/24hrs + ≥1 of: *anaemia *fever * ↑P.R *↑ESR
◾ Rt. lower abd. pain provoked by eating, D & wt loss (Major symptoms).
◾ Features of fat, protein or vit. malabs.
subac. or ac. Intestinal obstruction.
◾ Crohn’s colitis: similar to UC, but rectal sparing with perianal dis.
◾ Physical Examination:
◾ Wt. loss, anaemia.
◾ Abd. tenderness over the inflamed area.
◾ Palpable abd. mass. (D/D?)
◾ Perianal skin tags, fissures or fistulae (in 50% of pts).
CLINICAL FEATURES OF ULCERATIVE COLITIS:
◾ Cardinal symptoms: rectal bleeding with passage of mucus & bloody D.
◾ 1st attack is usually the most severe; followed by relapses & remissions.
◾ Rectal bleeding, mucus discharge & tenesmus.
◾ Some pass freq., small volume fluid stools, while others pass pellety stools.
◾ Constitutional symptoms do not occur.
CLINICAL FEATURES OF ULCERATIVE COLITIS(CONT…)
◾ Bloody D with mucus, often with abdominal cramps.
◾ Almost all patients are constitutionally well.
◾ Severe cases, anorexia,, malaise, wt loss & abd. pain.
◾ Pt is toxic, with signs of peritonitis (??)
◾ The Truelove–Witts criteria for acute severe UC:
◾ ≥6 bloody stools/24hrs
◾ anaemia <100 g/L (<10g/dL)
◾ fever ≥ 37.8°C
◾ P.R ≥ 90bpm
◾ ↑ESR> 30mm/hr
CLINICAL FEATURES OF CROHN’S DISEASE:
Rt- Lower abdominal pain, Diarrhea & wt. loss (due to anorexia or malabsorption);
features of fat, protein or vitamins deficiencies.
 Abdominal pain (acute /subacute intestinal obstruction),
 with watery Diarrhea , not containing blood or mucus
 inflammatory mass, intra-abdominal abscess
CLINICAL FEATURES OF CROHN’S DISEASE:
 similar to UC, but rectal sparing & presence of perianal dis. in CD.
 Many pts have symptoms of both small bowel & colonic dis.
 vomiting from jejunal strictures or severe oral ulceration.
 Few patients have isolated perianal disease.
PHYSICAL EXAMINATION:
 Wt. loss, anaemia with glossitis & angular stomatitis.
 Abd. tenderness over the inflamed area.
 An abd. mass may be palpable.(D/D?) (matted loops of thickened bowel/abscess)
 Perianal skin tags, fissures or fistulae (in 50%).
INVESTIGATIONS OF IB DISEASE:
 CBC: Hb =↓ : bleeding or malabs. of Fe, folic acid or vit. B₁₂.
 S. albumin =↓ protein-losing enteropathy, inflammatory disease or poor nutrition.
 ESR & CRP =↑: in exacerbations & in abscess formation.
 Serological tests: p-ANCA (?) &ASCA (?).
 Faecal calproctectin: has a ↑ sensitivity for detecting GIT inflammation & may be ↑, even when the CRP
is NL. It distinguishes IBD from IBS at Dx & for monitoring activity.
 Bacteriology: stool: microscopy, culture (Help to exclude superimposed enteric infection in patients with
exacerbations.), Clostridium difficile toxin & ova.
INVESTIGATIONS OF IB DISEASE(CONT…)
:cultures (Also advisable in febrile patients with known colitis or Crohn’s disease.)
 Flexible sigmoidoscopy: to Dx ac. severe presentations
 Ileocolonoscopy: later for dis. extent.
 UC: loss of vascular pattern, granularity, friability & contact bleeding, ± ulcers
 CD: patchy inflammation, with discrete, deep ulcers, strictures & perianal dis.
 Colonoscopy: In established dis., for active inflammation with pseudopolyps or CA.
INVESTIGATIONS OF IBD: ENDOSCOPY
image of ulcerative colitis
affecting the left side of the colon. The
image shows confluent superficial ulceration
and loss of mucosal architecture
Crohn's disease
(regional ileitis)
INVESTIGATIONS OF IB DISEASE(CONT…)
i. Barium enema: less sensitive.
ii. Barium follow-through: narrowed & ulcerated areas of the bowel, with multiple strictures.
iii. MRI enterography: sensitive for extraintestinal manifestations & assessing pelvic & perineal
involvement. It distinguishes b/w inflammation & fibrotic strictures
INVESTIGATIONS OF IB DISEASE(CONT…)
for dilatation of the colon, mucosal oedema or perforation. In SI CD, there
may be evidence of intestinal obstruction. or displacement of bowel loops by a mass.
to detect SI inflammation & strictures.
to screen for complications (perforation or abscess) in the acutely unwell.
MANAGEMENT OF IB DISEASE:
i. Team approach: physicians, surgeons, radiologists, nurse specialists, dietitians, counsellors & pt support groups
(emotional support).
i. Treatment acute attacks (induce remission) &
ii. Prevent relapses (maintain remission)
iii. Prevent bowel damage
iv. Detect dysplasia & prevent CA
v. Select appropriate pts for surgery
MANAGEMENT OF U C :
i.
iii.
5-ASA(amino salicylic acid)
ii. corticosteroids
AZA (azathioprine)
iv. biological Rx (anti-TNF)
v. colectomy is curative
MANAGEMENT OF U C :
i.
iii.
Mesalazine, Sulfasalazine : rectal suppository 1g are 1st line Rx.
ii. Mesalamine (5-ASA): Oral, rectal suppository
Topical corticosteroids: hydrocortisone enema if intolerant of topical mesalazine.
iv. Systemic corticosteroids & immunosuppressants: in resistant dis.; useful as steroid-sparing agents.
MANAGEMENT OF U C :
1) 5-ASA1g foam/liquid enema for 1month are 1stline Rx
2) Oral 5-ASA
3) Oral prednisolone (40mg/d, tapered by 5 mg/wk over 8wks)
4) Immunosuppressive Rx: thiopurine (AZA, 6-MP)
5) Severe ulcerative colitis. Pts who fail to respond to maximal oral therapy & those who present with ac. severe
colitis (meeting Truelove–Witts criteria):
MANAGEMENT OF U C :
1. Admit to hospital for intensive therapy & monitoring by a physician & surgeon
2. I.V fluids & correction of electrolyte imbalance
3. Transfusion if Hb< 100g/L(< 10g/dL)
4. IV methylprednisolone (60mg/d) or hydrocortisone (400 mg/d) by I.V.I or bolus
5. ABX until enteric infection excluded
6. Nutritional support for malnourished pts
7. S.C LMW heparin for prophylaxis of venous TE
MANAGEMENT OF ULCERATIVE COLITIS
 Avoidance of opiates & anti-diarrhoeal agents (can be given in mild cases)
 Consider medical rescue therapy with
1. Cyclosporine (2 mg/kg I.V.I or oral) or
2. Infliximab (5 mg/kg) in stable pts not responding to 3-5ds of corticosteroids (~60% of cases, can avoid the need
for urgent colectomy)
MAINTENANCE OF REMISSION OF UC:
Corticosteroids should never be used for maintenance therapy.
Rx for all pts with Lt.S or extensive dis.
1) Oral Mesalamine (5-ASA) o.d are the 1st line agents.
2) Sulfasalazine has ↑S.Es but is equally effective esp. in pts with coexistent arthropathy.
3) Thiopurines in pts who relapse.
MANAGEMENT OF CD :
1) Crohn’s disease
2) Corticosteroids
3) AZA(azathioprine)
4) MTX(methotrexate)
5) biological Rx (anti-TNF)
6) nutritional Rx
7) surgery for complications not curative
8) 5-ASAnot effective
MANAGEMENT OF CROHN’S DISEASE
1) CD is a progressive condition thus Rx should focus on monitoring the pt for dis. activity & complications & ensuring
mucosal healing.
◾Corticosteroids are the mainstay of Rx for active CD.
o ileal CD.: Budesonide 9mg o.d for 6 wks, tapering for 2wks.
o colonic CD: Prednisolone 40mg/d, tapering 5 mg/wk over 8 wks.
MANAGEMENT OF CROHN’S DISEASE
 admission to hospital for I.V corticosteroids.
 Anti-TNF agents , if perforating complications (e.g. abscess) have not occurred.

 Combination with an anti-TNF antibody & a Thiopurine is the most effective.
 20–30% of pts remain well following induction of remission, without the requirement for maintenance Rx.
MAINTENANCE THERAPY:
1) Rx with thiopurines is the core of maintenance therapy.
2) MTX is also effective.
3) Combination of an immunosuppressant & an anti-TNF antibody is the most effective.
4) Cigarette smokers should stop smoking.
SURGICAL TREATMENT:
1) Impaired quality of life (most imp.)
• Loss of occupation or education
• Disruption of family life
2) Failure of medical Rx
• Dependence on oral corticosteroids
• Complications of drug therapy
3) Fulminant colitis
4) Disease complications unresponsive to medical therapy
• Arthritis
• Pyoderma gangrenosum
5) Colon CAor severe dysplasia
OPERATIONS ARE OFTEN NECESSARY IN PTS. WITH:
1) Fistulae
2) Abscesses
3) Perianal disease
4) Small or large bowel obstruction
In contrast to UC, surgery is not curative & dis. recurrence is the rule.
The only method that ↓ post-operative recurrence is smoking cessation
MAINTENANCE THERAPY:
1) in pts with persistently active dis.
2) Rx with thiopurines is the core of maintenance therapy.
3) MTX is also effective.
4) Combination of an immunosuppressant & an anti-TNF antibody is the most effective.
5) Cigarette smokers should stop smoking.
INDICATIONS FOR SURGERY IN U C & CD:
1) Impaired quality of life (most imp.)
• Loss of occupation or education
• Disruption of family life
2) Failure of medical Rx
• Dependence on oral corticosteroids
• Complications of drug therapy
3) Fulminant colitis
4) Disease complications unresponsive to medical therapy
• Arthritis
• Pyoderma gangrenosum
5) Colon CAor severe dysplasia
1. Fistulae
2. Abscesses
3. Perianal disease
4. Small or large bowel obstruction
In contrast to UC, surgery is not curative & dis. recurrence is the rule.
The only method that ↓ post-operative recurrence is smoking cessation
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IBD.pptx

  • 1. DR. Daras AL- Wasebi
  • 2. INFLAMMATORY BOWEL DISEASE (IBD) ◾ IBDs are a group of chronic inflammatory conditions in which the body’s own immune system attacks parts of the digestive system, with a relapsing & remitting course. ◾ IBD is characterized by times of active disease (flares), when symptoms are present, and times of remission, when little or no symptoms are present.
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  • 4. INFLAMMATORY BOWEL DISEASES (IBD)  The two most common inflammatory bowel diseases are Crohn’s disease (CD) and ulcerative colitis (UC).  There is no cure for IBD but there are treatments to reduce and control the symptoms of the disease.
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  • 6. PATHOPHYSIOLOGY: ◾ IBD is a polygenic disease; has both environmental & genetic components. ◾ Activation of immune cells by unknown inciting agent (microorganism, dietary component, bact. or self-Ag)→ release of cytokines & inflammatory mediators. o ↑risk in 1stdegree relatives of pts with IBD (largest independent risk factor) o HLA-DR2 with UC & a CD-related gene. o SerumANCA in 70% of UC pts. o Abs to Saccharomyces cerevisiae (ASCA) in 70% of CD pts.
  • 7. PATHOPHYSIOLOGY (CONT.….) o Emotional stress o Intercurrent infection o GE o ABX or NSAIDs o Cessation of smoking o In both CDAnd UC the intestinal wall is infiltrated with acute & chronic inflammatory cells but there are importance differences b/w them in the distribution of lesions & in histological features.
  • 8. CLINICAL FEATURE OF IBD  The symptoms of IBD vary from person to person, and may change over time.  The most common symptoms for CD and UC are frequent and/or urgent bowel movements, diarrhea, bloody stool, abdominal pain and cramping.  People with IBD may also report symptoms such as fatigue, lack of appetite and weight loss.
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  • 10. ◾ Rectal bleeding; bloody D with mucus (Cardinal symptoms). ◾ 1st attack is the most severe (D/D?) followed by relapses & remissions. ◾ Proctitis: with tenesmus. Constitutional symptoms do not occur. ◾ L.S & pancolitis: abd. cramps. ◾ Severe cases:A, malaise, wt. loss & abd. pain. Pt is toxic, with signs of peritonitis (?). The Truelove–Witts criteria for acute severe UC: ◾ ≥ 6 bloody stools/24hrs + ≥1 of: *anaemia *fever * ↑P.R *↑ESR
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  • 13. ◾ Rt. lower abd. pain provoked by eating, D & wt loss (Major symptoms). ◾ Features of fat, protein or vit. malabs. subac. or ac. Intestinal obstruction. ◾ Crohn’s colitis: similar to UC, but rectal sparing with perianal dis. ◾ Physical Examination: ◾ Wt. loss, anaemia. ◾ Abd. tenderness over the inflamed area. ◾ Palpable abd. mass. (D/D?) ◾ Perianal skin tags, fissures or fistulae (in 50% of pts).
  • 14. CLINICAL FEATURES OF ULCERATIVE COLITIS: ◾ Cardinal symptoms: rectal bleeding with passage of mucus & bloody D. ◾ 1st attack is usually the most severe; followed by relapses & remissions. ◾ Rectal bleeding, mucus discharge & tenesmus. ◾ Some pass freq., small volume fluid stools, while others pass pellety stools. ◾ Constitutional symptoms do not occur.
  • 15. CLINICAL FEATURES OF ULCERATIVE COLITIS(CONT…) ◾ Bloody D with mucus, often with abdominal cramps. ◾ Almost all patients are constitutionally well. ◾ Severe cases, anorexia,, malaise, wt loss & abd. pain. ◾ Pt is toxic, with signs of peritonitis (??) ◾ The Truelove–Witts criteria for acute severe UC: ◾ ≥6 bloody stools/24hrs ◾ anaemia <100 g/L (<10g/dL) ◾ fever ≥ 37.8°C ◾ P.R ≥ 90bpm ◾ ↑ESR> 30mm/hr
  • 16. CLINICAL FEATURES OF CROHN’S DISEASE: Rt- Lower abdominal pain, Diarrhea & wt. loss (due to anorexia or malabsorption); features of fat, protein or vitamins deficiencies.  Abdominal pain (acute /subacute intestinal obstruction),  with watery Diarrhea , not containing blood or mucus  inflammatory mass, intra-abdominal abscess
  • 17. CLINICAL FEATURES OF CROHN’S DISEASE:  similar to UC, but rectal sparing & presence of perianal dis. in CD.  Many pts have symptoms of both small bowel & colonic dis.  vomiting from jejunal strictures or severe oral ulceration.  Few patients have isolated perianal disease.
  • 18. PHYSICAL EXAMINATION:  Wt. loss, anaemia with glossitis & angular stomatitis.  Abd. tenderness over the inflamed area.  An abd. mass may be palpable.(D/D?) (matted loops of thickened bowel/abscess)  Perianal skin tags, fissures or fistulae (in 50%).
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  • 21. INVESTIGATIONS OF IB DISEASE:  CBC: Hb =↓ : bleeding or malabs. of Fe, folic acid or vit. B₁₂.  S. albumin =↓ protein-losing enteropathy, inflammatory disease or poor nutrition.  ESR & CRP =↑: in exacerbations & in abscess formation.  Serological tests: p-ANCA (?) &ASCA (?).  Faecal calproctectin: has a ↑ sensitivity for detecting GIT inflammation & may be ↑, even when the CRP is NL. It distinguishes IBD from IBS at Dx & for monitoring activity.  Bacteriology: stool: microscopy, culture (Help to exclude superimposed enteric infection in patients with exacerbations.), Clostridium difficile toxin & ova.
  • 22. INVESTIGATIONS OF IB DISEASE(CONT…) :cultures (Also advisable in febrile patients with known colitis or Crohn’s disease.)  Flexible sigmoidoscopy: to Dx ac. severe presentations  Ileocolonoscopy: later for dis. extent.  UC: loss of vascular pattern, granularity, friability & contact bleeding, ± ulcers  CD: patchy inflammation, with discrete, deep ulcers, strictures & perianal dis.  Colonoscopy: In established dis., for active inflammation with pseudopolyps or CA.
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  • 24. INVESTIGATIONS OF IBD: ENDOSCOPY image of ulcerative colitis affecting the left side of the colon. The image shows confluent superficial ulceration and loss of mucosal architecture Crohn's disease (regional ileitis)
  • 25. INVESTIGATIONS OF IB DISEASE(CONT…) i. Barium enema: less sensitive. ii. Barium follow-through: narrowed & ulcerated areas of the bowel, with multiple strictures. iii. MRI enterography: sensitive for extraintestinal manifestations & assessing pelvic & perineal involvement. It distinguishes b/w inflammation & fibrotic strictures
  • 26. INVESTIGATIONS OF IB DISEASE(CONT…) for dilatation of the colon, mucosal oedema or perforation. In SI CD, there may be evidence of intestinal obstruction. or displacement of bowel loops by a mass. to detect SI inflammation & strictures. to screen for complications (perforation or abscess) in the acutely unwell.
  • 27. MANAGEMENT OF IB DISEASE: i. Team approach: physicians, surgeons, radiologists, nurse specialists, dietitians, counsellors & pt support groups (emotional support). i. Treatment acute attacks (induce remission) & ii. Prevent relapses (maintain remission) iii. Prevent bowel damage iv. Detect dysplasia & prevent CA v. Select appropriate pts for surgery
  • 28. MANAGEMENT OF U C : i. iii. 5-ASA(amino salicylic acid) ii. corticosteroids AZA (azathioprine) iv. biological Rx (anti-TNF) v. colectomy is curative
  • 29. MANAGEMENT OF U C : i. iii. Mesalazine, Sulfasalazine : rectal suppository 1g are 1st line Rx. ii. Mesalamine (5-ASA): Oral, rectal suppository Topical corticosteroids: hydrocortisone enema if intolerant of topical mesalazine. iv. Systemic corticosteroids & immunosuppressants: in resistant dis.; useful as steroid-sparing agents.
  • 30. MANAGEMENT OF U C : 1) 5-ASA1g foam/liquid enema for 1month are 1stline Rx 2) Oral 5-ASA 3) Oral prednisolone (40mg/d, tapered by 5 mg/wk over 8wks) 4) Immunosuppressive Rx: thiopurine (AZA, 6-MP) 5) Severe ulcerative colitis. Pts who fail to respond to maximal oral therapy & those who present with ac. severe colitis (meeting Truelove–Witts criteria):
  • 31. MANAGEMENT OF U C : 1. Admit to hospital for intensive therapy & monitoring by a physician & surgeon 2. I.V fluids & correction of electrolyte imbalance 3. Transfusion if Hb< 100g/L(< 10g/dL) 4. IV methylprednisolone (60mg/d) or hydrocortisone (400 mg/d) by I.V.I or bolus 5. ABX until enteric infection excluded 6. Nutritional support for malnourished pts 7. S.C LMW heparin for prophylaxis of venous TE
  • 32. MANAGEMENT OF ULCERATIVE COLITIS  Avoidance of opiates & anti-diarrhoeal agents (can be given in mild cases)  Consider medical rescue therapy with 1. Cyclosporine (2 mg/kg I.V.I or oral) or 2. Infliximab (5 mg/kg) in stable pts not responding to 3-5ds of corticosteroids (~60% of cases, can avoid the need for urgent colectomy)
  • 33. MAINTENANCE OF REMISSION OF UC: Corticosteroids should never be used for maintenance therapy. Rx for all pts with Lt.S or extensive dis. 1) Oral Mesalamine (5-ASA) o.d are the 1st line agents. 2) Sulfasalazine has ↑S.Es but is equally effective esp. in pts with coexistent arthropathy. 3) Thiopurines in pts who relapse.
  • 34. MANAGEMENT OF CD : 1) Crohn’s disease 2) Corticosteroids 3) AZA(azathioprine) 4) MTX(methotrexate) 5) biological Rx (anti-TNF) 6) nutritional Rx 7) surgery for complications not curative 8) 5-ASAnot effective
  • 35. MANAGEMENT OF CROHN’S DISEASE 1) CD is a progressive condition thus Rx should focus on monitoring the pt for dis. activity & complications & ensuring mucosal healing. ◾Corticosteroids are the mainstay of Rx for active CD. o ileal CD.: Budesonide 9mg o.d for 6 wks, tapering for 2wks. o colonic CD: Prednisolone 40mg/d, tapering 5 mg/wk over 8 wks.
  • 36. MANAGEMENT OF CROHN’S DISEASE  admission to hospital for I.V corticosteroids.  Anti-TNF agents , if perforating complications (e.g. abscess) have not occurred.   Combination with an anti-TNF antibody & a Thiopurine is the most effective.  20–30% of pts remain well following induction of remission, without the requirement for maintenance Rx.
  • 37. MAINTENANCE THERAPY: 1) Rx with thiopurines is the core of maintenance therapy. 2) MTX is also effective. 3) Combination of an immunosuppressant & an anti-TNF antibody is the most effective. 4) Cigarette smokers should stop smoking.
  • 38. SURGICAL TREATMENT: 1) Impaired quality of life (most imp.) • Loss of occupation or education • Disruption of family life 2) Failure of medical Rx • Dependence on oral corticosteroids • Complications of drug therapy 3) Fulminant colitis 4) Disease complications unresponsive to medical therapy • Arthritis • Pyoderma gangrenosum 5) Colon CAor severe dysplasia
  • 39. OPERATIONS ARE OFTEN NECESSARY IN PTS. WITH: 1) Fistulae 2) Abscesses 3) Perianal disease 4) Small or large bowel obstruction In contrast to UC, surgery is not curative & dis. recurrence is the rule. The only method that ↓ post-operative recurrence is smoking cessation
  • 40. MAINTENANCE THERAPY: 1) in pts with persistently active dis. 2) Rx with thiopurines is the core of maintenance therapy. 3) MTX is also effective. 4) Combination of an immunosuppressant & an anti-TNF antibody is the most effective. 5) Cigarette smokers should stop smoking.
  • 41. INDICATIONS FOR SURGERY IN U C & CD: 1) Impaired quality of life (most imp.) • Loss of occupation or education • Disruption of family life 2) Failure of medical Rx • Dependence on oral corticosteroids • Complications of drug therapy 3) Fulminant colitis 4) Disease complications unresponsive to medical therapy • Arthritis • Pyoderma gangrenosum 5) Colon CAor severe dysplasia
  • 42. 1. Fistulae 2. Abscesses 3. Perianal disease 4. Small or large bowel obstruction In contrast to UC, surgery is not curative & dis. recurrence is the rule. The only method that ↓ post-operative recurrence is smoking cessation