Inflammatory bowel disease

Causes of colonic inflammation

Infection - bacteria, viruses, parasites
Ulcerative colitis
Crohn's' disease
Radiation enteritis
Ischaemic colitis
Microscopic colitis
Drug-induced colitis

Ulcerative colitis

Prevalence in UK is about 80 /100,000
Peak age of onset 20 - 35 yrs
Characteristic feature - acute mucosal inflammation with crypt abscesses

Crohn’s disease

Prevalence in UK is about 40/100,000
Incidence is increasing possibly due to increased recognition
Characteristic feature - patchy transmural inflammation with non-caeseating granuloma

Pathophysiology

Both Crohn's disease and ulcerative colitis have some pathophysiological features in common
Both result from inappropriate activation of the mucosal immune system
This process is driven by the normal luminal flora
May result form defective barrier function of the intestinal epithelium
Genetic factors contribute to susceptibility as demonstrated by:
- Variable prevalence in different populations
- Increased incidence in first degree relatives
- Increased concordance in monozygotic twins
- Concordance in site and type of disease in affected families
Possible environmental factors include:
- Smoking
- Use of NSAIDs
- Luminal flora

Pathological features

Ulcerative colitis Crohn's disease

Lesions continuous - superficial Lesions patchy - penetrating

Rectum always involved Rectum normal in 50%

Terminal ileum involved in 10% Terminal ileum involved in 30%

Granulated ulcerated mucosa Discretely ulcerated mucosa

No fissuring Cobblestone appearance with fissuring

Normal serosa Serositis common

Muscular shortening of colon Fibrous shortening

Fibrous strictures rare Strictures common

Fistulae rare Enterocutaenous or intestinal fistulae in 10%

Anal lesions in <20% Anal lesions in 75%

Anal fistulae & chronic fissures

Malignant change well recognised Possible malignant change

Picture provided by Manickam Vairavan, Consultant surgeon, Sandwell and West Birmingham Hospitals NHS Trust.

Picture provided by David Lockwood, Princess Alexandra Hospital, Brisbane, Australia

Clinical features of inflammatory bowel disease

Ulcerative colitis

30% disease confined to rectum
15% develop more extensive disease over 10 years
20% total colonic involvement from onset
Patients generally fall into following categories:
- Severe acute colitis
- Intermittent relapsing colitis
- Chronic persistent colitis
- Asymptomatic disease
Assessment of disease severity
- Mild = < 4 stools per day. Systemically well
- Moderate = > 4 stools per day. Systemically well
- Severe = > 6 stools per day. Systemically unwell
- Systemic features include tachycardia, fever, anemia, hypoalbuminaemia
Endoscopic grading of ulcerative colitis
- 0 = normal
- 1 = loss of vascular pattern or granularity
- 2 = Granular mucosa with contact bleeding
- 3 = Spontaneous bleeding
- 4 = Ulceration

Crohn’s disease

Clinical features depend on site of disease
50% have ileocaecal disease
25% present with colitis
Systemic features are more common than in ulcerative colitis

Extraintestinal manifestations

Associated with disease activity
- Skin
  - Erythema nodosum
  - Pyoderma gangrenosum
- Joints
  - Asymmetrical non-deforming arthropathy
- Eyes
  - Anterior uveitis
  - Episcleritis
  - Conjunctivitis
- Hepatobiliary conditions
  - Acute fatty liver
- Thromboembolic disease
Unrelated to disease activity
- Joints
  - Sacroilitis
  - Ankylosing spondylitis
- Hepatobiliary conditions
  - Primary sclerosing cholangitis
  - Cholangiocarcinoma
  - Chronic active hepatitis
  - Gallstones
- Amyloid
- Nephrolithiasis

Medical management of inflammatory bowel disease

Treatment depends on
- Type of disease
- Site of disease
- Disease severity
Different drugs may be used for active disease and those in remission

5-Aminosalicylic acid

Used in mild / moderate ulcerative colitis and Crohn's disease
5-ASA block production of prostaglandins and leukotrienes
Sulfasalazine was first agent described
Now compounds available to release 5-ASA at site of disease activity
Mesalazine is conjugated to prevent absorption in small intestine
Topical preparation may be used in those with left-sided colonic disease
Maintenance therapy of proven benefit in those with ulcerative colitis
Of unproven benefit in those with Crohn's disease

Corticosteroids

Often used in those in whom 5-ASA therapy is inadequate
Also used in those presenting with acute severe disease
Can be given orally, topically or parenterally
Use should be limited to acute exacerbations of disease
Of no proven value as maintenance therapy in either ulcerative colitis or Crohn's disease
Use must be balanced against side effects

Immunosuppressive and immunomodulatory agents

Often used in those in whom steroids can not be tapered or discontinued
Agents used include:
- Azathioprine -effective in both ulcerative colitis and Crohn's disease
- Methotrexate - effective in Crohn's disease
- Cyclosporin
- Inflixitab - anti-TNF-alpha therapy

Surgery for inflammatory bowel disease

Indications for surgery - Ulcerative colitis

20% of patients with ulcerative colitis require surgery at some time
30% of those with total colitis require colectomy within 5 years

Emergency

Toxic megacolon

Perforation
Haemorrhage
Severe colitis failing to respond to medical treatment

Elective

Chronic symptoms despite medical therapy
Carcinoma or high grade dysplasia

Surgical options

Emergency

Total colectomy with ileostomy and mucus fistula

Elective

Panproctocolectomy and Brooke ileostomy
Panproctocolectomy and Kock continent ileostomy
Total colectomy and ileorectal anastomosis
- Maintains continence but proctitis persists
Restorative proctocolectomy with ileal pouch
- Need adequate anal musculature
- Need for mucosectomy unclear
- May need defunctioning ileostomy

Picture provided by Fernando Lisboa, Universidade Federal de Rio Grande do Norde, Brazil

Pouch design

Functional results of ileoanal pouch

Mean stool frequency is six per day
Perfect continence
- During day (90%)
- At night (60%)
Gross incontinence (5%)

Morbidity

50% develop significant complications
Small bowel obstruction (20%)
Pouchitis (15%)
Genitourinary dysfunction (6%)
Pelvic sepsis (5%)
Fistula (5%)
Pouch failure (6%)
Anal stenosis (5%)
Larger capacity pouches reduce stool frequency

Indications for surgery - Crohn’s disease

Absolute

Perforation with generalised peritonitis
Massive haemorrhage
Carcinoma
Fulminant or unresponsive acute severe colitis

Elective

Chronic obstructive symptoms
Chronic ill health or debilitating diarrhoea
Intra-abdominal abscess or fistula
Complications of perianal disease
Surgery should be as conservative as possible
No evidence that increased resection margins reduce risk of recurrence
If possible improve preoperative nutritional state

Surgical Options

Limited resections
30% undergoing ileocaecal resection require further surgery
Strictureplasty often successful
Bypass procedures rarely required

Bibliography

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