Ulcerative Colitis

1. Refers to two chronic diseases that cause inflammation of the intestine: Ulcerative colitis and Crohn's disease.

2. Although the diseases have some features in common, there are some important differences.

INFLAMMATORY BOWEL DISEASE

Epidemiology

Ulcerative Colitis:– High incidence areas: US, UK, northern Europe– Young adults, commoner in females

Crohn's Disease:– 1st peak 15-30 years of age, 2nd peak around 60

y

INCIDENCE IS ON THE RISE IN ASIAN (INDIA) POPULATION

Rise of Incidence in IBD in India

Familial aggregation Nicotine Consumption Oral Contraceptives Dietary Habits-Refined sugars, Fast

food, cereals, bakers yeast etc

Physical inactivity Early weaning Hygiene Infectious diseases- TB, Measles

Ulcerative Colitis

A mucosal disease usually involves rectum and extended proximally to involve all or a part of colon.

Small intestine is not involved

Ulcerative Colitis

When the whole colon is involved, inflammation extends 1-2 cm in Terminal ileum ( Back wash ileitis)

40-50% 30-40%

20%

ULCERATIVE COLITIS – CLINICAL PRESENTATION

The major symptoms of UC are:

- Diarrhea- Rectal bleeding- Tenesmus- Passage of mucus- Crampy abdominal pain- Loss of weight

UC – DISEASE PRESENTATION

MILD MODERATE SEVEREBOWEL MOVEMENTS

< 4 per day 4-6 per day

>6 per day

BLOOD IN STOOL

small moderate SevereFEVER none <37,5°C > 37,5°C TACHYCARDIA none <90 mean

pulse>90 mean pulse

ANEMIA mild >75% <75%SEDIMENTATION RATE

<30mm >30mm

HOW UC IS DIAGNOSED

Clinical history Physical examination Laboratory tests Colonoscopy X-ray findings Tissue biopsy (pathology)

Diagnosis of IBD (UC vs. CD) Allows visualization of large intestine and ileum Allows biopsies to examine colon

tissue Determines activity of disease Important for pre-cancer surveillance in UC and CD

COLONOSCOPY : IBD

COLONSCOPY : UC

Normal UC

SUPERFICIAL ULCERATION AND LOSS OF MUCOSAL ARCHITECTURE

Colonic pseudopolyps

Microscopic Findings in UC

DIFFERENT CLINICAL FEATURES

U. Colitis Crohn’s disease

Blood in stool Yes OccasionallyMucus Yes OccasionallySystemic symptoms

Occasionally Frequently

Pain Occasionally FrequentlyAbdominal mass

Rarely Yes

Perineal disease

No Frequently

DIFFERENT CLINICAL FEATURES

U. Colitis Crohn’s disease

Fistulas No YesSmall intestine obstruction

No Frequently

Colonic obstruction

Rarely Frequently

Response to antibiotic

No Yes

Recurrence after surgery

No Yes

DIFFERENT ENDOSCOPIC FEATURES

U. Colitis Crohn’s disease

Rectal sparing Rarely FrequentlyContinuous disease

Yes Occasionally

“Cobble stoning”

No Yes

Granuloma on biopsy

No Occasionally

Serpiginous ulcer, a classic finding in Crohn's disease

Pathologic features of Crohn's Disease and Ulcerative ColitisFeature Crohn's

DiseaseUlcerative

Colitis

Transmural inflammation

Yes Uncommon

Granulomas 50-75% No

Fissures Common Rare

Fibrosis Common No

Submucosal inflammation

Common Uncommon

Clinicopathological comparison of CD,UC and GITBFeatures % CD UC GITB

Diarrhoea 70 100 35

Hematoch. 40 100 0

Rectal Sym 10 100 0

Abd. Pain 55 25 85

Obst.Symt. 0 0 35

Fever 10 15 35

Wt loss 55 40 75

Lump 20 0 45

Fistula 20 0 0

Perianal les 20 5 0

Pallor 55 60 50

Smoking 25 5 25

Past h/o ATT 50 0 0

Past abd. surgery

25 5 15

Salient Distinguishing Features of GI TB

Granuloma more than 400 u in maximum dimension

More than 4 sites of granulomaper site

Band of epitheloid histiocytes in ulcer bases

Granuloma located in the caecum

Algorithm for pts with GI TB Pt with suspected TB Endoscopy with multiple deep

biospies Histopathology AFB smear AFB

Culture Positive for TB – Start ATT Negative for TB– search for extraintestinal

features of CD Laparascopy /Lap assited

enteroscopy+BX

ULCERATIVE COLITIS - COMPLICATIONS

Hemorrhage Perforation Stricture Toxic megacolon (transverse colon with a

diameter of more than 5.0 cm to 6.0 cm with loss of haustration)

Malabsorbtion Obstruction Possibility of malignant transformation?

Inflammatory Bowel Disease

CHRONIC DISORDER INCURABLE LIFE TIME TREATMENT

Goals of Therapy for UC

Inducing remission Maintaining remission Restoring and maintaining nutrition Maintaining patient’s quality of life Surgical intervention (selection of

optimal time for surgery)

TREATMENT

Medical treatment Aminosalicylates (5-ASA) Glucocorticoids Azathioprine or 6-MP Cyclosporine Infliximab Low roughage diet No milk Sometimes TPN

5-Aminosalicylic Acids

Sulfasalazine Olsalazine Balsalazide Asacol Rowasa Enema Pentasa Canasa Suppository

5-Aminosalicylic Acids

The mainstay treatment of mild to moderately active Ulcerative Colitis and Crohn's Disease

• 5-ASA may act by - Blocking the production of prostaglandins and

leukotrienes

5-ASA absorbed in small intestine - Do not reach colon - Hence need delivery system - 2 types of delivery systems

pH dependent resin or semi permeable membrane 5-ASA +bond (like sulfasalazine)

Oral 5-ASA Release Sites

Stomach

Small Intestine

Large Intestine

Azo bond

AZO-COMPOUNDS

Mesalamine in microgranules

Pentasa®

Mesalaminew/ eudragit-S

Asacol®

5-ASA AGENTS (AMINOSALICYLATES)Benefits

Well-tolerated Few side effects Relatively inexpensive Oral or Rectal Safe for all ages & pregnancy

Risks

Not helpful in severe disease side effects - skin rashes - Fever - Arthralgia - Agranulocytosis - Pancreatitis - Hepatitis - Male infertility

CORTICOSTEROIDS

Topical corticosteroids can be used as an alternative to 5-ASA in ulcerative proctitis or distal Ulcerative Colitis.

Oral prednisone or prednisolone is used for moderately severe Ulcerative Colitis or Crohn's Disease,( for about 1 month) in doses ranging up to 60 mg per day.

IV is warranted for patients who are sufficiently ill to require hospitalization; the majority will have a response within 7 to 10 days.

CORTICOSTEROIDS

Benefits Induces remissions in UC and CD

Inexpensive

Oral or rectal

Risks No long-term benefits

Numerous side effects

– Cushingoid changes

– Hypertension

– Diabetes

– Osteoporosis

– Acne

– Cataracts

– Depression

– Growth retardation

CORTICOSTEROIDS

No proven maintenance benefit in the treatment of either Ulcerative Colitis or Crohn's Disease.

Budesonide: – less side effects, – its use is limited to patients with distal ileal

and right-sided colonic disease

Immunosuppressive Agents

These agents are generally appropriate for patients in whom the dose of corticosteroids cannot be tapered or discontinued.

Azathioprine & 6-MP – The most extensively used immunosuppressive

agents.– The mechanisms of action unknown but may

include suppressing the generation of a specific

subgroup of T cells. – The onset of benefit takes several weeks up to

six months.

AZATHIOPRINE & 6-MP

Long-term (maintenance) treatments for UC or CD

Can treat fistulas in CD over long-term Primarily for patients unable to get off

steroids Requires continuous monitoring of

blood tests

AZATHIOPRINE & 6-MP

Benefits “Steroid-sparing” in UC and CD Long-term maintenance Relatively inexpensive

Risks Can lower blood counts and “immunity” Requires long-term monitoring Occasional allergies – Pancreatitis – Fever

Maintenance Therapies for Ulcerative Colitis

Aminosalicylates

Azathioprine/6-MP

Immunosuppressive Agents

Methotrexate – Effective in steroid-dependent active Crohn's

Disease and in maintaining remission.– Potential side effects and risks include nausea,

vomiting, infections, bone marrow suppression, liver inflammation,.

Cyclosporine – Severe Ulcerative Colitis not responding to IV

steroid &need urgent proctocolectomy.– 50% of the responders will need surgery within

a year.

CYCLOSPORINE

Benefits Effective in severe UC Works rapidlyRisks Renal insufficiency Seizures Hypertension Electrolytes abnormalities

20Patients

2

81

9

11

Cyclosporine in Patients withSevere Ulcerative Colitis

Cyclosporine

No Response: surgery

Response

Elective colectomy

Oral Cyclosporine

Lichtiger S et al. NEJM 1994

Anti-TNF Therapy: Infliximab Monoclonal antibody, binds soluble TNF. Prompt onset, effects takes 6 weeks to

max of 6m. Indicated in fistulizing Crohns,

refractory Crohn's Disease and refractory Ulcerative Colitis

BIOLOGIC THERAPY: INFLIXIMAB

Benefits Induces and maintains remissions in CD Rapidly relieves symptoms & fistula drainage Steroid-sparing Effective even when other therapies failRisks Reactions to intravenous infusions Development of antibodies and loss of response Reactivation of TB Expensive

Other therapies in UC

Probiotics Nicotine (immunomodulation & increase free oxygen

radicals Heparin (antiinflammatory & immunomodulatory)• Natalizumab (anti-adhesion molecule)• Daclizumab (monoclonal antibody)• Basiliximab (monoclonal antibody)• Visilizumab (monoclonal antibody)• Leukocytapheresis• Porcine whipworm (Trichuri – suis)• Nutritional therapy (short chain fatty acid butyrate and

fish oil containing eicosapentanoic acid)

Treatment of Active UP

Topical therapy preferred treatment

Corticosteroids and5-ASAs available in many forms – suppositories reach

the upper rectum – enemas reach

splenic flexure and the distal transverse colon

Proximal distribution of topical preparations

Adapted with permission from: Marshall JK, Irvine EJ. Am J Gastroenterol 2000; 95:

1628-1636.

Therapeutic Pyramid for Active UC

Severe

Moderate

Mild

Systemic Corticosteroids

Aminosalicylates

Surgery

Oral SteroidsAZA/6-MP

Cyclosporine

Infliximab

SURGERY IN IBD

Ulcerative Colitis Surgery (colectomy), is curative Colectomy & ileostomy Colectomy & ileo-anal Anastomosis (J-pouch)

Crohn’s Disease Surgery does not cure Disease recurs after a resection Resection of inflamed segments to treat

complications or “refractory” disease

Uncontrollable colonic hemorrhage Failure to control severe attacks or toxic

megacolon Colonic perforation Chronic symptoms despite medical therapy Medication side effects without disease control Dysplasia or Cancer Growth retardation

Surgery in UC : why & when?

Surgery in UC : why & when?

Intractability:

- Colitis refractory to medical management

- Often due to side effects of medical treatments

- Most common indication for operation

Dysplasia/Carcinoma:

- high-grade dysplasia : absolute indication

Massive Colonic Bleeding: - very infrequent; less than 5% of urgent UC colectomies

Toxic Megacolon: - acute colitis accompanied by significant colonic dilatation

- high fever, severe abdominal pain,tachycardia, leukocytosis

- predisposed to perforation

- treatment: IVF resuscitation, antibiotics, steroids, immunosuppressives

- clinical deterioration despite above : urgent operation

TYPES OF OPERATIONS

Total Proctocolectomy with End-Ileostomy: - removes entire colon, rectum, and anus - performed in one stage; avoids problems of multiple operations - disadvantages: permanent stoma, problems with healing perineal

wound

Total Abdominal Colectomy with Hartmann’s Closure or Mucous Fistula:

- used in acutely sick patients (fulminant colitis, toxic megacolon)

Total Proctocolectomy with Ileal Pouch-Anal Anastomosis: - gold standard - requires good anorectal function and sphincter tone - generally performed on patients younger than 65

Complications of UC Surgery

Mortality (<0.5%) 3-10 stools/24 hrs so bowel pattern not

normal Impotence (1.5%) Pouchitis (10-60%) Small bowel obstruction (20%) Decrease in female fertility (56-98%) Pouch-vaginal fistula (4%)

GOALS FOR SURGEON AND PATIENT

Restore quality of life

Herbal Food Supplements

Holarhena AntidysentricaOroxylum IndicumBombax MalabaricaMyristica FragrancePunica Granatum

IBD conclusion

It is a chronic disorders Need to exclude other possibilities Need to differentiate between the two Need long term management with

primary goal to induce then maintain remission and prevent complications of both the disease and drugs.