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INFLAMMATORY BOWEL
DISEASE

Describe the different types of IBD. Discuss the

management of ulcerative colitis.

Discuss etiology, clinical features and management

of ulcerative colitis.

What are the ulcerative lesions of the colon. Discuss

the management of ulcerative colitis.
4. A patient gives chronic history of diarrhoea and

blood in stool presents with multiple fistulae in the
perineum and multiple stricture in smal intestine. The
diagnosis is ?

a)

Crohn's disease

b)

Radiation enteritis

c)

Ulcerative Colitis

d)

Ischemic bowel disease

5. Pt. with recurrent diarrhoea, pseudopolyp, lead

pipe appearance on Ba enema has ?

a)

Ulcerative colitis

b)

Crohn's disease

c)

Irritable bowel syndrome

d)

Short bowel syndrome
6. Pyoderma ? gangrenosum is most commonly

associated with ?

a)

Ulcerative colitis

b)

Crohns disease

c)

Amoebic colitis

d)

Ischemic colitis

7. Most common cause of death in Crohn's disease is

due to ?

a)

Sepsis

b)

Thromboembolic complication

c)

Electrolyte disturbance

d)

Malignancy


8. Two 34 year old men have a stoma ? one a colostomy in the left

iliac fossa after rectal surgery, and other an ileostomy in the right

iliac fossa after a panproctocolectomy for ulcerative colitis. Contents

of the colostomy bag in the left iliac fossa are relatively small in

volume and consist of well-formed stools. Contents of the ileostomy

bag in the right iliac fossa are relatively copious non-smelly fluid.

What is the best explanation for the difference?

A.

More than 75% of fluid absorption from the entire gut takes place in

the colon

B.

Random variation

C.

The caecum absorbs more fluid than the smal intestine

D.

There is net secretion of fluid in the left (descending) colon

E.

The colon absorbs a smal but significant proportion of ingested plus

secreted fluid in the gut

Ulcerative colitis
UC is one of the 2 major types of IBD.
Characteristical y involves only the large bowel.
The exact etiology is unknown.
HLA?B27 is identified in most patients with ulcerative

colitis.

It is a lifelong il ness that has a profound emotional and

social impact on the affected patients.

Spreads proximal y from the anal verge in an

uninterrupted pattern to involve part or the entire colon.

UC occasional y involves the terminal ileum, as a result

of an incompetent ileocecal valve.

ETIOLOGY

Unknown.
Factors contributing to UC include:
genetic factors,
immune system reactions,
environmental factors,
NSAID use,
low levels of antioxidants,
psychological stress factors,
a smoking history,
and consumption of milk products.
Genetics

Genetical y susceptible individuals have

abnormalities of humoral and cell-mediated
immunity.

Enhanced reactivity against commensal intestinal

bacteria and this dysregulated mucosal immune
response predisposes to colonic inflammation.

A family history of ulcerative colitis (observed in 1 in

6 relatives) is associated with a higher risk for
developing the disease.

Immune reactions

Autoantibodies against intestinal epithelial cells may

be involved.

The presence of antineutrophil cytoplasmic

antibodies (ANCA) and anti? Saccharomyces
cerevisiae antibodies (ASCA) is a well-known feature
of inflammatory bowel disease.


Other etiologic factors

Vitamins A and E are found in low levels in patients

with ulcerative colitis .

Psychological and psychosocial stress can

precipitate exacerbations.

Smoking is negatively associated with ulcerative

colitis. This relationship is reversed in Crohn disease.

Milk consumption may exacerbate the disease.

Pathology

The rectum is involved in all circumstances.
It is a diffuse inflammatory disease, primarily affecting the

mucosa and superficial submucosa.

There are multiple minute ulcers.
When the disease is chronic, inflammatory polyps

(pseudopolyps) occur.

Microscopic ally, there is an increase in inflammatory cells in

the lamina propria, the walls of crypts are infiltrated by

inflammatory cells and there are crypt abscesses.

There is depletion of goblet cell mucin.
With time precancerous changes can develop (= severe

dysplasia or carcinoma in situ).
History

Patients predominantly complain of rectal bleeding.

Frequent stools and mucous discharge from the

rectum.

Tenesmus.

Severe dehydration, especial y in the elderly

population.

Extracolonic manifestations

Uveitis, pyoderma gangrenosum, pleuritis, erythema

nodosum, ankylosing spondylitis, primary sclerosing
cholangitis and spondyloarthropathies.

Uveitis is the most common.
Physical Examination

Physical findings are normal in patients with mild

disease.

Patients with severe disease can have signs of

volume depletion and toxicity, including the

following:

Fever

Tachycardia

Significant abdominal tenderness

Weight loss

In general, a poor prognosis is indicated by

(1) a severe initial attack,

(2) disease involving the whole colon and

(3) increasing age, especial y after 60 years.
Grading

mild ? rectal bleeding or diarrhoea with four or

fewer motions per day and the absence of systemic

signs of disease;

moderate ? more than four motions per day but no

systemic signs of il ness;

severe ? more than four motions a day together

with one or more signs of systemic il ness: fever over

37.5?C, tachycardia more than 90\ min,

hypoalbuminaemia less than 30 g\ l, weight loss

more than 3 kg.

Ulcerative Colitis

Crohn Disease

Only colon involved

Panintestinal

Continuous inflammation extending

Skip-lesions with intervening normal mucosa

proximal y from rectum

Inflammation in mucosa and submucosa only Transmural inflammation

No granulomas

Noncaseating granulomas

Perinuclear ANCA (pANCA) positive

ASCA positive

Bleeding (common)

Bleeding (uncommon)

Fistulae (rare)

Fistulae (common)
WORKUP

Best made with endoscopy.
Double-contrast barium enema examination.
ANCA and ASCA.
Anemia.
Thrombocytosis.
Hypoalbuminemia.
Hypokalemia.
Hypomagnesemia.
Elevation of ESR and CRP.
Stool studies to exclude other causes.
Barium enema

The principal signs are:
? loss of haustration, especial y in the distal colon;
? mucosal changes caused by granularity;
? pseudopolyps;
? in chronic cases, a narrow contracted colon.
Colonoscopy and biopsy

The mucosa is hyperaemic and bleeds on touch,
There may be a pus-like exudate.
Pseudopolyps.
Ulcers are seen that appear to coalesce.
Colonoscopic biopsy is done:
1. to establish the extent of inflammation;
2. to distinguish between UC and Crohn's colitis;
3. to monitor response to treatment;
4. to assess longstanding cases for malignant change.
Colonoscopy and biopsy

Extensive disease - Evidence of ulcerative colitis

proximal to the splenic flexure

Left-sided disease - Ulcerative colitis present in the

descending colon up to, but not proximal to, the
splenic flexure

Proctosigmoiditis - Disease limited to the rectum with

or without sigmoid involvement

Complications

ACUTE:

Toxic megacolon

Perforation

Haemorrhage

CHRONIC:

Cancer

Extra-intestinal manifestations
TREATMENT

Medical management with corticosteroids and anti-

inflammatory agents.

Symptomatic treatment with antidiarrheal agents

and rehydration.

Surgery is contemplated when medical treatment

fails or when a surgical emergency (eg, perforation
of the colon) occurs.

5-aminosalicylic Acid Derivatives

:

1.

Sulfasalazine is useful in treating mild-to-moderate ulcerative colitis and

maintaining remission. Sulfasalazine is 5-aminosalicylate (5-ASA) coupled

to a sulfapyridine. It is poorly absorbed in the proximal bowel, and the

bacteria in the colon uncouple the 5-ASA from the sulfa moiety, al owing

5-ASA to exert its anti-inflammatory effect on the colonic mucosa by

inhibiting prostaglandin synthesis. It acts local y in the colon to reduce the

inflammatory response and systemical y inhibits prostaglandin synthesis.

2.

Balsalazide is a prodrug that is converted into 5-aminosalicylic acid

through bacterial azo reduction. Metabolites of drug may decrease

inflammation by blocking the production of arachidonic acid metabolites

in colon mucosa.

3.

Mesalamine is the drug of choice for maintaining remission. It is useful for

the treatment of mild-to-moderate ulcerative colitis. It is better tolerated

and has less adverse effects than sulfasalazine. Enema and suppository

forms are typical y used in patients with distal colitis.
Tumor Necrosis Factor Inhibitor

These agents prevent the endogenous cytokine from

binding to the cell surface receptor and exerting
biological activity. These agents adversely affect
normal immune responses and al ow development of
superinfections; reactivation of latent TB has been
reported in patients with previous exposure to TB.
Infliximab, Adalimumab, Golimumab.

Immunosuppressant Agents

These agents regulate key factors of the immune

system. Effective in bringing steroid-resistant
disease under control. Azathioprine, Cyclosporine, 6
-Mercaptopurine, Tacrolimus.
Corticosteroids

Decrease inflammation by suppressing the migration

of polymorphonuclear leukocytes and reversing
increased capil ary permeability.

They are used for induction of remission in moderate

-to-severe active ulcerative colitis.

They have no role in maintaining remission; long-

term use can cause adverse effects.

Alpha 4 Integrin Inhibitors

Emerging as option for moderate-to-severe active

IBD in patients who have had an inadequate
response with, lost response to, or were intolerant to
a TNF blocker or immunomodulator; or had an
inadequate response with, were intolerant to, or
demonstrated dependence on corticosteroids.
Vedolizumab.
Antimicrobials

They prolong GI transit time and decrease secretion

via peripheral mu-opioid receptors. Loperamide,

Treatment of mild disease

In disease confined to the rectum, topical

mesalazine given by suppository is the preferred
therapy.

Left-sided colonic disease is best treated with a

combination of mesalazine suppository and an oral
aminosalicylate.
Treatment of Acute, Severe disease

Acute, severe ulcerative colitis

ie, >6 bloody bowel movements/d, with one of the

following: fever >38?C, hemoglobin level < 10.5
g/dL, heart rate >90 bpm, erythrocyte
sedimentation rate >30 mm/h, or C-reactive protein
level >30 requires hospitalization and treatment
with intravenous high-dose corticosteroids
(hydrocortisone 400 mg/d or methylprednisolone
60 mg/d).

Alternative induction medications like Cyclosporine,

tacrolimus, infliximab, adalimumab, and golimumab
are used in steroid-resistant disease.
Maintenance therapy

Once remission has been achieved, maintenance therapy is

recommended for all patients to prevent relapse.

Oral aminosalicylates are indicated for disease that

responded to ASA or steroids.

Patients who are unable to maintain remission or are

intolerant to 5-ASA, Azathioprine and 6-mercaptopurine are

alternatives.

Extended-release oral formulation of budesonide provides

the benefit of a powerful anti-inflammatory drug delivered

locally while avoiding many of the systemic side effects

associated with systemic steroids.

Probiotics .

Indications for surgery

It is the definitive therapy for ulcerative colitis.

Failure of medical management is the most common

indication for surgery.

Indications for urgent surgery in patients with ulcerative

colitis include (1) toxic megacolon refractory to medical

management, (2) fulminant attack refractory to medical

management, and (3) uncontrolled colonic bleeding.

Indications for elective surgery in ulcerative colitis

include (1) long-term steroid dependence, (2) dysplasia

or adenocarcinoma found on screening biopsy, (3) and

disease present for 7-10 years.
Types of Surgery

Total abdominal colectomy with ileostomy: done

in emergency setting as a "first aid procedure". The
only problem is that because the rectal stump is left
behind chances of haemorrhage are always there.

Proctocolectomy and ileostomy: has the lowest

complication rate.Indicated in patients who are not
candidates for restoration. The patient is left with a
permanent ileostomy.

Restorative proctocolectomy with an ileoanal

pouch: In this operation, a pouch is made out of
ileum as a substitute for the rectum and sewn or
stapled to the anal canal.This avoids a permanent
stoma. Complications are pelvic sepsis , poor
function and pouchitis or inflammation of the pouch
,women may suffer from reduced fertility.
Colectomy and ileorectal anastomosis: used if

there is minimal rectal inflammation.

Annual rectal inspection is required

Has the advantage of stoma avoidance and

minimal risk to sexual function.

Ileostomy with a continent intra-abdominal

pouch (Kock's procedure): rarely
used.Complications include early leak with
formation of fistulae and late subluxation of the
valve.Pouch survival at 10 years was 87% in one
study.
CROHN'S DISEASE

1.

In Crohn's disease al are seen except:

a)

Hyperplastic polyps

b)

Diverticulosis

c)

Fissuring ulcer

d)

Epitheloid granuloma

e)

Crypt abscess
2. Crohn's disease is associated with following ?

a)

Stomach not involved

b)

No granulomatous + Transmucosal fissures

c)

Continuous involvement

d)

Through and trough involvement of thickness of
bowel wal

3. Transmural inflammation with skip lesions is colon

are characteristic of ?

a)

Regional ileitis (Crohn's disease)

b)

Ischemic colitis

c)

Ulcerative colitis

d)

Non specific colitis
Crohn disease is an idiopathic, chronic inflammatory

process that can affect any part of the gastrointestinal

tract from the mouth to the anus.

Occurs as a result of an imbalance between

proinflammatory and anti-inflammatory mediators.

Approximately 30% of Crohn disease cases involve the

smal bowel, particularly the terminal ileum, another

20% involve only the colon, and 45% involve both the

smal bowel and colon.

The characteristic presentation is abdominal pain and

diarrhea, which may be complicated by intestinal

fistulization or obstruction.

Etiology

Genetic,

Microbial,

Immunologic,

Environmental,

Dietary,

Vascular,

Psychosocial factors

Smoking and the use of OCPs and NSAIDs.
PATHOPHYSIOLOGY

Chronic inflammation from T-cell activation leading to tissue

injury is implicated in the pathogenesis of Crohn's disease.

After activation by antigen presentation, unrestrained

responses of type 1 T helper (Th1) cells predominate as a

consequence of defective regulation. Th1 cytokines such as

interleukin (IL)-12 and TNF- stimulate the inflammatory

response.

Inflammatory cells recruited by these cytokines release

nonspecific inflammatory substances, including arachidonic

acid metabolites, proteases, platelet activating factor, and

free radicals, which result in direct injury to the intestine.

Microscopical y, the initial lesion starts as a focal

inflammatory infiltrate around the crypts, followed
by ulceration of superficial mucosa. Later,
inflammatory cells invade the deep mucosal layers
and, in that process, begin to organize into
noncaseating granulomas .The granulomas extend
through al layers of the intestinal wal and into the
mesentery and the regional lymph nodes.
Macroscopical y, the initial abnormality consists of

hyperemia and edema of the involved mucosa.

Later, discrete superficial ulcers form over lymphoid

aggregates and are seen as red spots or mucosal

depressions (see the image below). These can

become deep, serpiginous ulcers located

transversely and longitudinal y over an inflamed

mucosa, giving the mucosa a cobblestone

appearance. The lesions are often segmental, being

separated by healthy areas, and are referred to as

skip lesions

HISTORY

Low-grade fever.

Prolonged diarrhea with abdominal pain.

Weight loss.

Generalized fatigability.

Crampy or steady right lower quadrant or periumbilical pain.

The pain precedes and may be partially relieved by defecation.

Diarrhea is not grossly bloody and is often intermittent.

Colonic Crohn disease may be clinically indistinguishable from

ulcerative colitis, with symptoms of bloody mucopurulent diarrhea,

cramping abdominal pain, and urgency to defecate.

Those with perianal disease may have debilitating perirectal pain,

malodorous discharge from the fistula, and disfiguring scars from

active disease or previous surgery.
H\o Recurrent attacks of SAIO\AIO.

Enterovesical fistula may present as recurrent

urinary tract infections and pneumaturia.

Enterovaginal fistulae may present as as feculent

vaginal discharge.

Enterocutaneous fistulae may present as feculent

soiling of the skin.

Physical examination

Chronic intermittent fever

Diffuse or localized abdominal tenderness.

Ful ness or a discrete mass may be appreciated,

typical y in the right lower quadrant of the abdomen.

Inspection of the perianal region can reveal skin tags,

fistulae, ulcers, abscesses, and scarring.

Mucocutaneous or aphthous ulcers,erythema nodosum

and pyoderma gangrenosum.

Eye examination may reveal episcleritis.

Arthritis and arthralgia.
Complications

Intra-abdominal abscesses.

Fistulae\ sinus tracts .

Bowel strictures and adhesions.

Perforation.

Colonic malignancy.

Disease activity and scoring systems

Montreal classification system is based on the

following 3 variables:

Age at diagnosis

Disease distribution/location

Disease behavior


Age at diagnosis (A) has 3 categories, as follows :

A1 ? 16 years

A2 ? 17-40 years

A3 ? > 40 years

Disease distribution/location (L) has the following 4 categories, 1 of which is a modifier for

upper GI involvement :

L1 ? Ileal

L2 ? Colonic

L3 ? Ileocolonic

L4 ? Isolated upper GI disease; L4 is a modifier that can be added to L1-L3 when there is

concomitant upper GI involvement

Disease behavior (B) has 1 interim category (B1) and 2 specified categories, with an

additional modifier for perianal diseases (p), as follows :

B1 ? Nonstricturing, nonpenetrating; B1p: nonstricturing, nonpenetrating with perianal

involvement

B2 ? Stricturing; B2p: stricturing with perianal involvement

B3 ? Penetrating; B3p: penetrating with perianal involvement

WORKUP

Complete blood cell count
Hypoalbuminemia
Deficiencies in iron and micronutrients
Liv
Acute inflammatory markers, such as CRP level or ESR,

may correlate with disease activity.

Stool samples should be tested for the presence of

WBCs, occult blood, routine pathogens, ova, parasites,

and Clostridium difficile toxin.

Fecal calprotectin has been proposed as a noninvasive

surrogate marker of intestinal inflammation in IBD.
WORKUP

Plain radiography or CT of the abdomen can be

used to assess for bowel obstruction or intra-
abdominal abscesses.

Barium contrast studies.

CT enterography or MR enterography.

MRI of the pelvis or transrectal ultrasonography can

identify perianal fistulae and detect pelvic and
perianal abscesses.

Endoscopy and biopsy.

TREATMENT-Medical

Steroids are the mainstay of treatment.

5-ASA compounds.

Those who have symptoms and signs of a mass or an

abscess are also treated with antibiotics.

Azathioprine is now standard maintenance therapy.

Anti-TNF therapy.

Nutritional support.
TREATMENT-Surgical

Indications for surgery

Surgical resection will not cure CD. Surgery is therefore

focused on the complications of the disease.

? recurrent intestinal obstruction;
? bleeding;
? perforation;
? failure of medical therapy;
? intestinal fistula;
? fulminant colitis;
? malignant change;
? perianal disease.

1.Ileocaecal resection.
2. Segmental resection.
3. Colectomy and ileorectal anastomosis.
4. Emergency colectomy.
5. Laparoscopic surgery
6. Temporary loop ileostomy.
7. Proctocolectomy.
8. Strictureplasty.
9. Anal disease is usually treated conservatively.