Inflammatory Bowel Disease

Professor mohammed Ahmed

Bamashmos
• Inflammatory bowel disease is an idiopathic
and chronic intestinal inflammation
• Types :
– Ulcerative colitis : limited to the colon and rectum
– Crohn’s disease : affects any portion of the GI
tract from oesophagus to anus

– Both exhibit extra intestinal inflammatory

manifestations
• Epidemiology
– Ulcerative colitis – most common IBD
– Peak age of onset of UC & CD is 15- 30 years
– and 60 & 80
– M:F = 1:1 for UC and F>M for CD
– Crohn’s diseases is more common in
smokers, oral contraceptive users.
• Etiology and pathogenesis :
– Etiology and pathogenesis have not been defined
– Current etiologic theories concerning IBD focus on
environmental triggers, genetic factors, and
immunoregulatory defects and microbial exposure
– Two key points :
• Strong immune responses against normal flora
• Defects in epithelial barrier functions
– Though idiopathic, it is postulated that IBD results
from unregulated and exaggerated local immune
response to commensals in gut, in genetically
susceptible individuals
• Genitical susceptibility :
– Familial predisposition with no clear mendelian
inheritance
– Associated with HLA- DR1 , HLA- DR2, HLA-DR27
– Role of intestinal flora:
• Exacerbate immune response by providing Ag and
inducing constimulator and cytokines 🡪 t-cell activation
🡪 defects in barrier function
– Infection: Chlamydia, atypical bacteria, measeals
virus, helicobacter
– Psychosocial factors: sensitive, reserved persons,
death in family, divorce, conflict – STRESS. etc
– Environmental factors : diets and smoking
(Crohns’s)
• PATHOPHYSIOLOGY:
– The common end pathway is inflammation of the
mucosal lining of the intestinal tract, causing
ulceration, edema, bleeding, and fluid and
electrolyte loss.
– Both UC and CD , activated CD4+ T-cells in the
lamina propria and pheripheral blood secrete
inflammatory cytokines
• various antigenic stimuli🡪Cytokines, released
by macrophages 🡪bind to different receptors
and produce autocrine, paracrine, and
endocrine effects🡪 leads to intestinal damage
and increased permiability
– T cells, type 1 (Th-1)= Crohn disease,
– whereas, Th-2 cells = Ulcerative colitis
IBD:
• Both UC and CD have waxing and waning in
intensity and severity
• In most cases, symptoms correspond with
degree of inflammation
• When patient is actively symptomatic,
significant inflammation = flare-up of IBD
• When asymptomatic, inflammation absent (or
less) = in remission
 Ulcerative colitis (UC):
Pathophysiology –
• Affects only the large intestine (very rarely terminal
ileum may be inflamed superficially)
• Always starts in rectum and is continuous until some
proximal part of the colon ; and no "skip areas"
• Involves the mucosa and submucosa with deeper
layer unaffected ( except in fulminant disease).
Mucosa is:
- Erythematous, has a granular surface that looks like a sand paper

• In more severe diseases:

- Hemorrhagic, edematous and ulcerated; formation of crypt
abscesses

• In fulminant disease : A toxic colitis or a toxic megacolon may

develop ( wall become very thin and mucosa is severly ulcerated)

• As UC becomes chronic, colon becomes rigid and loses its haustral

(pouch-like) markings
• Confined to rectum in 25% of cases; pancolitis in 10% of cases
• when whole colon involved – 1-2 cm ileum involved = Backwash
ielitis
 Ulcerative colitis – clinical presentation

The major symptoms of UC are:

- Diarrhea
- Rectal bleeding
- Tenesmus
- Passage of mucus
- Crampy abdominal pain
- Loss of weight
- Psychological disturbances
• Patients with proctitis usually pass fresh blood
or blood-stained mucus either mixed with
stool or streaked onto the surface of normal
or hard stool
• When the disease extends beyond the rectum,
blood is usually mixed with stool or grossly
bloody diarrhea may be noted
• When the disease is severe, patients pass a
liquid stool containing blood, pus, fecal matter
• Other symptoms in moderate to severe
disease include: anorexia, nausea, vomitting,
fever, weight loss
• Investigation :
– Active phase: rise in CRP, platelet counts, ESR ,
decrease in Hb.
– Severe form : serum albumin will fall
– Dig.:- history, clinical symptoms , negative stool
examination for micro organisms; sigmoidoscopic
appearance ;histology
 Radiologic change of UC
• The plain abd radiograph can show a dilated
colon& small-bowel obstruction
• Contrast barium enema:
– Fine mucosal granularity
– Mucosa become thickenned and superficial ulcers
are seen (collar-button ulcers)– mucosa
penetration
– Loss of haustration
– Shortened and narrowed colon .
• Ileitis in UC (without the skip pattern)
• CT & U/S best for demonstrating mesenteric
inflammation, intra-abdominal abscesses and
fistulas
• Colonoscopy recommended for making
diagnosis and determining severity of disease
 Ulcerative colitis - complication
• Hemorrhage
• Perforation
• Stricture
• Toxic megacolon (transverse colon with a
diameter of more than 5 cm to 6 cm with loss of
haustration)
• Malabsorbtion
• Obstruction
• Possibility of malignant transformation?
Colonic pseudopolyps
Ulcerative colitis:the left side of the colon is affected
The image shows confluent superficial ulceration
and loss of mucosal architecture.
lead pipe appearance
A 22-year-old man presented with abdominal pain, passage of blood and mucus per rectum,
abdominal distention, fever, and disorientation. Findings from sigmoidoscopy confirmed
ulcerative colitis. Abdominal radiographs obtained 2 days apart show mucosal edema and
worsening of the distention in the transverse colon.
 Diagnosis of UC
– H&P
– CT
– Stool exam
– Sigmoidscopy
– Colonoscopy
– Barium enema
– Lab studies
 Crohn’s disease (CD)
• Crohn's disease differs from ulcerative colitis in the areas of
the bowel it involves - it most commonly affects the last
part of the small intestine and parts of the large intestine.
– In 75% of patients with small intestinal disease the terminal
ileum in involved in 90%

• Crohn's disease isn't limited to these areas and can attack

any part of the digestive tract
• Crohn's disease generally tends to involve the entire bowel
wall
• Can have non-continuous pattern-”skip lesions”, with areas
of severe inflammation with intervening normal mucosa
• May be complicated by strictures, fistulas and abscesses
Distribution of gastrointestinal Crohn's disease.
Based on data from American Gastroenterological Association.
 Pathophysiology :

• CD is a transmural process

• CD is segmental with skip areas in the midst of

diseased intestine

• In one –third of patients with CD perirectal

fistulas, fissures, abscesses, anal stenosis are
present
• mild disease is characterized by:
apthous or small superficial ulcerations
• In more active disease:
stellate ulcerations fuse longitudinally and
transversely to demarcate island of mucosa
that are histologically normal
• Cobblestone appearance is characteristic of
CD (both endoscopically and by barium
radiography)
• Active CD is characterized by focal inflammation
and formation of fistula tracts.

• The bowel wall thickens and becomes narrowed

and fibrotic, leading to chronic, recurrent bowel
obstruction.

• Aphtoid ulceration and focal crypt abscesses with

loose aggregation of macrophages which form
granulomas is formed in all the layers.

• Transmural inflammation that is accompanied by

fissures that penetrate deeply into the bowel wall
serpiginous ulcer, a classic finding in Crohn's disease
 Crohn’s disease – sign and symptoms

• Ileocolitis
- right lower quadrant pain and diarhhea
- palpable mass, fever and leucocytosis
- pain is colickly and relieved by defecation
- fistula formation leading to adjecent organs and bowel
causing recurrent bladder infections , dyspareunia or
foul smelling vaginal discharges.
• Jejunoileitis
- inflammatory disease is associated with loss of
digestive and absorptive surface 🡪 malabroption and
steatorrhoea
Crohn’s disease – sign and symptoms
Colitis and perianal disease
- low grade fever, malaise, diarrhea, crampy
abdominal pain, sometimes hematochezia
- pain is caused by passage of fecal material
through narrowed and inflamed segments of
large bowel
• Gastroduodenal disease
- nusea, vomiting, epigastric pain
- second portion of duodenum is more
commonly involved than the bulb
The normal colon shows regular haustra and a transparent
intact mucosa. The colon from the patient with Crohn's
disease shows numerous deep ulcerations and areas of more
normal appearing mucosa.
Endoscopic image of Crohn's colitis showing deep ulceration.
Crohn disease involving the terminal ileum. Note the "string sign"
in the right lower quadrant
 Crohn’s disease
Diagnostic tests are the same except:
1- With Crohn’s will find string sign (segments of stricture
separated by normal bowel)
2- With colonoscopy will find patchy areas of inflammations 🡪Skip
areas & rectal sparing in CD
3- Need biopsy for definitive diagnosis

• Complications:
– Fistula formation
– Peritonitis due to rupture of intraabdominal absecess
– Intestinal obstructions
– Massive hemorrhage
– Malabsorption
– Severe preianal diseases
• The fistulae become symptomatic with drainage of
fecal material around the anus (perianal fistulae),
seepage of bowel contents through the skin
(enterocutaneous fistulae), passage of feces through
the vagina (rectovaginal fistulae)& pneumaturia or
recurrent urinary tract infections (enterovesical
fistulae).
 Serologic Test

• pANCA and ASCA

• Perinuclear antineutrophil cytoplasmic

antibodies (pANCA) with ulcerative colitis, and
• anti-Saccharomyces cerevisiaeantibodies
(ASCA) have been found in patients with
Crohn’s disease.
IBD is associated with variety of
extraintestinal manifestation.
Almost one-third of the patients have
at least one.
 Extraintestinal manifestation
Dermatologic
1. Erythema nodosum occurs in up to 15% of CD patients and
10% of UC patients
The lesions of EN are hot, red, tender nodules measuring to 5cm
in diameter and are found on the anterior surface of the legs,
ankles, calves, thighs and arms
2. Pyoderma gangrenosum (PG) is seen in 1 to 12% of UC
patients and is less common in CD colitis. PG may occur years
before the onset of bowel symptoms.
Lesions are common on the dorsal surface of the feet and legs
but may occur on the arms, chest and even face.
Pyoderma gangrenosum
 Extraintestinal manifestation
Rheumatologic
Peripherial arthritis developes in 15 to 20% of IBD
patients, is more common in CD.
It is asymmetric, polyarticular and migratory.
Most often affects large joints of the upper and
lower extremities
Ankylosing spondylosis (AS) occurs in 10% of IBD.
Sacroilitis is symetrical, occurs equally in UC and CD,
often asymptomatic
 Extraintestinal manifestation
Ocular
The incidence of ocular complications in IBM
patients is 1 to 10%
The most common is conjunctivitis, anterior
uveitis, episcleritis
Symptoms include: ocular pain, photophobia,
blurred vision, headache
 Extraintestinal manifestation
Urologic
The most frequent genitourinary
complications are: calculi, ureteral
obstruction, fistulas
The highest frequency of nephrolithiasis (10-
20%) occurs in patients with CD.
Patients with IBD have an increased
prevelance of osteoporosis secondary to
vitamin D deficiency, calcium malabsorbtion,
malnutrition, corticosteroid use
More common cardiopulmonary
manifestations include endocarditis,
myocarditis, pleuropericarditis and
interstitial lung disease.
 Treatment
• Treatment of inflammatory bowel disease
involves drug therapy and in certain cases
surgery
• 5-ASA agents – (5-aminosalicylic acid)
– Main stay of management for mild to moderate UC
and CD
– Sulfasalazine and other 5ASA agents are used.
– Used effectively at inducing remission in both UC and
CD and in maintaining remission in UC.
– Newer 5-ASA preparation lack sulfa moiety of sulfa
salazine and are associated with few side effects.
– MESALAMINE
• Asacol 800- 1600 mg tid --🡪 UC as well as for CD
• Pentasa 0.5 – 1.0 mg BD 🡪 for diffuse CD also in UC
• Osalazine
• Glucocorticoids :
– Inducing remission of active UC and chrons disease.
– Not recommended for mild diseases.
– Used concurrently with other anti- inflammatory drugs
– ocular lesions, skin disease, and peripheral artheritis also
responds
– Prednisolone 40-60 mg once daily and tappering off in 3-6 wks.
– In severe 🡪 IV administrations of methylprednisolone 20 -40 mg
daily BD
– Higher dose in refractory disease
– Not recommended for maintenance therapy
– Budesonide may have less systemic effects >>> mild to moderate
ileocolonic CD.
• Immunosuppressive agents :
– 6- mercaptopurine
• Cause supression of T-cell activation and antigen
recognition
• 1.0 – 1.5 mg/kg daily
• More favourable then glucocorticoids
– Methotrexate 15 – 25 mg IM or PO weekly
– Cyclosporine IV 🡪 used in refractory cases of UC.
• Benefits is temporary
– Azathioprine
• Antibiotics
– Metronidazole : 250 – 500 mg TID
• Alternate first line agent or adjunctive therapy in mild
to moderate Crohns disease.
– Ciprofloxacin : 500mg XPO X BD

The two agents can be used concurrently in perianal

Crohns disease
• Infliximab -
– Antibody against tumor necrosis factor –alfha that
induces inflammatory cell lysis by binding to
tumor necrosis factor receptors on the cell
surface.
– IV infusions of 5 mg /kg used in fistulous Crohns
disease, refractory inflammatory type CD
unresponsive to conventional therapy and more
recently to SEVERE ulcerative colitis .
• Local therapy :
– Ulcerative colitis 🡪 rectum and distal left colon
can be treated effectively with 5-ASA and /or
glucocorticoids enemas or suppositories
• Antidiarrheal agents
– Contraindicated in severe exacerbations and toxic
megacolons.
• Low roughage diet
• Elemental diets
• Total parenteral nutrition and bowel rest in
severe disease
• Supplements of – Vit B12, calcium,
magnesium, folate, iron, vit A. ,Vit D and other
micronutritions
• Surgery :
– Impaired quality of life
– Failure to medical therapy
– Fulminant colitis
– Patients with fistulas , obstructions, abscess, perforations,
or bleeding rarely for medically refractory disease and
neoplastic transformations
– Multiple resections should be avoided
• For ulcerative colitis
– PANPROCTOCOLECTOMY with Ileostomy
– Proctocolectomy with ileal anal pouch anastomosis
• For Crohn disease is the segmental resection
Feature Ulcerative colitis Crohn’s disease
Epidemology 15- 40 yrs Major of cases occurs between
11- 35 yrs

-Lower incidence in smokers Smoking is risk factors

- Lower incidence in previous
appendectomy <20years

M:F= 1:1 F>M slightly

Extent Mucosal and submucosal Transmural

Location -Mainly rectum ( begins in this -Terminal ileum alone (30%)

location ) -ileum and colon (50%)
-Extend into left colon -Colon alone (20%)
contineously -Mouth to anus involved
-Does not involve other area - Avoids rectum

Gross feature -Inflammatory pseudo polyps -Thick bowel wall and narrow
-Areas of friable, bloody lumen 🡪 obstructions
residual mucosa -Apthous ulcers in bowel early
-Ulceration and hemorrhage -Skip lesions, strictures,
fistulas
-Deep linear ulcers with
cobbel stone patterns
-Fat creeping around serosa
Features Ulcerative colitis Crohn’s disease

Microscopic -Ulceration and crypts -Noncaseating granulomas

abscess containing neutrophils ( 60%)
-Dysplasia or cancer may be -Dysplasia and cancer less
present likely

Clinical findings Recurrent left sided Recurrent right lower

abdominal cramping with quadrant colicky pain .
bloody diarrhea and mucus - (obstruction) with diarrhea
- Bleeding occurs only with
colon or anal involvement
( fistulas , abscess)
Apthous ulcer in mouth

Radiology Lead pipe appearance in chronic String sign

disease
-Collar button ulcers

Complications -Toxic mega colon Fistulas , obstructions, colon

- Adenocarcinoma cancer (UC>CD)
Renal calculi
Malabsorbtion
Macrocytic anemia