INFLAMMATORY

BOWEL DISEASE

Dr.Pooja Sharda Janardan

 INTRODUCTION
• Inflammatory bowel disease (IBD) is a term for
two conditions (Crohn’s disease and ulcerative
colitis) that are characterized by chronic
inflammation of the gastrointestinal (GI) tract.
• The exact cause of inflammatory bowel
disease (IBD) is unknown.
• Prolonged inflammation results in damage to
the GI tract.
 ETIOLOGY
 Infectious Factors
 Genetic Factors (ATG16L1 and IRGM) NOD2
 Immunologic Mechanisms(INNATE
IMMUNITY)
 Psychological Factors
 Lifestyle, Dietary, and Drug-Related Causes
 ULCERATIVE COLITIS
• Ulcerative colitis is confined to the rectum and
colon and affects the mucosal and the
submucosal layers.
• In some instances, a short segment of terminal ileum
may be inflamed; this is referred to as backwash
ileitis.
• In UC, abscess formation in the crypts of the mucosa
occurs (crypts of Lieberkuhn) secondary to infiltration
of lymphocytes, plasma cells, and granulocytes.
• Crypt abscesses are usually visible only with
microscopy but may be visible when coalescence
results in ulceration.
• Reduced crypt density, distorted crypt architecture
and atrophy, and depletion of goblet cells are typical
findings.
•Extension and coalescence
of ulcers may surround areas
of uninvolved mucosa,
causing pseudopolyp
formation.
•Mucosal damage and
friability in UC can result in
significant diarrhea and
bleeding, although a small
percentage of patients
experience constipation.
 Crohn’s Disease
• Crohn’s disease is characterized as a transmural inflammatory
process. The terminal ileum is the most common site of the
disorder, but it may occur in any part of the GI tract from
mouth to anus.
• Patients often have normal bowel separating segments of
diseased bowel resulting in discontinuous disease.
• The mesentery first becomes thickened and edematous, and
then fibrotic.
• Ulcers are typically deep and elongated and extend along the
longitudinal axis of the bowel, at least into the submucosa.
• The “cobblestone” appearance of the bowel wall results from
deep mucosal ulceration intermingled with nodular
submucosal thickening.
• Bowel wall injury is generally extensive, and the
intestinal lumen is often narrowed.
• Small bowel stricture and subsequent obstruction is a
complication that may require surgery. Fistula
formation is also common.
• Fistulas often occur in highly inflamed areas, where
loops of bowel become matted together by fibrous
adhesions.
• Fistulas may connect a segment of the GI tract to skin
(enterocutaneous), two segments of the GI tract
(enteroenteric), or the intestinal tract with the
bladder (enterovesicular) or vagina.
• Fistulae associated with CD frequently require
surgical treatment.
• Nutritional deficiencies are common with CD.
Reported deficiencies include folate, vitamin
B12, vitamins A-D, calcium, magnesium, iron,
and zinc.
• Major contributing factors include decreased
food intake, intestinal loss, malabsorption,
hypermetabolic state, drug-nutrient
interactions, and those receiving long-term
total parenteral nutrition.
 RISK FACTORS
Auto-immunity
Age
Gender
Pregnancy
NSAIDs
Smoking (Crohn’s Disease)
Oral Contraception
Antibiotic overuse
Lieberkuhn crypts (Spherical/ Hemispherical)
 PHYSCIAL EXAMINATION
ULCERATIVE COLITIS CROHN’S DISEASE
• Hemorrhoids, anal fissures, • Abdominal mass and
or perirectal abscesses may tenderness
be present. • Perianal fissure or fistula
• Iritis,
• Uveitis
• Episcleritis,
• Conjunctivitis with ocular
involvement.
• Erythema nodosum,
Pyoderma Gangrenosum, or
aphthous ulceration
 COMPLICATIONS
TOXIC MEGACOLON-
• Non-obstructive dilation of the colon, which
can be total or segmental and is usually
associated with systemic toxicity.
• It is most commonly associated with
inflammatory bowel disease, especially
ulcerative colitis, yet any condition that leads
to inflammation of the colon can potentially
cause toxic megacolon.
 Role of CD4 cells
• There are a number of lines of evidence that suggest
that CD4+ T helper cells are major initiators in the
disease process.
• CD4+ T cells are key in mediating the host protective
and homeostatic responses.
• CD4+ T cells are also known to be the main drivers of
inflammatory bowel disease (IBD) when this balance
is perturbed.
• Many subsets of CD4+ T cells have been identified as
players in increasing chronic intestinal inflammation.
 Cont……….d
• CD4+ T cells are enriched in lesional tissue
from patients with CD and UC and blockade or
depletion of CD4+ T is effective in treating
patients with IBD.
• CD4+ T cell-depleting and blocking antibodies
caused remission from disease in a number of
CD and UC patients examined, suggesting a
prominent role of CD4+ T cells in propagating
disease
 Role of Th1 Cells
• Th1 cells are important for protecting against
infectious pathogens.
• These cells primarily produce interferon (IFN)-γ
and tumor necrosis factor (TNF) that, respectively,
activate macrophages and direct cytotoxic CD8+ T
cell responses, that in turn promote elimination
of intracellular pathogens such as viruses and
bacteria.
• In IBD, however, Th1 cells accumulate in the
intestinal tract of individuals with CD and are
directly associated with disease.
 Cont……….d
• Interleukin (IL)-12, which is secreted by antigen-
presenting cells, acts via signal transducer and
activator of transcription (STAT) to promote the
differentiation of naïve T cells into Th1 cells.
• During intestinal inflammation, IFN-γ in
combination with another Th1-associated
cytokine, TNF, was proposed to drive intestinal
epithelial cell beta catenin signaling and limit
their differentiation and proliferation
 GOALS OF THERAPY
• To treat the inflammation.
• To treat infection.
• Resolution of complications (eg, fistulae and
abscesses).
• To provide mucosal healing.
 Pharmacologic Therapy
• Major types of drug therapy used in IBD
include ASAs, corticosteroids,
immunosuppressive agents (azathioprine,
mercaptopurine, cyclosporine, and
methotrexate), antimicrobials (metronidazole
and ciprofloxacin), and agents to inhibit TNF-α
(anti–TNF-α antibodies) or leukocyte adhesion
and migration (natalizumab and vedolizumab).
 SULFASALAZINE
• Sulfasalazine has been used for years to treat
IBD but was originally intended to treat arthritis.
• It is cleaved by gut bacteria in the colon to
sulfapyridine (which is mostly absorbed and
excreted in the urine) and mesalamine.
• The active component of sulfasalazine is
mesalamine, which exerts its effects locally in
the GI tract; however, the mechanism of action
is not completely understood.
• Beneficial effects of Mesalamine may include
scavenging of free radicals, inhibition of
leukocyte motility, interference with TNF-α,
transforming growth factor-β (TGF-β) and
suppression of IL-1 production, and inhibition
of leukotriene and prostaglandin production.
• Side Effects- Flu-like symptoms, Painful red or
purple rash, Blistering, Peeling skin, Paleness,
Purple spots, Yellowish Skin, Nausea,
Vomiting.
• ADRs- Nephrotoxcity
 BUDESONIDE
• Corticosteroids are used to suppress acute
inflammation in the treatment of IBD, and may be
given parenterally, orally, or rectally. They modulate
the immune system and inhibit production of
cytokines and mediators. It is not clear whether the
most important steroid effects are systemic or local
(mucosal).
• Budesonide is a corticosteroid that is administered
orally in a controlled-release formulation designed to
release in the terminal ileum or the colon depending
on the product. The drug undergoes extensive first-
pass metabolism; so systemic exposure is thought to
be minimized.
 Immunosuppressive agents
• Azathioprine and mercaptopurine are effectively
used in long-term treatment of both CD and UC.
• These agents are generally reserved for patients who
fail ASA therapy or are refractory to or dependent on
corticosteroids.
• They may be used in conjunction with mesalamine
derivatives, corticosteroids, and TNF-α antagonists,
and must be used for extended periods of time,
ranging from a few weeks up to 12 months, before
benefits may be observed
• Cyclosporine has a short-term benefit in the
treatment of acute, severe UC to avoid
colectomy in patients failing corticosteroids.
• Used as continuous IV infusion of 2 to 4 mg/kg
daily.
• Cyclosporine poses a risk of nephrotoxicity and
neurotoxicity.
• Methotrexate 15 to 25 mg given intramuscularly
or subcutaneously once weekly may useful for
maintenance therapy of CD and may result in
steroid-sparing effects, while data supporting
use in UC are lacking.
 Biologic agents
• Infliximab - 5 mg/kg IV at 0, 2, and 6 weeks, then q8Weeks
• Targets TNF-α have become a key class of agents in the
treatment and maintenance of IBD.
• Infliximab is an IgG1 chimeric monoclonal antibody that is
administered IV and binds TNF-α and inhibits its
inflammatory effects.
• In addition, it lyses activated T cells and macrophages and
induces T-cell apoptosis.
• Infliximab is useful for moderate to severe active CD and UC
disease, as well as steroid-dependent or fistulizing disease,
as both an induction and a maintenance therapy.
CROHN’S DISEASE