Inflammatory Bowel Disease

Alon Orion
Inflammatory bowel diseases (IBDs)
are chronic inflammatory disorders of
unknown etiology involving the
gastrointestinal tract. Peak occurrence
is between ages 15 and 30 and
between ages 60 and 80, but onset
may occur at any age.
 Pathogenesis

Activation of immune cells by

unknown inciting agent
(microorganism, dietary component,
bacterial or self-antigen) leading to
release of cytokines and
inflammatory mediators.
 Genetic component
 Genetic component suggested by increased risk in
first-degree relatives of patients with IBD and
concurrence of type of IBD, location of Crohn's
disease (CD), and clinical course.
 Reported associations include HLA-DR2 in
Japanese patients with ulcerative colitis (UC) and
a CD-related gene called CARD15 on chromosome
16p.
 CARD15 (10% of CD risk), ANCA (70% of UC
patients), ASCA (60-70% of CD patients and in 10-
15% of UC patients).
 Granulomatous angiitis (vasculitis) may occur in
CD. Acute flares may be precipitated by infections
 Ulcerative Colitis
PATHOLOGY
Colonic mucosa inflammation; rectum almost
always involved, with inflammation extending
continuously (no skip areas) proximally for a
variable extent; histologic features include
epithelial damage, inflammation, crypt
abscesses, loss of goblet cells.
CLINICAL MANIFESTATIONS
Bloody diarrhea, mucus, fever, abdominal pain,
tenesmus, weight loss; spectrum of severity
(majority of cases are mild, limited to
rectosigmoid). In severe cases, dehydration,
 Ulcerative Colitis
COMPLICATIONS
Toxic megacolon, colonic perforation; cancer
risk related to extent and duration of colitis;
often preceded by or coincident with
dysplasia, which may be detected on
surveillance colonoscopic biopsies.
DIAGNOSIS
Sigmoidoscopy/colonoscopy: mucosal
erythema, granularity, friability, exudate,
hemorrhage, ulcers, inflammatory polyps.
Barium enema: loss of haustrations, mucosal
irregularity, ulcerations.
 Crohn’s Disease
PATHOLOGY
Any part of GI tract, usually terminal ileum and/or
colon; transmural inflammation, bowel wall thickening,
linear ulcerations, and submucosal thickening leading
to cobblestone pattern; discontinuous (skip areas);
histologic features include transmural inflammation,
granulomas (often absent), fissures, fistulas.
CLINICAL MANIFESTATIONS
Fever, abdominal pain, diarrhea (often without blood),
fatigue, weight loss, growth retardation in children;
acute ileitis mimicking appendicitis; anorectal fissures,
fistulas, abscesses. Clinical course falls into three broad
patterns: inflammatory, stricturing, and fistulizing.
 Crohn’s Disease
COMPLICATIONS
Intestinal obstruction; rarely toxic megacolon or
perforation; intestinal fistulas to bowel, bladder,
vagina, skin, soft tissue, often with abscess
formation; bile salt malabsorption leading to
cholesterol gallstones and/or oxalate kidney
stones; intestinal malignancy; amyloidosis.
DIAGNOSIS
Sigmoidoscopy/colonoscopy, barium enema,
upper GI and small-bowel series: nodularity,
rigidity, ulcers that may be deep or longitudinal,
cobblestoning, skip areas, strictures, fistulas. CT
may show thickened bowel loops or an abscess.
 Differential Diagnosis
INFECTIOUS ENTEROCOLITIS
 Shigella
 Salmonella
 Carnpylobacter
 Yersinia (acute ileitis)
 Escherichia coli serotype 0157:H7
 Gonorrhea
 Lyrnphogranulorna venereurn
 Clostridiurn difficile (pseudomembranous colitis)
 Tuberculosis
 Amebiasis
 Cytomegalovirus
 AIDS
 Differential Diagnosis
OTHERS
 Ischemic bowel disease
 Appendicitis
 Diverticulitis, drug-induced colitis (e.g., NSAIDs)
 Bleeding colonic lesion (e.g., neoplasm)
 Irritable bowel syndrome (no bleeding)
 EXTRAINTESTINAL
MANIFESTATIONS OF IBD
Joint
1. peripheral arthritis-activity dependent of
bowel disease; 2. ankylosing spondylitis and
sacroiliitis (associated with HLA-B27)-activity
independent of bowel disease
Skin
erythema nodosum, aphthous ulcers,
pyoderma gangrenosum.
Eye
conjunctivitis, iritis, uveitis.
 EXTRAINTESTINAL
MANIFESTATIONS OF IBD
Liver
fatty liver, primary sclerosing cholangitis (5%
of UC patients), cholangiocarcinoma, chronic
hepatitis.

Others
autoimmune hemolytic anemia, phlebitis,
pulmonary embolus, kidney stones, metabolic
bone disease.
Treatment
 Treatment
SUPPORTIVE
 Antidiarrheal agents (diphenoxylate and
atropine, loperamide) in mild disease.
 IV hydration and blood transfusions in
severe disease.
 Parenteral nutrition or as primary therapy
in CD; should not replace drug therapy;
important role in preoperative preparation
of malnourished patients.
 emotional support.
 Treatment
SULFASALAZINE AND AMINOSALICYLATES
Active component of sulfasalazine is 5-ASA linked to
sulfapyridine carrier; useful in colonic disease of mild to
moderate severity.
Efficacy in maintaining remission demonstrated only for
UC.
Toxicity (generally due to sulfapyridine component): dose
related-nausea, headache, rarely hemolytic anemia; rash,
neutropenia, pancreatitis, hepatitis, oligospermia.
Newer aminosalicylates are as effective as sulfasalazine
but with fewer side effects.
 Treatment

GLUCOCORTICOIDS
 Useful in severe disease and ileal or ileocolonic
CD.
 Prednisone, 40-60 mg PO;
 IV hydrocortisone, 300 mg, in hospitalized
patients.
 Non-systemic – 1. budesonide (CD) 2.
budesonide mmx (UC).
 Numerous side effects make long-term use
problematic.
 Treatment
IMMUNOSUPPRESSIVE AGENTS
Azathioprine, 6-mercaptopurine (Thiopurines) - Useful as
steroid-sparing agents and in intractable or fistulous CD (may
require 2- to 6-month trial before efficacy seen).
Toxicity- immunosuppression, pancreatitis. Avoid in pregnancy.
METRONIDAZOLE
Appears effective in colonic CD and refractory perineal CD.
Toxicity - peripheral neuropathy, metallic taste. Avoid in
pregnancy.
Other antibiotics (e.g., ciprofloxacin) may be of value in
terminal ileal and perianal CD, and broad-spectrum IV
antibiotics are indicated for fulminant colitis and abscesses.
 Treatment

OTHERS
 Cyclosporine (calcineurin inhibitor) in severe UC and
possibly intractable Crohn's fistulas.
 Anti-TNF:
lnfliximab (monoclonal antibody to TNF) IV induces. 1
responses in 65% of CD patients refractory to 5-ASA,
glucocorticoids, and 6-mercaptopurine. In UC, 27-49% of
.patients respond
Natalizumab is an anti-integrin antibody with activity. 2
against CD, but some patients develop progressive
.multifocal leukoencephalopathy
Vedolizumab. 3
 Surgery

UC
Colectomy (curative) for intractability, toxic
megacolon (if no improvement with
aggressive medical therapy in 24-48 h),
cancer, dysplasia.

CD
Resection for fixed obstruction, abscesses,
persistent symptomatic fistulas, intractability.