Transcript Stomach and Peptic Ulcer Disease

Inflammatory Bowel
Disease
Internal Medicine Lecture Series
November 21, 2007
Ron Barac, D.O.
Inflammatory Bowel
Disease


Crohn’s disease
Ulcerative colitis
Pathogenesis of IBD is unknown!
Familial Patterns of IBD
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10-25% occurrence of IBD in
relatives
Strong concordance by disease
category
Genetic vs. environmental influences
still unresolved
Etiological theories of IBD
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Genetic
Smoking
Dietary
Infection
Immunological
Psychogenic?
Epidemiology of IBD
Factor
Ulcerative Colitis
Crohn’s Disease
Incidence (per
100,000)
2-10
1-6
Prevalence (per
100,000)
35-100
10-100
Racial incidence
High in whites
High in whites
Ethnic incidence
High in Jews
High in Jews
Sex
Slight female
preponderance
Slight female
preponderance
Age of onset
15-25
?55-65
15-25
?55-65
Smoking
Fewer smokers than
expected
More smokers than
expected
Crohn’s disease
First
documented
case by
Morgagni in
1761
Crohn’s disease - Description

Chronic inflammation that may involve
any part of the GI tract from mouth to
anus.
• associated with many extraintestinal features
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Frequently manifested by abdominal pain
and diarrhea
Often complicated by intestinal
fistulization, obstruction or both.
Typically affects the ileum, colon, and/or
perianal region
Distribution is asymmetric/segmental
Tendency toward lifelong recurrence
Crohn’s Disease - Pathology
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Earliest/most frequent mucosal lesion: crypt injury
secondary to neutrophil infiltration
Distribution of crypt lesions is typically more focal
Crypt injury is followed by microscopic ulceration of
intestinal mucosa over a lymphoid follicle
Macrophage/other inflammatory cells invade and
proliferate in the lamina propria.
Loose aggregates of macrophages ultimately organize
into discrete noncaseating granulomas, which consist
of epithelioid cells with multinucleated giant cells.
While granulomas seem to be a pathognomonic
feature of Crohn’s disease, absence of granulomas
does not rule out the diagnosis.
Crohn’s Disease – Clinical
Presentation
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Pain - colicky RLQ/suprapubic region
Diarrhea
Fever - usually low grade, higher spiking fevers
signify complications
Weight loss - typically 10-20% of body weight
Gross bleeding - unusual, massive bleeding in only 12%
Perineal disease - fissures/fistulas and/or abscesses
Crohn’s disease

Flexible sigmoidoscopy:
• rectal sparing is common
• distal colon may be unremarkable or mildly
erythematous in 50-70% of patients
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Colonoscopy:
• contraindicated in acute Crohn’s disease
• mucosal involvement is discontinuous with
intervening “skip” areas of normal mucosa
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Plain films of abdomen
UGI/small bowel series
• 60-70% of patients have some ileum
involvement

Barium enema
Crohn’s Disease
Complications

Fistula formation
•
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•
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enterocutaneous
enterovesical
enteroenteric/enterocolic
rectovaginal/rectovesical
Intraabdominal abscess
Bowel obstruction
Growth failure in pediatric/adolescent patients
Malignancy
• gastrointestinal
• squamous cell CA of anus
• squamous cell CA of vulva
Ulcerative Colitis
First recognized
by Wilkes in
1859
Ulcerative Colitis
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Inflammatory disorder that affects
the rectum and extends proximally to
affect a variable extent of the colon.
Cause of the disease and factors
determining its clinical course are
unknown.
Ulcerative Colitis - Pathology
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Inflammation predominantly confined to
the mucosa/submucosa
Characteristic histologic finding in UC is
the crypt abscess
• crypt abscesses are not specific for UC though
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Crypt abscesses are comprised of PMNs
and degenerated or necrotic epithelial cells
in the crypts of Lieberkuhn.
Coalescence of adjacent crypt abscesses
produce the mucosal ulcerations which
typify ulcerative colitis.
Ulcerative Colitis – Clinical
Presentation
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Hematochezia
Diarrhea - not always present
Pain - lower abdominal/crampy,
relieved by BM’s
Fever - only seen in severe cases
Weight loss
Clinical assessment of disease
severity

Mild: (60% of patients)
• < 4 stools per day with or without blood,
with no systemic disturbances and normal
ESR.
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Moderate: (25% of patients)
• > 4 stools per day but with minimal
systemic disturbances
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Severe: (15% of patients)
• > 6 stools daily with blood and evidence of
systemic disturbance as shown by fever,
tachycardia, anemia, or an ESR > 30.
Ulcerative Colitis
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Flexible sigmoidoscopy:
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assess disease activity in acute UC
Rectal involvement in 95% cases of UC
Mucosal involvement is continuous and non-segmented
Mucosa is granular/friable with discrete ulcerations
Colonoscopy:
• relatively contraindicated in acute UC due to increased
risk of perforation.
• useful in chronic UC to evaluate disease extent, evaluate
strictures, and surveillance of colonic CA
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Plain films of abdomen
Barium enema:
• contraindicated in acute UC
• useful in chronic UC – “lead pipe” colon
• colonic strictures should be considered malignant until
proven otherwise
Ulcerative Colitis
Complications
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Toxic megacolon
Free perforation
Massive colonic hemorrhage
Colon cancer:
• Major risk factors are extent and duration of
disease
• Colonoscopic surveillance with biopsies should
be done yearly in patients with universal colitis
of 10 yrs. duration or left-sided colitis of 20
yrs. duration.
Exclusion of Infectious Colitis
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Exclusion of infectious Colitis may be clinically,
endoscopically, and histologically
indistinguishable from IBD.
• stool for ova and parasites
• stool cultures for enteric pathogens
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Patients with proctitis
• exclude STDs if there is a history of anal intercourse
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Patients with diarrhea and recent antibiotic use
• exclude pseudomembranous colitis
• check stools for C. difficile toxin
Extraintestinal Manifestations
of IBD
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33% of IBD patients will have one or more
manifestations in their lifetime.
Extraintestinal manifestations may be related to
bowel disease activity, may be independent of
bowel disease, or may occur as a consequence
of bowel disease.
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Dermatologic
Rheumatologic
Hepatobiliary
Ocular
Renal
Dermatologic manifestations
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Erythema nodosum
• most common skin manifestation of IBD
• occurs in 9% of UC, 15% of CD
• directly related to bowel disease activity and
resolves with control of the disease
• erythema nodosum is non-specific for IBD
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Pyoderma gangrenosum
• occurs in 2-5% UC, 1-2% of CD
• clinical course is independent of bowel disease
• treatment with intralesional/systemic steroids
Rheumatologic manifestations
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Axial arthritis
• Ankylosing spondylitis
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18-20% of patients with IBD, more common in males
clinical course independent of bowel disease
assoicated with HLA-B27 haplotype
“bamboo” spine on plain x-rays
• Sacroilitis
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independent of bowel disease
associated with HLA-B27 haplotype
plain films show obliteration of sacroiliac joint space
Peripheral arthritis
• Activity parallels bowel disease activity
• Peripheral arthritis in IBD is mono-articular (affects large
joints such as knee, wrist, ankles), asymmetric,
migratory, seronegative, and is unassociated with
deformity or erosive changes.
Hepatobiliary Manifestations
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Primary sclerosing cholangitis
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4-6% of patients with UC
70% of patients with PSC have UC
associated with DRW-52A haplotype
clinical course is independent of bowel disease
diagnosis made by ERCP; suggested by liver biopsy
cholangiocarcinoma is a complication of PSC
Pericholangitis
Cholelithiasis
• cholesterol stones may occur in CD patients with terminal
ileal involvement
• Occurs in 15-30% of patients with small bowel CD
• Resection or disruption of ileal absorptive surface causes
alteration of enterohepatic circulation and bile salt depletion
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Chronic active hepatitis
Ocular Manifestations
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Uveitis
• Clinical course is independent of bowel
disease activity
• Associated with HLA-B27 haplotype
• Clinical presentation is painful, injected
eye with opacity in the anterior
chamber.
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Episcleritis
Renal Manifestations
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Nephrolithiasis
• Urate stones associated with ulcerative colitis
• Oxate stones associated with Crohn’s disease
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Obstructive hydronephritis
• Associated with Crohn’s disease but not UC
• Caused by local extension of bowel
inflammation to ureters
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Pyelonephritis
IBD
TREATMENT
Aminosalicylates
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Used for both CD and UC
Active component is 5-aminosalicyclic acid
(5-ASA)
Mode of action
• inhibition of lipoxygenase enzyme in the
alternate arachidonic acid pathway resulting in
decreased production of leukotrienes
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Examples:
• sulfasalazine (Azulfidine), olsalazine
(Dipentum), mesalamine (Pentasa, Asacol),
topical mesalamine (Rowasa)
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Both oral/topical forms are effective in
maintaining remission in UC.
Sulfasalazine
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5-ASA linked by an azo bond to sulfapyridine
Azo bond is split by bacteria in distal ileum/colon
releasing the active 5-ASA moiety
90% of the adverse effects of sulfasalazine are
related to the sulfapyridine moiety
Adverse effects include:
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Rash, fever, headaches
Reversible male infertility
Folate deficiency
Agranulocytosis
Indications:
• Mild to moderate UC
• Mild to moderate Crohn’s colitis, ileocolitis, less effective
in Crohn’s ileitis
• Maintenance of remission in UC
Sulfasalazine – Safety in
Pregnancy and Breast
Feeding
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Crosses placenta and appears in milk
No adverse effect on pregnancy
No teratogenicity
No kernicterus
Mesalamine
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Active moiety is 5-ASA
Adverse effects:
• Nausea, flatulence, diarrhea
• Fever, rash
• Pancreatitis, pericarditis, colitis
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Indications:
• same as for sulfasalazine
STEROIDS
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Systemic corticosteroids:
• Indicated in short term treatment of
moderate/severe UC or CD
• Not shown to maintain remission in either UC
or CD
• Preparations:
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Oral: prednisone, prednisolone
Parental: hydrocortisone, corticotropin (ACTH)
Topical corticosteroids
• Indicated in treatments of proctitis or leftsided colitis
• Advantage is minimalization of systemic effects
of steroids
• Preparation: hydrocortisone enemas
Budesonide (controlled ileal
release)
• Corticosteroid with high 1st-pass hepatic
metabolism
• Used as an alternative to prednisone
• Effective in mild to moderately active Crohn’s
ileitis and/or right colon involvement
• Effective for prolongation of time to relapse
and maintenance
• More effective than mesalamine for
maintenance of remission of patients with
steroid-dependent Crohn’s disease
Metronidazole
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Indications:
• fulminant UC
• active CD (mild/moderate)
• perianal disease/fistulae
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Adverse effects:
• peripheral neuropathy
• disulfiram-like reaction
• teratogenicity precludes use in
pregnancy
Immunosuppressive agents
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6-Mercaptopurine (6-MP) and Azathioprine are the only
medications known to induce/maintain remission in CD
Indications:
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steroid-dependent
refractory disease
perianal disease
refractory fistulae
maintenance of remission
Disadvantage is delay in response to treatment
• mean time of clinical response is 3-4 months
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Complications of treatment:
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neutropenia
bone marrow suppression – 2% cases
pancreatitis – 3.3%
lymphoma
Cyclosporine:
• may have role in acute or severe UC/CD
• Has quick onset of action but limited by serious side effects.
Infiximab
• Chimeric mouse/human monoclonic antibody
against tumor necrosis factor alpha
• Used in moderate to severe Crohn’s and
ulcerative colitis
• Very active for fistulizing Crohn’s disease
• Useful for both induction & maintenance of
remission
• Patients should be evaluated for latent TB prior
to treatment (can also be associated with
reactivation of HBV infection)
• Possible association with rare lymphomas
Surgical Management of IBD
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Ulcerative colitis
• Proctocolectomy with ileostomy
• Ileoanal anastomosis
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Crohn’s disease
• Stricturoplasty
• Fistulectomy
• Segmental resection