Inflammatory Bowel Disease
Overview
– Ulcerative colitis and Crohn’s disease are two main
forms of IBD, can be differentiated on basis of
genetic predisposition, risk factors, and clinical,
endoscopic and histologic features
– Exact etiology of IBD is unknown, though thought
to be related to dysregulated mucosal immune
response to commensal gut flora in genetically
susceptible individuals
Pathophysiology
• Exact mechanism for IBD not well understood,
though to be related to combination of factors in
gut, including:
– Damage to epithelial mucin proteins and tight
junctions,
– Breakdown of homeostatic balance between host’s
mucosal immunity and enteric microflora
– Genetic polymorphisms in toll-like receptors (TLRs)
– Disrupted homeostatic balance between regulatory
and effector T-cells
Ulcerative colitis
Epidemiology
• Higher incidence than CD
– More commonly seen in North America and Europe
• Bimodal incidence pattern
– Onset 15-30 years or 50-70s year olds
• Genetic factors: Family history very important
– Ashkenazi Jews have 3-5x higher risk
• Environmental factors
– Smoking associated with paradoxically lower risk, milder disease
– Hx of prior GI infections, e.g. Shigella, Salmonella, Campylobacter,
during adulthood double risk of developing UC, thought to be 2/2
changes in gut flora triggering chronic inflammatory process
– Weak associations between NSAIDs, OCPs and increased risk of UC
– No data supports psychological stress as trigger for onset or relapse
Ulcerative Colitis
Clinical Presentation
•
Common presenting symptoms include rectal bleeding, diarrhea, urgency,
tenesmus, abdominal pain
– More rarely can see fistulas, weight loss, more common in CD
– In severe or advanced cases, patients may present with fever
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Clinical course characterized by alternating periods of remission and relapse
Montreal classification used to categorize extent and severity of disease
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E1 (proctitis): inflammation limited to the rectum
E2 (left-sided; distal): inflammation limited to the splenic flexure
E3 (pancolitis): inflammation extends to the proximal splenic flexure
S0 (remission): no symptoms
S1 (mild): four or less stools per day (with or without blood), absence of systemic symptoms,
normal inflammatory markers
– S2 (moderate): four stools per day, minimum signs of systemic symptoms
– S3 (severe): six or more bloods per day, pulse rate of ≥90 beats per min, temperature ≥37·5°C,
ESR >30
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Extraintestinal manifestations are more commonly seen in UC than CD
– include aphthous oral ulcers, iritis/uveitis/episcleritis, seronegative arthritis, ankylosing
spondylitis, sacroiliitis, erythema nodosum, pyoderma gangreosum, autoimmune hemolytic
anemias and primary sclerosing cholangitis
Ulcerative Colitis
Diagnosis
• Based on clinical symptoms confirmed by objective
findings from endoscopic and histologic examinations
• Initial w/u must r/o infectious and non-infectious
causes of diarrhea
• Endoscopic features
– loss of vascular pattern, erythema, granular and friable
mucosa, erosions, ulcerations and spontaneous bleedings
• Pathologic features
– distortion of crypt architecture, crypt abscess, infiltration
of lamina propria w/ plasma cells, eosinophils,
lymphocytes, lymphoid aggregates and mucin depletion
Ulcerative Colitis
Treatment
• Treatment should be tailored to disease
activity and extent of disease activity
– 5-ASA drugs: E.g. mesalazine, sulfasalazine
– Corticosteroids
– Immunosuppresants: E.g. azathioprine, 5mercaptopurine
– Biologics: E.g. infliximab, adalimumab
Ulcerative Colitis
Treatment
• Surgical treatment required in approximately 2030% of patients. Surgery is generally curative in
UC.
– Emergency: Life-threatening complications related to
fulminant disease unresponsive to medical treatment
– Urgent: Severe disease admitted to hospital and not
responding to intensive medical treatment
– Elective: Refractory disease intolerant to long-term
maintenance treatments or colorectal cancer.
Ulcerative Colitis
Prevention/Screening
• UC patients at increased risk of colorectal cancer
– 2% after 10 years, 8% after 20 years and 18% after 30 years
• Screening colonoscopy beginning at 8 years after disease
onset
• Following initial colonoscopy, subsequent screening
depends on extent of disease
– Proctitis/proctosigmoditis: Follow specific age guidelines for
surveillance of colorectal cancer
– Left-sided colitis/pancolitis: Every 1-2 years
– UC w/ PSC: Annually from time of dx of PSC
• Risk factors for CRC
– Duration and extent of disease
– Endoscopic and histologic severity of inflammation
Crohn’s Disease
Epidemiology
• Genetic factors
– Family hx well established as one of the strongest
risk factors for development for CD
• Environmental factors
– Lifestyle factors such as tobacco use, sedentary
lifestyle, exposure to air pollution, and
consumption of western diet
• Infectious factors
– CD often occurs after infectious gastroenteritis
Crohn’s Disease
Clinical Presentation
• Unlike in UC, Crohn’s disease can affect any portion of the GI tract
• Common presenting symptoms
– abdominal pain, bloody or watery diarrhea, incontinence, fistulas and
perianal symptoms. Extracolonic GI involvement associated with
aphthous ulcers, dysphagia, upper abdominal pain and vomiting.
• Patients with CD may have hx of other autoimmune disorders,
• Montreal classification used to categorize CD
– L-classification: Defines extent of disease
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L1: Disease confined to terminal ileum
L2: Disease confined to clon
L3: Disease involving ileum and colon
L4: Disease involving upper GI tract
L4+L3: Disease involving upper GI tract and distal disease
– B-classification: Defines phenotype
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B1: Without stricture formation, non-penetrating
B2: Stricturing
B3: Penetrating
B3p: Perinally penetrating
Crohn’s Disease
Diagnosis
• Clinical diagnosis based on H&P findings with objective
findings from history and laboratory studies
• As with UC, must r/o important non-infectious causes
(IBS, Behcet’s syndrome) and infectious causes
(Yersinia, enteroviruses etc.) that mimic CD
• Endoscopy is gold standard for diagnosis
• Radiologic tests may assist in diagnosis
– CT/MRI enterography or enteroclysis
– Abdominal U/S
• Biomarkers can also be used
– CRP, lactoferrin and calprotectin
Crohn’s Disease
Treatment
• All patients with CD should be counseled to quit smoking
• As with UC, initial medical treatment depends on
phenotype, disease activity, comorbidities and other
individual characteristics of patient
– In most cases, short course of antibotics, steroids, or anti-TNF
agent, e.g. infliximab, adalimumab, combined with thiopurines
or methotrexate for long-term maintenance
– 5-ASA derivatives, which are mainstay of UC, have shown to be
less useful in treatment of CD
• Superiority of combination of thiopurines and TNF blockers
• No current consensus on optimal length of therapy
• Unlike in UC, surgery is not curative in CD
Crohn’s Disease
Prevention/Screening
• Regular screen for active infection
– tuberculosis, infections hepatitis, CMV, HIV and C.
difficile
• Colorectal cancer screening
– In patients with more than a third of colon affected
(Montreal classification L3), first screening
colonoscopy should occur 8 years after onset,
repeated every 1-2 years once remission achieved,
and every 1-3 years once normal.
– Patients with PSC should undergo annual screenings
References
• Ordás I1, Eckmann L, Talamini M, et al.
Ulcerative colitis Lancet. 2012 Nov
3;380(9853):1606-19.
• Baumgart DC1, Sandborn WJ. Crohn's disease.
Lancet. 2012 Nov 3;380(9853):1590-605.