Inflammatory Bowel Disease

Inflammatory Bowel Disease
– 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
• 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
– 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
• 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
Clinical course characterized by alternating periods of remission and relapse
Montreal classification used to categorize extent and severity of disease
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
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
• 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 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
• Surgical treatment required in approximately 2030% of patients. Surgery is generally curative in
– 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
• 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
• 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
• 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
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
B1: Without stricture formation, non-penetrating
B2: Stricturing
B3: Penetrating
B3p: Perinally penetrating
Crohn’s Disease
• 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
• 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
• Regular screen for active infection
– tuberculosis, infections hepatitis, CMV, HIV and C.
• 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
• Ordás I1, Eckmann L, Talamini M, et al.
Ulcerative colitis Lancet. 2012 Nov
• Baumgart DC1, Sandborn WJ. Crohn's disease.
Lancet. 2012 Nov 3;380(9853):1590-605.