Inflammatory Bowel disease By Dr Khaled Ahmad, md, facs, fasmbs

Inflammatory bowel disease Inflammatory Bowel disease is comprised of 2 major disorders Ulcerative Colitis Crohn disease

Inflammatory bowel disease Ulcerative colitis : Chronic inflammatory condition Relapsing and remitting episodes of inflammation limited to mucosal layer of colon.

Inflammatory bowel disease Ulcerative colitis : Involves the rectum and typically extends in a proximal and continuous fashion to involve other portions of the colon.

Inflammatory bowel disease Crohn disease: Transmural inflammation and by skip lesions.

Inflammatory bowel disease Crohn disease: May lead to fibrosis and strictures and to obstructive clinical presentations Transmural inflammation results in sinus tracts, giving rise to microperforations and fistulae.

Inflammatory bowel disease Crohn disease: Involves the entire GI tract from mouth to perianal area Most commonly affected area = Ileum + proximal colon Phenotype of Crohn disease : inflammatory, structuring or penetrating

Inflammatory bowel disease

Inflammatory bowel disease

Inflammatory bowel disease 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

Inflammatory bowel disease Epidemiology Prevalence of Ulcerative colitis in adults in the USA = 238 per 100 000 population Prevalence of Crohn Disease in adults in the USA = 201 per 100 000 population. Incidence and prevalence of Crohn disease and ulcerative colitis appear to be lower in Asia and the Middle East

Inflammatory bowel disease Risk Factors Age and gender (Onset between 15-40 years) Slight Female predominance in Crohn Disease especially in later adolescence and early adulthood Slight male predominance in ulcerative colitis

Inflammatory bowel disease Risk Factors Racial and ethnicity (Incidence lower in black and Hispanic populations compared to whites) Genetic susceptibility (10-25% of individuals with IBD have a first degree relative with Crohn or ulcerative colitis)

Inflammatory bowel disease Risk Factors Smoking Associated with an increased risk of Crohn disease Paradoxically lower risk for milder disease in ulcerative colitis Current as well as past smokers are more likely to develop Crohn disease than those who never smoked. Smoking may also increase the risk of recurrence of Crohn disease

Inflammatory bowel disease Risk Factors Diet (Western style diet : processed, fried and sugary food associated with an increased risk of developing Crohn disease. Physical activity associated with a decrease in risk of Crohn Disease Obesity (accumulation of intra-abdominal fat may contribute to mucosal inflammation) Infections (imbalance in the gut microbiome may contribute to the developing of IBD)

Inflammatory bowel disease Risk Factors For UC : Hx of prior GI infections, e.g. Shigella, Salmonella, Campylobacter, during adulthood double risk of developing UC, thought to be changes in gut flora triggering chronic inflammatory process Weak associations between NSAIDs, OCPs and increased risk of UC

Inflammatory bowel disease Ulcerative colitis : Clinical manifestation Diarrhea, may be associated with blood Bowel movement frequent and small in volume Symptoms : colicky abdominal pain, urgency, tenesmus, incontinence Onset : gradual, symptoms are progressive over several weeks Patients may have fever, fatigue and weight loss

Inflammatory bowel disease Ulcerative colitis : Clinical manifestation Diagnosis based on presence of chronic diarrhea for more than 4 weeks Evidence of chronic colitis on endoscopy and biopsy Exclusion of other causes of colitis by history, lab studies

Inflammatory bowel disease Ulcerative colitis : Clinical manifestation 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

Inflammatory bowel disease 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

Inflammatory bowel disease Ulcerative colitis : Complications Complications include severe bleeding, toxic megacolon, perforation, strictures and the development of dysplasia and colorectal cancer

Inflammatory bowel disease Ulcerative colitis Double contrast barium enema Demonstrates extensive mucosal Ulceration and inflammation Throughout the colon

Inflammatory bowel disease Ulcerative colitis : Treatment Ulcerative proctitis : 5-ASA to induce remission Suppositories alone are effective in managing proctitis Proctosigmoiditis require enemas + suppositories

Inflammatory bowel disease Ulcerative colitis : Treatment Left-sided colitis, extensive colitis or pancolitis Mildly or moderately active left-sided colitis/extensive/pancolitis : combination therapy with oral 5- ASA medications, rectal 5-ASA or steroid suppositories, and 5- ASA or steroid enemas or foam preparations Failure to respond to combination therapy with oral 5-ASA medications and topical 5-ASA and steroids : Oral glucocorticoids (Glucocorticoids should be tapered after the patient has been stable for 2-4 weeks).

Inflammatory bowel disease Ulcerative colitis : Treatment

Inflammatory bowel disease Ulcerative colitis : Treatment Surgical treatment required in approximately 20-30% 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.

Inflammatory bowel disease Ulcerative colitis :Prevention and 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/ Primary sclerosing cholangitis = PSC: Annually from time of dx of PSC Risk factors for Colorectal cancer Duration and extent of disease Endoscopic and histologic severity of inflammation

Inflammatory bowel disease Crohn 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

Inflammatory bowel disease Crohn 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,

Inflammatory bowel disease Crohn Disease : Clinical presentation 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

Inflammatory bowel disease Crohn Disease : Diagnosis Clinical diagnosis based on history findings with objective findings from history and laboratory studies As with UC, must r/o important non-infectious causes (IBS, Behcet’s syndrome blood vessel inflammation ) 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

Inflammatory bowel disease Crohn 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

Inflammatory bowel disease Crohn 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 Primary sclerosing cholangitis (PSC) should undergo annual screenings