GIT 4th IBD 2015

Inflammatory bowel disease

Dr.Mohamed AlshekhaniMBChB-CABM-FRCP-EBGH.

Professor of Medicicne2015

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IBD: UC&CD

• Idiopathic (? immune-mediated) colitis , not due to infections, drugs, ischemia,cancer or radiation.

• IBD: Crohn disease & ulcerative colitis.

• Additional subtypes may exist.

• Most have distinct features of either Crohn disease or ulcerative colitis.

• 5- 10% have features of both diseases (indeterminate colitis).

• IBD most commonly diagnosed in 2nd or 3rd decade but may occur at any age.

• There may be a second peak in the seventh & eighth decades of life.

• There is no gender predominance.

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IBD: Pathogenesis

• A combination of genetic alterations, immune system dysregulation& environmental triggers.

• Ashkenazi (Eastern European) Jewish descendants have a higher prevalence.

• Environmental triggers as probable important factors for disease expression.

• CD may be attributed to an abnormal CD4+ T-cell T-helper 1 (Thl) response

• UC believed to be predominantly a CD4+ T-cell Th2 response.

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IBD: Pathogenesis

• Environmental factors:

• Infections, antibiotics, NSAIDs, other medications.

• Smoking is a risk factor for Crohn disease, whereas the cessation of smoking appears to be a risk factor for new diagnoses of ulcerative colitis in some older patients.

• An interesting north-south gradient, of similar pattern to other immune-mediated disease (such as multiple sclerosis).

• IBD is more prevalent in the west than third-world countries & in higher socioeconomic groups supporting that environmental or lifestyle factors may be important in the pathogenesis.

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Clinical features:

• The clinical manifestations of UC/CD can be very different.

• UC causes mucosal inflammation isolated to the colon.

• CD causes transmural bowel wall inflammation & affect the entire gastroenterologic tract from the mouth to the anus.

• Symptoms vary widely in severity &directly related to the extent of bowel involvement& the complications.

• IBD may be mild, causing only occasional symptoms, or severe, causing significant impact on quality of life.

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Clinical features: UC

• Almost always have a sense of bowel urgency due to rectal inflammation.

• Frequent watery bowel movements are typical& bleeding occurs with more severe inflammation.

• Onset is typically acute& patients often remember when 1st started.

• UC almost always starts in rectum & involves varying length of colon

• If limited to the rectum (proctitis).

• If extend from rectum to sigmoid or descending colon (left-sided colitis)

• If continue proximal to splenic flexure to include the entire colon (extensive colitis or pancolitis).

• Typical endoscopic features: continuous inflammation with varying severity of mucosal granularity, edema, loss of the normal vascular pattern, friability& ulceration.

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• A diffuse pattern of microulcerations is commonly seen& frank ulcers are atypical.

• The transition from abnormal to normal tissue is usually abrupt, with a very clear line of demarcation.

• Pseudopolyps (inflammatory polyps) may be seen in patients with long standing disease, sometimes with 100s throughout the colon.

• If a stricture develops, this suggests either wrong diagnosis or malignancy.

• Abdominal pain is an unusual manifestation & suggests a complication such as toxic megacolon or perforation.

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• Toxic megacolon is the most severe complication of UC.

• Associated with 40% mortality in patients undergoing emergency colectomy if a perforation has occurred (2% without perforation).

• Most patients have at least 1 week of bloody diarrhea symptoms that are unresponsive to medical therapy.

• O/E: tachycardia, fever, hypotension, decreased or absent BSs, lower abd distention&tenderness, often with peritoneal signs.

• On plain film radiography, the transverse colon is most affected, with dilatation > 6 cm.

• About 50% may improve with medical therapy (bowel rest, IV corticosteroids, antibiotics&fluids);

• Progressive abdominal distention& tenderness with hemodynamic instability are indications for immediate surgery.

Clinical features: CD

• Has variable manifestations &typically more indolent in onset.

• Most patients recall gradually feeling worse over time, sometimes with nonspecific symptoms.

• 1/3-12 have disease that involves both the small bowel & colon.

• 1/3 have disease confined to small bowel (most often the T ileum).

• 20% have isolated colonic disease.

• UGI involvement is less common (<10%) &rarely present without lower GIT findings.

• Perianal disease (fissures, fistulas, abscesses) occurs in 1/4.


• Symptoms depend on the location of die disease & presence of complications such as strictures or fistulas.

• If the colon is predominantly affected, diarrhea& bleeding similar to ulcerative colitis may be the main symptoms.

• When the small bowel is involved or any stricturing is present, post prandial pain & obstructive-type symptoms (pain, nausea, vomiting, bloating) may occur.

• Transmural disease may cause perforations, leading to acute symptoms of peritonitis or long-standing pain and/or fevers due to abscess or phlegmon formation.

• Fistulizing dis can lead to some of the most troublesome symptoms.

• Fistulas may occur around the anus(perianal fistulas), from bowel to bowel (entero-entero fistulas), from bowel to other organs (cnterovesicular or enterovaginal fistulas), or from the bowel to the skin (enterocutaneous fistulas).


• Symptoms from fistulas can range from occasional painless drainage to painful cycles of abscess formation followed by drainage.

• Typical endoscopic findings of Crohn disease are a patchy pattern of inflammation with spared regions of normal-appearing mucosa interspersed between abnormal regions ("skip lesions").

• It is common for the rectum to be completely spared.

• Aphthoid ulcerations can range from a few millimeters to a few centimeters in diameter&stricturing of the bowel is not unusual.

• As with UC, pscudopolyps may be seen in the colon; however, if a cluster of polyps is noted, this may represent an internal orifice of a fistula.

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Clinical features: extra-intestinal manifestations of IBD

• Occur in 15% over the course of the disease.

• Ocular: include episcleritis, iritis, or uveitis.

• Oral aphthous ulcers: are more common in Crohn disease than UC but may occur in the latter.

• Rheumatological:

• such as enteropathic peripherL arthritis are fairly common; typically symmetric, follow disease activity involve both large & small joints.

• Sacroiliitis & ankylosing spondylitis are associated with IBD; patients with ankylosing spondylitis are often HLAB27 positive & does not parallel disease activity.

Clinical features: extra-intestinal manifestations of IBD

• The most common dermatologic manifestations are erythema nodosum(painful subcutaneous nodules most often seen on the extensor surface of the leg)& pyoderma gangrenosum(ulcers on the skin that can mimic cellulitis).

• Erythema nodosum & pyoderma gangrenosum associated with ulcerative colitis typically resolve with treatment of the underlying disease.

• Primary sclerosing cholangitis is more common in patients with UC; may represent a distinct phenotype of disease with a particularly high rate of CRC.

• Some extraintestinal symptoms track with the luminal disease activity (episcleritis, iritis, skin manifestations& peripheral arthiritis) , others are independent of disease activity (uveitis, axial arthritis, primary sclerosing cholangitis).

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IBD diagnosis:Endoscopy with histopathology

• Is the gold standard for diagnosis.

• DD: acute infectious colitis, ischemia, or drug toxicity may have a similar endoscopic appearance.

• IBD will invariably show chronic inflammatory changes and/or granuloma formation on biopsy.

• It can occasionally be very difficult to distinguish both from chronic infections (tuberculosis, Yersinia,actinomycosis, lymphoma), NSAID-induced colitis, or small-bowel lymphoma.

• Cultures, NSAID avoidance, or serial studies with repeat biopsies may be necessary.

• If UC is suspected, colonoscopy with inspection of TI is a must.

• If CD is suspected, colonoscopy with ileoscopy & upper endoscopy should be performed to determine the full extent of disease.

• Backwash ileitis refers to distal ileal involvement with severe extensive UC & may be confused with ileocolonic CD.

IBD diagnosis: imagings

• Radiographic imaging plays a key role in evaluating the small bowel in Crohn disease &identifying complications of Crohn disease& ulcerative colitis.

• A small-bowel follow-through can reveal small-bowel Crohn disease that is out of the reach of upper endoscopy or colonoscopy&maydemonstrate fistulas or strictures.

• CT enterography has recendy gained a prominent role in evaluating Crohn disease because it allows better visualization of the extent& severity of disease&offers luminal images similar to those of small-bowel follow-through & reveal extraluminal findings such as lymphadenopathy, mesenteric fat inflammation, or abscess/phlegmon with no radiation exposure & as good as that of CT enterography.

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IBD diagnosis:imagings

• Ultrasound is used more frequently, more often in children than in adults.

• Small-bowel capsule endoscopy has allowed for a better understanding of proximal small-bowel Crohn disease, but it should only be performed after ruling out strictures by one of the above radiographic images or using smaller capsules ( patency capsule) because of concern about capsule retentions.

IBD diagnosis: Serological markers

• Recendy identified more often in IBD compared to non-IBD.

• They are related to Abs against microbial Ags or specific carbohyds.

• The accuracy is not high enough to be relied on & value is limited without confirmatory endoscopy & cannot establish or rule out a diagnosis of IBD or clearly differentiate CD from UC in patients with indeterminate col tis.

• The number& titre of identified serologic markers correlate with the risk of CD complications.

• Genetic markers are not currently clinically useful.

• Caution should be used when ordering tests for serologic & genetic markers for diagnosis, because a false-positive result can lead to unnecessary testing & false negatives can lead to neglect of a proper evaluation.

IBD diagnosis: studies for complicating infections

• For disease flares, stool studies (routine enteric pathogens, ova, parasites, C. difficile) should be performed, because superimposed infections are not uncommon.

• C. difficile is now well recognized as a cause of significant morbidity &mortality in patients with IBD& is being reported more often in ambulatory patients without recent antibiotic use.

• Patients with colitis (ulcerative colitis or Crohn colitis) whose disease becomes refractory to corticosteroid therapy should undergo colonoscopy with biopsies to evaluate for CMV, which is found in up to 30% of patients undergoing colectomy.

IBD diagnosis: Imagings for complications

• For obstructive symptoms, severe pain, or fever, three-dimensional imaging (CT or MRI) should be performed to rule out complications.

• If there is no evidence of infection or complications requiring surgery, medical therapy should be initiated.

Treatment:

• The treatment of CD&UC are similar but have slightly different approaches within the same classes of medications.

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Treatment of CD:

• The standard approach is to:

• (1) Initiate therapy with 5-aminosalicylate drugs at diagnosis.

• (2) Begin thiopurines with azathioprine or 6- mercaptopurine if a patient requires repeated courses of corticosteroids.

• (3) Begin therapy with anti-tumor necrosis factor (anti-TNF) agents if these other therapies are unsuccessful.

• This has been challenged by newer studies showing that 5-aminosalicylates have only minimal efficacy in Crohn disease& the success of treatment is significantly higher when anti-TNF therapy is begun alone or in combination with thiopurines earlier.

• Many have abandoned the use of 5-aminosalicylates entirely for Crohn disease except for those with mild Crohn colitis.

• Early referral soon after diagnosis to an expert can be very helpful to establish an initial treatment plan.

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Treatment of CD:

• Antibiotics can be useful as adjunctive therapy in patients with Crohn disease involving die colon & in perianal disease, having both an anti-inflammatory&antimicrobial effect.

• Methotrexate administered with 1 mg of folic acid can be used instead of thiopurines when azathioprine or 6-mercaptopurine is not tolerated.

• Natalizumab is effective for patients in whom anti-TNF therapy has been unsuccessful, but it has had limited use based on an association with progressive multifocal leukoencephalopathy due to JC virus infection.

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Treatment of CD:

• Surgery, historically reserved as the last line of treatment for Crohndisease&used more commonly if there is a limited segment of diseased bowel that can be managed with a minimally invasive procedure.

• Patients with perianal disease may need surgical therapy for drainage of abscesses or placement of a seton (a rubber band that is threaded into the orifice of a fistula & out through the anus to develop a loop through the fistula tract to prevent recur rent abscess formation) to aid in fistula healing.

• When there are no signs of active perianal infection, anti-TNF agents are very effective in healing perianal& other enterocutaneous fistulas.

• 40% of patients with Crohn disease require some type of bowel surgery within the first 5 years of their disease; 80% require surgery by 20 years of disease.

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Treatment of UC:

• The therapeutic approach to ulcerative colitis should follow the usual sequence of medical therapy.

• Unlike Crohn disease, patients with ulcerative colitis respond well to 5-aminosalicylate agents.

• Patients with proctitis or leftsided colitis should receive topical therapy with 5-aminosalicylate suppositories& enemas or hydrocortisone enemas.

• If patients require repeated courses of corticosteroids or become corticosteroid dependent, thiopurines should be initiated (mediotrexate has not been shown to be effective in ulcerative colitis).

• Anti-TNF agents should be used in patients who do not maintain remission with thiopurines.

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Treatment of UC:

• In hospitalized patients whose disease is refractory to corticosteroids, infliximab or cyclosporine can be very effective.

• If a patient responds &able to discontinue corticosteroids, infliximab can continued as a maintenance drug or cyclosporine can be used as a short-term bridge to a thiopurine for maintenance.

• Colectomy with end-ileostomy or ileal pouch-anal anastomosis (J-pouch) is usually considered the last resort of treatment; however, some patients may prefer surgery over the potential long-term toxicity from treatment with immunosuppressive medications.

• 20% ultimately require colectomy over the course of their lifetime.

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Treatment of IBD: Health Care Maintenance

• Patients require more frequent& intensive monitoring for long-term complications of therapy & aggressive disease-prevention strategies.

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• Osteopenia & osteoporosis:

• Common as a result of a chronic inflammatory state, corticosteroid use& malabsorption (especially in patients with Crohn disease of the small bowel).

• Patients should receive calcium&vitamin D supplementation as well as a baseline dual-energy X-ray absorptiometry (DEXA) scan.

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• Vaccinations:

• Immunosuppressed patients should receive influenza vaccination every year & pneumococcal vaccination every 5 years.

• Live vaccinations (varicella, intranasal influenza vaccines, measles, mumps, rubella)should be avoided in immunosuppressed patients.

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• CRC surveillance:

• Patients with UC (except those with only proctitis) &CD(with at least one third of the colon involved) are at increased risk of colorectal cancer after 8 years of disease& should undergo surveillance colonoscopy with biopsies every 1-2 years.

• If flat dysplasia is present, the benefits and risks of prophylactic colectomy should be discussed with the patient.

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• Smoking/NSAIDs:

• Because smoking (for Crohn disease)& NSAID use (for Crohn disease &ulcerative colitis) are known to exacerbate disease activity, patients should be routinely reminded to stop smoking & avoid or limit NSAID use.

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• DVT prophylaxis:

• Hospitalized patients with IBD are at an increased risk for DVT & should receive anticoagulation as a routine prophylactic measure.

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BO5 1:

• What is the % of indetermined colitis in patients with IBD:

• A. 90%

• B. 70%

• C. 50%.

• D.10%

• E. 30%.

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BO5 2:

• What is the age in years of most IBD patients:

• A. 5-100

• B. 10-30

• C. 30-40

• D.50-60

• E. 70-90

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BO5 3:

• The enviromental risk factor having different effects on UC & CD is:

• A. Antibiotis.

• B. Infections.

• C. NSAIDs.

• D.Smoking.

• E. Anxiety.

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BO5 4:

• Rectal involvement is characteristic of:

• A. CD.

• B. UC.

• C. Indetermnined colitis.

• D.All.

• E. None.

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BO5 5:

• Perianal disease is characteristic of:

• A. CD.

• B. UC.


• D.All.

• E. None.

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BO5 6:

• Perianal disease is characteristic of:

• A. CD.

• B. UC.


• D.All.

• E. None.

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BO5 7:

• Stricturing disease is characteristic of:

• A. CD.

• B. UC.


• D.All.

• E. None.

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BO5 7:

• Serological markers in IBD:

• A. Can differentiate CD from UC.

• B. Can exclude infectious complications.

• C. Can reclassify Indetermnined colitis.

• D. Can be of prognostic value in CD.

• E. Can differentiate IBD from IBS.

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BO5 9:

• In refractory IBD the following should be exclude except:

• A. Clostridium infection.

• B. CMV infection.

• C. Amebiasis.

• D. Stricture.

• E. None of the above.

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BO5 10:

• The top down use of treatment pyramid is used more for:

• A. CD.

• B. UC.

• C. Intedermined colitis.

• D. All.


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BO5 11:

• The 5 ASAs are more effective in:

• A. CD.

• B. UC.


• D. All.


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BO5 12:

• The antibiotics are used for induction treatment more in:

• A. CD.

• B. UC.


• D. All.


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BO5 13:

• The IBD patients with the following characteristics are at increased risk of CRC except:

• A. Ulcerative proctitis.

• B. Left-sided UC.

• C. CD colitis affecting 1/3 of the colon.

• D. IBD of > 9 years duration.


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BO5 14:

• The following extraintestinal features of IBD are independent of the intestinal disease activity except:

• A. Erythema nodosum.

• B. Episcleritis.

• C. Peripheral arthritis.

• D. Primary sclerosing cholangitis.

• E. Iritis.

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Thanks for attention

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Documents

GIT 4th IBD 2015