By Tasneem Jabr

Inflammatory bowel disease • is a group of inflammatory conditions of the colon and small intestine.

• It includes ulcerative colitis, Crohn’s disease, and indeterminate colitis

• Indetetrminate colitis :

– In 15% of patients with IBD

– differentiation of ulcerative colitis from Crohn’s colitis is impossible either grossly or microscopically (indeterminate colitis).

– These patients typically present with symptoms similar to ulcerative colitis.

– Endoscopic and pathologic findings usually include features common to both diseases.

Etiology • Many different etiologies for inflammatory bowel disease have been

proposed, but none are proven – Environmental factor (diet , life style , infections )

• Smoking : increases the risk for Crohn disease but may lower the risk of developing ulcerative colitis.

• Physical inactivity • Dietary factors low fiber (fruit and vegetables) and high fat diet (animal fat and

polyunsaturated fatty acids ) – Vitamin D deficiency is common among patients with IBD

• Infections Bacteria, such as Mycobacterium paratuberculosis and Listeria monocytogenes, and viruses, such as paramyxovirus and measles virus, have been suggested as etiologic agents in Crohn’s disease.

– Genetics • Family history (10% to 30% of patients report a family member with the same disease. • NOD2 Gene mutation – on chromosome 16 in CD

– interaction among the immune system, the mucosal barrier of the gut, and a variety of infectious agents is involved in the pathogenesis of IBD.

– A defect in the gut mucosal barrier, which increases exposure to intraluminal bacteria, toxins, or proinflammatory substances, also has been suggested.

– Although there is no clear evidence linking an immunologic disorder to inflammatory bowel disease, the similarity of many of the extraintestinal manifestations to rheumatologic disorders has made this theory attractive.

Ulcerative colitis Crohn’s disease

Incidence 8 -15 /100,000 1 -5 / 100,000.

Distribution Higher in the United States and Northern Europe. Lower in Asia, middle east ,Africa, and South America, and among the nonwhite population in the United States. In Northern European and white populations. higher in northern latitudes.

Age (bimodal incidence )

Incidence peaks during the 3rd decade of life and again in the 7th decade of life.

Peak incidence at 15 to 30 years Second peak at 55 to 60 years.

Sex Males > females Females > males

Ulcerative colitis Crohn’s disease

mucosa and submucosa

transmural

continuous involvement of the rectum and colon • rectum alone (proctitis) • rectum and sigmoid colon (proctosigmoiditis) •Rectum and left colon (left-sided colitis) • the rectum and entire colon (pancolitis). does not involve the small intestine, but the terminal ileum may demonstrate inflammatory changes (“backwash ileitis”).

•can affect any part of the gastrointestinal tract from mouth to anus •Terminal ileum and cecum are involved in Crohn’s disease in up to 41% of patients •the small intestine is involved in up to 35% of •patients.

Rectum is always involved Rectal sparing is common

No skip lesions Skip lesions

Ulcerative colitis Crohn’s disease

•Chronic bloody diarrhea •crampy abdominal pain. •Tenesmus (Proctitis ) •Fever, fatigue and weight loss Physical findings : •Physical findings are nonspecific and range from minimal abdominal tenderness and distention to frank peritonitis. • Rectal examination may reveal evidence of blood •Patients with prolonged diarrhea symptoms may have evidence of muscle wasting, loss of subcutaneous fat, and peripheral edema due to weight loss and malnutrition

• crampy abdominal pain (rt lower quadrent) • diarrhea with or without blood • fever ,fatigue and weight loss •Esophageal involvement may present with odynophagia or dysphagia •Gastroduodenal involvement may present with upper abdominal pain, nausea, and/or postprandial vomiting Physical findings : •abdominal tenderness or palpable abdominal mass (typically in the right lower quadrant) •Apthous ulcers •perianal skin tags, sinus tracts

Clinical presentation

Ulcerative colitis Crohn’s disease

Hemorrhage Fulminant colitis toxic megacolon strictures are uncommon ( presumed to be malignant until proven otherwise.)

Anal and Perianal Crohn’s Disease (35% )). •skin tags that are minimally symptomatic. •Fissures (deep or broad / multiple / lateral position •Perianal abscess and fistulas (enterovesical , enterocutaneous, enteroenteric enterovaginal) strictures , obstruction Malabsorbtion ( bowel CD and bile salt protein calorie malnutrition, hypocalcemia, vitamin deficiency (eg, vitamin B12), and metabolic bone disease

complications

colonic diameter ≥6 cm or cecal diameter >9 cm and the presence of systemic toxicity

Extraintestinal Manifestations • Fatty infiltration of the liver is present in 40% to 50% of patients - reversed by medical or

surgical treatment of colonic disease

• liver cirrhosis is found in 2% to 5%. – irreversible

• Primary sclerosing cholangitis (UC > CD)

– 40% to 60% of patients with primary sclerosing cholangitis have ulcerative colitis.

– Colectomy will not reverse this disease, and the only effective therapy is liver transplantation.

• Pericholangitis

• Bile duct carcinoma (rare ) : In long-standing inflammatory bowel disease.

• Arthropathy - 20 times greater than in the general population.

– Sacroiliitis (CD=UC) and ankylosing spondylitis (CD > UC) -

• Medical and surgical treatment of the colonic disease does not impact symptoms.

• Renal stones (CD) • Metabolic bone disease • Erythema nodosum (CD>UC)

– is seen in 5% to 15% - more in women – usually coincides with clinical disease activity. – The characteristic lesions are raised, red, and predominantly on the lower legs.

• Pyoderma gangrenosum (UC>CD) – is an uncommon but serious condition ( occurs almost exclusively in patients with IBD ) – The lesion begins as an erythematous plaque, papule, or bleb, usually located on the pretibial

region of the leg – The lesions progress and ulcerate, leading to a painful, necrotic wound. – Pyoderma gangrenosum may respond to resection of the affected bowel in some patients. In

others, this disorder is unaffected by treatment of the underlying bowel disease.

• Ocular lesion – in 10% of patients with IBD – uveitis, iritis, episcleritis, and conjunctivitis. – They usually develop during an acute exacerbation of the inflammatory bowel disease. – The etiology is unknown.

Diagnosis

• History and Physical examination

• Labs

• Endoscopy and biopsy

• Imaging

Laboratory studies • Blood tests

– Complete blood count ( anemia, elevated WBC count) – KFT, electrolytes : low albumin, and electrolyte abnormalities – LFT : UC and primary sclerosing cholangitis > elevation in serum alkaline

phosphatase concentration – Serum iron, vitamin D, and vitamin B12 levels(deficiency ) – C-reactive protein (CRP) and ESR (elevated)

• Stool studies – stool polymerase chain reaction (PCR) for C. difficile toxin – routine stool cultures (Salmonella, Shigella, Campylobacter, Yersinia), – specific testing for Escherichia coli O157:H7 – Microscopy for ova and parasite – inflammatory markers — fecal calprotectin or lactoferrin (elevated )

• If fecal calprotectin is normal, a diagnosis of IBD is unlikely. • If fecal calprotectin level is above the reference range, we proceed with endoscopy and

biopsy to confirm the diagnosis of IBD.

Endoscopy and biopsy

normal fine vasculature is easily visible, and the surface is shiny and smooth

Endoscopy and biopsy Ulcerative colitis Crohn’s disease

Endoscopic findings -Ileocolonoscopy

•loss of vascular markings (engorgement of the mucosa, giving it an erythematous appearance). • erosions, ulcers , touch friability, and spontaneous bleeding may be present. •Pus and mucus may also be present •Pseudopolyps •In severe cases : macro ulcerations, profuse bleeding, and copious exudates •No skip lesions •No rectal sparing

•The presence of normal vasculature adjacent to affected tissue • Aphthous ulcers •cobblestone appearance : the deep linear ulcers are the "cracks" between the stones, while areas of inflamed or normal tissue form the "stones". •Strictures •Skip areas •rectal sparing ** Upper endoscopy with biopsies

Biopsy •The mucosa may be atrophic •crypt abscesses

Mucosal ulcerations, an inflammatory cell infiltrate, and noncaseating granulomas

UC – endoscopy

ulceration of the mucosa No skip lesions

irregular, friable, and erythematous surface , with loss of the normal vascular markings. Psuedopolyps

Crohn’s endoscopy

can course for several centimeters along the longitudinal axis of the colon in Crohn disease.

serpiginous ulcer

Imaging Ulcerative colitis Crohn’s disease

Barium study Double contrast barium enema •used to diagnose chronic ulcerative colitis and to determine the extent of disease •may be normal in mild ulcerative colitis. •Ulcers ,psuedopolyps , colonic shortening and loss of haustration in long standing •Lead pipe colon •Barium enema should be avoided in patients who are severely ill since it may precipitate ileus with toxic megacolon.

barium small bowel follow-through •narrowing of the lumen with nodularity and ulceration •"string" sign (narrowed terminal ileum) • a cobblestone appearance •Strictures • fistulas and abscess formation, •and separation of bowel loops, a manifestation of transmural inflammation with bowel wall thickening

MRI with enterography Or CT with enterography

marked thickening of the bowel wall •disease distribution and extent • increased bowel wall enhancement and wall thickness, •hyperintensity (possibly reflecting edema), •mucosal lesions (eg, ulcers). •Strictures and enteric fistula •Perianal and pelvic imaging – MRI of the pelvis is used to detect perianal fistula and define the fistula tract

Ulcerative colitis – double contrast barium enema

Pseudopolyps mucosal ulceration

Chron’s – small bowel follow through

nodular filling defects arising on thickened folds in the terminal ileum

String sign Cobblestone appearance

Chron’s – small bowel follow through

abscess and fistulae Ileocecal fistulae

Prognosis Ulcerative colitis Crohn’s disease

Disease course symptoms are chronic and intermittent course can vary Risk factors for progressive disease include •Early onset •Smoking cessation •Poor mucosal healing in response to treatment

symptoms are chronic and intermittent course can vary Risk factors for progressive disease include •Age <40 years •Tobacco use •Perianal or rectal involvement •Glucocorticoid-requiring disease

Risk of colorectal cancer

Marked increase Extent : increases with pancolonic disease duration of symptoms : 2% after 10 years, 8% after 20 years, and 18% after 30 years.

Slightly increased

Mortality slightly higher overall mortality compared with the general population