Inflammatory Bowel Disease Part 1

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Onto this week's topic:

Inflammatory bowel disease refers to a group of three conditions: Crohn’s disease, ulcerative colitis, and indeterminate colitis. These conditions cause the intestines to become inflamed. The mechanism is thought to be that of autoimmune reaction where the body doesn’t recognize itself and ends up attacking itself, but the exact cause may be a combination of environmental and/or infectious and/or other factors. Genetics play a big part—there is increased risk of both Crohn’s disease and ulcerative colitis in relatives of patients with either disease, especially siblings; the risk is even higher if the disease onset is early in life. Additionally, Crohn’s disease is associated with CARD15/NOD2 gene mutation.

Crohn’s Disease is defined as a chronic, transmural inflammatory disorder potentially affecting the entire gut from mouth to anus (“gum to bum”). It has an incidence of 1~6/100,000 (number of newly diagnosed cases in a given time) and a prevalence of 10~100/100,000 (number of cases in the population at a given time). Onset of disease tends to be either before 30 (most common) or around 60 years of age; both sexes are equally affected, although the incidence is increasing (relative to ulcerative colitis) in young females. It is more common in Caucasians and Ashkenazi Jews.

Because it can occur anywhere in the GIT, the natural history can be unpredictable. The most common presentation is recurrent episodes of abdominal cramps, diarrhea, and weight loss. The most common site affected is the ileum and ascending colon; ileitis can present with post-prandial pain, vomiting, and RLQ mass—it may also mimic acute appendicitis—but linear ulceration leading to mucosal islands and classic “cobblestone” appearance on endoscopic finding will confirm Crohn’s disease. Fissures, fistulas, and abscesses are commonly in Crohn’s disease; deep fissures run risk of perforation into contiguous viscera, leading to the formation of fistulae and abscesses—enteric fistulae may communicate with skin, bladder, vagina, and other parts of bowel. Extra-intestinal manifestations are more common with colonic involvement. Granulomas are in 50% of surgical specimen. Young age, perianal disease, and need for corticosteroid therapy are indicators of poor prognosis.

Investigations include colonoscopy (more common) or endoscopy (less common) with biopsy; this should be done only when acute flare up has calmed down. In the meantime, CT/MRI enterography can be done to visualize the small bowel. CRP will be elevated in most new cases, and it is a useful factor to monitor when evaluating patient’s response to treatment. Stool cultures for bacteria, ova and parasites, and C. Difficile toxin should be done to exclude other causes of inflammatory diarrhea.

Management can be divided into the following categories:

·      Acute exacerbation

o   Fluids only

o   Antibiotics—metronidazole or ciprofloxacin

§  Works well for perianal disease

§  Can sometimes cause flare ups when discontinued

o   5-ASA—sulfasalazine or mesalamine

§  Efficacy controversial

§  Most evidence for mild colonic disease

o   Corticosteroids—prednisolone

§  Starting dose 40mg PO

§  IV methylprednisolone if severe

§  No proven role for steroids in maintaining remission

§  May mask intra-abdominal sepsis

o   Immunosuppressives—6-mercaptopurine (6-MP), azathioprine (Imuran), methotrexate (used less often)

§  Used to maintain remission than to treat inflammation

§  Used to decrease chance of relapse when corticosteroids are being withdrawn

§  May take more than 3 months to achieve beneficial effect

§  Usually continued for several years

§  May help heal fistulae and decrease disease activity

§  Side-effects:

·      Vomiting

·      Pancreatitis

·      Bone marrow suppression

·      Increased risk of malignancy

o   Biologics—infliximab (Remicade) IV, adalimumab (Humira) SC

§  Antibodies to TNF-α

§  Proven efficacy for treatment of fistulae and patients with medically refractory Crohn’s disease

§  First-line immunosuppressive therapy with infliximab and azathioprine more effective than used either alone

·      Surgical treatment

o   Usually reserved for complications such as fistulae, obstruction, abscess, perforation, bleeding, and medically refractory disease

o   Resection of bowel

o   Complications

§  <100cm ileum resection can lead to bile salt malabsorption and watery diarrhea—can be treated with cholestyramine or anti-diarrheal like loperamide

§  >100cm ileum resection can lead to steatorrhea—needs dietary fat restriction

§  If less than 50% or < 200cm of functional small intestines remain, then there is risk of developing short bowel syndrome *Short bowel syndrome (SBS, or simply short gut) is a malabsorption disorder caused by a lack of functional small intestine. The primary symptom is diarrhea, which can result in dehydration, malnutrition, and weight loss.

·      Lifestyle changes

o   Quit smoking!

o   No evidence that any specific diet that can change the natural history of Crohn’s disease, but some diet changes may improve symptoms

o   Anti-diarrheal agents—loperamide (Imodium), diphenoxylate (Lomotil), and codeine

§  Symptom relief

§  Decrease bowel motility

§  Should NOT be used during acute exacerbation or severe colitis due to risk of toxic megacolon.

o   Electrolyte replenishment in those with extensive small bowel involvement or extensive resection

§  Vit. D

§  Calcium

§  Magnesium

§  Zinc

§  Iron

§  Vit. B12

Complications include intestinal obstruction/perforation, fistula formation, and malignancy (although Crohn’s has a lower risk than that of ulcerative colitis). Prognosis is hard to predict due to highly variable course of disease, but there is increased mortality if disease onsets within the first 4~5 years of life, especially with more proximal disease. Surveillance colonoscopy is required (same as ulcerative colitis) if more than 1/3 of colon involved.