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Toronto Notes 2019
Small and Large Bowel
Gastroenterology G21
Management (see Figure 7)
Table 12. Management of Crohn’s Disease
Management
Lifestyle/Diet
Antidiarrheal Agents*
5-ASA**
Antibiotics Corticosteroids Immunosuppressives
Biologics
Surgical/ Experimental
Notes
Smoking cessation
Fluids only during acute exacerbation
Enteral diets may aid in remission only for Crohn’s ileitis, not colitis
No evidence for any non-enteral diet changing the natural history of Crohn’s disease, but may affect symptoms Those with extensive small bowel involvement or extensive resection require electrolyte, mineral, and vitamin supplements (vit D, Ca2+, Mg2+, zinc, Fe, B12)
Loperamide (Imodium®) > diphenoxylate (Lomotil®) > codeine (cheap but addictive)
All work by decreasing small bowel motility, used only for symptom relief
CAUTION if colitis is severe (risk of precipitating toxic megacolon), therefore avoid during flare-ups
Efficacy controversial: Is currently used for mild ileitis Sulfasalazine (Salazopyrin®): 5-ASA bound to sulfapyridine
Hydrolysis by intestinal bacteria releases 5-ASA (active component)
Dose-dependent efficacy
Mesalamine (Pentasa®): coated 5-ASA releases 5-ASA in the ileum and colon when inflammation is mild
e.g. metronidazole (20 mg/kg/d, bid or tid dosing) or ciprofloxacin
Best described for perianal Crohn’s, although characteristically relapse when discontinued
Prednisone: starting dose 40 mg OD for acute exacerbations; IV methylprednisolone if severe No proven role for steroids in maintaining remissions; masks intra-abdominal sepsis
6-mercaptopurine (6-MP), azathioprine (Imuran®); methotrexate (used less often) More often used to maintain remission than to treat active inflammation
Most commonly used as steroid-sparing agents
i.e. to lower risk of relapse as corticosteroids are withdrawn
May require >3 mo to have beneficial effect; usually continued for several years
May help to heal fistulae, decrease disease activity
Increases efficacy of biologicals plus lowers chances of biological dosing efficacy (tolerance) so often given in combination with biologics
Side effects: vomiting, pancreatitis, bone marrow suppression, increased risk of malignancy (i.e. lymphoma)
Infliximab IV (Remicade®) or adalimumab SC (Humira®): both = antibody to TNF-α
Proven effective for treatment of fistulae and patients with medically refractory CD
First-line immunosuppressive therapy with infliximab + azathioprine more effective than using either alone Ustekinumab, monoclonal antibody against P40 subunit of interleukin 12 and 23
Vedolizumab, monoclonal antibody directed against integrin α4β7 thereby reducing lymphocyte traffic to gut – now indicated for UC and Crohn’s
Surgical treatment (see General Surgery, GS28)
Surgery generally reserved for complications such as fistulae, obstruction, abscess, perforation, bleeding, and for medically refractory disease
If <50% or <200 cm of functional small intestine, risk of short bowel syndrome
At least 50% clinical recurrence within 5 yr; 85% within 15 yr; endoscopic recurrence rate even higher 40% likelihood of second bowel resection, 30% likelihood of third bowel resection
Complications of ileal resection
<100 cm resected → watery diarrhea or cholorrhea (impaired bile salt absorption) Treatment: cholestyramine or anti-diarrheals e.g. loperamide
>100 cm resected → steatorrhea (reduced mucosal surface area, bile salt deficiency) Treatment: fat restriction, medium chain triglycerides
Traditional Medical Management of Crohn’s
Induction of Maintenance Remission
5-ASA* ? ? Steroids + Immunosuppressive + + Antibiotics +
MTX + + Infliximab + +
*5-ASA use in Crohn’s is controversial. However, initial trial for mild ilelitis only is warranted (induction and maintenance if clinical response)
Note: Starting with immunosupressives plus immunomodulators (“bottom-up approach”) increasingly being used (Lancet 2008;371;660-667). Combination of azathioprine and infliximab has the highest remission rate yet described with medical treatment (NEJM 2010;362;1383-1395). Characteristically more than 1 yr between onset of symptoms and diagnosis of Crohn’s disease.
Nutrition Symptomatic therapy
(e.g. loperamide, acetaminophen)
5-ASA (mesalamine) Antibiotics (FlagylTM, CiproTM)
Corticosteroids
(e.g. budesonide, prednisone)
Immunosuppression
(e.g. azathioprine, 6-MP, methotrexate)
Immunomodulators
(e.g. TNF-antagonists: infliximab, adalimumab)
Experimental therapy or surgery
Figure 7. Traditional graded approach to induction therapy in Crohn’s disease
Note: immunosuppressants and immunomodulators are increasingly used initially (“top-down management strategy”)
*Cholestyramine: a bile-salt binding resin; for watery diarrhea with <100 cm of terminal ileum diseased or resected; however, non-specific anti-diarrheals are more convenient and often more potent
** 5-ASA use in Crohn’s is controversial; however, initial trial for mild ilelitis only is warranted (induction and maintenance if clinical response)
Prognosis
• highlyvariablecourse
• 10%disabledbythediseaseeventually,spontaneousremissionalsodescribed
• increasedmortality,especiallywithmoreproximaldisease,greatestinthefirst4-5yr • complicationsinclude
■ intestinal obstruction/perforation
■ fistula formation
■ malignancy (lower risk compared to UC)
• surveillancecolonoscopysameasulcerativecolitis(seeUlcerativeColitis)ifmorethan1/3ofcoloninvolved
Ulcerative Colitis
Definition
• inflammatorydiseaseaffectingcolonicmucosaanywherefromrectum(alwaysinvolved)tocecum
Epidemiology
• incidence2-10/100,000;prevalence35-100/100,000(morecommonthanCrohn’s) • 2/3onsetbyage30(withsecondpeakafter50);M=F
• smallhereditarycontribution(15%ofcaseshave1stdegreerelativewithdisease) • riskislessinsmokers
• inflammationlimitedtorectumorleftcolonismorecommonthanpancolitis