Basics
Description
- Inflammatory bowel disease (IBD) is characterized by chronic or relapsing immune activation and inflammation within the GI tract.
- Crohn's disease (CD) potentially involves any location of GI tract from mouth to anus, but with propensity for distal small bowel and proximal large bowel. Inflammation is often discontinuous but may involve all layers from mucosa to serosa.
- Ulcerative colitis (UC) affects the rectum and extends proximally to affect a variable extent of the colon. The inflammatory response in UC is largely confined to the mucosa and submucosa.
- CD distinguished from UC by disease proximal to colon, presence of perineal disease, fistulas, histologic granulomas, transmural inflammation vs. mucosa-limited disease.
- In indeterminate colitis, the clinical picture falls between the 2 diseases.
Epidemiology
- More common among Caucasians (1-4)
- Jewish population has an incidence 3-6 times greater than that of non-Jewish (2).
- CD prevalence higher in urban areas than rural areas and in higher socioeconomic classes (2).
- CD: Small excess risk among women, female-to-male ratio between 1 and 1.2:1
- UC: Nearly equal to slight male predominance
- Higher rates in northern climates and in well-developed areas
- Peak age of onset is between 15 and 25 years, with a second lesser peak between ages 55 and 65.
Incidence
- UC: Worldwide incidence remains relatively constant, ~24.5 cases per 100,000 (2)
- CD: Worldwide incidence rising progressively, similar to UC in certain areas in North America and Europe; ranges from 0.1 to 16 per 100,000
Prevalence
In Western countries: (2)
- UC: 150-250 cases per 100,000
- CD: 100-200 cases per 100,000
Risk Factors
- Environment (1-4)
- Higher socioeconomic level
- Oral contraceptives (conflicting data)
- NSAIDs/COX-2 selective inhibitors
- Refined sugars, lack of fresh fruits/vegetables postulated, but no causal explanation found
- Smoking: Nicotine and/or smoking byproducts may directly affect mucosal immune responses.
- UC = Disease of ex-smokers and nonsmokers
- CD associated with smoking
- Stress
- Infection correlation remains unproven
- Risk of IBD may increase following episode of acute gastroenteritis with odds ratio 1.4.
Genetics
- ~10-25% have first-degree relatives with IBD (1).
- Concordance for same disease category within families especially with CD, which shows concordance for disease location, type, severity
- Monozygotic twins have higher concordance for IBD than dizygotic twins.
- Mutations within NOD2 gene (IBD1) on chromosome 16 are linked to CD. NOD2 mediates innate immune response to microbial pathogens, activating nuclear factor kappa B (2).
- HLA-DR2 associated with UC, particularly in the Japanese.
- Extraintestinal manifestations of CD are more commonly seen in HLA-A2, HLA-DR1, and DQw5.
Pathophysiology
- Immunologic mechanism within lamina propria implicated in pathogenesis of inflammation and involves both humoral and cellular responses (1).
- Inflammatory response postulated to start with exogenous sensitization to luminal antigens, presumably bacterial, possibly facilitated by undefined genetic influences.
Associated Conditions
- Rheumatologic: Arthralgia, arthritis, ankylosing spondylitis, sacroiliitis (5)
- Hepatobiliary: Primary sclerosing cholangitis, bile duct carcinoma, fatty liver
- Dermatological: Erythema nodosum, pyoderma gangrenosum, aphthous stomatitis
- Ophthalmological: Iritis, uveitis, episcleritis
Diagnosis
History
- Abdominal pain, diarrhea, usually bloody in UC; tenesmus with rectal involvement(1,3-5)
- Fever fatigue, malaise, night sweats
- Weight loss; growth retardation in children
Physical Exam
- General: Fever, pallor, cachexia, tachycardia, hypotension
- Abdominal exam: Tenderness, distention, rebound, guarding, mass, or altered bowel sounds
- On rectal examination: Evaluate for anal strictures, rectal mass; fecal occult blood positivity
- In CD: If perianal disease, evidence of fissures, skin tags; fistulas or abscess
- Extraintestinal inspection of mouth, eyes, skin, and joints: Aphthous ulcers, uveitis, episcleritis; erythema nodosum, reactive arthritis
Tests
Lab
- CBC: Anemia; leukocytosis with a left shift (1,5)
- Elevated ESR or C-reactive protein
- Electrolyte abnormalities; abnormal liver function tests; hypoalbuminemia
- Stool examination: Fecal leukocytes, stool for Clostridium difficile, culture, ova, and parasite
- Stool for calprotectin, lactoferrin, alpha-1 antitrypsin to delineate markers of intestinal inflammation or warning signs of recurrence
- Antineutrophil cytoplasmic antibodies with perinuclear staining in 50-70% of patients with UC, 15% in CD
- Antibodies to Saccharomyces cerevisiae in 60-70% of patients with CD, 5% in UC
- Anti-CBir1 antibodies seen in 50% cases of CD and are associated with internal penetrating and fibrostenosing patterns.
- Suboptimal sensitivity of antibodies argues against use for screening for IBD.
Imaging
- Plain abdominal films (1-4)
- To rule out toxic megacolon, perforation, obstruction, sacroiliitis
- Air-contrast barium enema/upper GI/small bowel series/CT/CT enterography/MR enterography for localization of disease
- Loss of smooth mucosa, thickened bowel wall, ulcerations, dilated bowel, abscess, stricture, fistula, and perirectal disease in CD
Surgery
Flexible sigmoidoscopy/colonoscopy (1,5)
Ulcerative colitis
- Loss of mucosal vascularity, diffuse erythema, friability, granularity, mucosal edema, small punctate ulcers, exudates consisting of mucus, blood, and pus
- Uniform involvement extending continuously from rectum proximally but for variable distance
- Extent of disease:
- ~50% have disease confined to rectosigmoid region, 30% extend to splenic flexure, and <20% extend more proximally.
- Backwash ileitis: Entire colon involved with minimal involvement terminal ileum
Crohn's disease
- Focal intestinal inflammation, transmural, discontinuous (skip areas), ulcerations, which may be tiny, aphthous erosions or deep, serpiginous ulcers, cobblestone appearance of mucosa
- 1/3 of cases involve only small bowel, most commonly the terminal ileum.
- ≅50% have ileocolitis
- ≅20% have disease limited to colon
- Consider EGD if nausea and vomiting to rule out upper GI tract involvement
- Capsule endoscopy may be helpful in patients with suspected CD and negative work-up.
Pathological Findings
- Architectural distortion, cryptitis and crypt abscesses, infiltration with inflammatory cells
- Granulomas, sinus tracts, fistula and fibrosis, fat wrapping (encroachment of mesenteric fat onto the serosal surface of the bowel) in CD
Differential Diagnosis
- Irritable bowel syndrome
- Colitis: Ischemic (rectum usually spared), radiation proctitis, infectious (rule out chronic intestinal infections: TB, amoebiasis, yersinia)
- Colonic neoplasms; chronic diverticulitis
- Beh §et's syndrome
- Lymphoma, NSAIDs enteropathy/colopathy, eosinophilic gastroenteritis (small bowel disease)
Treatment
Medication
First Line
- 5-aminosalicylates (5-ASA) (1-4)
- Sulfasalazine (Azulfidine): 500-1,000 mg q.i.d.
- Mesalamine (Asacol 2.4-4.8 g/daily Pentasa 1,000 mg q.i.d.)
- Balsalazide (Colazal): 2.25 g tid
- Olsalazine (Dipentum): 500 mg b.i.d.
- Mesalamine enemas (Rowasa) or suppositories (Canasa) or hydrocortisone enemas for topical therapy for distal UC
- Glucocorticoids
- Moderate-to-severe disease
- No benefit in continuing after remission; taper and discontinue over a 2- to 3-month period.
- Oral prednisone (40-60 mg/day)
- Budesonide (9 mg/day) for CD involving the terminal ileum and/or ascending colon
- IV prednisolone 45-60 mg/day or IV hydrocortisone (300 mg/day) or methyl-prednisolone (36-48 mg/day) in severely ill
Second Line
- Immunosuppressive therapy when glucocorticoids fail or as steroid-sparing therapy
- Azathioprine, 6-mercaptopurine, methotrexate
- Positive response may take 3-4 months.
- IV cyclosporine in severely ill UC patients
- Antibiotics usually used in CD to treat fistulas, abscesses, bacterial overgrowth: Metronidazole, ciprofloxacin, and rifaximin (under investigation)
- Anti-tumor necrosis factor (TNF) antibody
- Approved for moderate/severe CD and inadequate response to standard therapy
- Infliximab approved for rescue therapy in acute, steroid-refractory, severe UC
- Risk of latent TB and hepatitis B reactivation; check PPD, HBsAg
- IV infliximab 5 mg/kg at weeks 0, 2, and 6 with maintenance infusions every 8 weeks
- SQ adalimumab 160 mg week 0, 80 mg at week 2; maintenance 40 mg every other week
- SQ certolizumab 400 mg weeks 0, 2, and 4; maintenance 400 mg every 4 weeks
- Natalizumab, monoclonal Ab to α-4 integrin
- Approved for moderate-to-severe CD and active inflammation without response to ASA, steroids, immunomodulators, and TNF
- Increased risk of reactivation of latent human JC polyoma virus can lead to progressive multifocal leukoencephalopathy.
Additional Treatment
Issues for Referral
- Refer to gastroenterology to establish diagnosis and management of disease
- Surgical consultation for complications such as perforation, obstruction, fistula, or hemorrhage
Surgery
Ulcerative colitis
- Reserved for specific complications, intractable disease, dysplasia, or carcinoma (1-4)
- 25-30% of UC patients may require surgery.
- Colectomy is curative.
- Surgical options include total proctocolectomy plus permanent ileostomy, temporary ileostomy, ileal pouch-anal anastomosis.
- Emergency surgery for massive hemorrhage, perforation, or toxic megacolon that does not respond to treatment in 48-72 hours.
Crohn's disease
- Reserved for drug-refractory disease or complications: Strictures, intra-abdominal (1,3) abscesses, toxic dilation of colon, or perforation
- 70-75% of CD patients require at least one operation during course of their disease.
- Rarely curative; risk of short bowel syndrome; can lead to long-lasting remission in some patients; recurs frequently after surgery
Ongoing Care
Diet
- Specific nutritional replacement therapy is determined by patient's nutritional status and if clinical course expected to be protracted.
- NPO in severely ill patients +/- parenteral nutrition in patients with severe protein calorie malnutrition, short gut syndrome, severe disease.
- Diet may be advanced from clear liquids to low residue and then regular as tolerated.
- Lactose-free diet if lactose intolerant
Prognosis
Ulcerative colitis
- ~80% have intermittent attacks, but length of remission varies from weeks to years.
- Patients with extensive colitis more likely to have severe attacks; colectomy rate higher.
- Patients with proctitis have a favorable course.
- 70% remain with only rectal involvement.
- More extensive disease can develop with time.
- Mortality rate for a severe attack of UC <2% with the use of more potent medications.
Crohn's disease
- Over a 4-year period
- 22% remain in remission
- 25% have chronically active symptoms
- 54% have fluctuating course
- Modest increase in mortality
- Highest in first 4 or 5 years after diagnosis
- Most deaths from peritonitis and sepsis
- Patients with proximal small bowel disease may have a higher risk of mortality.
- Risk of colorectal cancer is similar in CD and UC of similar extent. Annual surveillance colonoscopy after 8-10 years of pancolitis.
Complications
- Bowel perforation (1,3-5)
- In UC: GI hemorrhage from bleeding ulcerations, toxic megacolon, primary
- Sclerosing cholangitis in UC; increased risk of bile duct and colon cancer
- In CD: Perianal fissures, abscesses, fistulae. Urinary tract or vaginal fistulas not uncommon, intra-abdominal abscesses, intestinal obstruction/small bowel strictures from active inflammation or fibrotic stenosis, gallstone disease
- Increased risk of small bowel adenocarcinoma in small bowel CD, but rare
- Nutritional and metabolic (weight loss, decreased protein, and electrolytes), anemia (iron, folate, or B12 deficiency), bile salt diarrhea with ileal disease, venous thrombosis, uric acid and oxalate renal stones, osteoporosis
- Extraintestinal manifestations
- Fertility does not seem to be impaired (2).
- Course during pregnancy is determined in part by disease activity at conception. Recommend delaying pregnancy until disease is inactive.
- Endoscopy with conscious sedation (meperidine, versed) can be performed, if needed.
- 5-ASA drugs, corticosteroids, and even azathioprine appear to be safe.
- Methotrexate is contraindicated.
- Mode of delivery in CD is controversial. Avoid episiotomy in active perianal disease due to risk of fistula formation; consider cesarean delivery.
References
1Sleisenger MH, Fordtran JS. Gastrointestinal and liver disease, 9th ed. Philadelphia, PA: Elsevier Science, 2010.2Mehta N, Saha S, Chien KS, Powrie RO, Greene MF, Camann W De Swiet's medical disorders in obstetric practice. New York: Blackwell, 2010:256-292.3Kornbluth A, Sachar DB Ulcerative Colitis Practice Guidelines in Adults: American College of Gastroenterology, Practice Parameters Committe. Am J Gastroenterol, 2010. [View Abstract]4Lichenstein GR, Hanauer SB, Sandborn WJ. Management of Crohn's disease in adults. Practice Parameters Committee of American College of Gastroenterology. Am J Gastroenterol. 2009;104(2):465-483.5Bernstein CN, Fried M, Krabshuis JH. World Gastroenterology Organization practice guidelines for diagnosis and management of IBD in 2010. Inflamm Bowel Dis. 2010;16:112-124. [View Abstract]
Codes
ICD9
- 555.9 Regional enteritis of unspecified site
- 556.8 Other ulcerative colitis
- 558.9 Other and unspecified noninfectious gastroenteritis and colitis
- 557.9 Unspecified vascular insufficiency of intestine
ICD10
- K50.90 Crohn's disease, unspecified, without complications
- K51.90 Ulcerative colitis, unspecified, without complications
- K52.9 Noninfective gastroenteritis and colitis, unspecified
- K55.9 Vascular disorder of intestine, unspecified
SNOMED
- 24526004 inflammatory bowel disease (disorder)
- 34000006 Crohn's disease (disorder)
- 64766004 ulcerative colitis (disorder)
- 30588004 ischemic colitis (disorder)
Clinical Pearls
- Crohn's disease and ulcerative colitis are the 2 major forms of idiopathic inflammatory bowel disease.
- No single symptom, sign, or diagnostic test establishes the diagnosis.