para>CD can mimic UC with continuous bowel involvement; 10-15% of cases are difficult to differentiate; diagnosed as IBD unclassified (IBD-U).
TREATMENT
- Disease severity: Crohn Disease Activity Index (CDAI)
- Asymptomatic: spontaneously, after medical/surgical intervention, or while on steroids (CDAI <150)
- Mild to moderate CD: ambulatory patients able to tolerate PO intake without dehydration, obstruction, or >10% weight loss. No abdominal tenderness, toxicity, or mass (CDAI 150 to 220)
- Moderate to severe CD: Patients who have failed initial treatment or who continue to have mild symptoms such as fever, weight loss, and abdominal pain (CDAI 220 to 450).
- Severe: persistent symptoms despite outpatient therapy with glucocorticoids and/or biologics, or fulminant disease (peritonitis, cachexia, intestinal obstruction, abscess) (CDAI >450)
- General strategies
- Step-up approach: Begin treatment with milder therapy (5-ASA, antibiotics) followed by more aggressive agents (steroids, immunomodulators, anti-TNF agents), as needed.
- Top-down approach: Early management with immunomodulators and/or anti-TNF agents before patients receive steroids, become steroid-dependent, or require surgery.
GENERAL MEASURES
Additional therapies depend on location of disease.
- Oral lesions: triamcinolone acetonide in benzocaine and carboxymethyl cellulose or topical sucralfate for aphthous ulcers, cheilitis, and/or granulomatous sialadenitis
- Gastroduodenal CD: no clinical trials, although slow-release mesalamine may be beneficial, as it is partially released in proximal small bowel. Case reports note success of anti-TNF therapies. Symptomatic relief possible from proton pump inhibitors, H2-receptor blockers, and/or sucralfate.
- Ileitis: supplementation of fat-soluble vitamins, iron, B12, folate, and calcium to prevent bone loss
- Treatment toxicity: pancreatitis, bone marrow toxicity, lymphoma, nonmelanoma skin cancer, infections (TB, histoplasmosis, others), malignancy
MEDICATION
First Line
- Asymptomatic patients: observation alone
- Mild CD
- 5-Aminosalicylates have minimal role in CD management. They can be used for colonic CD without deep ulcerations or penetration/fibrostenosing disease (2)[C].
- Antibiotics use is controversial. Controlled trials have not consistently demonstrated efficacy (2)[C].
- Glucocorticoid therapy: controlled ileal release budesonide (9 mg/day for 8 to 16 weeks, then discontinued over 2 to 4-week taper) for distal ileum and/or right colon involvement (2,3)[A]
- Consider adjunctive therapy: antidiarrheals (loperamide); bile acid-binding resin (cholestyramine 4 to 12 g/day); probiotics (either alone or in combination may prevent recurrent inflammation and reduce symptoms in acute CD).
- Induction/maintenance: 5-ASA is not recommended (3)[C]. Controlled ileal release budesonide, 9 mg/day, is effective for maintenance for up to 6 months (2)[A].
- Moderate to severe CD
- Induction: prednisone 40 to 60 mg/day (2)[A] or controlled-release budesonide (for isolated, moderate ileitis) or anti-TNF agents as initial induction agent or for lack of response to corticosteroid or immunomodulator (2,3)[A]
- Maintenance: no role for mesalamine. If steroids required for induction, use immunomodulator (2,3)[B] or biologic (anti-TNF agent) (2)[A],(3)[B] for maintenance.
- Except for budesonide, do not use steroids for maintenance (1)[A].
- Severe disease: immunomodulators, anti-TNF agents ± steroids
- Azathioprine or 6-mercaptopurine: thiopurine methyltransferase (TPMT) and LFTs prior to initiation. Check CBC/LFTs q2-3mo.
- Methotrexate: effective for steroid-dependent and steroid-refractory CD (2)[B]
- Folic acid 1 mg/day; follow LFTs
- Anti-TNF therapies: active disease, fistulae, steroid sparing, some extraintestinal disease. Infliximab, adalimumab, certolizumab pegol
- Check for evidence of TB and HBV infection prior to initiation of anti-TNF therapy.
- Avoid live vaccines.
- Monitoring: Consider anti-drug Ab levels to assess for immunogenicity. Serum concentrations of anti-TNF agents may also correlate with disease activity.
- Combination therapy
- Azathioprine + infliximab is more effective than either alone if no previously treatment with either.
- Rare complication: hepatosplenic T-cell lymphoma (fatal, mostly seen in young males)
- Anti-adhesion molecules: prevent inflammatory cells from entering GI tract
- Vedolizumab: gut-specific, can be used in anti-TNF failures or anti-TNF naive patients as induction and maintenance; given IV, no risk of progressive multifocal leukoencephalopathy (PML); FDA approved May 2014
- Natalizumab: non-gut-specific, PML risk (1/1,000). Can minimize risk by testing for John Cunningham (JC) virus antibody. However, can avoid risk of PML now with vedolizumab.
ADDITIONAL THERAPIES
Complications
- Peritonitis: bowel rest and antibiotic therapy (7 to 10 days parenteral antibiotics, followed by 2- to 4-week course of PO ciprofloxacin and metronidazole); surgery, as indicated
- Consider holding steroids which mask sepsis.
- Abscess: antibiotics, percutaneous drainage, or surgery with resection of affected segments
- Small bowel obstruction: IV hydration, nasogastric (NG) suction, total parenteral nutrition (TPN) for malnutrition, resolution typically in 24 to 48 hours. Surgery for nonresponders
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
Vaccinations in CD
- Check titers; avoid live vaccines (MMR, varicella, zoster) in patients on immunosuppressive therapy (steroids, 6MP, AZA, MTX, or anti-TNF).
- Regardless of immunosuppression: HPV, influenza, pneumococcal, meningococcal, hepatitis A, B; Tdap
PATIENT EDUCATION
Crohn and Colitis Foundation of America (800) 343-3637; www.ccfa.org
REFERENCES
11 Baumgart DC, Sandborn WJ. Crohn's disease. Lancet. 2012;380(9853):1590-1605.22 Lichtenstein GR, Hanauer SB, Sandborn WJ, et al. Management of Crohn's disease in adults. Am J Gastroenterol. 2009;104(2):465-483.33 Talley NJ, Abreu MT, Achkar JP, et al. An evidence-based systematic review on medical therapies for inflammatory bowel disease. Am J Gastroenterol. 2011;106(Suppl 1):S2-S25.
ADDITIONAL READING
Bernstein CN. Treatment of IBD: where we are and where we are going. Am J Gastroenterol. 2015;110(1):114-126.
CODES
ICD10
- K50.919 Crohn's disease, unspecified, with unspecified complications
- K50.00 Crohn's disease of small intestine without complications
- K50.10 Crohn's disease of large intestine without complications
- K50.019 Crohn's disease of small intestine with unsp complications
- K50.812 Crohn's disease of both small and lg int w intestinal obst
- K50.114 Crohn's disease of large intestine with abscess
- K50.80 Crohn's disease of both small and lg int w/o complications
- K50.913 Crohn's disease, unspecified, with fistula
- K50.111 Crohn's disease of large intestine with rectal bleeding
- K50.819 Crohn's disease of both small and lg int w unsp comp
- K50.013 Crohn's disease of small intestine with fistula
- K50.112 Crohn's disease of large intestine w intestinal obstruction
- K50.912 Crohn's disease, unspecified, with intestinal obstruction
- K50.911 Crohn's disease, unspecified, with rectal bleeding
- K50.918 Crohn's disease, unspecified, with other complication
- K50.811 Crohn's disease of both small and lg int w rectal bleeding
- K50.814 Crohn's disease of both small and large intestine w abscess
- K50.813 Crohn's disease of both small and large intestine w fistula
- K50.113 Crohn's disease of large intestine with fistula
- K50.118 Crohn's disease of large intestine with other complication
- K50.011 Crohn's disease of small intestine with rectal bleeding
- K50.014 Crohn's disease of small intestine with abscess
- K50.119 Crohn's disease of large intestine with unsp complications
- K50.914 Crohn's disease, unspecified, with abscess
- K50.018 Crohn's disease of small intestine with other complication
- K50.012 Crohn's disease of small intestine w intestinal obstruction
- K50.818 Crohn's disease of both small and lg int w oth complication
ICD9
- 555.9 Regional enteritis of unspecified site
- 555.0 Regional enteritis of small intestine
- 555.1 Regional enteritis of large intestine
- 555.2 Regional enteritis of small intestine with large intestine
SNOMED
- 34000006 Crohn's disease (disorder)
- 397173003 Crohn's disease of intestine
- 7620006 Crohn's disease of large bowel
- 56689002 Crohn's disease of small intestine
- 196977009 Crohn's disease of terminal ileum (disorder)
- 71833008 Crohn's disease of small AND large intestines
CLINICAL PEARLS
- The incidence of CD has risen over the past 4 decades.
- MRE allows assessment of luminal and extraluminal CD without radiation exposure.
- Assess for TB and HBV infection prior to initiating anti-TNF therapy.
- Cigarette smoking doubles the risk of developing CD; tobacco cessation may reduce frequency of flares and need for surgery.
- Test for C. difficile infection when evaluating diarrhea in all CD patients.
- Hospitalized CD patients require deep vein thrombosis prophylaxis.