section name header

General Reference ⬇

Nejm 2002;347:417

Pathophys and Cause ⬆ ⬇

Cause:Unknown; genetic, microbial, immunologic, environmental, dietary, vascular, even psychosocial factors potentially causative agents. Inherited susceptibility for an aberrant immunologic response to 1 or more of these provoking factors. Genetic component in some types on chromosome 16, impacting macrophages; and another on chromosome 5 affecting cytokine receptors

Pathophys: Focal inflammatory infiltrate around crypts, then ulceration of superficial mucosa, then inflammatory cells organize into noncaseating granulomas. Crypt abscesses, destruction of the crypt and atrophy of the colon.

Epidemiology ⬆ ⬇

Males = females; increased in Jews, and relatives of patients, smokers (unlike ulcerative colitis)

Signs and Symptoms ⬆ ⬇

Sx:Onset age 11-35 yr (75%). Cramps, partly relieved by bowel movement; diarrhea, wt loss, obstruction

Si:Inflammatory mass. Extraintestinal manifestations: iritis; erythema nodosum; sclerosing cholangitis; pyoderma gangrenosum; arthritis (20%), especially of knee, ankle, PIP joints, and may even develop clear-cut ankylosing spondylitis

Course ⬆ ⬇

Teenagers get the most malignant form of ileocolitis, older people more often have a more localized disease.

Complications ⬆ ⬇

Abscesses; strictures and fistulas; malabsorption; small bowel obstruction; anemias; renal stones, usually oxalate for unclear reasons; gallstones; sclerosing cholangitis; stress and depression result, do not cause (Ann IM 1991;114:381); rare avascular necrosis of femoral head resulting from steroid tx (Nejm 1993;329:1314)

in pregnancy, moderate increase in spontaneous abortions, otherwise healthy babies and no significant increase in risk for mother even if need surgery, steroids, or sulfa (Nejm 1985;312:1616)

Lab and Xray ⬆ ⬇

Lab:Path:Small bowel or colonic bx may show noncaseating granulomas and distorted glandular architecture; endoscopy (colonoscopy) may demonstrate diagnostic findings

Treatment ⬆

Rx:

(Nejm 1996;334:84; Ann IM 1990;112:50)

Medical of acute disease/flare: depends on flare location and severity

1st:

  • Mesalamine (Asacol) (5-ASA) 800-1600 mg po tid-qid
  • Steroids like prednisolone 40 mg po qd × 2 wk then taper 5 mg qd over 6 wk (Nejm 1994;331:842); or budesonide LA (Entocort-CIR) 9 mg po qd × 8 wk (Nejm 1998;339:370) but not quite as effective as po steroids and much more expensive (Med Let 2002;44:6)
  • Azathioprine (Imuran) or 6-MP (Ann IM 1995;123:132) adjusted by CBC and platelets, helps heal fistulas over 2-4 mo (Ann IM 1989;111:641; Nejm 1980;302:981), induces/maintains remissions

Others: danger of infection, including TB reactivation in immunosuppressive agents

  • Infliximab (Remicade) (Nejm 1997;337:1029), a monoclonal antibody to TNF-alpha.gif 5 mg/kg iv infusion at week 0, 2, and 6 helps >50% within 1 month when given to pts w refractory fistula-producing disease (Lancet 2002;359:1541), though pts develop antibodies to it over time w incr infusion reactions and decr response (Nejm 2004;350:876, 934; 2003;348:601). Better than azathioprine (Nejm 2010;362:1383)
  • Adaluminab (Humira) IgG1 recombinant monoclonal antibody to TNF; 160 mg in 40 mg injections day 1, then 80 mg day 15, then 40 mg at day 29 and q 2 wk. OK to continue aminosalicylates, corticosteroids, and/or immunomodulatory agents
  • Natalizumab (Antegren) (Nejm 2003;348:24) 3-6 mg iv × 2; monoclonal antibody vs integrin, but can induce progressive multifocal leukoencephalopathy (Nejm 2005;353:362, 1912)
  • Metronidazole (Flagyl) 250 mg bid-qid × 2-4 mo helps perianal and colonic disease
  • Certolizumab pegol, a Fab fragment that binds TNF (Nejm 2007;357:228)

Medical remission maintenance: (steroids not worth the risk—ACP J Club 1999;130[2]:36)

  • Imuran/6-MP as above, plus
  • Methotrexate 15 mg im q 1 wk, esp if induced w mtx (Nejm 2000;342:1627)
  • Mesalamine (Pentasa) 500 mg po qid given chronically (GE 1993;104:435), or Asacol 800 mg po tid

Surgical: becoming rarer with advances in medical treatments