Chapter 151: Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders of unknown etiology involving the gastrointestinal (GI) tract. Peak occurrence is between ages 15 and 30 and between ages 60 and 80, but onset may occur at any age. Epidemiologic features are shown in Table 151-1. Pathogenesis of IBD involves activation of immune cells by unknown inciting agent (? microorganism, dietary component, bacterial or self-antigen) leading to release of cytokines and inflammatory mediators. Genetic component suggested by increased risk in first-degree relatives of pts with IBD and concurrence of type of IBD, location of Crohn’s disease (CD), and clinical course. Reported associations include HLA-DR2 in Japanese pts with ulcerative colitis (UC) and a CD-related gene called CARD15 on chromosome 16p. CARD15 mutations may account for 10% of CD risk. Other potential pathogenic factors include serum antineutrophil cytoplasmic antibodies (ANCA) in 70% of pts with UC (also in 5–10% of CD pts) and antibodies to Saccharomyces cerevisiae (ASCA) in 60–70% of CD pts (also in 10–15% of UC pts and 5% of normal controls). Granulomatous angiitis (vasculitis) may occur in CD. Acute flares may be precipitated by infections, nonsteroidal anti-inflammatory drugs (NSAIDs), and stress. Onset of UC often follows cessation of smoking.
TABLE 151-1: Epidemiology of IBD
 ULCERATIVE COLITISCROHN’S DISEASE
Incidence (North America) per person-years0–19.2 per 100,0000–20.2 per 100,000
Age of onset15–30 and 60–8015–30 and 60–80
EthnicityJewish > non-Jewish white > African American > Hispanic > Asian
Male/female ratio0.51–1.580.34–1.65
SmokingMay prevent disease (OR 0.58)May cause disease (OR 1.76)
Oral contraceptivesNo increased riskOR 2.82
AppendectomyProtective (risk 13–26% lower)Not protective
Monozygotic twins6–18% concordance38–58% concordance
Dizygotic twins0–2% concordance4% concordance
Antibiotic use in the first year of life2.9× the risk of developing childhood IBD 
Abbreviations: IBD, inflammatory bowel disease; OR, odds ratio.

ULCERATIVE COLITIS

PATHOLOGY

Colonic mucosal inflammation; rectum almost always involved, with inflammation extending continuously (no skip areas) proximally for a variable extent; histologic features include epithelial damage, inflammation, crypt abscesses, loss of goblet cells.

CLINICAL MANIFESTATIONS

Bloody diarrhea, mucus, fever, abdominal pain, tenesmus, weight loss; spectrum of severity (majority of cases are mild, limited to rectosigmoid). In severe cases, dehydration, anemia, hypokalemia, hypoalbuminemia.

COMPLICATIONS

Toxic megacolon, colonic perforation; cancer risk related to extent and duration of colitis; often preceded by or coincident with dysplasia, which may be detected on surveillance colonoscopic biopsies.

DIAGNOSIS

Sigmoidoscopy/colonoscopy: mucosal erythema, granularity, friability, exudate, hemorrhage, ulcers, inflammatory polyps (pseudopolyps). Barium enema: loss of haustrations, mucosal irregularity, ulcerations.

CROHN’S DISEASE

PATHOLOGY

Any part of GI tract, usually terminal ileum and/or colon; transmural inflammation, bowel wall thickening, linear ulcerations, and submucosal thickening leading to cobblestone pattern; discontinuous (skip areas); histologic features include transmural inflammation, granulomas (often absent), fissures, fistulas.

CLINICAL MANIFESTATIONS

Fever, abdominal pain, diarrhea (often without blood), fatigue, weight loss, growth retardation in children; acute ileitis mimicking appendicitis; anorectal fissures, fistulas, abscesses. Clinical course falls into three broad patterns: (1) inflammatory, (2) stricturing, and (3) fistulizing.

COMPLICATIONS

Intestinal obstruction (edema vs. fibrosis); rarely toxic megacolon or perforation; intestinal fistulas to bowel, bladder, vagina, skin, soft tissue, often with abscess formation; bile salt malabsorption leading to cholesterol gallstones and/or oxalate kidney stones; intestinal malignancy; amyloidosis.

DIAGNOSIS

Sigmoidoscopy/colonoscopy, barium enema, upper GI and small-bowel series: nodularity, rigidity, ulcers that may be deep or longitudinal, cobblestoning, skip areas, strictures, fistulas. CT may show thickened, matted bowel loops or an abscess.

DIFFERENTIAL DIAGNOSIS

TABLE 151-2: Diseases That Mimic IBD
Infectious etiologies
Bacterial
 Salmonella
 Shigella
 Toxigenic
 Escherichia coli
 Campylobacter
 Yersinia
 Clostridium difficile
 Gonorrhea
 Chlamydia trachomatis
Mycobacterial
 Tuberculosis
 Mycobacterium avium
Parasitic
 Amebiasis
 Isospora
 Trichuris trichiura
 Hookworm
 Strongyloides
Viral
 Cytomegalovirus
 Herpes simplex
 HIV
Fungal
 Histoplasmosis
 Candida
 Aspergillus
Noninfectious etiologies
Inflammatory
 Appendicitis
 Diverticulitis
 Diversion colitis
 Collagenous/lymphocytic colitis
 Ischemic colitis
 Radiation colitis/enteritis
 Solitary rectal ulcer syndrome
 Eosinophilic gastroenteritis
 Neutropenic colitis
 Behçet’s syndrome
 Graft-versus-host disease
Neoplastic
 Lymphoma
 Metastatic
 Carcinoma
 Carcinoma of the ileum
 Carcinoid
 Familial polyposis
Drugs and Chemicals
 NSAIDs
 Phosphosoda
 Cathartic colon
 Gold
 Oral contraceptives
 Cocaine
 Ipilimumab
 Mycophenolate mofetil
Abbreviations: IBD, inflammatory bowel disease; NSAIDs, nonsteroidal anti-inflammatory drugs.

INFECTIOUS ENTEROCOLITIS

Shigella, Salmonella, Campylobacter, Yersinia (acute ileitis), Plesiomonas shigelloides, Aeromonas hydrophila, Escherichia coli serotype O157:H7, Gonorrhea, Lymphogranuloma venereum, Clostridium difficile (pseudomembranous colitis), tuberculosis, amebiasis, cytomegalovirus, AIDS.

OTHERS

Ischemic bowel disease, appendicitis, diverticulitis, radiation enterocolitis, bile salt–induced diarrhea (ileal resection), drug-induced colitis (e.g., NSAIDs), bleeding colonic lesion (e.g., neoplasm), irritable bowel syndrome (no bleeding), microscopic (lymphocytic) or collagenous colitis (chronic watery diarrhea)—normal colonoscopy, but biopsies show superficial colonic epithelial inflammation and, in collagenous colitis, a thick subepithelial layer of collagen; response to aminosalicylates and glucocorticoids variable.

EXTRAINTESTINAL MANIFESTATIONS OF UC AND CD

  1. Joint: peripheral arthritis—parallels activity of bowel disease; ankylosing spondylitis and sacroiliitis (associated with HLA-B27)—activity independent of bowel disease
  2. Skin: erythema nodosum, aphthous ulcers, pyoderma gangrenosum, cutaneous CD
  3. Eye: conjunctivitis, episcleritis, iritis, uveitis
  4. Liver: fatty liver, “pericholangitis” (intrahepatic sclerosing cholangitis), primary sclerosing cholangitis, cholangiocarcinoma, chronic hepatitis
  5. Others: autoimmune hemolytic anemia, phlebitis, pulmonary embolus (hypercoagulable state), kidney stones, metabolic bone disease

Treatment: Inflammatory Bowel Diseases

SUPPORTIVE

Antidiarrheal agents (diphenoxylate and atropine, loperamide) in mild disease; IV hydration and blood transfusions in severe disease; parenteral nutrition or defined enteral formulas—effective as primary therapy in CD, although high relapse rate when oral feeding is resumed; should not replace drug therapy; important role in preoperative preparation of malnourished pt; emotional support.

SULFASALAZINE AND AMINOSALICYLATES

Active component of sulfasalazine is 5-aminosalicylic acid (5-ASA) linked to sulfapyridine carrier; useful in colonic disease of mild to moderate severity (3–6 g PO qd); maintenance of remission (2−4 g PO qd). Toxicity (generally due to sulfapyridine component): dose related—nausea, headache, rarely hemolytic anemia—may resolve when drug dose is lowered; idiosyncratic—fever, rash, neutropenia, pancreatitis, hepatitis, etc.; miscellaneous—oligospermia. Newer aminosalicylates are as effective as sulfasalazine but with fewer side effects. Enemas containing 4 g of 5-ASA (mesalamine) may be used in distal UC, one nightly retained qhs until remission, then q2hs or q3hs. Suppositories containing 500 mg of 5-ASA may be used in proctitis.

GLUCOCORTICOIDS

Useful in severe disease and ileal or ileocolonic CD. Prednisone, 40–60 mg PO qd, then taper; IV hydrocortisone, 100 mg tid or equivalent, in hospitalized pts; IV adrenocorticotropic hormone drip (120 U qd) may be preferable in first attacks of UC. Nightly hydrocortisone retention enemas in proctosigmoiditis. Numerous side effects make long-term use problematic.

IMMUNOSUPPRESSIVE AGENTS

Azathioprine, 6-mercaptopurine—50 mg PO qd up to 2.0 or 1.5 mg/kg qd, respectively. Useful as steroid-sparing agents and in intractable or fistulous CD (may require 2- to 6-month trial before efficacy seen). Toxicity—immunosuppression, pancreatitis, ?carcinogenicity. Avoid in pregnancy.

METRONIDAZOLE

Appears effective in colonic CD (500 mg PO bid) and refractory perineal CD (10–20 mg/kg PO qd). Toxicity—peripheral neuropathy, metallic taste, ?carcinogenicity. Avoid in pregnancy. Other antibiotics (e.g., ciprofloxacin 500 mg PO bid) may be of value in terminal ileal and perianal CD, and broad-spectrum IV antibiotics are indicated for fulminant colitis and abscesses.

OTHERS

Cyclosporine (potential value in a dose of 4 [mg/kg]/d IV for 7–14 days in severe UC and possibly intractable Crohn’s fistulas); experimental—tacrolimus, methotrexate, chloroquine, fish oil, nicotine, others. Infliximab (monoclonal antibody to tumor necrosis factor [TNF]) 5 mg/kg IV induces responses in 65% (complete in 33%) of CD pts refractory to 5-ASA, glucocorticoids, and 6-mercaptopurine. In UC, 27–49% of pts respond.
Adalimumab is a humanized version of the anti-TNF antibody that is less likely to elicit neutralizing antibodies in the pt. Pegylated versions of anti-TNF antibody may be used once monthly.
Natalizumab is an anti-integrin antibody with activity against CD, but some pts develop progressive multifocal leukoencephalopathy. Vedolizumab is specific for α4β7 integrin and is more gut selective in its effects.

SURGERY

UC: Colectomy (curative) for intractability, toxic megacolon (if no improvement with aggressive medical therapy in 24–48 h), cancer, dysplasia. Ileal pouch—anal anastomosis is operation of choice in UC, but contraindicated in CD and in elderly. CD: Resection for fixed obstruction (or stricturoplasty), abscesses, persistent symptomatic fistulas, intractability.

Figures

FIGURE 151-1
hmom20_ch151_f001.png
Medical management of IBD. 5-ASA, 5-aminosalicylic acid. CD, Crohn’s disease; UC, ulcerative colitis.