1. Genetic Predisposition (Susceptible Host)

• likelihood of finding inflammatory bowel disease in a 1st degree relative of the patient is 5-25%
• siblings and parents of patients are 17-35x and 35-70x, respectively, more likely to develop Crohn's Disease than the general population
• high concordance in monozygotic twins

2. Specific Triggers

• neither exogenous (infectious, drugs, toxins) or endogenous (immune) triggers have been identified thus far
• there is no convincing evidence to implicate a particular bacteria, myobacteria, virus, or protozoan
• a defininte immunogenic etiology has not been established, i.e., autoimmune, defect in antigen processing, or immunoregulation

1. Abdominal Pain

• position of pain reflects site of bowel involvement:
  • right lower quadrant (RLQ) - terminal ileum or cecal
  • periumbilical - colonic or diffuse small bowel
  • epigastric - gastroduodenal
  • odynphagia & dysphagia - esophageal
• pain is persistent, severe, and can awaken patient from sleep
• worse with eating and, if colon involved, with defecation
• RLQ pain may be associated with tenderness, and a fullness or distinct mass on palpation
• pain is the result of transmural inflammation resulting in irritation of the serosa, gut dysmotility, and/or distension

2. Diarrhea

• ranges from 2-10 loose movements/day +/- nocturnal defecation
• bloody diarrhea often with colonic involvement or small bowel disease with ulceration

3. Weight Loss

• multifactoral etiology for malnutrition -> weight loss:
  • sub-optimal intake (anorexia)
  • malabsorption of fats, proteins, carbohydrates, with deficiencies of iron, folic acid, calcium, magnesium, zinc, vitamins D, K, B12
  • increased energy requirements associated with inflammation
  • increased stooling

4. Fever

• low grade or spiking (to 40 C)
• may persist for long periods

5. Growth Retardation

• due to chronic undernutrition or high-dose steroids
• may precede the clinical illness by months or years
• may continue during states of remission

6. Perirectal Disease

• perirectal inflammation with fissures, fistulas, tags, or adhesions

1. Hepatic

• chronic hepatitis
• fatty liver
• cirrhosis
• hepatic abscess
• hepatic granuloma
• hepatic steatosis

2. Biliary

• cholecystitis (acalculous, granulomatous)
• cholelithiasis
• pericholangitis
• sclerosing cholangitis

1. Arthralgias and Arthritis (in 15% of patients)

• may be present several years before the onset of gastrointestinal symptoms
• large joints of the legs more commonly affected
• arthritis is non-deforming, transient, asymmetric and more common with colonic involvement
• activity of joint disease often parallels the activity of the bowel disease

2. Ankylosing Spondylitis

• in 2-6% of patients
• course tends to be independent of the bowel disease

3. Clubbing

• particularly with small bowel disease

1. Early Changes

• superfical aphtoid lesions of mucosa overlying lymphoid follicles; granulomas

2. Later changes

1. Single Contrast

• to identify colonic fissures
• contraindicated in suspected cases of severe colitis

2. Double Contrast (Air-Barium)

• to define mucosal defects - narrowing, stenotic areas, cobblestoning, filling defects

1. Prednisone

• 1-2 mg/kg/day po od or bid (maximum 40-60 mg/d)
• an anti-inflammatory agent
• role is to induce remission in those with small or large bowel disease
• once in remission, decrease dose by 5 mg/week
• may require parenteral therapy if active disease is serious
• long-term, low-dose daily therapy does not prevent relapses or decrease the disease progression
• contraindicated if intra-abdominal sepsis
• side effects: growth suppression, posterior subcapsular cataracts, glaucoma, aseptic necrosis of the femoral head, vertebral collapse, hypertension, depression, acne, hirsutism, striae (may be minimized by alternate day low dose therapy)

2. Sulfasalazine

• 30-50 mg/kg/day po bid-tid
• an anti-inflammatory agent by decreasing prostaglandin and leukotriene synthesis
• role is to induce remission in those with large bowel disease
• sustained-release aminosalicylic acid (5-ASA) may be superior to placebo in treating ileitis
• side effects: nausea, vomiting, abdominal pain, headaches for up to 2 weeks after onset; hypersensitivity rash, bone marrow suppression, pancreatitis, reversible male infertility

3. Antibiotics

4. Immunosuppressive Therapy

• azathiprine, 6-mercaptopurine
• may decrease steroid doses in those patients with severe disease on high steroid dosages and improve disease symptoms after 3-4 months of therapy

1. Elemental Diet

• use during acute exacerbations
• as effective as TPN + complete bowel rest in inducing remission
• may act to decrease inflammation of the bowel by decreasing antigenic stimulation of the gut
• less effective in inducing remission in patients with colonic involvement, fistulas, and perianal disease
• may administer by nocturnal tube feeds

2. Total Parenteral Nutrition (TPN)

• indications:
  • severe acute exacerbations
  • severe disease + malnutrition
  • extensive bowel resection leading to a short gut syndrome
  • reverse growth retardation
• usually used as adjunctive therapy to medications

3. Others

• mineral and/or vitamin deficiencies with specific therapy

1. Bowel Resection

• 50-70% of children require surgery within 10-15 years after diagnosis
• indications:
  • failure of pharmacologic/nutritional therapy
  • steroid toxicity
  • others - obstruction, hemorrhage, perforation, fistula
• procedure is not curable but to put the disease into remission with the risk of recurrence dependent upon the extent and severity of the disease

2. Strictures

• surgical resection or strictureplasty for localized strictures

3. Severe Perirectal Disease

• may treat conservatively (abscess drainage, anal fistulotomy, partial internal sphincterectomy, and/or proctectomy) or by fecal diversion with an ileostomy or colostomy