eMedicine Specialties > Pediatrics: General Medicine > Gastroenterology
Crohn Disease: Treatment & Medication
Updated: Oct 8, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
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Treatment
Medical Care
The general goals of treatment for children with Crohn disease (CD), or Crohn's disease, are (1) to achieve the best possible clinical, laboratory, and histologic control of the inflammatory disease with the least adverse effects from medication; (2) to promote growth with adequate nutrition; and (3) to permit the patient to function as normally as possible (eg, in terms of school attendance, participation in activities). Treatment has changed over the past few years, reflecting the development of new agents that can target specific locations in the GI tract and specific cytokines.
Typically, therapy for pediatric Crohn disease is administered in a step-up approach. Patients with mild disease are treated with preparations of 5-aminosalicylic acid (5-ASA), antibiotics, and nutritional therapy. If no response occurs or if disease is more severe than initially thought, corticosteroid and immunomodulatory therapy with 6-mercaptopurine (6-MP) or methotrexate (MTX) is attempted. Finally, biologic and surgical therapies, at the tip of the treatment pyramid, are used. More recently, adult data have supported the use of biological therapy earlier in the course of disease (a "top-down" approach) as a more effective treatment method.6
- 5-ASA preparations
- Although commonly used, recent adult meta-analyses have suggested that oral 5-ASA preparations do not demonstrate clinically important treatment effect for active Crohn disease and are not superior to placebo for the maintenance of remission in Crohn disease.7
- Topical 5-ASA therapy is available in suppository and enema forms for the treatment of distal colitis.
- Nutritional therapy
- Nutritional therapy is another important modality for the treatment of disease, malnutrition, and growth failure observed in Crohn disease. A dramatic reversal of malnutrition and a change in growth velocity can be expected in all children treated with adequate nutrition in conjunction with medical therapy to control symptoms of Crohn disease. Additionally, exclusive enteral nutrition has been shown to be as effective as corticosteroids for the induction of remission and might promote better GI tract mucosal healing.8
- Because most patients have appetite suppression, overnight nasogastric feeds are often used. Although the exact mechanism of action is unknown, beneficial effects could be due to alteration of the intestinal flora, decrease in the antigen load, and decrease in inflammatory cytokine levels.
- Corticosteroids
- These are the mainstay of therapy for acute exacerbations because they suppress acute inflammation, thereby providing rapid symptomatic relief.
- Systemic corticosteroids are not indicated for maintenance therapy.
- Enteric coated ileal-release preparations have been developed for the treatment of ileal and cecal Crohn disease with decreased systemic effects.
- Immunomodulators
- Immunomodulators have been used to induce and maintain long-term remission in chronically active, steroid-dependent or steroid-refractory, moderate-to-severe pediatric Crohn disease.
- 6-mercaptopurine (6-MP) and its prodrug, azathioprine, are effective for the induction and maintenance of remission and reduction of corticosteroid exposure in pediatric Crohn disease. Three months is often required to achieve therapeutic efficacy, although the onset of action varies.
- Thiopurine methyltransferase (TPMT) activity should be measured prior to initiation of therapy to identify patients predisposed to altered drug metabolism, increasing the risk of leukopenia.
- Measurement of 6-thioguanine nucleotide (6-TG) metabolites are helpful in assessing compliance and adjusting therapy.
- Methotrexate (MTX) is effective in inducing and maintaining remission in chronic Crohn disease in adults and has been shown to be effective and well tolerated for maintenance of remission in children.9 The onset of action is shorter for MTX than for 6-MP, and the once-weekly dosing is sometimes preferred. Whether oral therapy is as effective as parenteral administration is unclear.
- Antibodies to tumor necrosis factor (TNF)-alpha
- Infliximab, a chimeric monoclonal antibody to TNF-alpha, is effective in patients who have an inadequate response to conventional therapy and for the treatment of fistulizing Crohn disease. Infliximab has been approved for the treatment of pediatric Crohn disease. Current clinical practice is to use it as an intravenous (IV) infusion of 5 mg/kg at 0 weeks, 2 weeks, and 6 weeks, followed by maintenance IV infusions every 8 weeks.
- The most common adverse events to infliximab therapy are acute and delayed infusion reactions, associated with the formation of antibodies to infliximab (ATI), occurring in 16-39% of children. Premedication does not seem to prevent infusion reactions; however, after an infusion reaction occurs, premedication may be indicated to prevent subsequent infusion reactions.
- Adalimumab, a fully humanized anti-TNF-alpha antibody, is a safe and effective substitute for patients who are allergic to infliximab or develop high titers of human antichimeric antibodies (HACA).
- One area of concern with the use of these medications is that multiple patients have been reported to develop a rare hepatosplenic T-cell lymphoma when treated with dual therapy of 6-MP or azathioprine as well as a TNF-alpha inhibitor. Although this has been a rare complication, all reported cases have been in adolescents and young adults.
- Antibiotics: A few, small studies have shown the usefulness of antibiotic therapy in the treatment of Crohn disease. Metronidazole, as well as the combination of metronidazole and ciprofloxacin, is useful in both the management of perianal disease and small bowel and colonic disease.
- Alternative and complimentary therapies: Patients and their families frequently use alternative and complimentary therapies. A potential beneficial effect has been observed with omega-3 fatty acids found in fish oil. Probiotics might provide some treatment benefit, although studies have provided inconsistent results.
Surgical Care
- Surgery is considered when medical therapy fails.10
- Indications include intractable disease with growth failure, obstruction or severe stenosis, abscess requiring drainage, perianal fistulae, intractable hemorrhage, and perforation.
- Recurrence of disease at the anastomotic site is common after resection.
- Surgical treatment for Crohn disease, unlike that for ulcerative colitis (UC), is not curative.
- Laparoscopic techniques have more recently become the standard of care for most inflammatory bowel disease surgeries, resulting in decreased recovery time.11
Consultations
- Crohn disease is a chronic disease that needs to be treated by a team of experts consisting of pediatricians, pediatric gastroenterologists, psychologists, nutritionists, social workers, and nurses.
- A critical factor in successful management of this disease is the willingness of the patient to participate and cooperate with the team.
- Parents and patients must be educated and receive support to effectively treat this disorder.
Diet
- Patients are advised to avoid food that is difficult to digest because it is rich in insoluble fiber (eg, uncooked vegetables, popcorn, seeds, nuts) in order to prevent intestinal obstruction. The obstruction may be due to narrowing or stricture secondary to the inflammation in the small intestine. No other empiric dietary restrictions are recommended, although patients are advised to avoid any foods that tend to exacerbate their disease.
- Nutritional therapies are used for treatment of mild and moderate-to-severe disease, maintenance of remission, and nutritional rehabilitation. In addition to the beneficial nutritional effect, the formula is thought to have anti-inflammatory properties.
Activity
- The goal of the therapy is to allow normal unrestricted activity.
- Patients with osteoporosis secondary to prolonged corticosteroid therapy should avoid high speed and high impact contact sports to minimize the risk of fracture.
Medication
The goals of pharmacotherapy in Crohn disease (CD), or Crohn's disease, are to reduce morbidity and prevent complications.
5-aminosalicylic Acid Derivative
These agents are used to treat mild-to-moderate disease and to maintain remission.
Mesalamine (Asacol, Pentasa, Rowasa, Canasa)
A 5-ASA product. Inhibits leukotriene biosynthesis by lipoxygenase pathway of arachidonic acid metabolism and interferes with myeloperoxidase activity and reactive oxygen species. The currently approved PO mesalamine products in the United States differ only in the mechanism of drug delivery. Mesalamine is FDA-approved for UC but is widely used off-label for CD.
Mesalamine products have not been approved for use in children but are considered standard of care for inflammatory bowel disease and are supported by numerous reports in the literature.
Asacol has mesalamine within a Eudragit-S coating that dissolves and releases the mesalamine at pH 7, which typically occurs in the terminal ileum. Pentasa is 5-ASA in ethylcellulose and has a time-release coating. Release of mesalamine from Pentasa begins at the pylorus; because of this, the drug is often used when proximal intestinal Crohn disease is suggested. Despite its proximal release, no convincing data indicate the site of release translates into clinical superiority.
Rectal dosage forms deliver high concentrations of mesalamine to the left colon as high as the splenic flexure (enema with 30 min retention) or to the rectum for use in proctitis (supp). Although effective, associated with relatively high relapse rate upon discontinuation. Widespread use of topical agents is limited by patient acceptance in many cases; often, patients with active rectal disease have difficulty holding in enema.
Adult
Asacol: 1.2 g PO qid
Pentasa: 1 g PO qid
Rowasa enema: 4 g PR hs
Canasa suppository: 500 mg PR qd/bid
Pediatric
50-100 mg/kg/d PO divided tid/qid
Decreases effect of iron, digoxin, and folic acid; mesalamine increases effect of PO anticoagulants, MTX, and PO hypoglycemic agents
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Headaches, diarrhea, and rash; case reports of acute pancreatitis and one case report of pericarditis
Corticosteroids
These agents are used to treat active moderate-to-severe disease. They are not indicated for maintenance therapy. Budesonide is available in ileal controlled-release form and is used for the treatment of ileal and/or right-sided colonic disease.
Prednisone (Deltasone, Orasone)
Exercise the anti-inflammatory effects through decreased capillary permeability, impaired neutrophil chemotaxis, release of anti-inflammatory cytokines, decrease of production of eicosanoids, and stabilization of lysosomal membrane.
Adult
60 mg PO qd
Pediatric
2 mg/kg PO qd or divided bid; not to exceed 60 mg qd
Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, and fungal or tubercular skin infections; gastric ulceration
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use
Methylprednisolone (Medrol, Solu-Medrol)
Anti-inflammatory effects by means of decreased capillary permeability, impaired neutrophil chemotaxis, release of anti-inflammatory cytokines, decreased production of eicosanoids, and stabilization of lysosomal membrane.
Adult
24 mg IV bid
Pediatric
2 mg/kg IV bid; not to exceed 48 mg qd
Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, and fungal or tubercular skin infections; GI ulceration
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use
Budesonide (Entocort EC)
Exerts anti-inflammatory effect by means of decreased capillary permeability, impaired neutrophil chemotaxis, release of anti-inflammatory cytokines, decrease of production of eicosanoids, and stabilization of lysosomal membrane.
Adult
9 mg PO qd
Pediatric
Not established; limited data suggest 0.45 mg/kg/d PO; not to exceed 9 mg/d
Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, and fungal or tubercular skin infections; GI ulceration
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use
Hydrocortisone (Cortenema, Anusol-HC)
Rectally administered corticosteroid similar to IV and PO corticosteroids; significant amounts of corticosteroids can be absorbed systemically when administered by enema or suppository. Various products containing hydrocortisone available for rectal use. Useful for treating distal colonic disease.
Adult
Cortenema: 1 enema 100 mg/60 mL PR bid
Anusol-HC: 1 suppository 25 mg PR bid
Pediatric
Administer as in adults
Corticosteroid clearance may decrease with estrogens; may increase digitalis toxicity secondary to hypokalemia
Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Impaired wound healing; contraindications apply but generally of decreased severity; as much as 75% of administered rectal dose may be absorbed if lower colon severely inflamed
Immunosuppressive agents
These agents are used to treat moderate-to-severe disease, to treat steroid-dependent or steroid-refractory disease, and to maintain remission.
6-Mercaptopurine (Purinethol)
6-MP and its prodrug azathioprine are purine analogs that interfere with protein synthesis and nucleic acid metabolism. Cytotoxic effect on lymphoid cells. Onset of action delayed 2-3 mo.
Adult
1-1.5 mg/kg PO qhs
Pediatric
Administer as in adults
Toxicity increases when administered with allopurinol
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Hypersensitivity reactions include fever, rash, arthralgia, nausea, vomiting, diarrhea, and pancreatitis; nonallergic toxicity includes leukopenia, anemia, thrombocytopenia, and hepatitis
Azathioprine (Imuran)
Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which lowers autoimmune activity.
Adult
2-3 mg/kg PO qhs
Pediatric
Administer as in adults
Toxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of MTX metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Increases risk of neoplasia; caution with liver disease and renal impairment; hematologic toxicities may occur; may decrease sperm count
Methotrexate (Folex PFS, Rheumatrex)
Impairs DNA synthesis and induces apoptosis and reduces IL-1 production. For treatment of moderate-to-severe disease and maintenance of remission. Onset of action delayed.
Adult
25 mg IM/PO qwk
Pediatric
Not established; suggested pediatric dosing:
10-19 kg: 5 mg IM/PO qwk
20-29 kg: 10 mg IM/PO qwk
30-39 kg: 15 mg IM/PO qwk
40-49 kg: 20 mg IM/PO qwk
>50 kg: 25 mg IM/PO qwk
PO aminoglycosides may decrease absorption and blood levels of concurrent PO MTX; charcoal lowers levels; coadministration with etretinate may increase hepatotoxicity; folic acid or its derivatives contained in some vitamins may decrease response; coadministration with NSAIDs may be fatal; indomethacin and phenylbutazone can increase plasma levels; may decrease phenytoin serum levels; probenecid, salicylates, procarbazine, and sulfonamides, including trimethoprim-sulfamethoxazole (TMP-SMZ), may increase effects and toxicity; may increase plasma levels of thiopurines
Documented hypersensitivity; alcoholism, hepatic insufficiency, documented immunodeficiency syndromes, preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, clinically significant anemia)
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Monitor CBC counts monthly and liver and renal function q1-3mo during therapy (more frequently during initial dosing, dose adjustments, or with risk of elevated levels [eg, dehydration]); toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; discontinue if blood counts decrease substantially; aspirin, NSAIDs, or low-dose steroids may be administered concomitantly (possibility of increased toxicity with NSAIDs, including salicylates, not tested)
Biologic therapy
These agents are used in the treatment of active disease or fistulizing disease unresponsive to other medical therapy.
Infliximab (Remicade)
Chimeric IgG1k monoclonal antibody that neutralizes cytokine TNF-a and inhibits its binding to TNF-a receptor. Reduces infiltration of inflammatory cells and TNF-a production in inflamed areas.
Adult
Induction: 5 mg/kg as single IV infusion at weeks 0, 2, and 6 wk
Maintenance: 5 mg/kg IV q8wk
Note: May increase to 10 mg/kg IV q8wk for patients who respond, then lose their response; discontinue treatment in those who do not response by week 14
Pediatric
Administer as in adults
None reported
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
TNF-alpha modulates cellular immune responses; anti-TNF therapies, such as infliximab, may adversely affect normal immune responses and allow development of superinfections; more cases of lymphoma were observed in TNF alpha-blockers compared to controlled groups; may increase risk of reactivation of tuberculosis in patients with particular granulomatous infections
Adalimumab (Humira)
Recombinant human IgG1 monoclonal antibody specific for human TNF. Binds specifically to TNF-alpha and blocks interaction with p55 and p75 cell-surface TNF receptors.
Adult
Induction: 160 mg SC once (administer by either by dividing dose into 4 injections on day 1 or over 2 days), then follow with 80 mg SC once at week 2
Maintenance: 40 mg SC q2wk beginning at week 4
Pediatric
Not established
May interfere with immune response to live virus vaccine (eg, MMR) and reduce efficacy; MTX decreases clearance (available data do not support adjusting dose of either adalimumab or MTX); coadministration with anakinra (an IL-1 antagonist that also blocks TNF) may cause additive adverse effects, particularly development of serious infections
Documented hypersensitivity; active infection
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Causes immunosuppression; may be associated with serious infections (some fatal) including reactivation of tuberculosis, sepsis, or opportunistic infections; increases risk for lymphoma development; associated with CNS demyelination (rare); discontinue if serious infection develops; autoantibody development may occur causing lupus-like syndrome; may cause hypersensitivity reactions including anaphylaxis and hematologic adverse effects (ie, pancytopenia, aplastic anemia); exacerbation of CHF or new onset CHF has been observed with TNF-blocking agents
Antibiotics
These agents are used in the treatment of mild-to-moderate disease, fistulizing, and perianal disease. Antibiotics may change the microbial flora of the intestine and have a potential effect on cell-mediated immune system.
Metronidazole (Flagyl)
Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa.
Adult
10-20 mg/kg PO divided bid/tid
Pediatric
Administer as in adults
Cimetidine may increase toxicity; may increase effects of anticoagulants; may increase toxicity of lithium and phenytoin; disulfiram-like reaction may occur with PO ethanol
Documented hypersensitivity; first trimester of pregnancy
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust dose in hepatic disease; monitor for seizures and peripheral neuropathy; possible carcinogenic effects after high-dose, long-term treatment
Ciprofloxacin (Cipro)
Inhibits bacterial DNA synthesis and, consequently, growth.
Adult
250-500 mg PO bid
Pediatric
<18 years: Not recommended
>18 years: Administer as in adults
Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; reduces therapeutic effects of phenytoin; probenecid may increase serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor prothrombin time [PT])
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
In prolonged therapy, periodically evaluate functions of organ systems (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy
More on Crohn Disease |
| Overview: Crohn Disease |
| Differential Diagnoses & Workup: Crohn Disease |
 Treatment & Medication: Crohn Disease |
| Follow-up: Crohn Disease |
| Multimedia: Crohn Disease |
| References |
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References
Kugathasan S, Judd RH, Hoffmann RG, et al. Epidemiologic and clinical characteristics of children with newly diagnosed inflammatory bowel disease in Wisconsin: a statewide population-based study. J Pediatr. Oct 2003;143(4):525-31. [Medline].
Griffiths AM, Buller HB. Inflammatory bowel diseases. In: Walker WA, Durie P, eds. Textbook of Pediatric Gastrointestinal Diseases. 3rd ed. 2000.
Tysk C, Lindberg E, Jarnerot G, Floderus-Myrhed B. Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking. Gut. Jul 1988;29(7):990-6. [Medline].
Zholudev A, Zurakowski D, Young W, Leichtner A, Bousvaros A. Serologic testing with ANCA, ASCA, and anti-OmpC in children and young adults with Crohn's disease and ulcerative colitis: diagnostic value and correlation with disease phenotype. Am J Gastroenterol. Nov 2004;99(11):2235-41. [Medline].
Lee SS, Kim AY, Yang SK, et al. Crohn disease of the small bowel: comparison of CT enterography, MR enterography, and small-bowel follow-through as diagnostic techniques. Radiology. Jun 2009;251(3):751-61. [Medline].
D'Haens G, Baert F, van Assche G, et al. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial. Lancet. Feb 23 2008;371(9613):660-7. [Medline].
Akobeng AK, Gardener E. Oral 5-aminosalicylic acid for maintenance of medically-induced remission in Crohn's Disease. Cochrane Database Syst Rev. 2005;(1):CD003715. [Medline].
Borrelli O, Cordischi L, Cirulli M, et al. Polymeric diet alone versus corticosteroids in the treatment of active pediatric Crohn's disease: a randomized controlled open-label trial. Clin Gastroenterol Hepatol. Jun 2006;4(6):744-53. [Medline].
Turner D, Grossman AB, Rosh J, et al. Methotrexate following unsuccessful thiopurine therapy in pediatric Crohn's disease. Am J Gastroenterol. Dec 2007;102(12):2804-12; quiz 2803, 2813. [Medline].
[Guideline] Strong SA, Koltun WA, Hyman NH, Buie WD. Practice parameters for the surgical management of Crohn's disease. Dis Colon Rectum. Nov 2007;50(11):1735-46. [Medline]. [Full Text].
von Allmen D, Markowitz JE, York A, Mamula P, Shepanski M, Baldassano R. Laparoscopic-assisted bowel resection offers advantages over open surgery for treatment of segmental Crohn's disease in children. J Pediatr Surg. Jun 2003;38(6):963-5. [Medline].
Alfadhli AA, McDonald JW, Feagan BG. Methotrexate for induction of remission in refractory Crohn's disease. Cochrane Database Syst Rev. 2005;CD003459. [Medline].
Beattie RM. Enteral nutrition as primary therapy in childhood Crohn's disease: control of intestinal inflammation and anabolic response. JPEN J Parenter Enteral Nutr. Jul-Aug 2005;29(4 Suppl):S151-5; discussion S155-9, S184-8. [Medline].
Belluzzi A, Brignola C, Campieri M, et al. Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease. N Engl J Med. Jun 13 1996;334(24):1557-60. [Medline].
Castellaneta SP, Afzal NA, Greenberg M, et al. Diagnostic role of upper gastrointestinal endoscopy in pediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr. Sep 2004;39(3):257-61. [Medline].
Colombel JF, Sandborn WJ, Rutgeerts P, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial. Gastroenterology. Jan 2007;132(1):52-65. [Medline].
Crandall WV, Mackner LM. Infusion reactions to infliximab in children and adolescents: frequency, outcome and a predictive model. Aliment Pharmacol Ther. Jan 2003;17(1):75-84. [Medline].
Danzi JT. Extraintestinal manifestations of idiopathic inflammatory bowel disease. Arch Intern Med. Feb 1988;148(2):297-302. [Medline].
Debray D, Pariente D, Urvoas E, et al. Sclerosing cholangitis in children. J Pediatr. Jan 1994;124(1):49-56. [Medline].
Devroede GJ, Taylor WF, Sauer WG, et al. Cancer risk and life expectancy of children with ulcerative colitis. N Engl J Med. Jul 1 1971;285(1):17-21. [Medline].
Durno CA, Sherman P, Williams T, et al. Magnetic resonance imaging to distinguish the type and severity of pediatric inflammatory bowel diseases. J Pediatr Gastroenterol Nutr. Feb 2000;30(2):170-4. [Medline].
Escher JC, Taminiau JA, Nieuwenhuis EE, et al. Treatment of inflammatory bowel disease in childhood: best available evidence. Inflamm Bowel Dis. Jan 2003;9(1):34-58. [Medline].
Fagerberg UL, Loof L, Myrdal U, et al. Colorectal inflammation is well predicted by fecal calprotectin in children with gastrointestinal symptoms. J Pediatr Gastroenterol Nutr. Apr 2005;40(4):450-5. [Medline].
Frokjaer JB, Larsen E, Steffensen E, et al. Magnetic resonance imaging of the small bowel in Crohn's disease. Scand J Gastroenterol. Jul 2005;40(7):832-42. [Medline].
Garland CF, Lilienfeld AM, Mendeloff AI, et al. Incidence rates of ulcerative colitis and Crohn's disease in fifteen areas of the United States. Gastroenterology. Dec 1981;81(6):1115-24. [Medline].
Griffiths AM, Nguyen P, Smith C, MacMillan JH, Sherman PM. Growth and clinical course of children with Crohn's disease. Gut. Jul 1993;34(7):939-43. [Medline].
Guilhon de Araujo Sant'Anna AM, et al. Wireless capsule endoscopy for obscure small-bowel disorders: final results of the first pediatric controlled trial. Clin Gastroenterol Hepatol. Mar 2005;3(3):264-70. [Medline].
Hanauer SB, Stromberg U. Oral Pentasa in the treatment of active Crohn's disease: A meta-analysis of double-blind, placebo-controlled trials. Clin Gastroenterol Hepatol. May 2004;2(5):379-88. [Medline].
Hildebrand H, Karlberg J, Kristiansson B. Longitudinal growth in children and adolescents with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. Feb 1994;18(2):165-73. [Medline].
Hyams J, Crandall W, Kugathasan S, et al. Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn's disease in children. Gastroenterology. Mar 2007;132(3):863-73; quiz 1165-6. [Medline].
Hyams JS, Markowitz J, Treem W. Characterization of hepatic abnormalities in children with inflammatory bowel disease. Inflamm Bowel Dis. 1995;1:27-33.
Hyams JS, Wyzga N, Kreutzer DL, et al. Alterations in bone metabolism in children with inflammatory bowel disease: an in vitro study. J Pediatr Gastroenterol Nutr. Mar 1997;24(3):289-95. [Medline].
Jacobstein DA, Markowitz JE, Kirschner BS, et al. Premedication and infusion reactions with infliximab: results from a pediatric inflammatory bowel disease consortium. Inflamm Bowel Dis. May 2005;11(5):442-6. [Medline].
Khan K, Schwarzenberg SJ, Sharp H, et al. Role of serology and routine laboratory tests in childhood inflammatory bowel disease. Inflamm Bowel Dis. Sep 2002;8(5):325-9. [Medline].
Kirschner BS. Safety of azathioprine and 6-mercaptopurine in pediatric patients with inflammatory bowel disease. Gastroenterology. Oct 1998;115(4):813-21. [Medline].
Kugathasan S, Loizides A, Babusukumar U, et al. Comparative phenotypic and CARD15 mutational analysis among African American, Hispanic, and White children with Crohn's disease. Inflamm Bowel Dis. Jul 2005;11(7):631-8. [Medline].
Lenaerts C, Roy CC, Vaillancourt M, et al. High incidence of upper gastrointestinal tract involvement in children with Crohn disease. Pediatrics. May 1989;83(5):777-81. [Medline].
Levine A, Broide E, Stein M, et al. Evaluation of oral budesonide for treatment of mild and moderate exacerbations of Crohn's disease in children. J Pediatr. Jan 2002;140(1):75-80. [Medline].
Lofberg R, Rutgeerts P, Malchow H, et al. Budesonide prolongs time to relapse in ileal and ileocaecal Crohn's disease. A placebo controlled one year study. Gut. Jul 1996;39(1):82-6. [Medline].
Markowitz J, Daum F, Aiges H, et al. Perianal disease in children and adolescents with Crohn's disease. Gastroenterology. May 1984;86(5 Pt 1):829-33. [Medline].
Markowitz J, Grancher K, Kohn N, et al. A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn's disease. Gastroenterology. Oct 2000;119(4):895-902. [Medline].
McLeod RS, Churchill DN. Urolithiasis complicating inflammatory bowel disease. J Urol. Sep 1992;148(3 Pt 2):974-8. [Medline].
Miele E, Markowitz JE, Mamula P, Baldassano RN. Human antichimeric antibody in children and young adults with inflammatory bowel disease receiving infliximab. J Pediatr Gastroenterol Nutr. May 2004;38(5):502-8. [Medline].
Ogura Y, Bonen DK, Inohara N, et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature. May 31 2001;411(6837):603-6. [Medline].
Peacock K, Porn U, Howman-Giles R, et al. 99mTc-stannous colloid white cell scintigraphy in childhood inflammatory bowel disease. J Nucl Med. Feb 2004;45(2):261-5. [Medline].
Polito JM 2nd, Childs B, Mellits ED, et al. Crohn's disease: influence of age at diagnosis on site and clinical type of disease. Gastroenterology. Sep 1996;111(3):580-6. [Medline].
Scholbach T, Herrero I, Scholbach J. Dynamic color Doppler sonography of intestinal wall in patients with Crohn disease compared with healthy subjects. J Pediatr Gastroenterol Nutr. Nov 2004;39(5):524-8. [Medline].
Stephens MC, Baldassano RN, York A, et al. The bioavailability of oral methotrexate in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. Apr 2005;40(4):445-9. [Medline].
Thomas AG, Holly JM, Taylor F, Miller V. Insulin like growth factor-I, insulin like growth factor binding protein-1, and insulin in childhood Crohn's disease. Gut. Jul 1993;34(7):944-7. [Medline].
Uhlen S, Belbouab R, Narebski K, et al. Efficacy of methotrexate in pediatric Crohn's disease: a French multicenter study. Inflamm Bowel Dis. Nov 2006;12(11):1053-7. [Medline].
Vasiliauskas EA, Plevy SE, Landers CJ, et al. Perinuclear antineutrophil cytoplasmic antibodies in patients with Crohn's disease define a clinical subgroup. Gastroenterology. Jun 1996;110(6):1810-9. [Medline].
Verhave M, Winter HS, Grand RJ. Azathioprine in the treatment of children with inflammatory bowel disease. J Pediatr. Nov 1990;117(5):809-14. [Medline].
Wedemeyer J, Kirchhoff T, Sellge G, et al. Transcutaneous perianal sonography: a sensitive method for the detection of perianal inflammatory lesions in Crohn's disease. World J Gastroenterol. Oct 1 2004;10(19):2859-63. [Medline].
Wilschanski M, Sherman P, Pencharz P, et al. Supplementary enteral nutrition maintains remission in paediatric Crohn's disease. Gut. Apr 1996;38(4):543-8. [Medline].
Further Reading
Keywords
Crohn disease, CD, Crohn colitis, Crohn's disease, regional enteritis, granulomatous colitis, ileitis, terminal ileitis, inflammatory bowel disease, IBD, diarrhea, rectal bleeding, abdominal pain, growth failure, malnutrition, pubertal delay, bone demineralization, ulcerative colitis, UC, growth deceleration, anorexia, skin tags, fissures, abscesses, fistula, granuloma, erythema nodosum, pyoderma gangrenosum, orofacial granulomatosis, angular stomatitis, aphthous stomatitis, acrodermatitis enteropathica, alopecia, episcleritis, uveitis, iritis, conjunctivitis, arthralgia, arthritis
ankylosing spondylitis, sacroiliitis, osteopenia, osteoporosis, iron deficiency anemia, vitamin B12 deficiency anemia, folate deficiency anemia, autoimmune hemolytic anemia, thrombocytosis, thrombosis, primary sclerosing cholangitis, autoimmune hepatitis, granulomatous hepatitis, cholelithiasis, portal vein thrombosis, nephrolithiasis, obstructive uropathy, glomerulonephritis, amyloidosis, pancreatitis, granulomatous lung disease, fibrosing alveolitis, pulmonary vasculitis, pericarditis, myocarditis, vasculitis
