Crohn Disease
Crohn Disease: Excerpt from The 5-Minute Pediatric Consult
Douglas Jacobstein, MDRobert Baldassano, MDPetar Mamula, MD
Crohn Disease - BASICS
Crohn Disease - description
Crohn disease (CD) is a chronic inflammatory bowel disease that can affect any part of the GI tract.
Crohn Disease - epidemiology
- More than 1/3 of patients 1st present in childhood or adolescence.
- Family history is present in 30% of patients <30 years old.
- In adulthood, Male = Female; in childhood, Male > Female (1.6:1)
Crohn Disease - incidence
- The incidence rate in children is 4.56/100,000 in North America.
- Highest incidence in the white population
Crohn Disease - risk factors
Crohn Disease - genetics
- 1st-degree relatives have a 5–25% higher risk than the normal population.
- Family members of patients with CD have increased risk for both CD and ulcerative colitis.
- Offspring and siblings have an 8% risk of developing inflammatory bowel disease (IBD).
- Concordance in monozygotic twins is 44.4%; in dizygotic twins, 3.8%.
- Susceptibility regions are located on different chromosomes (6, 12, 16).
- CARD15 mutation is present in ~14–18% of patients.
Crohn Disease - pathophysiology
- Interaction and combination of environmental factors, genetic susceptibility, host’s intestinal flora, and a yet-unspecified triggering factor lead to a dysregulated immune response, causing chronic intestinal inflammation.
- Patients with the CARD15/NOD2 mutation have dysregulated response to bacterial products, which changes innate low-grade to a high-grade inflammatory response.
- There is highly significant association between CD and the IL23R gene on chromosome 1p31, which encodes a subunit of the receptor for the pro-inflammatory cytokine interleukin-23.
- Initially, the T-helper-1 lymphocyte pathway is activated, causing inflammatory cytokines to generate microscopic inflammation, which infiltrates all layers of intestine with cryptitis or crypt abscesses, and distortion of crypt architecture.
- Macroscopically, the intestinal wall is edematous, mesentery may be thickened, local lymph nodes enlarged, and fat extends from the mesentery and “creeps” over the serosal surface.
- Granulomas are found in 20–40% of biopsies and, if found, are pathognomonic.
- Normal bowel can exist in continuity with affected bowel (skip areas).
Crohn Disease - DIAGNOSIS
Crohn Disease - signs & symptoms
Crohn Disease - history
- Frequency of signs and symptoms:
- Weight loss: 85%
- Diarrhea: 80%
- Abdominal pain: 85%
- Fever: 40%
- Rectal bleeding: 50%
- Growth failure: 35%
- Nausea and vomiting: 25%
- Rectal disease: 25%
- Extraintestinal signs: 25%
- Perianal disease: 25%
- Symptoms depend on the intestinal site and the disease activity.
- Sites most often affected, in decreasing frequency, are terminal ileum, right colon, isolated colon, proximal small bowel, and upper GI tract (i.e., stomach, duodenum, esophagus).
- Chronic diarrhea
- Weight loss
- Growth failure (Careful charting of recent growth parameters, especially growth velocities from school or medical records, is essential.)
- Delayed puberty
- Recent travel (enteric infections)
- Antibiotic use (Clostridium difficile)
- Family history of IBD
- Extraintestinal disease:
- Arthritis
- Erythema nodosum
- Pyoderma gangrenosum
- Mouth ulcers
- Episcleritis
- Uveitis
- Thromboembolic disease
- Vasculitis
- Renal stones
- Amyloidosis
- Sclerosing cholangitis
- Pancreatitis
Crohn Disease - physical exam
- Growth delay and weight loss, delayed puberty
- Abdominal examination:
- Hyperactive bowel sounds
- Right lower quadrant (RLQ) mass and tenderness
- Palpable thickened loop of intestine
- Rectal and perianal examination: Skin tag, fissure, fistula, and abscess
Crohn Disease - tests
Crohn Disease - lab
- CBC; microcytic anemia due to iron deficiency, normocytic anemia due to chronic disease, macrocytosis suggesting nutrient deficiency: Iron, BESR, C-reactive protein, stool calprotectin (disease activity)
- Electrolytes (hydration, renal function)
- Transaminases, alkaline phosphatase, γ-glutamyl transpeptidase (hepatobiliary disease)
- Stool for occult blood and presence of white cells
- Stool cultures, Clostridium difficile toxin A and B
- Perinuclear antineutrophil cytoplasmic antibody (pANCA) and anti-Saccharomyces cerevisiae antibody (ASCA) may be helpful in differentiating among types of IBD.
Crohn Disease - imaging
- Consider plain abdominal x-ray in acute presentation, to rule out obstruction or perforation.
- Barium upper GI and small bowel follow-through; to evaluate extent of disease in small bowel not accessible to endoscopy
- Barium enema has been replaced by colonoscopy in acute colitis; useful in evaluation of complications such as strictures and fistulas
- CT scan and ultrasound useful for evaluation of complications (abscess, phlegmon)
- MRI and abdominal ultrasound are increasingly being used for assessment of disease extent and activity.
- Colonoscopy and upper endoscopy with multiple biopsies are the gold-standard tests for initial evaluation and diagnosis of CD.
- Video capsule endoscopy can be used to access small bowel not visualized at the time of endoscopy.
Crohn Disease - differencial diagnosis
- Ulcerative colitis
- Appendicitis
- Infection:
- Mycobacterium tuberculosis
- Salmonella
- Shigella dysenteriae
- Campylobacter jejuni
- Aeromonas spp.
- Yersinia enterocolitica
- Clostridium difficile
- Escherichia coli
- Giardia lamblia
- Cryptosporidium
- Strongyloides
- Hemolytic-uremic syndrome
- Henoch-Schönlein purpura
- Irritable bowel syndrome
- Peptic ulcer disease
- Autoimmune enteropathy, immunodeficiency
- Cow’s milk protein allergy
- Small intestinal lymphoma
Crohn Disease - TREATMENT
Crohn Disease - medication
- The goal of therapy is resolution of all symptoms, appropriate growth, and good quality of life. The therapy is used in a stepwise fashion.
- Several 5-aminosalicylic acid (5-ASA) preparations are being used according to their intestinal site of activation, because of their anti-inflammatory properties:
- Mesalamine (Asacol; terminal ileum, colon): 50–100 mg/kg/d (maximum 4.8 g/d for active disease and 3.2 g/d to maintain remission)
- Mesalamine (Pentasa; duodenum, jejunum, ileum, colon): 50–100 mg/kg/d (maximum, 4 g/d for active disease and 3 g/d to maintain remission)
- Balsalazide (Colazal; 6.75 g/d; 110–170 mg/kg/d): Can be given to small children as liquid preparation
- Mesalamine (Rowasa): 4-g enemas and 500-mg suppositories daily to b.i.d. PR
- Corticosteroids can control intestinal inflammation: 1–2 mg/kg/d oral prednisone (maximum, 60 mg). Initially, patient is treated for several weeks and tapered off within several weeks. Topical hydrocortisone is useful in localized left-sided colonic disease and is available in liquid and foam enemas. Corticosteroid with controlled ileal release, budesonide (9 mg/d) is available.
- Nutritional therapy is frequently used in Europe and Canada as a 1st-line therapy:
- Elemental and polymeric diet is reported to be effective in inducing remission in active disease.
- To correct growth failure, an increase in caloric intake is recommended and can be given as overnight nasogastric feeding if oral supplements are not tolerated.
- Azathioprine, 2–3 mg/kg/d, and its metabolite 6-mercaptopurine, 1–1.5 mg/kg/d, are used for the immunomodulatory properties in patients who are unresponsive to corticosteroids, or dependent on them, and for perianal disease. Adverse events include liver toxicity and leukopenia.
- Frequent laboratory follow-up is necessary, and WBC should be maintained >3 to 4 × 109/L and platelets >100 × 109/L.
- Methotrexate, 15–25 mg IM or PO once a week
- Other immunomodulatory therapy used infrequently: Cyclosporine, tacrolimus (FK-506), thalidomide, etc.
- Antibiotics:
- Metronidazole: 15 mg/kg/d
- Ciprofloxacin: 20 mg/kg/d
- Infliximab, a biologic, chimeric anti–tumor necrosis factor-α antibody (5 mg/kg IV infusion, given every 2–3 months, after initial 3-dose induction therapy at 0, 2, and 6 weeks) for severe and fistulizing disease unresponsive to other therapy
- Other biologic therapy currently in clinical trials
- Complementary therapy (probiotics, prebiotics)
Crohn Disease - surgery
- Surgery is used in patients with localized disease that is unresponsive to other therapy, intractable bleeding, stricturizing disease, especially in case of proximal intestinal dilatation, and perforation. Several types of procedures are available: strictureplasty, abscess drainage, and intestinal resection (side-to-side anastomosis is widely accepted).
- Most of these procedures are performed laparoscopically, which reduces recovery time.
- Surgery is not curative, and postoperative recurrence at the site of anastomosis is common.
Crohn Disease - FOLLOW UP
Crohn Disease - complications
- Intestinal obstruction due to strictures, or adhesions
- Abscess or phlegmon formation
- Enteroenteric, enterovesical, enterovaginal, and enterocutaneous fistulas
- Perforation
- Gallstones, kidney stones
- Intestinal lymphoma, colon cancer
- Malabsorption resulting in deficiency (e.g., vitamin BMassive hemorrhage is rare (1%).
- Growth failure is frequent; final height is reduced and puberty is delayed in CD affecting prepubertal children.
- Osteopenia and osteoporosis secondary to inflammation, nutritional deficiency, and therapeutic side effects (corticosteroids)
- Toxic megacolon is a rare but serious complication.
Crohn Disease - patient monitoring
- The morbidity of this disease is high. The majority of patients experience recurring disease.
- Most patients have good general health in between disease and go on to lead productive lives.
- Carcinoma surveillance is necessary on a regular basis.
- After 5 and 20 years of disease, the probability of survival is 98% and 89% of expected survival, respectively.
- Death is a rare complication (2.4% in a large series).
Crohn Disease - bibliography
- Cabre E, Gassull MA. Nutritional and metabolic issues in inflammatory bowel disease. Curr Opin Clin Nutr Metab Care. 2003;6(5):569–576.
- Escher J, Taminiau J, Nieuwenhuis E, et al. Treatment of inflammatory bowel disease in childhood: Best available evidence. Inflamm Bowel Dis. 2003;9:34–58.
- Hildebrand H, Karlberg J, Kristiansson B. Longitudinal growth in children with IBD. J Pediatr Gastroenterol Nutr. 1994;18(2):165–173.
- Mamula P, Markowitz JE, Baldassano RN. Inflammatory bowel disease in early childhood and adolescence: Special considerations. Gastroenterol Clin North Am. 2003;32(3):967–995, viii.
- Navarro F, Hanauer SB. Treatment of inflammatory bowel disease: Safety and tolerability issues. Am J Gastroenterol. 2003;98(12 suppl):S18–S23.
- Ogura Y, Bonen D, Inohara N, et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature. 2001;411:603–606.
- Seidman E, Leleiko N, Ament M, et al. Nutritional issues in pediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 1991;12:424.
- Spray C, Debelle GD, Murphy MS. Current diagnosis, management and morbidity in paediatric inflammatory bowel disease. Acta Paediatr. 2001;90(4):400–405.
Crohn Disease - CODES
Crohn Disease - icd9
555.9 Regional enteritis
Crohn Disease - FAQ
- Q: Should the diet of patients with CD be restricted?
- A: Balanced nutrition is required to assure appropriate growth and development. The only foods not recommended are poorly digestible vegetables (if eaten raw), nuts, and popcorn, which can cause obstruction in the narrowed, inflamed intestine. Patients with secondary lactose intolerance should use lactase supplements, or avoid milk products while ensuring adequate calories and calcium intake.
- Q: What is the cause of CD?
- A: Both genetic and environmental factors are important in the development of CD. Possible environmental factors include aseptic environment in the 1st few years of life, lack of breast-feeding, frequent use of antibiotics or aspirin, and diet.
- Q: Where can I learn more about CD?
- A: The Crohn and Colitis Foundation of America (CCFA, www.CCFA.org) is a nonprofit organization dedicated to the care of people with CD and ulcerative colitis.
- Q: What new therapies will be used in the near future?
- A: Biologic agents, which use our recently improved knowledge of the immune system, either to downregulate inflammatory mediators or upregulate immunomodulatory mediators. It is hoped that this new class of therapies will greatly improve our care of people with CD.
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Book Source Details
- Book Title: The 5-Minute Pediatric Consult
- Author(s): M. William Schwartz MD; et al.
- Year of Publication: 2008
- Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.
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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
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More About This Book:
Title: The 5-Minute Pediatric Consult
Authors: M. William Schwartz MD; et al.
Publisher: Lippincott Williams & Wilkins
Copyright: 2008
ISBN: 0-7817-7577-9
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