II. Epidemiology

  1. Prevalence: 201 per 100,00 in U.S.
  2. Peak onset: 15-30 years (onset up to age 40)
  3. Women more often affected than men
  4. Familial aggregation
    1. First degree relative confers 2-4 fold risk
    2. Second degree relative confers less increased risk

III. Pathophysiology

  1. Etiology unknown
  2. Related genetic mutation: NOD2 (Chromosome 16 in IBD1)
    1. Associated with increased Crohn's Relative Risk
      1. One NOD 2 mutation: 2 fold Relative Risk
      2. Two NOD 2 mutations: 15-35 fold Relative Risk
    2. Proposed Mechanism
      1. Related to defective bacterial sensing by Monocytes
      2. Results in hyper-immune response to bacterial LPS
    3. References
      1. Ahmad (2002) Gastroenterology 122:854 [PubMed] (or open in [QxMD Read])
  3. Chronic granulomatous inflammation
    1. Transmural extension to entire bowel wall
    2. Ulcerative Colitis only affects mucosa
  4. Effects entire Gastrointestinal tract, mouth to anus
    1. Distal ileum and proximal colon most often involved
    2. Isolated colonic involvement in 25% of cases
  5. Irregular involvement ("Skip lesions")

IV. Symptoms

  1. Fever
  2. Weight loss
  3. Fatigue
  4. Nausea
  5. Anorexia
  6. Abdominal Pain (Low abdominal ache or cramp)
  7. Diarrhea (85%)
  8. Rectal bleeding
    1. Much less prominent than in Ulcerative Colitis
    2. Non-bloody Diarrhea is typical for Crohn's Disease

V. Symptoms: Based on location

  1. Ileum and colon (35%)
    1. Diarrhea
    2. Abdominal cramping or Abdominal Pain
    3. Weight loss
  2. Colon only (32%)
    1. Diarrhea
    2. Rectal bleeding
    3. Perirectal Abscess
    4. Fistula
    5. Perirectal ulcer
    6. Associated with skin lesions and arthralgias
  3. Small Bowel only (28%)
    1. Diarrhea
    2. Abdominal cramping or Abdominal Pain
    3. Weight loss
    4. Associated with fistulas and abscesses
  4. Gastroduodenal region (5%)
    1. Anorexia
    2. Weight loss
    3. Nausea and Vomiting
    4. Associated with Bowel Obstruction

VI. Signs: Gastrointestinal

  1. Stool Occult Blood positive
  2. Anal Disease(20%)
    1. Perirectal fistula
    2. Anal Skin Tag
    3. Anal Ulceration or Anal Fissure
    4. Perirectal Abscess
  3. Right Lower Quadrant abdominal palpable mass (common)

VII. Signs: Extra-abdominal manifestations

  1. See Gynecologic Manifestations of Crohn's Disease
  2. Similar to manifestations in Ulcerative Colitis
  3. Anemia (>9%)
  4. Anterior Uveitis (17%)
  5. Episcleritis (29%)
  6. Aphthous Stomatitis (>4%)
  7. Cholelithiasis (>13%)
  8. Erythema Nodosum (>2%)
  9. Inflammatory arthropathy (>10%)
  10. Nephrolithiasis (>8%)
  11. Osteoporosis (>2%)
  12. Pyogenic gangrenosum (>0.5%)
  13. Scleritis (18%)
  14. Venous Thromboembolism (>10%)

VIII. Signs: Extra-abdominal Manifestations (10% Incidence)

  1. Similar findings in Ulcerative Colitis
    1. See Ulcerative Colitis extraintestinal manifestations
  2. Minimal increased Colon Cancer risk

IX. Labs

  1. Complete Blood Count with platelet
    1. Mild Anemia: Chronic blood loss
    2. Mild Leukocytosis: Crohn's Disease exacerbation
    3. Marked Leukocytosis
      1. Severe colitis
      2. Toxic Megacolon
      3. Intra-abdominal abscess
  2. Comprehensive metabolic panel (Liver Function Tests, Renal Function tests)
  3. Acute phase reactants
    1. C-Reactive Protein (C-RP)
    2. Erythrocyte Sedimentation Rate (ESR)
  4. Stool studies
    1. Stool Culture
    2. Ova and Parasites
    3. Clostridium difficile Toxin
  5. Markers of nutritional status
    1. Serum Ferritin
    2. Serum Iron
    3. Total Iron Binding Capacity
    4. Serum Vitamin B12
    5. Serum Folate
    6. Serum Albumin
    7. Serum Prealbumin
    8. Vitamin D
    9. Serum Calcium
  6. Diagnostic labs
    1. Fecal lactoferrin
      1. Sidhu (2010) Aliment Pharmacol Ther 31(12): 1365-70 [PubMed] (or open in [QxMD Read])
    2. Fecal Calprotectin
      1. Kallel (2010) Eur J Gastroenterol Hepatol 22(3): 340-5 [PubMed] (or open in [QxMD Read])
    3. Escherichia coli outer membrane porin Antibody
    4. Saccharomyces cerevisiae Antibody
    5. Perinuclear Antineutrophil Cytoplasmic Antibody (pANCA)

XI. Diagnosis: Colonoscopy with Ileoscopy

  1. Focal Ulcerations: aphthous, stellate, or linear
  2. Skip areas
  3. Rectal sparing
  4. Cobblestone appearance
  5. Strictures

XII. Imaging

  1. Newer studies
    1. CT Abdomen
    2. MRI Abdomen
    3. Capsular Endoscopy
  2. Older studies with lower Test Sensitivity and Test Specificity
    1. Small Bowel follow-through
    2. Barium Enema with retrograde terminal ileum filling
      1. May show classic thumbprinting
      2. Defect protrudes into lumen

XIII. Management: General Measures

  1. No immunosuppressants if infectious colitis possible
  2. Tobacco Cessation
  3. Update vaccinations
    1. Hepatitis B Vaccine
    2. Influenza Vaccine
    3. Pneumococal Vaccine
  4. Avoid exacerbating factors
    1. Pregnancy
    2. NSAIDs
    3. Oral Contraceptives
  5. Consider baseline DEXA Scan and Vitamin D level
  6. Consider concurrent Vitamin Supplementation
    1. Folic Acid
    2. Vitamin B12
    3. Vitamin D Supplementation
    4. Fat soluble vitamins
    5. Calcium Supplementation
  7. Prior to starting an anti-TNF agent
    1. Chest XRay
    2. Purified Protein Derivative (PPD) or Quantiferon

XIV. Management: Protocol based on severity

  1. Mild to Moderate (Weight loss <10%, tolerating P.O.)
    1. Step 1: Start Salicylate (5-ASA preparations)
      1. Mesalamine (Rowasa, Pentasa, Asacol) or
      2. Sulfasalazine (Azulfidine)
    2. Step 2: Anaerobic agent if Salicylate not effective
      1. Metronidazole 10-20 mg/kg/day or
      2. Ciprofloxacin 1 gram/day
    3. Step 3: Treat as moderate to severe if refractory
    4. Step 4: Maintenance therapy for remission
      1. Mesalamine (Rowasa) 3.2 to 4 grams per day
  2. Moderate to Severe (Significant systemic symptoms)
    1. Step 1: Systemic Corticosteroids
      1. Prednisone 40 mg PO qd for 8-12 weeks
        1. Consider Budesonide instead of Prednisone
      2. Budesonide (Entocort EC)
        1. Minimal absorption and may be preferred over Prednisone as first line agent
        2. Dose: 9 mg PO qAM for up to 8 weeks
      3. Methylprednisolone IV for severe fulminant disease
      4. Taper once control is achieved
        1. Initial: Taper by 5-10 mg weekly
        2. Below 20 mg: Taper by 2.5 to 5 mg weekly
    2. Step 2: Consider immunosuppresant for maintenance
      1. Start while tapering Corticosteroid off
      2. Azathioprine 50 mg orally daily (maximum 2-2.5 mg/kg/day) or
      3. 6-Mercaptopurine 60 mg orally daily (maximum 1.5 mg/kg/day)
    3. Step 3: Anti-tumor necrosis factors
      1. Indicated if refractory to Steps 1 and 2
      2. Agents
        1. Adalimumab (Humira) 160 mg SQ once initially, then 80 mg SQ once at week 2, then 40 mg every 2 weeks
        2. Certrolizumab pegol (Cimzia) 400 mg SQ once at weeks 0, 2, and 4, then 400 mg every 4 weeks
        3. Infliximab (Remicade) 5 mg/kg IV once at weeks 0, 2, and 6, then 5 mg/kg every 8 weeks
    4. Step 4: Consider other immunomodulator if refractory
      1. Methotrexate 25 mg weekly
      2. Tacrilimus and Cyclosporine have also been used
  3. References
    1. Knutson (2003) Am Fam Physician 68(4):707-14 [PubMed] (or open in [QxMD Read])
    2. Wall (1999) Pharmacotherapy 19:1138-52 [PubMed] (or open in [QxMD Read])
    3. Hanauer (2003) Gastroenterology 125:906-10 [PubMed] (or open in [QxMD Read])

XV. Management: Available preparations

  1. Similar to Ulcerative Colitis Management
  2. Antiinflammatory agents
    1. Corticosteroids
    2. Oral 5 ASA preparations
      1. Not effective for small bowel Crohn's Disease
      2. Sulfasalazine (Azulfidine)
        1. Inexpensive but significant side effects
      3. Olsalazine (Dipentum)
        1. Diarrhea commonly occurs
      4. Mesalamine (Asacol, Pentasa, Canasa, Rowasa)
      5. Balsalazide (Colazal)
    3. Immunosuppressive agents
      1. 6-Mercaptopurine
      2. Azathioprine
      3. Methotrexate
  3. Fish Oil (Enteric Coated)
    1. Dose: 2.7 g qd
    2. Marked reduction in relapse in 1 year (28% vs 69%)
    3. Serum markers of inflammation also reduced
    4. Reference
      1. Belluzzi (1996) N Engl J Med 334:1557-60 [PubMed] (or open in [QxMD Read])
  4. Metronidazole (Flagyl)
    1. Effective for Crohn's Disease and perianal disease
  5. Monoclonal Antibody (anti-tumor necrosis factor agents)
    1. Adalimumab (Humira)
    2. Certrolizumab pegol (Cimzia)
    3. Infliximab (Remicade)
  6. Other agents currently being researched
    1. Thalidomide (not used in women who can conceive)
    2. Mycophenalate (Cellcept)
    3. Tacrolimus
    4. IL-10, 11 and 18
    5. Probiotics

XVI. Management: Intestinal resection (75% of patients)

  1. Efficacy
    1. Not Curative (unlike for Ulcerative Colitis)
    2. Symptoms nearly always recur after surgery
      1. Five years: 30% symptoms recur
      2. Ten years: 50% symptoms recur
      3. Fifteen years: 70% symptoms recur
    3. Surgery associated with improved quality of life
      1. Delaney (2003) J Am Coll Surg 196:714-21 [PubMed] (or open in [QxMD Read])
  2. Indications
    1. Colon obstruction
    2. Intractable pain or other symptoms

XVII. Complications: Gastrointestinal

  1. Colon Cancer
    1. Much lower risk than with Ulcerative Colitis
  2. Rectal disease (50% of Crohn's Disease patients)
    1. Rectal Fissure
    2. Rectocutaneous fistula
    3. Perirectal Abscess

XVIII. Prognosis: Risk for intestinal resection

  1. Poor prognostic indicators (relapse)
    1. Crohn's involving Small Intestine
    2. Perianal fistulas
  2. Favorable prognostic indicators
    1. Ileocecal disease
    2. Colorectal disease
    3. Relapse-free period of 10 years
  3. References
    1. Bernell (2000) Ann Surg 231:38-45 [PubMed] (or open in [QxMD Read])

XIX. Monitoring

  1. Colon Cancer screening
    1. Periodic Colonoscopy after 15 years of disease (annual in some cases)
  2. Serum Alkaline Phosphatase annually for both Ulcerative Colitis or Crohn's Disease
    1. Evaluate for Primary Sclerosing Cholangitis

Images: Related links to external sites (from Google)

Ontology: Crohn Disease (C0010346)

Definition (NCI) A gastrointestinal disorder characterized by chronic inflammation involving all layers of the intestinal wall, noncaseating granulomas affecting the intestinal wall and regional lymph nodes, and transmural fibrosis. Crohn's disease most commonly involves the terminal ileum; the colon is the second most common site of involvement.
Definition (MEDLINEPLUS)

Crohn's disease causes inflammation of the digestive system. It is one of a group of diseases called inflammatory bowel disease. The disease can affect any area from the mouth to the anus. It often affects the lower part of the small intestine called the ileum.

Crohn's disease seems to run in some families. It can occur in people of all age groups but is most often diagnosed in young adults. Common symptoms are pain in the abdomen and diarrhea. Bleeding from the rectum, weight loss, joint pain, skin problems and fever may also occur. Children with the disease may have growth problems. Other problems can include intestinal blockage and malnutrition.

Treatment may include medicines, nutrition supplements, surgery or a combination of these options. Some people have long periods of remission, when they are free of symptoms.

NIH: National Institute of Diabetes and Digestive and Kidney Diseases

Definition (NCI) A condition in which the gastrointestinal tract is inflamed over a long period of time. Crohn disease usually affects the small intestine and colon. Symptoms include fever, diarrhea, stomach cramps, vomiting, and weight loss. Crohn disease increases the risk of colorectal cancer and small intestine cancer. It is a type of inflammatory bowel disease (IBD).
Definition (MSH) A chronic transmural inflammation that may involve any part of the DIGESTIVE TRACT from MOUTH to ANUS, mostly found in the ILEUM, the CECUM, and the COLON. In Crohn disease, the inflammation, extending through the intestinal wall from the MUCOSA to the serosa, is characteristically asymmetric and segmental. Epithelioid GRANULOMAS may be seen in some patients.
Definition (CSP) gastrointestinal disorder characterized by chronic inflammatory infiltrates, fibrosis affecting all layers of the serosa, and development of noncaseating granulomas; most common site of involvement is the terminal ileum with the colon as the second most common.
Concepts Disease or Syndrome (T047)
MSH D003424
ICD10 K50 , K50.9, K50.90
SnomedCT 34000006, 196984001, 196975001, 155760003, 266517004
English Regional enterocolitis, Cicatrizing enterocolitis, Crohn's Disease, Crohns Disease, Enteritis, Regional, Regional enteritis (Crohn's disease), CROHN'S DISEASE, INFLAMMATORY BOWEL DISEASE, REGIONAL ENTERITIS, Crohn's disease, NOS, Granulomatous enteritis, NOS, Regional enteritis, NOS, DISEASE CROHNS, Crohn's disease, unspecified, regional enterocolitis, INFLAMMATORY BOWEL DISEASE 1, IBD1, CROHN DIS, CROHNS DIS, eleocolitis, enteritis (regional), Crohn's disease (diagnosis), granulomatous enteritis, crohn's disease, Crohn's ileitis, Crohn's, Disease Crohns, Crohn's enteritis, REGIONAL ENTERITIS, CROHN DISEASE, Crohn Disease, Crohn disease, Crohn's disease [regional enteritis], Crohn's disease NOS, Crohn Disease [Disease/Finding], crohn diseases, disease crohn, crohn's diseases, regional enteritis, Disease;Crohns, crohns diseases, disease crohn's, crohn s, crohns disease, crohns's disease, enteritis regional, crohns's, crohn s disease, Regional Enteritis, Regional enteritis, Granulomatous enteritis, Crohn's disease, Crohn's regional enteritis, CD - Crohn's disease, RE - Regional enteritis, Crohn's disease (disorder), Crohn, Regional enteritis - Crohn's disease, Regional enteritis - Crohn, Enteritis, Granulomatous, Crohns disease
Portuguese DOENCA DE CROHN, Enterite de Crohn, Enterite Granulomatosa, Doença de Crohn, Enterite Regional
German MORBUS CROHN, Crohn-Enteritis, Krankheit, Crohn, Enteritis, granulomatöse, Crohn-Krankheit [Enteritis regionalis] [Morbus Crohn], Crohn-Krankheit, nicht naeher bezeichnet, Enteritis regionalis, Morbus Crohn
Dutch Crohn enteritis, Crohn, Ziekte van Crohn, niet gespecificeerd, ziekte van Crohn, Ziekte van Crohn [enteritis regionalis], Enteritis regionalis, Enteritis, granulomateuze, Ziekte van Crohn
French Crohn, Entérite régionale, MALADIE DE CROHN, Maladie de Crohn, Entérite de Crohn, Entérite granulomateuse
Italian Enterite di Crohn, Di Crohn, Enterite granulomatosa, Enterite regionale, Malattia di Crohn, Morbo di Crohn
Spanish Enteritis de Crohn, Crohn, Crohn's regional enteritis, Crohn's disease, Regional enteritis - Crohn, Enteritis Granulomatosa, enfermedad de Crohn (trastorno), enfermedad de Crohn, enteritis granulomatosa, enteritis regional, Enfermedad de Crohn, Enteritis Regional
Japanese クローン腸炎, クローンチョウエン, クローンビョウ, 大腸炎-肉芽腫性, 回腸炎-終末, 腸炎-限局性, クローン病, 終末回腸炎, 肉芽腫性腸炎, 瘢痕形成性小腸結腸炎, 回腸末端炎, 結腸クローン病, 限局性小腸結腸炎, 回腸炎-限局性, 限局性回腸炎, 限局性腸炎, Crohn病, 腸炎-肉芽腫性, 回結腸炎, 肉芽腫性大腸炎
Swedish Crohns sjukdom
Czech enteritida granulomatózní, enteritida regionální, Crohnova nemoc, Crohnova enteritida
Finnish Regionaalinen enteriitti
Russian ILEIT TERMINAL'NYI, ENTERIT REGIONAL'NYI, KRONA BOLEZN', ENTERIT GRANULOMATOZNYI, ILEIT REGIONAL'NYI, ILEOKOLIT, KOLIT GRANULOMATOZNYI, ИЛЕИТ РЕГИОНАЛЬНЫЙ, ИЛЕИТ ТЕРМИНАЛЬНЫЙ, ИЛЕОКОЛИТ, КОЛИТ ГРАНУЛОМАТОЗНЫЙ, КРОНА БОЛЕЗНЬ, ЭНТЕРИТ ГРАНУЛОМАТОЗНЫЙ, ЭНТЕРИТ РЕГИОНАЛЬНЫЙ
Korean 상세불명의 크론병, 크론 병[국한성 창자염]
Croatian CROHNOVA BOLEST
Polish Choroba Crohna-Leśniowskiego, Choroba Crohna, Odcinkowe zapalenie jelita cienkiego
Hungarian Crohn-betegség, Crohn enteritis, Crohn, Crohn betegség

Ontology: Terminal Ileitis (C0678201)

Concepts Disease or Syndrome (T047)
ICD10 K50.0
SnomedCT 235709008
English Terminal Ileitis, ileitis (terminal), terminal ileitis, terminal ileitis (diagnosis), Distal ileitis, Ileitis terminal, Terminal ileitis, Terminal ileitis (disorder)
Dutch terminale ileïtis, distale ileïtis, ileitis terminalis
French Iléite terminale, Iléite distale
German distale Ileitis, Ileitis terminal, terminale Ileitis
Italian Ileite terminale, Ileite distale
Portuguese Ileíte terminal, Ileíte distal
Spanish Ileítis distal, Ileítis terminal, ileítis terminal (trastorno), ileítis terminal
Japanese 末端回腸炎, マッタンカイチョウエン
Czech Distální ileitida, Terminální ileitida
Hungarian Distalis ileitis, Terminalis ileitis, Terminalis csípőbélgyulladás