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Crohn disease

Last updated: January 3, 2024

Summarytoggle arrow icon

Crohn disease (CD) is an inflammatory bowel disease (IBD) of unclear etiology. Unlike ulcerative colitis, CD is not limited to the colon but can manifest anywhere in the gastrointestinal tract. Clinical features commonly include diarrhea, weight loss, and abdominal pain but differ according to disease severity. Extraintestinal manifestations may occur in the eyes, joints, and skin. Diagnosis is based primarily on characteristic endoscopic features (ulcerations, skip lesions, cobblestone appearance) and evidence of intestinal inflammation on imaging. Medical management aims to induce and maintain remission; it is tailored to the patient and influenced by the location and severity of CD. Acute flares are typically managed with corticosteroids but steroid-sparing regimes (e.g., thiopurine analogs, biologics) may also be used. Maintenance therapy (e.g., immunomodulators, biologics) focuses on limiting the frequency and duration of inflammatory episodes. Though surgery is ultimately required in up to half of patients with CD, surgical resection is generally not curative. Complications of CD include malabsorption, iron and vitamin deficiency, strictures, bowel obstruction, intraabdominal abscesses, and increased risk of bowel cancer.

Epidemiologytoggle arrow icon

  • Prevalence: 1 case per 500 population
  • Incidence: ∼ 6 cases per 100,000 population per year [1]
  • Sex: =
  • Typical age of onset: bimodal distribution with one peak at 15–35 years and another one at 55–70 years [2][3]
  • Populations with higher prevalence [4]
    • Individuals of Northern European descent
    • Individuals of Ashkenazi Jewish descent

Epidemiological data refers to the US, unless otherwise specified.

Etiologytoggle arrow icon

Smoking tobacco is the primary modifiable risk factor for CD. Therefore, smoking cessation is especially important in patients with CD.

Pathophysiologytoggle arrow icon

Inflammation

Inflammation is most likely caused by immune dysregulation.

Abscess and fistula formation

  • Intestinal aphthous ulcers transmural fissures and inflammation of the intestinal walls → adherence of other organs or the skin penetration of tissue → microperforation and abscess formation → macroperforation into these structures → fistula formation

Clinical featurestoggle arrow icon

CD typically has a chronic intermittent course with episodic acute flares and periods of remission. Clinical features differ according to the severity of CD. Patients with mild CD may be asymptomatic while patients with fulminant CD have severe symptoms.

Constitutional symptoms [6]

  • Low-grade fever
  • Weight loss
  • Fatigue

Gastrointestinal symptoms [6]

CD most commonly affects the terminal ileum and colon, but involvement of any part of the GI tract (from mouth to anus) is possible. In contrast to ulcerative colitis, rectal involvement is uncommon.

Perianal fistulas and abscesses are often the first signs of CD.

Extraintestinal symptoms [8]

Extraintestinal manifestations of CD are present in 20–30% of patients with CD. [9]

Classificationtoggle arrow icon

Crohn Disease Activity Index (CDAI)

The CDAI is a validated system commonly used in clinical trials to categorize disease activity but with limited utility in clinical practice. [11][12]

Crohn Disease Activity Index [13]
Score Multiplier

Number of liquid stools per day

  • Number of stools
  • × 2

Abdominal pain

  • 0 = none
  • 1 = mild
  • 2 = moderate
  • 3 = severe
  • × 5

General condition

  • 0 = generally well
  • 1 = slightly below average
  • 2 = poor
  • 3 = very poor
  • 4 = terrible
  • × 7

Presence of complications

  • 0 = absence
  • 1 = presence
  • × 20

Fever

  • 0 = no
  • 1 = yes
  • × 20

Use of antidiarrheal medications

  • 0 = no
  • 1 = yes
  • × 30

Abdominal mass present

  • 0 = no
  • 2 = indeterminate
  • 5 = definite
  • × 10

Hematocrit

  • Expected Hct – observed Hct
  • × 6

Body weight

  • × 1

Interpretation [11]

  • < 150: remission
  • 150–220: mild to moderate disease
  • 221–450: moderate disease
  • > 450: severe disease

Montreal classification

Classifies CD according to the course and phenotype. Primarily used to standardize and streamline communication between health care providers and facilitate epidemiological studies.

Revised Montreal classification of Crohn disease [14]
Age at diagnosis (A) A1 ≤ 16 years
A2 17–40 years
A3 > 40 years
Location (L) L1 Terminal ileum
L2 Colon
L3 Ileocolonic region
L4 Upper GI tract (modifier)
Behavior (B) B1 Nonstricturing, nonpenetrating
B2 Stricturing
B3 Penetrating
p Perianal (modifier)

Diagnosticstoggle arrow icon

Endoscopy, cross-sectional imaging, and laboratory studies are required for the initial evaluation of suspected CD, evaluation of an acute flare, and monitoring response to therapy.

Approach [11][15]

Small bowel evaluation is an essential part of the initial diagnostic workup of CD. Almost one-third of patients with CD have only small bowel disease and this may not be visible on ileocolonoscopy. [11][16]

Endoscopy

Ileocolonoscopy [11]

  • Indication: all patients with suspected CD
    • Assesses the distribution and severity of the disease
    • Aids differentiation of CD from other diseases (e.g., ulcerative colitis)
    • Monitors disease activity (e.g., active disease, remission)
    • Can be used therapeutically (e.g., stricture dilatation)
  • Supportive findings [11][15][17]

Other endoscopic techniques [11]

Discontinuous areas of inflammation, cobblestone appearance of the affected mucosa, and mucosal ulcerations are hallmark endoscopic findings of CD. [19]

Characteristic endoscopic features and evidence of chronic intestinal inflammation on histology are the most important factors to establish a diagnosis of CD. [20][21]

Imaging [6][11][16][20]

Cross-sectional imaging is preferred as it permits evaluation of the entire gastrointestinal tract (including the small bowel), can identify complications (e.g., bowel obstruction, abscess, fistula), and can assess for differential diagnoses of CD. [16]

Indications

  • Suspected CD (part of initial evaluation)
  • Localization of inflammation and assessment of severity [11][16]
  • Evaluation of suspected acute flare or complications (e.g., abscess)
  • Serial imaging to assess response to therapy

Modalities and supportive findings

  • Cross-sectional enterography (MRE, CTE): preferred imaging modality for CD ; [11][16][20]
  • CT abdomen and pelvis (with IV contrast): preferred in acutely ill patients who cannot tolerate PO contrast
  • Small bowel follow-through: : can identify luminal complications such as internal fistulas and narrowed segment(s) of bowel (string sign) [16]
  • Additional modalities [11][16]
    • Ultrasound abdomen
      • Consider for initial evaluation of suspected CD and for disease monitoring. [16]
      • Supportive finding (of active disease): bowel wall thickening (> 4 mm)
    • Plain x-ray abdomen: Consider for expedited assessment of complications.
    • CT or MRI enteroclysis: Consider for evaluation of an acute flare or response to therapy. [16]
    • MRI abdomen and pelvis (with IV contrast) [16]

Laboratory studies [6][11]

Anemia in CD may result from chronic disease, iron deficiency, and/or vitamin B12 deficiency.

Pathologytoggle arrow icon

Treatmenttoggle arrow icon

Management of CD is complex and includes medications with potentially significant adverse effects.

General principles [11][20]

  • Tailor therapy to the severity of CD, phase of the disease (acute flare or remission), and risk of progression of CD.
  • Surgery may be required to manage complications and is an option for isolated short-segment disease.
  • Lifestyle modifications (e.g., smoking cessation) may decrease the incidence of complications.
  • Regular monitoring of disease activity and screening for complications are essential aspects of long-term management.

Management of acute flare of CD

Infectious disease screening and prophylaxis [20]

Perform prior to initiating therapy if feasible as most medications for CD can cause immunosuppression.

Pharmacotherapy [11][28]

  • Induction phase
    • Used to manage acute flares.
    • Agents that have a rapid onset of action (e.g., corticosteroids, biologics) are used.
    • Should be continued until there is objective evidence of remission (typically < 3 months) [11]
      • Endoscopic evidence of remission (e.g., healing ulcers) is currently the best indicator of remission of colonic CD. [11][29]
      • Noninvasive markers of intestinal inflammation (fecal calprotectin, cross-sectional imaging) are suitable alternatives to evaluate for remission.
  • Maintenance phase
    • Used to maintain remission, typically in patients with moderate or severe CD and those at high risk of progression of CD. [30]
    • Biologics and immunomodulators are the principal agents of maintenance therapy.
    • Typically continued for a prolonged period of time. [31]

Symptoms do not accurately correlate with disease activity. Use objective markers of disease severity (e.g., biomarkers, imaging, endoscopy) to assess the severity of CD, guide treatment, and verify remission. [11][20]

Overview of commonly used medications [11]

Corticosteroids can be used to induce remission but should be discontinued once the acute flare has been managed. Immunomodulators and biologics are the mainstays of maintenance therapy but can also be used to induce remission. [11][20]

Treatment regimens based on disease severity

Medical management of Crohn disease [11][12][28][32]
Severity of CD Typical clinical features [11] Common regimens
Induction of remission
(management of acute flare) [11]
Maintenance of remission
Mild to moderate CD
  • Ambulatory patient
  • Normal dietary intake
  • Weight loss (< 10%)
  • No major complications
Moderate to severe CD [28]
Severe to fulminant CD

Almost 20% of patients with CD are steroid refractory. [11]

Do not use corticosteroids for maintenance therapy in CD. They do not promote mucosal healing and potentially increase the risk of complications. [11]

Supportive therapy

Poor pain control and/or increased opioid use may indicate inadequate disease management. [34]

Antidiarrheals should not be used in patients with bowel obstruction, abdominal tenderness, or signs of systemic infection (e.g., fever). [37]

Surgery [11]

Half of patients with CD require major abdominal surgery within 10 years of diagnosis. [11][21]

  • Indications
    • Severe complications (e.g., bowel obstruction; , intraabdominal abscess, perianal abscess) [11]
    • Unsuccessful medical therapy
    • Symptom control in disease localized to a short segment of the bowel [11][38]
  • Procedures [38]
    • Surgical drainage of abscess [11][38]
    • Laparoscopic or open resection of the diseased bowel segment (small bowel resection, segmental colectomy) [38]
    • Strictureplasty (bowel-sparing technique) [11][38]

Surgery can lead to remission but is not curative, and short bowel syndrome may occur following multiple procedures.

Management checklist for acute flare of Crohn diseasetoggle arrow icon

Long-term managementtoggle arrow icon

Vaccinations [6]

Live vaccines should be avoided in patients receiving immunosuppressive therapy. [6][20]

Monitoring of disease activity [11][20]

  • Endoscopic monitoring
    • Schedule an endoscopic exam 6–9 months after treatment is initiated. [39]
    • Routine monitoring endoscopy is not recommended in the remission phase. [40]
  • Periodic cross-sectional imaging (MRE, CTE) : especially in patients with small bowel disease. [11]
  • Serial CRP and fecal calprotectin: to assess inflammatory status and treatment efficacy (treating-to-target) [11][29]

Screening for complications and malignancies [6][20]

Differential diagnosestoggle arrow icon

Crohn disease vs. ulcerative colitis

Crohn disease and ulcerative colitis

Crohn disease

Ulcerative colitis

Pathophysiology
  • Mediated by dysfunctional IL-23-Th17 signaling
Frequency/type of defecation
  • Increased
  • Typically nonbloody, watery diarrhea
  • May be bloody in more severe cases
Nutritional status
  • Mostly normal, but weight loss and malnutrition may occur in severe disease [41]
Physical examination
  • Mostly constant pain in RLQ
  • Palpable abdominal mass
  • Low-grade fever
Extraintestinal manifestations
Fistulas
  • Rare
Other complications
  • Abscess
  • Strictures (obstructions)
  • Perianal fissures
Cancer risk
Antibodies
Endoscopy and imaging
Location
  • Typical location: terminal ileum and colon with rectal sparing
  • May affect the entire GI tract
Pattern of inflammation
  • Continuous
Typical diagnostic findings
Histology
  • Neutrophilic inflammation of the crypts
Treatment
Medication
Surgery
  • Noncurative surgery may become necessary to alleviate symptoms


The crone and the fat granny skipped over the wrecked cobblestones: the most important features of Crohn disease are creeping fat, granuloma, skip lesions, rectal sparing, and cobblestone sign.

Other differential diagnoses

The differential diagnoses listed here are not exhaustive.

Complicationstoggle arrow icon

Fistulizing CD [43]

  • Overview
    • Occur in one-third of patients with CD
    • Typically involve the perianal region
    • Internal fistulas may involve the bladder, vagina, and/or another portion of the intestine.
    • Recurrences are common
  • Clinical features: depend on location of the fistula (see “Fistulas”)
  • Management: Interdisciplinary management including gastroenterology and surgery is required. [44]

Other intestinal complications

Systemic complications

We list the most important complications. The selection is not exhaustive.

Special patient groupstoggle arrow icon

Prognosistoggle arrow icon

CD is a chronic disease that is currently not curable. Patients with any of the following features are at high risk of progression to severe disease and may require more aggressive treatment to prevent complications of CD. [11][12][20]

Failure to achieve and maintain remission on therapy is associated with worse clinical outcomes, including stricture and fistula formation and the need for surgery. [29]

Referencestoggle arrow icon

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