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 . 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. include malabsorption, iron and vitamin deficiency, strictures, bowel obstruction, intraabdominal abscesses, and increased risk of bowel cancer.
- Prevalence: 1 case per 500 population
- Incidence: ∼ 6 cases per 100,000 population per year 
- Sex: ♂ = ♀
- Typical age of onset: bimodal distribution with one peak at 15–35 years and another one at 55–70 years 
Populations with higher prevalence 
- Individuals of Northern European descent
- Individuals of Ashkenazi Jewish descent
Epidemiological data refers to the US, unless otherwise specified.
- Cause: Immune dysregulation and dysbiosis, which promotes chronic inflammation, the ultimate cause of which is not fully understood.
- Risk factors 
Inflammation is most likely caused by immune dysregulation.
- Dysregulation of IL-23-Th17 signaling → unrestrained Th17 cell function → inflammation → local tissue damage (edema, erosions/ulcers, necrosis) → obstruction, fibrotic scarring, stricture, and strangulation of the bowel 
- Mutations in the nucleotide oligomerization binding domain 2 (NOD2) protein are likely involved in the development of CD.
CD typically has a chronic intermittent course with episodic acute flares and periods of remission. Clinical features differ according to the . Patients with may be asymptomatic while patients with have severe symptoms.
- Low-grade fever
- Weight loss
Gastrointestinal symptoms 
- Chronic diarrhea
- Lower gastrointestinal bleeding (uncommon)
- Abdominal pain, typically in the RLQ
- Palpable abdominal mass in the RLQ
- Features of
Extraintestinal symptoms 
Extraintestinal manifestations of CD are present in 20–30% of patients with CD. 
- Liver/bile ducts: cholelithiasis
- Urogenital system: urolithiasis (mostly calcium oxalate stones)
- Oral aphthae
Pyoderma gangrenosum: a neutrophilic dermatosis
- Associated with various conditions (e.g., , rheumatoid arthritis, and trauma)
- Manifests with very painful, rapidly-progressive, red spots that can change into purulent pustules or deep ulcerated lesions with central necrosis
- Commonly located at extensor side of the lower limbs
- Treated with immunosuppressants (e.g., corticosteroids, cyclosporine A)
The CDAI is a validated system commonly used in clinical trials to categorize disease activity but with limited utility in clinical practice. 
|Crohn Disease Activity Index |
Number of liquid stools per day
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Presence of complications
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Use of antidiarrheal medications
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Abdominal mass present
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|Revised Montreal classification of Crohn disease |
|Age at diagnosis (A)||A1||≤ 16 years|
|A3||> 40 years|
|Location (L)||L1||Terminal ileum|
|L4||Upper GI tract (modifier)|
|Behavior (B)||B1||Nonstricturing, nonpenetrating|
- Conduct a thorough history and physical examination (including digital rectal examination).
- Document any .
- Evaluate for the presence of perianal fistulas.
- Perform endoscopy and obtain intestinal biopsies.
- Obtain cross-sectional imaging to:
- Obtain laboratory studies (blood and stool) to:
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. 
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 
- Skip lesions: segmental and/or discontinuous pattern of involvement (interspersed with normal tissue)
- Linear and/or serpiginous ulcerations
- Small aphthous ulcerations
- Cobblestone sign: inflamed edematous sections interspersed with deep ulcerations that resemble cobblestones
- Erythema, fissures, strictures, and fistulas
Other endoscopic techniques 
- Upper endoscopy: if upper GI involvement is suspected 
- Video capsule endoscopy : Consider in patients with suspected small bowel CD (as an alternative to cross-sectional imaging).
- Deep enteroscopy (e.g., ): Consider for small bowel biopsy or stricture dilation. 
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 . 
- Suspected CD (part of initial evaluation)
- Localization of inflammation and assessment of severity 
- 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 ; 
- Edematous thickening of the intestinal wall
- Mucosal enhancement, mesenteric fat stranding
- Creeping fat: excessive mesenteric fat around the affected segments of bowel 
- Can also identify:
- CT abdomen and pelvis (with IV contrast): preferred in acutely ill patients who cannot tolerate PO contrast
- : : can identify luminal complications such as internal fistulas and narrowed segment(s) of bowel (string sign) 
Additional modalities 
- Consider for initial evaluation of suspected CD and for disease monitoring. 
- 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. 
- MRI abdomen and pelvis (with IV contrast) 
- Ultrasound abdomen
Laboratory studies 
- To rule out differential diagnoses of CD
To monitor disease activity
- Fecal calprotectin and/or fecal lactoferrin: proteins associated with neutrophil activation ; 
- Inflammatory markers: CRP, ESR, platelets
- To identify complications
Management of CD is complex and includes medications with potentially significant adverse effects.
General principles 
- Tailor therapy to the , phase of the disease (acute flare or remission), and .
- 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
- Hemodynamic support as needed (e.g., for ): ,
- Consult gastroenterology early to determine choice of induction therapy.
- Screen for and administer prophylaxis against common infectious diseases.
- Patients with severe or fulminant CD typically require hospitalization.
- Initiate thromboprophylaxis as needed (e.g., presence of hospitalization). 
- Identify and treat malnutrition and micronutrient deficiency.
Infectious disease screening and prophylaxis 
- Update immunization status at diagnosis: See “ ” for details.
- Screen for viral infections (hepatitis B, hepatitis C, HIV, Epstein-Barr virus) and tuberculosis. 
- Consult infectious disease before initiating therapy if screening tests are positive. 
- 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) 
- Maintenance phase
Symptoms do not accurately correlate with disease activity. Use objective markers of disease severity (e.g., biomarkers, imaging, endoscopy) to assess the , guide treatment, and verify remission. 
Overview of commonly used medications 
- Primarily used to induce remission
Agents used (depending on ):
- Controlled ileal release budesonide
- Oral prednisolone
- IV methylprednisone
Anti-TNF-α antibodies: e.g., adalimumab, infliximab, certolizumab
- Increasingly used as a primary agent to induce remission.
- Also used to maintain remission and manage CD refractory to immunomodulators
- Anti-leukocyte trafficking antibody (vedolizumab) and anti-p40 antibody; (ustekinumab) : used mainly to induce and maintain remission in
- Anti-TNF-α antibodies: e.g., adalimumab, infliximab, certolizumab
Immunomodulators: e.g., thiopurine analogs (azathioprine, 6-mercaptopurine), methotrexate
- Primarily used to maintain remission
- Can be used as a steroid-sparing regimen to induce remission
- 5-aminosalicylic acid derivative: sulfasalazine (mesalamine is not routinely recommended)
- Antibiotics: no longer recommended for the primary treatment of CD
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. 
Treatment regimens based on disease severity
|Medical management of Crohn disease |
|Severity of CD||Typical clinical features ||Common regimens|
| Induction of remission |
(management of acute flare) 
|Maintenance of remission|
|Mild to moderate CD|| |
|Moderate to severe CD || |
|Severe to fulminant CD|
Almost 20% of patients with CD are steroid refractory. 
- Pain management 
- Antidiarrheal therapy: loperamide OR cholestyramine 
- Lifestyle modifications 
- Dietary optimization
Half of patients with CD require major abdominal surgery within 10 years of diagnosis. 
- Procedures 
- Assess .
- Obtain IV access and initiate IV fluid therapy as needed (e.g., severe dehydration, acute complications)
- Maintain NPO status until workup is complete.
- Obtain laboratory studies: CBC, CMP, CRP, ESR, blood culture
- Obtain stool studies: stool culture, Clostridium difficile toxin, ova and parasite study, fecal calprotectin
- Order appropriate imaging.
- Consult gastroenterology to discuss management.
- Consult surgery if intraabdominal complications are suspected (e.g., bowel obstruction, bowel perforation).
- Start broad-spectrum antibiotics if an abscess or systemic infection is identified (e.g., ).
- Avoid antidiarrheal medication if the patient is acutely ill.
- Initiate DVT prophylaxis as needed.
- Ensure immunizations are up to date at each follow-up (see “ ” for details).
- Recommend pneumococcal vaccine and yearly influenza vaccine (inactivated).
- Consider herpes zoster vaccination.
Monitoring of disease activity 
- Schedule an endoscopic exam 6–9 months after treatment is initiated. 
- Routine monitoring endoscopy is not recommended in the remission phase. 
- Periodic cross-sectional imaging (MRE, CTE) : especially in patients with small bowel disease. 
- Serial CRP and fecal calprotectin: to assess inflammatory status and treatment efficacy (treating-to-target) 
Screening for complications and malignancies 
- Intestinal cancer
- Skin cancer: periodic thorough skin examinations 
- Cervical cancer: annual pap smear 
- Anemia and malnutrition: e.g., CBC, iron-binding studies, folate, vitamin B12, LDH, vitamin D, albumin 
- Osteoporosis: DXA in patients with > 3 months cumulative lifetime exposure to corticosteroids 
|Crohn disease and ulcerative colitis|
|Pathophysiology|| || |
|Frequency/type of defecation|| |
|Nutritional status|| || |
|Other complications|| |
|Cancer risk|| |
|Endoscopy and imaging|
|Pattern of inflammation|| || |
|Typical diagnostic findings|
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
- Infectious gastroenteritis/colitis
- Noninfectious colitis (ischemic, after radiation therapy, after ingestion of drugs, etc.)
- Malignant intestinal transformations
The differential diagnoses listed here are not exhaustive.
Fistulizing CD 
- Clinical features: depend on location of the fistula (see “Fistulas”)
- Management: Interdisciplinary management including gastroenterology and surgery is required. 
Other intestinal complications
- Colorectal cancer (especially in the case of pancolitis)
- Short bowel syndrome and associated issues after surgery
- Stenosis/strictures → bowel obstruction/(sub)ileus
- → peritonitis
- Impaired bile acid reabsorption
- Abscess formation/phlegmons
- Signs of malabsorption syndrome
We list the most important complications. The selection is not exhaustive.
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. 
- Young age at diagnosis (< 30 years of age)
- Early need for steroid use
- Small bowel involvement
- Perianal or rectal disease
- Previous stenosis, fistula, and/or abscess
- Visceral adiposity