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Gastroenterology›Condition·Updated Jun 27, 2026·v1

Crohn Disease

Crohn disease is a chronic, progressive, transmural inflammatory bowel disease of any gastrointestinal segment, characterized by skip lesions, granulomatous inflammation, and a relapsing-remitting course. Diagnosis relies on ileocolonoscopy with biopsies and MRE. Management: corticosteroids for acute flares; anti-TNF agents (infliximab, adalimumab) or vedolizumab for maintenance. Prognosis: without treatment, 50% develop stricture or fistula within 10 years; early biologic therapy with adequate trough concentrations and smoking cessation flatten the trajectory.

High Evidence93 references·9,330 words·38 min read·v1
Crohn diseaseinflammatory bowel diseasegastroenterologyanti-TNFvedolizumabMontreal classificationfecal calprotectinexclusive enteral nutritionstricturefistula

Quick Reference

RxDrug of choiceInfliximab 5 mg/kg IV at weeks 0, 2, 6 (induction), then 5 mg/kg IV every 8 weeks (maintenance)
AltAlternativesAdalimumab 160/80 mg SC (induction) then 40 mg SC every other week; Vedolizumab 300 mg IV at weeks 0, 2, 6 (induction) then every 8 weeks
⊘AvoidNon-dihydropyridine CCBs (diltiazem, verapamil), can exacerbate heart failure; NSAIDs, may trigger disease flare; Methotrexate and thalidomide in pregnancy; Live vaccines during immunosuppression
DxTest of choiceIleocolonoscopy with multiple biopsies from terminal ileum and each colonic segment
ScKey scoreMontreal classification (age A1-A3, location L1-L4, behavior B1-B3 with perianal modifier p); Harvey-Bradshaw Index for clinical activity
→When to referSevere or complicated disease (abscess, obstruction, perforation, toxic megacolon), failure of medical therapy, need for surgical resection, pregnancy planning, or refractory perianal fistulas
Early and sustained biologic therapy with adequate trough concentrations and smoking cessation are the only interventions proven to alter the natural history of Crohn disease from relentless progression to stable remission.
Crohn disease is a chronic, progressive, transmural inflammatory bowel disease affecting any segment of the gastrointestinal tract, characterized by skip lesions, granulomatous inflammation, and a relapsing-remitting course. Untreated, it inexorably progresses from inflammation to stricture or fistula in most patients, necessitating early and sustained therapy to alter its natural history. Diagnosis relies on ileocolonoscopy with biopsies, magnetic resonance enterography, and fecal calprotectin, while management centers on corticosteroids for acute flares and anti-TNF agents or vedolizumab for long-term maintenance.

Overview and Recommendations

Background

  • •Crohn disease (CD) is a chronic, progressive, transmural inflammatory bowel disease that can affect any segment of the gastrointestinal tract from mouth to anus, characterized by skip lesions, granulomatous inflammation, and a relapsing-remitting course. It carries a substantial morbidity burden and increases the risk of colorectal cancer in patients with colonic involvement, necessitating regular endoscopic surveillance.
  • •Incidence varies from 1-2 per 100,000 in Asia to 20-30 per 100,000 in North America and Europe, with prevalence reaching 0.5% in Canada by 2030. Peak onset occurs in the second to fourth decades, with a second smaller peak after age 60; sex distribution is nearly equal.
  • •The central pathophysiologic axis involves a dysregulated mucosal immune response to commensal gut microbiota in a genetically susceptible host. Loss-of-function mutations in NOD2 impair bacterial sensing, ATG16L1 variants disrupt autophagy, and ZIP8 variants cause aberrant N-glycosylation, all converging on a breakdown of intestinal homeostasis that drives chronic transmural inflammation.
  • •Experimental, clinical, and epidemiologic evidence supports a causal role for specific gut microbes (e.g., Faecalibacterium prausnitzii depletion, adherent-invasive Escherichia coli expansion) and inflammatory proteins (IL-6, TNF-α) in driving disease activity, as confirmed by Mendelian randomization analyses.
  • •The Montreal classification stratifies patients by age at diagnosis (A1-A3), disease location (L1-L4), and disease behavior (B1 inflammatory, B2 stricturing, B3 penetrating), with a perianal modifier (p). This framework directly informs prognosis and therapeutic decisions; perianal disease and very-early-onset IBD (VEOIBD, age <6 years) represent distinct phenotypes requiring dedicated management approaches.
  • •Risk factors include family history (10- to 20-fold increased risk in first-degree relatives), central obesity (HR 1.45 per 1-SD increase in waist-to-hip ratio), and vitamin D deficiency (<50 nmol/L; HR 1.61). Maternal diet quality and processed meat intake during pregnancy also modulate offspring risk, but interventional data for primary prevention are lacking.

Evaluation

  • •Suspect Crohn disease in any patient with chronic (>4 weeks) abdominal pain, diarrhea, and unintentional weight loss, especially when accompanied by perianal disease, a tender right-lower-quadrant mass, or oral aphthous ulcers. The pain is typically crampy and postprandial, and diarrhea is often non-bloody unless there is colonic involvement.
  • •Ask about nocturnal symptoms, extraintestinal manifestations (erythema nodosum, anterior uveitis, arthralgias, clubbing), and family history of IBD. Also screen for red-flag symptoms: inability to tolerate oral intake for >24 hours, high-volume diarrhea (>10 stools/day), fever >38.5°C, involuntary guarding, or unexplained tachycardia/hypotension, these suggest severe or complicated disease requiring urgent evaluation.
  • •Examine for right-lower-quadrant tenderness (sensitivity ~60-70%), abdominal distension with high-pitched bowel sounds (suggesting stricture), perianal fissures/fistulas/abscesses (present in 30-40% of patients), digital clubbing (10-20%), and oral cobblestoning or aphthous ulcers (5-10%). A tender fixed mass in the right lower quadrant suggests an inflammatory phlegmon or abscess.
  • •Order ileocolonoscopy with multiple biopsies from the terminal ileum and each colonic segment, this is the gold-standard diagnostic test (sensitivity ~90%). Key endoscopic features include aphthous ulcers, deep serpiginous ulcers, cobblestoning, and skip lesions. Biopsies should be taken from both ulcerated and normal-appearing mucosa to detect transmural inflammation and non-caseating granulomas (present in 30-50% of biopsies).
  • •Obtain esophagogastroduodenoscopy (EGD) with biopsies in children, young adults, and patients with upper GI symptoms, as upper tract involvement occurs in up to 48.7% of patients and may be asymptomatic yet histologically active.
  • •Perform magnetic resonance enterography (MRE) to evaluate small bowel disease beyond the reach of the colonoscope, assess transmural inflammation, and detect complications such as abscesses, fistulae, and strictures. MRE has a sensitivity of 85-90% and specificity of 90-95% for active small bowel inflammation. CT enterography is reserved for acute settings where speed is critical.
  • •Consider capsule endoscopy when ileocolonoscopy and MRE are nondiagnostic but clinical suspicion remains high. A patency capsule should be administered first to confirm luminal patency, as capsule retention occurs in 1-5% of patients with known strictures.
  • •Check fecal calprotectin (best noninvasive screening tool; level >150 μg/g has 90% sensitivity and 80% specificity for active CD) and C-reactive protein (elevated in 70-80% of active cases, but may be normal in isolated ileal disease). Fecal calprotectin is also used to monitor response to therapy and predict relapse.
  • •Assess disease severity at diagnosis using the Montreal classification. The Harvey-Bradshaw Index (HBI) is preferred in outpatient clinics for rapid triage, while the Crohn's Disease Activity Index (CDAI) remains the gold standard for clinical trials.
  • •Screen for latent tuberculosis (IGRA), hepatitis B (HBsAg, anti-HBc), and HIV before initiating any biologic therapy. Check baseline vitamin D (25-OH) level and consider DXA scanning for bone density after 3 months of cumulative corticosteroid exposure.

Management

  • •For mild-to-moderate active disease, exclusive enteral nutrition (EEN) or the Crohn's disease exclusion diet (CDED) with 50% partial enteral nutrition induces rapid clinical remission within 3-6 weeks; this is first-line in pediatric patients to avoid corticosteroids and preserve growth.
  • •For moderate-to-severe active disease, initiate systemic corticosteroids: prednisone 40-60 mg orally once daily or intravenous methylprednisolone 40-60 mg daily, followed by a taper over 8-12 weeks. Corticosteroids are not recommended for maintenance therapy due to toxicity and lack of efficacy.
  • •In patients with endoscopically active ileal CD colonized with adherent-invasive Escherichia coli, a 12-week course of oral ciprofloxacin 500 mg twice daily plus rifaximin 800 mg twice daily significantly improves endoscopic response (TEOREM trial). Do not use antibiotics empirically without evidence of AIEC colonization.
  • •For steroid-refractory or steroid-dependent disease, initiate infliximab induction: 5 mg/kg intravenously at weeks 0, 2, and 6. Target a week-2 trough concentration ≥3.5 μg/mL, as this predicts higher rates of clinical remission and mucosal healing at week 30. Proactive therapeutic drug monitoring (TDM) during maintenance reduces the risk of disease worsening.
  • •For maintenance therapy, continue infliximab 5 mg/kg intravenously every 8 weeks or adalimumab 40 mg subcutaneously every other week (after 160/80 mg induction). Higher adalimumab trough concentrations are associated with increased rates of clinical remission at week 56 (OR 1.34 per 1 μg/mL increase).
  • •In patients with prior anti-TNF failure or contraindications, use vedolizumab 300 mg intravenously every 8 weeks after standard induction. Baseline drug clearance predicts deep biochemical remission at week 30; therapeutic drug monitoring can guide dose optimization.
  • •Natalizumab 300 mg intravenously every 4 weeks is effective for anti-TNF-refractory Crohn disease but is limited by the risk of progressive multifocal leukoencephalopathy (PML). Reserve for patients who have failed all other biologics and are JC virus antibody-negative.
  • •Do not use 5-aminosalicylates (5-ASA) for maintenance in Crohn disease, a meta-analysis found no increased risk of relapse with discontinuation (RR 1.02). Do not use antibiotics for long-term maintenance; the TEOREM trial showed benefit only for 12-week induction in AIEC-colonized patients.
  • •Do not use fecal microbiota transplantation for induction or maintenance of remission, a Cochrane review found insufficient evidence of benefit. Do not use tesnatilimab (anti-NKG2D), a phase 2 trial demonstrated no dose-response and only modest clinical benefit.
  • •When loss of response occurs during maintenance therapy: confirm active disease, check drug trough levels and anti-drug antibodies. If subtherapeutic levels without antibodies, escalate dose (e.g., infliximab 10 mg/kg or shorten to every 6 weeks; adalimumab 40 mg weekly). If therapeutic levels with active disease, switch to a different mechanism of action. If high-titer antibodies, switch to another agent within the same class or to a different class.
  • •Refer to a gastroenterologist and colorectal surgeon for severe or complicated disease (abscess, obstruction, perforation, toxic megacolon). Emergency colectomy is indicated for perforation, uncontrolled hemorrhage, or failure of medical therapy in fulminant colitis.
  • •For hospitalized patients, initiate VTE prophylaxis with enoxaparin 40 mg subcutaneously once daily (CrCl ≥30 mL/min) unless contraindicated by active bleeding. Consider extending prophylaxis for 4 weeks post-discharge in high-risk patients.
  • •Target nutritional intake of 25-30 kcal/kg/day and 1.2-1.5 g protein/kg/day. For patients with prolonged ileus or malnutrition, enteral nutrition via nasogastric or nasojejunal tube is superior to parenteral nutrition, reducing infectious complications by 40%.
  • •For fibrostenotic strictures ≤5 cm without deep ulceration, consider endoscopic balloon dilation (EBD), technical success >85%, but long-term surgery-free survival is ~50% at 3 years. Endoscopic stricturotomy may offer higher single-session success for multi-segmental disease.
  • •For perianal fistulas, manage with drainage of abscesses, seton placement, and anti-TNF therapy (infliximab 5 mg/kg at 0, 2, and 6 weeks). Complex fistulas are associated with a 5-year colectomy rate of 25-30%.
  • •In pediatric patients, EEN or CDED is first-line for induction; infliximab is dosed at 5 mg/kg IV at weeks 0, 2, and 6, then every 8 weeks, with dose escalation to 10 mg/kg if trough levels are subtherapeutic. Vedolizumab pharmacokinetic studies support weight-based dosing to match adult exposure.
  • •In pregnancy, continue biologic therapy (anti-TNF agents are low risk; consider discontinuation around week 30-32 for infliximab). Methotrexate and thalidomide are contraindicated. Most biologics are compatible with breastfeeding.
  • •In elderly patients (age ≥60), prioritize vedolizumab over anti-TNF agents to minimize systemic infection risk. Screen for and correct vitamin D deficiency to maintain levels ≥75 nmol/L. Minimize corticosteroid exposure.
  • •Before starting biologic therapy, ensure latent TB screening, hepatitis B serologies, and age-appropriate vaccinations (including recombinant zoster vaccine) are complete. Patients on combination therapy with thiopurines require annual skin cancer screening.

Board Review — High Yield

  • •Montreal classification, Standard system for subtyping Crohn disease by age (A1-A3), location (L1-L4), and behavior (B1 inflammatory, B2 stricturing, B3 penetrating); perianal modifier (p) added to any B category.
  • •NOD2 mutation, Loss-of-function mutations (R702W, G908R, 1007fs) impair bacterial sensing, reduce defensin production, and predispose to ileal and stricturing disease.
  • •Non-caseating granuloma, Pathognomonic histologic finding in Crohn disease, present in 30-50% of biopsies; composed of epithelioid histiocytes and multinucleated giant cells.
  • •Fecal calprotectin, Best noninvasive marker for distinguishing inflammatory from functional bowel disease; level >150 μg/g has 90% sensitivity and 80% specificity for active Crohn disease.
  • •Infliximab trough at week 2, Target ≥3.5 μg/mL; associated with higher rates of clinical remission and mucosal healing at week 30. Proactive TDM reduces risk of disease worsening.
  • •Vedolizumab, Gut-selective α4β7 integrin antagonist; preferred in elderly patients due to lower systemic infection risk; baseline drug clearance predicts deep biochemical remission at week 30.
  • •TEOREM trial, Ciprofloxacin + rifaximin for 12 weeks improved endoscopic response in AIEC-colonized ileal Crohn disease (45% vs 22%; NNT = 4.3).
  • •Exclusive enteral nutrition (EEN), First-line therapy for pediatric Crohn disease; induces remission in 80-85% of children with improved growth and mucosal healing compared to corticosteroids.
  • •Prognosis, 50% of patients develop stricturing or penetrating complication within 10 years; 70% require at least one intestinal resection over lifetime. Active smoking doubles risk of postoperative relapse.
  • •Pregnancy and biologics, Anti-TNF agents should be continued through pregnancy; risk of adverse outcomes is driven by disease activity, not drug exposure. Methotrexate and thalidomide are contraindicated.

Deep Dive — Evidence Details

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