Chronic transmural inflammation that can involve any segment of the GI tract; skip lesions and fistulizing disease.
Also known as: Crohn disease, Crohn's disease, CD, regional enteritis
Overview
Chronic, idiopathic, immune-mediated inflammatory bowel disease characterized by transmural inflammation that may involve any segment of the gastrointestinal tract from mouth to anus, with skip lesions and a propensity to form strictures, fistulas, and abscesses.
Epidemiology
Incidence ~5-10 per 100,000/year in North America; prevalence ~250 per 100,000. Bimodal age peaks at 15-30 and 50-70. Female slight predominance. Highest incidence in Ashkenazi Jews, Northern European descent. Smoking doubles risk.
Try two board-style Crohn Disease questions
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Question 1GastrointestinalMedium
A 28-year-old man with Crohn's disease maintained on vedolizumab presents with three days of fever, chills, and worsening right lower quadrant abdominal pain. Temperature is 38.6°C, blood pressure is 118/74 mm Hg, and pulse is 102/min. The abdomen is tender in the right lower quadrant without rebound or guarding. CT of the abdomen and pelvis with contrast demonstrates a 12-cm intra-abdominal abscess with a fistulous tract to the sigmoid colon. Which of the following is the most appropriate next step in management?
AUrgent surgical bowel resection
BCT-guided percutaneous drainage
CEscalation of vedolizumab dosing
DBroad-spectrum IV antibiotics alone
EColonoscopy with mucosal biopsies
Reveal answer & full explanation
Correct answer: B — CT-guided percutaneous drainage
AUrgent surgical bowel resection
BCT-guided percutaneous drainage✓
CEscalation of vedolizumab dosing
DBroad-spectrum IV antibiotics alone
EColonoscopy with mucosal biopsies
Why CT-guided percutaneous drainage is correct
IV broad-spectrum antibiotics plus drainage is suggested for a Crohn's abscess larger than 2 cm (ACG 2025), and ECCO 2024 (Statement 4.4) names antibiotics plus percutaneous, image-guided drainage as first-line. Typical antibiotic options include piperacillin-tazobactam or a carbapenem.
Hold vedolizumab: the US label says not to give it until a serious infection resolves, and ACG 2025 advises holding immunosuppression until the abscess is drained.
Drainage is mostly a bridge, not definitive care: a fistula-associated abscess usually still needs resection, and ECCO 2024 reports the lowest risk of postoperative intra-abdominal septic complications when surgery follows successful drainage by 2-4 weeks. Operating amid uncontrolled sepsis raises complication and stoma rates.
Biologic therapy is resumed only after the infection has completely resolved.
Why the others are wrong
Urgent surgical bowel resection — Reserved for free perforation, peritonitis, collections not amenable to drainage, or failed percutaneous drainage; this hemodynamically stable patient without rebound or guarding should be drained first. The trap is anchoring on the abscess size and fistula: he will probably need a resection, but as a planned operation once sepsis is controlled (ECCO 2024 Statement 4.3), and the question asks for the next step, not the eventual one.
Colonoscopy with mucosal biopsies — Does not treat the abscess and risks perforation through inflamed, penetrating bowel; it buzzword-matches "Crohn's disease → endoscopic assessment" while ignoring the infectious emergency.
Escalation of vedolizumab dosing — Intensifying immunosuppression during an undrained abscess worsens infection risk and contradicts the label's instruction to withhold vedolizumab during serious infection; this is premature closure, treating a septic complication as if it were a refractory medical flare.
Broad-spectrum IV antibiotics alone — Antibiotics belong in the treatment, and his stable vital signs make a medical-only trial tempting, but a 12-cm collection with a fistulous tract will not resolve without source control; ACG 2025 suggests drainage for any Crohn's abscess larger than 2 cm, with antibiotics given alongside drainage rather than instead of it. The trap is stopping at medical therapy because he is not in shock.
Additional high-yield points
Carefully selected patients may be managed medically after successful drainage, with a low threshold for surgery if disease is medically refractory (ECCO 2024 Statement 4.5).
Question 2GastrointestinalMedium
A 30-year-old man with ileocolonic Crohn's disease has been maintained on adalimumab for 18 months but now reports recurrent abdominal pain and diarrhea. Laboratory testing shows an adalimumab trough level of 3 mcg/mL (therapeutic target ≥7.5 mcg/mL) and positive anti-adalimumab antibodies at 150 AU/mL. Which of the following is the most appropriate next step?
AAdd azathioprine to the current regimen
BSwitch to oral tofacitinib therapy
CIncrease the adalimumab dose to weekly
DSwitch to an adalimumab biosimilar
ESwitch to vedolizumab or ustekinumab
Reveal answer & full explanation
Correct answer: E — Switch to vedolizumab or ustekinumab
AAdd azathioprine to the current regimen
BSwitch to oral tofacitinib therapy
CIncrease the adalimumab dose to weekly
DSwitch to an adalimumab biosimilar
ESwitch to vedolizumab or ustekinumab✓
Why Switch to vedolizumab or ustekinumab is correct
This is loss of response from immunogenicity: a subtherapeutic adalimumab trough (3 mcg/mL, below the ~7.5 mcg/mL target) together with high-titer neutralizing anti-adalimumab antibodies (150 AU/mL).
When antidrug antibodies are high and the drug level is low, the antibodies are clearing and neutralizing the drug, so the rational move is to change agents rather than give more of the same drug.
Switching to a different mechanism of action—gut-selective vedolizumab (anti-integrin) or ustekinumab (anti-IL-12/23)—sidesteps the established antibody response, consistent with AGA therapeutic drug monitoring guidance.
Why the others are wrong
Add azathioprine to the current regimen — adding an immunomodulator can blunt antibody formation early, but once high-titer antidrug antibodies are established it rarely recaptures response during active disease; right idea, wrong timing.
Increase the adalimumab dose to weekly — dose escalation overcomes low levels from pharmacokinetic failure (low drug, no antibodies), not antibody-mediated neutralization, so it fails in this setting.
Switch to an adalimumab biosimilar — a biosimilar shares the originator's epitopes, so existing anti-adalimumab antibodies cross-react and neutralize it as well; changing the product without changing the mechanism does not escape immunogenicity.
Switch to oral tofacitinib therapy — tempting because an oral small molecule cannot provoke antidrug antibodies and tofacitinib is approved for ulcerative colitis after anti-TNF failure, but it is not approved for Crohn's disease, in which its trials did not show efficacy; borrowing a UC-only agent would leave this active ileocolonic Crohn's disease inadequately treated.
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Composite of clinical, endoscopic, radiologic, and histologic features. Hallmarks: discontinuous inflammation, skip lesions, transmural disease, terminal ileal involvement, non-caseating granulomas (when present), fistulizing or stricturing behavior.
Labs
CBC (microcytic anemia from iron deficiency or anemia of chronic disease)
CRP, ESR (inflammatory markers; correlate with activity)
BMP, LFTs, albumin (nutritional status, PSC)
Iron studies, B12, folate, vitamin D
Fecal calprotectin (>250 mcg/g supports active inflammation)
Stool studies: C. diff, culture, ova/parasites — exclude infection at diagnosis and flares
Serology: ASCA+/pANCA- pattern supports Crohn over UC (limited sensitivity; not for primary diagnosis)
QuantiFERON, hepatitis B/C, HIV, varicella titers, TB skin test — before biologic therapy
Imaging
Ileocolonoscopy with biopsy of terminal ileum and each colonic segment — establishes diagnosis; aphthous → linear/serpiginous ulcers, cobblestoning, skip lesions, ileal involvement
CT or MR enterography — small bowel disease, fistulas, abscess, stricture; MRE preferred in young patients to limit radiation
Pelvic MRI for perianal fistula assessment
Capsule endoscopy if proximal small bowel disease suspected and no stricture
Upper endoscopy if upper GI symptoms (more common in pediatric Crohn)
Diagnostic algorithm
Feature
Crohn Disease
Ulcerative Colitis
Location
Mouth to anus; terminal ileum most common
Colon only; starts at rectum
Distribution
Skip lesions
Continuous
Depth
Transmural
Mucosa/submucosa only
Rectal involvement
Variable; may be spared
Always involved
Granulomas
Non-caseating in ~30%
Absent
Fistulas/strictures
Common
Rare
Smoking
Worsens
Protective (paradoxically)
Surgery
Not curative
Curative (colectomy)
Serology
ASCA+/pANCA-
pANCA+/ASCA-
Bloody diarrhea
Sometimes
Hallmark
Crohn disease vs ulcerative colitis — clinical and pathologic distinctions.
Treatment
First-line
Smoking cessation — single most impactful intervention
Nutritional optimization; supplement iron, B12, vitamin D
Induction: corticosteroids (prednisone, budesonide ileal-release for ileocecal disease) for acute flares — NOT for maintenance
Biologic anti-TNF — infliximab, adalimumab, certolizumab — induction and maintenance; combine with thiopurine (azathioprine) for synergistic effect (SONIC trial)
Anti-integrin — vedolizumab (gut-selective α4β7) — induction and maintenance
Anti-IL-12/23 — ustekinumab — induction and maintenance
Anti-IL-23 — risankizumab, guselkumab, mirikizumab — induction and maintenance
JAK inhibitor — upadacitinib — induction and maintenance for moderate-severe Crohn after inadequate response or intolerance to an anti-TNF (boxed warning: serious infection, mortality, malignancy, MACE, thrombosis)
Second-line / adjunct
Immunomodulators — azathioprine, 6-mercaptopurine, methotrexate — for steroid-sparing maintenance and combination with biologics
Antibiotics — ciprofloxacin, metronidazole — for perianal/fistulizing disease, abscess
5-ASA agents (mesalamine) — limited efficacy in Crohn; not first-line
Surgery — for stricture, fistula refractory to medical therapy, abscess (usually delayed elective resection after percutaneous drainage; urgent if drainage fails or is not feasible), perforation, dysplasia, or medically refractory disease; NOT CURATIVE — recurrence at anastomosis common
Complication management: intra-abdominal abscess >2 cm → IV antibiotics + CT-guided percutaneous drainage, hold biologics/immunosuppression until the abscess is drained and infection controlled, then usually delayed elective resection (ACG 2025); inflammatory phlegmon or inflammatory obstruction without abscess or perforation → bowel rest, NGT decompression, IV steroids ± IV antibiotics before considering surgery; colonic stricture that cannot be traversed or adequately biopsied → surgical resection because malignancy cannot be excluded
Malabsorption (B12 — terminal ileum, fat-soluble vitamins, bile salts → diarrhea and oxalate kidney stones)
Colorectal cancer (especially with colonic disease >8-10 yr or PSC)
Small bowel adenocarcinoma (in chronically inflamed segments)
Extraintestinal manifestations and treatment side effects (infection, lymphoma with thiopurines/anti-TNF, demyelinating disease)
PANCE pearls
Skip lesions, transmural inflammation, terminal ileal involvement, and granulomas distinguish Crohn from UC.
Smoking DOUBLES Crohn risk and worsens course — paradoxically protective in UC. Always counsel cessation.
Early advanced therapy is preferred over step-up with corticosteroids or immunomodulators in moderate-severe disease (AGA 2025; PROFILE trial 2024). SONIC showed infliximab + azathioprine outperformed either drug alone in biologic- and immunomodulator-naive patients.
Check TPMT or NUDT15 before starting thiopurines to avoid severe myelosuppression.
Vaccinate before biologics: hepatitis B, pneumococcal, influenza, HPV; AVOID live vaccines (MMR, varicella, yellow fever) once on biologic therapy.
Perianal Crohn requires combined medical (anti-TNF + antibiotics) and surgical (seton placement, drainage) management; pelvic MRI maps fistula anatomy.
Surgery is NOT curative in Crohn — bowel-sparing approach (stricturoplasty, limited resection); endoscopic recurrence rates 70% at 1 year without postoperative prophylaxis.
Colorectal cancer surveillance: colonoscopy every 1-3 yr starting 8-10 yr after disease onset for colonic involvement.
Loss of response to anti-TNF: check trough level and antidrug antibodies. Low trough without antibodies → dose-escalate; low trough with high-titer antibodies → switch agents (a different anti-TNF or a different class, not a biosimilar of the same drug); adequate trough with active disease → switch to a different mechanism. Adding a thiopurine lowers antibody formation.
References
ACG 2025 — Lichtenstein GR et al. ACG Clinical Guideline: Management of Crohn's Disease in Adults. Am J Gastroenterol 2025;120:1225-1264
AGA 2025 — Scott FI et al. AGA Living Clinical Practice Guideline on the Pharmacologic Management of Moderate-to-Severe Crohn's Disease. Gastroenterology 2025;169:1397-1448
SONIC Trial — Colombel JF et al. Infliximab, Azathioprine, or Combination Therapy for Crohn's Disease. NEJM 2010;362:1383-1395
ECCO 2024 — Gordon H et al. ECCO Guidelines on Therapeutics in Crohn's Disease: Medical Treatment. J Crohns Colitis 2024;18:1531-1555
PROFILE Trial — Noor NM et al. A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn's disease (PROFILE): a multicentre, open-label randomised controlled trial. Lancet Gastroenterol Hepatol 2024;9:415-427
AGA 2017 TDM — Feuerstein JD et al. American Gastroenterological Association Institute Guideline on Therapeutic Drug Monitoring in Inflammatory Bowel Disease. Gastroenterology 2017;153:827-834
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