Crohn Disease
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.
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Risk factors
- Family history (NOD2/CARD15, ATG16L1, IL23R polymorphisms)
- Smoking (DOUBLES risk and worsens course — opposite of UC)
- Western diet (high fat/processed, low fiber)
- Antibiotic exposure in childhood
- Appendectomy (modest)
- Urban residence, northern latitudes
- NSAID use can trigger flares
Pathophysiology
Dysregulated mucosal immune response to commensal gut microbiota in genetically susceptible individuals. Innate immune defects (NOD2) impair bacterial clearance; Th1/Th17 responses drive transmural inflammation. Granulomas (non-caseating) in ~30% of biopsies. Transmural extension produces strictures, fistulas, and abscesses.
Clinical presentation
Symptoms
- Chronic diarrhea (often non-bloody but can be bloody if colonic)
- Crampy abdominal pain, especially RLQ (ileocecal disease)
- Weight loss, fatigue, low-grade fever
- Perianal disease: fistulas, fissures, abscesses, skin tags
- Aphthous oral ulcers
- Symptoms of stricture: postprandial pain, bloating, vomiting, obstruction
- Extraintestinal: arthritis, episcleritis/uveitis, erythema nodosum, pyoderma gangrenosum, primary sclerosing cholangitis (less than UC), kidney stones (oxalate), gallstones
Signs / physical exam
- RLQ tenderness, palpable mass (inflammatory phlegmon)
- Perianal fistulas, skin tags, fissures, abscesses
- Aphthous ulcers, glossitis
- Pallor (anemia), cachexia
- Clubbing (chronic disease)
- Skin: erythema nodosum, pyoderma gangrenosum
- Eye: scleritis, uveitis
- Joints: peripheral arthritis, sacroiliitis
Classic findings
Young adult with months of crampy RLQ pain, intermittent diarrhea, weight loss, and perianal fistula or abscess.
Differential diagnosis
- Ulcerative colitis — Continuous rectal involvement, mucosal-only inflammation, no skip lesions or fistulas, bloody diarrhea
- Intestinal tuberculosis — Ileocecal stricturing, caseating granulomas, TB risk factors; QuantiFERON, AFB stain/culture
- Behçet disease — Oral and genital ulcers, uveitis, ileocecal ulcers
- Infectious colitis (Yersinia, Salmonella, Campylobacter, C. diff, CMV) — Acute onset, exposure history, positive stool studies
- NSAID enteropathy — NSAID use; mid-small bowel ulcers and diaphragm-like strictures
- Lymphoma / small bowel adenocarcinoma — Refractory stricture or mass on imaging; biopsy
- Ischemic colitis — Older patient, watershed areas (splenic flexure), atherosclerotic risk factors
- Diverticulitis — Older patient, sigmoid predominant, fever, leukocytosis, CT findings
Diagnostic workup
Diagnostic criteria
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 |
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) — maintenance
- Anti-IL-12/23 — ustekinumab — induction and maintenance
- Anti-IL-23 — risankizumab — induction and maintenance
- JAK inhibitor — upadacitinib — induction and maintenance for moderate-severe Crohn
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 (drainage), perforation, dysplasia, or medically refractory disease; NOT CURATIVE — recurrence at anastomosis common
Complications
- Strictures with bowel obstruction
- Fistulas (enteroenteric, enterocutaneous, enterovesical, enterovaginal, perianal)
- Abscesses (intra-abdominal, perianal)
- Perforation
- GI bleeding
- 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.
- Top-down therapy (early biologic + immunomodulator) is superior to step-up in moderate-severe disease (SONIC trial showed infliximab + azathioprine > either alone).
- 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.
References
- ACG 2018 — Lichtenstein GR et al. ACG Clinical Guideline: Management of Crohn's Disease in Adults. Am J Gastroenterol 2018;113:481-517
- AGA 2021 — Feuerstein JD et al. AGA Clinical Practice Guidelines on the Medical Management of Moderate to Severe Luminal and Perianal Fistulizing Crohn's Disease. Gastroenterology 2021;160:2496-2508
- SONIC Trial — Colombel JF et al. Infliximab, Azathioprine, or Combination Therapy for Crohn's Disease. NEJM 2010;362:1383-1395
- ECCO 2020 — Torres J et al. ECCO Guidelines on Therapeutics in Crohn's Disease: Medical Treatment. J Crohns Colitis 2020;14:4-22
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