Gastrointestinal · PANCE / PANRE

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

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) — 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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