Crohn Disease

See Inflammatory Bowel Disease for shared epidemiology, classification, clinical features, diagnosis, and medical treatment as originally framed by the colon-focused chapter chunk. This page now also incorporates a full small-bowel-focused treatment of Crohn disease. Content below is from two textbook reference chapters (Sabiston Ch52 - Inflammatory Bowel Disease and Sabiston Ch50 - Small Bowel Anatomy, Physiology, Obstruction & Crohn Disease), not primary literature.

Unlike UC (where surgery is curative), Crohn's surgery is generally reserved for complications — it does not cure the disease, and recurrence after resection is expected to some degree.

History

First documented case described by Morgagni in 1761. Dalziel (Scottish surgeon) described nine cases of intestinal inflammatory disease in 1913. The landmark 1932 paper by Crohn and colleagues provided the detailed pathologic and clinical description that crystallized this entity and gave it its name.

Incidence and epidemiology

Crohn disease is the most common primary surgical disease of the small bowel. Annual incidence in the US is 3–20 per 100,000 and rising. Estimated direct/indirect US costs exceed $800 million/year. Typically attacks young adults in their 2nd–3rd decades, with a smaller second incidence peak in the 6th decade (bimodal distribution). More common in urban dwellers; earlier reports suggested a higher female predominance but more recent data show roughly equal sex distribution. Risk is about twice as high in smokers as nonsmokers. Some studies show increased incidence in women using oral contraceptives, though more recent studies show no difference. Relatively uncommon worldwide in African Americans, but rates in African Americans in the US are similar to those in Caucasians. Ashkenazi Jews have a 2- to 4-fold higher incidence than age/gender-matched controls. Individuals born in spring months (April–June) are more likely to develop Crohn's; migrants from low-risk to high-risk regions develop Crohn's at rates similar to the high-risk region within one generation.

Etiology

Cause remains unknown; most likely contributing factors are infectious, immunologic, and genetic, with environmental/dietary/smoking/psychosocial factors of lesser but non-negligible importance.

• Infectious agents: mycobacterial infections (particularly Mycobacterium paratuberculosis) and enteroadherent E. coli have received the most attention, but neither has been proven causative; antimycobacterial therapy has not reliably ameliorated disease.
• Immunologic factors: humoral and cell-mediated immune responses against intestinal cells suggest an autoimmune phenomenon; cytokines (IL-1, IL-2, IL-8, TNF-α) contribute to the inflammatory response, though it remains controversial whether immune dysregulation is causative or an effect of the disease process.
• Genetic factors: the single strongest risk factor for developing Crohn's is having a first-degree relative with it. Risk increases 30-fold for siblings, 14- to 15-fold for all first-degree relatives. Dizygotic twin concordance is ~4% vs. 20–50% in monozygotic twins. Genes most strongly/frequently associated: NOD2, MHC, MST1 (3p21); other implicated loci on chromosomes 16q, 5q, 19p, 7q, 3p. NOD2 is associated with decreased Paneth cell antimicrobial peptide expression; heterozygosity confers 2- to 4-fold increased risk, homozygosity 17- to 40-fold. NOD2 also predicts ileal stenosis, fistula, and Crohn-related surgery. CARD15 impairs NF-κB activation and is also useful in distinguishing Crohn's from UC (more strongly associated with Crohn's, especially in patients of northern European descent). See Table 50.5 in the source for the full gene-by-phenotype breakdown (diagnosis, prognosis, behavior [stricturing/penetrating/ inflammatory/granulomatous], location, activity, surgery risk, dysplasia/cancer risk, extraintestinal manifestations, pharmacogenetics). More recent genome-wide studies in monozygotic twins have found no reproducible intra-pair differences in whole genome sequence or tissue-specific variants directly in inflamed mucosa, suggesting somatic mutation is not a major driver and simple Mendelian inheritance cannot explain the pattern — multifactorial causation (including environmental factors) is likely.
• Environmental factors: low-risk Asian countries adopting a Western lifestyle have seen rising incidence. Smoking is the single largest environmental risk factor (2-fold increased risk), with smoking-associated single nucleotide polymorphisms identifying a genetic disposition to this environmental risk. Other risk-increasing factors: oral contraceptives, aspirin, NSAIDs, decreased dietary fiber, increased fat intake. Dysbiosis (decreased Bacteroides/Firmicutes, increased Gammaproteobacteria/Actinobacteria) is associated with higher risk; invasive mucosal-adherent E. coli survive within macrophages and induce higher TNF-α production.

Flag — discrepancy with Colonic Physiology: that page (ASCRS Ch. 2) reports Bacteroidetes abundance as significantly higher, not lower, in Crohn's disease vs. healthy controls and vs. ulcerative colitis. Both sources are textbook-level; gut-microbiome IBD findings vary meaningfully by cohort/methodology, so this may be genuine study-to-study heterogeneity rather than an error in either textbook — flagged, not silently reconciled. Update: ASCRS Ch43 - Inflammatory Bowel Disease Pathobiology independently reports decreased (not increased) Bacteroidetes in IBD generally, agreeing with this page's original figure — now 2 sources against 1, but still not treated as resolved given the cohort/methodology caveat above.

Pathology

Most common sites: small intestine and colon. A large multi-institutional study proposed a three-category model (ileal Crohn's, colonic Crohn's, ulcerative colitis) for risk stratification of surgical complications and genetic risk scoring by location. Ileal involvement is associated with IL10, CRP, NOD2, ZNF365, STAT3 mutations; ileocolonic with ATG16L1, TCF4, TCF7L2; colonic with HLA, TLR4, TLR1, TLR2, TLR6. Small and large bowel are both involved in ~55% of patients; small bowel disease alone in ~30%; colon alone in ~15%. Disease is characteristically discontinuous and segmental ("skip areas" of normal bowel between diseased segments). Perirectal/perianal involvement occurs in about a third of patients, particularly with colonic involvement. Can involve mouth, esophagus, stomach, duodenum, and appendix, though these are rarely the sole site of disease.

• Gross pathologic features: thickened, gray-pink or dull purple-red bowel loops, with areas of thick gray-white exudate/fibrosis on the serosa. A striking finding is creeping fat — circumferential mesenteric fat wrapping around the bowel wall (Fig. 50.16). As disease progresses, the bowel wall becomes increasingly thickened, firm, rubbery, and almost incompressible (Fig. 50.17). Uninvolved proximal bowel may dilate secondary to obstruction of the diseased segment. Involved segments are often adherent to adjacent loops/viscera, with internal fistulas common in these areas; mesentery is thickened with enlarged lymph nodes. The earliest gross lesion on opening the bowel is a superficial aphthous ulcer; with progression, ulceration becomes more pronounced and complete transmural inflammation results — ulcers are characteristically linear and may coalesce into transverse sinuses with islands of normal mucosa between, giving the characteristic cobblestone appearance.
• Microscopic features: mucosal/submucosal edema may precede gross changes. Chronic inflammatory infiltrate with extensive edema, hyperemia, lymphangiectasia, intense mononuclear cell infiltration, and lymphoid hyperplasia. Characteristic lesions are noncaseating granulomas with Langerhans giant cells, appearing later in the disease course, found in the bowel wall or regional lymph nodes in 60–70% of patients (Fig. 50.18).

Montreal classification (Table 50.6)

Categorizes patients by:

• Age at diagnosis: A1 ≤16, A2 17–40, A3 >40
• Behavior: B1 nonstricturing/nonpenetrating, B2 stricturing, B3 penetrating (+P modifier for perianal disease, addable to B1–B3)
• Location: L1 ileal, L2 colonic, L3 ileocolonic, L4 isolated upper GI tract (addable to L1–L3)

Developed to provide reproducible staging, predict remission/relapse, and direct therapy.

Paris classification (pediatric-onset, Table 44.5, ASCRS Ch44): adapts Montreal for children — age at diagnosis subdivided as A1a ≤10yo/A1b 10–17yo (vs. Montreal's single A1 ≤16 cutoff); the L4 upper-GI modifier split into L4a (proximal to ligament of Treitz) and L4b (distal to ligament of Treitz, proximal to distal 1/3 ileum) rather than treated as one category; and a growth modifier (G0 no growth delay, G1 growth delay present) absent from the adult Montreal system, reflecting pediatric IBD's distinct growth-impairment concern.

Clinical manifestations

Can occur at any age; typical patient is a young adult in the 2nd–3rd decade with an insidious onset and slow, protracted course. Characteristic symptomatic periods of abdominal pain and diarrhea interspersed with asymptomatic periods of varying length; over time symptomatic periods become more frequent, severe, and longer-lasting. Most common symptom is chronic diarrhea, followed by intermittent colicky abdominal pain most often in the lower abdomen; pain may be severe and right-lower-quadrant, mimicking acute appendicitis. Unlike UC, bowel movements are typically fewer and stools rarely contain mucus/pus/blood. Systemic symptoms (low-grade fever, weight loss, loss of strength, malaise) present in about a third of patients.

Main intestinal complications are obstruction (from acute exacerbation of active disease or chronic fibrosing lesions narrowing the lumen) and perforation. Free perforation with generalized peritonitis is rare; more commonly, fistulas form between sites of perforation and adjacent structures (small/large bowel, urinary bladder, vagina, stomach, skin — usually at a prior laparotomy site). Localized abscesses can occur near perforation sites. Colitis patients may develop toxic megacolon. Bleeding is typically indolent/chronic, but massive GI bleeding can occasionally occur, particularly in duodenal Crohn's with chronic ulcer formation.

Cancer risk: long-standing Crohn's predisposes to small intestine and colon carcinoma, typically arising at sites of chronic inflammation, more commonly in the ileum. Most are not detected until advanced stages with a poor prognosis. Relative risk of small bowel cancer is ~100-fold increased though absolute risk remains small. Colorectal cancer risk with colonic involvement and long disease duration is a greater concern; dysplasia is the putative precursor lesion (as with UC), and patients with long-standing colonic Crohn's should have an equally aggressive colonoscopic surveillance regimen as extensive UC. Small bowel adenocarcinoma associated with Crohn's has an aggressive behavior with a strong probability of extracellular mucin; mucinous-appearing/fistulous/adhesion- retraction areas in surgical specimens should always be examined by a pathologist for dysplasia/ malignancy. Extraintestinal cancers (squamous cell carcinoma of vulva/anal canal, Hodgkin and non-Hodgkin lymphoma) may also be more frequent, especially in patients treated with immunomodulators.

Perianal disease (fissure, fistula, stricture, abscess) is common — occurs in 25% of patients overall, with incidence varying sharply by disease location/extent (12% with isolated ileal disease up to 92% with combined colonic+rectal disease — see "Perianal (anorectal) Crohn's disease" below for the full breakdown). It may be the sole presenting feature in 5% of patients and may precede intestinal disease onset by months to years. Anal Fistula (ASCRS Ch13) explicitly excludes Crohn's/extrasphincteric fistulas from its cryptoglandular treatment ladder (LIFT, ERAF, FiLaC, VAAFT, etc.) and directs readers to Crohn's-specific management instead — now covered in full below, following ASCRS Ch47 - Anorectal Crohn's Disease. Rectovaginal fistula is a Crohn's-specific manifestation covered in its own dedicated page, Rectovaginal Fistula (ASCRS Ch15) — incidence has notably declined in the biologic era (e.g. 5.7% to 1.7% cumulative 5-year rate across two treatment periods in one cohort); that page also covers ACCENT-2 infliximab-in-RVF subset data (64% short-term response, but no long-term healing benefit over placebo) and notes surgical RVF-repair success is generally lower for Crohn's than non-Crohn's patients.

Extraintestinal manifestations present in ~30% of patients: skin lesions (erythema nodosum, pyoderma gangrenosum — Fig. 50.19), arthritis/arthralgias, uveitis/iritis, aphthous stomatitis, and (less commonly) amyloidosis, pancreatitis, and nephrotic syndrome. These may precede, accompany, or follow the underlying bowel disease.

Diagnosis

No single diagnostic test exists; a multimodal approach (labs, endoscopy, radiology, pathology) is required.

• Laboratory: serologic markers — perinuclear antineutrophil cytoplasmic antibody (and target proteins BPI, lactoferrin, cathepsin G, elastase), anti-Saccharomyces cerevisiae antibody (ASCA), anti-CBir1 (outer membrane porin of flagellin), OmpC-IgG (outer membrane porin of E. coli) — can predict IBD development even in patients thought low-risk, and ASCA helps differentiate Crohn's from UC. CRP and ESR are nonspecific and have largely been abandoned as primary markers. Fecal calprotectin (sensitivity 69%, specificity 82% for small bowel inflammation at >140 ng/mL) and fecal lactoferrin (sensitivity 69%, specificity 79% at >6 ng/mL) are useful screening tools for early small bowel Crohn's; calprotectin correlates with CRP and ESR, while lactoferrin correlates only with CRP. ASCRS Ch44 adds a pooled figure once IBD diagnosis is already established: combined pANCA+ASCA testing is 70% sensitive/93% specific for differentiating UC from Crohn's, and fecal calprotectin's pooled diagnostic accuracy across studies is 93–95% sensitivity/90–96% specificity (<50 mcg/g supports avoiding invasive testing) — see also Inflammatory Bowel Disease's "Diagnostic Evaluation" section.
• Radiology: CT enterography (CTE) or MR enterography (MRE) are often used as initial assessment — both accurate for disease activity/bowel damage; MRE may be superior for detecting strictures and ileal wall enhancement, though CTE is used more for cost/availability. Barium enema historically used to identify features like the Kantor string sign (long narrowed terminal ileum segments, Fig. 50.20) in long-standing disease; segmental/irregular involvement and fistulas also visible. CTE is useful for demonstrating transmural thickening and extramural complications (Fig. 50.22). Ultrasound has limited value, especially for disease proximal to the terminal ileum (misses up to 67% in one study), but may help assess undiagnosed RLQ pain. A multicenter MRE cohort study (ASCRS Ch44) reports MRE sensitivity/specificity varying by disease location (better for small-bowel than colonic disease); novel diffusion-weighted and delayed-enhancement MR techniques are being explored for quantifying bowel-wall fibrosis specifically, and transperineal/transanal ultrasound plus MR pelvis are used for perianal-fistula characterization (see Rectovaginal Fistula and Anal Fistula).
• Endoscopy: ileocolonoscopy with terminal ileum biopsy is the gold standard. May show aphthous ulcers with granularity and normal-appearing surrounding mucosa; discrete ulcers/cobblestoning and discontinuous segments favor Crohn's over UC. Balloon enteroscopy (single-, double-balloon, spiral) allows evaluation of small bowel beyond ileocolonoscopy reach; double-balloon is the most established technique (240–360 cm enteral intubation vs. 90–150 cm for push enteroscopy or 50–80 cm for ileocolonoscopy), with ~1% complication risk (pancreatitis, perforation, bleeding). CDEIS or SES-CD (Simple Endoscopic Score for Crohn's Disease, Table 44.8) scoring used to define extent/ severity once diagnosis is confirmed — SES-CD grades four domains (presence/size of ulcers, extent of ulcerated surface, extent of affected surface, presence/type of narrowing/stricture) each 0–3 across five bowel segments and is generally preferred over CDEIS for routine use given its greater simplicity. Capsule endoscopy (FDA-approved 2001) is useful for superficial mucosal abnormalities (≥3 ulcers without NSAID use is the most common abnormal-finding criterion); limited by capsule retention risk (13% in Crohn's vs. 1–2.5% general population); severity measured by the CECDAI/Niv score.
• Differential diagnosis: bacterial (Salmonella, Shigella), intestinal TB, and protozoal (amebiasis) infections can mimic Crohn's as an ileitis; in the immunocompromised host, rare mycobacterial and CMV infections. Acute distal ileitis may mimic early Crohn's but can also be unrelated, caused by Campylobacter or Yersinia — these usually resolve spontaneously and should not be biopsied/resected if noted incidentally at surgery. Crohn colitis vs. ulcerative colitis distinction can be difficult in 5–10% of patients (see Table 50.7 for a detailed symptom/radiologic/proctoscopic comparison) — UC almost always involves the rectum most severely with continuous proximal extension and does not extend deep into the bowel wall; Crohn's may be worse on the right side, sometimes spares the rectum, and shows skip lesions, linear/deep/scattered ulceration, and (unlike UC) frequent anal fissure/fistula/abscess. Caveat on histologic reliability (ASCRS Ch44): even among expert GI pathologists, inter-observer accuracy for distinguishing UC from Crohn's on biopsy is only 64–74% — the diagnosis remains fundamentally multimodal rather than histology-driven, and up to 10% of adult-onset (30% pediatric-onset) IBD is ultimately unclassifiable (IBD-U) at initial workup; see Inflammatory Bowel Disease's "IBD-Unclassified (IBD-U) and Indeterminate Colitis" content for reclassification rates.

Management

Medical therapy

No cure exists. Medical therapy aims for steroid-free remission and prevention of exacerbations/ complications; endoscopic healing has emerged as the therapeutic goal given its poor correlation with symptoms alone. Surgery is advocated for neoplastic/preneoplastic lesions, obstructing stenoses, suppurative complications, or medically intractable disease. Narcotic analgesia should be avoided except perioperatively given tolerance/abuse potential in chronic disease. Clinical remission = Crohn Disease Activity Index (CDAI) below 150 (Box 50.4, 8 clinical factors); response = drop of 100 points. CDAI 150–220 = mild-moderate; 220–450 = moderate-severe (after failure of first-line therapy); >450 = severe fulminant disease with failed medical therapy and obstruction/peritonitis/ abscess complications.

• Aminosalicylates (sulfasalazine, mesalamine): sulfasalazine's benefit is mainly in colonic disease; its use for small bowel Crohn's maintenance has fallen out of favor. Mesalamine (4 g/day) demonstrated efficacy without increased side effects; rare interstitial nephritis (1%) requires periodic renal monitoring. Mechanistic caveat and modern trial evidence (ASCRS Ch46): 5-ASAs work as topical mucosal anti-inflammatories, which explains their UC efficacy but limits their relevance to Crohn's full-thickness bowel disease — multiple well-designed placebo-controlled RCTs and meta-analyses (including the ECCO CD guideline's own meta-analysis, RR 1.03) found no efficacy for induction or maintenance at any disease location; the older National Cooperative Crohn's Disease Study (NCCDS) and European Cooperative Crohn's Disease Study (ECCDS) trials gave mixed early results specifically for isolated colonic disease but lacked modern endoscopic/ biochemical endpoints. A possible remaining niche is Crohn's proctitis — rectal 5-ASA (500–1000mg suppository at bedtime, or 4g/60cc enema 1–2x/day) for disabling urgency/tenesmus/ agoraphobia symptoms, as an adjunct rather than primary therapy. 5-ASAs are not FDA-approved for CD in the US (though approved in Europe/Canada/Australia/Japan), and ACG/ECCO guidelines concluded they lack efficacy for CD induction.
• Corticosteroids: fast-acting/effective for inducing remission but not ideal for maintenance. Budesonide (9 mg/day) has high first-pass hepatic metabolism, targeting the ileum/right colon while mitigating systemic steroid effects; more effective than placebo or mesalamine for mild- moderate active ileal disease and is the preferred primary treatment there. Comes as a 3mg capsule; for disease proximal to the terminal ileum, the "open-capsule technique" (ASCRS Ch46) — opening half a 3mg capsule and sprinkling its contents on food — extends its reach to small bowel; the MMX® formulation instead releases throughout the entire colon. A Cochrane meta-analysis confirms budesonide's efficacy over placebo for induction but inferiority to conventional steroids, with a lack of efficacy for maintenance. Prednisone for moderate-severe disease; >50% of patients (particularly smokers) become "steroid dependent," with chronic use causing osteoporosis and increased relapse rates. High-dose (40–60 mg/day) until symptom resolution and weight gain resumption; parenteral for severe disease once abscess is excluded. No standard taper; generally 5–10 mg/week to 20 mg, then 2.5–5 mg weekly to cessation — in practice (ASCRS Ch46) many clinicians reduce the dose by 50% every 5–7 days, with a slower taper over additional weeks if steroid exposure has been prolonged, to avoid Addisonian-crisis-range withdrawal symptoms. DEXA scan, calcium, and vitamin D supplementation, with consideration of bisphosphonates, are warranted once steroid therapy begins. Chronic steroid use is among the most significant risk factors for postoperative infectious/wound complications and is considered a "bad omen"/tipping point toward more complicated disease — steroid dependency is itself an indication for surgery.
• Antibiotics: metformin-era metronidazole initially reported effective but later found no better than placebo for inducing remission; ciprofloxacin, rifaximin, clofazimine, ethambutol, isoniazid, and rifabutin have varying success. Clear role in septic complications and perianal disease; mechanism of action in Crohn's unclear; long-term use limited by side effects. May help as adjuncts for perianal disease, enterocutaneous fistulas, or active colonic disease, but not recommended for maintenance or remission induction.
• Immunosuppressive agents: azathioprine (AZT), 6-mercaptopurine (6-MP), and methotrexate (MTX) effective for maintenance therapy in moderate-severe disease; AZT/6-MP for maintaining steroid-induced remission, weekly IV MTX for both induction and maintenance. Slow onset requires steroid bridging until transition is complete. Relatively safe; most common side effects are pancreatitis, hepatitis, fever, rash; more concerning are chronic liver disease, bone marrow suppression, and malignant transformation potential. Thiopurine methyltransferase (TPMT) genetic polymorphisms affect AZT/6-MP metabolism — decreased TPMT activity carries significantly increased fatal bone marrow suppression risk; genotype testing may help identify predisposed patients. NUDT15 variant testing is a second, distinct pre-thiopurine pharmacogenomic check (ASCRS Ch44) — relevant especially in patients of East/South Asian ancestry, who carry higher myelosuppression risk than TPMT testing alone would predict; see also the therapeutic-drug- monitoring detail below and on Inflammatory Bowel Disease. TPMT genotype distribution (ASCRS Ch46): ~80% of the population are normal metabolizers; ~10% are hyperactive "shunters" (increased hepatotoxicity risk, manageable by co-prescribing low-dose allopurinol at 25% of the usual thiopurine dose); ~10% are heterozygous/intermediate-activity (need a higher-than-average dose); 0.3% are homozygous-deficient (will not respond clinically and carry the highest myelosuppression risk). EBV safety flag (ASCRS Ch46, genuinely new to the wiki): young men with positive EBV status carry a small but demonstrable risk of hepatocellular T-cell lymphoma — a universally fatal condition — on thiopurine therapy; EBV-naive patients are separately at risk of hemophagocytosis. Methotrexate's side-effect profile spans GI (mucositis/diarrhea, mitigated by weekly folate), bone marrow (anemia/leukopenia), hepatic (steatosis/fibrosis/cirrhosis, avoid cumulative dose >1g), pulmonary (pneumonitis/PCP pneumonia), renal (rare insufficiency — monitor GFR), and reproductive (teratogenic — abstinence/contraception required). Other agents: cyclosporine and FK-506 (tacrolimus) — FK-506 effective for fistula improvement (not remission) in severe/steroid-refractory perianal disease; cyclosporine not found efficacious except in uncontrolled studies at low dose.
• Anti-TNF therapy: considered a breakthrough. Infliximab (chimeric monoclonal anti-TNF-α) effective and safe as monotherapy for moderate-severe disease, effective for both induction and maintenance; ~two-thirds of patients achieve perianal fistula closure, though not every fistulizing/ extraintestinal-disease patient responds. Other FDA-approved anti-TNF agents: adalimumab (humanized IgG1, self-administrable; 160mg induction at week 0, 80mg at week 2, 40mg every 2 weeks thereafter), certolizumab (humanized antibody fragment linked to PEG, does not cross the placenta/excrete in breast milk — preferred in pregnancy/nursing; 400mg induction at weeks 0, 2, 4, then 400mg every 4 weeks — ASCRS Ch46). Similar safety profiles across the three: increased risk of TB reactivation, invasive fungal/opportunistic infection, demyelinating CNS lesions, latent MS activation, CHF exacerbation, and possible increased melanoma risk. Flare on anti-TNF therapy prompts measurement of serum drug concentration and antidrug antibodies to guide dose increase, agent switch (same class), or class switch. Smoking cessation is an important adjunct — smoking is an independent predictor of needing maintenance biologic therapy.
• Novel therapies: leukocyte trafficking inhibitors, interleukin inhibitors, antiadhesion molecule antibodies — often used after anti-TNF failure/intolerance. Natalizumab (anti-α4 integrin, 300mg IV every 4 weeks) effective for induction/maintenance but withdrawn after progressive multifocal leukoencephalopathy (PML) cases, later reinstated for refractory disease — PML risk is as high as 1 in 100 patients who are JC-virus-antibody-positive (ASCRS Ch46), requiring surveillance before starting and every 6 months thereafter; because vedolizumab is gut-selective it carries no PML risk, which has largely driven natalizumab's abandonment for CD in practice. Vedolizumab (humanized anti-α4β7 integrin, blocks MadCAM-1 interaction) more gut-specific, avoids the neurologic side effects of less selective α4 inhibitors, but has slow onset of action; approved 2014 for anti-TNF/ immunosuppressant nonresponders. Ustekinumab (humanized IgG1 anti-IL-12/23, targets shared p40 subunit) shown effective in anti-TNF-refractory disease with similar efficacy in two large trials; approved 2016. Other agents in development target NF-κB, MAPK, and PPAR-γ signaling with variable/ still-developing results.
• Nutritional therapy: variable success; chemically defined elemental diets shown in some studies to reduce disease activity (particularly small-bowel-localized disease) and reduce corticosteroid- induced toxicities; liquid polymeric diets similarly effective and more palatable. Standard elemental diets have not reliably prevented relapse, with few exceptions. TPN useful in active disease but complication rates exceed enteral nutrition; primary role is questionable, but there is a secondary role in replenishing nutrient stores, allowing protein synthesis/healing, and preparing patients for surgery.
• Smoking cessation: implication as a causative factor has been hard to prove, but smoking clearly worsens disease course — associated with late bimodal-onset disease, increased relapse/maintenance failure, and severity in a linear dose-response relationship. Tobacco exposure independently predicts need for maintenance biologic therapy.

Advanced therapy, monitoring, and post-surgical management (BSG 2025 guideline)

The medical-therapy subsection above is textbook-level (mechanism/class only, no trial evidence or positioning) — until this ingest, Crohn's had no primary-guideline backing at all in this wiki, unlike Ulcerative Colitis (which gained full guideline coverage from ACG 2025 - Ulcerative Colitis Guideline and AGA 2024 - Moderate-to-Severe UC Pharmacotherapy Guideline earlier in the same ingest session). This subsection adds GRADE-based recommendations from BSG 2025 - IBD Guidelines (Adults) — see that page for full detail; only headline positioning is repeated here.

Advanced therapy roster (all "conditional" strength recommendations, certainty/magnitude noted):

Agent	Recommendation	Certainty / magnitude	Notes
Adalimumab	Suggested	Moderate / moderate	Combination with a purine analogue recommended — lowers NNT for remission 4→2
Infliximab	Suggested	Moderate / moderate	Combination with a purine analogue recommended — ~20% higher maintenance magnitude than monotherapy
Ustekinumab	Suggested	Moderate / moderate	Usable after purine analogue and/or anti-TNF failure
Risankizumab	Suggested	Low / small	SEQUENCE trial: non-inferior to ustekinumab for remission at wk 24, superior for endoscopic remission at wk 48 (anti-TNF-experienced patients)
Upadacitinib	Suggested	Low / small	First oral agent effective for both induction and maintenance in Crohn's; reserved for after anti-TNF failure given VTE/MACE boxed warning
Vedolizumab	NOT suggested	Low / trivial	Genuine disease-specific divergence from its favorable UC positioning — trivial effect size across all direct Crohn's trial evidence regardless of biologic exposure status; not precluded case-by-case, but not a guideline-endorsed default
Antibiotics	NOT suggested	High / trivial	No individual agent/combination robustly studied; small class-wide induction effect only
Probiotics	NOT suggested	Very low	Insufficient evidence

Therapeutic drug monitoring — adds concrete numbers to what the disease page previously only covered qualitatively (TPMT testing above): target purine analogue metabolites 6-TGN 235–450 pmol/8×10⁸ RBCs, MMP <5700 pmol/8×10⁸ RBCs, checked ~4 weeks after starting and 3-monthly alongside FBC/U&E/LFT. PANTS-study-derived anti-TNF trough targets at later time points (week 14+): 6.1–10.0 mg/L for infliximab, 10.1–12.0 mg/L for adalimumab — evidence insufficient to formally recommend routinely targeting these levels, but useful context for dose-escalation decisions on secondary loss of response.

Exclusive enteral nutrition (EEN): well-established in pediatric Crohn's (~73% remission, intention-to-treat) but not formally graded for adults — Cochrane data show no difference vs. steroids without allowing firm conclusions (very low certainty). Best-supported adult use is preoperatively: ~6 weeks preoperative EEN associated with lower postoperative abscess/leak rates and lower CRP in observational studies. Practical protocol: whole-protein/peptide/elemental formulas equally efficacious: gradual volume increase to a target ~25–30 kcal/kg/day energy, 1 g/kg/day protein; refeeding-syndrome bloods (K, phosphate, Mg) monitored daily while ramping in at-risk patients; continue 6–8 weeks once established to induce mucosal healing.

Withdrawal of therapy: infliximab withdrawal after ≥1 year of stable remission is not suggested — both RCTs examining this (SPARE, STOP-IT) showed materially elevated relapse risk on withdrawal (roughly 1 in 3 patients relapse within 1–2 years, though retreatment on relapse is usually effective). By contrast, withdrawing the immunomodulator while continuing anti-TNF is not associated with a significant relapse-risk increase, if attempted after >2 years of combination therapy and >6 months of corticosteroid-free remission. ASCRS Ch46 frames this as a structured de-escalation decision (Fig. 46.3): confirm deep remission first (clinical symptoms + normal biomarkers + endoscopic/small-bowel-imaging confirmation, drug levels checked beforehand — a low level suggests the biologic wasn't the source of remission and de-escalation is more likely to succeed), then surveil every ~3 months (CRP, fecal calprotectin, symptoms) for a year plus colonoscopy/cross-sectional imaging at 6–12 months; restart the prior successful regimen if biomarkers rise or recurrence is confirmed.

Non-surgical stricture management: CREOLE study found adalimumab avoided escalation to steroids/dilation/surgery in 64% of symptomatic ileal strictures at 24 weeks (a prognostic score using clinical + MRE features predicts response) — relevant alongside the strictureplasty/resection decision-making in "Specific problems" below. Endoscopic balloon dilation is appropriate for ileocolonic anastomotic strictures <4cm without sharp angulation, though most patients need repeat dilation.

Post-surgical recurrence prevention (see also "Prognosis" below for the older Fig. 50.25 textbook algorithm this refines): anti-TNF (infliximab or adalimumab) or vedolizumab is suggested after ileocolonic resection for patients with significant recurrence risk factors (young age at diagnosis, active smoking, penetrating disease, perianal disease, multiple prior surgeries), by patient preference, or with endoscopic evidence of recurrence at 6 months — recommended to start within 90 days post-surgery where indicated (NMA data: adalimumab HR 0.1, infliximab HR 0.36, for preventing clinical relapse vs. placebo — a notably more proactive stance than "wait for 6-month scope, then decide" alone). 5-ASA and purine analogue monotherapy are not suggested for this purpose — trivial effect size (NNT 13–14) despite reaching statistical significance in some trials. Endoscopic recurrence is still best assessed by ileocolonoscopy at 6 months post-resection using the Rutgeerts score (Table 44.9, ASCRS Ch44): i0 no lesions, i1 ≤5 aphthous lesions, i2 >5 aphthous lesions or skip areas of larger lesions or lesions confined to the ileocolonic anastomosis, i3 diffuse aphthous ileitis with diffusely inflamed mucosa, i4 diffuse inflammation with larger ulcers, nodules, and/or narrowing — i2 or higher predicts clinical recurrence and is the threshold typically used to escalate therapy, as the textbook algorithm below describes. Additional recurrence-risk data (ASCRS Ch46): off medical therapy, endoscopic recurrence approaches 90% by 3 years and clinical recurrence reaches 60%, with 50% of patients needing additional surgery within 10 years of ileocolic resection. A recent meta-analysis found histologically positive margins (OR 1.7, 95% CI 1.3–2.1) and plexitis (OR 2.3, 95% CI 1.1–4.9) significantly increase postoperative recurrence risk — surgically actionable pathology findings not previously in the wiki. The only RCT directly testing prophylaxis timing (routine azathioprine starting at 8 weeks vs. endoscopically-guided therapy at 6–12 months) found no difference between strategies, but had substantial methodologic flaws (mismatched cohorts, low accrual, high attrition) limiting its weight. Probiotics, 5-ASA, and budesonide show no benefit over placebo for postoperative prophylaxis specifically, across numerous RCTs — extending the "5-ASA/purine analogue monotherapy not suggested" note above to these additional agents.

Perioperative optimization: laparoscopic resection should be considered for localised ileocaecal disease when not responding to or relapsing after medical therapy, or by patient preference; malnutrition screening/correction (immune-enhancing nutritional supplements reduce postoperative complications, OR 0.26 in a meta-analysis) as part of preoperative optimisation; corticosteroids stopped/minimised preoperatively where possible (≥20mg prednisolone associated with increased complications; equivalent IV hydrocortisone given if steroid-dependent and NPO). Immunosuppressive agents (purine analogues, methotrexate) and biologics can be continued perioperatively — reassuring large observational data (PUCCINI, French REMIND studies) found no significant postoperative infection increase with anti-TNF exposure regardless of drug concentration or timing; similarly reassuring (smaller) data for vedolizumab and ustekinumab. JAK inhibitor perioperative safety data are limited (one retrospective series: 13.2% VTE rate after tofacitinib exposure before colectomy in ulcerative colitis — prolonged VTE prophylaxis suggested; no Crohn's-specific data yet). Pharmacological VTE prophylaxis recommended for essentially all IBD

Framing difference, not contradiction: Preoperative Evaluation & Perioperative Risk Optimization (ASCRS Ch6) covers this same PUCCINI finding but situates it among a messier, older literature it explicitly calls "quite conflicting and controversial" — a meta-analysis (Wong) at OR 1.5 for infectious complications, single-institution data as high as OR 3.5, NSQIP cohort data OR 1.25–1.47 depending on the infectious outcome, and vedolizumab-specific data suggesting increased risk (contrasting with the "similarly reassuring" vedolizumab data cited here). Both pages are drawing on overlapping evidence; the difference is synthesis confidence (a guideline's graded "reassuring" read vs. a textbook chapter's narrative "still unsettled" read), not a factual conflict — flagged rather than silently merged. patients admitted for acute illness or surgery, extended post-discharge after major abdominal surgery per UK practice.

Microbiome therapies, treat-to-target, and trial-level nuance (ASCRS Ch46)

Genuinely new structure and trial-level detail beyond the BSG section above.

• Microbiome-directed therapies: antibiotics show a small class-wide induction effect (2011 meta-analysis RR 0.85 vs. placebo, p=0.03) undermined by high study heterogeneity; a 2019 Cochrane update of 13 RCTs confirmed modest-but-not-clinically-significant benefit; ACG/ECCO don't recommend them for induction or maintenance, consistent with the "NOT suggested" BSG verdict above. Probiotics are similarly ineffective and possibly not without risk. Dietary interventions (18-RCT/1878-patient Cochrane meta-analysis) show heterogeneous, low-quality evidence with some signal for symptom-based/restrictive diets but no firm conclusions. Fecal microbiota transplant: a 17-patient pilot RCT in steroid-induced-remission CD found no primary-efficacy-endpoint benefit, though endoscopic scores/CRP improved; possible efficacy suggested for UC but not Crohn's. Safety flag: the FDA issued a Safety Alert in March 2020 after 2 patients with chronic medical conditions died of FMT-transmitted enteropathogenic/ shigatoxin-producing E. coli — worth noting given FMT's otherwise-established role for recurrent C. difficile (see Infectious Colitis).
• Combination-therapy trial evidence — names the trials the BSG "combination with a purine analogue recommended" verdict above is built on: SONIC (infliximab+azathioprine vs. either alone: mucosal healing RR 1.82, better 26-week clinical remission, lower serious adverse events RR 0.56); REACT (early combined immunosuppression vs. conventional step-up: lower complication rates, but no steroid-free-remission difference — REACT2's mucosal-healing-endpoint follow-up was still enrolling as of this chapter's writing). DIAMOND is a genuine nuance/complication to the "combination recommended" picture: adalimumab+thiopurine was not superior to adalimumab alone for remission (RR 0.95), though endoscopic improvement was better at week 26 (RR 1.32) — a benefit lost by 1 year, and the trial used a lower AZA dose than typical CD practice (a generalizability caveat). Net read: combination therapy's benefit looks more secure for infliximab (SONIC) than for adalimumab (DIAMOND).
• Treat-to-target framework — genuinely new structural concept for the wiki: STRIDE (Selecting Therapeutic Targets in IBD, an IOIBD initiative) defines the treatment target as resolution of symptoms/altered bowel habit plus endoscopic remission (absent ulceration) or MRE/CTE-defined resolution of inflammation — assessed at 3-month (patient-reported) and 6–9-month (endoscopic) intervals, a shift from the older symptom-only "step-up on flare" paradigm. The CALM trial tested this directly: a tight-control strategy (escalating therapy on CDAI>150 + fecal calprotectin>250 + CRP>5, or on failure to drop CDAI by 70–100 points at randomization/ post-randomization) produced superior endoscopic remission and lower CD-related hospitalization versus purely symptom-driven care.
• Therapeutic drug monitoring — three trials, genuinely mixed results (nuances the single- PANTS-study BSG picture above with real primary-trial-level disagreement): TAXIT (263 patients, dose-adjusted to a target trough concentration of 3–7μg/mL vs. empiric dosing) found no effect on 1-year clinical remission, but fewer flares and a 28% cost reduction. TAILORIX (122 biologic-naive patients, three dose-intensification strategies vs. a symptom-guided control arm) found no benefit of TDM over symptom-guided management at 1 year — though underpowered, with a low control-arm dose-escalation threshold flagged as a limiting factor. PAILOT (78 pediatric patients on adalimumab, proactive vs. reactive TDM) found proactive monitoring significantly better. Net read: TDM's value looks more established in pediatrics (PAILOT) and for cost/flare outcomes (TAXIT) than for adult clinical remission specifically (TAILORIX) — a genuinely contested question this wiki flags rather than resolves.
• Biosimilars: a 220-patient non-inferiority RCT (treatment-switch design between originator infliximab and infliximab-dyyb) found week-6 response rates of 69.4% (infliximab-dyyb) vs. 74.3% (originator), establishing non-inferiority. Biosimilar TNFi agents can be used for de novo induction and maintenance at lower cost; amino acid sequences match the originator but glycosylation patterns can differ, affecting solubility/clearance/immunogenicity. Data on switching between two different biosimilars (rather than originator-to-biosimilar) remains insufficient to support routine practice.

Surgical treatment (colonic-focused, from the Inflammatory Bowel Disease chapter chunk)

Approximately 70% of patients will require surgical resection within 15 years after diagnosis. Indications for surgery include failure of medical treatment, bowel obstruction, fistula or abscess formation, steroid dependence, and dysplasia or malignancy.

Declining surgery rates over time (ASCRS Ch48): the need for surgery has fallen markedly across eras, predating the introduction of biologics. In a population-based cohort diagnosed 1955-1989, 73% of patients overall required surgery (44% at 1 year, 61% at 5 years, 71% at 10 years); in a cohort diagnosed 2003-2004 followed to 2011, only 29% required surgery (14.6% at 1 year, 24.6% at 5 years, 28.5% at 7 years). The largest drop appears more reflective of increased corticosteroid use and earlier diagnosis/therapy initiation (from improved diagnostics) than of biologics specifically. IBD "surgical home" models with dedicated IBD-focused colorectal surgeons have been shown to reduce unplanned care/disease activity and improve quality of life. Full chapter summary: ASCRS Ch48 - Crohn's Disease Surgical Management.

Indications for surgery:

• Failure to grow in children (as with UC).
• Obstruction secondary to fibrostenotic disease.
• Perforating disease with associated abscess or phlegmon.
• Symptomatic fistulas — a relative indication covering many fistula types. A symptomatic ileosigmoid fistula causing diarrhea from bypassed bowel is a clear example. Enterocutaneous fistulas are not automatically an indication unless associated with obstruction/significant discomfort; the same is true of enteroenteric fistulas.
• Significant abdominal pain associated with obstruction.
• Cancer or dysplasia — as with UC, an indication for resection; because Crohn's disease (like UC) can be multifocal in the colon, total proctocolectomy is preferred over segmental resection when dysplasia/cancer is the indication.

Surgical options (colonic):

• Ileocolic resection — the single most common operation for Crohn's (the ileocecal area is involved in nearly half of patients — Fig. 50.23). Because the terminal ileum sits near several pelvic structures, a proximal perforation can track into the sigmoid colon (far more common) or bladder, producing an ileosigmoid or ileovesical fistula. Lends itself well to a laparoscopic approach, except with extensive fistulizing disease or a significant phlegmon making dissection of the right colon mesentery/terminal ileum off retroperitoneal structures difficult. Margin selection: choose bowel that feels grossly normal and has a normal-thickness bowel-mesenteric junction — a palpable, discrete mesenteric junction is a good indicator the lumen there is free of significant Crohn's inflammation. Anastomotic technique: hand-sewn end-to-end is preferred by the Colon and Rectum chapter's authors over side-to-side stapled, since it's easier to evaluate/dilate endoscopically if disease recurs; the anastomosis should be made very wide. (See "Anastomotic technique" below for the Small Bowel chapter's more detailed, somewhat contrasting discussion.)
• Segmental colon resection — increasingly used over the last two decades, for two reasons: (1) recognition of the colon's role in water absorption plus the likelihood of repeat operations over a Crohn's patient's lifetime, and (2) newer, more potent medications allowing better postoperative suppression of recurrence. Best suited to isolated colonic strictures with relatively normal, distensible "skipped" segments in between. Carries a meaningfully higher recurrence risk than more extensive resection, so should always be paired with postoperative chemoprophylaxis.
• Subtotal colectomy with ileorectal anastomosis — suited to patients with relative rectal sparing and an otherwise diseased colon; segmental resection is preferable when there are areas of normal intervening colon. Also carries a higher recurrence rate. Depending on the amount of retained rectum, an ileal pouch–rectal anastomosis can reduce postoperative bowel-movement frequency; may require temporary diversion (loop ileostomy) to support healing depending on anastomotic height.
• Proctocolectomy with IPAA — historically only a passing mention for Crohn's, now considered more often given newer immunosuppressive options, in educated patients without obvious perianal disease who understand the higher morbidity risk and less favorable functional results (more bowel movements) compared with IPAA for UC, and the higher risk of needing conversion to an end ileostomy if fistulizing disease develops. Technique is the same as for UC — see the dedicated procedure page.

Cancer risk (surgical implication): if a cancer is identified, total colectomy (not segmental resection) should be performed — colonic procarcinogenic mutations can track along the colon, and the risk of a subsequent cancer elsewhere in the colon is high.

Cancer/dysplasia epidemiology detail (ASCRS Ch48): CRC causes 1 in 12 IBD-patient deaths. Colitis-associated cancer shares molecular alterations with sporadic CRC but with different timing — APC loss occurs early in sporadic CRC but late in colitis-associated cancer, while p53 loss occurs early in colitis-associated cancer (the reverse of the sporadic sequence) — and cancer development is accelerated by inflammatory activity. Mean age at diagnosis is 51.5 years, about 20 years earlier than the general population. Cumulative CRC risk is 2.9% at 10 years, 5.6% at 20 years, and 8.3% after 30 years of disease; with equivalent duration, CD's cancer risk appears lower than UC's, but this may reflect differences in disease distribution rather than true biological difference (see Inflammatory Bowel Disease's "Colorectal cancer surveillance in IBD" section for the shared surveillance framework, which doesn't yet carry these duration-based cumulative-risk figures). Colorectal strictures carry particularly elevated cancer risk: Yamazaki (132 patients/175 strictures) found malignant strictures in 9 patients (6.8% of stricture patients), all short-segment; a separate 640-patient Hungarian cohort found a 6.5% CRC rate among 62 stricture patients, with all four stricture-associated-CRC patients being male smokers.

Postoperative complications and recurrence: many Crohn's patients are on immunosuppressive medications at the time of surgery and are hypoalbuminemic from protein-losing enteropathy — both raise infectious-complication risk. Steroids and biologics administered within several months preoperatively both increase infectious complication risk (opinions differ on the relative risk by drug class); this should prompt an explicit discussion with the patient about the possibility of a temporary diverting stoma if an anastomosis is being considered. Recurrence risk factors: smoking, age <30 at Crohn's onset, and having already had 2 or more operations for fistulizing disease. Early, intensive medical therapy started soon after surgery may reduce recurrence risk. Regular endoscopic surveillance of the lower GI tract is important to catch recurrent disease before it becomes therapy-resistant fibrosis.

Perioperative steroid/biologic management detail (ASCRS Ch48): HPA-axis recovery after steroid cessation can take as little as 2 days or as long as 1 year (basis for the "stress-dose steroids if steroid-treated within the past year" convention) — but much of that dosing/duration evidence is poorly supported/anecdotal, and perioperative high-dose steroids impair wound healing. Zaghiyan's pilot study gave no perioperative steroids to IBD patients steroid-treated within the year but not on steroids at surgery time, with all cases of hypotension/bradycardia/tachycardia resolving spontaneously without fluid bolus, vasopressor, or steroid rescue — supporting simply maintaining patients on their usual preoperative dose rather than empiric high-dose "stress dosing." Risk of infectious complications is dose-dependent, highest above 40mg prednisolone-equivalent; elective surgery should target weaning off steroids for 1 week preop, or to <20mg-equivalent if complete cessation isn't feasible. 6-MP/azathioprine alone doesn't increase complications, and combined with steroids doesn't further elevate risk beyond steroids alone; no evidence implicates methotrexate; immunomodulators are typically just held the morning of surgery and resumed per the GI plan rather than stopped preoperatively. For biologics (Table 48.2 postop septic-complication risk factors: corticosteroid use, malnutrition/hypoalbuminemia, anemia/acute blood loss, emergency surgery, anti-TNFα therapy, vedolizumab therapy, penetrating disease/fistula/intraoperative abscess, recurrent disease, smoking) — anti-TNFα pharmacokinetic data are conflicting (50% of patients on anti-TNFα at surgery had no detectable preop drug levels, and complications don't correlate with trough levels), with heterogeneous studies both supporting and refuting an anti-TNFα complication link; a reasonable strategy is delaying elective surgery 4 weeks (2 half-lives) from the last dose, or considering temporary diversion with ≥2 other risk factors. Vedolizumab evidence is similarly conflicted but has been linked to increased SSI risk in some studies — delay 6 weeks (2 half-lives) or consider diversion. Ustekinumab does not appear to increase postoperative septic-complication risk. Not yet independently verified against primary literature.

Postoperative recurrence-prevention trial evidence (ASCRS Ch48): Regueiro's small RCT of early postop infliximab (5mg/kg) for 1 year vs. placebo found markedly lower 1-year endoscopic recurrence with infliximab (9.1% vs. 84.6%, P=0.0006). The larger multicenter follow-up PREVENT trial missed its primary clinical-recurrence endpoint, though infliximab patients still had lower endoscopic recurrence scores — a genuine gap between the two trials' conclusions on the same question, not resolved here. De Cruz randomized 174 high-risk patients to early colonoscopy (with treatment step-up guided by recurrence risk) vs. standard clinical observation, and found early-colonoscopy-guided step-up outperformed conventional drug therapy alone for postop recurrence prevention — but even low-risk patients with early remission still warrant ongoing surveillance rather than being considered "done." This complements, without yet being cross-checked against, the Fig. 50.25 risk-stratified surveillance algorithm and the STRIDE/CALM treat-to-target framework already on this page (see "Microbiome therapies, treat-to-target, and trial-level nuance" above).

Nutritional support and TPN (ASCRS Ch48) — genuinely new content, not previously on this page: exclusive enteral nutrition (EEN) induces remission in pediatric Crohn's and is as effective as corticosteroids there (meta-analysis: OR 4.5, 95% CI 1.64-12.32, for intestinal healing vs. corticosteroids); in adults EEN is less effective for inducing remission but may help maintain remission in quiescent disease. Preoperative optimization matters: in one Chinese study, 59.0% of screened patients were at risk for malnutrition (likely an underestimate for a surgical-candidate, failed-medical-management population specifically). Patients with weight loss >10% in 3-6 months, BMI <18.5 kg/m², or albumin <30 g/L benefit from intensive enteral/parenteral nutritional support, reducing SSI and postoperative septic-complication risk. Malnutrition is an independent risk factor for postoperative morbidity/mortality irrespective of immunosuppressive/biologic therapy status.

Surgical treatment (small-bowel-focused, from this chapter chunk)

Surgery does not cure Crohn's; the goal has shifted from radical resection to an operation achieving inflammation-free margins with minimal surgery — removing just grossly inflamed tissue (i.e., dilation or strictureplasty to increase luminal diameter), ignoring adjacent areas of bowel that are clearly diseased if not causing a complication. Fistulizing disease rarely requires operative intervention unless the fistula involves the bladder, vagina, or skin, in which case a bowel resection with fistulotomy may be needed. Early in the history of surgical therapy, wider resections were performed hoping for cure or significant remission; this instead led to a greater incidence of recurrence and short bowel syndrome (a devastating surgical complication). Operative treatment of a complication should be limited to the segment of bowel involved with the complication — no attempt should be made to resect more bowel, even when grossly evident disease is apparent elsewhere. Frozen section is unreliable and should be performed only when malignant disease is suspected. Even after resection of a diseased segment, endoscopic recurrence occurs in up to 70–90% within 1 year.

Primary anastomosis vs. initial ostomy with delayed reconstruction: an important decision given that Crohn's patients are often malnourished, on intensive immunosuppressive therapy, or presenting with intraabdominal sepsis. Standard surgical principles direct the decision: patients with adequate nutrition and minimal intraabdominal sepsis can safely undergo primary anastomosis at the initial operation, whereas malnourished/septic patients are best served by diversion if possible. Surgery is safe for patients on perioperative infliximab or immunosuppression, per large case series, though caution is still warranted in the setting of high-dose immunosuppression.

Anastomotic technique: creating a wider anastomosis with a stapled functional end-to-end technique may decrease fecal stasis and subsequent bacterial overgrowth implicated in anastomotic recurrence. A randomized controlled trial comparing side-to-side stapled vs. end-to-end anastomosis found no difference in overall complication rates, anastomotic leak rates, or symptomatic recurrence rates, with only a slight increase in endoscopic recurrence with end-to-end (43% vs. 38%). A newer antimesenteric functional end-to-end hand-sewn technique (Kono-S anastomosis) was created to minimize anastomotic restenosis and demonstrated a significantly lower rate of stenosis and recurrence in one trial. Although further RCTs are needed, this is a promising novel surgical approach that may decrease the need for additional biologic therapy. See Anastomotic Construction for the full step-by-step Kono-S construction technique (supporting column, antimesenteric incisions, Heineke-Mikulicz closure) and now also the full trial-level evidence (ASCRS Ch48 added: Kono's original 69-vs-73-patient comparison, two further multicenter studies, and the first published RCT — all favoring Kono-S on recurrence/leak — plus the side-to-side-vs-end-to-end RCT/meta-analysis evidence, including the CAST trial), not repeated here.

Surgery-rate context and mesenteric excision (ASCRS Ch48): a Fazio RCT (152 patients, 2cm vs. 12cm proximal resection margin from macroscopic disease) found no difference in recurrence between limited and extended resection, even when microscopic disease was present at the margin — reinforcing that complete extirpation of microscopic disease is not a valid surgical goal. A separate, more recent Irish report comparing wide mesenteric excision with conventional closer division (64 patients) found surgical recurrence of 40% (conventional) vs. 2.9% (wide excision), p=0.003 — but with significant limitations (historical control, non-standardized postop prophylaxis, no anastomotic-technique data) that keep this from being definitive. Not yet independently verified against primary literature.

Laparoscopic surgery is safe and feasible in appropriately selected patients (e.g., localized abscesses, simple intraabdominal fistulas, perianastomotic recurrent disease, disease limited to the distal ileum). A large comparative study evaluating laparoscopic colectomy for Crohn colitis found significantly shorter median operative time, earlier return of bowel function, and shorter hospital stay vs. open. Multiple RCTs confirm more rapid recovery of bowel function and shorter hospital stay with similar disease recurrence rates vs. open procedures; long-term follow-up shows improved body image/cosmesis satisfaction and less incisional hernia incidence with laparoscopic ileocolonic resection. The LIR!C trial (randomized multicenter) found laparoscopic resection of uncomplicated ileocecal disease (terminal ileum <40 cm) that had failed steroid treatment could be an alternative to anti-TNF therapy.

MIS detail and robotic/SILS approaches (ASCRS Ch48): Milsom and Maartense both conducted prospective RCTs of MIS ileocecectomy showing improved postop pulmonary function, morbidity, and LOS vs. open, with long-term follow-up supporting improved body-image perception/cosmesis and decreased bowel-obstruction/hernia risk; evidence does not support the concern that diminished tactile feedback leads to missed strictures or incomplete resection. Robotic MIS is feasible with reduced morbidity/LOS vs. open but longer operative times and no clear demonstrated advantage over laparoscopic MIS yet, though conversion rates are lower than laparoscopy in some series. Intracorporeal anastomosis (avoiding the need to deliver a foreshortened Crohn's mesentery through a small extraction site) may reduce SSI rate; combining it with a small (<4cm) transverse extraction incision may decrease/eliminate incisional hernia. Single-incision laparoscopic surgery has small studies supporting safety but no clear benefit over conventional laparoscopy. Robotic- assisted strictureplasty and a robotic nonresectional intracorporeal side-to-side isoperistaltic anastomosis for stricturing disease have both been described in small series.

Enhanced recovery in IBD: Enhanced Recovery After Surgery (ERAS) (ASCRS Ch7) notes IBD patients have higher baseline perioperative risk on an ERAS pathway (NSQIP data: IBD diagnosis independently associated with prolonged LOS and higher readmission/morbidity/mortality odds vs. non-IBD colectomy; one single-institution study found postoperative ileus in 28.8% of IBD patients vs. 14.8% of colorectal cancer patients on the same protocol) — but still derive net benefit from ERAS (reduced SSI/ileus/anastomotic leak, shorter LOS/lower cost vs. IBD patients on standard perioperative care), just from a higher starting risk. Not yet reflected elsewhere on this page. ASCRS Ch48 adds: a recent review found only about a dozen English-language ERP studies including any IBD patients, and only 28.9% of the total patients across those studies had a stated surgical indication of IBD, with most lacking IBD-specific data (biologic therapy, steroids, immune modulation) — a caution on the evidence base's thinness even though the direction of effect (safe, likely shorter LOS without increased readmission/morbidity) agrees with the ASCRS Ch7 note above.

Specific problems (small bowel)

• Acute ileitis (nonstricturing, nonpenetrating): presents with acute RLQ pain mimicking acute appendicitis; at exploration the appendix is normal but the terminal ileum is edematous, beefy red, with a thickened mesentery and enlarged lymph nodes. This is a self-limited manifestation of early Crohn's, but is often unrelated — bacteriologic agents such as Campylobacter and Yersinia can cause acute ileitis. Intestinal resection should not be performed. In the absence of appendix or cecal inflammation, appendectomy should still be performed (in the absence of clear disease at the appendix/cecum) to eliminate the appendix as a future source of RLQ pain confusion.
• Stricturing disease: intestinal obstruction is the most common indication for surgical therapy in Crohn's, often partial, with nonoperative management indicated initially. Success of nonoperative management can often be predicted by symptom chronicity at the affected site; distinguishing acute exacerbation from chronic stricture can use stool lactoferrin/calprotectin (favor acute inflammation) or genetic markers (e.g., NOD2, TLR4, CX3CR1, which may predict success of medical therapy). For a chronic strictured segment, medical therapy is rarely effective; operative intervention is required for complete obstruction and for partial obstruction not resolving with nonoperative management. The treatment of choice for intestinal obstruction in Crohn's is segmental resection of the involved segment with primary reanastomosis — may involve segmental resection and primary anastomosis of a short ileal segment, or an ileocecectomy if both ileum and cecum are involved (Fig. 50.23). Fibrosis-vs-inflammation distinction (ASCRS Ch48): once obstruction is diagnosed, CT or MR enterography (the current small-bowel imaging standard) is used to assess the relative contribution of fibrosis vs. inflammation, since inflammatory stenoses are likely to respond to medical therapy while fibrotic strictures typically need surgery. CT enterography findings of inflammation include mucosal hyperenhancement, mesenteric fat stranding ("comb sign"), and mesenteric hypervascularity — but CT is not successful at identifying degree of fibrosis, and upstream dilation isn't a reliable discriminator (mesenteric hypervascularity was the only CT finding predictive of fibrosis on multivariate analysis). MRI findings of inflammation include T2 hypersignal, mucosal enhancement, ulceration, and blurred margins; a homogeneous enhancement pattern and percent enhancement gain over time can discriminate severe fibrosis — though most lesions show a mixed pattern. No antifibrotic therapies for stricturing disease currently exist. Endoscopic balloon dilation (new to this page): an alternative that can delay/avoid surgery. Ideal candidate: single short-segment (<4cm) fibrostenotic or anastomotic stricture, without fistula/abscess/marked angulation; dilation diameter ≥14mm, with 16-18mm associated with less frequent re-dilation and >20mm carrying increased perforation/bleeding risk in small bowel strictures; multifocal disease is an independent risk factor for dilation failure. A pooled analysis (Bettenworth; 1463 patients, 3000+ procedures) found 89% overall technical success (anastomotic strictures = 62% of procedures), but at 2-year follow-up three-quarters of patients needed re-dilation and half underwent surgical resection, with major adverse events (perforation, bleeding, sepsis) in 2.8%.
• Strictureplasty: in selected patients with obstruction from single or multiple strictures, an option that widens the lumen while avoiding intestinal resection. Performed via a longitudinal incision through the narrowed area followed by transverse closure — Heineke-Mikulicz style for shorter segments (Fig. 50.24A), or a Finney-pyloroplasty-style/side-to-side isoperistaltic technique for longer diseased segments (>10 cm, Fig. 50.24B). Best used in patients with multiple short areas of narrowing over long segments, those who have had several prior resections, and those with chronic fibrous obstruction. Preserves intestinal length with complication and recurrence rates comparable to resection/reanastomosis. Given concerns about carcinoma at chronically strictured segments, full-thickness biopsy with frozen section at the stricture site has been advocated at the time of strictureplasty to rule out malignant disease before performing it. Contraindications (Box 50.5): excessive tension due to rigid/thickened bowel segments, perforation, fistula/abscess formation at the intended strictureplasty site, hemorrhagic strictures, multiple strictures within a short segment, malnutrition/hypoalbuminemia (<2.0 g/dL), and suspicion of cancer at the intended site. Technique detail and outcome data (ASCRS Ch48): Heineke-Mikulicz suits short-segment (<10cm) strictures; Finney suits 10-25cm strictures; the Jaboulay strictureplasty (also for 10-25cm strictures) spares length via a lateral diverticulum but risks a blind-loop stasis/bacterial- overgrowth complication (Lee, 1982, described it as a short "bypass"). For strictures >25cm, or multiple short strictures in tandem (where repeated Heineke-Mikulicz closures would be unsafe), Michelassi's isoperistaltic side-to-side strictureplasty divides bowel/mesentery at the midpoint of the strictured segment and creates a longitudinal, tapered-end anastomosis between the two loops — one 20-patient series with 7.5-year follow-up showed radiographic/endoscopic/histopathologic regression of previously active disease with restored intestinal function. Early complications (bleeding, sepsis) occur in 8-15% of strictureplasties across techniques. Reese found surgical recurrence more likely after strictureplasty than resection (p=0.09), with a significantly longer recurrence-free interval after resection (p=0.01); overall strictureplasty recurrence rates run 18-29%, though in one study only 4.6% of recurrences were actually at the prior strictureplasty site itself.
• Bypass procedures: historically common, now largely reserved for specific circumstances — two types exist, exclusion bypass (proximal transected ileum anastomosed to transverse colon end-to-side, with or without a distal mucous fistula from the retained ileal segment) and continuity (simple) bypass (side-to-side ileotransverse colonic anastomosis without transection). Currently, bypass with exclusion is used only for severe gastroduodenal Crohn's not amenable to strictureplasty, older poor-risk patients, patients who've had several prior resections and cannot afford to lose more bowel, and select ileocecal-disease patients with an abscess/phlegmon densely adherent to the retroperitoneum where resection would risk entering an abscess or endangering a normal structure.
• Penetrating disease: fistula and abscess formation in Crohn's are relatively common, usually involving adjacent small bowel, colon, or other surrounding viscera (e.g., bladder). A radiographically demonstrable enteroenteral fistula with no sepsis/complications is not itself an indication for surgery. Penetrating disease is particularly sensitive to anticytokine therapy, and a conservative surgical approach to fistula is most appropriate. Enterocutaneous fistulas may develop but are rarely spontaneous, more often following resection or drainage of intraabdominal abscesses; treatment entails fistula outflow reduction, infection prevention, and nutrition/skin care optimization; if conservative management fails, excision of the fistula tract and primary anastomosis is preferred, with preoperative optimization important given that penetrating disease patients tend to have longer operative times, higher reoperation rates, increased length of stay, and more postoperative complications. If fistula forms between two or more adjacent loops of diseased bowel, the involved segments should be excised; if fistula involves an adjacent normal organ (bladder, colon), only the diseased small bowel segment and fistulous tract need be resected, with the defect in the normal organ simply closed. Most patients with ileosigmoid fistulas do not necessarily require resection of the sigmoid unless it is also found to have Crohn's disease, in which case it should be resected along with the diseased small bowel segment. Fistula-location frequency, abscess management, and psoas abscess (ASCRS Ch48): Hirten characterized relative fistula frequency by location — 29% enterocolonic, 18-24% enteroenteric, 6-16% enterocutaneous, 4-9% rectovaginal, 2-8% enterovesical, rare enterosalpingeal/enterogastric — usually originating from the ileocecal region/terminal ileum. Penetration to the retroperitoneum can cause a psoas abscess, prone to epithelialize into a recalcitrant recurrent-abscess source usually requiring surgery; after resection, the cavity may be unroofed/curetted with an omental pedicle flap to aid healing. Small abscesses/phlegmons are initially treated with antibiotics (adding corticosteroids is safe when active inflammatory disease coexists) — Felder's series of 24 patients treated with high-dose corticosteroids for phlegmon found two-thirds resolved completely and the rest shrank >50%, but 58% still eventually needed resection, mostly electively. Accessible intra-abdominal abscesses >3cm should undergo percutaneous drainage (PCD) plus antibiotics (technical success >90%); a 2016 meta-analysis (Clancy, 6 studies/333 patients) comparing primary surgical resection (55%) vs. PCD alone (45%) found significantly higher recurrent-abscess risk with PCD alone (OR 6.54), a 70.7% pooled rate of PCD-alone patients eventually needing surgery, and 17.9% needing surgery even after apparently successful drainage — though up to 30% of PCD patients per this meta-analysis avoided surgery altogether. The ongoing MICA trial (GETAID) is examining predictive factors of anti-TNF response after abscess formation. Müller-Wille found preoperative PCD significantly lowered postoperative septic complications (25% vs. 69% without); Zhang (288 patients, 180 penetrating) found intra-abdominal sepsis specifically — not penetrating behavior alone — predicted worse postoperative outcomes. Not yet independently verified against primary literature.
• Perforation: free perforation into the peritoneal cavity is uncommon in Crohn's. Typically, penetration presents as a localized abscess densely adherent to the diseased segment of bowel rather than free perforation. In cases of free perforation, the segment of involved bowel should be resected, and in the presence of minimal contamination a primary anastomosis can be performed; if generalized peritonitis is present, a safer option may be to create an ostomy until intraabdominal sepsis is controlled, restoring continuity after 4–6 weeks. Abscesses without free perforation can be treated with percutaneous drainage and antibiotics; however, fistula or uncontrolled sepsis may develop, requiring resection with or without primary anastomosis. An abscess smaller than 3 cm, in a patient not on biologics and without an associated fistula, can be treated with antibiotics alone; abscesses not meeting these criteria should undergo percutaneous drainage — early treatment of an abscess is key to resolution regardless of drainage route. Colonic-stricture perforation specifics (ASCRS Ch48): when perforation follows an obstructing small bowel stricture, it typically occurs immediately proximal to the completely obstructing segment (relative closed-loop obstruction) — best treated with resection and primary anastomosis if the patient's condition allows. When it follows an obstructing colonic stricture, the site is more commonly the cecum, best treated with total abdominal colectomy and ileostomy, with the extent of distal resection tailored to whether the distal colon/rectum are disease-free; toxic colitis leading to perforation is managed the same way.
• Gastrointestinal bleeding: anemia from chronic blood loss is common; life-threatening hemorrhage is rare. Hemorrhage is more common with colonic than small bowel Crohn's. As with other complications, the involved segment should be resected and intestinal continuity restored. Arteriography may help localize bleeding before surgery. For bleeding associated with duodenal Crohn's, endoscopic intervention is usually successful; duodenotomy with oversewing of the bleeding ulcerative area is indicated if endoscopy fails. Additional detail (ASCRS Ch48): acute severe GI hemorrhage has a 1-2% incidence overall and does not correlate with disease activity; bleeding can be duodenal, jejunoileal, ileocolic, or colonic. Unlike UC (diffuse mucosal ulceration), Crohn's hemorrhage is more often from a focal erosion into an intestinal vessel or occasionally an inflammatory pseudopolyp, making source localization important to avoid unnecessary resection. Up to 30% of Crohn's patients with hemorrhage have a bleeding duodenal ulcer, and positive gastric lavage should trigger upper endoscopy; colonoscopy within 24 hours locates the source 60-78% of the time (endoscopic control is not often successful but helps localize the bleed for resection). CT angiography and traditional mesenteric angiography can also localize bleeding; when angiography localizes it, methylene blue injection can stain a 10-40cm bowel segment to guide operative resection.
• Urologic complications: occur in up to a third of patients, most commonly ureteral obstruction secondary to ileocolic disease with retroperitoneal inflammatory compression. Surgical treatment of the primary intestinal disease is adequate in most patients; in a few cases of long-standing inflammatory disease, periureteric fibrosis may be present and require ureterolysis with or without ureteral stenting.
• Colorectal disease: the same principle applies to patients with disease limited to the colon as to those with disease limited to the small bowel — surgical resection should be limited to the main segment involved. Indications for surgery include lack of response to medical management and complications of Crohn colitis (obstruction, hemorrhage, perforation, toxic megacolon). Depending on the diseased segments, procedures commonly include segmental colectomy with colocolonic anastomosis, total abdominal colectomy with ileorectal anastomosis, total proctocolectomy with ileoanal anastomosis, and (in patients with extensive perianal and rectal disease) abdominoperineal resection with end ileostomy. Strictureplasty has limited usefulness in colonic Crohn disease, and concerns of malignant transformation at an area of colonic obstruction should limit its application. A particularly troubling problem after abdominoperineal resection in Crohn patients is delayed healing of the perineal wound — more than half of perineal wounds remain open at 6 months. Persistent nonhealing wounds require excision with secondary closure; large cavities/sinuses may need well-vascularized muscle pedicles (gracilis, semimembranosus, rectus abdominis) or omentum, or an inferior gluteal myocutaneous flap. Continence-preserving operations such as IPAA or continent ileostomy (Kock pouch) may be considered in very carefully selected patients with Crohn's isolated to the colon after thorough counseling about increased anastomotic failure/wound complication risk — these procedures should never be considered in patients with evidence of terminal ileal or perianal disease, which carry a significantly increased recurrence rate in the pouch, fistulas to the anastomosis, and peripouch abscesses. Recurrence/reoperation/stoma rates by procedure — Table 48.3 (ASCRS Ch48): segmental resection carries 26-55% colon/rectal disease recurrence, 4-14% small bowel disease recurrence, 11-66% further intestinal surgery, and 5-44% permanent stoma; total abdominal colectomy carries 24-66% colon/rectal recurrence, 8-21% small bowel recurrence, 30% further surgery, 25-50% permanent stoma; total proctocolectomy carries up to 39% small bowel recurrence (colon/rectal recurrence n/a), 9-32% further surgery, and up to 100% permanent stoma. Only total proctocolectomy with end ileostomy minimizes disease-recurrence risk, though even it carries up to 39% small bowel recurrence with up to 32% requiring surgery at 10 years. Smoking is associated with need for further surgery/eventual proctectomy; perianal disease, young age, and female sex are independent risk factors for recurrence and eventual permanent stoma. These figures apply to rectal-sparing Crohn's colitis management, not to patients with dysplasia. IPAA in Crohn's — outcome data (ASCRS Ch48): older retrospective series of patients later found to have Crohn's (rather than the presumed UC) after IPAA showed up to 56% requiring pouch excision, with a further proportion undergoing indefinite diversion — patients with preoperative features suggestive of Crohn's (subtle perianal disease, discontinuous inflammation) did particularly poorly with no meaningful symptom-free interval, though patients who did well had UC-comparable functional results. Two more recent series suggest lower pouch-loss rates: a large Cleveland Clinic series (2013) found 13.3% pouch failure in Crohn's vs. 5.1% in UC; a separate series (Li) of intentional IPAA/ileorectal anastomosis for Crohn's found a 15.5% indefinite-diversion rate. Highly selected patients — Crohn's colitis with no perianal disease and no small bowel disease — may reasonably consider restorative IPAA with aligned patient/surgeon risk tolerance and shared decision-making. This extends, without contradicting, this page's existing brief IPAA mention above. Ileosigmoid fistula management detail (ASCRS Ch48): typically the inflamed terminal ileum adheres to an otherwise disease-free sigmoid colon. More than half of ileosigmoid fistulas are not recognized preoperatively despite imaging/endoscopic evaluation. 75% can be managed by simple division of the fistulous adhesion plus standard terminal-ileal resection, with the sigmoid defect debrided and closed; the remainder require sigmoid colon resection (when the sigmoid itself is Crohn's-involved, the fistulous opening is large, there is extensive sigmoid fibrosis, or the tract enters near the mesentery, which is difficult to close primarily).
• Perianal disease: fissures and fistulas are common, particularly with colonic involvement. Treatment should be nonoperative unless an abscess or complex fistula develops, and even then surgery should be cautious and limited to the specific problem with minimal tissue loss. Nonsuppurative, chronic fistulization or fissuring is treated with antibiotics, immunosuppressive agents (AZT or 6-MP), and infliximab, which has shown the best results in fistula closure as it is most widely supported by evidence; cyclosporine or FK-506 have shown some benefit in several uncontrolled studies. Wide excision of abscesses or fistulas is not indicated; more conservative interventions, including liberal placement of drainage catheters and noncutting setons, are preferable. Definitive fistulotomy is indicated for most patients with superficial, low transsphincteric, and low intersphincteric fistulas, recognizing that some degree of anal stenosis may occur as a result of chronic inflammation — Anal Stenosis (ASCRS Ch12) adds outcome detail: in one 224-patient cohort of anorectal Crohn's complications, 65 presented with anal stenosis, most with stenosis as their only complaint; 17 of a subgroup ultimately required proctectomy or diverting stoma. In a separate 44-patient cohort, 75% underwent mechanical dilation and 43% eventually required proctectomy — figures underscoring real continence/bowel- preservation risk, and a caution that manual dilation itself may worsen scarring/stenosis in this population. High transsphincteric, suprasphincteric, and extrasphincteric fistulas are usually treated with noncutting setons. Fissures are usually lateral, relatively painless, large, and indolent, and often respond to conservative management. Unresolved discrepancy: Anal Fissure (ASCRS Ch12) instead describes Crohn's fissures as "deep, painful ulcerations" — directly conflicting with this page's "relatively painless" characterization above. Both are textbook-level sources; flagged here rather than silently reconciled. Update (2026-08-25): ASCRS Ch47 (now ingested — see "Perianal (anorectal) Crohn's disease" below) also describes atypical CD fissures/cavitating ulcers as causing pain, siding with Ch12 against this page's "relatively painless" Sabiston-sourced text (now 2-against-1) — still not treated as resolved, per this wiki's discrepancy-flagging convention. Abscesses should be drained, but large excisions of tissue should not be performed. Advancement flap closure of perineal fistulas may be required in certain cases. Selective construction of diverting stomas has good results combined with optimal medical therapy to induce remission of inflammation. Proctectomy is infrequent but required in a subset of patients with persistent, unremitting disease despite conservative medical and surgical therapy. Primary-guideline update (BSG 2025 - IBD Guidelines (Adults)): workup should combine pelvic MRI with exam under anaesthesia (± endoanal ultrasound) by an experienced colorectal surgeon — proctitis at assessment predicts worse fistula-healing outcomes (OR 2.85). Infliximab is suggested as first-line biologic for perianal Crohn's, started as soon as adequate sepsis drainage is achieved (pooled anti-TNF data: RR 1.94 for fistula induction of remission, RR 1.79 for maintenance, vs. placebo) — consistent with, and now evidence-graded, what the textbook content above already taught. The PISA-II trial (the only perianal Crohn's surgical RCT since the prior BSG guideline) found MRI-assessed fistula closure higher with combined surgery (advancement flap/LIFT) plus anti-TNF than anti-TNF alone (12% vs 9%). Refractory disease significantly affecting quality of life should be offered faecal stream diversion — reversal rates are low and proctectomy may ultimately still be required. A phase III mesenchymal stem cell therapy trial (Cx601/darvadstrocel + fibrin glue) failed its primary combined-remission endpoint at 24 weeks despite promising phase II data — not yet a viable option outside trials. See the "Perianal (anorectal) Crohn's disease" section below for a discrepancy flag: ASCRS Ch47 cites a positive 212-patient phase 3 adipose-derived-stem-cell trial for the same drug class.
• Duodenal disease: occurs in fewer than 5% of Crohn patients, most commonly in the duodenal bulb. Operative intervention is uncommon; the primary indication for surgery is duodenal obstruction not responding to medical therapy, with endoscopic balloon dilation and surgery being the mainstays of treatment. Gastrojejunostomy to bypass the disease, rather than duodenal resection, is the procedure of choice. Strictureplasty has been performed successfully in selected patients and may avoid the marginal ulceration and diarrhea associated with gastrojejunostomy. Fuller gastroduodenal picture (ASCRS Ch48): clinically significant foregut Crohn's is rare overall (0.5-4% of patients), though 30-50% have macroscopic and 40-70% histologic upper-GI disease on endoscopy; ≥2/3 of these are asymptomatic and >90% have coexisting more-distal disease. Fecal calprotectin is not reliable for gastroduodenal disease. A "bamboo joint"-like appearance in the gastric cardia and Kerckring-fold notching characterize gastric/duodenal Crohn's respectively. Surgery for gastroduodenal disease is uncommon (<1% of all Crohn's surgery at tertiary centers). Gastroduodenal fistulas almost always result from penetration by another diseased site (terminal ileum, transverse colon) rather than primary gastroduodenal disease — takedown requires Kocherization with primary repair (jejunal serosal patch for larger defects). For duodenal stricture, options are stricturoplasty (Heineke-Mikulicz/Finney, preferred for short-segment disease) or bypass (gastroduodenostomy/gastrojejunostomy/duodenojejunostomy, preferred with dense scarring, first/fourth-portion stricturing, or >2 strictures) — bypass carries low morbidity but a 25-33% reoperation rate for marginal ulceration/recurrence; vagotomy does not reduce marginal ulceration and need not be performed. Pancreaticoduodenectomy is reserved for severe ampullary dysfunction/cholangitis only.
• Upper small bowel disease (jejunum/ileum, excluding the terminal ileum) — new to this page (ASCRS Ch48): affects 3-10% of patients; obstruction and sepsis are the most common surgical indications (massive hemorrhage/carcinoma much rarer). As elsewhere, the approach has shifted from extensive resection toward resecting only the macroscopically diseased segment and/or bowel- sparing strictureplasty. Jejunoileitis carries a particularly high reoperation rate (up to 30%) and real short bowel syndrome risk (reported in 8.5% of cases at 20 years post-surgery) — reinforcing the bowel-preservation emphasis running through this page's strictureplasty content above. A significant proportion of small bowel strictures are missed on preoperative workup, so the entire small bowel should be examined at exploration (calibration sphere or cuffed catheter for multifocal disease); fibrostenotic strictures with luminal diameter <20mm are a clear indication for strictureplasty/resection, though cutoffs vary with bowel size and prior resections, and less critical strictures may not mandate treatment in the current medical-therapy era. Marking strictures with metal clips and recording locations/remaining bowel length in the operative report matters for long-term management.

Perianal (anorectal) Crohn's disease (ASCRS Ch47)

A full dedicated treatment — until this ingest, perianal Crohn's was covered only in the brief "Clinical manifestations" mention above and cross-references to Anal Fistula/ Rectovaginal Fistula, both of which explicitly deferred Crohn's-specific fistula management to this "still-pending" chapter.

Epidemiology and pathogenesis: perianal fistula incidence rises sharply with disease location/ extent — 12% with isolated ileal disease, 15% ileocolonic, 41% colonic disease sparing the rectum, 92% combined colonic+rectal disease; perineal fistulas specifically correlate with colonic (rather than isolated ileal) disease. Recurrent fistula activity risk is 48% at 1 year and 59% at 2 years. Two proposed pathogenesis mechanisms: (1) rectal inflammation causing ulcers/shallow fistulas that extend deeper under the pressure of defecation and persistent fecal exposure — thought to explain CD-related fistulas specifically; (2) infected anal glands penetrating the intersphincteric space — thought to explain idiopathic/cryptoglandular fistulas (the mechanism Anal Fistula's cryptoglandular ladder addresses, hence its exclusion of Crohn's fistulas).

Abscess: up to 62% of perianal CD patients develop an anorectal abscess (perianal, ischiorectal, intersphincteric, or supralevator space — ischiorectal most common at 40% of CD-related perirectal abscesses). Perianal/ischiorectal abscesses present with the expected erythema/swelling/tenderness/ fluctuance; intersphincteric/supralevator abscesses may have few overt signs, often needing CT/endorectal ultrasound/MRI for diagnosis. Prompt surgical drainage is required to control sepsis regardless of medical therapy plans — general anesthesia typically advised except for the most superficial collections.

Fistula classification: Parks anatomical classification by relationship to the external sphincter (intersphincteric, transsphincteric, suprasphincteric, extrasphincteric), layered with an AGA empiric simple-vs-complex system specific to CD — simple: low (superficial/low intersphincteric/ low transsphincteric), single external opening, no pain/fluctuance suggesting abscess, no RVF, no anorectal stricture; complex: high (high intersphincteric/high transsphincteric/extrasphincteric/ suprasphincteric), may have multiple openings, may be associated with abscess/RVF/anorectal stricture/active rectal disease at endoscopy.

Diagnosis: multimodal — physical exam (external openings, induration, fluctuance, a palpable "cord" of fistula tract, DRE for internal openings/wall defects/stricture/sphincter tone, anoscopy), examination under anesthesia (EUA), and imaging. A triple-blinded study found EUA, MRI, and endorectal ultrasound (ERUS) individually 91%/87%/91% accurate, with any two modalities combined reaching 100% accuracy. MRI's likelihood ratio for confirming complex disease (22.7) far exceeds clinical exam (2.1) or ERUS (6.2) in a separate comprehensive synthesis, and MRI is regarded as the gold-standard perianal-CD imaging modality by multiple societies including ECCO. EUA without preceding imaging is likely adequate for simple fistulas; preoperative pelvic MRI is recommended before EUA when fistulas are complex.

Medical management: eradicating infection (surgical drainage) is always the first step, followed by endoscopic evaluation for active proctitis requiring treatment. Antibiotics (ciprofloxacin, metronidazole) are used as a bridge to immunosuppressant therapy rather than sole treatment — evidence is modest (a systematic review/meta-analysis found RR 0.8 for reduced fistula drainage, NNT 5) but two RCTs found ciprofloxacin improved response when combined with biologics (73% vs. 39% with infliximab; 71% vs. 47% with adalimumab). Thiopurines are best used combined with anti-TNF rather than as first-line therapy given delayed onset (3+ months) — a meta-analysis found 54% fistula response with thiopurines vs. 21% placebo (OR 4.44) — so they're used to maintain rather than induce fistula closure. Calcineurin inhibitors (tacrolimus, cyclosporine) are reserved for severe/refractory disease given toxicity and the need for close drug-level monitoring. Biologics — concrete RCT-level detail, a level of precision new to the wiki's perianal-Crohn's coverage: infliximab (an 85-patient RCT found ≥50% fistula closure maintained ≥4 weeks in 68%/56% at 5/10 mg/kg vs. 26% placebo; the larger ACCENT II trial, 306 patients, found week-54 complete fistula closure in 39% of infliximab-maintenance patients vs. 19% placebo); adalimumab (CHARM trial: 30% vs. 13% fistula closure at 26 weeks); certolizumab (PRECiSE trials: 54% vs. 43% fistula closure, not statistically significant); vedolizumab (GEMINI 2 subgroup: 28% vs. 11% fistula closure at 14 weeks, 33% vs. 11% at 52 weeks); ustekinumab (small retrospective series: 61%/31% symptom improvement/closure). Combining anti-TNF with thiopurines, ciprofloxacin, or EUA may further improve response, remission durability, and patient tolerance. This is consistent with, and now supplies concrete numbers behind, the BSG-sourced "infliximab suggested as first-line biologic" verdict in "Specific problems" below.

Surgical management — options depend on fistula anatomy, complicating factors (proctitis, abscess), and disease activity; both fistulotomy and definitive repair should be avoided in active proctitis/abscess given wound-healing/failure risk:

• Fistulotomy: safe for simple fistulas without proctitis; one series of 41 fistulotomies found 73%/93% wound healing at 3/6 months with 12% minor incontinence. CDAI >150 has been suggested as a relative contraindication.
• Draining seton: for complex fistulas without abscess, typically placed at EUA alongside medical therapy — loose, thin, silastic setons maintain tract patency, decrease inflammation, and help prevent recurrent abscess. May remain months to years; removal is coordinated with the gastroenterology team, typically once active proctitis is medically addressed and after anti-TNF induction is complete. A systematic review of 10 studies/305 seton+anti-TNF patients found closure rates 13.6–100% and recurrence 0–83% — wide variability reflecting heterogeneous disease severity and follow-up.
• Endorectal advancement flap: for CD patients without active proctitis — success rates ~60–64% reported, though with recurrence up to 57% and incontinence up to 9.4% in various series; concomitant small bowel disease and smoking both predict worse outcomes. Relative contraindications: proctitis, cavitating ulceration, anal stenosis. The "advancement rectal sleeve" (circumferential excision of anal-canal mucosa from dentate line to anorectal ring, full- thickness rectal flap mobilization, anastomosis to the dentate line) is a described alternative for severe, complex disease when proctectomy is being considered.
• LIFT (Ligation of the Intersphincteric Fistula Tract): two small retrospective series — 67% healing at 12 months in 15 patients with no incontinence in one; 75%/33% healing at <1yr/>1yr follow-up in the other, with better outcomes in small-bowel-predominant vs. colonic CD.
• Fibrin glue and fistula plugs: highly variable reported healing (0–100%, small case series with short follow-up); one multicenter RCT found fistula plug and seton-removal-alone had similar efficacy in CD patients.
• Mesenchymal stem cell therapy: a phase 3 RCT of 212 CD patients with complex fistulas found adipose-derived stem cell injection achieved significantly higher fistula closure than placebo (56.3% vs. 38.6%, p=0.010) with shorter time to remission; a meta-analysis of 11 studies found improved healing with MSCs vs. placebo at both 6–24 weeks (OR 3.06) and 24–52 weeks (OR 2.37).

Discrepancy, not resolved: the BSG-sourced bullet in "Specific problems" below cites "a phase III mesenchymal stem cell therapy trial (Cx601/darvadstrocel + fibrin glue)" that failed its primary combined-remission endpoint at 24 weeks — apparently the same drug (Cx601/darvadstrocel is adipose-derived stem cell therapy) as this chapter's positive 212-patient trial. Both are plausibly real and non-contradictory (Cx601/darvadstrocel had an earlier EU-approved positive pivotal trial and a later negative confirmatory/US trial that blocked FDA approval), but the wiki has not independently verified which trial is which — flagged here rather than silently reconciled. See BSG 2025 - IBD Guidelines (Adults) for the source of the negative citation.

Rectovaginal fistula in CD: ~10% incidence in CD women, median onset age 34, most associated with colonic disease distribution. See Rectovaginal Fistula for full surgical-technique detail (advancement flap, Martius flap, gracilis flap) — that page's existing 10-patient uncontrolled stem-cell series has now been complemented by this chapter's phase 3 RCT data above (subject to the same discrepancy flag), and a separate smaller RCT of stem cell injection specifically for RVF found 51% vs. 35% remission at 24 weeks. Up to 60% of CD-RVF patients require temporary fecal diversion, up to half require a permanent stoma.

Non-fistulizing complications:

• Anal fissures and ulcers: fissures with an idiopathic appearance are treated like non-CD fissures; atypical CD fissures are often multiple, off-midline, with a granulating base and overhanging edges (occasionally progressing to large cavitating ulcers with significant tissue loss). Sphincter-tone-lowering therapies (botulinum toxin, lateral internal sphincterotomy) should generally be avoided given the hypotonic sphincters and continence risk many CD patients already carry — LIS may still suit a select subgroup with a single characteristic midline fissure, hypertonic sphincter, and disease-free rectum. Systemic anti-TNF therapy is the treatment gold standard (one large retrospective study: 43% complete healing, maintained in 73% of responders at 175 weeks); the likelihood of eventual anoproctectomy is ~80% in patients with cavitating ulcers specifically.
• Skin tags: Type 1 (edematous, tender, sometimes cyanotic — sequelae of fissures/ulcers/ hemorrhoids via lymphedema) vs. Type 2 (painless, broad-to-narrow "elephant ear" tags, often multiple; ~19% cumulative 10-year incidence). Generally managed conservatively (sitz baths, hygiene); excision reserved for remission-phase patients with hygiene/quality-of-life impact, given uncertain complication risk in active disease.
• Hemorrhoids: uncommon in CD (only 20 of 50,000 hemorrhoid patients in one cohort had CD). Poor historical surgical outcomes with hemorrhoidectomy in CD likely reflect an association with severe distal disease rather than the procedure itself causing harm; a modern series of 36 CD patients undergoing excisional hemorrhoidectomy found only 4 complications, suggesting carefully selected patients (luminal remission, no steroids, CDAI <150) may do well — but conservative management remains generally preferred.
• Anal stricture: occurs in 17% of perianal CD, rarely without other perianal disease. Asymptomatic strictures don't require specific treatment beyond addressing underlying proctitis/ perianal disease; symptomatic strictures are dilated (manual, balloon, or Hegar), often repeatedly — repeat dilation should not be regarded as treatment failure so long as symptomatic relief occurs between dilations. About half of patients with anorectal stricture eventually undergo proctectomy.
• Anal cancer: adenocarcinoma and squamous cell carcinoma risk both increased with long- standing perianal CD, arising within the anal canal or in chronic fistula tracts. A long-standing previously-asymptomatic fistula that acutely becomes symptomatic, or a newly inflamed chronic fissure, should raise suspicion for malignant degeneration given the tendency for late diagnosis. Treatment mirrors sporadic anal cancer.

Diversion and proctectomy: severe perianal CD requires temporary or permanent fecal diversion in 10–20% of cases, with risk increased by active rectal disease and anal stricture. A staged approach to complete proctectomy is often most appropriate when active inflammation is present: rectal transection at the levator level with a permanent stoma first, followed by a limited perineal anoproctectomy once the patient has recovered, using an intersphincteric dissection that spares the external sphincter to minimize perineal wound size/risk. Primary perineal-wound closure is associated with poor healing in up to one-third of patients with CD; nonhealing wounds may require skin grafting or myocutaneous flap reconstruction.

Prognosis

Crohn disease is a chronic inflammatory disorder that is not medically or surgically curable; therefore therapeutic approaches aim to induce and maintain symptomatic control, improve quality of life, and minimize long-term complications. Approximately 71% of patients require surgery within 10 years of diagnosis, and 50% require a second procedure within 20 years.

Era context (ASCRS Ch48): this Sabiston-sourced 71%-at-10-years figure matches almost exactly the older of two cohorts Ch48 cites — patients diagnosed 1955-1989 (73% overall, 71% at 10 years). A more recent cohort diagnosed 2003-2004 and followed to 2011 found only 29% overall required surgery (28.5% at 7 years) — a marked decline attributed more to earlier diagnosis/increased corticosteroid use than to biologics specifically. Not a discrepancy (both figures are accurate for their respective eras) but worth reading this page's 71%/10-year figure as historical rather than reflective of current practice. Symptomatic recurrence varies from 40% to 80%; endoscopic recurrence is much higher, with up to 90% of patients having visible lesions within 5 years. Smoking cessation is the only clearly modifiable risk factor. Surgery is generally indicated when the patient fails to respond to medical therapy or develops complications; multiple studies show significant quality-of-life improvement after surgical intervention. Although postsurgical recurrence is high, algorithms using careful endoscopic surveillance combined with maintenance immunomodulators, anti-TNF antibodies, anti-integrin therapy, and even investigational traditional Chinese medicine all play a role in preventing postoperative recurrence (Fig. 50.25's algorithm stratifies patients by predicted risk of clinical recurrence — "high"-risk patients go straight to anti-TNF or AZT/6-MP with surveillance endoscopy, "low"-risk patients start with 3 months of metronidazole before surveillance endoscopy — with therapy escalated or continued based on whether endoscopic recurrence is found). Standardized mortality rates increase in patients whose disease began before age 20 and in those who have had disease for longer than 13 years. Long-term survival studies suggest a death rate approximately two to three times higher than the general population, most commonly related to chronic wound complications and sepsis. Gastrointestinal cancer is the leading cause of disease-related deaths in Crohn patients; other causes include sepsis, thromboembolic complications, and electrolyte disorders.

Open items / gaps

• ASCRS Ch48 ("Crohn's Disease: Surgical Management") reconciled into the existing Sabiston- sourced surgical sections throughout this page rather than as a standalone new section, since most of its content deepened material already here. New additions: declining surgery-rate trend data by era (see "Era context" under Prognosis); CT/MR enterography fibrosis-vs-inflammation imaging distinction and endoscopic balloon dilation outcome data for obstruction; Hirten's fistula- location frequency and detailed abscess/percutaneous-drainage/psoas-abscess management for penetrating disease; colonic-stricture-perforation specifics; expanded cancer/dysplasia epidemiology (age at diagnosis, cumulative risk by duration, stricture-associated-cancer cohort data); expanded GI bleeding localization detail; a new nutritional-support/TPN subsection; a new perioperative steroid and biologic (anti-TNF/vedolizumab/ustekinumab) management subsection including Table 48.2 risk factors; substantially expanded anastomotic-type trial evidence (moved primarily to Anastomotic Construction, summarized here); postoperative recurrence-prevention trial evidence (Regueiro, PREVENT, De Cruz); expanded MIS/robotic/SILS detail and an ERP evidence- quality caveat; expanded strictureplasty technique/outcome detail; Table 48.3 recurrence/stoma rates by colonic procedure type; IPAA-in-Crohn's outcome data; ileosigmoid fistula management detail; and a full gastroduodenal-disease picture plus a new "Upper small bowel disease" bullet. Every named trial/study in this batch (Fazio's margin RCT, Muñoz-Juárez, CAST, the German RCT, the Irish mesenteric-excision report, Regueiro, PREVENT, De Cruz, Bettenworth, Clancy, Zhang, Felder, Yamazaki, the Hungarian stricture cohort, Zaghiyan, Reese, the Cleveland Clinic/Li IPAA series) is textbook/secondary-level only, not independently verified against primary literature. No new discrepancies were identified — Ch48's content was consistent with what was already on this page.
• ASCRS Ch47 supplied the previously "still-pending" full perianal-Crohn's treatment — see "Perianal (anorectal) Crohn's disease" above, full chapter summary on ASCRS Ch47 - Anorectal Crohn's Disease. Resolves three other pages' explicitly-flagged pending cross-links (Anal Fistula, Anal Stenosis, Hemorrhoids) and extends (without resolving) the existing Crohn's-fissure pain-characterization discrepancy with Anal Fissure — now 2-against-1 against the Sabiston-sourced "relatively painless" text. Also flags a new, unresolved discrepancy of its own: this chapter's positive 212-patient phase 3 mesenchymal-stem-cell-therapy trial (56.3% vs. 38.6% closure) vs. the BSG-sourced bullet elsewhere on this page citing a failed phase III trial of the same drug class (Cx601/darvadstrocel) — plausibly two different (EU-positive vs. US-negative) trials of the same drug, but not independently verified. Every named trial in Ch47 (ACCENT II, CHARM, PRECiSE, GEMINI 2, the 212-patient stem-cell RCT) is textbook/secondary-level only.
• ASCRS Ch46 added microbiome-therapy coverage, named combination-therapy/treat-to-target/TDM trials, biosimilar data, and postoperative-recurrence risk factors — see "Microbiome therapies, treat-to-target, and trial-level nuance" above, full chapter summary on ASCRS Ch46 - Medical Therapy for Crohn's Disease. Flags a genuine unresolved tension in TDM evidence (TAXIT/PAILOT positive vs. TAILORIX negative) and in combination-therapy evidence (SONIC positive for infliximab vs. DIAMOND equivocal for adalimumab) rather than resolving them. Also flags an important safety note not previously in the wiki: EBV-positive young men on thiopurine therapy carry a small but real hepatocellular T-cell lymphoma risk. Every named trial (SONIC, REACT/REACT2, DIAMOND, CALM, TAXIT, TAILORIX, PAILOT, the infliximab-dyyb non-inferiority RCT, the FMT pilot RCT) is textbook/secondary-level only. Chapter 47 ("Anorectal Crohn's Disease") begins next — flagged as a likely reconciliation target against this page's existing perianal-disease content and the ASCRS Ch13/14/15 fistula pages.
• ASCRS Ch44 added diagnostic-scoring detail: Paris pediatric classification (Montreal extension), Rutgeerts score grading (i0–i4), SES-CD's four graded domains, the pANCA+ASCA combined-testing stat, an MRE multicenter accuracy note, and NUDT15 as a second pre-thiopurine pharmacogenomic test alongside TPMT. Also flagged: even expert-pathologist UC-vs-Crohn's histologic accuracy is only 64–74%, reinforcing that diagnosis stays multimodal. See ASCRS Ch44 - IBD Diagnosis and Evaluation for the full chapter summary and Inflammatory Bowel Disease for shared cross-cutting detail (IBD-U rates, imaging, activity scoring systems, CRC surveillance framework).
• Medical management now has primary-guideline backing (see "Advanced therapy, monitoring, and post-surgical management" above, from BSG 2025 - IBD Guidelines (Adults)) — this was the wiki's single biggest IBD gap and is now closed. Not yet cross-checked against any Crohn's-specific ACG or AGA guideline (only UC-specific versions of those have been ingested). Note vedolizumab's Crohn's-specific "not suggested" stance is a genuine efficacy finding, not a guideline-methodology disagreement — see BSG 2025 - IBD Guidelines (Adults)'s limitations note for why this differs from vedolizumab's favorable UC positioning.
• No primary trial data yet on segmental vs. more extensive resection recurrence rates specifically (as opposed to the general post-surgical advanced-therapy recommendations now added above), or on specific postoperative chemoprophylaxis regimen head-to-head efficacy beyond what's summarized above.
• Perianal Crohn's fistula management now has a dedicated subsection above (setons, fistulotomy, infliximab, diverting stoma, proctectomy), but LIFT and other anal-fistula-specific surgical techniques familiar from cryptoglandular fistula management are not discussed by either source chapter — worth checking primary literature if this becomes clinically relevant.
• The Colon and Rectum chapter chunk's preference for hand-sewn end-to-end ileocolic anastomosis and this Small Bowel chapter chunk's more nuanced discussion (stapled functional end-to-end vs. hand-sewn end-to-end vs. Kono-S) are not fully reconciled here — both are presented as the respective source chapters describe them; worth flagging if primary-literature ingest later clarifies current practice consensus.
• Short bowel syndrome, mentioned here only as a historical cautionary consequence of overly wide resection, is not yet developed as its own topic — expected later in this same chapter (Miscellaneous Problems section).