Inflammatory Bowel Disease

Umbrella page for material shared by Ulcerative Colitis and Crohn Disease — epidemiology, classification, clinical features, diagnosis, and medical treatment. Surgical indications/options are disease-specific and live on the individual UC and Crohn's pages. Epidemiology/classification/ clinical-features/diagnosis content is drawn from textbook reference chapters (Sabiston Ch52 - Inflammatory Bowel Disease, ASCRS Ch43 - Inflammatory Bowel Disease Pathobiology), not primary literature; the therapeutic-drug-monitoring, pregnancy, and perioperative-management sections further below are guideline-backed (BSG 2025 - IBD Guidelines (Adults)).

Epidemiology and etiology

Largely a disease of the Western world, though incidence is rising elsewhere as diets westernize. US prevalence: IBD in >1 million individuals; UC has the highest reported incidence in Europe (followed by US), Crohn's the highest in the US (followed by Europe); Europe has the highest overall IBD prevalence.

Genetic predisposition: >10% of IBD patients have a family history; genome-wide association studies have linked >230 IBD susceptibility loci.
Smoking is the most-studied environmental factor and has opposite effects: suppresses UC symptoms, exacerbates Crohn's.
Early-life antibiotic use and NSAID use have both been proposed as predisposing factors.

Pathobiology (below) draws on ASCRS Ch43 - Inflammatory Bowel Disease Pathobiology, which frames IBD as arising from a complex, incompletely understood interaction between host factors (genetics, immunity) and environmental factors (urbanization, diet, smoking, NSAIDs), mediated through the intestinal microbiome — no single organism or gene has been identified as solely responsible.

Host factors: genetics

Population-based studies show an eight- to tenfold greater risk of IBD among relatives of UC/CD patients; monozygotic-twin concordance is 50% for Crohn's vs. <10% in dizygotic twins (CD has a stronger genetic component than UC, where monozygotic concordance is only 10–15%). Most genetic susceptibility is polygenic (hundreds of contributing loci, each individually accounting for only a small fraction of disease variance — 13.1% for CD, 8.2% for UC), but rare monogenic defects cause early-onset (<5 years) and very-early-onset (<2 years) CD via epithelial-barrier disruption and impaired bacterial clearance (defects in IL-10 signaling or regulatory T-cell activity are a recognized cause). NOD2 (an intracellular bacterial-product receptor, discovered 2001) was the first identified CD susceptibility gene — NOD2-defective dendritic cells show impaired autophagy induction and bacterial clearance; IRGM and ATG16L1 (also autophagy-related) implicate innate immunity/autophagy/phagocytosis broadly in CD pathogenesis; IL23R and PTPN2 link CD to other autoimmune disease. Epigenetic mechanisms (DNA methylation, histone modification, microRNA-mediated post-transcriptional regulation) are an emerging area — DNA methylation differences exist between normal and inflamed CD/UC tissue, and IBD patients have distinct miRNA expression profiles in both target organs and peripheral blood.

Host factors: immunity

The mucosal immune system normally maintains a delicate balance of controlled inflammation (Th1, Th17, Th2, Th3, Th9, and Treg cell populations); in IBD, the adaptive immune system responds to self-antigens, driving chronic inflammation and tissue damage. UC has traditionally been framed as a Th2-mediated disease and CD as Th1-mediated, though the underlying mechanisms are increasingly understood as interrelated and more complex than this dichotomy suggests. Key cytokine roles: IL-17 and IL-22 initiate/amplify local inflammatory signals and promote colitis-inducing counter-regulatory mechanisms; IFN-γ (triggered by macrophage/dendritic-cell IL-2 release via STAT4 activation) drives innate-immune inflammatory cytokine production; IL-1 activates T cells to produce IL-8/IL-6; IL-6 helps differentiate Th17 and Treg cells; IL-12 promotes Th1 differentiation; IL-23 stimulates IL-17/TNF-α/IL-6 production; TNF-α acts on Th2 surface receptors, promoting macrophage proliferation and inhibiting Treg cells. The first line of mucosal defense is the epithelium itself (Paneth cells producing antimicrobial peptides), followed by lamina propria macrophages/dendritic cells (innate response) and T/B cells plus Peyer's patches (adaptive response, gut-associated lymphoid tissue).

Intestinal microbiome

Gut microbiota composition in IBD patients differs significantly from healthy controls: decreased diversity/richness overall; increased Fusobacterium and Proteobacteria phylum members (Enterobacteriaceae, E. coli); decreased Firmicutes (e.g. Faecalibacterium prausnitzii, Ruminococcus, Oscillibacter) and Bacteroidetes.

Corroborates, and extends, an existing flagged discrepancy: this chapter's Firmicutes/ Bacteroidetes-decreased framing agrees with the original Sabiston-sourced description on Crohn Disease, not with Colonic Physiology (ASCRS Ch. 2)'s report of elevated Bacteroidetes in Crohn's — see the existing flag on Crohn Disease. Now 2-against-1 across the wiki's sources, but still not silently resolved; gut-microbiome IBD findings are known to vary by cohort/methodology.

This dysbiosis is not seen in unaffected twins/relatives, suggesting it reflects disease state or environmental effects rather than genetics alone. Table 43.1 (source chapter) catalogs specific organisms studied as candidate IBD drivers across bacteria (Mycobacterium avium, E. coli, the Firmicutes/Bacteroidetes genera above), viruses (Caudovirales bacteriophages, Synechococcus phage S, Retroviridae), and fungi (Saccharomyces cerevisiae, Candida albicans) — but no single organism has been established as sufficient to cause disease (e.g. adherent-invasive E. coli strains found in Crohn's lesions are also present in 33% of healthy controls). Virome and mycobiome changes appear to occur independently of bacterial-composition changes. Antimicrobial agents strongly influence microbiome composition/diversity; case-control and cohort data support antibiotic exposure as an IBD risk factor — a meta-analysis of 8 case-control/3 cohort studies (7,208 patients) found antibiotic exposure significantly associated with Crohn's disease (OR 1.74) but not ulcerative colitis (OR 1.08), with metronidazole and fluoroquinolones the most strongly implicated individual classes.

Environmental factors

Urbanization: IBD prevalence remains highest in wealthy Western countries, but incidence is rising sharply in newly industrializing nations across Asia, Africa, South America, and the Middle East as lifestyle/diet/smoking/pollution/healthcare-delivery patterns westernize (e.g. Brazil's UC incidence rose from 1.0 to 4.5/100,000 between 1986–2005; Hong Kong's IBD incidence rose from 1.3–2.1/100,000 having been barely recognized in the 1960s–1980s) — strong evidence that environmental factors play a major pathogenic role, and growing up in a rural environment is significantly protective (IRR 0.58).

Smoking: confirms and quantifies the opposite-direction effect already noted above — active/ passive smoking roughly doubles CD risk (OR 1.76) and increases fistula/stricture/surgery risk, while being significantly protective against UC (OR 0.58 in a 13-study meta-analysis). The mechanism is unclear but may involve microvascular/oxidative-stress-mediated changes to gut barrier function, mucus production, and the microbiome; genetic polymorphisms in nicotine-metabolizing enzymes (CYP2A6, GSTP1) may modulate individual susceptibility to smoking's divergent CD/UC effects.

NSAIDs: evidence is mixed and dose-dependent. High-dose/frequent NSAID use (>5×/month) is associated with a greater risk of active CD (RR 1.65) and with increased risk of developing both CD and UC at ≥15 uses/month; low-dose NSAID use (<200mg/day, less than daily) was not associated with increased disease activity in one cohort. A 2018 systematic review/meta-analysis of 18 publications found NSAID use overall not significantly associated with CD or UC exacerbation, while acetaminophen use was not associated with exacerbation in any study reviewed. Proposed mechanisms center on cyclooxygenase (COX-1/COX-2) inhibition and loss of the prostaglandin-mediated mucosal-defense/wound- healing/immune-modulation functions those enzymes support.

Diet: a Cochrane review found the effect of dietary interventions on CD/UC uncertain, though observational data associate greater meat/animal-product consumption with IBD onset and greater fruit/vegetable consumption with lower incidence; proposed mechanisms include direct microbiome alteration and indirect effects on mucosal barrier/gut enzymes/bile acids/hormones.

Classification

UC graded by extent: proctitis/proctosigmoiditis (rectum/sigmoid only), left-sided, or pancolitis (entire colon). Formalized in the Montreal classification (E1 ulcerative proctitis, E2 left-sided disease to the splenic flexure, E3 extensive/pancolitis proximal to the splenic flexure) plus a severity axis (S0 clinical remission, S1 mild ≤4 bloody BM/day with no systemic toxicity, S2 moderate ≥5 BM/day with mild toxicity, S3 severe ≥6 bloody BM/day with toxicity — severity in pediatric patients (Paris classification) instead uses the Pediatric Ulcerative Colitis Activity Index, PUCAI >65 defining "ever severe"). Both classifications have demonstrated high inter-observer agreement. See Ulcerative Colitis for how this compares to the newer, more multidimensional ACG UC Disease Activity Index.
Crohn's: originally the Vienna Classification, updated to the Montreal Classification — classifies by age of onset, bowel location, and disease behavior (inflammatory, fibrostenotic, or fistulizing), plus a perianal-disease subdivision. Many patients progress inflammatory → fibrostenotic → fistulizing over time (abscess formation when a fibrostenotic segment perforates and drains into an adjacent structure). Top-down medical therapy aims to interrupt this progression before it reaches fibrosis/fistulization. Full detail (incl. the pediatric Paris-classification modifications) on Crohn Disease's own Montreal classification section.
Endoscopic and clinical activity scoring systems (Mayo endoscopic subscore, SES-CD, Rutgeerts score, CDAI, Harvey-Bradshaw Index, and newer PROMs) are a distinct, genuinely new topic for the wiki — see the dedicated section below.

Clinical presentation

Diarrhea is common to both, but bloody diarrhea/significant hemorrhage is much more common in UC (UC also brings tenesmus, urgency, anemia); abdominal pain tends to predominate in Crohn's. Stool cultures should be obtained first in any new presentation to exclude infectious causes (Salmonella, Giardia, community-acquired C. difficile).

Perianal Crohn's (~25% of Crohn's patients): large anal skin tags (bluish, waxy — not true hemorrhoids, should not be excised due to delayed wound healing), anal fissures (often painless, may be multiple — unlike typical non-Crohn's fissures), anorectal abscesses/fistulas, anal stenosis. Always perform a DRE.

Extraintestinal manifestations

Up to half of IBD patients have one or more; slightly more prevalent in Crohn's than UC.

Joints (most common): arthritis broadly; sacroiliitis is one of the most common single manifestations; ankylosing spondylitis (HLA-B27 positive) can progress to decreased cervical flexion — anesthesia-relevant, may need fiberoptic intubation.
Skin: erythema nodosum (red, painful, swollen nodules — responds to systemic steroids) and pyoderma gangrenosum (extremely painful ulcerating lesions at sites of trauma, surgical incisions, or stomas). "Pathergy" — pyoderma worsens with surgical manipulation/debridement, so it should be treated nonoperatively (intralesional steroids, topical tacrolimus, biologics), not surgically.
Eyes: uveitis, iritis, episcleritis — refer to ophthalmology.
Hepatobiliary — primary sclerosing cholangitis-IBD: affects ~2% of IBD overall (pooled), substantially higher in ulcerative colitis than Crohn's; conversely, most PSC patients (often

50–80%) have concurrent IBD. Runs a course largely independent of bowel disease activity, can progress to cirrhosis/liver failure/transplant. PSC-IBD is a distinct phenotype (BSG 2025 - IBD Guidelines (Adults)): pan-colonic or right-sided colitis with relative/absolute rectal sparing, backwash ileitis, and a milder symptomatic course (less corticosteroid use, fewer hospitalisations) that can mask ongoing risk — histologic inflammation is often mild with focal basal plasmacytosis rather than typical UC-pattern changes. Despite the milder symptomatic course, PSC-IBD carries a 3–4x increased colorectal dysplasia/cancer risk versus IBD alone (OR 3.24) and a 4x risk versus non-IBD PSC patients diagnosed under 40 — annual surveillance colonoscopy is recommended from 8 years after IBD symptom onset, or from PSC diagnosis if that comes first, continuing even post-liver-transplant (lifelong high-risk category). Higher pouchitis rates after IPAA in PSC-IBD (14–90% across studies), though pouch failure rates are similar to non-PSC IBD — relevant cross-link to Ulcerative Colitis surveillance and Ileal Pouch-Anal Anastomosis (IPAA).
Joints — spondyloarthropathy, drug-specific guidance (BSG 2025 - IBD Guidelines (Adults)): anti-TNF is first-line for concurrent axial/peripheral spondyloarthropathy (SpA) and IBD. Ustekinumab and risankizumab are licensed for IBD + psoriatic arthritis/psoriasis but not for axial SpA specifically; tofacitinib and upadacitinib have UK licences spanning UC/Crohn's and PsA/axial SpA to varying degrees (tofacitinib not licensed for Crohn's). Etanercept, abatacept, secukinumab, ixekizumab, and brodalumab should be avoided in IBD patients with concurrent SpA — they lack IBD efficacy and carry a risk of causing IBD exacerbation (etanercept specifically linked to IBD relapse when used for SpA). Separately, anti-TNF therapy itself can paradoxically induce psoriasis/psoriasiform rash in 2–5% of treated IBD patients (risk factors: smoking, ileocolonic Crohn's, female sex, younger age at initiation) — this doesn't automatically warrant anti-TNF discontinuation; options include topical management, in-class drug switch, or biologic class change depending on severity.
EIM-activity association framework (ASCRS Ch44, Table 44.2): EIMs are usefully stratified by whether they track intestinal disease activity or not, which shapes management — treating the bowel disease may not resolve an EIM that runs its own independent course. Associated with intestinal activity: oral aphthous ulcers, erythema nodosum, peripheral arthropathy, episcleritis. Unclear association: pyoderma gangrenosum, ankylosing spondylitis-adjacent peripheral arthropathy patterns. No association with intestinal activity: ankylosing spondylitis itself, uveitis, PSC — consistent with PSC's "independent course" framing above.
Other common manifestations of IBD activity/treatment (distinct from classic EIMs): anemia (iron deficiency from chronic blood loss/malabsorption, or anemia of chronic disease), osteopenia/ osteoporosis (chronic inflammation + corticosteroid exposure), cholelithiasis, nephrolithiasis, tubulointerstitial nephritis, and venous thromboembolism (VTE risk detailed in the Perioperative management section below).

Diagnosis

Endoscopy is the primary diagnostic method — colonoscopy to assess extent and examine the terminal ileum.

UC: inflammation begins at the dentate line and extends proximally, continuously (no skip lesions). Endoscopic severity is commonly graded with the Mayo Clinic Scoring System (grade 1 normal-ish → grade 4 significant bleeding/friability).
Crohn's: patchy/discontinuous ("skip") inflammation; deeper, punched-out ulcerations covered with fibrin; longer serpiginous ulcers described as "bear claw" ulcerations, often worse on the mesenteric side. Ileocolic distribution in nearly half of patients, followed by colonic-only involvement; can also affect small bowel or upper GI tract. Terminal ileum intubation is important when Crohn's is suspected.

Histology:

UC: neutrophils in the lamina propria, goblet-cell mucin depletion, crypt abscesses (nonspecific), inflammation restricted to the mucosa (superficial), continuous — no transmural sinus tracts, deep fissuring ulcers, or granulomas in an area that isn't deeply ulcerated.
Crohn's: transmural inflammation (seen on resected specimens); noncaseating granulomas in roughly a third of patients; transmural lymphoid aggregates in non-deeply-ulcerated areas; "skip"/patchy involvement, sometimes called "focal active enteritis" on biopsy.
Differential for both: infectious colitis, drug-induced colitis.

IBD undetermined / indeterminate colitis: up to 10–15% of patients have overlapping UC/Crohn's features on biopsy. "Indeterminate colitis" is specifically the diagnosis made on a colectomy specimen when features of both are present — more common in fulminant disease where heavy inflammation obscures precise classification.

Extended detail (ASCRS Ch44): before colectomy, this ambiguous presentation is labelled IBD-Unclassified (IBD-U) rather than indeterminate colitis — a distinction based on specimen type, not disease biology. IBD-U affects ~10% of adult-onset and up to 30% of pediatric-onset IBD. About a quarter of patients labelled IBD-U are ultimately reclassified within 5 years of diagnosis, two-thirds of those to UC. Pathologists' inter-observer accuracy at distinguishing UC from CD on biopsy is only 64–74% even among expert GI pathologists — histology is a valuable component of the diagnostic picture, but not a standalone arbiter.

Distinguishing features (ASCRS Ch44, Table 44.1) — consolidating the histology/endoscopy bullets above into a single comparison: Crohn's can involve any part of the GI tract with often skip lesions and full-thickness bowel-wall involvement, creeping fat, possible fistulas, common deep ulceration/fissures, and common strictures; UC is limited to the distal rectum extending proximally in continuous fashion (rare skip lesions, and only as a consequence of treatment response) with mucosal-only involvement (unless fulminant colitis), no creeping fat, rare fistulas, deep ulceration/fissures only in fulminant colitis, and rare strictures. On histology specifically (Table 44.4): Paneth cell metaplasia is present in UC but uncommon in CD; pyloric gland metaplasia is rare in UC but present in CD (both are markers of chronic mucosal injury/repair, just distributed differently by disease); neuronal hyperplasia and muscular hypertrophy are common/present findings that are comparatively rare/absent in UC.

Extended PSC-IBD detail (ASCRS Ch44) — extends the PSC-IBD entry above: the histologic milder- symptomatic-course pattern is corroborated (higher endoscopic-activity/medical-treatment-response rate despite milder symptoms); adds two surgically-relevant findings not previously on this page — timing of colectomy relative to liver transplantation for PSC is associated with post-transplant prognosis (implying colectomy-timing decisions in PSC-IBD patients should weigh transplant planning, not just colonic disease activity), and restorative ileoanal pouch reconstruction after liver transplantation for PSC is associated with poorer pouch graft survival than IPAA performed outside the transplant context — a consideration for surgical counseling in this population, not yet elaborated further on Ileal Pouch-Anal Anastomosis (IPAA).

Laboratory evaluation (ASCRS Ch44): baseline workup includes CBC, electrolytes, creatinine, liver enzymes, bilirubin, and iron studies. CRP correlates better with disease severity in Crohn's than in UC, but can be normal in up to 30% of patients with active CD — a normal CRP does not rule out active disease. ESR has limited clinical utility despite extensive historical use. First- presentation diarrhea should prompt stool culture, ova and parasites, and C. difficile toxin assay (especially with recent hospitalization/antibiotic use); anal swabs for STIs and Chlamydia NAAT are appropriate with a history of anal receptive intercourse. Combined +pANCA/+ASCA serology has 70%/93% sensitivity/specificity for differentiating UC from CD once an IBD diagnosis is already established — a distinct use case from Crohn's-specific small-bowel-inflammation calprotectin/lactoferrin screening detailed on Crohn Disease. Fecal calprotectin, used more broadly here as an initial-evaluation triage tool, has pooled sensitivity 93–95% and specificity 90–96% across several meta-analyses; a level <50 mcg/g has a high enough negative predictive value that patients may reasonably avoid invasive testing — variable cutoffs and age-dependent normal ranges (higher in children and the elderly) limit generalizability.

Diagnostic imaging: abdominal X-rays have limited utility except in severe/toxic colitis (perforation, toxic megacolon evaluation mandating urgent colectomy). CT — particularly CT enterography (CTE), using large-volume/low-density/neutral oral contrast plus IV contrast — is widely available and detects moderate-to-severe small bowel/colonic inflammation, abscess, bowel obstruction with transition points, and enteric fistulas; findings of luminal stenosis, increased wall thickness, and pre-stenotic dilation correlate well with surgical-specimen fibrosis severity. Cumulative radiation exposure is a real concern in CD patients undergoing repeated CT — newer iterative-reconstruction protocols reduce dose 34–74% with preserved diagnostic utility. MR enterography (MRE) has become the preferred cross-sectional small-bowel modality despite cost/ availability limitations: in a multicenter cohort, MRE had low sensitivity for colonic disease detection/extent (64%/22%) but high specificity (93%/96%), while sensitivity and specificity for small bowel disease detection (97%/96%) and extent (80%/95%) were both significantly higher than ultrasound. Novel techniques (diffusion-weighted imaging, magnetization transfer, delayed- enhancement MRE) show promise for quantifying stricture fibrosis (sensitivity 86–96%, specificity 89–100% in small correlative series) but need protocol standardization. Ultrasound — given IBD patients' high cumulative radiation exposure, transabdominal small bowel US (low-cost, radiation- free) is increasingly used, with reported sensitivity/specificity in the 66–100%/63–92% range across studies depending on target (extent of disease vs. fibrosis severity); newer techniques (contrast-enhanced US, elastography) show promise in small series but need further validation. Transperineal and transanal ultrasound for perianal fistulas/abscesses have demonstrated high sensitivity (>90% in a meta-analysis) and may have a role in following known perianal disease given lower cost than MRI. MR pelvis remains the gold-standard perianal-Crohn's imaging study — 80–100% sensitivity for fistula tracts, more modest (69%) specificity for the internal opening.

Endoscopy practicalities: colonoscopy with terminal ileal intubation is the gold-standard diagnostic test for colonic/terminal-ileal IBD symptoms — a minimum of two representative biopsies should be taken from the terminal ileum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum, retrieved in separate vials and reviewed by a GI pathologist where available, using standard terminology (Table 44.3) to describe findings and improve cross-provider communication. In severe acute colitis, flexible sigmoidoscopy with biopsies is sufficient to establish a diagnosis and exclude other causes of colitis, given the extent of inflammation and perforation risk of a full colonoscopy. Upper GI endoscopy is not routinely required for adult IBD assessment unless upper-GI-tract-specific symptoms are present. For possible isolated small bowel Crohn's with a spared terminal ileum on colonoscopy, capsule endoscopy or double-balloon/push enteroscopy (detailed further on Crohn Disease) may be needed when cross-sectional imaging is inconclusive or for occult small bowel bleeding.

Genetic studies: over 240 GWAS-identified loci are associated with IBD (see Host factors: genetics above), but despite strong twin-study evidence for a genetic contribution, the clinical utility of genetic testing for diagnosis remains limited given the diversity of presentation and phenotypes. Current guidelines recommend genetic testing only in specific scenarios: suspected monogenic disorders (e.g. IL-10 receptor mutations), very-early-onset IBD (<5 years old), young patients with aggressive/refractory disease, or to assess thiopurine-metabolism-related mutations (TPMT and NUDT15 — the latter not previously named on this wiki, complementary to the TPMT testing already detailed in the Therapeutic drug monitoring section below) before initiating thiopurine therapy.

Endoscopic and clinical activity scoring systems

Genuinely new territory for the wiki — previously only CDAI and Harvey-Bradshaw Index were named in passing (see Medical treatment below); ASCRS Ch44 provides the fuller scoring landscape used for grading disease severity, monitoring treatment response, and standardizing communication between providers and across trials.

Endoscopic scores — UC: the Mayo endoscopic subscore (0–3: 0 normal/inactive, 1 erythema/ decreased vascular pattern/mild friability, 2 marked erythema/absent vascular pattern/friability/ erosions, 3 ulceration/spontaneous bleeding) is the most frequently employed in clinical practice — see Ulcerative Colitis for its role as the current endoscopic-improvement treatment-goal threshold (subscore 0–1). It is a simple four-point scale measuring only the most inflamed segment, with moderate inter-rater variability. Over 15 more complex indices exist to summarize both severity and extent, including the Modified Mayo Endoscopic Score (MMES) — sum of the Mayo score across all 5 colonic segments × length of inflamed segment during withdrawal (in dm), divided by number of segments inflamed. Current literature is insufficient to recommend one index over another; clinicians should use whichever is most commonly used locally for care-team communication.

Endoscopic scores — Crohn's: the simplified endoscopic activity score for Crohn's disease (SES-CD) is the most commonly employed in clinical practice and research, has excellent inter-observer agreement, and is more responsive than the more complex Crohn's disease endoscopic index of severity (CDEIS). SES-CD scores the terminal ileum, right colon, transverse colon, left colon, and rectum across four domains — size of ulcers, ulcerated surface, affected surface, and presence of narrowings — each scored 0–3, summed across all five segments for the total SES-CD.

Post-resection recurrence — Rutgeerts score: for patients who have previously had an ileocolic resection, the Rutgeerts score grades the extent of inflammation in the neoterminal ileum (i0 no lesions, through i4 diffuse inflammation with large ulcers/nodules/stenosis) and is strongly associated with risk of symptomatic recurrence, though inter-rater reliability is only modest. Endoscopic recurrence is classified as i2 or greater. This is a genuinely new, surgically-relevant addition to the wiki — directly applicable to post-ileocolic-resection surveillance colonoscopy timing/interpretation, a topic not previously covered on Crohn Disease.

Activity scores: the Mayo score (0–12, combining stool frequency/rectal bleeding/physician global assessment/endoscopic subscore) is often described in UC literature but rarely used in routine practice; UC patients are more often characterized simply as mild/moderate/severe per Truelove and Witt's criteria (already on this page, above) or the newer ACG UC Disease Activity Index (see Ulcerative Colitis). For Crohn's, the CDAI is used in clinical trials (score <150 = remission) but is too complex for routine practice; the Harvey-Bradshaw Index (general well-being, abdominal pain, liquid stools/day, abdominal mass, complications — each simply scored) is highly correlated with CDAI and much easier to administer, making it the more broadly used clinical-setting option. More than 20 newer patient-reported outcome measures (PROMs) have been described, some patient-response-only (e.g. IBD-10) and others combining patient responses with labs (CRP/fecal calprotectin) and/or clinical assessment (e.g. the Monitor IBD At Home questionnaire, HB-PROp/c) — these show good correlation with other indices but need external validation and head-to-head comparison before any one can be recommended over another.

Colorectal cancer surveillance in IBD

A cross-cutting topic for both diseases — genuinely new depth for the wiki. Both Ulcerative Colitis and Crohn Disease previously had only brief surveillance mentions (sourced from Sabiston); this section replaces/extends both.

IBD carries an increased CRC risk based on ample population-based, cohort, and case-control evidence. IBD-associated CRC is associated with younger age at diagnosis and a higher risk of death even after adjustment for stage. Risk factors include earlier onset of disease, longer disease duration, active inflammation, colonic strictures, PSC (see above), and family history of CRC. The evidence base for endoscopic surveillance itself is low-quality observational data, but surveillance has been consistently associated with a decreased risk of CRC, earlier-stage CRC at diagnosis, and lower CRC mortality.

Society-recommended surveillance schedule: surveillance for all UC patients and CD patients with colonic involvement (excluding those with a history of proctitis alone); begin colonoscopy surveillance at 8 years following symptom onset, or at diagnosis if PSC is present. Risk-stratified intervals thereafter: annual for high-risk patients (PSC, family history of CRC, stricture, or prior dysplasia); every 1–3 years for intermediate-risk patients (including those with active mucosal inflammation); every 3–5 years for low-risk patients. Surveillance should ideally occur during disease remission to improve histopathology reliability.

Technique: chromoendoscopy (dye-spraying to improve dysplasia detection, already noted on Ulcerative Colitis) may improve detection versus standard-definition colonoscopy, but data are inconsistent — two recent RCTs found no added benefit of chromoendoscopy over high-definition colonoscopy in detecting colitis-associated dysplasia, so guidelines now recommend high-definition colonoscopy with chromoendoscopy if local expertise exists, rather than mandating it universally. There is a lack of consensus on the incremental yield of random colonic biopsies in addition to targeted biopsies of abnormal-appearing mucosa; until further data are available, four random biopsies every 10cm plus targeted biopsies of any visible lesion, reviewed by a GI pathologist, is the recommended default protocol.

Terminology (SCENIC guidelines): the term "dysplasia-associated lesion or mass" (DALM) is no longer employed; dysplastic lesions are now described by visibility (visible on colonoscopy vs. invisible, found only on random biopsy), morphology (polypoid — pedunculated/sessile — vs. nonpolypoid — superficially elevated/flat/depressed), border (distinct vs. indistinct), and presence of ulceration (Table 44.11) — a more precise descriptive framework than the retired DALM label.

Medical treatment

Treatment philosophy has shifted over the last two decades from "bottom-up" (safest/cheapest medications first, escalate on failure) to "top-down" (more potent medications used earlier) — aiming to suppress disease before structural damage (fibrosis, fistulas) accumulates. Note: many of these drugs are associated with higher postoperative complication rates and with reactivation of latent infections — relevant to preop planning.

Drug class	Examples	Indication	Route
Biologics	Infliximab, adalimumab	UC, CD	IV / SC
	Golimumab	UC	IV
	Natalizumab	CD	IV
	Vedolizumab	UC, CD	IV
	Ustekinumab	UC, CD	IV, SC
Aminosalicylates	Sulfasalazine	UC, CD	PO
	Mesalamine	UC, CD	PO, enema, suppository
Immunosuppressives	Conventional steroids	UC, CD	PO, IV, suppository
	Budesonide	UC, CD	PO, rectal foam
	Antimetabolites	UC, CD	PO
	Tofacitinib	UC	PO
Probiotics	Lactobacillus, Bifidobacterium	UC, CD	Food/tablets/capsules/powders
Antibiotics	Ciprofloxacin, metronidazole	UC, CD	PO, IV
	Rifaximin	Off-label	PO

Aminosalicylates — sulfasalazine's sulfapyridine ring limits use in sulfa allergy and requires folic acid supplementation; active moiety is 5-ASA. Mesalamine formulations target different GI segments by design (Pentasa dissolves in the stomach and releases throughout the GI tract; Asacol uses a pH-dependent release beginning in the terminal ileum, coating the whole colon; "MMX" formulations are once-daily, releasing throughout the colon for better compliance). Topical suppository (Canasa) or enema (Rowasa) forms, given at bedtime, are most effective for mild-to- moderate distal disease.

Corticosteroids — still prominent for severe disease: inexpensive, fast-acting, no insurance preauthorization needed. Side effects: cushingoid appearance, aseptic hip necrosis, hypertension, mood changes (up to psychiatric presentations), hyperglycemia, increased postoperative infectious complications, cataracts, striae, growth retardation in children. Outpatient pulse dosing: prednisone 40–60 mg/day tapering 5–10 mg every 2 weeks down to 10 mg/day, then 5 mg every 2 weeks to discontinuation. Inpatient: IV hydrocortisone 100 mg q6–8h depending on severity.

Immunomodulators — thiopurines (azathioprine, 6-mercaptopurine) are steroid-sparing, typically started after 1–2 failed steroid-wean attempts; TPMT genotyping is recommended before starting (poor metabolizers are at higher risk of leukopenia/pancreatitis); oral, once-daily, weight-based; 3–4 month lag to effect, so not useful for acute flares; long-term use raises non-Hodgkin lymphoma risk. Methotrexate is an alternative steroid-sparing option (IM or oral — IM particularly useful if diarrhea/absorption is a concern), with LFT elevation and pulmonary fibrosis as key side effects; also requires folic acid supplementation.

Biologics — anti-TNF-α therapy began with infliximab (FDA approval for Crohn's, 1998), followed by adalimumab (2007), certolizumab pegol and natalizumab (2008), golimumab for UC (2013), vedolizumab (anti-α4β7 integrin, 2014), ustekinumab (anti-IL-12/23, 2016), and tofacitinib (JAK inhibitor, UC, 2018). Side effects include reactivation of latent infections (TB, histoplasmosis, actinomycosis, hepatitis) — screen with TB skin test or QuantiFERON gold plus a hepatitis panel before starting (no reliable test exists for histoplasmosis exposure). Combination thiopurine + anti-TNF therapy carries a low but notable risk of hepatosplenic T-cell lymphoma, particularly in young men.

Symptom severity assessment: Truelove and Witts classification (diarrhea frequency, blood in stool, fever, tachycardia, anemia, ESR); fecal calprotectin/lactoferrin as inflammatory markers. Formal endoscopic and clinical activity scores (Mayo score, CDAI, Harvey-Bradshaw Index, and the full endoscopic-scoring suite) are detailed in "Endoscopic and clinical activity scoring systems" above.

Therapeutic drug monitoring (BSG 2025 guideline)

Applies across both diseases; adds concrete numbers to what was previously only qualitative mentions of TPMT testing above. Full detail on BSG 2025 - IBD Guidelines (Adults).

Purine analogue metabolites: target 6-TGN 235–450 pmol/8×10⁸ RBCs, MMP <5700 pmol/8×10⁸ RBCs (or MMP:6-TGN ratio >11 suggests hypermethylation — consider low-dose purine analogue + allopurinol 100mg/day instead). TPMT genotyping/phenotyping before starting (as above); NUDT15 variant testing also relevant, especially in patients of East/South Asian ancestry (higher myelosuppression risk), though not yet widely available in the UK.
Anti-TNF trough levels: reactive TDM (checking levels + antidrug antibodies on secondary loss of response) is well-supported; the PANTS study suggests later-time-point (week 14+) optimal trough targets of 6.1–10.0 mg/L for infliximab and 10.1–12.0 mg/L for adalimumab, though evidence is insufficient to formally recommend routinely targeting such high levels. Combination with an immunomodulator reduces anti-drug antibody formation.
Vedolizumab/ustekinumab exposure-efficacy data are less consistent; dose escalation (shortening the interval) may help in partial responders, but routine trough-level testing isn't yet evidence-supported for these agents.

Pregnancy (BSG 2025 guideline)

A topic essentially absent from this wiki before this ingest — full detail on BSG 2025 - IBD Guidelines (Adults).

Pre-conception: aim for ≥3 months of corticosteroid-free clinical remission before conception — active disease at conception roughly doubles the risk of disease activity/relapse during pregnancy and is independently associated with adverse foetal outcomes (low birth weight, preterm birth, small-for-gestational-age, spontaneous abortion). Stop methotrexate ≥3 months pre-conception (both sexes — teratogenic); stop JAK inhibitors and S1P modulators ≥3 months pre-conception.
During pregnancy: continue anti-TNF therapy throughout pregnancy — reduces relapse risk with no increased adverse-pregnancy-outcome signal versus non-pregnant IBD patients (some retrospective data link continuation beyond 24 weeks to higher maternal infection/complication rates, but not to worse foetal outcomes). Vedolizumab and ustekinumab appear low-risk with less extensive data. JAK inhibitors (tofacitinib, upadacitinib, filgotinib) and S1P modulators (ozanimod, etrasimod) are contraindicated during conception, pregnancy, and lactation. 5-ASAs and purine analogues are considered low-risk and should be continued if needed for disease control. Corticosteroids: moderate risk, likely lower with budesonide than prednisolone given reduced placental transfer — active disease requiring steroids is itself the bigger foetal risk, so undertreatment is not the safer choice.
Delivery and postpartum: caesarean section generally preferred for active perianal disease or in patients with an ileal pouch-anal or ileorectal anastomosis; otherwise delivery mode is obstetric/patient-preference-driven. VTE prophylaxis is important postpartum, especially after caesarean section in active IBD. Breastfeeding is considered low-risk/should continue for essentially all standard IBD medications (5-ASA, purine analogues, corticosteroids, anti-TNF, vedolizumab, ustekinumab) — except JAK inhibitors and S1P modulators, which are not recommended during lactation.
Infant vaccination: live vaccines (including BCG) should be withheld until 12 months of age in infants with in-utero exposure to biologics — several fatal disseminated BCG infections have been reported in infants vaccinated before 1 month of age after infliximab/adalimumab exposure. Standard inactivated-vaccine schedules proceed normally; exposed infants mount appropriate antibody responses to them.

Perioperative management and superadded infection (BSG 2025 guideline)

VTE prophylaxis: IBD carries ~2x baseline VTE risk versus non-IBD, further elevated with active inflammation (HR 8.4) and hospitalisation for any reason (~1.5x). Pharmacological VTE prophylaxis is recommended for essentially all IBD patients admitted for acute illness or surgery unless contraindicated — including ASUC patients (does not worsen colonic bleeding). Elevated risk persists 60–90 days post-discharge; UK practice extends prophylaxis post-discharge after major abdominal surgery.
Perioperative drug management: corticosteroids should be stopped/minimised preoperatively where possible (equivalent IV hydrocortisone if steroid-dependent and NPO). Immunosuppressive agents (purine analogues, methotrexate) and biologics (anti-TNF, vedolizumab, ustekinumab) can be continued perioperatively — large observational studies (PUCCINI, French REMIND) found no significant postoperative infection increase with anti-TNF exposure. JAK inhibitor perioperative safety data are limited (one series: 13.2% VTE rate after tofacitinib exposure before colectomy in ulcerative colitis) — prolonged VTE prophylaxis suggested in these patients.
CMV and C. difficile superinfection: CMV present in up to 10–30% of steroid-refractory IBD; best diagnosed via colonic tissue immunohistochemistry/PCR (serum tests correlate poorly); treated with IV ganciclovir then oral valganciclovir to complete a 2–3 week course, continuing background immunosuppression unless disseminated disease. C. difficile — see Infectious Colitis for full detail; IBD is an independent CDI risk factor regardless of antibiotic/PPI exposure, and CDI in IBD carries higher colectomy, complication, and mortality rates than in non-IBD patients. ASCRS Ch51 - Infectious Colitis (2026-08-25) puts a sharper point on why this matters clinically: IBD patients with a superimposed infectious colitis are, unless promptly recognized, often instead treated for an IBD exacerbation by escalating immunosuppression — which can precipitate sepsis and perforation. Its own illustrative case: a patient presumed to have a UC exacerbation, treated with prolonged steroids, went to surgery and was found to have severe amebic colitis with no IBD at all. See Infectious Colitis's "Infectious colitis in immunocompromised patients" section for the fuller picture (also covering HIV and transplant patients). ASCRS Ch52 - Clostridium difficile Infection (2026-08-25) adds a specific genetic risk factor and a severity number for this exact bullet: the TNFRSF14 locus has been associated with a sixfold increase in CDI risk in IBD patients in one study, and IBD-specific CDI risk factors also include low albumin, hemoglobin <9 g/dL, active colitis, biologic use, and antibiotic use — with at least one study estimating a sixfold increase in colectomy need when CDI complicates IBD (consistent with, and more specific than, this bullet's existing "higher colectomy... rates" claim). Ch52's own key-concepts summary states plainly: "CDI in IBD patients should be treated with vancomycin" — consistent with Infectious Colitis's vancomycin-first treatment table.

Open items / gaps

Ch44 (IBD Diagnosis and Evaluation) closed several diagnostic-workup gaps: added a full endoscopic/clinical activity-scoring suite (Mayo endoscopic subscore, MMES, SES-CD, CDEIS, Rutgeerts score, Mayo score, CDAI, Harvey-Bradshaw Index) and a risk-stratified colorectal cancer surveillance framework (SCENIC terminology, chromoendoscopy-vs-standard-definition RCT evidence, 4-random-biopsies-per-10cm protocol) — both previously absent. Also added IBD-U/indeterminate colitis reclassification rates, extended PSC-IBD detail, and quantified lab/imaging diagnostic-accuracy figures (pANCA+ASCA, fecal calprotectin, MRE). Every cited study/RCT is at the textbook/secondary level only — see ASCRS Ch44 - IBD Diagnosis and Evaluation's own Open items for what would be highest-value to independently ingest.
Both UC and Crohn's now have primary-guideline-sourced medical management — see Ulcerative Colitis (from ACG 2025 - Ulcerative Colitis Guideline and AGA 2024 - Moderate-to-Severe UC Pharmacotherapy Guideline) and Crohn Disease's new "Advanced therapy, monitoring, and post-surgical management" section (from BSG 2025 - IBD Guidelines (Adults)). The wiki's IBD medical-management asymmetry flagged earlier in this ingest session is now closed.
The shared drug-class table above is still textbook-level (mechanism/route only) — UC-specific positioning lives on Ulcerative Colitis, Crohn's-specific positioning lives on Crohn Disease, and genuinely cross-cutting content (TDM, pregnancy, perioperative management, PSC-IBD, spondyloarthropathy) now lives here.
BSG's UC-specific recommendations were not exhaustively transcribed to Ulcerative Colitis during this ingest (see BSG 2025 - IBD Guidelines (Adults)'s Limitations) — UC ground was already well covered by the other two guidelines, so BSG content prioritized Crohn's and cross-cutting topics. Flag if a specific BSG UC recommendation is needed and missing.
Fecal calprotectin/lactoferrin use in practice: UC-specific cutoffs and monitoring guidance is on Ulcerative Colitis; Crohn's-specific cutoffs still not separately detailed.
See Ulcerative Colitis and Crohn Disease for disease-specific surgical open items.

Colorectal LLM Wiki