Ulcerative colitis (Colitis ulcerosa, UC) is a form of inflammatory bowel disease (IBD). Ulcerative colitis is a form of colitis, a disease of the intestine, specifically the large intestine or colon, that includes characteristic ulcers, or open sores, in the colon with rising incidence worldwide, including in the US where prevalence is about 1.253 million people.. The main symptom of active disease is usually diarrhea mixed with blood, of gradual onset. Ulcerative colitis is, however, a systemic disease that affects many parts of the body outside the intestine. Because of the name, IBD is often confused with irritable bowel syndrome (“IBS”), a troublesome, but much less serious condition. Ulcerative colitis has similarities to Crohn’s disease, another form of IBD. Ulcerative colitis is an elapsing and remitting condition, with symptoms such as rectal bleeding, urgency, and tenesmus.

Ulcerative colitis (UC) moved from isolated 19th-century case reports to one of the two defined forms of inflammatory bowel disease (IBD) over roughly 150 years.^[1] Samuel Wilks reported the first case of non-infectious colitis in 1859. Most historical reviews credit William Hale White’s 1888 case series with establishing the term ulcerative colitis.^[1][2] Before the 1932 description of regional ileitis by Crohn, Ginzburg, and Oppenheimer, colonic Crohn’s disease and UC were often confused with each other. This means 19th-century physicians could not have distinguished UC from Crohn’s disease.^[1][3] Corticosteroids, introduced in the mid-1950s, sharply reduced the historically high mortality of severe UC. Anti-TNF therapy, starting in 2005, opened the era of biologic and small-molecule therapy.^[4][2]

Ulcerative colitis (UC) is classified along two complementary axes that together drive treatment selection: anatomic extent, described by the Montreal classification as proctitis (E1), left-sided colitis (E2), or extensive colitis (E3), and disease activity/severity.^[5][6] Current definitions of severity integrate patient-reported outcomes, endoscopic scores (Mayo Endoscopic Score or UCEIS), biomarkers, disease course, and disease impact, rather than symptoms alone.^[5] Validated indices include the Truelove and Witts criteria, the Mayo Score and its modified versions, and endoscopic indices. In clinical practice, patients are grouped into three treatment-relevant tiers: mild to moderate, moderate to severe, and acute severe ulcerative colitis (ASUC). ASUC has replaced the older term “fulminant colitis”.^[6][7]

Ulcerative colitis (UC) arises from a gene–environment interaction. In a genetically susceptible host, environmental exposures lead to a defective epithelial barrier, gut microbial dysbiosis, and a dysregulated mucosal immune response. Together these start and sustain continuous mucosal inflammation of the colon.^[6][8] There is no single causative agent. Genetics, barrier failure, dysbiosis, and immune dysregulation each contribute, but none is sufficient on its own.^[9] The adaptive immune response in UC is classically an atypical Th2 response driven by NKT cells through IL-13. This contrasts with the Th1 pattern of Crohn’s disease, and both diseases share a Th17/IL-23 axis.^[10][11] Each mechanistic node maps to an approved drug class: anti-TNF, anti-integrin, anti-IL-12/23 or IL-23, JAK inhibitors, and sphingosine-1-phosphate (S1P) receptor modulators. This mapping is the main clinical value of understanding UC pathogenesis.^[6]

No single cause of ulcerative colitis (UC) has been identified. The current model is that UC results from a dysregulated innate and adaptive mucosal immune response against the commensal gut microbiota. This response occurs in genetically susceptible individuals and is triggered or shaped by environmental exposures and a defective epithelial barrier.^[8][6][12] Genetic risk is polygenic and explains only a small fraction of disease variance. Family history is the strongest individual risk factor. Environmental associations include an inverse association with current smoking and appendectomy, and positive associations with former smoking, enteric infection, antibiotic exposure, and Westernized diet. Dysbiosis is consistently present, but it is both a cause and a consequence of inflammation.

Ulcerative colitis should be differentiated from other causes of diarrhea. It is very important to differentiate it from Crohn’s disease as the management of both conditions is different though the initial presentation may be confused for any of these disorders.^[13][14]

Ulcerative colitis (UC) is most common in early-industrialized regions such as North America, Northern and Western Europe, and Oceania. In these regions incidence has stabilized or declined since 1990, while prevalence continues to rise.^[15][1] Incidence is now rising rapidly in newly industrialized countries of Asia, Latin America, and the Middle East. UC therefore can no longer be regarded as a disease confined to Western populations.^[16] In the United States, UC prevalence is approximately 378 per 100,000 population, or about 1.25 million people.^[17] UC is most often diagnosed in the second to fourth decades of life, but elderly-onset disease accounts for a growing share of new diagnoses. There is no consistent sex predominance.^[8]

Ulcerative colitis (UC) develops from the interaction of genetic susceptibility, environmental exposures, gut dysbiosis, and dysregulated mucosal immunity; no single risk factor is necessary or sufficient.^[18][9] A family history of inflammatory bowel disease (IBD) is the strongest known risk factor, conferring roughly 4–10 times the background risk in first-degree relatives.^[19][20] UC risk is characteristically increased in former smokers and reduced in current smokers and after appendectomy for appendicitis in early life, the inverse of the pattern seen in Crohn’s disease.^[10][4] Most environmental associations derive from observational, largely retrospective data subject to recall bias and reverse causation, and should be interpreted as risk markers rather than proven causal or modifiable targets.^[21]

Patients with ulcerative colitis (UC) extending beyond the rectum have an increased risk of colitis-associated colorectal cancer (CRC), driven mainly by disease duration, extent, and cumulative inflammation, with the highest risk in patients with concomitant primary sclerosing cholangitis (PSC). Contemporary population-based data show a relative risk of approximately 1.4–1.7 compared with the general population, substantially lower than historical estimates but still above the threshold at which colonoscopic surveillance is recommended.^[22][23] All major societies recommend an index (baseline) colonoscopy approximately 8 years after symptom onset to re-stage disease extent and stratify risk, with immediate and annual surveillance for patients with PSC.^[22][24][25] Subsequent surveillance intervals (1, 3, or up to 5–10 years) are individualized according to inflammatory activity, extent, PSC, prior dysplasia, strictures, post-inflammatory polyps, and family history of CRC. Surveillance should be performed in remission, with high-definition colonoscopy, preferably with dye-based chromoendoscopy, by endoscopists trained in IBD surveillance. Random biopsies are now reserved for high-risk patients or for white-light-only examinations. Proctitis alone does not warrant IBD-specific surveillance.^[22]

Ulcerative colitis (UC) is a lifelong relapsing–remitting disease with no reliable medical cure; proctocolectomy is the only definitive cure.^[26] In population-based cohorts, the cumulative risk of relapse is approximately 70–80% at 10 years, about 10–15% of patients follow an aggressive course, nearly half require at least one UC-related hospitalization, and the 5- and 10-year cumulative risk of colectomy is approximately 10–15%.^[27] Major complications include acute severe ulcerative colitis with toxic megacolon, perforation or massive hemorrhage, venous thromboembolism, extraintestinal manifestations, and colitis-associated colorectal cancer (CRC).^[3] Contemporary CRC risk is substantially lower than historical referral-center estimates, and surveillance colonoscopy is risk-stratified, beginning 8 years after symptom onset or at diagnosis of primary sclerosing cholangitis (PSC).^[6][24] Large nationwide cohorts show a modest excess all-cause mortality (adjusted HR ~1.4 in Sweden), although relative mortality has declined over time.^[28]

Patients with ulcerative colitis present with a history of bloody diarrhea mixed with mucus, of gradual onset. Some patients may present with a sudden attack of diarrhea, fever and abdominal pain. The extra intestinal symptoms may include joint swelling and pain, inflammation of the eye and skin involvement.^[29]

Ulcerative colitis shows intestinal and extra intestinal findings on physical examination. These include abdominal tenderness, fever, pallor, inflammation of the iris and uvea, skin rash, inflammation of the joints, aphthous ulcers and clubbing of the fingers.^[29][30]

The laboratory findings in a patient with ulcerative colitis include anemia, low albumin, elevated ESR, elevated serum alkaline phosphatase, deranged LFTs and electrolyte abnormalities.^[31][32]

Xray of the abdomen is not required for the diagnosis of ulcerative colitis. Xray may sometimes be one in case colitis is suspected. Xray is normal in mild to moderate disease and can show dilation and/or “thumb printing sign” in fulminant cases.^[33]

CT scan can b helpful in the diagnosis of severe ulcerative colitis and in differentiating ulcerative colitis from Crohn’s disease. Initial changes in the mucosa may not be detected by a CT scan.^[33]

MRI can b helpful in the diagnosis of severe ulcerative colitis and in differentiating ulcerative colitis from Crohn’s disease. Initial changes in the mucosa may not be detected by a CT scan.^[33][34]

Other imaging findings for ulcerative colitis can be seen by the help of barium enema. Barium enema may show micro ulcerations. barium enema must be avoided in severe cases as it can lead to the manifestation of toxic megacolon.^[34]

Other diagnostic studies like upper endoscopy, colonoscopy, tissue biopsy and histological analysis can help with the diagnosis of ulcerative colitis.^[35][30]

Medical therapy of ulcerative colitis (UC) follows a two-phase paradigm: induction of remission followed by maintenance of remission. The agent and route are selected according to disease extent (proctitis, left-sided colitis, or extensive colitis) and disease activity (mild-to-moderate, moderate-to-severe, or acute severe).^[5] The current treatment target is corticosteroid-free remission with endoscopic (mucosal) healing rather than symptom control alone.^[6][8] 5-aminosalicylic acid (5-ASA) is first-line for mild-to-moderate disease. Moderate-to-severe disease is managed with early initiation of an advanced therapy (biologic or oral small molecule), with corticosteroids used only as a short-term bridge.^[5][36] Acute severe UC requires hospitalization, intravenous corticosteroids, and an early decision about rescue therapy or colectomy.^[37]

Because ulcerative colitis (UC) is confined to the colon and rectum, proctocolectomy removes the target organ and cures the intestinal disease.^[38]

Indications for surgery fall into three tiers: emergent, urgent, and elective. Emergent indications are perforation, uncontrolled hemorrhage, and refractory toxic megacolon. The main urgent indication is acute severe UC (ASUC) that fails intravenous corticosteroids or medical rescue therapy. Elective indications include medically refractory disease, intolerable drug toxicity, and dysplasia or colorectal cancer that cannot be managed endoscopically.^[5][39]

For most patients who want to avoid a permanent stoma, restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the procedure of choice. Total proctocolectomy with end ileostomy remains a curative alternative with equivalent quality of life.^[38] The most common long-term complication of IPAA is pouchitis, which is managed along a chronicity spectrum.^[40]

Limited evidence exists for the efficacy of alternative treatments for ulcerative colitis. Dietary modification, fish oil supplements, short chain fatty acid enema, herbal therapy, helminth therapy, probiotics, are the most common homepathic remedies used in ulcerative colitis. Data is lacking in regards to the efficacy of these therapies. Using these treatment modalities should not preclude physician-recommended, evidence-based interventions.

The cause of ulcerative colitis is unknown, therefore primary preventive strategies are also unknown. Nonsteroidal anti-inflammatory drugs (NSAIDs) may make symptoms worse.

Due to the risk of colon cancer associated with ulcerative colitis. screening with colonoscopy is recommended for secondary prevention of ulcerative colitis. Adherence to maintenance therapy is recommended for secondary prevention of acute exacerbation of colitis.

Ulcerative colitis (UC) moved from isolated 19th-century case reports to one of the two defined forms of inflammatory bowel disease (IBD) over roughly 150 years.^[1] Samuel Wilks reported the first case of non-infectious colitis in 1859. Most historical reviews credit William Hale White’s 1888 case series with establishing the term ulcerative colitis.^[1][2] Before the 1932 description of regional ileitis by Crohn, Ginzburg, and Oppenheimer, colonic Crohn’s disease and UC were often confused with each other. This means 19th-century physicians could not have distinguished UC from Crohn’s disease.^[1][3] Corticosteroids, introduced in the mid-1950s, sharply reduced the historically high mortality of severe UC. Anti-TNF therapy, starting in 2005, opened the era of biologic and small-molecule therapy.^[4][2]

• 1859: Samuel Wilks published the first case describing a distinct, non-infectious inflammatory disease of the bowel. This set it apart from the infectious diarrhoeal illnesses common at the time.^[1][2]
  • Looking back, Wilks’s index case had ileal involvement, and it is now thought to have been Crohn’s disease rather than classic UC.^[1]
• 1888: William Hale White’s case series is usually credited with bringing the term ulcerative colitis into the medical vocabulary.^[1]
  • Some secondary sources still credit Wilks with the term in 1859, so attribution remains disputed.^[2]
• Late 1800s: Sporadic case reports from Europe and the United States built up, and UC changed from an anecdotal finding into a recognizable diagnosis.^[1][5]
• 1909: A symposium at the Royal Society of Medicine in London reviewed 317 UC cases collected from seven London hospitals between 1888 and 1907. This was the first collaborative study of the disease. It recorded only two to three admissions per hospital per year.^[1]

• 1932: Crohn, Ginzburg, and Oppenheimer described regional ileitis as a separate disease. This established the two-disease model of IBD.^[1][3][5]
• Before 1932, colonic Crohn’s disease and UC were often grouped together. Older case series should therefore be read with care.^[1][3]

Era	Milestone	Clinical significance
Before 1955	Surgery was the main treatment	The natural course of moderate-to-severe UC was very poor, with mortality above 50%.[4]
1955	Corticosteroids introduced	This was the first major turning point in medical therapy. It sharply lowered mortality from severe UC.[4][2]
2005	Infliximab approved after the ACT 1 and ACT 2 trials	This began the anti-TNF and biologic era.[4][2]
2014–present	Anti-integrin (vedolizumab), anti–IL-12/23 and selective anti–IL-23 agents, JAK inhibitors, and S1P receptor modulators	These widened treatment options and made corticosteroid-free remission a realistic treatment goal.[4][2]

• 1939: Chopra and Ray described 120 UC cases in Kolkata, India.^[1]
• 1956: The first UC case report from China was published. This reflects the later appearance of IBD in developing regions.^[1]
• Kaplan and Windsor describe four stages in the global evolution of IBD:^[1]
  1. Emergence: the Western world in the late 19th and early 20th centuries; developing countries today.
  2. Acceleration in incidence: newly industrialized countries.
  3. Compounding prevalence: Western regions today.
  4. Prevalence equilibrium: projected for the future.
• UC is now a global disease. Incidence is rising fastest in newly industrialized countries in Asia, Latin America, and Africa.^[6][1] For current incidence and prevalence figures, see Ulcerative colitis epidemiology and demographics.

Ulcerative colitis (UC) is classified along two complementary axes that together drive treatment selection: anatomic extent, described by the Montreal classification as proctitis (E1), left-sided colitis (E2), or extensive colitis (E3), and disease activity/severity.^[1][2] Current definitions of severity integrate patient-reported outcomes, endoscopic scores (Mayo Endoscopic Score or UCEIS), biomarkers, disease course, and disease impact, rather than symptoms alone.^[1] Validated indices include the Truelove and Witts criteria, the Mayo Score and its modified versions, and endoscopic indices. In clinical practice, patients are grouped into three treatment-relevant tiers: mild to moderate, moderate to severe, and acute severe ulcerative colitis (ASUC). ASUC has replaced the older term “fulminant colitis”.^[2][3]

The Montreal classification is the standard system for describing colonic involvement in UC and is used by both ACG and AGA guidance.^[1][4][2]

Montreal classification of ulcerative colitis extent

Category	Montreal code	Extent	Approximate frequency at diagnosis
Ulcerative proctitis	E1	Limited to the rectum (distal to the rectosigmoid junction, within ~18 cm of the anal verge)	~29%[1][2]
Left-sided (distal) colitis	E2	Extends proximally from the rectum up to the splenic flexure	~40%[1][2]
Extensive colitis / pancolitis	E3	Extends proximal to the splenic flexure, up to the entire colorectum	~31%[1][2]

• Extent determines whether topical, oral, or combined therapy is appropriate, and it correlates with prognosis.^[2]
• Extent is dynamic. Up to ~30% of patients progress to more extensive disease within 10 years, so extent should be reassessed periodically.^[2]
• Although extent broadly affects prognosis, current ACG guidance states that extent alone should not limit therapeutic options. A patient with limited disease may still have severe, refractory disease that requires advanced therapy.^[1][4]

Severity is no longer a single symptom-based number. The 2025 ACG update defines it as a composite of four domains:^[1]

• Patient-reported outcomes (PROs): rectal bleeding, stool frequency, and bowel urgency. Urgency is now validated as a distinct PRO and is among the most bothersome symptoms reported by patients.
• Inflammatory burden: endoscopic extent and severity, plus fecal calprotectin, C-reactive protein (CRP), and serum albumin.
• Disease course: hospitalizations, corticosteroid requirement, and prior medication failure.
• Disease impact: health-related quality of life and social functioning.

The field distinguishes disease activity from disease severity. Activity is a cross-sectional measure of current symptomatic and endoscopic inflammation. Severity is a longitudinal measure of cumulative disease burden and risk of complications.^[5]

Index	Components / thresholds	Clinical use and limitations
Truelove and Witts criteria (1955)	Clinical and laboratory parameters (bloody stool frequency, heart rate, temperature, hemoglobin, ESR)	The original clinical index. It is now used mainly to define ASUC and the need for hospitalization. It gives no quantitative or longitudinal measure and omits urgency, nocturnal symptoms, extraintestinal manifestations, and endoscopy.[1][4]
Mayo Score (Disease Activity Index)	Range 0–12. Four subscores (stool frequency, rectal bleeding, physician global assessment, endoscopy), each scored 0–3.	The most widely used index in practice and trials.[6][1]
Modified Mayo Score and PRO2	The Modified Mayo Score excludes the subjective physician global assessment. PRO2 combines stool frequency and rectal bleeding.	Both are now standard clinical trial endpoints.[6][1]
Mayo Endoscopic Score (MES) and UC Endoscopic Index of Severity (UCEIS)	MES 0–1 defines endoscopic remission and MES 2–3 defines endoscopic activity. Ulcers and/or spontaneous bleeding define severe endoscopic activity.	ACG recommends using a validated endoscopic index to report endoscopic severity and to define treatment targets.[1][7]
Composite / burden tools	The DUBLIN score (MES × Montreal extent) and the multidimensional Disease Severity Index, which integrate inflammatory burden, complications, treatment intensity, and disease impact.	These capture cumulative burden beyond cross-sectional activity. They are used mainly in research and specialist settings.[5][7]

Interpretation of the total Mayo Score

Total Mayo Score	Activity category
0–2, with no subscore >1	Remission
3–5	Mild
6–10	Moderate to severe
11–12	Severe

In AGA guidance and clinical trials, moderate to severe UC is generally defined as a Mayo Score of 6–12 with an endoscopic subscore of 2 or 3.^[6][3]

Contemporary guidelines group adult UC into three treatment-relevant tiers.^[2][8][3]

Tier	Representative definition	Management implication
Mild to moderate	Fewer than 4–6 bowel movements/day, mild to moderate rectal bleeding, no constitutional symptoms, and low overall inflammatory burden[8]	5-aminosalicylates (oral and/or rectal, selected by extent) are first-line therapy.[8][2]
Moderate to severe	Frequent bloody stools with urgency, elevated inflammatory markers, and Mayo Score 6–12 with endoscopic subscore 2–3[3][9]	Corticosteroids for induction only, as a bridge to biologics or oral small molecules for maintenance.[2][3]
Acute severe UC (ASUC) (modified Truelove–Witts criteria)	≥6 bloody stools/day plus ≥1 sign of systemic toxicity: heart rate >90 beats/min, temperature >37.8°C, hemoglobin <10.5 g/dL, or ESR >30 mm/h[2][3]	Hospitalization and IV corticosteroids. Rescue infliximab or cyclosporine if refractory to IV steroids.[3][9]

• ASUC is a medical emergency. Short-term colectomy risk is ~25–30% in hospitalized patients.^[3]
• Before assigning severity or escalating therapy, exclude infectious mimics, particularly Clostridioides difficile and cytomegalovirus (CMV).
  C. difficile is found in ~3% of ASUC cases, and ACG strongly recommends testing all hospitalized patients.^[1][2]
• Document objective inflammation (fecal calprotectin, CRP, endoscopy, or imaging) before attributing symptoms to active UC and starting corticosteroids.^[10]
• Certain features predict an aggressive course and colectomy at any severity tier. They warrant earlier treatment intensification:^[8][3]
  • Age <40 years at diagnosis
  • Extensive colitis
  • Severe endoscopic disease (large or deep ulcers)
  • Prior hospitalization
  • Elevated CRP or low albumin

• In every UC assessment, record Montreal extent (E1–E3) together with a validated clinical index (Mayo or Modified Mayo) and an endoscopic index (MES or UCEIS). This anchors therapy selection and allows longitudinal comparison.^[1]
• Endoscopic remission (MES 0–1) is a treatment target beyond symptom control.^[1]
• Avoid classifying severity on symptoms alone. Doing so can miss objective inflammation, or can overcall severity when IBS-type symptoms occur without active disease.^[10]
• Use the defined ASUC criteria rather than the obsolete term “fulminant colitis”.^[2][3]
• Do not let limited extent restrict therapy. Severe, refractory proctitis may still require advanced therapy.^[1]

Ulcerative colitis (UC) arises from a gene–environment interaction. In a genetically susceptible host, environmental exposures lead to a defective epithelial barrier, gut microbial dysbiosis, and a dysregulated mucosal immune response. Together these start and sustain continuous mucosal inflammation of the colon.^[1][2] There is no single causative agent. Genetics, barrier failure, dysbiosis, and immune dysregulation each contribute, but none is sufficient on its own.^[3] The adaptive immune response in UC is classically an atypical Th2 response driven by NKT cells through IL-13. This contrasts with the Th1 pattern of Crohn’s disease, and both diseases share a Th17/IL-23 axis.^[4][5] Each mechanistic node maps to an approved drug class: anti-TNF, anti-integrin, anti-IL-12/23 or IL-23, JAK inhibitors, and sphingosine-1-phosphate (S1P) receptor modulators. This mapping is the main clinical value of understanding UC pathogenesis.^[1]

• Inflammation is confined to the mucosa. It begins in the rectum and extends proximally in a continuous pattern to a variable length of the colon.^[6]

UC is a multifactorial disorder with four interacting domains:^[1][2][7]

• Genetic susceptibility
  • Genome-wide association studies have identified more than 200 IBD risk loci. These loci are enriched for genes involved in intestinal barrier function and T-cell immunity.^[1][2]
  • Known risk variants explain only about 19–26% of IBD heritability.^[8]
  • Genotyping therefore does not predict disease onset or phenotype and has no routine clinical role.^[2]
• Environmental triggers
  • Smoking has a distinctive relationship with UC. Current smoking is associated with a lower risk, while former smokers and recent quitters have a higher risk.^[6]
  • Other modifiers include appendectomy, NSAIDs, antibiotics, enteric infections, and diet. Many of these act by reshaping the microbiome.^[2][6]
• Epithelial barrier dysfunction is an early and possibly primary event (see below).
• Immune dysregulation consists of aberrant innate and adaptive responses to luminal microbial antigens.

Barrier failure is detectable early in the disease. It is increasingly viewed as a primary driver rather than only a consequence of inflammation.^[7][6]

• Mucus layer defects: reduced mucin 2 (MUC2) synthesis and goblet cell depletion make the mucus barrier thinner and more permeable.^[7][6]
• Tight junction disruption: downregulation of occludin, claudins, and tricellulin increases paracellular permeability.^[7]
• Pre-clinical changes:
  • Foci of epithelial apoptosis appear before endoscopic disease.^[7]
  • Unaffected first-degree relatives show increased intestinal permeability.^[7]
• Epithelial stress pathways: two mechanisms link genetic and environmental hits to epithelial inflammation.^[7][6]
  • Reduced colonocyte PPAR-γ expression. PPAR-γ normally restrains NF-κB.
  • Unresolved endoplasmic reticulum stress, for example through the XBP1 pathway.
• Once the barrier fails, luminal microbial antigens reach immune cells in the lamina propria. This sets up a self-reinforcing cycle of inflammation and further barrier injury.^[7][9]

• Characteristic changes in the UC microbiome:^[6][8]
  • Reduced microbial diversity.
  • Depletion of commensals that produce short-chain fatty acids (SCFAs), such as Faecalibacterium prausnitzii.
  • Expansion of facultative pathobionts, including Escherichia coli and other Enterobacteriaceae and Proteobacteria.
• No single causative organism: no pathogen reproducibly causes UC. Disease reflects altered proportions of normally resident taxa and opportunistic pathobionts.^[3][8]
• Dysbiosis is both cause and consequence:^[10][9]
  • The inflamed mucosa is rich in oxygen and nitrate, which favors aerotolerant Proteobacteria and perpetuates inflammation.
  • The direction of causality remains unresolved.
• Functional consequences: loss of SCFAs (colonocyte fuel and inducers of regulatory T cells) and activation of toll-like receptor–NF-κB signaling amplify release of pro-inflammatory cytokines.^[6][10]

• After antigens cross the epithelium, dendritic cells, macrophages, and neutrophils are activated.^[2]
• A hallmark of UC is mucosal neutrophil accumulation with neutrophil extracellular traps (NETs). NETs amplify TNF and IL-1β signaling.^[2]
• Dendritic cells shift to a pro-inflammatory, less tolerogenic phenotype and induce fewer regulatory T cells.^[2]

• Atypical Th2 response: non-classic NKT cells produce IL-5 and IL-13.^[4][5]
  • IL-13 is directly cytotoxic to epithelial cells.
  • It induces apoptosis and disrupts tight junctions.
• Th9 cells: these PU.1⁺ cells are induced by epithelial IL-33 and produce IL-9.^[5][11]
  • They are more enriched in UC mucosa than in Crohn’s disease.
  • They impair epithelial proliferation and barrier function.
• Th17 cells: these RORγt⁺ cells are driven by IL-23 and produce IL-17, IL-21, and IL-22. They are present in both UC and Crohn’s disease.^[5][12]
• Effector:regulatory T-cell imbalance: impaired regulation by IL-10 and TGF-β sustains inflammation.^[4]
  • Loss-of-function mutations in IL-10 or its receptor cause severe early-onset colitis.
• T-cell plasticity: T cells can change phenotype, for example Th17 cells converting to Th1 cells or mixed FOXP3⁺IL-17⁺ cells appearing. Together with redundancy in the cytokine network, this helps explain why blocking a single cytokine often fails.^[13]

T-cell subsets in UC versus Crohn’s disease

T-cell subset	Inducing signal	Signature cytokines	Predominant disease
Atypical Th2 (NKT-driven)	—	IL-5, IL-13	UC
Th9	IL-33	IL-9	UC
Th1	IL-12	IFN-γ, TNF, IL-6	Crohn’s disease
Th17	IL-23	IL-17, IL-21, IL-22	Both
Treg (reduced Treg:effector ratio)	—	IL-10, TGF-β	Both

Adapted from Neurath 2017 and Neurath 2019.^[12][5]

Pathogenic target	Mechanism	Representative agents
TNF	Neutralizes a dominant pro-inflammatory cytokine	Infliximab, adalimumab, golimumab
α4β7 integrin–MAdCAM-1	Blocks gut-selective lymphocyte trafficking	Vedolizumab
IL-12/IL-23 (p40); IL-23 (p19)	Inhibits the Th17/IL-23 axis	Ustekinumab; mirikizumab
JAK–STAT signaling	Oral inhibition of multiple cytokine pathways	Tofacitinib, filgotinib, upadacitinib
S1P receptor	Retains lymphocytes in lymph nodes	Ozanimod, etrasimod

Table sources: Gros 2023, Le Berre 2023, Neurath 2019.^[1][2][5]

Each agent blocks only one node of a redundant inflammatory network. As a result, only about 30–60% of patients respond to any given advanced therapy. This explains primary non-response and supports sequencing or combining mechanisms.^[1][13]

No single cause of ulcerative colitis (UC) has been identified. The current model is that UC results from a dysregulated innate and adaptive mucosal immune response against the commensal gut microbiota. This response occurs in genetically susceptible individuals and is triggered or shaped by environmental exposures and a defective epithelial barrier.^[1][2][3] Genetic risk is polygenic and explains only a small fraction of disease variance. Family history is the strongest individual risk factor. Environmental associations include an inverse association with current smoking and appendectomy, and positive associations with former smoking, enteric infection, antibiotic exposure, and Westernized diet. Dysbiosis is consistently present, but it is both a cause and a consequence of inflammation.

• Polygenic, low-penetrance architecture: Genome-wide association studies have identified more than 240 inflammatory bowel disease (IBD) risk loci. Most loci are shared between UC and Crohn’s disease.^[3][2] Known loci explain only about 4–7.5% of disease variance in UC (vs. about 8–13% in Crohn’s disease), so genetic testing has no predictive or diagnostic role in routine adult practice.^[3]
• Family history: About 8–14% of patients with UC report a family history of IBD. First-degree relatives have an approximately 4-fold increased risk.^[4][5]
• UC-predominant barrier genes: Loci involved in epithelial barrier and cell-adhesion function are characteristic of UC. Examples are HNF4A, CDH1 (E-cadherin), LAMB1, and ECM1.^[4][3]
• HLA region: The strongest UC association is in the MHC class II (HLA-DR) region. The HLA-DRB1*0103 allele is associated with extensive disease and a higher risk of colectomy.^[6]
• Shared immune pathways: Genes in the IL-23/Th17 pathway (IL23R, IL12B, STAT3, JAK2, TYK2) and IL-10 signaling are implicated in both UC and Crohn’s disease. Several of these pathways are now direct drug targets.^[3]
• Disease-divergent loci: Some variants have opposite effects in the two diseases. NOD2 and PTPN22 variants increase Crohn’s disease risk but appear protective in UC. For this reason, Crohn’s-centric genetics should not be applied to UC.^[7]
• Ancestry: Most GWAS data come from European and East Asian cohorts. Studies in African American populations have replicated HLA-DRB1 and identified ancestry-specific UC loci (ZNF649, LSAMP). Trans-ancestry meta-analysis has added further novel IBD loci.^[8][9]
• Very-early-onset IBD: This is the main exception to polygenic risk. Monogenic defects, most notably in IL-10 and IL-10 receptor signaling, can be causative and clinically actionable.^[3]

The rising global incidence of UC suggests a dominant environmental contribution, as does the convergence of risk in immigrants toward that of high-incidence host countries.^[1] Most associations come from observational, often retrospective studies.

• Enteric infection/antibiotics
• Westernized diet
• Urban living, oral contraceptives, vitaming D deficiency
• NSAIDs

• UC is consistently associated with reduced microbial diversity. Butyrate-producing Firmicutes (e.g., Faecalibacterium prausnitzii, Lachnospiraceae) are depleted, and facultative pathobionts (e.g., Proteobacteria, Escherichia) are expanded.^[10][11]
• No single causative organism has been identified. In the pathobiont model, otherwise-commensal microbes become pro-inflammatory under permissive host conditions.^[12]
• Causality runs in both directions and is unresolved. Inflammation increases luminal oxygen and nitrate, which favors Proteobacteria. Cross-sectional microbiome signatures should therefore not be read as evidence of causation.^[10]

• Adaptive immunity: UC shows an atypical Th2-skewed and Th17 effector response with regulatory T cell imbalance. Mediators include TNF, IL-13, IL-5, IL-17, IL-21, IL-22, and IL-23–regulated pathways.^[1][6]
• Innate immunity: Contributors include neutrophil accumulation with extracellular-trap formation, pro-inflammatory dendritic cells and macrophages, and innate lymphoid cells.^[1][13]
• Barrier failure: A defective mucus layer and impaired cell adhesion allow microbial antigens to penetrate the mucosa. This fits the UC-predominant barrier-gene associations described above.^[3]
• Therapeutic relevance: These pathways are the basis of current targeted therapies: anti-TNF agents, anti-α4β7 integrin (vedolizumab), anti-IL-12/23 and anti-IL-23 agents (ustekinumab, mirikizumab), JAK inhibitors (tofacitinib), and S1P-receptor modulators (ozanimod). See the medical therapy microchapter for details.^[2]

• UC is not a single-gene or single-pathogen disease. Genetic or microbiome testing to “find the cause” is not indicated in routine adult UC because it does not change management.^[3]
• First-degree relatives have about a 4-fold increased risk, which is relevant to counseling and diagnostic suspicion. No validated primary prevention strategy exists.^[5][1]
• In new-onset or flaring disease, take a history of recent enteric infection, antibiotic use, and smoking cessation. These are associations rather than proven causes.^[4][12]

• Whether dysbiosis is a cause or a consequence of inflammation remains unresolved.^[10]
• Most heritability is still unexplained. Rare variants, epigenetics, and gene–environment interactions are active research areas.^[1]
• Environmental associations are mostly retrospective and prone to recall bias and reverse causation. Some, such as the smoking and appendectomy effects, may differ by region.^[4][5]

Ulcerative colitis should be differentiated from other causes of diarrhea. It is very important to differentiate it from Crohn’s disease as the management of both conditions is different though the initial presentation may be confused for any of these disorders.^[1][2]

The following conditions may present in a similar manner as ulcerative colitis, and should be excluded:

• Crohn’s disease
• Infectious colitis, which is typically detected on stool cultures
  • Pseudomembranous colitis, or Clostridium difficile-associated colitis, bacterial upsets often seen following administration of antibiotics
• Ischemic colitis, inadequate blood supply to the intestine, which typically affects the elderly
• Radiation colitis in patients with previous pelvic radiotherapy
• Chemical colitis resulting from introduction of harsh chemicals into the colon from an enema or other procedure.

The most common disease that mimics the symptoms of Crohn’s disease is ulcerative colitis, as both are inflammatory bowel diseases that can affect the colon with similar symptoms. It is important to differentiate these diseases, since the course of the diseases and treatments may be different. In some cases, however, it may not be possible to tell the difference, in which case the disease is classified as indeterminate colitis.^{[1][2][3][4][5][6]}

Comparisons of various factors in Crohn’s disease and ulcerative colitis

	Crohn’s disease	Ulcerative colitis
Terminal ileum involvement	Commonly	Seldom
Colon involvement	Usually	Always
Rectum involvement	Seldom	Usually[7]
Involvement around the anus	Common[8]	Seldom
Bile duct involvement	No increase in rate of primary sclerosing cholangitis	Higher rate[9]
Distribution of Disease	Patchy areas of inflammation (Skip lesions)	Continuous area of inflammation[7]
Endoscopy	Deep geographic and serpiginous (snake-like) ulcers	Continuous ulcer
Depth of inflammation	May be transmural, deep into tissues[8]	Shallow, mucosal
Fistulae	Common[8]	Seldom
Stenosis	Common	Seldom
Autoimmune disease	Widely regarded as an autoimmune disease	No consensus
Cytokine response	Associated with Th1	Vaguely associated with Th2
Granulomas on biopsy	Can have granulomas[8]	Granulomas uncommon[7]
Surgical cure	Often returns following removal of affected part	Usually cured by removal of colon
Smoking	Higher risk for smokers	Lower risk for smokers[7]
Risk of Cancer	Lower than UC	Higher

Organism			Age predilection	Travel History	Incubation Size (cell)	Incubation Time	History and Symptoms			Diarrhea type∞				Food source	Specific consideration
							Fever	N/V	Cramping Abd Pain	Small Bowel	Large Bowel	Inflammatory	Non-inflammatory
Viral	Rotavirus		<2 y	–	<102	<48 h	+	+	–	+			+	–	Mostly in day cares, most common in winter.
	Norovirus		Any age	–	10 -103	24-48 h	+	+	+	+			+	–	Most common cause of gastroenteritis, abdominal tenderness,
	Adenovirus		<2 y	–	105 -106	8-10 d	+	+	+	+			+	–	No seasonality
	Astrovirus		<5 y	–		72-96 h	+	+	+	+			+	Seafood	Mostly during winter
Bacterial	Escherichia coli	ETEC	Any age	+	108 -1010	24 h	–	+	+	+			+	–	Causes travelers diarrhea, contains heat-labile toxins (LT) and heat-stable toxins (ST)
		EPEC	<1 y	–	10†	6-12 h	–	+	+	+			+	Raw beef and chicken	–
		EIEC	Any ages	–	10†	24 h	+	+	+		+		+	Hamburger meat and unpasteurized milk	Similar to shigellosis, can cause bloody diarrhea
		EHEC	Any ages	–	10	3-4 d	–	+	+		+	+		Undercooked or raw hamburger (ground beef)	Known as E. coli O157:H7, can cause HUS/TTP.
		EAEC	Any ages	+	1010	8-18 h	–	–	+		+		+	–	May cause prolonged or persistent diarrhea in children
	Salmonella sp.		Any ages	+	1	6 to 72 h	+	+	+		+	+		Meats, poultry, eggs, milk and dairy products, fish, shrimp, spices, yeast, coconut, sauces, freshly prepared salad.	Can cause salmonellosis or typhoid fever.
	Shigella sp.		Any ages	–	10 – 200	8-48 h	+	+	+		+	+		Raw foods, for example, lettuce, salads (potato, tuna, shrimp, macaroni, and chicken)	Some strains produce enterotoxin and Shiga toxin similar to those produced by E. coli O157:H7
	Campylobacter sp.		<5 y, 15-29 y	–	104	2-5 d	+	+	+		+	+		Undercooked poultry products, unpasteurized milk and cheeses made from unpasteurized milk, vegetables, seafood and contaminated water.	May cause bacteremia, Guillain-Barré syndrome (GBS), hemolytic uremic syndrome (HUS) and recurrent colitis
	Yersinia enterocolitica		<10 y	–	104 -106	1-11 d	+	+	+		+	+		Meats (pork, beef, lamb, etc.), oysters, fish, crabs, and raw milk.	May cause reactive arthritis; glomerulonephritis; endocarditis; erythema nodosum. can mimic appendicitis and mesenteric lymphadenitis.
	Clostridium perfringens		Any ages		> 106	16 h	–	–	+		+		+	Meats (especially beef and poultry), meat-containing products (e.g., gravies and stews), and Mexican foods.	Can survive high heat,
	Vibrio cholerae		Any ages	–	106-1010	24-48 h	–	+	+	+			+	Seafoods, including molluscan shellfish (oysters, mussels, and clams), crab, lobster, shrimp, squid, and finfish.	Hypotension, tachycardia, decreased skin turgor. Rice-water stools
Parasites	Protozoa	Giardia lamblia	2-5 y	+	1 cyst	1-2 we	–	–	+	+			+	Contaminated water	May cause malabsorption syndrome and severe weight loss
		Entamoeba histolytica	4-11 y	+	<10 cysts	2-4 we	–	+	+		+	+		Contaminated water and raw foods	May cause intestinal amebiasis and amebic liver abscess
		Cryptosporidium parvum	Any ages	–	10-100 oocysts	7-10 d	+	+	+	+			+	Juices and milk	May cause copious diarrhea and dehydration in patients with AIDS especially with 180 > CD4
		Cyclospora cayetanensis	Any ages	+	10-100 oocysts	7-10 d	–	+	+	+			+	Fresh produce, such as raspberries, basil, and several varieties of lettuce.	More common in rainy areas
	Helminths	Trichinella spp	Any ages	–	Two viable larvae (male and female)	1-4 we	–	+	+		+		+	Undercooked meats	More common in hunters or people who eat traditionally uncooked meats
		Taenia spp	Any ages	–	1 larva or egg	2-4 m	–	+	+	+			+	Undercooked beef and pork	Neurocysticercosis: Cysts located in the brain may be asymptomatic or seizures, increased intracranial pressure, headache.
		Diphyllobothrium latum	Any ages	–	1 larva	15 d	–	–	–	+			+	Raw or undercooked fish.	May cause vitamin B12 deficiency

∞Small bowel diarrhea: watery, voluminous with less than 5 WBC/high power field

Large bowel diarrhea: Mucousy and/or bloody with less volume and more than 10 WBC/high power field
† It could be as high as 1000 based on patient’s immunity system.

The table below summarizes the findings that differentiate inflammatory causes of chronic diarrhea^{[10][11][12][13][13]}

Cause	History	Laboratory findings	Diagnosis	Treatment
Diverticulitis	Bloody diarrhea Left lower quadrant abdominal pain Abdominal tenderness on physical examination Low grade fever	Leukocytosis Elevated serum amylase and lipase Sterile pyuria on urinalysis	Abdominal CT scan with oral and intravenous (IV) contrast	bowel rest, IV fluid resuscitation, and broad-spectrum antimicrobial therapy which covers anaerobic bacteria and gram-negative rods
Ulcerative colitis	Diarrhea mixed with blood and mucus, of gradual onset. Signs of weight loss Rectal urgency Tenesmus Blood is often noticed on underwear Different degrees of abdominal pain	Anemia Thrombocytosis A high platelet count Elevated ESR (>30mm/hr) Low albumin	Endoscopy	Induction of remission with mesalamine and corticosteroids followed by the administration of sulfasalazine and 6-Mercaptopurine depending on the severity of the disease.
Entamoeba histolytica	Abdominal cramps Diarrhea Passage of 3 – 8 semiformed stools per day Passage of soft stools with mucus and occasional blood Fatigue Intestinal gas (excessive flatus) Rectal pain while having a bowel movement (tenesmus) Unintentional weight loss	cysts shed with the stool	detects ameba DNA in feces	Amebic dysentery Metronidazole 500-750mg three times a day for 5-10 days Tinidazole 2g once a day for 3 days is an alternative to metronidazole Luminal amebicides for E. histolytica in the colon: Paromomycin 500mg three times a day for 10 days Diloxanide furoate 500mg three times a day for 10 days Iodoquinol 650mg three times a day for 20 days For amebic liver abscess: Metronidazole 400mg three times a day for 10 days Tinidazole 2g once a day for 6 days is an alternative to metronidazole Diloxanide furoate 500mg three times a day for 10 days must always be given afterwards.

Ulcerative colitis (UC) is most common in early-industrialized regions such as North America, Northern and Western Europe, and Oceania. In these regions incidence has stabilized or declined since 1990, while prevalence continues to rise.^[1][2] Incidence is now rising rapidly in newly industrialized countries of Asia, Latin America, and the Middle East. UC therefore can no longer be regarded as a disease confined to Western populations.^[3] In the United States, UC prevalence is approximately 378 per 100,000 population, or about 1.25 million people.^[4] UC is most often diagnosed in the second to fourth decades of life, but elderly-onset disease accounts for a growing share of new diagnoses. There is no consistent sex predominance.^[5]

The older description of a static north–south gradient, with identical worldwide distribution of UC and Crohn’s disease, has been replaced by a model of four epidemiologic stages through which regions move as they industrialize.^[2] These stages have now been quantified using 522 population-based studies from 82 regions covering 1920–2024.^[3]

Epidemiologic stages of inflammatory bowel disease

Stage	Incidence and prevalence pattern	Representative regions
1. Emergence	Low incidence and low prevalence	Developing countries
2. Acceleration in incidence	Incidence rising rapidly; prevalence still low	Newly industrialized countries in Asia, the Middle East, and Latin America
3. Compounding prevalence	Incidence slowing, plateauing, or declining; prevalence rising steadily	North America, Western Europe, Oceania
4. Prevalence equilibrium	Prevalence plateaus as deaths in an aging IBD population balance new diagnoses	Not yet observed; modeled for several high-income regions by about 2045[3]

• Early-industrialized regions: Since 1990, most population-based studies from North America and Europe report stable or declining UC incidence.^[1] The highest UC incidence rates worldwide are reported from Northern Europe, particularly Scandinavia.^[1][6]
• United States: The age- and sex-standardized incidence of IBD is 10.9 per 100,000 person-years.^[4] In a US employment-based claims cohort, UC incidence did not change between 2010 and 2019.^[7]
• Newly industrialized regions: Incidence is rising sharply. For example, UC incidence in Brazil had an average annual percentage change of +14.9% from 1988 to 2012.^[1] In transitioning regions, UC incidence typically rises before Crohn’s disease incidence.^[2] UC incidence in Japan has increased steadily since the 1960s.^[7]
• Children: Incidence of pediatric-onset IBD continues to rise.^[8]

• The highest prevalence is reported in Europe, reaching about 505 per 100,000 in Norway, and in North America.^[1]
• UC prevalence in North America exceeds 400 per 100,000.^[6]
• United States: A pooled, insurance-standardized analysis of 4 administrative datasets estimated UC prevalence at 378 per 100,000 (about 1.25 million Americans). Overall IBD prevalence was 721 per 100,000.^[4]
• Japan and the United States: In employment-based claims data from 2010 to 2019, UC prevalence rose in both countries. In the US it rose from 158 to 233 per 100,000; in Japan it reached an age-standardized 98 per 100,000 by 2019.^[7]
• Trajectory: UC begins early in life and carries low mortality, so prevalence keeps compounding in high-income regions. Prevalence equilibrium is projected there by about 2045, while incidence continues to rise in Asia, Africa, and Latin America.^[3]

• UC can present at any age. It is most commonly diagnosed in the second to fourth decades, with peak onset at about 30–40 years.^[5][9]
• In US data, IBD incidence peaks in the third decade of life. It then stays at a lower, relatively stable level through the fourth to eighth decades, with no discrete second peak.^[4]
• Elderly-onset UC: Patients older than 60 years account for up to 20% of new UC diagnoses. This share is growing with population aging and complicates management because of comorbidity and polypharmacy.^[5]

• Men and women are affected roughly equally. Some adult series show a slight male predominance.^[5]
• The sex ratio varies by population. Men predominate among patients with UC in Japan, whereas women slightly predominate in a US employment-based cohort.^[7]

• In the United States, IBD prevalence is 812 per 100,000 in White, 504 in Black, 458 in Hispanic, and 403 in Asian Americans. IBD is therefore less often diagnosed in Black, Asian, and Hispanic Americans, though it still occurs in substantial numbers.^[4]
• People of Ashkenazi Jewish ancestry have a 2- to 5-fold higher risk of UC.^[10][11] Ethnic differences in IBD risk have diminished over time, which points to environmental contributions.^[12]
• Migration: Children of migrants who move from low- to high-incidence countries develop IBD risk approaching that of the host population. This supports a strong gene–environment interaction.^[12][9]
• For genetic, environmental, and lifestyle determinants of UC, see Ulcerative colitis risk factors.

Ulcerative colitis (UC) develops from the interaction of genetic susceptibility, environmental exposures, gut dysbiosis, and dysregulated mucosal immunity; no single risk factor is necessary or sufficient.^[1][2] A family history of inflammatory bowel disease (IBD) is the strongest known risk factor, conferring roughly 4–10 times the background risk in first-degree relatives.^[3][4] UC risk is characteristically increased in former smokers and reduced in current smokers and after appendectomy for appendicitis in early life, the inverse of the pattern seen in Crohn’s disease.^[5][6] Most environmental associations derive from observational, largely retrospective data subject to recall bias and reverse causation, and should be interpreted as risk markers rather than proven causal or modifiable targets.^[7]

• Family history: First-degree relatives of a person with UC have approximately 4–10 times the background risk (adjusted incidence rate ratios 4–10 across population studies; pooled relative risk ~8, 95% CI 5.9–10.7).^[3][4][8]
• Offspring risk: Absolute risk is approximately 6% when a parent has UC (vs ~9% with parental Crohn’s disease). Risk increases with the number of affected relatives and younger age at the relative’s diagnosis, and is higher between siblings than across generations. Maternal and paternal transmission risks are roughly equivalent.^[8]
• Twin concordance: ~15–19% in monozygotic vs ~4% in dizygotic twins, substantially lower than in Crohn’s disease, indicating a dominant contribution of non-genetic factors.^[3][4]
• Susceptibility loci: Genome-wide association studies have identified more than 240 IBD risk loci, most shared between UC and Crohn’s disease, implicating HLA genes, epithelial barrier genes (e.g., HNF4A, CDH1), and IL-23/T-cell pathways (IL23R, STAT3, JAK2). These loci explain only ~7.5–8.2% of UC disease variance.^[9][10][3]
• Clinical implication: Genetic risk scores have no validated role in predicting onset or phenotype, and no preventive intervention has been validated for at-risk relatives.^[9]

• Age: UC can occur at any age; incidence peaks in early-to-mid adulthood (UC peak approximately 30–40 years), and prevalence rises with age before declining after ~80 years. A reproducible bimodal age distribution is not well supported.^[10][11]
• Sex: No consistent sex predominance.^[10]
• Race and ethnicity (United States): IBD prevalence is highest in White Americans (812 per 100,000) and lower in Black (504), Hispanic (458), and Asian (403) Americans; the gap is narrowing. The UC-to-Crohn’s disease ratio is higher in Asian (1.6:1) and Hispanic (1.8:1) than in White or Black (1.2:1) Americans.^[11]
• Jewish ancestry: Historically associated with higher IBD rates.
• Geography and migration: Incidence has historically been highest in northern Europe, Canada, and Australasia but is rising sharply in newly industrialized regions of Asia, the Middle East, and South America in parallel with Westernization. Migrants from low- to high-incidence regions, and particularly their children, acquire the host-country risk, implicating early-life environmental exposures.^[10]

The strength of evidence varies widely; credibility grading is drawn from umbrella reviews and meta-analyses of observational studies.^[7][12]

Factor	Association with UC onset
Former smoking	Increased risk (OR ~1.6–1.8)
Current smoking	Decreased risk (OR ~0.58); milder disease course
Appendectomy for appendicitis before ~20 years	Decreased risk (~69% reduction; OR ~0.31)
Prior bacterial gastroenteritis (Salmonella, Shigella, Campylobacter)	Approximately 2-fold increased risk
Vitamin D deficiency	Increased risk (OR ~2.0)
Oral contraceptives and hormone replacement therapy	Increased risk (oral contraceptives OR ~1.18)
Antibiotic exposure	Increased risk in Western cohorts (OR ~1.40)
Cesarean delivery	Increased risk (OR ~1.17)
Diet	Increased risk with high total energy intake, high n-6 polyunsaturated fatty acids, soft drinks, and processed “Western” diets
Isotretinoin	Increased risk reported
NSAIDs	Weak association with onset and relapse
Urban living / industrialization	Inconsistent
Psychological stress	No association with new-onset UC in pooled European prospective data

Several Western risk factors (urban living, antibiotic exposure, the protective effect of appendectomy, and the effect of smoking) do not replicate uniformly in Asian and Middle Eastern populations, and Western data should not be applied uncritically to these patients.^[6][12][10]

• Breastfeeding, high vitamin D levels, tea consumption, physical activity, and Helicobacter pylori colonization are associated with lower IBD risk.^[7]
• Current smoking and early-life appendectomy for appendicitis (see table above).^[5][6]

• UC is associated with dysbiosis characterized by reduced microbial diversity, loss of short-chain fatty acid–producing anaerobes (Firmicutes, Roseburia, Lachnospiraceae), and expansion of facultative anaerobes and Proteobacteria, including adherent Escherichia coli pathobionts, in an oxygen- and nitrate-rich inflamed mucosal environment.^[13][14]
• No single causative organism has been reproducibly identified, and dysbiosis appears to be both a contributor to and a consequence of mucosal inflammation.^[2][15]

• Document a detailed family history of IBD (number and type of affected relatives, age at their diagnosis); it is the most informative single risk descriptor, and siblings carry higher risk than offspring.^[8]
• Recognize recent smoking cessation or a recent episode of bacterial gastroenteritis as a plausible antecedent of new-onset UC.^[5][10]
• Do not recommend starting or resuming smoking to prevent or treat UC despite the epidemiologic protective signal; counsel cessation per usual standards.^[10][6]
• Modest twin concordance does not imply low familial risk; family history still raises risk several-fold.^[3]
• Genetic and microbiome testing have no validated role in predicting UC onset or guiding prevention outside research settings.^[9][2]
• No dietary, antibiotic, or supplement regimen is proven to prevent UC.^[9][7]

Patients with ulcerative colitis (UC) extending beyond the rectum have an increased risk of colitis-associated colorectal cancer (CRC), driven mainly by disease duration, extent, and cumulative inflammation, with the highest risk in patients with concomitant primary sclerosing cholangitis (PSC). Contemporary population-based data show a relative risk of approximately 1.4–1.7 compared with the general population, substantially lower than historical estimates but still above the threshold at which colonoscopic surveillance is recommended.^[1][2] All major societies recommend an index (baseline) colonoscopy approximately 8 years after symptom onset to re-stage disease extent and stratify risk, with immediate and annual surveillance for patients with PSC.^[1][3][4] Subsequent surveillance intervals (1, 3, or up to 5–10 years) are individualized according to inflammatory activity, extent, PSC, prior dysplasia, strictures, post-inflammatory polyps, and family history of CRC. Surveillance should be performed in remission, with high-definition colonoscopy, preferably with dye-based chromoendoscopy, by endoscopists trained in IBD surveillance. Random biopsies are now reserved for high-risk patients or for white-light-only examinations. Proctitis alone does not warrant IBD-specific surveillance.^[1]

Population	Recommendation
UC extending beyond the rectum (left-sided or extensive)	Index colonoscopy ~8 years after symptom onset to re-stage extent (with segmental biopsies) and assign a surveillance interval
UC with PSC (including after liver transplantation for PSC)	Colonoscopy at the time of PSC diagnosis, then annually
UC endoscopically confirmed as confined to the rectum	No IBD-specific surveillance; age-appropriate population CRC screening; reassess if symptoms suggest proximal extension
Childhood-onset UC	Consider surveillance at transition to adult care (age 16–18 years) at 1–3-year intervals
Age ≥75 years or significant comorbidity/frailty	Shared decision on continuing; discontinue when procedural risk exceeds expected benefit within life expectancy

• Disease extent should be defined by the maximal historical extent, including histologic extent; the index colonoscopy should include biopsies from each colonic segment to document histologic activity and extent.^[3][1]
• UC with concurrent Lynch syndrome or another hereditary CRC syndrome should follow the most intensive applicable surveillance program.^[1]

• Fixed: disease duration, extent (proximal to the splenic flexure), PSC, family history of CRC in a first-degree relative, young age at diagnosis, male sex, older age.
• Modifiable / dynamic: cumulative endoscopic and histologic inflammation (the key modifiable risk factor), colonic stricture, post-inflammatory polyps, prior dysplasia, and smoking (HR 1.17 per 10 pack-years for colorectal neoplasia).^[1]
• Risk factors should be reviewed at least annually in clinic and after every surveillance examination, and intervals adjusted accordingly.^[1]

Guideline	Annual (high risk)	Intermediate interval	Longest interval (low risk)
BSG 2025 (GRADE methodology; good practice statements)[1]	Moderate active inflammation after optimized therapy, dysplasia, PSC, colonic stricture, or calculated moderate 5-year advanced colorectal neoplasia (aCRN) risk	3 years: mild active inflammation, extensive colitis, post-inflammatory polyps, first-degree relative with CRC (any age, Lynch syndrome excluded), or small calculated risk	10-year colonoscopic reassessment plus population CRC screening if none of these factors, or calculated 5-year aCRN risk close to population risk (<3.6%)
ECCO (2017 consensus; 2023 malignancy guideline)[5]	Extensive colitis with severe active inflammation; stricture or dysplasia in past 5 years; PSC; first-degree relative with CRC <50 years	2–3 years: extensive colitis with mild–moderate inflammation, post-inflammatory polyps, first-degree relative with CRC ≥50 years	5 years: none of the above
AGA 2021 (clinical practice update; best practice advice)[3]	PSC, moderate–severe inflammation of any extent, first-degree relative with CRC <50 years, dense pseudopolyposis, invisible dysplasia or higher-risk visible dysplasia within past 5 years	Every 1–5 years, guided by cumulative risk factors and the quality of prior examinations	Up to 5 years for low-risk patients with quiescent disease and high-quality prior examinations
ACG (2019; updated 2025)[6][7]	PSC	Every 1–3 years based on combined risk factors and findings on prior colonoscopy	—
NICE CG118 (2011; reviewed 2026)[8]	Extensive colitis with moderate–severe active inflammation; stricture in past 5 years; dysplasia in past 5 years in patients declining surgery; PSC or liver transplant for PSC; first-degree relative with CRC <50 years	3 years: extensive colitis with mild active inflammation, post-inflammatory polyps, first-degree relative with CRC ≥50 years	5 years: extensive quiescent colitis or left-sided colitis

• The BSG 2025 guideline endorses the use of a validated multivariable calculator that estimates 5- and 10-year aCRN risk from up to eight clinical factors as an alternative to the “single highest risk factor” approach (IBD dysplasia calculator). It is validated for ages 18–75 and up to 30 years of surveillance follow-up, and does not incorporate family history, which must be considered separately.^[1]
• Two consecutive good-quality colonoscopies without endoscopic or histologic inflammation predict a very low risk of future advanced neoplasia and should prompt reassessment of the need for continued intensive surveillance.^[1]

• Surveillance is ideally performed when the colitis is in remission, because active inflammation impairs dysplasia detection and its histologic interpretation.^[1][3]
• Low-volume (2 L) polyethylene glycol preparation is recommended over 4 L PEG in the BSG 2025 guideline: equivalent cleansing success (RR 0.98; moderate certainty) with greater willingness to repeat (high certainty). Sulfate- and picosulfate-based preparations appear comparably effective.^[1]
• Inadequate preparation (e.g., Boston Bowel Preparation Scale <6) is associated with IBD PCCRC (OR 5.9); a repeat examination within 3–6 months is suggested rather than the standard 1-year repeat used in non-IBD practice.^[1]

Modality	Guideline position
High-definition (HD) vs standard-definition (SD) white-light endoscopy	HD recommended over SD (SCENIC: strong recommendation, low-quality evidence; BSG 2025: recommended)[4][1]
Dye-based chromoendoscopy (DCE; indigo carmine or methylene blue) with HD colonoscopy	Suggested over HD white light (SCENIC: conditional, low-quality evidence; BSG 2025: suggested, low certainty). With SD colonoscopy, DCE is recommended (SCENIC: strong, moderate-quality)[4][1]
Virtual chromoendoscopy (NBI, i-SCAN, FICE)	SCENIC: NBI not suggested in place of HD-WLE or DCE (conditional). BSG 2025: no recommendation possible[4][1]
Computer-aided detection (CADe)	Not recommended for IBD surveillance (BSG 2025 expert opinion)[1]

• Targeted biopsy or resection of all visible lesions is the cornerstone of modern surveillance; most dysplasia in UC is now endoscopically visible.^[4][3]
• Segmental biopsies (from each colonic segment and the rectum) should be taken to document histologic activity and extent, which determine future intervals.^[1][3]
• Non-targeted (random) quadrantic biopsies every 10 cm:
  • Required when HD white light is used without dye or virtual chromoendoscopy (approximately 4 biopsies every 10 cm in previously inflamed segments; AGA best practice advice 8).^[3]
  • Should be considered even when dye spray is used in high-risk groups: PSC, dysplasia within the colitis segment in the past 5 years, before segmental colectomy, a retained rectum, and the rectal cuff of an ileal pouch (BSG 2025 expert opinion).^[1]
  • In a community-based dye-spray cohort, random biopsies detected dysplasia in only 1.2% of colonoscopies overall but in 12.8% of patients with prior neoplasia.^[1]

• Lesions should be described with the modified Paris classification: polypoid (≥2.5 mm tall), nonpolypoid (<2.5 mm), or invisible (dysplasia found on non-targeted biopsy). The terms “DALM,” “adenoma-like mass,” and “flat dysplasia” should be abandoned.^[3][4]
• Lesion reports should include site, morphology, size, whether borders are clearly delineated, ulceration, features of submucosal fibrosis or invasion, and surrounding inflammation.^[1]
• Any suspected dysplasia should be reviewed by a second (preferably GI) pathologist and discussed at an IBD multidisciplinary team (MDT) meeting. p53 immunohistochemistry can help distinguish dysplasia from reactive atypia. Non-conventional dysplasia subtypes (e.g., goblet cell–deficient, crypt cell, serrated) carry similar or higher risk than conventional dysplasia. Serrated epithelial change without dysplasia does not by itself shorten the surveillance interval.^[1]

Detailed management of dysplasia is addressed in the treatment microchapters; the points below determine subsequent screening intervals.

• Adenomas or serrated lesions arising outside any segment ever affected by colitis are managed according to sporadic post-polypectomy guidelines.^[1]
• After complete endoscopic removal of polypoid dysplasia, surveillance colonoscopy is recommended rather than colectomy (SCENIC: strong, very low-quality evidence). For nonpolypoid dysplasia, surveillance is suggested (conditional, very low-quality).^[4] The pooled CRC incidence after endoscopic resection of IBD dysplasia is ~0.2 per 100 person-years.^[1]
• BSG 2025 post-resection intervals (good practice statements):^[1]
  • Polypoid low-grade dysplasia (LGD) <2 cm resected en bloc: annual surveillance for 5 years.
  • High-grade dysplasia (HGD), or LGD with higher-risk features (polypoid ≥2 cm, nonpolypoid, multifocal, or piecemeal resection): repeat at 3–6 months, then annually for 5 years.
  • After 5 years without recurrence and without high-risk patient factors, de-escalation may be considered.
• Invisible dysplasia (confirmed by a GI pathologist) should prompt referral to an endoscopist with IBD expertise for repeat HD chromoendoscopy (SCENIC: conditional, very low-quality evidence).^[4]
• Colectomy should be discussed for endoscopically unresectable visible dysplasia, invisible or multifocal dysplasia with high progression risk, settings where surveillance is ineffective (severe pseudopolyposis, strictures), or coexisting risk factors such as PSC or uncontrolled inflammation.^[1]

• After limited resection (segmental, subtotal, or total colectomy with retained rectum) for dysplasia or cancer, surveillance is suggested at 3–6 months and then annually for 5 years.^[1]
• After restorative proctocolectomy with ileal pouch–anal anastomosis (IPAA), surveillance of the pouch and rectal cuff is not routinely required for all patients, but should be offered to those with risk factors (e.g., prior dysplasia or CRC, PSC). Non-targeted biopsies of the rectal cuff are appropriate in this group.^[1]

• Schedule an index colonoscopy ~8 years after symptom onset for every patient with UC, regardless of the extent documented at diagnosis.
• Start annual colonoscopy at diagnosis of PSC and continue after liver transplantation.
• Assign the next interval using documented risk factors (inflammation grade, extent, PSC, stricture, post-inflammatory polyps, prior dysplasia, family history) or a validated multivariable calculator, and record the interval explicitly in the report.
• Perform surveillance in remission, with split-dose low-volume preparation, using an HD colonoscope, preferably with dye-based chromoendoscopy and targeted biopsies.
• Take segmental biopsies for histologic activity at every surveillance colonoscopy; add quadrantic random biopsies every 10 cm in PSC, recent dysplasia, retained rectum/pouch cuff, or when chromoendoscopy is not used.
• Repeat the examination within 3–6 months when bowel preparation is inadequate or active inflammation limits assessment.
• Refer all dysplasia within a colitis-affected segment for second pathologist review and IBD MDT discussion.
• Optimize control of inflammation; persistent inflammation shortens the surveillance interval and is the principal modifiable risk factor.
• Build recall systems (registries, automated reminders) to improve concordance; delayed surveillance is a leading cause of PCCRC.
• Patients with proctitis alone should follow general population CRC screening.

• Lower contemporary risk: relative risk ~1.4–1.7 in modern cohorts vs historical cumulative risks of up to 18% at 30 years.
• Uniform start at ~8 years: the older practice of delaying the first colonoscopy to 12–15 years for left-sided colitis has been abandoned; all patients beyond proctitis are re-staged at ~8 years.
• Visible dysplasia paradigm: most dysplasia is visible with HD and chromoendoscopy; random biopsies are no longer routine for every patient.
• Endoscopic resection over reflex colectomy: completely resected visible dysplasia, including selected nonpolypoid lesions, is managed with continued surveillance.
• Terminology: DALM, ALM, and “flat dysplasia” are replaced by polypoid, nonpolypoid, and invisible dysplasia.
• Risk-tailored intervals: BSG 2025 introduces a minimum 3-year interval for patients under active surveillance, 10-year reassessment for population-level risk, and multivariable risk calculators.
• Cumulative inflammation (endoscopic and histologic) is recognized as the dominant modifiable risk factor.
• Pathology: non-conventional dysplasia subtypes and mandatory double reporting are now emphasized.

• The index colonoscopy is a staging examination: histologic extent often exceeds endoscopic extent and determines the surveillance category.
• Persistent histologic inflammation counts as a risk factor even when the mucosa looks endoscopically normal.
• PSC trumps everything: annual surveillance from diagnosis, including after liver transplantation, with random biopsies added to targeted sampling.
• Approximately 32–33 random biopsies are needed to exclude dysplasia with 80–90% confidence; this is why lesion detection with HD/chromoendoscopy has replaced random sampling as the primary strategy.^[1]
• A colonic stricture in longstanding UC must be considered malignant until proven otherwise.
• UC-associated CRC often arises in younger patients, is more often right-sided, and has a worse stage-adjusted prognosis than sporadic CRC.
• Finding an early, surgically curable cancer on surveillance is still a surveillance success; not all colitis-associated CRC is preventable.

• Failing to start surveillance because the patient “only had left-sided colitis” at diagnosis without re-staging.
• Performing surveillance during a flare and accepting the examination as adequate.
• Accepting poor bowel preparation and deferring the repeat examination by a year or more.
• Using random biopsies instead of careful inspection of the mucosa, or omitting random biopsies in high-risk patients.
• Biopsying a resectable lesion extensively before referral, which can cause submucosal fibrosis and hinder en bloc resection.
• Labeling an adenoma within a colitis-affected segment as “sporadic” and applying sporadic polyp intervals.
• Not referring dysplasia for second pathologist review and MDT discussion.
• Losing patients to follow-up without a recall system; delayed surveillance is a leading cause of post-colonoscopy CRC.
• Offering IBD surveillance to patients with proctitis alone, or omitting general population screening for them.
• Relying on commercial CADe systems that were not trained on IBD mucosa.

Ulcerative colitis (UC) is a lifelong relapsing–remitting disease with no reliable medical cure; proctocolectomy is the only definitive cure.^[1] In population-based cohorts, the cumulative risk of relapse is approximately 70–80% at 10 years, about 10–15% of patients follow an aggressive course, nearly half require at least one UC-related hospitalization, and the 5- and 10-year cumulative risk of colectomy is approximately 10–15%.^[2] Major complications include acute severe ulcerative colitis with toxic megacolon, perforation or massive hemorrhage, venous thromboembolism, extraintestinal manifestations, and colitis-associated colorectal cancer (CRC).^[3] Contemporary CRC risk is substantially lower than historical referral-center estimates, and surveillance colonoscopy is risk-stratified, beginning 8 years after symptom onset or at diagnosis of primary sclerosing cholangitis (PSC).^[4][5] Large nationwide cohorts show a modest excess all-cause mortality (adjusted HR ~1.4 in Sweden), although relative mortality has declined over time.^[6]

• Left-sided colitis is the most frequent distribution at diagnosis.^[2] Across population-based cohorts, 30–60% present with proctitis, 16–45% with left-sided colitis, and 14–35% with extensive colitis.^[1]
• Proximal extension occurs in 10–30% of patients over time, approximately 10–19% at 5 years and 11–28% at 10 years.^[2][7]
• Fewer than 5% of patients are later reclassified as Crohn’s disease.^[1][2]

• Most patients have a mild-to-moderate course that is most active at diagnosis, followed by variable periods of remission or mild activity.^[2]
• Cumulative relapse risk is approximately 70–80% at 10 years; about 10–15% of patients experience an aggressive course.^[2]
• UC is increasingly regarded as a progressive disease: persistent inflammation is associated with phenotypic extension, structural bowel damage, colorectal dysfunction, neoplasia, hospitalization, and colectomy.^[8]

• Younger age at onset (<40 years); onset after age 60 tends to be milder^[1]
• Extensive colitis
• Deep ulcerations and failure to achieve mucosal healing
• High perinuclear antineutrophil cytoplasmic antibody (pANCA) titers
• Fever or weight loss at diagnosis, short interval to first flare, and active disease in the preceding year^[9]

• Almost 50% of patients require UC-related hospitalization, and the 5-year risk of re-hospitalization is ~50%.^[2]
• Within 5 years of diagnosis, ~20% of patients are hospitalized and ~7% undergo colectomy.^[4]
• The 5- and 10-year cumulative colectomy risk is ~10–15%; older estimates of 20–40% reflect pre-biologic, referral-center populations. Achieving mucosal healing is associated with a lower colectomy risk.^[2]

• Acute severe ulcerative colitis may be complicated by toxic megacolon (nonobstructive colonic dilatation, classically of the transverse colon, with systemic toxicity), bowel perforation, and massive hemorrhage.^[3][10]
• Venous thromboembolism risk is increased, particularly during active disease and hospitalization.^[3]

• Structural damage: benign strictures, pseudopolyps, a shortened ahaustral (“lead-pipe”) colon, colonic dysmotility, and anorectal dysfunction.^[1][8]
• Hematologic: iron deficiency anemia and anemia of chronic disease.^[3]
• Neoplasia: dysplasia and colitis-associated CRC (see below).

Extraintestinal manifestations (EIMs) are common; one review estimated EIMs, including PSC, in approximately 27% of patients with UC.^[4]

• Musculoskeletal: peripheral arthropathy, sacroiliitis, ankylosing spondylitis
• Cutaneous: erythema nodosum, pyoderma gangrenosum
• Ocular: episcleritis, uveitis
• Hepatobiliary: primary sclerosing cholangitis
• Oral: aphthous ulcers^[3]

• UC confers approximately a 1.7-fold higher CRC risk than the general population, with a cumulative risk of ~4.5% at 20 years.^[4]
• Contemporary cumulative estimates (~1%, ~3%, and ~7% at 10, 20, and 30 years) are substantially lower than the classic referral-center estimates (2%, 8%, and 18%).^[10]
• In population-based cohorts, ~1.5% of patients were diagnosed with CRC after 15 years of follow-up.^[2]
• Isolated proctitis carries little or no excess risk.^[11]

• Longer disease duration and greater anatomic extent
• Cumulative inflammatory burden (severity and persistence of endoscopic/histologic inflammation), an independent and modifiable risk factor^[8]
• Concomitant PSC
• Family history of CRC, especially a first-degree relative diagnosed before age 50
• Colonic stricture, dense pseudopolyposis, prior dysplasia, and a tubular/shortened colon^[12][5]

• PSC occurs in a minority of patients with UC, whereas most patients with PSC have inflammatory bowel disease, most commonly UC; the association is bidirectional.^[13][4]
• PSC-associated UC is a distinct phenotype: often extensive but endoscopically mild colitis with right-sided predominance, rectal sparing, and backwash ileitis.^[1]
• CRC risk is approximately 4-fold higher in UC with PSC than in UC alone.^[14]
• Long-term outcome in PSC-UC is driven largely by hepatobiliary disease, including end-stage liver disease, cholangiocarcinoma, and need for liver transplantation.^[13]
• Whether colectomy modifies PSC progression or post-transplant recurrence is uncertain; observational data conflict, and colectomy decisions are driven by colonic indications.^[13]

• A meta-analysis of population-based inception cohorts found no significant excess overall mortality but increased mortality from gastrointestinal causes.^[15]
• Larger nationwide cohorts show a modest excess: in Sweden, all-cause mortality in UC was increased (HR ~1.4), relative mortality declined over time, and incident IBD cases diagnosed 2002–2014 had an estimated life span 2.3 years shorter than matched comparators.^[6] UK primary-care data also show increased mortality in IBD compared with matched controls.^[16]
• Individuals with UC have a lower life expectancy than the general population.^[4]

• Chronic diarrhea, rectal bleeding, fatigue, and work disability substantially impair quality of life even when survival is near-normal.^[4][2]

• Proctitis and limited left-sided disease carry a comparatively benign course and little excess CRC risk; extensive colitis, young onset, and PSC mark higher-risk phenotypes.^[1][11]
• Mucosal healing is associated with lower colectomy risk, and reducing cumulative inflammatory burden lowers neoplasia risk.^[2][8]