- Clinical science
inflammatory bowel disease (IBD) characterized by chronic mucosal inflammation of the rectum, colon, and cecum. Common symptoms include bloody diarrhea, abdominal pain, and fever. Laboratory findings typically show elevated inflammatory markers and the presence of autoantibodies (pANCA). Definitive diagnosis requires biopsies showing abnormal colonic mucosa and characteristic histopathology. Aminosalicylic acid derivatives are the mainstay of treatment, although severe episodes typically require corticosteroids and immunosuppressants to achieve remission. In the case of distal colitis, some drugs may be administered topically (e.g., via enema), whereas more proximal inflammation requires systemic treatment. Proctocolectomy is curative and indicated for complicated UC or dysplasia. Individuals with UC are predisposed to colorectal cancer and should thus undergo regular surveillance colonoscopy.(UC) is an
- Approx. 600,000 adults in the U.S. are affected by UC 
- Higher in the white than in the black, Hispanic, or Asian populations
- Highest among individuals of Ashkenazi Jewish descent.
- Slightly higher in men than women 
- 15–35 years 
- Another smaller peak may be observed in individuals > 55 years 
Epidemiological data refers to the US, unless otherwise specified.
|Bowel movements/day||< 4||4–6||> 6|
|Blood in stools||Intermittent||Frequent||Continuous|
|Temperature||< 37.5°C (99.5°F)||≤ 37.8°C (99.68°F)||> 37.8°C (100.4°F)|
|Heart rate||< 90/min||≤ 90/min||> 90/min|
|Hemoglobin||> 11.5 g/dL||≥ 10.5 g/dL||< 10.5 g/dL|
|ESR||< 20 mm/h||≤ 30 mm/h||> 30 mm/h|
Montreal classification of extent and severity of ulcerative colitis 
|E1: Ulcerative proctitis||Mucosal involvement limited to the rectum|
|E2: Left-sided/distal ulcerative colitis||Mucosal involvement limited to part of the colorectum distal to the splenic flexure|
|E3: Extensive ulcerative colitis/pancolitis||Mucosal involvement extends to the proximal of the splenic flexure|
|S0: Clinical remission||No mucosal involvement, asymptomatic|
|S1: Mild ulcerative colitis||≤ 4 stools/day (with or without blood), no signs of systemic illness, ESR normal|
|S2: Moderate ulcerative colitis||> 4 stools/day, only minimal signs of systemic illness|
|S3: Severe ulcerative colitis||≥ 6 stools/day with blood, heart rate ≥ 90/min, temperature ≥ 37.5°C (99.5°F), Hb < 10.5 g/dL, ESR > 30 mm/h|
- Dysregulation of intestinal epithelium: increased permeability for luminal bacteria → activation of macrophages and dendritic cells → antigen presentation to macrophages and naive CD4+ cells leads to
- Dysregulation of the immune system: upregulation of lymphatic cell activity in bowel walls (T cells, B cells, plasma cells) → enhanced immune reaction and cytotoxic effect on colonic epithelium → inflammation with local tissue damage (ulcerations, erosions, necrosis) in the submucosa and mucosa
- Pattern of involvement
The rectum is always involved in UC!
Risk factors 
- Genetic predisposition (e.g., )
- Ethnicity (white populations, individuals of Ashkenazi Jewish descent)
- Family history of inflammatory bowel disease
- Episodes of previous intestinal infection
- Increased fat intake (esp. saturated fat and animal fat)
- Oral contraceptive intake
- NSAIDs may exacerbate UC
Protective factors 
- Smoking has a protective effect
- Skeletal: (most common extraintestinal manifestation of ulcerative colitis): sacroiliitis, , 
- Ocular: ; , episcleritis, iritis
- Biliary: primary sclerosing cholangitis ( )
- Cutaneous: aphthous stomatitis,, , pyostomatitis vegetans (multiple aphthae and pustules of the oral mucosa)
- General: fatigue, fever
- In children/adolescents: growth retardation and delayed puberty
Course of the disease
- Definition: inflammation of the terminal ileum in the context of ulcerative colitis
- Epidemiology: affects approx. 10–20% of all patients diagnosed with ulcerative colitis
- Localization: typically affects an area a few centimeters proximal to the ileocecal valve
- Pathophysiology: the pathological mechanism is not fully understood.
- Differential diagnosis: Clinically, backwash ileitis is hardly relevant but its presence makes it harder to differentiate ulcerative colitis from Crohn disease
- ↑ ESR, ↑ CRP, leukocytosis
- Thrombocytosis in some cases
- ↑ Perinuclear ANCA (pANCA)
- In case of concurrent gamma-glutamyl transferase: elevated
- Stool analysis
Endoscopy (e.g., colonoscopy) with histological examination is considered the best test to definitively diagnose UC.
- Typical findings: : See “Gross pathology” below.
- Pattern of disease involvement 
- Recommendations 
Observe caution in taking biopsies from patients with severe disease, as the risk of perforation is high.
Imaging studies may serve as useful adjunct diagnostic procedures for UC, particularly when it comes to detecting complications.
- Plain radiography
- Barium enema radiography
- CT: Detection of bowel wall thickening is possible in severe disease.
- MRI: can be helpful in assessing disease severity and extent of bowel wall involvement
- Ultrasound: can detect bowel wall thickening (manifests with absent hyperechoic reflection from the lumen)
- Early stages
- Loss of mucosal folds
- Loss of haustra
- Deep ulcerations
- Raised areas of normal mucosal tissue that result from repeated cycles of ulceration and healing
- Ulceration → formation of granulation tissue → deposition of granulation tissue → epithelization
- Morphologically resemble polyps but do not undergo neoplastic transformation
- Found in advanced disease
- Early stages
- Chronic disease
Differential diagnosis considerations
- Crohn disease (see “ ”)
- Exudative-inflammatory diarrhea
- Ischemic colitis
- Infectious colitis
- Radiation colitis
- Celiac disease
- Inflammatory diarrhea
- Definition: An idiopathic form of colitis that is characterized by a normal macroscopic appearance of bowel on colonoscopy and collagenous or lymphocytic infiltrates on microscopy.
- Forms: collagenous colitis and lymphocytic colitis
- Etiology: unknown
- Clinical findings
- Pathological findings
The differential diagnoses listed here are not exhaustive.
Initially, UC is treated conservatively with drugs to induce and maintain disease remission. Curative proctocolectomy is generally indicated if medical therapy fails or complications arise.
- Supplementation of nutritional deficiencies (e.g., iron)
- Supplementation of nutrition: severe cases may warrant consideration of a feeding tube or parenteral nutrition.
Medical therapy 
- Antidiarrheal agents (e.g., loperamide): can only be used in the absence of a flare
- Anticholinergic medication (e.g., propantheline, dicyclomine): relieves abdominal cramping
- NSAIDs, opioids, and anticholinergics should be avoided in severe disease.
5-aminosalicylic acid derivatives (5-ASAs)
- Mechanism of action
- Side effects
- Most of the side effects are caused by the sulfapyridine component of sulfasalazine.
- GI irritation: nausea, diarrhea
- Headache, fatigue; , malaise, depression
- Megaloblastic anemia and folate deficiency due to interference with dihydropteroate synthase
- Immune thrombocytopenia 
- Transient oligospermia
- Sulfa drug: allergic reactions, sulfonamide toxicity
- Drug interactions: coadministration of nephrotoxic drugs (e.g. NSAIDs, aminoglycosides, lithium) → ↑ risk of renal impairment
- Additional information
- Can be administered orally, as suppositories; , or as enemas
- Sulfapyridine has proven to have beneficial effects in patients with rheumatic disease.
- If no improvement or 5-ASA agents are not tolerated
- Oral and topical 5-ASAs
- Topical corticosteroids (e.g., budesonide) → systemic corticosteroids only if no response
- Anti-TNF therapy; (adalimumab, golimumab, or infliximab)
- Vedolizumab (integrin receptor antagonist)
- Tofacitinib (JAK3 inhibitor)
Severe or refractory disease
- High‑dose oral and topical 5-ASAs
- Systemic corticosteroids
- Anti-TNF therapy; (e.g., adalimumab, golimumab, or infliximab)
- Calcineurin antagonists (e.g., cyclosporine, tacrolimus)
- Thiopurines (6-mercaptopurine, azathioprine) may be considered but are no longer recommended as monotherapy due to lack of efficacy 
- Vedolizumab (integrin receptor antagonist)
- Tofacitinib (JAK3 inhibitor)
- Referral for surgical proctocolectomy (see below)
- Curative approach with full recovery
- Reduce risk of colorectal cancer
- Procedure: proctocolectomy with an ileal pouch-anal anastomosis (IPAA or J pouch)
- Anastomotic leak
- Pouchitis (↑ stool frequency, malaise, and possibly incontinence caused by bacterial overgrowth)
- (both acute and chronic)
- Perforation → peritonitis (see “”)
- Fulminant colitis; : severe bowel inflammation that typically causes > 10 stools per day, lower gastrointestinal bleeding, abdominal pain, and abdominal distention
↑ Risk of cancer (see ” ”)
- Risk increases with increased duration and/or extent of disease (e.g., pancolitis).
- Risk is not significantly increased in patients with mild UC
- Prevention: Screening colonoscopy with biopsies every 1–3 years starting 8 years after the initial diagnosis to screen for colorectal cancer 
- Colonic stricture
We list the most important complications. The selection is not exhaustive.
On average, the life expectancy of patients with UC is normal.