Ulcerative colitis

A chronic inflammatory condition characterised by relapsing and remitting episodes of inflammation, limited to the mucosal layers of the colon.

Epidemiology

• Disease of Western world
• Increasing prevalence over time
• Bimodal onset
  • 15-30yo
  • 50-80yo

Risk factors

• Genetic
• Sleep deprivation
• Possibly infection

Protective factors

• Smoking - tends to suppress symptoms and lower risk
• Appendicectomy

Pathophysiology

• Almost invariably involves the rectum, beginning at the dentate line
• Tends to involve more proximal parts of the colon in a continuous fashion
  • Ulcerative proctitis - disease confined to the rectum
  • Ulcerative proctosigmoiditis - disease limited to the rectum and sigmoid colon
  • Left-sided colitis - disease that extends as far proximally as the splenic flexure
  • Extensive colitis - disease extending proximal to the splenic flexure
• Natural history
  • Typically, intermittent exacerbations alternating with long periods of complete symptomatic remission
  • Those who present with just proctitis have a more benign long-term course
  • 15% proceed to surgery

Presentation

• Usually present with diarrhoea, which may be bloody or not
  • Bowel movements are frequent and small in volume due to proctitis
  • Bloody diarrhoea suggests UC as opposed to CD
• Colicky abdominal pain, urgency, tenesmus, incontinence
• Usually gradual onset of symptoms over several weeks or months
• Systemic symptoms - fever, fatigue, weight loss, anaemia
• Most have a mild index attack, but 27% have a moderate and 1% severe (see severity below)
• Extra-intestinal manifestations: see 'Crohn disease' - same

Investigations

• Check for inflammatory and nutritional markers
  • Albumin, Hb, iron
• Serologic markers
  • Antibodies against Saccharomyces cerevisiae (ASCA) - positive in 35-50% of Crohn's, and <1% of UC

• • Perinuclear antineutrophilic cytoplasmic antibodies (p-ANCA)
    • (Helpful in differentiating Crohn's and UC - ASCA positive, p-ANCA negative suggests CD, whereas p-ANCA is more likely to be elevated in UC)

• Stool MCS + CDT
• ALP may be elevated in PSC
• AXR:
  • Patients with severe disease may show proximal constipation, mucosal thickening/'thumbprinting', colonic dilatation
• Barium enema
  • Avoid in unwell patients - may precipitate ileus with toxic megacolon
• CT and MRI
  • May demonstrate marked thickening of the bowel wall - non-specific
  • Lower sensitivity than barium enema for the detection of subtle early mucosal disease
• Endoscopy
  • Use Mayo Clinic Scoring System to grade
  • Inflammation involving rectum and extending proximally in a continuous and circumferential pattern with a sharp cut-off between involve and uninvolved mucosa
  • Can also have a 'caecal patch' of inflammation around the appendiceal orifice which is non-continuous with other areas of inflammation
  • Backwash ileitis may be seen in patients with UC with active right-sided colitis - typically diffuse, rather than the patchy inflammation seen in CD ileum
  • Loss of vascular markings due to engorgement of the mucosa
  • Petechiae
  • Exudates
  • Oedema
  • Erosions
  • Touch friability/spontaneous bleeding
  • Non-neoplastic pseudo-polyps

• • Severe: macro-ulcerations, profuse bleeding, copious exudates

• Biopsies of bowel
  • Nothing fully specific for UC, but presence of two or more features is suggestive
    • Crypt abscesses; crypt branching, shortening and disarray; and crypt atrophy
    • Epithelial cell abnormalities - goblet cell/mucin depletion and Paneth cell metaplasia
    • Increased lamina propria cellularity (polymorphonuclear leucocytes), basal plasmacytosis, basal lymphoid aggregates, and lamina propria eosinophils
  • Absence of mural sinus tracts, deep fissural ulcers, and granulomas, as well as by the absence of transmural lymphoid aggregates in an area not deeply ulcerated

Diagnostic criteria

• Chronic diarrhoea for >4 weeks
• Evidence of active inflammation on endoscopy
• Chronic inflammation on biopsy
• Exclusion of other causes of colitis/proctitis

Differential diagnosis

• Infectious colitis
  • C diff
  • CMV
  • Salmonella, Giardia
  • Parasites and other infectious agents
• Proctitis
  • Gonorrhoea, chlamydia, syphilis
  • HSV
• Medication colitis
  • NSAIDs
  • Retinoic acid
  • Checkpoint inhibitors
  • Mycophenolate
  • Gold
• Ischaemic colitis
• Radiation proctitis/colitis
• Crohn disease
  • More likely than UC if no gross bleeding, perianal disease present, and fistulas
  • Granulomas on biopsy
• IBD undetermined/indeterminate colitis
  • See discussion under 'Crohn disease'
• Diversion colitis
• Solitary rectal ulcer syndrome
• Graft versus host disease
  • History of bone marrow transplantation
  • Differentiate on histology - GVHD has crypt wall necrosis with the accumulation of degenerative material in the dead crypt cells

Severity

Montreal classification:

	Mild	Moderate	Severe
Diarrhoea frequency	<5	5, with blood	>5, with blood
Systemic features	None	Low-grade fever	Fever, tachycardia
Symptoms	Mild	Moderate	Severe
ESR	Normal	Mildly elevated	>30mm/hour
Weight loss	None	None	Yes
Anaemia	None	Mild	Hb <105

Truelove and Witts

• • See separate topic 'toxic megacolon'
  • Severe: severe diarrhoea (6 or more motions per day) with macroscopic blood, fever >=37.8, HR > 90, Hb <105, elevated CRP or ESR
  • Fulminant: Bloody stools >=10/day, accompanied by abdominal pain and distension, in addition to the above criteria.

Medical management

Principles:

• • See 'Crohn disease' topic for background on goals and medications available
  • Leave the ins and outs to gastro, but need to have a broad awareness of classes and strategies used

Medication classes (see Crohn's topic for details):

• • Induction of remission
    • Mainstay has been steroids, enemas, oral or IV
    • If that fails or for severe disease, sometimes need immunomodulators
  • Maintenance therapy
    • Aminosalicylates (a.k.a. 5-ASA/5-aminosalicylic acid)
    • Can include steroids, but preferably not
    • Immunomodulators
    • Biologics
    • Calcineurin inhibitors - cyclosporin/tacrolimus, sometimes used as rescue therapy for ASUC
    • Antibiotics - low-quality data to support use as induction agents
• Initial therapy for active proctitis or distal colitis (distal to splenic flexure):
  • Mesalazine orally and rectally. Rectal topical therapy is probably the easiest way to target treatment to the affected area, but may not be effective for many reasons. Rectal preparation best given before bed, tolerated better at night.
    • Isolated ulcerative proctitis: suppositories
    • Extends >20cm from anal verge: foam or enema
    • Proximal to sigmoid: enema
  • If 5-aminosalicylates are ineffective, add rectal steroids (e.g. 'Predsol' prednisolone enemas 20mg/100mL, can start off with a 1-2 week course).
  • Continue until symptoms have resolved, then taper over several weeks.
  • If symptoms recur, restart induction therapy.
• For induction therapy for colitis proximal to splenic flexure
  • For mild-mod disease, PO prednisolone/5-aminosalicylate
  • For severe, probably need an immunomodulator
• For unresponsive active colitis
  • Oral prednisolone 40-50mg PO daily, then taper over 6-8 weeks
• For acute severe ulcerative colitis (Truelove and Witts criteria)
  • Hydrocortisone 100mg IV q6h 3-5 days
  • If they fail to respond to that, 'salvage therapy' is infliximab (possibly cyclosporin), and possibly upadacitinib
• Standard maintenance regime:
  • Mesalazine 1-3g orally per day and a mesalazine rectal preparation 2-3 times per week
  • If more severe, or frequent relapses, add an immunomodulator or biologic (usually infliximab)

Elective surgical management

Indications for surgery

• • Failure to respond to maximal medical therapy (severe disease)
  • Patient preference
  • Dysplasia/malignancy
    • Colectomy indicated if multiple areas of low-grade dysplasia or areas of high-grade dysplasia are found
    • Especially difficult to identify suspicious areas with active colitis
    • If high-grade dysplasia is found on random biopsy, 42% chance of finding cancer after proctocolectomy
    • Cancer can develop in areas of low-grade dysplasia without necessarily
    • Close surveillance an alternative if patient willing
  • Failure to grow/thrive (children)
  • Severe extra-intestinal disease which may respond to surgery

Surgical options:

• • Total proctocolectomy with either end ileostomy or IPAA
    • No difference in overall quality of life
  • End ileostomy
    • Be wary of patients with PSC - risk factor for both chronic pouchitis and peristomal varices - preference for IPAA given life-threatening nature of varices
  • IPAA (ileal pouch-anal anastomosis)
    • Patient selection
      • UC not responding to medical therapy
      • Dysplasia/malignancy
    • Construction process:
      • Three-stage:  (preferred for patients who are hospitalised with refractory disease, or are on biologics/steroids, obese, young women wishing to preserve fertility)

• • • • 1. Subtotal colectomy with end ileostomy and rectal stump
        2. Proctectomy with IPAA and loop ileostomy
        3. Ileostomy takedown

• • • • Two-stage: (favoured in well patients with malignancy)

• • • • 1. Total proctocolectomy with IPAA and loop ileostomy
        2. Ileostomy takedown

• • • • One-stage:

• • • • 1. Total proctocolectomy with IPAA and no diversion

• • • • • Appropriate if no immunosuppression, good nutritional state, and no tension on IPAA

• • • Often difficult to get enough length for a tension-free ileal anastomosis
      • Check whether you have enough length before you form a pouch! Can leave as end ileostomy. If the apex of the pouch can reach 6cm below the inferior margin of symphysis pubis, then a tension-free anastomosis can usually be constructed.
      • Completely mobilise small bowel to root of mesentery, but preserve ileocolic vessels
      • Transverse incisions on visceral peritoneum of the mesentery - 'mesenteric releases'
      • Careful division of select vascular arcades in small bowel mesentery - can divide terminal branches of SMA, because they are likely to be the thing creating most tension. Jamieson's says ileocolic itself can be divided if necessary for an S pouch, and the major continuation of SMA for a J pouch. Put a bulldog clamp on before division to test if it leads to ischaemia.
    • Pouch configuration
      • Stapled anastomosis requires a short cuff of rectum, which is a potential source of symptoms - 'cuffitis' and cancer.
      • Hand-sewn anastomosis can be done with a mucusectomy - remove all rectal mucosa down to anorectal junction, so might have a lower rate of cancers. Maybe worse continence. Usually done from outside with an anal retractor (lone star). Note that this might make it harder for the pouch to reach down.
      • Preference for stapled J-pouch - simplest and easiest, least complications
      • Or, 'double-stapled' if you are also talking about the staple for the pouch-anal anastomosis (using the circular staple for that one)
      • W-pouch below - uncommonly done
      • S-pouch - can provide a bit more reach and larger reservoir

• Outcomes:
  • Expect to have up to 6 loose bowel motions per day - need good anal sphincter control
  • Function often improves over the first 6 months
• Ileostomy closure
  • Anastomosis should be thoroughly investigated prior to closure
  • DRE, endoscopy, gastrografin
• Complications
  • SBO (20%)
  • Sexual dysfunction
  • Ileostomy complications
  • Leak
    • Sepsis
    • Fistula
  • Anastomotic stricture
    • Often a reflection of tension
  • Pouchitis
    • Medical management - abx, probiotics, budesonide enemas. Consider immunosuppressive therapy
    • Surgical therapy if refractive - diversion or pouch excision

• Uncommon procedures
  • Total proctocolectomy with continent ileostomy ('Kock's Pouch')
    • Continence maintained by an intussuscepted segment of ileum positioned between the ileal reservoir and the end ileostomy
    • Very prone to dessusception, which requires revision
    • Not done much any more
    • Works best in thin patients
  • Subtotal colectomy with ileorectal anastomosis
    • Avoids complications of pelvic dissection - sexual function for both men and women
    • Still need rectal surveillance
    • Suitable for patients with limited rectal involvement, but that is rare with UC

Emergency surgical management

• Indications
  • Acute fulminant colitis, including toxic megacolon (see separate topic)
  • Significant GIT haemorrhage (uncommon in modern era)
• Choice of surgery
  • Subtotal colectomy with end ileostomy or Hartmann's procedure are least morbid options
    • Indicated for sick patients
  • Shouldn't do IPAA initially

Peri-op management:

• Pre-op
  • Anti-TNF agents (infliximab, adalimumab, certolizumab) - associated with increased operative complications - controversial
    • Ideally last dose >4/52 pre-op
    • UC - possible a/w pelvic sepsis after IPAA - 3-stage approach favoured in patients on anti-TNF drugs
    • CD - possible increase in complications, but controversial and not clear

• • • Vedolizumab
      • Ideally last dose 4-8/52 pre-op
      • UC - no increased risk of infection
      • CD - similar rates of infection to anti-TNF drugs
    • Ustekinumab
      • Similar complication rates to anti-TNFs
      • Ideally last dose 4/52 pre-op
    • Restart 4/52 post-op where necessary

• • Corticosteroids

• • • Well-established detrimental effect on anastomotic healing
    • UC: should do delayed IPAA formation in patients who cannot be weaned to <20mg/day for 6/52 pre-op
    • CD - high risk of infection is generally ameliorated by stoma instead of primary anastomosis
      • Should still be reduced if possible

• • Nutrition

• • • UC - no pre-op TPN
    • CD - poorly studied in biologic era, but no clear role for pre-op TPN
      • Still need to optimise nutrition

• • Planning

• • • Pre-op imaging is crucial +/- capsule endoscopy
    • Looking for important disease in other areas of GIT
    • Planning extent of resection

• Post-op
  • A well-functioning stoma allows a much better quality of life than a poorly-functioning anorectum

• • • Leakage
    • Skin irritation
    • Difficulty maintaining a seal
    • Retraction
    • Ischaemia
    • Mucocutaneous separation
    • Pyoderma gangrenosum can develop around stoma sites (2-5% of those who have stomas for IBD)
      • Early recognition and corticosteroid treatment
      • Good stoma care

• • Ileostomy creation high-risk for readmission

• • • AKI + dehydration common

• • Infection - high-risk overall, particularly with immunosuppression

• • • Intra-abdominal sepsis reportedly 8%, median nine days post-op
    • High-risk: previous intestinal resection + triple therapy immunosuppressed (22% overall risk)
    • Anastomotic leaks: particularly those with multiple previous resections
      • Stapled side-to-side anastomosis have lower leak rates

• • Stump blow-out

• • • Oversewing staple line and decompressing rectal tube are purported to decrease blowout rate, but limited evidence
    • Can also bring above fascia to secure either below skin or as mucus fistula

• • Pouch complications:
  • VTE - more common than would be expected - consider 4 weeks prophylactic enoxaparin
  • ERAS is vital

Cancer risk/endoscopic surveillance

• 20% malignancy after 30 years of colitis - tends to arise in a field of dysplasia, which appears abnormal
• Start 8-10 years post-diagnosis - main goal is to detect dysplasia
• Limited evidence that screening actually reduces mortality
• Divide patients into three groups
  • Low risk - every 5 years
  • Moderate risk - every three years
  • High risk (extensive or active disease, or any previous dysplasia, or other high-risk features including first-degree relatives) - every year
• Four-quadrant random biopsies every 10cm, for a total of at least 32 biopsies, in addition to suspicious lesions
• Conservative advice would be, any high-grade dysplasia on random biopsy should have total proctocolectomy
• Areas of dysplasia should have EMR. If unresectable endoscopically, should have proctocolectomy.