Ulcerative colitis is a chronic inflammatory bowel disease that affects the colon. This document provides an overview of the definition, epidemiology, etiology, clinical features, diagnosis, and management of ulcerative colitis. It defines ulcerative colitis and describes the extent of disease involvement. Key points include that the goal of management is sustained remission through the use of medications such as aminosalicylates, immunomodulators, biologics, and surgery if needed.

1. Ulcerative colitis
Dr.Sabona Bulto (Internal medicine
resident)
July 23, 2020

2. Outlines
 Definition
 Epidemiology
 Etiology & pathogenesis
 Clinical features
 Diagnosis
 Management

3. Definition
 Ulcerative colitis - chronic inflammatory condition characterized by
relapsing and remitting episodes of inflammation limited to
the mucosal layer of the colon.
 It almost invariably involves the rectum
 Typically extends in a proximal and continuous fashion to involve other
portions of the colon.

4.  Different terms have been used to describe the degree of involvement
 Ulcerative proctitis - disease limited to the rectum
 Ulcerative proctosigmoiditis - disease limited to the rectum & sigmoid
colon
 Left-sided or distal UC - disease that extends up to splenic flexure
 Extensive colitis - extending proximal to the splenic flexure but sparing
the cecum
 Pancolitis - extends throughout the colon to cecum

5. EPIDEMIOLOGY
 The incidence and prevalence - vary with geographic location & ethnicity.
 About 800,000 people in the US & 1.4 million in Europe afflicted .
 The peak incidence of UC occurs in the 2nd & 3rd decades of life.
 Smaller peak in older adults, between the ages of 60 and 70 years.
 M:F ,nearly 1 : 1, applies to all age groups

6. Map of worldwide incidence (1990-2016) in quintiles for UC

8. ETIOLOGY AND PATHOGENESIS
 Etiology - currently unknown but is likely multifactorial.
 Complex interaction of 3 elements: genetic susceptibility, host
immunity, & environmental factors.
 Overly aggressive T-cell mediated immune responses to specific
components of the intestinal microbiota in genetically susceptible
individuals, and that disease expression is triggered by additional
environmental factors.
 Dysregulation of the enteric immune response leads to the development of
acute and chronic inflammation and the pathologic feature of mucosal
damage.

9. Pathogenesis of IBD

10. PATHOLOGIC FEATURES
 Macroscopically, the mucosa appears hyperemic, edematous, & granular
in mild disease.
 As disease progresses, the mucosa becomes hemorrhagic, with visible
punctate ulcers.
 These ulcers can enlarge and extend into the lamina propria.
 Epithelial regeneration with recurrent attacks results in the formation of
pseudopolyps
 It is typical of long-standing UC but may also develop rapidly in acute
disease.

11. Surgical specimen of resected colon from a patient with severe UC
showing numerous pseudopolyps.

12. Microscopically
 Edema of the lamina propria and congestion of capillaries and venules,
often with extravasation of red blood cells.
 Followed by an acute inflammatory cell infiltrates.
 Cryptitis and crypt abscesses with neutrophilic accumulations in the crypt
lumens.
 Features that reflect chronicity and thus argue against a dx of infectious
or colitis
 Distorted crypt architecture, crypt atrophy, increased intercryptal
spacing to fewer than 6 crypts per millimeter, an irregular mucosal
surface, basal lymphoid aggregates, and a chronic inflammatory
infiltrate.

13. Photomicrographs of a colonic biopsy specimen showing the histology of UC.
A, Diffuse chronic inflammation of the lamina propria and crypt distortion are
present
B, The base of a single distorted colonic crypt

14. CLINICAL FEATURES
 Varies depending on the location of disease, the intensity of inflammation,
& presence of specific intestinal and extraintestinal complications.
 Common symptoms:- urgency, rectal bleeding, diarrhea, passage of
mucus, tenesmus, and abdominal pain.
 In more severe cases, fever and weight loss may be prominent.
 Hematologic changes:- anemia, leukocytosis, and thrombocytosis

15. Physical examination
 Often normal, especially in patients with mild disease.
 Moderate to severe UC :- abdominal tenderness to palpation, fever,
hypotension, tachycardia, and pallor.
 Rectal examination may reveal evidence of blood.
 Patients with prolonged diarrhea symptoms may have evidence of
muscle wasting, loss of subcutaneous fat, and peripheral edema due
to weight loss and malnutrition.

16. Extraintestinal Manifestations
 6-25% of all patients with IBD
 Many of them are common to CD & UC.
 More common among patients with colonic involvement.
 ¼ of those affected have >1 EIM.
 Some EIMs occur as a direct result of the bowel disease.
 Mucocutaneous, joint, and ocular EIMs occurs due to influx of mononuclear
cells activated in the intestine.

19. Diffuse episcleritisAnterior uveitis
Erythema nodosum Pyoderma gangrenosum

20. Acute complication
 Severe bleeding
 Up to 10% of patients
 Massive hemorrhage - 3% at some time in their disease course
 Fulminant colitis
 >10 stools/d, continuous bleeding, abdominal pain, distension, fever
and anorexia.
 At high risk of developing toxic megacolon
 Toxic megacolon
 Colonic diameter ≥6 cm or cecal diameter >9 cm with systemic toxicity
 Severe bloody diarrhea, abdominal pain and distension
 Toxic appearing patient with altered sensorium, tachycardia, fever,
postural hypotension, with or without signs of localized or generalized
peritonitis.
 Perforation
 Most commonly occurs as a consequence of toxic megacolon.
 May also occur in first episode of UC due to lack of scarring from prior
attacks of colitis.
 Has been associated with 50% mortality

21. Diagnosis
 Established through a complete assessment of the clinical
presentation with
 Confirmatory evidence from radiologic, endoscopic, and,
pathologic findings.
 Initial evaluation - thorough Hx, P/E & basic laboratory tests
 Recent travel history, medication (including antibiotics and NSAIDs),
diet
 Hx of predisposing factors - recent infectious gastroenteritis, and a
family history of IBD and GI cancer.
 Features of EIMs

22. Laboratory Studies
 CBC
 ESR
 CRP
 LFT
 Albumin
 Serum electrolytes
 Fecal calprotectin or lactoferrin
 Stool studies- O/P, culture, CDI toxin
 Serologic testing -ASCA & ANCA, E.histolytica

23. Imaging
Plain Films
 Severe disease- lumenal margin of the colon becomes edematous &
irregular.
 Thickening of the colonic wall
 Prognostic signs :- islands of residual mucosa surrounded by extensive
deep ulcerations, distention of the small bowel, & dilatation of the colon
 Marked colonic dilatation >> fulminant colitis or toxic megacolon
 Perforation.
 The presence of fecal material

24. Plain abdominal film of a patient with severe UC
The transverse colon is dilated (arrow), the colon wall is thickened, and mucosal
islands are visible. Distended loops of small bowel are apparent.

25. Plain abdominal film of a patient with mild left-sided UC
Showing a stool-filled proximal colon, but no stool in the involved segment of

26. Double contrast barium enema
 May be normal in mild UC
 Diffusely reticulated pattern with superimposed punctate
collections of barium in microulcerations.
 More severe disease :- spiculated collar button ulcers, shortening of
the colon, loss of haustrae, narrowing of the luminal caliber,
pseudopolyps & filiform polyps.
 It should be avoided in patients who are severely ill since it may
precipitate ileus with toxic megacolon.

27. Extensive mucosal ulceration and
inflammation throughout the colon
Mucosal pseudopolyps (arrows) and a stricture
arising in the descending colon.
Shows a featureless colon with complete loss of
folds in the sigmoid colon.

28. Endoscopy & biopsy
 First attack of UC, sigmoidoscopy with biopsies usually is sufficient to confirm
the dx.
 The hallmark of UC : - symmetric and continuous inflammation that begins at
the anorectal junction.
 Typical Endoscopic findings
 Erythema
 Edema/loss of the usual fine vascular pattern
 Granularity of the mucosa
 Friability/spontaneous bleeding
 Pseudopolyps
 Erosions
 Ulcers

29. Seminar on mgt of UC

30. A.Extensive ulceration of the mucosa.The surface is irregular, friable, and erythematous,
with loss of the normal vascular markings.
B.Pseudopolyps may form as a reaction to inflammation; these can become quite
extensive (C).

31. Biopsy features
 Crypt abscesses, crypt branching, shortening and disarray, and crypt
atrophy.
 Epithelial cell abnormalities >> mucin depletion and Paneth cell
metaplasia
 Inflammatory features >> increased lamina propria cellularity, basal
plasmacytosis, basal lymphoid aggregates, and lamina propria
eosinophils.
 Basal plasmacytosis may also be a predictor of relapse in patients
with seemingly well-controlled UC with complete mucosal healing.

35. Assessment of disease activity
 Is important for prognostication and therapeutic decision making.
 The most commonly used is that of Truelove and Witts.

37. The UCEIS demonstrated excellent correlation with disease severity and
good intra- and inter-observer reliability.

38. Sample endoscopic images of ulcerative colitis using the Mayo
endoscopic subscore and the Ulcerative Colitis Endoscopic Index of

40. MANAGEMENT
Goal
 Sustained and durable period of steroid-free remission.
 Normal health-related quality of life (QoL)
 Prevention of morbidity including hospitalization and surgery
 Prevention of CRC
 An emerging goal - mucosal healing

41. ACG RECOMMENDATIONS
 We suggest treating patients with UC to achieve mucosal healing
(defined as resolution of inflammatory changes (Mayo endoscopic
subscore 0 or 1)) to increase the likelihood of sustained steroid-free
remission and prevent hospitalizations and surgery (conditional
recommendation, low quality of evidence).
 We suggest FC as a surrogate for endoscopy when endoscopy is not
feasible or available to assess for mucosal healing (conditional
recommendation, very low quality of evidence).

42. Definition of remission
 Corticosteroid-free remission - based on symptoms, endoscopic
findings, or disease impact without ongoing corticosteroid use.
 Symptomatic remission - relates to improvement in PROs
 Endoscopic healing - restoration of intact mucosa without friability.
 Deep remission - combination of symptomatic remission and
endoscopic healing ; preferred goal of management.

43. Options
 Medical management
 Aminosalicylates –Sulfasalazine , Balsalazide, Mesalamine
 Glucocorticoids - Prednisone, Methylpredinsolone
 Immunomodulators – AZA, 6MP, Cyclosporine, Tacrolimus
 Biologics
 Anti-TNF - Infliximab, Golimumab, Certolizumab
 Alfa Integrin Inhibitors – Natalizumab, Vedolizumab
 IL 12/23 inhibitor- Ustekunumab
 Newer agents
 Kinase inhibitors – Tofacitinib
 S1P Inhibitors- Ozanimod
 Adjunctive therapy
 Surgical management

44. Aminosalicylates
 Approximately 90% of sulfasalazine reaches the colon, and only a small
amount is absorbed in the small intestine.
 In the colon azoreductase cleaves the azo bond to release 5-ASA, the
active constituent moiety.
 5-ASA effect its anti-inflammatory activity topically, but possibly also
through absorption and via the microenteric circulation.
 3-6 g/day dose of sulfasalazine induces remission in 39% to 62% of
patients with mildly to moderately active UC.
 They have not been evaluated in a RCT in patients with severely active
disease.

45.  The dose of 5-ASA that induces remission is recommended for
maintenance.
 Complete remission should be the target before considering dose
reduction.
 5-ASA, mesalamine can be rectally administered as enemas,
suppositories or foam.
 AEs of sulfasalazine
 Common: Fever, rash, nausea, vomiting, and headache
 Less common : Hypersensitivity reactions, reversible sperm
abnormalities, & impairment of folate absorption.

47. Glucocorticoids
 Effective first-line therapy for moderately to severely active UC.
 Can be given for systemic (PO/IV) or topical (liquid, foam or enema) Rx
 IV glucocorticoids commonly used in severely active disease.
 Options for IV: Hydrocortisone (100 mg IV TID), prednisolone (30 mg IV
BID), or methylprednisolone (16 - 20 mg IV TID).
 Glucocorticoids have no maintenance benefits in IBD.
 Immunomodulatory or biologic agents should be considered in patients
with
 Steroid-dependent,
 2 courses of glucocorticoids for induction remission within 1 year, or
 Parenteral glucocorticoids to induce remission.

48. GLUCOCORTICOIDS
Principles
 Use an effective dose
 Do not overdose
 Do not treat for excessively long periods
 Anticipate side effects

49. Immunomodulators
Thiopurines - AZA & 6-MP
 The most widely used immunomodulator agents
 Exert their immunosuppressive effects by inhibition of purine and
protein synthesis in lymphocytes.
 They are inactive pro-drugs with subtle structural differences.
 AZA remains widely used , although there are less robust data
supporting its efficacy in the treatment of UC.

51. Methotrexate Treatment of UC
 MTX long lacked data supporting its use in UC.
 METEOR study, RCT- 111
 Steroid-dependent UC pts to received either parenteral MTX 25
mg weekly or placebo for 24 weeks.
 At the end of the trial, there was no statistically significant
difference in steroid-free remission or endoscopic healing between
the 2 groups.
 However, patients were more likely to be in clinical remission with
MTX when compared to placebo (42% compared to 24%, P =
0.04).

52. Cyclosporine A (CSA)
 Potent inhibitor of cell-mediated immunity through calcineurin
inhibition pathway-> diminishing T-cell activation.
 Its use in IBD is primarily in patients with acute severe, steroid-refractory
UC.
 IV CSA monotherapy may be as effective as IV glucocorticoids in patients
with severely active UC
 Can be considered as bridge therapy to control active disease in
patients with steroid-refractory UC while waiting for elective surgery or the
onset of action of AZA or 6-MP.
 CYSIF trial (RCT, N= 115) & CONSTRUCT trial (open-label RT, N= 270)
 Both trials demonstrated that infliximab and CSA are similarly effective as
rescue therapy in acute severe UC.

53. CSA AEs
 Paresthesias, tremors, headache, hypertrichosis, & gingival hyperplasia.
 Hypertension, seizures, electrolyte and liver biochemistry abnormalities,
nephrotoxicity, anaphylaxis, and opportunistic infections.
 These complications are mostly dose dependent.
 Careful monitoring for AEs is critical during CSA therapy.
 Baseline serum electrolytes, creatinine, cholesterol, and liver
biochemical values should be measured.
 CSA therapy should be avoided in patients with an impaired creatinine
clearance.
 Patients on long-term CSA therapy should receive PCP prophylaxis.

54. Biologic Therapies
Anti-TNF Therapy
 The mechanism of action is most likely multifactorial, all pointing toward the
ability to control the mucosal immune response.
 The antibody can bind to and clear soluble TNF, but it also binds to cell-
bound TNF-> induce apoptosis.
 3 agents are approved for the treatment of UC: Infliximab, adalimumab, &
Golimumab.
 Infliximab is the only anti-TNF agent with robust data to use it as rescue
therapy in steroid non-responders with acute severe UC.
 Results from 2 large, multicenter, RCT trials (ACT 1 & 2) showed efficacy of
infliximab therapy in UC.

55. ACT trials

57. Adjunctive Therapies
 Antidiarrheal and anticholinergic agents
 should be used sparingly in those with ongoing active inflammation.
 Parenteral vitamin B12 supplementation or the addition of
cholestyramine
 In patients with ileal disease or resection
 Iron supplementation
 Antibiotics, probiotics & intestinal microbiota transplantation
 Nutritional Rx – Short chain FA, Fish oil, Curcumin
 Cytapheresis

58. Mgt approach
 Should be guided by
 Specific diagnosis (Montreal classification)
 Disease activity (mild, moderate, or severe)
 Disease prognosis
 Mildly active UC should be reassessed to determine response to
induction therapy within 6 weeks.

59. Management of mild to moderate UC
Ulcerative proctitis or proctosigmoiditis
 Topical 5-ASA - first-line treatment, preferred over topical steroids .
 5-ASA suppositories and/or enemas -> induce remission in >90% of pts.
 Maintain remission in approximately 75% of pts.
 Complete healing usually requires 4-6 wks or longer, and continued
treatment for 6-8 wks followed by a gradual taper and discontinuation.
 No response to topical therapy - combination of oral and topical 5-
ASA/steroids.
 No response to combination therapy -> oral glucocorticoids.

60. Maintenance therapy
 Not recommended in pts with a first episode of mild
ulcerative proctitis.
 Recommended : ulcerative proctitis >1 relapse in year and in all
patients with proctosigmoiditis.
 Discontinuation - > considered only if they have been in remission for 2
years and are averse to taking medication.
Maintenance regimen
 Topical therapy for induction of remission
 One 5-ASA suppository in patients with proctitis
 5-ASA enema every night in patients with proctosigmoiditis
 Oral 5-ASA to achieve remission or multiple relapses on topical therapy
 Continue on oral 5-ASAs

61. Left-sided colitis, extensive colitis, & pancolitis
 Most benefit from combination therapy with oral & topical 5-ASA medications
or topical steroid.
 Oral 5-ASA exert their effect in 2-4 wks and are effective in 40-80% of pts.
 Patients who do not respond in 2 weeks
 Should be treated with topical combined with oral 5-ASA
 If not responded to the combination of oral 5-ASA and topical 5-
ASA/steroids within 2-4 weeks
 MMX budesonide suggested prior to the use of other oral glucocorticoids.

62. ACG Recommendations

63. Maintenance therapy
 Recommended in all patients
 5-ASA medications are highly effective
 Combination therapy with oral and intermittent rectal therapy may be
better than oral therapy alone.
 Glucocorticoids should be tapered after the patient has been stable
for 2-4 weeks.

64. Mgt algorithm for the mild-to-moderate active UC

65. MGT OF MODERATELY TO SEVERELY ACTIVE UC
 Should be treated with oral glucocorticoids and a combination of
high dose oral 5-ASA (eg, mesalamine 4.8 g/d) & topical therapy
with 5-ASA or steroids.
 Initiation of oral glucocorticoids should not be delayed until the
results of stool studies and cultures are available.
 Anticholinergic, antidiarrheal agents, NSAIDs, and opioid drugs
should be discontinued due to the risk of precipitating toxic
megacolon.
 There is no role of antibiotics in patients with severe colitis without
signs of systemic toxicity.
 Bowel rest is not recommended in in the absence of fulminant
disease.

66. ACG Recommendations

67. Maintenance therapy
 In patients who respond, IV glucocorticoids should be converted to
equivalent dose of oral glucocorticoids in 3-5 days.
 Oral glucocorticoids should be tapered after the patient has been stable
for 2-4 weeks.
 Rectal 5-ASA/steroids can be gradually tapered over 2-4 months.
 Oral 5-ASA medications should be continued at the same dose.
 Steroid dependent patients or pts who cannot tolerate 5-ASA medications
should be maintained with 6-MP/AZA or an anti-TNF agent.

68. Algorithm for the management of severely active UC

69. TREATMENT OF FULMINANT UC
 Should be admitted & treated with IV glucocorticoids.
 All patients should be treated with broad-spectrum antibiotics
(eg, ciprofloxacin and metronidazole).
 Should be kept NPO.
 CBC, electrolyte, albumin, LFT, ESR & CRP - Q12-24 hrs.
 Nutritional support if malnourished.
 VTE prophylaxis
 Intravenous fluid & electrolyte replacement
 Blood transfusions - maintain Hgb ≥10 g/dL

70. Subsequent therapy
 Patients who fail to improve by the 3rd day of intensive Rx
-> cyclosporine or infliximab, or undergo colectomy.
 Infliximab can induce remission rapidly and can be used for the
maintenance of remission.
 Cyclosporine is used as a short-term "bridge" to therapy with the
slower onset, longer acting medications, including AZA or 6-MP.
 Colectomy
 For pts who fail treatment with cyclosporine or infliximab within 4-7
days & those with toxic megacolon who don’t respond to therapy
within 72 hrs.

71. SURGICAL THERAPY
 10-20% of patients with UC require surgical treatment.
 Goals : to remove the entire diseased colon while preserving
continence and sexual function and elimination of CRC risk
 Emergency, urgent or elective surgery

72. Schematic diagrams of various surgical options for the management of UC.
A, Conventional (Brooke) ileostomy with a subtotal colectomy and a Hartman
pouch.
B, Subtotal colectomy with ileorectal anastomosis.
C, Conventional (Brooke) ileostomy with a total proctocolectomy.
D, Continent ileostomy (Koch pouch) with total proctocolectomy.
E, Restorative proctocolectomy with ileal pouch-anal anastomosis (RPC-IPAA)

73. Mgt of UC related complication
Strictures and Fibro-stenotic Disease
 Colonic strictures -5%
 Hypertrophy and thickening of muscularis mucosa rather than fibrosis.
 Most commonly in extensive and long-standing colitis
 Typically short -2 to 3 cm
 Occur distal to the splenic flexure
 High index of suspicion of malignancy – esp. when the strictures are
located proximal to the splenic flexure.
 Multiple biopsies are recommended at colonoscopy
 Surgical resection of the stricture is advised, particularly in patients
with long-standing disease.

74. Toxic Megacolon
 Iv rehydration, NPO, tube decompression
 DVT & ulcer prophylaxis
 All antimotility agents, opiates & anticholinergics should be
discontinued
 Broad-spectrum antibiotics empirically
 IV corticosteroids
 Approximately 50% of acute dilatation resolves with medical Rx
 Patients who do not improve after 48 - 72 hrs of medical rx should
undergo surgery.
 Patients with progressive abdominal distention, development of
rebound tenderness, or hemodynamic instability should undergo
immediate colectomy.

75. Free perforation
 Can develop in the absence of colonic dilatation -1%
 Classic physical findings of peritonitis may be absent
 Sigmoid colon - most at risk for free perforation
 The mortality has been reported to be >50%.

76. Dysplasia & CRC
 The risk of developing CRC is low during the first 8-10 yrs after a dx
 The risk increases by 0.5-1%/yr after the first 10 yrs
 Cumulative risk of CRC for all UC
 <1% at 10 yrs, 0.4-2% at 15 yrs, &1.1-2.5% at 20yrs
 RF: Duration and extent of the disease co-existing PSC, M gender,
family hx of CRC, age at dx, severity of inflammation.
 The estimated cancer risks in patients who have
 Polyp with low-grade dysplasia-10 – 30%
 Polyp with high-grade dysplasia -30 -40%
 Dysplasia within a lesion or mass (DALM) - 80%

77. Surveillance colonoscopy
 Has been associated with lower rates of CRC & mortality.
 Surveillance began at 8 years after dx and at time of dx in patients with
PSC.
 Surveillance intervals: 1-3 yrs & annually in those with PSC
 Colectomy is recommended for HGD & multifocal LGD

78. References
 Sleisenger and Fordtran’s 11th Edition
 Harrison’s, principles of Internal medicine, 20th
edition
 ACG 2019 practical guidelines
 Uptodate 2018

79. Thank you!