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TainaSipponen

Ulcerative Colitis

Essentials

  • Ulcerative colitis may be the cause of recurrent or prolonged (bloody) diarrhoea.
  • Treatment decisions and medication choices are based on the severity of the symptoms and the extent of the disease (proctitis, left-sided colitis or extensive colitis).
  • Patients with acute severe colitis require hospitalisation.
  • Owing to the increased risk of developing carcinoma, regular endoscopic screening is indicated in ulcerative colitis.

Epidemiology

  • Globally, there are at least 5 million people with ulcerative colitis and the incidence is increasing http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00966-2/.
  • The occurrence of ulcerative colitis is high in the Nordic countries, Western Europe, North America and Australia and increasing in several Asian countries.
  • The pathogenetic mechanism is not known.
  • Having close relatives with an inflammatory bowel disease increases the risk of developing ulcerative colitis.

Signs and symptoms

  • Diarrhoea, stools mixed with blood and mucus, abdominal pain, sometimes weight loss
  • The symptoms have usually persisted for several weeks or months.
  • Recurrent relapses are typical as are remissions, either spontaneous or drug-induced. About 10-20% of patients have continuous symptoms.
  • The disease can be divided into mild, moderate and severe forms (table T1).

The severity of ulcerative colitis

SeverityDefinition
Mild colitisDiarrhoea < 4 times / 24 hours (with or without blood), no systemic symptoms, Hb > 115 g/l, normal inflammatory markers
Moderate colitisDiarrhoea > 4 times / 24 hours, absent or mild systemic symptoms, Hb HASH(0x2f625d8) 105 g/l, normal inflammatory markers
Severe colitisDiarrhoea HASH(0x2f625d8) 6 times / 24 hours and tachycardia, fever, Hb < 105 g/l, elevated inflammatory markers (ESR > 30 mm/h and/or CRP > 30 mg/l)
  • Extraintestinal involvement is possible (arthritis, uveitis, episcleritis, erythema nodosum, pyoderma gangrenosum and primary sclerosing cholangitis).

Diagnosis and investigations

  • Complete blood count, CRP, plasma creatinine and albumin, ALT, ALP, tissue transglutaminase antibodies, faecal calprotectin, faecal nucleic acid testing for bacteria and culture of certain positive findings, feacal nucleic acid testing for Clostridium difficile toxin gene
  • Ileocolonoscopy: loss of the typical vascular pattern, mucosal erythema, easy bleeding upon touch, erosions and ulcerations
    • Classification of the extent of inflammatory changes
      • Limited to the rectum, i.e. proctitis
      • Left-sided colitis
      • Extensive colitis (the changes extend past the splenic curve)
    • Classification of the severity of inflammatory changes
      • Mild: decreased vascular pattern, mild erythema, mild contact bleeding
      • Moderate: erythema, absent vascular pattern, contact bleeding, erosions
      • Severe: erythema, absent vascular pattern, contact bleeding, spontaneous bleeding, ulceration, mucopurulent exudate
  • The histological findings are typical but not specific (diffuse acute and chronic inflammatory changes that are limited to the mucosa and submucosa; ulceration as the inflammation worsens).
    • Biopsies are necessary even when the colonic mucosa has a normal appearance.
  • The clinical criteria for severe colitis
    • Diarrhoea > 6 times / 24 hours and one of the following:
      • fever > 37.5 °C
      • tachycardia > 90/min
      • anaemia, Hb < 105 g/l
      • ESR > 30 mm/h or CRP > 30 mg/l

Differential diagnosis

Treatment Vedolizumab for Induction and Maintenance of Remission in Ulcerative Colitis, Methotrexate for Maintenance of Remission in Ulcerative Colitis

  • The severity of symptoms and extent of the disease influence the treatment of ulcerative colitis.
  • Disease limited to the rectum (proctitis) and the lower part of the sigmoid colon is treated with topical therapy.
  • Mild colitis
  • If 5-ASA therapy does not improve symptoms promptly in moderate disease, a glucocorticoid is added to the regimen.
  • Combination therapy with 5-ASA tablets and suppositories is more effective than therapy with tablets only.
  • In glucocorticoid-dependent ulcerative colitis, a thiopurine is introduced as maintenance therapy (azathioprine or 6-mercaptopurine) Azathioprine and 6-Mercaptopurine for Maintenance of Remission in Ulcerative Colitis.
    • TPMT and NUDT15 genotype testing is recommended before starting treatment as reduced activity of these genes predisposes to the adverse effects of the drug.
    • Substitution of thiopurine therapy with other maintenance drugs is recommended for consideration in Epstein-Barr virus antibody negative patients and in patients over 65 years of age.
    • Hepatitis B surface antigen andHIV antigen and antibodies testing before the start of treatment
    • Safety monitoring tests at weeks 0, 2, 4 and 8 and every 3-4 months for the first year: complete blood count, ALT, alkaline phosphatase.Ina stablesituation, safety monitoring tests every 6 months after the first year of treatment are sufficient.
    • Blood 6-thioguanine testing may be useful if adequate treatment response has not been achieved.
  • Biological or other medication is considered if repeated glucocorticoid treatment is needed during thiopurine medication, or if the patient has thiopurine intolerance. Such therapy should be carried out in units with specific experience on the treatment.
  • The management of severe colitis is carried out in specialist centres.
    • Ciclosporin or infliximab can be used to induce remission in severe colitis refractory to intravenous glucocorticoids.
    • Red cell transfusions and parenteral nutrition as necessary
    • Surgical opinion must be sought immediately if signs of bowel dilatation are observed or if the patient has severe colitis refractory to pharmacotherapy.
    • Thrombosis prophylaxis with a low molecular weight heparin is recommended.
    • Untreated severe colitis may result in toxic dilatation of the colon (toxic megacolon) which is associated with the risk of perforation.
  • In ulcerative colitis refractory to medical therapy the surgical option considered is panproctocolectomy and the formation of an ileoanal anastomosis.

Arrangement of treatment

  • Indications for a specialist's consultation or referral to a specialist
    • The symptoms of a recurrent episode are not alleviated within 1-2 weeks.
    • Glucocorticoids cannot be withdrawn after 3 months of therapy.
    • Pregnancy, even if no symptoms are present
    • Extraintestinal manifestations (liver, skin, joints, lower back, eyes)

Follow-up

  • Endoscopic monitoring Strategies for Detecting Colon Cancer and/or Dysplasia in Patients with Inflammatory Bowel Disease
    • The activity and extent of symptomatic disease is monitored with colonoscopy as necessary.
    • Owing to the risk of cancer, colonoscopy is recommended for all patients with left-side or extensive ulcerative colitis about 8 years after symptom onset.
    • Colonoscopy is recommended in the quiescent phase of the disease as a so-called chromoendoscopy using either injectable dye or the light technique of a scope to detect possible dysplastic changes. Detected dysplastic changes may be suitable for endoscopic removal.
    • Thereafter, follow-up examinations are programmed to take place every 1-5 years as dictated by e.g. disease duration, associated diseases and the extent and activity of the disease in order to detect the development of dysplasia.
    • If severe dysplasia or repeatedly mild dysplasia is found in biopsies without a change detectable by chromoendoscopy and suitable for endoscopic removal, surgical treatment is indicated.
      • In colitis limited to the rectum, i.e. proctitis, endoscopy follow-up is not required.
  • Laboratory monitoring
    • Monitoring clinical activity: basic blood count with platelets, CRP and faecal calprotectin
    • In a remission situation, every 6-12 months is sufficient.
    • Recommendation for monitoring drug therapy
      • 5-aminosalicylic acid users: 3 months after starting the medication and then annually: basic blood count with platelets, ALT, alkaline phosphatase, plasma creatinine
      • Thiopurines: see above.
      • Before starting biological therapy or JAK inhibitors, in addition to basic laboratory tests (complete blood count, ALT, alkaline phosphatase, plasma creatinine), HIV antigen and antibodies, hepatitis B surface antigen, interferon gamma release assay (IGRA measuring interferon gamma or the number of interferon gamma releasing cells; see local guidance for details).
      • JAK inhibitors: complete blood count, ALT, alkaline phosphatase, plasma creatinine at the initial situation, 4-8 weeks after the start and thereafter every 3-6 months; lipids 8-12 weeks after the start and thereafter every 12 months
      • During the maintenance phase of a biological drug, basic blood count with platelets, ALT, alkaline phosphatase every 6 months

Surgical treatment

  • Indications
    • Acute severe, pharmacotherapy-resistant colitis
    • Persistently active colitis poorly responding to pharmacotherapy
    • Colonoscopy has revealed dysplasia unsuitable for endoscopic removal.
    • Cancer found on colonoscopy
  • Implementation
    • The operation involves the removal of the entire large intestine and rectum and doing either an ileoanal anastomosis in the anus (J-pouch) or a permanent ileostomy.
    • Depending on the situation with regard to the colitis and on the medication used, the surgical treatment may be performed in one or more phases.

    References

    • Kontola K, Oksanen P, Huhtala H, et al. Increasing Incidence of Inflammatory Bowel Disease, with Greatest Change Among the Elderly: A Nationwide Study in Finland, 2000-2020. J Crohns Colitis 2023;17(5):706-711 [PubMed]
    • D'Haens G, Dubinsky M, Kobayashi T, et al. Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med 2023;388(26):2444-2455 [PubMed]
    • Danese S, Vermeire S, Zhou W, et al. Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials. Lancet 2022;399(10341):2113-2128 [PubMed]
    • Spinelli A, Bonovas S, Burisch J, et al. ECCO Guidelines on Therapeutics in Ulcerative Colitis: Surgical Treatment. J Crohns Colitis 2022;16(2):179-189 [PubMed]
    • Raine T, Bonovas S, Burisch J, et al. ECCO Guidelines on Therapeutics in Ulcerative Colitis: Medical Treatment. J Crohns Colitis 2022;16(1):2-17 [PubMed]
    • Feagan BG, Danese S, Loftus EV Jr, et al. Filgotinib as induction and maintenance therapy for ulcerative colitis (SELECTION): a phase 2b/3 double-blind, randomised, placebo-controlled trial. Lancet 2021;397(10292):2372-2384 [PubMed]
    • Maaser C, Sturm A, Vavricka SR, et al. ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 1: Initial diagnosis, monitoring of known IBD, detection of complications. J Crohns Colitis 2019;13(2):144-164 [PubMed]
    • Sipponen T, Färkkilä M. [Inflammatory bowel diseases]. In: Färkkilä M, Isoniemi H, Heikkinen M, Puolakkainen P (eds.). [Gastroenterology and hepatology]. Duodecim Publishing Company Ltd 2018. Available in Finnish.