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

• The occurrence of ulcerative colitis is high in the Nordic countries, Western Europe, North America and Australia. The annual incidence in Finland is about 25 new cases/100 000 individuals/year, and the prevalence rate is about 550/100 000 individuals.
• 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).

• 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, stool culture or faecal nucleic acid testing for bacteria, 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 or
    • 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

• Other colitis (microscopic colitis Microscopic Colitis, colitis of Crohn's disease Crohn's Disease, infectious colitis Prolonged Diarrhoea in Adults, ischaemic colitis Diseases Causing Rectal Bleeding, radiation colitis), diverticulitis Diverticulitis and Diverticulosis, tumours Colorectal Cancer, functional diarrhoea Functional Bowel Disorders and the Irritable Bowel Syndrome (IBS).

Treatment Omega 3 Fatty Acids for Maintenance of Remission in Ulcerative Colitis, Lymphoma Risk Among Inflammatory Bowel Disease Patients Treated with Azathioprine or 6-Mercaptopurine, Fish Oil for Induction of Remission in Ulcerative Colitis, Probiotics for Induction of Remission in Ulcerative Colitis, Methotrexate for Induction of Remission in Ulcerative Colitis, Tacrolimus (Fk506) for Induction of Remission in Refractory Ulcerative Colitis, Vedolizumab for Induction and Maintenance of Remission in Ulcerative Colitis, Open Versus Laparoscopic (Assisted) Ileo Pouch Anal Anastomosis for Ulcerative Colitis and Familial Adenomatous Polyposis, Methotrexate for Maintenance of Remission in Ulcerative Colitis, Probiotics Versus Mesalazine or Placebo for Maintenance of Remission in Ulcerative Colitis, Oral 5-Aminosalicylic Acid for Maintenance of Remission in Ulcerative Colitis, Curcumin 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.
  • Mesalazine suppositories in proctitis
  • 5-ASA (5-aminosalicylic acid) enemaRectal 5-Aminosalicylic Acid for Induction of Remission in Distal Ulcerative Colitis
  • Topical cortisone preparations (hydrocortisone foam in aerosol pack, for example)
  • Budenoside enema
• Mild colitis
  • Mesalazine 1.6-4.0 g/day or sulphasalazine 3-4 g/day Oral 5-Aminosalicylic Acid for Induction of Remission in Ulcerative Colitis
• If 5-ASA therapy does not improve symptoms promptly in moderate disease, a glucocorticoid is added to the regimen.
  • Budesonide MMX 9 mg/day for no longer than 8 weeksOral Budesonide for Induction of Remission in Ulcerative Colitis
  • Prednisone or prednisolone 30-40 mg/day for 1-2 weeks, followed by dose reduction and the course is completed within 4-12 weeks.
• Combination therapy with 5-ASA tablets and suppositories is more effective than therapy with tablets only.
• In steroid-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.
  • Laboratory tests on weeks 0, 2, 4, 6 and 8 and thereafter every 3 months: complete blood count, ALT, alkaline phosphatase
  • Thiopurine S-methyltransferase (TPMT) test identifies patients (0.3 % of the population) with low TPMT activity and hence susceptible to adverse effects of thiopurines (myelosuppression, pancytopenia and possibly secondary neoplasias).
• 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.
  • TNF-alpha inhibitors (infliximab Tumour Necrosis Factor Alpha Blocking Agents (Infliximab) for Induction of Remission in Ulcerative Colitis, adalimumab, golimumab)
  • Integrin inhibitor vedolizumab Vedolizumab for Induction and Maintenance of Remission in Ulcerative Colitis
  • Janus kinase inhibitor tofacitinib
  • Interleukin 12 and 23 inhibitor ustekinumab
• The management of severe colitis is carried out in specialist centres.
  • CiclosporinCyclosporine A in Severe Ulcerative Colitis or infliximabTumour Necrosis Factor Alpha Blocking Agents (Infliximab) for Induction of Remission in Ulcerative Colitis 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 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 Colonoscopic Surveillance for Cancer in Ulcerative Colitis, 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 ulcerative colitis about 8 years after symptom onset. 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. Severe dysplasia, or repeatedly detected mild dysplasia, is an indication for surgery.
    • 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
  • Monitoring drug therapy: basic blood count with platelets (including neutrophils during azathioprine or mercaptopurine therapy), ALT, alkaline phosphatase, creatinine (during 5-ASA therapy)