What are the diagnosis criteria and management options for ulcerative colitis?

Ulcerative Colitis Diagnosis Criteria and Management

The diagnosis of ulcerative colitis requires a combination of clinical history, laboratory tests, endoscopy with histopathology, and exclusion of infectious causes, as there is no single gold standard diagnostic test. 1

Diagnostic Criteria

Clinical Presentation

• Typical symptoms include bloody diarrhea with or without mucus, rectal bleeding, stool consistency and frequency changes, urgency, tenesmus, and variable degrees of abdominal pain often relieved by defecation 1
• Medical history should document recent travel, possible infectious contacts, medication use, smoking status, family history of IBD or colorectal cancer, and previous appendectomy 1
• Physical examination findings depend on disease severity - patients with mild to moderate disease may have unremarkable examinations except for blood on rectal examination, while those with severe disease may present with fever, tachycardia, weight loss, abdominal tenderness, and reduced bowel sounds 1

Laboratory Evaluation

• Initial laboratory tests should include full blood count, electrolytes, liver and renal function, iron studies, vitamin D level, C-reactive protein (CRP), and fecal calprotectin 1
• Stool specimens must be collected to exclude infectious causes, particularly Clostridium difficile 1
• In patients with severe clinical activity, elevated CRP is generally associated with elevated ESR, anemia, and hypoalbuminemia, which can serve as predictive biomarkers for colectomy risk in acute severe colitis 1

Endoscopic Evaluation

• Ileocolonoscopy with biopsy is essential for definitive diagnosis 1
• Inflammation typically begins at the anal verge and extends proximally in a continuous, confluent, and concentric fashion with clear demarcation between inflamed and normal areas 1
• In patients with acute severe colitis, flexible sigmoidoscopy rather than full colonoscopy is recommended to confirm diagnosis and exclude infection 2, 1
• The Mayo scoring system is commonly used to assess endoscopic severity, with scores ranging from 0 (normal) to 3 (spontaneous bleeding) 1

Histopathological Assessment

• For reliable diagnosis, a minimum of two biopsies from at least five sites around the colon (including the rectum) and the ileum should be obtained 1
• Basal plasmacytosis is the earliest diagnostic feature with the highest predictive value for UC diagnosis 1
• Established disease shows widespread crypt architectural distortion, mucosal atrophy, diffuse transmucosal inflammatory infiltrate with basal plasmacytosis, and active inflammation causing cryptitis and crypt abscesses 1
• A decreasing gradient of inflammation from distal to proximal favors UC diagnosis 1

Imaging Studies

• Non-invasive imaging like abdominal X-ray, CT, or ultrasound can help define disease extent and complications 1
• In acute severe colitis, plain abdominal radiograph should be performed to exclude colonic dilatation (≥ 5.5 cm) and estimate the extent of disease 2

Management

Treatment Based on Disease Severity and Extent

Mild to Moderate Disease

• First-line therapy for induction and maintenance of remission is 5-aminosalicylic acid (5-ASA) 3
• For proctitis (distal disease), topical 5-ASA drugs are used as first-line agents 4
• UC patients with more extensive disease should be treated with a combination of oral and topical 5-ASA drugs 4

Moderate to Severe Disease

• Oral corticosteroids are recommended for induction of remission as a bridge to maintenance medications 3
• Maintenance therapy options include:
  • Thiopurines (azathioprine) 2
  • Anti-TNF agents (infliximab, adalimumab, golimumab) - preferably combined with thiopurines, at least for infliximab 2, 5
  • Vedolizumab (anti-α4β7 integrin) 2
  • Ustekinumab (anti-IL-12/IL-23) 3
  • JAK inhibitors (tofacitinib) 3
  • Sphingosine-1-phosphate modulators (ozanimod) 3

Severe Acute Colitis

• Patients with severe UC need to be hospitalized for treatment 4
• Intravenous corticosteroids are first-line therapy 4
• If refractory to steroids, calcineurin inhibitors (cyclosporine, tacrolimus) or anti-TNF agents (infliximab) should be used 4

Special Situations

Steroid-Dependent UC

• Patients with steroid-dependent disease should be treated with a thiopurine, anti-TNF (preferably combined with thiopurines for infliximab), vedolizumab, or methotrexate 2
• In case of treatment failure, second-line medical therapy with an alternative anti-TNF, vedolizumab, or colectomy should be considered 2

Steroid-Refractory UC

• Options include admission for IV steroid therapy, which has been reported to induce remission in a high proportion of patients 2
• Alternative salvage medical therapies include oral or rectal cyclosporine, oral or rectal tacrolimus, or infliximab 2
• If disease persists despite these interventions, surgery is likely to be the outcome 2

Monitoring Response to Treatment

• Response should be determined by a combination of clinical parameters, endoscopy, and laboratory markers such as CRP and fecal calprotectin 1
• In patients who clinically respond to medical therapy, mucosal healing should be assessed endoscopically or by fecal calprotectin approximately 3-6 months after treatment initiation 1
• Mucosal healing is associated with reduced risk of colectomy and lower inflammation at 5 years 1

Surgical Management

• Indications for emergency surgery include refractory toxic megacolon, colonic perforation, or severe colorectal bleeding 4
• Proctocolectomy should be considered in refractory cases or in the presence of high-grade epithelial dysplasia 6
• Up to 10% of patients who have a colectomy for refractory UC only have distal colitis 2

Cancer Surveillance

• Patients with UC require colonoscopy at 8 years from diagnosis for surveillance of dysplasia 3
• The risk of colorectal cancer after 20 years of disease duration is 4.5%, and people with UC have a 1.7-fold higher risk for colorectal cancer compared with the general population 3
• Patients with extensive colitis have higher risk of colectomy and colorectal cancer compared to those with limited disease 1

Common Pitfalls and Caveats

• Disease extent can change after diagnosis - up to half of patients with proctitis or proctosigmoiditis will develop more extensive disease over time 1
• Repeat endoscopy with histopathological review may be necessary if diagnostic doubt remains 1
• Infectious causes must be excluded before confirming diagnosis, particularly C. difficile 1
• Microbial testing is recommended in patients with colitis relapse, particularly for C. difficile and Cytomegalovirus infection 1
• Despite advances in medical therapies, the highest response to these treatments ranges from 30% to 60% in clinical trials 3
• Within 5 years of diagnosis, approximately 20% of patients with UC are hospitalized and approximately 7% undergo colectomy 3