What is the treatment for ulcerative colitis (UC) with diarrhea?

Treatment of Ulcerative Colitis with Diarrhea

For mild to moderate UC with diarrhea, start with combination therapy of topical mesalazine 1 g daily plus oral mesalazine 2-4 g daily, which is more effective than either agent alone and directly targets the inflammatory cause of diarrhea. 1

Treatment Algorithm Based on Disease Extent

Distal UC (Proctitis and Left-Sided Disease)

First-line therapy for distal UC causing diarrhea is combination topical mesalazine 1 g daily (suppositories for proctitis, enemas for left-sided disease) plus oral mesalazine 2-4 g daily. 2, 1

• Topical mesalazine suppositories deliver medication more effectively to the rectum and are better tolerated than foam or enemas for proctitis 2
• Topical mesalazine is superior to topical corticosteroids and should be first-line; reserve topical steroids only for patients intolerant of topical mesalazine 2, 1
• A critical pitfall: proximal constipation can paradoxically worsen diarrhea in distal UC—treat this with stool bulking agents or laxatives 2, 1

If combination therapy fails after adequate trial, escalate to oral prednisolone 40 mg daily, continuing topical mesalazine as adjunctive therapy. 2, 1

Extensive or Left-Sided UC

For mild to moderate extensive UC with diarrhea, initiate oral mesalazine 2-4 g daily or balsalazide 6.75 g daily as first-line therapy. 2, 1

• Avoid olsalazine in pancolitis as it has a higher incidence of diarrhea compared to other 5-ASA formulations 2
• Sulfasalazine has more side effects than newer 5-ASA drugs but may benefit selected patients with reactive arthropathy 2
• The optimal dose is 4.8 g/day of mesalazine for active disease, as efficacy is dose-dependent 3, 4

When prompt response is needed or mesalazine fails, add prednisolone 40 mg daily. 2, 1

• Taper prednisolone gradually over 8 weeks according to clinical response 2, 1
• Critical warning: rapid steroid tapering is associated with early relapse—avoid tapering faster than 8 weeks 2, 1
• Topical mesalazine or steroids may be added for troublesome rectal symptoms, though unlikely to be effective alone 2

Steroid-Dependent or Refractory Disease

Long-term steroid use should be avoided; patients with chronic active steroid-dependent disease require azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day as steroid-sparing agents. 2, 1

• Ciclosporin may be effective for severe, steroid-refractory colitis 2
• Infliximab 5 mg/kg IV at weeks 0,2, and 6, then every 8 weeks is FDA-approved for moderately to severely active UC with inadequate response to conventional therapy 5, 4
• Vedolizumab is also FDA-approved for moderately to severely active UC 6

Severe UC with Diarrhea Requiring Hospitalization

Patients meeting Truelove and Witts' criteria (bloody stool frequency ≥6/day plus tachycardia >90/min, temperature >37.8°C, hemoglobin <10.5 g/dL, or ESR >30 mm/h) require immediate hospitalization. 2, 1

Hospital management includes:

• Intravenous fluid and electrolyte replacement 1
• Intravenous corticosteroids 1
• Daily monitoring of vital signs, stool frequency, complete blood count, inflammatory markers (CRP can substitute for ESR at 30 mg/L), electrolytes, albumin 2, 1
• Daily abdominal radiography if colonic dilatation detected 1
• Subcutaneous heparin for thromboprophylaxis 1
• Nutritional support 1
• Joint medical and surgical management with colorectal surgeon 1

Critical Pitfalls to Avoid

Always exclude infectious causes of diarrhea before attributing symptoms to UC flare and escalating immunosuppressive therapy, though treatment need not wait for microbiological results. 2, 1

• Disease activity should be confirmed by sigmoidoscopy before treatment escalation 2
• Combination therapy (topical plus oral) is consistently more effective than monotherapy for controlling diarrhea in distal disease 2, 1
• Lifelong maintenance therapy is generally recommended for all patients to prevent recurrent diarrhea episodes, especially for left-sided or extensive disease 1
• Starting mesalazine at 4.8 g/day rather than lower doses with subsequent escalation is more effective 3, 4