Indeterminate Colitis

Indeterminate colitis is a pathological term for colonic inflammatory bowel disease that cannot be classified as ulcerative colitis or Crohn disease after examination of a resected colon. Inflammatory bowel disease unclassified is the clinical term for colitis with no small bowel disease and non-specific findings after full evaluation.

It accounts for 5% to 15% of inflammatory bowel disease. In children, the share is larger (up to 20%) and many are reclassified as ulcerative colitis or Crohn disease over time (30% to 80% in some series).

Typical settings are fulminant colitis, severe colitis with transmural inflammation and deep ulcers, and colitis in a patient with atypical features such as rectal sparing or patchy disease.

Pathophysiology.

It reflects shared immune mechanisms of ulcerative colitis and Crohn disease, with genetic and microbial triggers.

Bloody diarrhoea, urgency, abdominal pain, weight loss, fever in severe disease, and extraintestinal manifestations (arthritis, uveitis, skin and liver disease).

Red flags.

• Toxic megacolon.
• Severe haemorrhage.
• Perforation.
• Weight loss with anaemia in older adults.

Repeat the evaluation: ileocolonoscopy with multiple biopsies, upper endoscopy, small bowel magnetic resonance enterography or capsule endoscopy, stool tests for infection and calprotectin, and blood tests (haemoglobin, albumin, C-reactive protein). Serology (pANCA and ASCA) does not settle the diagnosis. Review pathology by an experienced gastrointestinal pathologist.

Differential diagnosis.

• Ulcerative colitis.
• Crohn colitis.
• Infective colitis.
• Ischaemic colitis.
• Drug induced colitis (NSAID, immune checkpoint inhibitor).
• Diversion colitis.

Treat the dominant pattern, usually ulcerative colitis, and review the diagnosis at each stage.

• Mesalazine (mild to moderate disease): 2.4 to 4.8 g orally once daily for induction; maintenance 1.2 to 2.4 g daily; maximum 4.8 g daily; monitor renal function before and yearly; avoid in salicylate allergy; reduce or avoid when eGFR is under 30 mL/min.
• Prednisolone (moderate to severe disease): 40 mg orally once daily, tapered by 5 mg weekly over 8 weeks; maximum 60 mg daily; monitor glucose, blood pressure, mood and bone health; use with calcium and vitamin D.
• Infliximab: 5 mg/kg IV at weeks 0, 2 and 6, then every 8 weeks; maximum 10 mg/kg each dose; monitor infection, infusion reactions and liver enzymes; screen for tuberculosis and hepatitis B first; avoid in moderate to severe heart failure.
• Azathioprine (steroid sparing): 2 to 2.5 mg/kg orally once daily; maximum 3 mg/kg daily; monitor blood counts and liver enzymes every 1 to 2 weeks for 8 weeks and then every 3 months; check thiopurine methyltransferase and NUDT15 first; reduce in renal impairment and with allopurinol.

Colectomy is required for toxic megacolon, perforation, haemorrhage and refractory disease. Ileal pouch anal anastomosis is possible but has a higher risk of pouch failure and Crohn like complications; counsel patients before surgery.

Monitoring. Clinical review, calprotectin and C-reactive protein every 3 to 6 months; colonoscopy for dysplasia from 8 years after onset.

Referral and escalation. Inflammatory bowel disease team; colorectal surgery for severe disease.