Normal Colonoscopy, Abnormal Biopsies
Microscopic colitis is a chronic inflammatory condition of the colon that causes persistent, watery, non-bloody diarrhoea — often 5 to 10 episodes per day. Its defining paradox: the colonic mucosa appears macroscopically normal during colonoscopy. The diagnosis is made exclusively through histological examination of random biopsies taken from the right and left colon, revealing one of two subtypes.
Two Subtypes
Collagenous colitis is characterised by a thickened subepithelial collagen band (greater than 10 micrometres, compared to the normal 3 to 5) and an increase in intraepithelial lymphocytes. Lymphocytic colitis shows increased intraepithelial lymphocytes (greater than 20 per 100 epithelial cells) without significant collagen thickening. Both subtypes produce similar symptoms — watery diarrhoea, abdominal cramping, urgency, and nocturnal episodes — and respond to similar treatments. Some pathologists consider them a spectrum of the same disease.
Who Gets It
Microscopic colitis is more common than previously recognised. Population-based studies estimate an incidence of 10 to 20 per 100,000 person-years — comparable to Crohn's disease. It predominantly affects women over 60, but can occur at any age. Strong associations exist with autoimmune conditions (coeliac disease, thyroid disease, rheumatoid arthritis), certain medications (PPIs, NSAIDs, SSRIs, and particularly the anti-diabetic drug acarbose), and smoking — which is a risk factor for collagenous colitis specifically.
The Diagnostic Gap
Because the colonic mucosa looks normal macroscopically, microscopic colitis is frequently missed if biopsies are not taken. Guidelines now recommend that random biopsies should be obtained during colonoscopy in all patients investigated for chronic watery diarrhoea, even when the mucosa appears visually normal. Fecal calprotectin is mildly elevated (typically 50 to 200 micrograms per gram) in approximately 50 to 60 percent of microscopic colitis patients — helpful when raised, but a normal result does not exclude the diagnosis.
Treatment
Budesonide (a topically acting corticosteroid with limited systemic absorption) is the first-line treatment, with response rates exceeding 80 percent. However, relapse upon discontinuation is common (60 to 80 percent), and many patients require low-dose maintenance therapy. Cholestyramine (a bile acid sequestrant) is useful as adjunctive therapy, particularly when bile acid malabsorption coexists. Immunomodulators (azathioprine, methotrexate) and biologics (anti-TNF agents) are reserved for refractory cases. Medication review is essential — withdrawal of offending drugs (PPIs, NSAIDs) can produce remission without additional treatment.