A Common Cause of Chronic Diarrhea That Looks Normal
Microscopic colitis is a chronic inflammatory condition of the colon that causes persistent watery diarrhea — but unlike inflammatory bowel disease, the colon often looks completely normal on visual inspection during colonoscopy. The diagnosis is made by examining biopsies under the microscope (hence the name).
It is far more common than once thought. In adults over 65 with chronic diarrhea, microscopic colitis accounts for a substantial percentage of cases — sometimes more than IBS or inflammatory bowel disease. At Zimmer Medical Group, we consider microscopic colitis in any patient with chronic watery diarrhea and have a low threshold for biopsies during colonoscopy in this setting.
Two Main Types
Microscopic colitis comes in two histologic types:
- Lymphocytic colitis — increased lymphocytes in the surface epithelium
- Collagenous colitis — thickened collagen band beneath the surface epithelium
Symptoms and treatment are essentially identical for both. Some patients have features of both types.
Recognizing the Symptoms
Classic features include:
- Chronic, watery, non-bloody diarrhea (often 5–15+ episodes per day)
- Symptoms typically present for weeks to years before diagnosis
- Frequently nighttime diarrhea (more concerning than functional diarrhea like IBS)
- Abdominal cramping
- Fecal incontinence in older adults
- Weight loss in some patients
- Fatigue
- Symptoms can be continuous or relapsing-remitting
Bleeding, fever, and severe abdominal pain are uncommon and should prompt evaluation for other diagnoses.
Who Is Most at Risk
Strong risk factors include:
- Older age (peak incidence 60–70s)
- Female sex (3–8:1 female predominance)
- Smoking
- Certain medications (see below)
- Other autoimmune conditions: celiac disease, thyroid disease, rheumatoid arthritis, type 1 diabetes
- Family history (genetic predisposition)
Medications Frequently Implicated
Several common medications can trigger or worsen microscopic colitis:
- NSAIDs (ibuprofen, naproxen) — strong association
- Proton pump inhibitors — see our long-term PPI use article
- SSRIs (sertraline, fluoxetine, others)
- Statins
- Beta blockers
- Acarbose
- Ranitidine (now off market) and other H2 blockers
- ACE inhibitors
Many patients see substantial improvement just by stopping or substituting the implicated medication. Reviewing the medication list is one of the most important steps in evaluation.
Diagnosis Requires Colonoscopy with Biopsy
The diagnosis cannot be made on stool tests alone. Colonoscopy is required because:
- The colon often looks normal — biopsies must be taken even from normal-appearing mucosa
- Multiple biopsies from both right and left colon are needed
- Microscopic features definitively distinguish microscopic colitis from other diagnoses
Stool tests should still be done first to exclude infectious causes. Celiac disease testing (tTG-IgA) should be checked in any patient with chronic diarrhea before scoping.
Distinguishing From Other Causes
Several conditions can cause similar symptoms:
- Celiac disease — very common in microscopic colitis patients; should always be tested
- Bile acid diarrhea — increasingly recognized as a cause of chronic watery diarrhea
- Lactose intolerance
- IBS-D — but IBS rarely causes nighttime diarrhea
- Inflammatory bowel disease — usually shows visible damage and may cause bleeding
- Hyperthyroidism
- Diabetic diarrhea
- Pancreatic insufficiency
- Chronic infection — Giardia, C. difficile
A thoughtful workup distinguishes these.
Treatment Approach
Step 1: Eliminate Triggers
- Stop or substitute implicated medications when possible
- Smoking cessation
- Reduce alcohol and caffeine if they worsen symptoms
- Trial of lactose-free diet
- Avoid NSAIDs
Step 2: Anti-Diarrheal Therapy
- Loperamide (Imodium) — often very effective for symptom control; safe for chronic use in microscopic colitis
- Bismuth subsalicylate (Pepto-Bismol) — modestly effective; concerns about chronic salicylate use limit prolonged daily use
- Cholestyramine or colesevelam — particularly helpful when bile acid malabsorption coexists
Step 3: Budesonide
Budesonide (Entocort) is the most evidence-supported treatment for moderate to severe microscopic colitis:
- High first-pass metabolism in the liver, so systemic side effects are minimal
- Typical induction: 9 mg daily for 6–8 weeks
- Maintenance: 6 mg daily, then often tapered to lowest effective dose
- Most patients respond within weeks
- Recurrence after discontinuation is common; many patients need long-term maintenance therapy
Budesonide is the standard of care recommended by major societies including the American Gastroenterological Association.
Step 4: Other Options for Refractory Cases
- Mesalamine (5-ASA) — modest evidence
- Immunomodulators (azathioprine, methotrexate) — for severe refractory cases
- Biologic therapy (anti-TNF) — rarely needed
- Diverting ileostomy — extremely rare, last-resort option
Coexisting Celiac Disease
Up to 10–20 percent of microscopic colitis patients have celiac disease. Both conditions need treatment. A gluten-free diet may improve microscopic colitis symptoms in patients with both diagnoses.
What Patients Should Know
- Microscopic colitis is real, treatable, and not "just IBS"
- It does not increase colon cancer risk
- It does not progress to inflammatory bowel disease
- Most patients respond well to treatment
- The disease tends to relapse, so ongoing management may be needed
- Reviewing all medications is a critical step
When to See Your Doctor
- Chronic watery diarrhea persisting more than 4 weeks
- Diarrhea that wakes you from sleep
- Diarrhea associated with weight loss or fatigue
- Diarrhea after starting a new medication (especially PPIs, NSAIDs, SSRIs)
- Diagnosed IBS that has not responded to typical treatment
- Family history of celiac or autoimmune disease plus chronic diarrhea
For older adults with new or worsening diarrhea, evaluation should not be delayed — fluid loss and incontinence are particularly impactful at this age.
The American College of Gastroenterology clinical guidelines provide further detail on microscopic colitis.
Chronic diarrhea that hasn't been adequately explained or treated? Contact Zimmer Medical Group for a structured evaluation that includes microscopic colitis as a real possibility — and effective treatment when found.
