What is the diagnosis and treatment for a middle-aged to older adult, possibly female, with chronic diarrhea, abdominal pain, and weight loss, suspected to have microscopic colitis?

Microscopic Colitis: Diagnosis and Treatment

Diagnosis

Microscopic colitis should be diagnosed via colonoscopy with biopsies from multiple colonic segments, as the colonic mucosa appears grossly normal endoscopically and diagnosis requires histological confirmation. 1

When to Suspect Microscopic Colitis

Consider microscopic colitis in patients presenting with:

• Chronic watery, non-bloody diarrhea as the hallmark symptom 1, 2
• Age ≥50 years (mean presentation around 60-65 years) 1, 2
• Female sex (particularly collagenous colitis with 77% female predominance; lymphocytic colitis 68%) 1
• Nocturnal diarrhea or fecal incontinence 3, 2
• Weight loss 1, 2
• Duration of diarrhea <12 months 1
• Coexistent autoimmune diseases (thyroid disease, rheumatoid arthritis) 1
• Use of triggering medications: NSAIDs, PPIs, SSRIs, or statins 1, 2

Diagnostic Workup

Initial laboratory evaluation:

• Complete blood count, serum albumin, ferritin, and C-reactive protein 1
• Liver enzymes and renal function for baseline assessment 1
• Stool testing for Clostridioides difficile is mandatory in all cases of diarrhea, regardless of antibiotic history 1

Endoscopic evaluation:

• Colonoscopy with biopsies from multiple colonic segments is required (not just rectosigmoid, as disease may be patchy) 1
• Obtain biopsies from descending colon in addition to rectosigmoid, as rectal biopsies alone may miss the diagnosis 1
• Fecal calprotectin may help prioritize endoscopy but cannot exclude microscopic colitis 1

Histological criteria:

• Lymphocytic colitis: >20 intraepithelial lymphocytes per 100 epithelial cells 1
• Collagenous colitis: thickened subepithelial collagen band >10 μm plus increased lymphocytes 1

Critical Differential Diagnoses to Exclude

In elderly patients, aggressively rule out:

• Colorectal cancer (most critical) 1
• Ischemic colitis 1
• Inflammatory bowel disease (15% of new IBD diagnoses occur after age 60) 1
• Celiac disease (5-7% association with microscopic colitis) 1
• Bile acid diarrhea (present in 41% of collagenous colitis, 29% of lymphocytic colitis) 1, 3

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Treatment

Budesonide 9 mg once daily is the first-line treatment for induction of remission in symptomatic microscopic colitis, with proven superiority over other agents. 4

Step 1: Identify and Discontinue Triggering Medications

Before initiating pharmacotherapy, discontinue potential triggers when clinically feasible: 1, 4

• NSAIDs
• Proton pump inhibitors
• Selective serotonin reuptake inhibitors
• Statins

Step 2: First-Line Pharmacotherapy Based on Symptom Severity

For mild symptoms:

• Loperamide (antidiarrheal) as initial symptomatic therapy 4, 5, 2
• Bismuth salicylate as alternative (conditionally recommended, low-quality evidence) 4

For moderate-to-severe symptoms:

• Budesonide 9 mg once daily for up to 8 weeks (strongly recommended, moderate-quality evidence) 4, 6
• Swallow tablets whole; do not crush, chew, or break 6
• Take with or without food 6
• Avoid grapefruit juice (inhibits CYP3A4 metabolism) 6

Alternative first-line options (if budesonide contraindicated):

• Mesalamine (conditionally recommended, moderate-quality evidence) 4
• Prednisolone/prednisone (conditionally recommended, very low-quality evidence) 4

Step 3: Maintenance Therapy for Relapsing Disease

Approximately one-third of patients achieve spontaneous remission and do not require maintenance therapy. 3 However, for patients with symptom recurrence after stopping induction therapy:

• Budesonide maintenance: start at 6 mg daily, taper to lowest effective dose 4
• Reduces clinical relapse risk by 66% (RR 0.34,95% CI 0.19-0.6) 4, 3
• Continue for 6-12 months before attempting discontinuation 4
• Monitor for bone loss with prolonged use; consider osteoporosis screening and prevention 4, 6

Step 4: Refractory Disease Management

If symptoms persist despite budesonide therapy: 1, 4

• Re-evaluate for coexisting celiac disease (perform serologic testing and duodenal biopsies)
• Consider bile acid diarrhea (SeHCAT scan or serum 7α-hydroxy-4-cholesten-3-one testing)
• Assess for post-inflammatory functional bowel disorders
• Re-confirm medication discontinuation (NSAIDs, PPIs, SSRIs)
• Consider rare immunomodulators (infliximab, adalimumab, vedolizumab, thiopurines, methotrexate) in exceptional cases 2, 7

Treatments NOT Recommended

Do not use the following (insufficient evidence or proven ineffective): 4

• Combination cholestyramine plus mesalamine (no superiority over mesalamine alone)
• Boswellia serrata
• Probiotics

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Key Clinical Pitfalls to Avoid

• Do not assume normal endoscopy excludes microscopic colitis—biopsies are mandatory 1
• Do not obtain biopsies only from rectosigmoid—disease may be patchy, requiring descending colon sampling 1
• Do not use systemic corticosteroids for maintenance therapy—budesonide has lower systemic effects 4, 6
• Do not ignore medication triggers—NSAIDs, PPIs, and SSRIs are strongly associated with disease 1, 4
• Do not overlook bile acid diarrhea—present in 29-41% of microscopic colitis cases and requires specific treatment 1, 3
• Monitor for adrenal suppression and hypercorticism with prolonged budesonide use, especially in patients with liver disease 6

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Treatment Goals

The primary goal is symptom relief and improved quality of life, not histological remission. 1 Unlike inflammatory bowel disease, persistent histological inflammation in microscopic colitis does not predict colorectal cancer risk or need for surgery. 1 Treatment decisions should focus on morbidity reduction and quality of life improvement rather than endoscopic or histologic endpoints.