Microscopic colitis is a chronic inflammatory bowel disease with significant ramifications for the quality of life of those it affects. Due to its nonspecific symptoms, the disease risks being underdiagnosed compared to other types of inflammatory bowel disease (IBD), even though epidemiological studies show that the incidence of microscopic colitis has exceeded other types of IBD in some countries. Physicians should be familiar with the nuances of microscopic colitis and management strategies to tackle this debilitating, underrecognized condition appropriately.
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What Is Microscopic Colitis?
Microscopic colitis is a chronic inflammatory disease of the colon that was first described in 1980. It occurs most commonly in females between the ages of 60 and 65. Unlike other types of IBD (Crohn's disease and ulcerative colitis), intestinal inflammation caused by microscopic colitis can only be seen when looking at a sample of affected colonic tissue under a microscope, and it does not increase the risk of developing colon cancer. (19)
There are two clinically distinct forms of microscopic colitis:
- In lymphocytic colitis, the surface layer of the large intestinal lining contains more white blood cells (lymphocytes) than normal.
- In collagenous colitis, the collagen layer under the colon's mucosal lining is thicker than normal.
Microscopic Colitis Signs & Symptoms
The hallmark symptom of microscopic colitis is chronic non-bloody diarrhea, defined as at least three loose or watery stools daily for over four weeks. Most patients experience four to nine watery stools daily, although severe disease can cause upwards of 15 daily bowel movements. (22)
Other symptoms that typically accompany diarrhea include:
Like other forms of IBD, patients with microscopic colitis may also experience symptoms that extend beyond the gastrointestinal (GI) tract, including:
Root Causes of Microscopic Colitis
The exact cause of microscopic colitis remains unknown, but researchers believe a combination of factors contributes to its development. Immune dysregulation is central to most theories surrounding the etiology and pathophysiology of the disease. (38)
Genetics
Few genome-wide studies have explored the genetic association with microscopic colitis. However, those that have suggest that human leukocyte antigen (HLA) variants are associated with an increased risk for collagenous colitis. (38)
The increased concomitance of other autoimmune diseases with microscopic colitis also supports the role of genetics in its pathogenesis. Microscopic colitis often co-occurs with other autoimmune disorders, such as celiac disease, rheumatoid arthritis, and type 1 diabetes (19).
Collagen accumulation in collagenous colitis is affiliated with abnormal collagen due to increased expression of transforming growth factor (TGF) beta-1 (22).
Altered Epithelial Barrier Function
Altered epithelial barrier function of the intestine, leading to hyperpermeability, immune dysregulation, and intestinal inflammation, is also a proposed mechanism in the pathogenesis of microscopic colitis. Exposure to various environmental factors in genetically susceptible individuals likely turns on genetic switches that increase intestinal permeability and dysregulated immune responses.
These environmental factors may include:
- Gastrointestinal bacterial and viral infections, including Clostridioides difficile, Escherichia, Norovirus, and Epstein-Barr virus (24, 36)
- Environmental and food allergies
- Smoking
- Medications: non-steroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), selective serotonin reuptake inhibitors (SSRIs), hormonal contraceptives and hormone replacement therapy (HRT), beta-blockers, and statins
How to Diagnose Microscopic Colitis
Endoscopic evaluation of the colon with mucosal biopsies is required to diagnose microscopic colitis and distinguish between its two subtypes. However, laboratory analysis is warranted before colonoscopy to rule out other common causes of chronic diarrhea.
Here is a step-by-step algorithm that can assist doctors in accurately diagnosing microscopic colitis:
Step 1: Narrow the Differential
Routine blood work is an appropriate first step in evaluating a patient with suspected microscopic colitis to rule out other causes of chronic diarrhea.
These tests can help doctors narrow the differential:
- Complete blood count (CBC)
- Comprehensive metabolic panel (CMP)
- Thyroid panel
- Erythrocyte sedimentation rate (ESR)
- Stool culture
- Ova and parasite testing
- Celiac antibodies
- Fecal calprotectin
Patients with microscopic colitis may have anemia, hypokalemia (low potassium), hypoalbuminemia (low albumin), elevated inflammatory markers (i.e., ESR, calprotectin), and celiac disease (3).
Step 2: Colonoscopy
No single lab test can diagnose microscopic colitis, so patients must be referred for colonoscopy and biopsy. The American Society of Gastrointestinal Endoscopy (ASGE) recommends taking at least eight biopsies from the right, transverse, left, and sigmoid colon during a colonoscopy. (38)
Histopathologic findings that confirm microscopic colitis are:
- Lymphocytic Colitis: 20 or more intraepithelial lymphocytes per 100 surface epithelial cells
- Collagenous Colitis: a thickened subepithelial collagenous band exceeding 10 micrometers
Step 3: Labs to Better Understand the Root Cause of Microscopic Colitis
Several types of tests can help illuminate the root cause of a patient's microscopic colitis and refine therapeutic recommendations to expedite symptom resolution.
Comprehensive Stool Analysis
Bile acid malabsorption, pancreatic insufficiency, intestinal hyperpermeability, and dysbiosis can exacerbate immune dysregulation and GI symptom severity. A comprehensive stool analysis is collected at home by the patient and measures biomarkers for these various imbalances, including:
- Pancreatic elastase
- Fecal bile acids
- Fecal fat
- Zonulin
- Fecal secretory IgA
- PCR and culture methods assess the abundance and diversity of the intestinal microbiome
These are examples of popular comprehensive stool tests:
- GI-MAP by Diagnostic Solutions
- GI360 by Doctor's Data
- GI Effects Comprehensive Profile - 3 day by Genova Diagnostics
Adverse Food Reactions
Identifying foods that trigger an immune response or exacerbate GI symptoms helps guide dietary modifications to reduce intestinal inflammation and symptom severity.
These panels may be a good starting point to uncover underlying food sensitivities and allergies:
- 96 IgG Food Sensitivity & 15 Common IgE Combo Panel by Alletess Medical Laboratory
- P88 Dietary Antigen Test by Precision Point
- Array 4 by Cyrex Labs
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Treatment Plan for Microscopic Colitis
Medical guidelines and a comprehensive laboratory evaluation direct effective treatment decisions.
1. Reduce Inflammation
Here's Why This Is Important:
Reducing inflammation directly addresses the underlying immune-mediated process that causes the characteristic symptoms of chronic diarrhea and abdominal discomfort. Controlling inflammation leads to disease remission and intestinal healing.
How Do You Do This?
Per the American Gastroenterological Association (AGA) guidelines, an 8-week course of oral budesonide 9 mg daily is the best-documented treatment for achieving remission of active disease. Discontinuation can be considered after eight weeks of therapy; however, two-thirds of patients will experience symptom relapse, requiring maintenance therapy with 6 mg of budesonide daily.
Second-line pharmacologic agents that can be considered for patients in whom budesonide is not an option include mesalamine, bismuth subsalicylate, prednisone, and cholestyramine (32).
Prolonged use of budesonide may increase the risk of bone loss over time, leading many to search for alternative anti-inflammatory options with a lower side effect profile. Natural supplements with anti-inflammatory properties that may be considered alternative or adjunctive therapies to prescription medications include Boswellia serrata, curcumin, psyllium (Plantago ovata), and ginger.
Lifestyle modifications should be emphasized as an essential first step, including the avoidance of all NSAIDs and, if possible, the discontinuation of other medications associated with increased disease risk. Patients who smoke should also be counseled on smoking cessation.
Diet has a profound influence on GI inflammation levels. Western dietary patterns high in fat, sugars, and processed foods are linked to intestinal dysbiosis, intestinal permeability, and increased risk of IBD. Conversely, an anti-inflammatory diet, like the Mediterranean diet, can reduce GI inflammation. Specifically, unprocessed foods like fruits, vegetables, whole grains, nuts, and seeds, which are good sources of fiber and flavonoids, should be emphasized.
As you begin to transition to an anti-inflammatory diet, try incorporating these foods and spices into your diet:
- Berries
- Green leafy vegetables
- Fatty fish
- Extra virgin olive oil
- Nuts and seeds
- Turmeric
- Ginger
- Garlic
- Green tea
Identified food allergies and sensitivities should also be avoided. Food sensitivities can be eliminated for 4-8 weeks and then rechallenged one at a time to test tolerance.
Patients with celiac disease must adhere to a life-long gluten-free diet:
- Safe Grains, Starches, and Flours: amaranth, arrowroot, buckwheat, corn, flax, millet, oats, potato, quinoa, rice, sorghum, soy, tapioca, teff
- Grains to Avoid: barely (includes malt), rye, wheat (includes kamut, semolina, spelt, and triticale)
2. Palliate GI Symptoms
Here's Why This Is Important:
Symptoms of active microscopic colitis severely impact health-related quality of life. Chronic diarrhea can cause persistent physical discomfort, disrupt daily activities, reduce productivity, and contribute to anxiety, stress, and social isolation. (34, 55)
How Do You Do This?
The following agents can be used intermittently or regularly for the symptomatic management of diarrhea:
- Loperamide is an antidiarrheal that slows intestinal motility, increasing fluid absorption and reducing stool frequency.
- Bismuth subsalicylate, known for its anti-inflammatory and antimicrobial properties, helps reduce diarrhea by inhibiting intestinal inflammation, stimulating fluid reabsorption, and inhibiting intestinal secretions. Since bismuth neurotoxicity may result from long-term use, it is preferred to dose in an intermittent regimen of eight weeks on and eight weeks off (8).
- Cholestyramine is a bile acid sequestrant that binds bile acids in the intestine. This can be particularly effective for patients whose diarrhea is triggered by bile acid malabsorption.
There are many natural alternatives to medications that can help relieve GI symptoms:
- 20-35 grams of soluble, nonfermentable fiber, such as psyllium, daily improves abdominal pain, bloating, and altered bowel habits
- Enteric-coated peppermint oil 182 mg significantly reduces abdominal pain and discomfort
- Ginger in doses of up to 4 grams daily can help relieve symptoms of indigestion, nausea, abdominal pain, and bloating
- Saccharomyces boulardii dosed at 5 to 40 billion CFU per day can effectively treat a variety of inflammatory and non-inflammatory diarrheal conditions
3. Restore Gastrointestinal Homeostasis
Here's Why This Is Important:
Long-term disease remission will rely upon successfully addressing the underlying factors contributing to immune system dysregulation, intestinal permeability, and intestinal inflammation.
How Do You Do This?
The 5-R protocol is an all-encompassing five-step framework to restore a healthy and balanced gastrointestinal system. This approach helps to identify, eliminate, and heal various gut-related issues contributing to disease. The steps are as follows:
- Remove offending triggers contributing to intestinal permeability, including food sensitivities, pathogens, medications, environmental toxins, and stressors.
- Replace digestive enzymes required for optimal digestion and nutrient absorption.
- Reinoculate the gut with beneficial gut bacteria with probiotic supplements and fermented foods.
- Repair the gut lining with a nutrient-dense diet and gut-healing supplements.
- Rebalance and maintain the gut ecosystem with healthy lifestyle habits, including avoidance of excessive alcohol, regular exercise, stress management, and quality sleep.
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Key Takeaways:
- Microscopic colitis, classified as lymphocytic or collagenous colitis, is a form of inflammatory bowel disease that causes chronic watery diarrhea. Although serious health sequelae aren't associated with microscopic colitis like its other IBD counterparts, the chronic diarrhea that accompanies the disease significantly impacts the quality of life of those affected.
- Standard treatment protocols that rely on the steroid budesonide induce disease remission, but the health risks associated with long-term steroid use drive patients toward alternative treatment solutions.
- Dietary and lifestyle modifications, botanical medicine, and nutritional supplements can help patients achieve long-term disease remission without reliance upon pharmacologic maintenance therapy.
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