Microscopic Colitis: Symptoms, Types, Causes and Treatment

Microscopic colitis is a frequently under-recognized chronic inflammatory bowel disease that can significantly affect quality of life. While its symptoms can mimic other gastrointestinal conditions, diagnosis requires a careful combination of clinical suspicion and microscopic examination of colon tissue. This article unpacks the key aspects of microscopic colitis, from its often confusing symptoms to its nuanced causes and modern treatment approaches.

Symptoms of Microscopic Colitis

Microscopic colitis often presents with subtle but disruptive symptoms that can be easily mistaken for other gastrointestinal problems. Understanding these symptoms is crucial for prompt recognition and management, especially since the disease is frequently missed in early stages.

Symptom	Description	Affected Population	Source(s)
Diarrhea	Chronic, watery, non-bloody stools	Common, especially elderly	1 2 3 5 6 7 10 11
Abdominal pain	Cramping or discomfort	Variable	1 2 3 4 5 10
Nocturnal symptoms	Diarrhea at night	Some patients	3 5
Fecal incontinence	Inability to control stools	Subset of patients	3
Constipation	Paradoxical in some cases	About 1/3 of patients	5
Extraintestinal symptoms	Arthralgias, fatigue, IBS-like symptoms	Overlap common	1 4 5
Psychiatric symptoms	Anxiety, depression due to symptoms	Subset with severe disease	4

Table 1: Key Symptoms of Microscopic Colitis

Chronic Watery Diarrhea: The Hallmark

The most recognized symptom is persistent, watery, non-bloody diarrhea. This can range from a few episodes per day to frequent, urgent stools, sometimes even at night—a feature that helps distinguish it from irritable bowel syndrome (IBS) 1 2 3 6 10 11. Surprisingly, about one-third of patients may not experience diarrhea at all but instead report constipation as their main complaint 5.

Other Gastrointestinal and Systemic Symptoms

• Abdominal pain and cramping are common but less prominent than diarrhea.
• Fecal urgency and incontinence can occur, particularly in severe cases and among older adults, leading to embarrassment and social withdrawal 3.
• Nocturnal symptoms (diarrhea waking the patient at night) are reported in some 3 5.
• IBS-like symptoms—such as bloating and alternating bowel habits—are frequently observed, and more than a third of patients may fulfill IBS diagnostic criteria 4.

Impact Beyond the Gut

• Joint pain (arthralgias) and fatigue can accompany intestinal symptoms, though these are less specific 1 5.
• Psychological distress is notable in patients with severe or persistent symptoms. Anxiety, depression, and somatization are more common than in the general population, likely due to the chronic, disruptive nature of the disease 4.

Symptom Variability and Overlap

Microscopic colitis can easily be mistaken for IBS or other forms of inflammatory bowel disease (IBD) because of overlapping symptoms. The lack of visible changes on colonoscopy adds to the confusion, making biopsy essential for diagnosis 2 3 5 7 10.

Types of Microscopic Colitis

Microscopic colitis is not a single disease but rather an umbrella term encompassing several subtypes that share clinical features but differ under the microscope. Knowing the distinctions is important for both diagnosis and understanding potential management differences.

Type	Defining Feature	Prevalence/Notes	Source(s)
Collagenous colitis	Thickened subepithelial collagen band (>10μm)	More common in women, middle-aged/elderly	1 2 3 5 6 7 9
Lymphocytic colitis	Increased intraepithelial lymphocytes (>20 per 100 epithelial cells)	Slightly younger age at diagnosis	1 2 3 5 6 7 9
Incomplete/variant forms	Features of both or less pronounced findings	Less common, under study	3 7 8 9

Table 2: Types of Microscopic Colitis

Collagenous Colitis

This subtype is defined by a thickened layer of collagen just beneath the surface lining of the colon. It is more common in women and tends to affect people in their 50s and older. The clinical presentation is often indistinguishable from other types, but the collagen band is a key diagnostic clue on biopsy 1 3 5 6 7 9.

Lymphocytic Colitis

Lymphocytic colitis features an increased number of lymphocytes (a type of white blood cell) within the lining of the colon, without the thickened collagen band seen in collagenous colitis. Patients tend to be slightly younger, but the symptomatic overlap is substantial 1 3 5 6 7 9.

Incomplete or Variant Forms

Some patients show less pronounced or mixed features, sometimes called “incomplete microscopic colitis.” These cases are actively being studied, and the clinical implications are still being clarified 3 7 8 9.

Subtype Overlap and Evolution

There is considerable overlap between lymphocytic and collagenous colitis—some researchers believe they might represent different stages or manifestations of the same disease process. The absence of architectural distortion in the colon helps distinguish them from classic IBDs like Crohn’s disease or ulcerative colitis 3 7 8.

Causes of Microscopic Colitis

While the precise causes of microscopic colitis remain elusive, research has identified a mix of genetic, immune, environmental, and medication-related risk factors. Understanding these can help patients and clinicians recognize triggers and manage the disease more effectively.

Factor	Description/Examples	Key Insights	Source(s)
Autoimmunity	Links to celiac, thyroid, rheumatoid disease	Strong association	5 6 11 12
Genetics	HLA gene variants, especially 8.1 haplotype	Overlap with Crohn's	12
Medications	NSAIDs, PPIs, SSRIs, others	Risk increased but not proven causal	6 11 12
Smoking	Active and former smokers at higher risk	Modifiable risk factor	11 12
Age/Sex	Older adults, more common in females	Epidemiological pattern	1 2 5 6 11
Immune checkpoint inhibitors	Novel trigger in cancer patients	Budesonide may help	14
Environmental antigens	Food sensitivities, infections	Proposed triggers	5 6 7

Table 3: Causes and Risk Factors for Microscopic Colitis

Autoimmune and Genetic Predisposition

Microscopic colitis often coexists with autoimmune diseases such as celiac disease, thyroid disorders, and rheumatoid arthritis. Up to 40% of patients may have an autoimmune comorbidity 5 6 11. Recent genetic studies have identified specific HLA gene variants (notably the ancestral 8.1 haplotype) that increase susceptibility. There is some evidence of genetic overlap with Crohn’s disease, suggesting shared immune pathways 12.

Medications

Several commonly used drugs are associated with an increased risk of microscopic colitis:

• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Proton pump inhibitors (PPIs)
• Selective serotonin reuptake inhibitors (SSRIs) While causality is debated, these medications are frequently reported in patient histories 6 11 12. Withdrawal of offending agents may lead to symptom improvement.

Smoking

Smoking is a well-established risk factor, with both current and former smokers being more likely to develop microscopic colitis than never-smokers. Smoking cessation is advised 11 12.

Age and Sex

The condition is most common in older adults, especially women, typically developing in the sixth or seventh decade of life 1 2 5 6 11.

Emerging and Less Common Triggers

• Immune checkpoint inhibitors used in cancer therapy can trigger microscopic colitis, with budesonide showing promise as a first-line therapy in such cases 14.
• Dietary antigens and food sensitivities may play a role for some patients, and a history of alimentary hypersensitivity is not uncommon 5 6.

Environmental and Infectious Factors

Although not fully proven, infections and other antigens in the colon are suspected to trigger the abnormal immune response seen in microscopic colitis 6 7.

Treatment of Microscopic Colitis

Treatment of microscopic colitis aims to relieve symptoms, induce remission, and improve quality of life. Fortunately, several therapeutic options exist, ranging from lifestyle modifications to advanced immunosuppressive therapies.

Therapy	Role/Approach	Effectiveness	Source(s)
Budesonide	First-line, locally acting steroid	High remission, but relapse common	1 3 6 9 11 13 14
Anti-diarrheals	Symptom management	Adjunctive, not curative	11
Bile acid binders	Cholestyramine for bile acid diarrhea	Helpful in select cases	9 11
Colloidal bismuth	Alternative therapy	Evidence from RCTs	6
Immunomodulators	For refractory cases (azathioprine, methotrexate)	Variable response	9 11
Biologics (anti-TNF)	For severe, refractory disease	Promising in small studies	11
Drug withdrawal	Stopping offending medications	May lead to improvement	6 11 12
Lifestyle	Smoking cessation, diet modification	Supportive	11 12

Table 4: Treatment Options in Microscopic Colitis

Budesonide: The Gold Standard

Budesonide, a steroid with minimal systemic absorption, is the most effective and well-studied therapy for inducing and maintaining remission. Clinical trials show high rates of symptom improvement, but relapses are common (up to 80%) after stopping therapy. Long-term or repeated courses may be necessary in some patients 1 3 6 9 11 13 14.

• Short-term use: Rapid symptom relief and histological improvement.
• Long-term maintenance: May be needed for frequent relapses, with careful monitoring.

Supportive and Adjunctive Therapies

• Anti-diarrheal agents (loperamide, diphenoxylate) can provide symptomatic relief but do not alter disease course 11.
• Bile acid binders (e.g., cholestyramine) are useful if bile acid malabsorption is suspected 9 11.
• Colloidal bismuth has shown benefit in randomized trials, though is less commonly used 6.

Immunomodulators and Biologics

For patients who do not respond to or cannot tolerate budesonide:

• Immunomodulators (azathioprine, methotrexate) have variable effectiveness and are considered for refractory cases.
• Biologics (anti-TNF agents) can be effective in severe, resistant cases, though data are limited 9 11.

Withdrawal of Offending Medications

If a patient is taking a drug suspected to trigger microscopic colitis (like NSAIDs or PPIs), discontinuing it may lead to symptom resolution 6 11 12.

Management of Special Situations

• Immune checkpoint inhibitor-induced colitis: Budesonide is effective and may allow continuation of cancer therapy 14.
• Lifestyle modifications: Smoking cessation and addressing dietary triggers can be supportive strategies 11 12.

Relapse and Long-term Management

Relapses are common after stopping budesonide. Strategies include:

• Tapering medication rather than abrupt cessation
• Maintenance therapy for those with frequent recurrences
• Regular follow-up and quality-of-life assessment 13

Conclusion

Microscopic colitis is a subtle but impactful disease that requires a high index of suspicion for diagnosis. Its varied presentation, potential overlap with other conditions, and diverse risk factors make it a clinical challenge. However, modern therapies—especially budesonide—offer effective ways to restore health and quality of life.

Key takeaways:

• Microscopic colitis often presents with chronic watery diarrhea, but constipation or mixed symptoms can also occur.
• There are two main types: collagenous and lymphocytic colitis, distinguished by microscopic features.
• Autoimmune conditions, genetic factors, certain medications, and smoking all increase the risk.
• Budesonide is the most effective therapy, but relapses are common; adjunctive therapies and lifestyle changes may help.
• Proper diagnosis requires colon biopsy, as endoscopy alone is insufficient.
• Awareness of concomitant IBS-like symptoms and psychological distress is important for holistic patient care.

Understanding microscopic colitis empowers patients and clinicians to seek appropriate diagnosis and treatment, ultimately leading to better health outcomes and improved quality of life.