Lymphocytic Colitis: Symptoms, Types, Causes and Treatment

Lymphocytic colitis is an under-recognized but important cause of chronic watery diarrhea. Though once grouped under the umbrella term “microscopic colitis,” this condition is now understood as a distinct clinical and histological entity. For patients, it can present with a wide spectrum of symptoms, have diverse causes, and respond variably to therapy. This article offers a thorough exploration of lymphocytic colitis, focusing on its symptoms, types, possible causes, and evidence-based treatment options.

Symptoms of Lymphocytic Colitis

Living with lymphocytic colitis can be frustrating and disruptive. Most patients experience persistent, watery diarrhea, but a range of other symptoms may also occur. Importantly, standard colonoscopy or imaging tests often appear normal, making diagnosis dependent on microscopic examination of colon tissue. Understanding the typical symptom profile is crucial for early recognition and effective management.

Symptom	Frequency	Notes/Associations	Source(s)
Diarrhea	90–96%	Chronic, watery, often non-bloody	1 2 3 4 6 7
Abdominal pain	~47%	Cramping, intermittent	1 3 4
Weight loss	32–41%	Mild to moderate	1 3
Fecal incontinence	12–20%	More common in elderly	3
Rectal urgency	~30%	Sudden urge to defecate	3
Bloating	~20%	May co-exist with other symptoms	3
Nocturnal stools	Common	Diarrhea may persist at night	3
Associated autoimmune symptoms	30–50%	Arthritis, thyroid disease, celiac, diabetes	1 4 7 10

Table 1: Key Symptoms

Chronic Watery Diarrhea

The hallmark symptom is persistent, non-bloody, watery diarrhea. Patients typically report several loose stools per day, sometimes exceeding 10, and the problem may last for months. Notably, the diarrhea can occur both during the day and at night, impacting sleep and quality of life. In about 63% of cases, diarrhea presents as a single attack lasting several months, but for others, it may be chronic and either intermittent or continuous 1 2 3 8.

Abdominal Discomfort and Weight Loss

Nearly half of patients experience abdominal pain, which is usually crampy and may fluctuate in intensity. Weight loss is also reported in up to 41% of cases, usually mild to moderate. This is often due to fluid loss and changes in diet as patients attempt to manage symptoms 1 3.

Urgency, Incontinence, and Bloating

Rectal urgency—where patients feel a sudden, strong need to defecate—can be distressing and may lead to episodes of fecal incontinence, especially in older adults. Bloating and flatulence are less common but still notable, contributing to overall discomfort 3.

Associated Conditions

A significant proportion of patients also have autoimmune conditions such as thyroid disorders, celiac disease, type 1 diabetes, or even arthritis. These associations suggest a possible immunological component to the disease 1 4 7 10. Family history of other bowel or autoimmune diseases may also be present in about 10–12% of patients 1 8.

Types of Lymphocytic Colitis

While lymphocytic colitis is considered a single disease entity, there are important distinctions both within it and in comparison to related disorders. Understanding these variations helps tailor diagnosis and management.

Type/Variant	Features	Distinguishing Factor	Source(s)
Classic LC	Chronic watery diarrhea, normal colon	Increased intraepithelial lymphocytes	6 9 4 8
Incomplete/Variant	Less pronounced histology	Fewer lymphocytes, milder inflammation	9
Collagenous colitis	Similar symptoms	Thickened subepithelial collagen band	6 8 9
Drug-induced LC	Follows medication exposure	Resolves after drug discontinuation	11 14

Table 2: Types and Variants

Classic Lymphocytic Colitis

This is defined by a combination of clinical features (chronic watery diarrhea, normal colonoscopy) and microscopic findings—most notably, an increased number of lymphocytes within the lining of the colon (typically ≥20 per 100 epithelial cells) 6 9. The lamina propria also shows mild chronic inflammation, but there is minimal architectural distortion.

Incomplete or Variant Forms

Some cases don’t meet the full histologic criteria for classic LC but still show increased lymphocytes and mild inflammation. These “incomplete” or “variant” forms are recognized by pathologists and may represent early or resolving disease 9.

Lymphocytic vs. Collagenous Colitis

Both lymphocytic and collagenous colitis fall under the umbrella of “microscopic colitis.” They share similar clinical presentations, but collagenous colitis is distinguished by a thickened collagen layer beneath the surface of the colon lining on biopsy. The two conditions may represent a spectrum or different stages of the same underlying process, though this remains debated 6 8 9. Collagenous colitis is more common in women, while lymphocytic colitis has a more even sex distribution 4 7 8.

Drug-Induced Lymphocytic Colitis

Certain medications—most notably NSAIDs, some antidepressants, and other drugs—can induce a lymphocytic colitis–like histological pattern. Stopping the offending agent often leads to resolution, making medication history crucial in diagnosis 11 14.

Causes of Lymphocytic Colitis

The exact cause of lymphocytic colitis remains elusive, but research points to a complex interplay of immune, environmental, infectious, and drug-related factors.

Cause Category	Key Details/Examples	Evidence/Notes	Source(s)
Autoimmune	Thyroid disease, celiac, diabetes	High association rates	1 4 10
Infectious	Possible bacterial/viral triggers	E. coli, Campylobacter implicated	5 12 13
Drug-induced	NSAIDs, PPIs, others	Onset after exposure; reversible	11 14
Genetic/familial	Family history of IBD, celiac	Seen in 10–12% of cases	1 8
Idiopathic	No clear cause	Most cases	1 8 9

Table 3: Potential Causes

Immune-Mediated and Autoimmune Factors

A strong association with other autoimmune diseases suggests an immune-mediated mechanism. Up to 40% of patients report coexisting autoimmune disorders, especially thyroid disease, celiac disease, and diabetes 1 4 10. The presence of autoantibodies and a family history of inflammatory bowel or celiac disease in a subset of patients also supports this theory 1 8.

Infectious Triggers

Several studies suggest that infections may play a role in initiating lymphocytic colitis in susceptible individuals. Some patients report a sudden onset of diarrhea following an episode of gastroenteritis, and certain bacteria (notably E. coli and Campylobacter) have been detected in association with the disease 5 12 13. There also appears to be a seasonal pattern to disease onset, with higher incidence in summer and fall, further hinting at an infectious component 5.

Drug-Induced Lymphocytic Colitis

Medications are a well-recognized cause. Drugs most commonly implicated include nonsteroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), selective serotonin reuptake inhibitors (SSRIs), and certain cholesterol-lowering agents 11 14. Stopping the suspected drug can often lead to resolution of symptoms and normalization of colon biopsies.

Genetic and Familial Factors

Genetic predisposition is suggested by a positive family history in about 10–12% of patients, including relatives with ulcerative colitis, Crohn’s disease, collagenous colitis, or celiac disease 1 8. However, the specific genes involved remain unidentified.

Idiopathic Cases

For most patients, no clear cause is found. These cases are considered idiopathic, but likely represent the combined effects of immune, environmental, and possibly yet-unknown factors 1 8 9.

Treatment of Lymphocytic Colitis

Treatment is tailored to symptom severity, underlying causes, and patient preferences. Many cases resolve spontaneously or respond to simple interventions, while others require targeted medical therapy.

Treatment	Indication/Use	Response Rate/Efficacy	Source(s)
Drug withdrawal	Suspected drug-induced	Often leads to remission	11 14
Antidiarrheals	Mild symptoms	Partial, symptomatic relief	3 10
Budesonide	Moderate/severe cases	79–86% remission; effective	15 17 18
Mesalazine	Some benefit in studies	Not significantly better than placebo	17 18
Bismuth subsalicylate	Mild cases	Mixed results; not conclusive	3 17
5-ASA agents	Alternative therapy	Some report improvement	16
Steroids (other)	Severe cases	Effective, but more side effects	1 16
Dietary/lifestyle	Supportive	Adjunct to therapy	3 4

Table 4: Treatment Approaches

General and Supportive Measures

In mild cases, simply stopping a suspected causative drug (such as NSAIDs or PPIs) may lead to rapid improvement 11 14. Dietary adjustments, such as reducing lactose or caffeine, may also help some patients. For those with mild symptoms, over-the-counter antidiarrheal agents like loperamide can provide partial relief 3 10.

Budesonide: The Mainstay of Therapy

Budesonide, a corticosteroid with high topical activity and low systemic absorption, is the most effective and well-supported therapy for active lymphocytic colitis. Multiple randomized controlled trials have demonstrated that an 8-week course of oral budesonide induces clinical remission in 79–86% of patients—significantly better than placebo 15 17 18. Budesonide also leads to histological remission in more than two-thirds of cases 15 18. Relapses can occur after discontinuation, but most patients respond again to repeat treatment 15.

Mesalazine and Other Drugs

Mesalazine (5-aminosalicylic acid) has been evaluated for lymphocytic colitis but, unlike in ulcerative colitis, has not shown significant benefit over placebo in well-designed studies 17 18. Bismuth subsalicylate, which is sometimes effective in collagenous colitis, has not demonstrated convincing efficacy for lymphocytic colitis in controlled trials 17. Other steroids (e.g., prednisone) can be used for severe or refractory cases, but have more systemic side effects compared to budesonide 1 16.

Long-Term Outlook and Maintenance

Most patients have a benign course with eventual resolution of symptoms, either spontaneously or with treatment 2 16. Only a minority require long-term or maintenance therapy. After discontinuing budesonide, relapses are common, but usually respond to another short course of the drug 15 16.

When to Seek Specialist Care

Patients with persistent or severe symptoms, weight loss, or uncertainty about the diagnosis should be referred to a gastroenterologist for further evaluation and possible colonoscopic biopsy.

Conclusion

Lymphocytic colitis is a chronic inflammatory condition of the colon that can significantly impact quality of life. Early recognition and appropriate management are crucial for symptom relief and long-term well-being. The following are key takeaways:

• Symptoms: Chronic watery diarrhea is the hallmark; abdominal pain, weight loss, urgency, and associated autoimmune symptoms are also common.
• Types: Classic, incomplete/variant, and drug-induced forms exist. Lymphocytic and collagenous colitis are related but distinct.
• Causes: The condition is multifactorial—autoimmune, infectious, drug-induced, genetic, and idiopathic factors all play a role.
• Treatment: Budesonide is the most effective evidence-based therapy. Drug withdrawal, antidiarrheals, and supportive care are important in milder cases. Most patients have a favorable long-term prognosis.

Proper diagnosis and tailored treatment can restore quality of life for most patients with lymphocytic colitis. If you experience persistent, unexplained diarrhea, consult your healthcare provider—relief is possible.