Microscopic Colitis (Lymphocytic, Collagenous)

Clinical Manifestations

• Lymphocytic colitis and collagenous colitis are forms of microscopic colitis (normal gross appearance)
  
• Primarily characterized by chronic, watery, non-bloody diarrhea.
  
• Onset can be sudden in about 40% of cases but is often insidious.
  
• Patients typically experience 4-9 watery stools per day, which can be accompanied by fecal urgency, incontinence, and nocturnal episodes.
  
• Abdominal pain is reported in up to half of the patients with active disease.
  
• Other associated symptoms may include weight loss, arthralgia, and uveitis, leading to a reduced quality of life.
  
• Laboratory findings are generally nonspecific but may include mild anemia and the presence of various autoantibodies.

Diagnostic Criteria and Biopsy Findings

A diagnosis of microscopic colitis is suspected in patients, particularly middle-aged and older adults, presenting with chronic diarrhea. The definitive diagnosis is established through a colonoscopy with biopsies of the colonic mucosa that show characteristic histologic changes.

• Diagnostic Subtypes and Biopsy Findings:
• Lymphocytic Colitis: Defined by the presence of ≥20 intraepithelial lymphocytes (IELs) per 100 surface epithelial cells. The colon's crypt architecture is usually normal.
• Collagenous Colitis: This subtype is identified by a thickened subepithelial collagen band of ≥10 micrometers.
• Incomplete Microscopic Colitis: This term describes cases with an increase in inflammatory cells but without meeting the full criteria for lymphocytic or collagenous colitis.

During evaluation, it's important to exclude other causes of diarrhea, such as infections and celiac disease, through stool studies and blood tests. While the colon may appear normal or show mild, non-specific changes during endoscopy, biopsies are essential for diagnosis.

First-Line Treatment

The initial goal of treatment is to achieve clinical remission (defined as < 3 stools / day with no watery stools during a one-week period)

• Initial Measures: Patients are advised to avoid medications known to cause microscopic colitis, such as NSAIDs, PPI, SSRI, Statins, Immune Checkpoint, Hormone therapy, OCPs, and to stop smoking. Antidiarrheal agents like loperamide can be used for symptomatic relief, especially for nocturnal diarrhea.
• Active Disease: For patients with active disease (≥3 stools or ≥1 watery stool per day), the first-line treatment is a course of oral budesonide (9 mg daily for six to eight weeks).  Budesonide is a glucocorticoid with low systemic exposure that has been shown to be effective in inducing clinical and histologic remission in both lymphocytic and collagenous colitis. After the initial course, the dose is typically tapered. Predisone is only used in patients where budesonide is not feasible

Second-Line and Subsequent Treatment Options

For patients who do not respond to or have persistent symptoms despite first-line therapy, other options are available.

• For Mild, Persistent Symptoms use loperamide and:
• Cholestyramine (4g 4x/day): A bile acid sequestrant used to manage diarrhea potentially caused by bile acid malabsorption.
• Bismuth Subsalicylate (Three 262mg tabs 3x/day): May be used if 2wk trial of cholestyramine is ineffective, though data supporting its use is limited.
• For Non-Responders or Glucocorticoid Intolerance not responding to above 2^nd line Tx:
• Re-evaluation for other causes of diarrhea is recommended. (celiac, thyroid dz, carcinoid syndrome, VIPoma, persistent NSAIDs)
• Biologic Agents and Immunomodulators: For refractory cases, anti-TNF agents (like infliximab or adalimumab) or immunomodulators (like azathioprine) may be considered.  Vedolizumab is another potential option for severe, refractory symptoms.
• Surgery: In rare cases of medically refractory disease, surgery such as an ileostomy or colectomy may be necessary.

Natural Course