Microscopic colitis

Section: Colorectal Sub-section: Colitis Curriculum: Curriculum, page 23

Definition

Microscopic colitis is a chronic inflammatory disease of the colon that is characterized by chronic, watery, non-bloody diarrhea. It typically occurs in middle-aged patients and has a female preponderance. The colon appears typically normal or almost normal on colonoscopy in patients with microscopic colitis. The diagnosis is established by biopsy of the colonic mucosa demonstrating characteristic histologic changes.

Epidemiology

• F>M
• Typically in middle age

Pathophysiology

• The pathogenesis of microscopic colitis is unclear; however, it is likely to be multifactorial, involving mucosal immune responses to luminal factors in a genetically predisposed individual
• NSAIDs have been implicated as a causal trigger
• Other drugs: PPIs, statins, SSRIs, histamine antagonists

Clinical presentation

• Chronic, non-bloody, watery diarrhea
• Four and nine watery stools per day, but in rare cases, bowel movements can exceed 15 or up to 2 liters per day
• Fecal urgency (70 percent), incontinence (40 percent), and nocturnal episodes (50 percent).
• Weight loss due to fluid loss or decreased oral intake.
• Extraintestinal symptoms, such as arthralgia, arthritis, or uveitis can occur

Diagnosis

• Biopsy of colonic mucosa
• Endoscopic appearance of the colon is typically normal. Macroscopic features can include slight edema, erythema, friability, exudative lesions, and scars

Histology

The inflammatory cell response is similar in lymphocytic and collagenous colitis, consisting mainly of mononuclear infiltrates, with few neutrophils and eosinophils in the lamina propria

Key histologic features that are used to diagnose collagenous and lymphocytic colitis:

• Collagenous colitis
  • Characterized by a colonic subepithelial collagen band ≥10 micrometers in diameter.
• Lymphocytic colitis
  • Characterized by ≥20 intraepithelial lymphocytes (IEL) per 100 surface epithelial cells.
  • Crypt architecture is usually not distorted, but focal cryptitis may be present.
• Incomplete microscopic colitis or microscopic colitis not otherwise specified (NOS)
  • used to describe a subgroup of patients with diarrhea, an increase in cellular infiltrate in the colonic lamina propria, and either an abnormal collagenous layer or IELs short of fulfilling the criteria for collagenous colitis and lymphocytic colitis

Histologic key features of different forms of microscopic colitis

	LC	CC	MCi or MCnos
IELs	>20 IELs	Normal to slightly increased	5-20 IELs
Subepithelial collagen layer	Normal to slightly thickened	>10 micrometers	5-10 micrometers
Surface epithelium damage	+	++	(+)
Lamina propria inflammation	++	++	+/++

LC: lymphocytic colitis; CC: collagenous colitis; MCi: microscopic colitis incomplete; MCnos: microscopic colitis not otherwise specified; IELs: intraepithelial lymphocytes.

Management

Management goal: remission, <3 stools per day

Induction: First line:

• Avoid culprit medications
• Antidiarrheal agent
• Budesonide 9 mg daily for six to eight weeks - then taper oral budesonide to 6 mg for two weeks, followed by 3 mg for another two weeks, and then discontinue therapy.
  • In patients who are not in clinical remission at eight weeks, or if symptoms recur on tapering, the budesonide dose of 9 mg can be continued for 12 weeks or longer before tapering the dose.
  • Randomized trials in patients with collagenous colitis suggest that budesonide is effective for short-term treatment of microscopic colitis and can improve quality of life. A meta-analysis of eight randomized trials that included 248 patients randomized to glucocorticoids versus placebo found that short-term clinical response rates were significantly higher with budesonide, as compared with placebo Second line:
• In patients who do not respond to budesonide, we suggest concomitant therapy with Cholestyramine.
• If the combination of budesonide and cholestyramine is not effective, we suggest a trial of Bismuth subsalicylate . Third line:
• Reserve the use of Anti-TNF for microscopic colitis that is refractory to a combination of budesonide, antidiarrheals, cholestyramine and/or bismuth subsalicylate once other causes of diarrhea have been excluded. Fourth line:
• Surgery for patients with microscopic colitis that is refractory to medical therapy.

Maintenance

• Symptomatic relapse occurs in up to 80 percent of patients after cessation of initial budesonide treatment
• In patients with relapse following remission use continuous maintenance therapy at the lowest dose that maintains clinical remission (no more than 6 mg per day then tapered to the lowest effective dose and continued for 6 to 12 months)
• Risk of steroid related side effects