AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

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Background

Collagenous colitis (CC) was described concurrently in 1976 by Lindstrom and by Freeman. In 1980, Read described microscopic colitis, which is clinically indistinguishable from CC but is differentiated from it by colonic biopsy features. Later, the term lymphocytic colitis (LC) was proposed by Lazenby to replace the term microscopic colitis and to distinguish it from infectious colitis and inflammatory bowel disease (ulcerative colitis and Crohn disease). The term microscopic colitis is now used to describe both CC and LC, and these conditions should be considered in any patient with unexplained nonbloody diarrhea. Patients undergoing either sigmoidoscopy or colonoscopy for unexplained diarrhea who have normal endoscopic findings should have biopsy samples taken to diagnose or rule out either form of microscopic colitis.

LC and CC are relatively rare conditions that are diagnosed when a patient with chronic watery nonbloody diarrhea has an endoscopically or radiographically normal colon, but colonic biopsies show unique inflammatory changes. Because the mucosa is not ulcerated or otherwise disrupted, the diarrhea generally does not contain blood or pus.

Pathophysiology

• The characteristic feature of LC is an infiltration of lymphocytes into the colonic epithelium. CC shares this feature but additionally shows a distinctive thickening of the subepithelial collagen table. LC and CC have been suggested to represent different phases of a single pathophysiologic process, with LC possibly being a precursor or earlier phase of CC; however, this has not been proven.

• The diarrhea in CC is more likely due to the inflammatory process than to the subepithelial collagen layer, although this layer may serve as a cofactor in the role of a diffusion barrier.

• Increased levels of immunoreactive prostaglandin E2 in stool water may contribute to a secretory diarrhea.

• Some patients with CC and concurrent collagenous infiltration of the duodenum and/or the ileum have demonstrated altered small bowel dysfunction, demonstrated by reduced D-xylose absorption.

• Some individuals have bile acid malabsorption demonstrated by the Se-75-homotaurocholate (SeHCAT) test, in which a positive test result is shown by retention of less than 11% of the administered dose of radioactivity after 7 days.

• Some patients with CC may have increased mucosal secretion of vascular endothelial growth factor, a fibrosis-enhancing peptide.

Frequency

United States

True incidence is not known. The disease has been increasingly diagnosed over the past 20 years, but it is still uncommon. A recently published population-based study found the incidence of microscopic colitis to increase significantly from 1.1 per 100,000 persons in the late 1980s to 19.6 per 100,000 persons by the end of 2001. Rates increased with age. Prevalence at the end of the study period was 103.0 per 100,000 persons (39.3 for CC and 63.7 for LC).

Mortality/Morbidity

Morbidity is limited to the consequences of diarrhea and malabsorption, including metabolic abnormalities such as hypokalemia and dehydration, weight loss, fatigue, and vitamin deficiencies. This is not considered a life-threatening condition; however, profuse watery diarrhea may lead to severe dehydration and electrolyte abnormalities requiring intensive resuscitation.

Sex

LC affects similar numbers of men and women, while CC is up to 20 times more frequent in women than in men.

Age

Both conditions are observed most commonly in people older than 40 years, with peak incidence in the sixth and seventh decades of life, and the incidence of both conditions increases with age. Isolated cases have been reported in younger populations, including children.

CLINICAL

Section 3 of 11  

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History

• A protracted course of nonbloody diarrhea occurs. Diarrhea may be of high volume; some patients may eliminate more than 1500 mL of fluid per day.


• Symptoms may have been present from several months to 2-3 years before medical attention is sought and a diagnosis is made. In fact, perhaps half of patients proven to have microscopic colitis meet the Rome, Rome II, and Manning symptom-based criteria for diarrhea-predominant irritable bowel syndrome and may be so misdiagnosed until endoscopic biopsies of the colon are taken.


• Less frequent complaints include abdominal cramping, fecal incontinence, and weight loss, although weight loss may be seen in 40% or more of patients with CC.


• Incontinence is probably more a reflection of the advanced age of those individuals who are affected, and patients with this problem may do well if treated with antidiarrheal agents.

Physical

• Physical examination usually does not reflect specific abnormalities.
• Severely affected individuals may show signs of dehydration, malnutrition, and weight loss.

Causes

No definite etiology has been determined, but evidence now indicates that drug consumption may trigger underlying inflammatory factors in the colons of affected individuals, while others may exacerbate the diarrhea in patients with idiopathic microscopic colitis. While many drugs, either alone or in combination, may cause diarrhea as an adverse effect, nonsteroidal anti-inflammatory drugs (NSAIDs) show a strong trend (p=0.057) toward increasing the risk of CC. Antidepressant selective serotonin reuptake inhibitors (SSRIs) as a group increase the risk of CC, but, among this class of medications, sertraline alone significantly increases the risk of LC. Anecdotal reports of at least 17 drugs have been associated with the onset of the microscopic colitides. Among these, ranitidine, carbamazepine, ticlopidine, and flutamide have been suspected in some cases, although the only report of a rechallenge has been with ranitidine.

• Some patients have had histologic findings consistent with both CC and LC at different points during the course of disease. This raises the possibility that these may be different manifestations of the same medical condition or different points along a continuum.


• Many case reports describe patients with preexisting presumed autoimmune conditions, such as celiac sprue and rheumatoid arthritis, who subsequently are diagnosed with LC. Patients diagnosed with LC also have had uveitis, idiopathic pulmonary fibrosis, juvenile diabetes mellitus, pernicious anemia, autoimmune thyroid disease, and idiopathic thrombocytopenic purpura. The coincidence of celiac sprue and LC raises the possibility of a luminal agent being responsible for the colitis; however, removal of gluten from the diet is ineffective in treating the colitis.


• LC was diagnosed in a patient who failed to respond to antibiotic therapy for diarrhea associated with Campylobacter jejuni infection in the stool. The infection theoretically might have stimulated an autoimmune response that resulted in LC.


• Increased mast cells in some LC patients might indicate that degranulation products could serve as a chemoattractant for inflammatory cells.


• While only 14% of patients with LC were smoking actively when diagnosed, 23% were former smokers, suggesting that smoking may actually be protective against the development of LC. Excessive production of nitric oxide by inducible nitric oxide synthase (iNOS) may result in cytotoxicity through the generation of peroxynitrite that is formed when nitric oxide reacts with superoxide. Corticosteroids inhibit iNOS biosynthesis in some cells, and newer inhibitors of this enzyme may have a future role in the management of LC and other forms of colitis. Nitric oxide diffuses into cells and can induce inflammatory cell damage by causing nitration reactions. Increased nitric oxide generation has been reported in CC. The absence of nitrotyrosine staining, which is an indicator of active inflammation typically seen in ulcerative colitis, may correspond to the lesser degree of inflammation in CC compared with ulcerative colitis.


• Diarrhea associated with CC has been proven to be due to reduced net Na⁺ and Cl^- absorption, with the thickened collagen layer serving as a diffusion barrier. The epithelium nearly completely loses its ability to absorb these ions. In fact, the shift in net chloride flux is to secretion rather than absorption.


• Secretion of vascular endothelial growth factor, a fibrosis-enhancing peptide, is noted to be increased by the mucosa in some patients with CC. This may play a part in the pathogenesis.

DIFFERENTIALS

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Other Problems to be Considered

Infectious colitis (other than Clostridium difficile infection)
Ischemic colitis
Laxative abuse

WORKUP

Section 5 of 11  

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Lab Studies

• Blood studies
• • Results usually are within the reference range, but anemia, hypokalemia, hypoalbuminemia, elevation of the erythrocyte sedimentation rate, or a combination of these findings may be present.
  • HLA-A1 is more frequent in patients with LC (67%) than in controls (28%) or in patients with CC (26%).
  • HLA-B3 has not been reported in patients with LC. A frequency of 26% is expected in controls and also is observed in patients with CC.
  • The HLA patterns observed in other gastrointestinal conditions, such as Crohn disease, have not been found in LC.
  • Approximately 50% of both patients with CC and patients with LC may have circulating autoantibodies, especially antiparietal cell, antithyroglobulin, and antimicrosomal antibodies.

• Stool studies
• • Some affected patients have a diminished ability to absorb water resulting from reduced colonic absorption of sodium and chloride. Chloride/bicarbonate exchange across the colonic mucosa also may be reduced.
  • Stool evaluation on occasion may show the presence of leukocytes. In these circumstances, the stool should be tested for enteric bacterial pathogens, ova and parasites, and C difficile.
  • A prolonged (24- to 72-h) stool collection occasionally may demonstrate steatorrhea in affected individuals. A finding of greater than 7 g of fecal fat excretion per 24 hours in an individual ingesting 100 g of fat per day usually is indicative of fat malabsorption, and, even if microscopic colitis is present, a diagnosis of concurrent sprue should be considered.

Imaging Studies

• Findings on plain abdominal radiograph, barium enemas, and CT scans typically are normal or nonspecific and show no evidence of colonic mucosal damage or wall abnormality.

Other Tests

• Immunohistochemical studies of biopsies in LC and CC cases demonstrate abnormalities consistent with a mixed histocompatibility-restricted mechanism.
• The excessive intraepithelial lymphocytes observed in LC are predominantly CD4⁺ T cells rather than CD8⁺.

Procedures

• Biopsies obtained by sigmoidoscopy or colonoscopy generally are necessary to diagnose LC or CC.


• If a colonoscopy is performed, biopsies should be taken from the rectosigmoid and from the right side of the colon.


• In individuals with LC or CC, the mucosa appears normal endoscopically or occasionally mild mucosal edema may be seen. It does not show the more readily apparent changes of inflammatory bowel disease such as friability, ulceration, and pseudopolyps. Most patients have similar degrees of histologic abnormality in the right and left sides of the colon.


• Approximately 95% of patients with microscopic colitis will have diagnostic rectosigmoid or descending colon biopsies; but, if left-sided colonic biopsies are nondiagnostic in a patient in whom clinical suspicion remains high, total colonoscopy for right-sided biopsies may confirm the diagnosis.

Histologic Findings

• Surface epithelium shows a chronic inflammatory infiltrate of plasma cells, lymphocytes, and eosinophils in the lamina propria.


• Intraepithelial lymphocytosis, with greater than 20 lymphocytes per 100 epithelial cells, is pathognomonic of the diagnosis of LC (see Media file 1),  although lesser numbers of IEL may be present in some patients with LC.


• Epithelial cell damage is demonstrated by cell flattening, subepithelial blebs, and denuded epithelium. Fixed specimens may show epithelial loss and detachment.


• Crypts typically have normal architecture, unlike Crohn disease or ulcerative colitis. However, minimal crypt distortion may be present. Typically, evenly spaced parallel crypts of equal diameter are present.


• CC shares the histologic features of LC but additionally demonstrates a thickened subepithelial collagen layer (usually >10 µm) in the lamina propria.


• For comparison, a representative biopsy of CC is shown in Media file 2.


• In some biopsy specimens, the surface epithelium may be denuded or partially detached from the collagen layer, even simulating pseudomembranes in rare cases. This either may be artifactual or may be due to a defect in adherence to the subepithelial membrane.

TREATMENT

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Medical Care

• Evaluating treatment options is impaired by the fairly frequent occurrence of spontaneous remission of symptoms. Treatment choices are primarily empirical, and only limited controlled trials for any therapy exist to date. The best study-based evidence is for the use of budesonide and bismuth subsalicylate.


• A trial of dietary restriction and avoidance of potentially aggravating drugs (particularly nonsteroidal anti-inflammatory drugs) may alleviate symptoms in some patients, but many will require medical therapy.


• Treatment should be initiated with the least toxic regimen or medication, with stronger medication used only if milder treatment fails. Generally, 1 month should be allowed before deeming a particular medication ineffective in the treatment of CC or LC.


• One possible treatment algorithm is as follows:
• • First line: Loperamide (Imodium AD) or diphoxylate/atropine (Lomotil)
  
  
  • Second line: Bismuth subsalicylate, three 262 mg tab tid for 1-2 months (effective in up to 90% of patients); mesalamine, 3 g/d for 8 wk; or cholestyramine (especially if bile acid malabsorption is documented), at a mean dose of 8 g/d.
  
  
  • Third line: If patient is still not responding, a 2-month course of budesonide or a 2-week course of high-dose prednisone (60-80 mg/d) before tapering can be prescribed. Longer courses of budesonide may be beneficial, and, while systemic adverse effects may occur, little or no adrenal suppression should be anticipated. Longer courses of prednisone (up to 2 mo before tapering) may be needed in some patients, but recurrence is common after its discontinuation.
  
  
  • Fourth line: Some refractory cases may benefit from azathioprine (approximately 2 g/kg/d) or 6-mercaptopurine, but responses often take months to occur.
  
  
  • Patients who respond to treatment, but experience a recurrence, will often respond again to the same previously effective medication.

Surgical Care

If colitis is refractory to continued medical therapy or if effective medication cannot be tolerated, colectomy or ileostomy might be the only effective therapy; however, this seldom is necessary.

Consultations

Consultation with a gastroenterologist often is needed to make the diagnosis and to work through the treatment algorithm.

Diet

• Patients should avoid or eliminate possible secretagogues, such as caffeine, and, when appropriate, lactose-containing products.
• A low-fat diet is advisable if steatorrhea is documented.

MEDICATION

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Medication is indicated only if discontinuing dietary components or medications considered possibly responsible for the illness fails to alleviate the symptoms. As above, treatment is initiated with the least toxic effective agents. If a patient fails to respond to simple antidiarrheal drugs, anti-inflammatory or immunosuppressive medications may be required.

Drug Category: Antidiarrheal agents

Appropriate in mild cases.

Drug Name	Diphenoxylate hydrochloride/atropine sulfate (Lomotil)
Description	Antidiarrheal agent chemically related to narcotic analgesic meperidine. A subtherapeutic dose of anticholinergic atropine sulfate is added to discourage overdosage, in which case diphenoxylate may clinically mimic the effects of codeine. Each tab of Lomotil (or 5 cc of elixir) contains 2.5 mg diphenoxylate hydrochloride and 0.025 mg atropine sulfate.
Adult Dose	2 cap (or 10 cc elixir) PO qid until symptoms are under control; then use smallest effective dose
Pediatric Dose	<2 years: Not recommended <12 years: Use liquid Lomotil; do not use tab Initial: 0.3-0.4 mg/kg PO qd divided qid; adjust dose downward according to overall nutritional status and degree of dehydration >12 years: Administer as in adults
Contraindications	Documented hypersensitivity; diarrhea caused by C difficile or other enterotoxin-producing bacterial pathogens; obstructive jaundice
Interactions	Lomotil may delay metabolism of drugs in liver; CNS depressants, MAOIs, and antimuscarinic agents may increase the toxicity of this drug combination
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Overdosage may result in severe respiratory depression; carefully monitor and maintain fluid and electrolyte levels; because a subtherapeutic dose of atropine has been added to diphenoxylate hydrochloride, consider precautions relating to atropine; caution patient regarding activities requiring mental alertness, such as driving or operating dangerous machinery; explain potential reactions with concurrent administration of alcohol, barbiturates, or other tranquilizers

Drug Name	Bismuth subsalicylate (Pepto-Bismol)
Description	Controls diarrhea by reducing fluid secretion into intestinal lumen, by binding bacterial toxins, or by acting as an antimicrobial agent.
Adult Dose	3 tab PO in morning, 2 tab PO at noon, and 3 tab PO at night for an 8-wk trial
Pediatric Dose	<3 years: Use special caution 3-6 years: One-third tab PO, repeat q0.5-1h prn; not to exceed 8 doses/24 h 6-9 years: Two-thirds tab PO, repeat q0.5-1h prn; not to exceed 8 doses/24 h 9-12 years: 1 tab PO, repeat q0.5-1h prn; not to exceed 8 doses/24 h >12 years: Administer as in adults
Contraindications	Documented hypersensitivity; children with chickenpox and flu; diarrhea with high fever, mucus, or blood is possible contraindication
Interactions	Coadministration with anticoagulants may increase risk of bleeding; may increase toxicity of aspirin and hypoglycemics; decreases effects of tetracyclines and uricosurics
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	May cause temporary and harmless darkening of tongue and/or black stool; alcohol consumption may cause abdominal cramps, nausea, and vomiting; drink plenty of clear fluids to help prevent dehydration

Drug Category: Anion exchange resins

Diarrhea in patients with LC and possible bile salt malabsorption may respond to exchange resins.

Drug Category: Antispasmodics

Some patients with cramping pain associated with diarrhea will respond to antispasmodic medication.

Drug Category: Topical anti-inflammatory drugs

Drugs that reduce inflammatory changes at level of the colonic wall may be needed in subset of colitic patients who fail to respond to antidiarrheal medication.

Drug Name	Mesalamine (Asacol, Pentasa)
Description	Controlled-released formulations of 5-ASA and cause fewer side effects than sulfasalazine due to absence of the sulfa moiety. Pentasa is ethylcellulose-coated 5-ASA coated with an acrylic-based resin that dissolves in neutral or alkaline pH found in the terminal ileum or the colon. Dissolution of the coating of these tablets releases active 5-ASA where it can be topically active. These medications are more costly than sulfasalazine but typically better tolerated. Asacol is dispensed in 400-mg tabs. Pentasa is available in 250-mg tab.
Adult Dose	Asacol: 400-1200 mg PO tid Pentasa: 1000 mg PO qid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Decreases effect of iron, digoxin, and folic acid; mesalamine increases effect of oral anticoagulants, methotrexate, and oral hypoglycemic agents
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Impaired hepatic and renal function; can cause acute tolerance syndrome, which may be difficult to distinguish from inflammatory bowel disease; elderly people may have difficulty administering and retaining rectal suppositories; caution in patients with renal or hepatic impairment

Drug Category: Corticosteroids

Systemic anti-inflammatory agents that are readily absorbed from the gastrointestinal tract. Have a multitude of significant side effects when used over a prolonged period of time. Patients who fail to respond adequately to topical anti-inflammatory drugs may benefit from a course of corticosteroid therapy.

Drug Name	Budesonide (Entocort EC)
Description	Topical glucocorticoid delivered to the small bowel and ascending colon in a time-dependent manner. Active drug is coated with methylcellulose which dissolves at pH of 5.5 or greater, starting in the duodenum. Does not suppress the hypothalamus-pituitary-adrenal axis to a significant degree.
Adult Dose	9 mg PO qd for up to 8 wk
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; systemic fungal infections; ileocolostomy during immediate or early postoperative period
Interactions	Ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin, and other CYP3A4 enzyme inhibitors may significantly increase serum levels of budesonide
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	If improvement fails to occur within 2-3 wk, discontinue therapy; symptomatic improvement may be misleading and should not be used as sole criterion in judging efficacy (sigmoidoscopic examination and x-ray visualization are essential for adequate monitoring); caution where there is a probability of impending perforation or abscess, pyogenic infections, intestinal anastomoses, obstruction, extensive fistulas and sinus tracts; caution in patients with tuberculosis or other infections, hypertension, diabetes mellitus, osteoporosis, peptic ulcer disease, glaucoma or cataracts

Drug Category: Immunosuppressant drugs

Have been administered to small number of patients with LC who have not responded to other medical therapy. Specific indications and recommended dosages have not been established yet.

Drug Name	Methotrexate (Folex, Rheumatrex)
Description	Previously known as amethopterin. Antimetabolite that inhibits dihydrofolic acid reductase. Also used in certain neoplastic diseases, severe psoriasis, and adult rheumatoid arthritis.
Adult Dose	Not established; suggested dose is 7.5 mg PO qwk or 2.5 mg PO q12h for 3 doses/wk; not to exceed 20 mg/wk Use relatively low doses in elderly people; closely monitor for early signs of toxicity
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; alcoholism; hepatic insufficiency; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia); pregnancy
Interactions	Oral aminoglycosides may decrease absorption and blood levels of concurrent oral methotrexate (MTX); charcoal lowers MTX levels; coadministration with etretinate may increase hepatotoxicity of MTX; folic acid or its derivatives contained in some vitamins may decrease response to MTX; indomethacin and phenylbutazone can increase MTX plasma levels; may decrease phenytoin serum levels; severe gastrointestinal toxicity and bone marrow suppression has occurred in some patients who have concurrently taken high-dose MTX with some NSAIDs; probenecid, salicylates, procarbazine, and sulfonamides, including TMP-SMZ, may increase effects and toxicity of MTX; may increase plasma levels of thiopurines
Pregnancy	X - Contraindicated in pregnancy
Precautions	Monitor CBCs monthly and liver and renal function q1-3mo during therapy; monitor more frequently during initial dosing, dose adjustments, or when risk of elevated MTX levels, eg, dehydration; MTX has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; discontinue if significant drop in blood counts occurs; aspirin, NSAIDs, or low-dose steroids may be administered concomitantly with MTX (possibility of increased toxicity with NSAIDs, including salicylates, has not been tested)

FOLLOW-UP

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Prognosis

• Approximately 20% of patients may have a spontaneous remission without specific therapy.
• More than half of patients treated for LC experienced resolution of symptoms after 6 months of treatment, while only 15% of patients had significant persistent symptoms.
• In some patients, the diarrhea may wax and wane over many years; however, more than 80% of patients can expect diarrhea and histologic abnormalities to resolve within 3 years.
• Rare cases with severe and protracted diarrhea have been fatal; these cases are likely thought to be due to epithelial membrane sloughing and resultant altered mucosal permeability.
• Although some small studies have suggested otherwise, microscopic colitis (either CC or LC) does not appear to increase the risk of colon cancer.

Patient Education

• For excellent patient education resources, visit eMedicine's Esophagus, Stomach, and Intestine Center and Crohn Disease Center. Also, see eMedicine's patient education articles Colitis,
  Celiac Sprue, and Crohn Disease.

MISCELLANEOUS

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Medical/Legal Pitfalls

• Patients who fail to respond to reasonable medical therapy should be evaluated for other conditions that may mimic LC or CC clinically.


• The adverse effects of corticosteroids and immunosuppressants/immunomodulators may be serious. Such drugs would be difficult to justify in a patient later found to have irritable bowel syndrome or infectious or other causes of colitis or enteritis that should have been treated differently.


• Performing a colonoscopy on patients with chronic diarrhea is commonly accepted and widely practiced, but performing biopsies in all such individuals, even with normal findings on endoscopy, has a low yield. Patients clinically assessed as having diarrhea-predominant irritable bowel syndrome who do not respond to conventional medical therapy may in fact have microscopic colitis, and these patients may benefit from colonoscopy with biopsies.
• • Limit biopsies to those subgroups of patients in whom microscopic colitis is most likely.
  
  
  • Those subgroups would include patients with watery, severe, debilitating, or nocturnal diarrhea; substantial weight loss; an elevated erythrocyte sedimentation rate; or patients who are immunosuppressed.

Special Concerns

• As with the management of inflammatory bowel disease, antidiarrheal and nonimmunosuppressive medications have an acceptable risk in pregnant patients when clinical symptoms are significant and might threaten pregnancy.
• Methotrexate may induce spontaneous abortion and is contraindicated during pregnancy. 6-mercaptopurine and azathioprine may cause fetal harm but so may refractory colitis. Consequently, risk versus benefit must be carefully discussed before prescribing these medications to a pregnant patient.

MULTIMEDIA

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Media file 1:  Lymphocytic colitis (LC) showing marked chronic inflammatory cell infiltrate of the surface epithelium (on right) with preservation of crypt architecture. Subepithelial collagen layer is not thickened.
	View Full Size Image
Media type:  Photo

Media file 2:  Collagenous colitis (CC) showing similar inflammatory cell infiltration as in lymphocytic colitis (LC), with the characteristically thickened subepithelial collagen layer.
	View Full Size Image
Media type:  Photo

REFERENCES

Section 11 of 11

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• Maxson CJ, Klein HD, Rubin W. Atypical forms of inflammatory bowel disease. Med Clin North Am. Nov 1994;78(6):1259-73. [Medline].
• Mosnier JF, Larvol L, Barge J, Dubois S, De La Bigne G, Henin D, et al. Lymphocytic and collagenous colitis: an immunohistochemical study. Am J Gastroenterol. Apr 1996;91(4):709-13. [Medline].
• Mullhaupt B, Guller U, Anabitarte M, Guller R, Fried M. Lymphocytic colitis: clinical presentation and long term course. Gut. Nov 1998;43(5):629-33. [Medline].
• Pardi DS. Microscopic colitis. Mayo Clin Proc. May 2003;78(5):614-6; quiz 616-7. [Medline].
• Pardi DS, Loftus EV Jr, Smyrk TC, Kammer PP, Tremaine WJ, Schleck CD, et al. The epidemiology of microscopic colitis: a population based study in Olmsted County, Minnesota. Gut. Apr 2007;56(4):504-8. [Medline].
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Article Last Updated: May 8, 2007