Microscopic Colitis (Collagenous and Lymphocytic Colitis) 

Updated: Mar 25, 2021
Author: Harika Balagoni, MD; Chief Editor: BS Anand, MD 

Overview

Background

Microscopic colitis (MC) is a chronic inflammatory condition of the colon, predominantly subdivided into collagenous colitis (CC) and lymphocytic colitis (LC).

Microscopic colitis typically presents as chronic, nonbloody diarrhea with an endoscopically and radiologically normal colon but which demonstrates inflammatory changes on mucosal biopsies. Lymphocytic colitis is characterized histologically by chronic inflammatory infiltration in the lamina propria with lymphocyte and plasma cell proliferation. The diagnosis is confirmed when an epithelium lymphocyte count of more than 20 lymphocytes per 100 epithelial cells are observed. Collagenous colitis is characterized by thickened subepithelial collagen (>10 µm).[1]

Another variant of microscopic colitis exists, called incomplete MC; its histopathology does not fit into either of the collagenous colitis or lymphocytic colitis criteria.[1, 2] This variant is characterized by both thickening of the collagen plate and an increase in the number of intraepithelial lymphocytes.

Ever since microscopic colitis was described, its incidence has steadily increased and accounts for about 8-16% of chronic nonbloody diarrhea.[3] Microscopic colitis should be considered as a differential diagnosis in the workup of chronic diarrhea, especially in the elderly population.

Microscopic colitis is usually found in the elderly population in their sixth or seventh decade and has a significant female predominance.[4, 5]

Historical background

Collagenous colitis was described concurrently in 1976 by Lindstrom[6] and Freeman et al.[7] In 1980, Read and colleagues described microscopic colitis, which is clinically indistinguishable from collagenous colitis but is differentiated from it by specific biopsy features.[8] Later, Lazenby et al proposed the term "lymphocytic colitis" to replace the term "microscopic colitis" and to distinguish it from infectious colitis and inflammatory bowel disease (ulcerative colitis and Crohn disease).[9]

For patient education resources, see Crohns Colitis Foundation, Digestive Disorders Center as well as Common Causes of Colitis, Celiac Sprue, and Crohn's Disease.

Pathophysiology

The pathogenesis of microscopic colitis (MC) is not clearly understood. The etiology is likely multifactorial, potentially including luminal factors, immune dysregulation, and genetic predisposition.[10] It may be mediated in part by the adaptive immune system and by cytotoxic responses triggered by mucosal injury from different factors.[11] Some studies have also shown an association between microscopic colitis and human leukocyte antigen (HLA)-DQ, as noted in celiac disease.[12] A positive correlation between DQ2/DQ8 alleles and lymphocytic colitis (LC) has been noted in some studies. The odds ratio of lymphocytic colitis with positive DQ2-alleles has been found to be as high as 3.[13]

Another significant association has been observed between 5-HTTLPR (serotonin-transporter-linked polymorphic region) polymorphism and microscopic colitis. 5-HT (serotonin) plays a significant role in regulating intestinal motility and secretion. Serotonin levels have been found to be high in patients with microscopic colitis and ulcerative colitis (UC), suggesting a possible association in its pathogenesis.[14]

The interleukin (IL)-6-174 gene polymorphism also has a possible association with microscopic colitis by influencing the inflammation pathway. IL-6 promotes T- and B-lymphocyte maturation and also contributes to macrophage recruitment, causing acute to chronic immune responses and to differentiation of Th2 and Th17 lymphocytes.[15]

Etiology

No definitive etiology has been determined for microscopic colitis (MC), but evidence indicates that drug consumption may trigger underlying inflammatory factors in the colon of affected individuals, whereas other agents may exacerbate diarrhea in patients with idiopathic microscopic colitis.[16] Although many drugs, either alone or in combination, may cause diarrhea as an adverse effect,[17] nonsteroidal anti-inflammatory drugs (NSAIDs) show a strong trend (P = 0.057) toward increasing the risk of collagenous colitis (CC), and rechallenge has been shown to cause recurrence of collagenous colitis.

Antidepressant agents such as selective serotonin reuptake inhibitors (SSRIs) as a group increase the risk of collagenous colitis, but in this class of medications, sertraline alone significantly raises the risk of lymphocytic colitis (LC).[18] Anecdotal reports of a large number of additional drugs have been associated with the onset of microscopic colitis. Among these, ranitidine (confirmed by rechallenge), aspirin, acarbose, ticlopidine, and proton pump inhibitors have high-level evidence of causality, whereas flutamide, simvastatin, carbamazepine, and lisinopril have intermediate-level evidence.

Some patients have had histologic findings consistent with both collagenous colitis and lymphocytic colitis at different points during the course of their disease. This raises the possibility that these may be different manifestations of the same medical condition, or they may be at different points along a continuum.

Many case reports describe patients with preexisting presumed autoimmune conditions (eg, celiac sprue, psoriasis, and rheumatoid arthritis) who are subsequently diagnosed with microscopic colitis. Patients diagnosed with lymphocytic colitis have also been reported to have uveitis, idiopathic pulmonary fibrosis, juvenile diabetes mellitus, pernicious anemia, autoimmune thyroid disease, and idiopathic thrombocytopenic purpura. Approximately one third of patients with celiac disease have histologic findings consistent with microscopic colitis. For this reason, microscopic colitis should be considered in patients diagnosed with celiac disease who have diarrhea that fails to respond to a gluten-free diet. However, removal of gluten from the diet is ineffective in treating microscopic colitis in the absence of celiac disease.

Microscopic colitis and inflammatory bowel disease (IBD) (Crohn disease or ulcerative colitis) have been diagnosed concurrently or sequentially in a small number of cases, with either diagnosis preceding the other. It is hypothesized that the two diseases may be part of one disease spectrum rather than two separate entities.

Smoking increases the risk of microscopic colitis[19, 20] as well as the age at diagnosis. Active smoking is associated with a higher incidence of microscopic colitis, and it is more strongly implicated in collagenous colitis than lymphocytic colitis.[21, 22] Clinical symptoms of collagenous colitis may be worse in smokers than nonsmokers, and smokers are less likely to achieve clinical remission.[23]

In some patients with diabetes mellitus and diarrhea, there is evidence of an increase in the thickness of the subepithelial collagen bands. However, no correlation has been reported between collagen thickness, age, and the duration of diabetes.[24]

Epidemiology

Microscopic colitis (MC) is strongly associated with other autoimmune disorders, such as celiac disease, polyarthritis, and thyroid disorders.[4]  Up to 20-60% of patients with lymphocytic colitis and 17-40% of patients with collagenous colitis (CC) have an autoimmune disease.[4, 25] In fact, histologic features of microscopic colitis in the colon are present in 30% of patients with celiac disease.

An increased risk of microscopic colitis is associated with smoking, as well as the use of certain drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), and selective serotonin reuptake inhibitors (SSRIs).[10, 19, 26, 27]

Tong et al, in their systematic review and meta-analysis of epidemiologic studies on microscopic colitis found that the incidence of collagenous colitis and lymphocytic colitis (LC) was 4.14 per 100,000 person-years and 4.85 per 100,000, respectively.[28] The study showed significant female predominance with a female-male incidence ratio of 3.05 for collagenous colitis and 1.92 for lymphocytic colitis, as well as a median age of diagnosis in the sixth decade. Overall, the investigators noticed a steady increase in the incidence of microscopic colitis across different countries since year 2000. The incidence in the United States, Sweden, and Spain appears to have stabilized since year 2000.

Both conditions are observed more commonly in individuals older than 40 years, with a 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.

Prognosis

Natural history/prognosis

The clinical course of microscopic colitis (MC) varies throughout the literature. Approximately 20% of patients with microcytic colitis may have a spontaneous remission without specific therapy.[11]

More than half of patients treated for lymphocytic colitis (LC) experienced resolution of symptoms after 6 months of treatment, whereas 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 thought to be due to epithelial membrane sloughing and the resultant altered mucosal permeability.

Although some small studies have suggested otherwise, microscopic colitis (either collagenous colitis [CC] or lymphocytic colitis) does not appear to increase the risk of colon cancer or adenoma.[10]

 

Presentation

History & Physical Examination

History

The presenting complaint of microscopic colitis (MC) is usually chronic watery, nonbloody diarrhea,[10] usually between 4-6 loose stools per day,[29] and frequently associated with other symptoms (eg, fecal urgency/incontinence, nocturnal stools).[10] Less frequent complaints include abdominal cramping, fecal incontinence, fatigue, nocturnal diarrhea, and weight loss, although weight loss may be seen in 40% or more of patients with collagenous colitis (CC).[29, 30]

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 the patients proven to have microscopic colitis meet the Rome II and Manning symptom-based criteria for diarrhea-predominant irritable bowel syndrome (IBS) and, thus, they may be misdiagnosed until endoscopic biopsies of the colon are taken.

Incontinence is probably more a reflection of the advanced age of affected individuals; patients with this problem may do well if treated with antidiarrheal agents.

Physical examination

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

 

DDx

Diagnostic Considerations

Rule out microscopic colitis (MC) in those who fulfill the criteria for functional bowel disease, especially in the presence of risk factors for microscopic colitis and/or in the absence of response to therapy for irritable bowel syndrome (IBS).

Microscopic colitis should be considered as a differential diagnosis in the workup of chronic diarrhea, especially in the elderly population. In addition, microscopic colitis should be considered in patients diagnosed with celiac disease who have diarrhea that fails to respond to a gluten-free diet. 

Differential diagnosis

Different small bowel diseases and conditions may mimic microscopic colitis, including the following:

  • Concurrent lymphocytic colitis (LC) and lymphocytic gastritis[31]

  • Celiac disease: Collagenous colitis (CC) may represent a diffuse manifestation of gluten sensitivity; therefore, it is reasonable to evaluate patients for celiac disease[32]

  • Infectious colitis (other than Clostridium difficile infection)

  • Ischemic colitis

  • Laxative abuse

  • Bile acid malabsorption

Important considerations

Patients whose condition fails to respond to reasonable medical therapy should be evaluated for other conditions that may clinically mimic lymphocytic colitis and collagenous colitis.

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 an irritable bowel syndrome (IBS) 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 has a low yield, even with normal findings on endoscopy. Patients clinically assessed as having diarrhea-predominant IBS (IBS-D) in whom conventional medical therapy is refractory 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, such as 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 (IBD), antidiarrheal and nonimmunosuppressive medications have an acceptable risk in pregnant patients when clinical symptoms are significant and might threaten the 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, the risk versus benefit considerations must be carefully discussed before prescribing these medications to a pregnant patient.

Differential Diagnoses

 

Workup

Approach Considerations

A thorough history and physical examation with routine blood work including complete blood cell count, metabolic profile, thyroid profile, stool studies, and celiac serologies are indicated in patients with suspected microscopic colitis (MC). The presentation of irritable bowel syndrome-diarrhea predominant (IBS-D) is very similar to microscopic colitis. Multiple scoring systems have been proposed to noninvasively stratify such patients into one of these categories, but they are not yet validated.[33] Factors such as age over 50 years, female sex, weight loss, absence of abdominal pain, current smoking, nocturnal diarrhea, duration of diarrhea less than 6 months, and use of nonsteroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), and selective serotonin reuptake inhibitors (SSRIs) are all factored into these systems.

In the absence of a formally validated metric of disease activity, evaluate disease activity and clinical remission in microscopic colitis by the Hjortswang criteria (clinical remission: mean of < 3 stools per day and a mean < 1 watery stool per day during a 1-week registration).[10]

United European Gastroenterology (UEG) and the European Microscopic Colitis Group (EMCG) recommendations include the following[10] :

  • Ileocolonoscopy, with biopsies from at least the right and left colon

  • Not histologically monitoring patients with microscopic colitis

  • Fecal calprotectin is not useful for excluding or monitoring microscopic colitis

  • Screening for celiac disease in patients with microscopic colitis

  • Considering testing for bile acid diarrhea in those experiencing nonresponse to budesonide treatment

Laboratory Studies

Blood studies

Most of the blood test results in patients with microscopic colitis (MC) are usually within the reference range, but anemia, hypokalemia, hypoalbuminemia, elevation of the erythrocyte sedimentation rate, or a combination of these findings may be present.

Approximately 50% of patients with collagenous colitis (CC) and those with lymphocytic colitis (LC) may have circulating autoantibodies, especially rheumatoid factor (RF); antinuclear, antimitochondrial, antineutrophilic cytoplasmic antibodies (ANCA); and antiparietal cell, antithyroglobulin, and antimicrosomal antibodies.[34]

Stool studies

Increased levels of the stool inflammatory markers (eg, fecal calprotectin, leukocyte esterase) have been detected in stool from patients with collagenous colitis, whereas the levels of these markers in patients with irritable bowel syndrome (IBS) did not differ from healthy controls.[35]

On occasion, stool evaluation may show the presence of leukocytes and elevated fecal calprotectin. In these circumstances, the stool should be tested for enteric bacterial pathogens, ova and parasites, and C difficile.

It is also important to rule out bile acid malabsorption as well as steatorrhea. A prolonged (24-h 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 is usually indicative of fat malabsorption, and, even if microscopic colitis is present, a diagnosis of concurrent sprue should be considered.

Other tests

Immunohistochemical studies of biopsies in lymphocytic colitis and collagenous colitis cases demonstrate abnormalities consistent with a mixed histocompatibility-restricted mechanism.[36]

The excessive intraepithelial lymphocytes observed in lymphocytic colitis are predominantly CD4+ T cells rather than CD8+.

Imaging Studies and Procedures

Imaging Studies

Findings on plain abdominal radiographs, barium enemas, and computed tomography (CT) scans are typically normal or nonspecific and show no evidence of colonic mucosal damage or wall abnormality in persons with microscopic colitis (MC).

Procedures

Biopsies obtained by sigmoidoscopy or colonoscopy are necessary to diagnose lymphocytic colitis (LC) or collagenous colitis (CC).[3, 25, 37]  

If a colonoscopy is performed, multiple biopsies should be taken from different segments of the right and left side of the colon. Approximately 95% of patients with microscopic colitis will have diagnostic left colon biopsies[37] ; but, if these biopsies are nondiagnostic at sigmoidoscopy in a patient in whom clinical suspicion remains high, total colonoscopy for right-sided biopsies may confirm the diagnosis.

Although endoscopic findings are increasingly recognized in patients with microscopic colitis, they are nonspecific.[10] In individuals with lymphocytic or collagenous colitis, 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 (IBD) such as friability, ulceration, and pseudopolyps. Most patients have similar degrees of histologic abnormality in the right and left sides of the colon.

Histologic Findings

Collagenous colitis (CC) demonstrates a thick colonic subepithelial collagenous deposit (≥10 μm) and an increased inflammatory infiltrate in the lamina propria, whereas lymphocytic colitis (LC) reveals a pronounced intraepithelial lymphocytic (IEL) inflammation (≥20 per 100 surface epithelial cells) and an increased inflammatory infiltrate in the lamina propria but in the absence of a thickened collagen band (< 10 μm).[10]

Incomplete microscopic colitis (MCi) comprises incomplete collagenous colitis (defined by a thickened subepithelial collagenous band >5 µm but < 10 µm) and incomplete lymphocytic colitis (defined by >10 IELs but < 20 IELs and a normal collagenous band).[10] Both types show a mild inflammatory infiltrate in the lamina propria. The criteria apply to hematoxylin and eosin (H&E)-stained slides.

In summary, histologic features of microscopic colitis include the following:

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

  • Intraepithelial lymphocytosis, with more than 20 lymphocytes per 100 epithelial cells, is pathognomonic of the diagnosis of lymphocytic colitis (LC) (see the following image), although lesser numbers of IELs may be present in some patients with lymphocytic colitis.

    Microscopic Colitis (Collagenous and Lymphocytic C Microscopic Colitis (Collagenous and Lymphocytic Colitis). Lymphocytic colitis (LC) showing marked chronic inflammatory cell infiltrate of the surface epithelium (on right) with preservation of the crypt architecture. The subepithelial collagen layer is not thickened.
  • Epithelial cell damage is demonstrated by cell flattening, subepithelial blebs, and denuded epithelium. Fixed specimens may show epithelial loss and detachment.

  • Crypts may have minimal architectural distortion as in Crohn disease or ulcerative colitis. However, typically, evenly spaced parallel crypts of equal diameter are present.

  • Collagenous colitis shares the histologic features of lymphocytic colitis but additionally demonstrates a thickened subepithelial collagen layer (usually >10 µm) in the lamina propria, compared to a normal thickness of 5-7 µm.

  • For comparison, a representative biopsy of collagenous colitis is shown in the following image.

    Microscopic Colitis (Collagenous and Lymphocytic C Microscopic Colitis (Collagenous and Lymphocytic Colitis). Collagenous colitis (CC) showing similar inflammatory cell infiltration as in lymphocytic colitis (LC), with the characteristically thickened subepithelial collagen layer.
  • 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

Approach Considerations

United European Gastroenterology (UEG) and the European Microscopic Colitis Group (EMCG) recommend the following for treatment of microscopic colitis (MC)[10] :

  • For induction of remission in collagenous colitis (CC) or lymphocytic colitis (LC): Oral budesonide

  • Oral budesonide is effective for maintaining remission in patients with collagenous colitis; it is suggested for maintaining remission in patients with lymphocytic colitis 

  • Budesonide in microscopic colitis is not associated with an increased risk of serious adverse events

  • The risk of osteoporotic bone fractures does not appear to be increased in patients with microscopic colitis who are treated with budesonide; however, there may be an associated reduction in bone mineral density with prolonged use

  • Mesalazine therapy is not recommended for induction of remission in patients with microscopic colitis. No studies exist for maintenance

  • Not enough evidence exists for recommending bismuth subsalicylate, loperamide, nor antibiotics in cases of microscopic colitis. However, given loperamide’s documented effects in chronic diarrhea, loperamide is favored in mild microscopic colitis disease

  • For microscopic colitis and bile acid diarrhea, bile acid binders are suggested for treatment

  • Probiotics, prednisolone or other corticosteroids than budesonide, as well as methotrexate are not recommended as treatment of microscopic colitis

  • Recommended treatment includes thiopurines, anti-tumor necrosis factor (anti-TNF) drugs, or vedolizumab in patients with budesonide-refractory microscopic colitis to induce and maintain clinical remission

  • Consider surgery as the last option in selected patients with microscopic colitis if all medical therapy fails

Medical Care

Medical treatment

Medical treatment is not different for different subtypes of microscopic colitis (MC). Similar responses to treatment have been reported throughout the literature. The following treatment guidelines are based on the American Gastroenterological Association (AGA) Institute guidelines.[38, 39]

Patients are also advised to avoid any offending medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), and selective serotonin reuptake inhibitors (SSRIs) if a chronological relationship is established or if symptoms persist in spite of treatment

Antidiarrheal agents such as loperamide may be used in mild cases (< 3 stools per day) or in conjunction with other therapies for symptomatic relief.

The treatment algorithm is as follows[38, 39] :

  • First line: Budesonide 9 mg daily for at least 8 weeks. Once symptom remission has been achieved, patients can be gradually tapered off budesonide. If no recurrence of symptoms occurs, no maintenance therapy is needed. If patients develop recurrent symptoms after stopping budesonide, they can go on maintenance therapy with the lowest effective dose of budesonide: 3-6 mg daily for 6-12 months.
  • Second line: If the patient unable to tolerate budesonide or if it is not feasible, second-line treatment is with mesalamine or bismuth salicylate or oral prednisone or prednisolone.

Alternative therapies like cholestyramine can be used in mild cases of microscopic colitis. However, the use of cholestyramine along with mesalamine is not recommended due to decreased absorption of mesalamine.

Multiple other agents such as Boswellia serrata, probiotics, and octreotide have been studied but did not show consistent results. Some small studies have shown efficacy with anti-tumor necrosis factor (TNF) therapy or immunomodulators like methotrexate or azathioprine in refractory cases.[40, 41, 42]

In rare scenarios, where patients continue to have significant diarrhea in spite of medical therapy, colectomy might be considered.

Diet and activity

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.

Consultations

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

 

Guidelines

Guidelines Summary

Statements and recommendations on the management of microscopic colitis (MC) were released by United European Gastroenterology (UEG) and the European Microscopic Colitis Group (EMCG) in August 2020.[10]

The two main MC histologic subtypes are collagenous colitis (CC) and lymphocytic colitis (LC); however, incomplete forms exist (incomplete MC [MCi]).

Pathogenesis and Risk Factors

The pathogenesis of MC is complex and multifactorial, potentially including luminal factors, immune dysregulation, and genetic predisposition. Risk factors include the following:

  • Former and, particularly, current smoking is associated with an increased risk of CC and LC. Insufficient evidence exists to assess the influence of smoking cessation on the disease course.

  • Women have a higher risk of developing CC or LC than men.

  • Chronic or frequent use of proton pump inhibitors (PPIs), nonsteroidal anti-inflammatory drugs (NSAIDs), or selective serotonin reuptake inhibitors (SSRIs) is associated with a greater risk of MC, but a causal relationship is not implied.

  • AGA suggests considering withdrawing drugs that are suspected of having a chronologic relationship between the introduction of the agent(s) and the diarrheal onset.

  • MC does not raise the risk of colorectal cancer or adenoma. A special surveillance colonoscopy program is not recommended.

Clinical Manifestations

The most common MC symptom is chronic watery, non-bloody diarrhea that is often associated with other symptoms, including fecal urgency/incontinence, and nocturnal stools.

Rule out MC in those who fulfill the criteria for functional bowel disease, especially in the presence of MC risk factors and/or in the absence of response to therapy for irritable bowel syndrome (IBS).

Patients with MC have impaired health-related quality of life, depending on the activity, disease severity, and associated comorbidities.

Diagnosis

Although endoscopic findings are increasingly recognized in patients with MC, they are nonspecific.

For CC, the histopathologic criteria (on hematoxylin–eosin [H&E]-stained slides) are a thickened subepithelial collagenous band of 10 µm or greater, combined with an increased inflammatory infiltrate in the lamina propria.

For LC, the histopathologic criteria (on H&E-stained slides) are an increased number of intraepithelial lymphocytes (IELs) of at least 20 per 100 surface epithelial cells combined with an increased inflammatory infiltrate in the lamina propria and a not significantly thickened collagenous band (< 10 µm).

Incomplete MC comprises incomplete CC (defined by a thickened subepithelial collagenous band >5 µm but < 10 µm) and incomplete LC (defined by >10 IELs but < 20 IELs and a normal collagenous band). Both types show a mild inflammatory infiltrate in the lamina propria. These criteria apply to H&E-stained slides.

Treatment

UEG/EMCG recommend the following for treatment:

  • For induction of remission in CC or LC: Oral budesonide

  • Oral budesonide is effective for maintaining remission in patients with CC and LC

  • Other potential treatment options would be, mesalamine or bismuth salicylate or oral prednisone or prednisolone

  • For MC and bile acid diarrhea, suggested treatment is with bile acid binders

  • Consider treatment with thiopurines, anti-tumor necrosis factor (anti-TNF) drugs, or vedolizumab in patients with MC whose condition fails to respond to budesonide to induce and maintain clinical remission

  • Consider surgery as the last option in selected patients with MC if all medical therapies fail

 

Medication

Medication Summary

Medication is indicated in microscopic colitis (MC) only if discontinuing dietary components or medications considered possibly responsible for the illness fails to alleviate the symptoms. As discussed earlier, treatment is initiated with the least toxic, effective agents. If the condition fails to respond to simple antidiarrheal drugs, anti-inflammatory or immunosuppressive medications may be required. A treatment algorithm is discussed in Medical Care.

Antidiarrheal agents

Class Summary

Antidiarrheal agents may be appropriate in mild cases of microscopic colitis.

Loperamide (Imodium AD)

Poorly absorbable opiate that decreases colonic smooth muscle contraction and propulsive activity. Slows intestinal motility and delays colonic transit. Reduction of gastrointestinal secretion may contribute to the antidiarrheal effect. Well-tolerated and safe drug when taken in recommended dosages.

Diphenoxylate hydrochloride/atropine sulfate (Lomotil)

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.

Bismuth subsalicylate (Pepto-Bismol)

Controls diarrhea by reducing fluid secretion into the intestinal lumen, by binding bacterial toxins, or by acting as an antimicrobial agent.

Anion exchange resins

Class Summary

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

Cholestyramine (Questran, LoCholest)

Absorbs bile salts in the intestine, resulting in an insoluble complex that is excreted in feces.

Antispasmodics

Class Summary

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

Hyoscyamine (Levsin SL, Levbid, Symax, Cystospaz)

Anticholinergic agent with limited and generally symptomatic utility in patients with colitis. Levsin or Levsin SL (sublingual) is dispensed as 0.125-mg tab, Cystospaz as 0.15-mg tab, and Levbid or Symax as 0.375-mg tabs.

Topical anti-inflammatory drugs

Class Summary

Drugs that reduce inflammatory changes at the level of the colonic mucosa may be needed in a subset of patients with colitis who fail to respond to antidiarrheal medication.

Sulfasalazine (Azulfidine EN-tabs)

Prodrug complexing the active component of 5-aminosalicylic acid (5-ASA) with an inactive sulfapyridine moiety to prevent systemic absorption in the upper gastrointestinal tract. In the colon, the diazo bond is cleaved by the bacterial flora and the active 5-ASA is released to function as a topical anti-inflammatory drug. Adverse effects typically are due to sulfapyridine rather than to 5-ASA.

Mesalamine (Asacol, Pentasa)

Controlled-released formulations of 5-ASA that cause fewer side effects than sulfasalazine due to the absence of the sulfa moiety. Pentasa is ethylcellulose-coated 5-ASA 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.

Corticosteroids

Class Summary

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.

Prednisone (Deltasone, Orasone, Sterapred)

Inexpensive corticosteroid available in many strengths, which simplifies tapering schedules. Methylprednisolone (Medrol), dexamethasone (Decadron), or hydrocortisone can be used instead of prednisone. Dosage should be adjusted based on relative potencies.

Budesonide (Entocort EC)

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.

Immunosuppressant drugs

Class Summary

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

Azathioprine (Imuran), 6-mercaptopurine (Purinethol)

Azathioprine is an antimetabolite available in tablet form for oral administration or in 100-mg vials for IV injection and is an imidazolyl derivative of 6-mercaptopurine. It is cleaved in vivo to mercaptopurine. Both compounds are eliminated rapidly from blood and are oxidized or methylated in the erythrocytes and the liver. No azathioprine or mercaptopurine is detectable in urine 8 h after administration.

Methotrexate (Folex, Rheumatrex)

Previously known as amethopterin. Antimetabolite that inhibits dihydrofolic acid reductase. Also used in certain neoplastic diseases, severe psoriasis, and adult rheumatoid arthritis.

 

Questions & Answers

Overview

What is microscopic colitis (MC)?

What is the pathophysiology of microscopic colitis (MC) (collagenous colitis [CC] and lymphocytic colitis [LC])?

What causes microscopic colitis (MC) (collagenous colitis [CC] and lymphocytic colitis [LC])?

What conditions are associated with microscopic colitis (MC) (collagenous colitis [CC] and lymphocytic colitis [LC])?

What else increases the risk of microscopic colitis (MC) (collagenous colitis [CC] and lymphocytic colitis [LC])?

What are the sex- and age-related demographics of microscopic colitis (MC) (collagenous colitis [CC] and lymphocytic colitis [LC])?

What is the prognosis of microscopic colitis (MC) (collagenous colitis [CC] and lymphocytic colitis [LC])?

Presentation

Which clinical history findings are characteristic of microscopic colitis (MC) (collagenous colitis [CC] and lymphocytic colitis [LC])?

Which physical findings are characteristic of microscopic colitis (MC) (collagenous colitis [CC] and lymphocytic colitis [LC])?

DDX

When should microscopic colitis (MC) (collagenous colitis [CC] and lymphocytic colitis [LC]) be ruled out?

What is included in the differential diagnosis of microscopic colitis (MC) (collagenous colitis [CC] and lymphocytic colitis [LC])?

What are important considerations in microscopic colitis (MC) (collagenous colitis [CC] and lymphocytic colitis [LC])?

What are special concerns in microscopic colitis (MC) (collagenous colitis [CC] and lymphocytic colitis [LC])?

What are the differential diagnoses for Microscopic Colitis (Collagenous and Lymphocytic Colitis)?

Workup

What should be considered in the workup approach for microscopic colitis (MC) (collagenous colitis [CC] and lymphocytic colitis [LC])?

What are the roles of blood studies and stool samples in the workup of microscopic colitis (MC) (collagenous colitis [CC] and lymphocytic colitis [LC])?

What is the role of immunohistochemical studies in the workup of microscopic colitis (MC) (collagenous colitis [CC] and lymphocytic colitis [LC])?

What is the role of imaging studies in the workup of microscopic colitis (MC) (collagenous colitis [CC] and lymphocytic colitis [LC])?

Which procedures have a role in the workup of microscopic colitis (MC) (collagenous colitis [CC] and lymphocytic colitis [LC])?

Which histologic findings are characteristic of microscopic colitis (MC) (collagenous colitis [CC] and lymphocytic colitis [LC])?

Treatment

What is the role of surgery in the treatment of microscopic colitis (MC) (collagenous colitis [CC] and lymphocytic colitis [LC])?

How is microscopic colitis (MC) (collagenous colitis [CC] and lymphocytic colitis [LC]) treated?

Which dietary modifications are used in the treatment of microscopic colitis (MC) (collagenous colitis [CC] and lymphocytic colitis [LC])?

Which specialist consultations are beneficial to patients with microscopic colitis (MC) (collagenous colitis [CC] and lymphocytic colitis [LC])?

Medications

What is the role of medications in the treatment of microscopic colitis (MC) (collagenous colitis [CC] and lymphocytic colitis [LC])?

Which medications in the drug class Immunosuppressant drugs are used in the treatment of Microscopic Colitis (Collagenous and Lymphocytic Colitis)?

Which medications in the drug class Corticosteroids are used in the treatment of Microscopic Colitis (Collagenous and Lymphocytic Colitis)?

Which medications in the drug class Topical anti-inflammatory drugs are used in the treatment of Microscopic Colitis (Collagenous and Lymphocytic Colitis)?

Which medications in the drug class Antispasmodics are used in the treatment of Microscopic Colitis (Collagenous and Lymphocytic Colitis)?

Which medications in the drug class Anion exchange resins are used in the treatment of Microscopic Colitis (Collagenous and Lymphocytic Colitis)?

Which medications in the drug class Antidiarrheal agents are used in the treatment of Microscopic Colitis (Collagenous and Lymphocytic Colitis)?