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Microscopic Colitis – Causes, Symptoms, Diagnosis, Treatment

Microscopic colitis is a chronic, non-bloody diarrhea inflammatory bowel disease, of the colon characterized by chronic diarrhea, normal colonic mucosa, and abnormal histologic hallmarks that can be seen only with a microscope. Inflammation is the body’s normal response to injury, irritation, or infection of tissues. Microscopic colitis is a type of inflammatory bowel disease—the general name for diseases that cause irritation and inflammation in the intestines.

Types of Microscopic Colitis

The two types of microscopic colitis are collagenous colitis and lymphocytic colitis. Health care providers often use the term microscopic colitis to describe both types because their symptoms and treatments are the same. Some scientists believe that collagenous colitis and lymphocytic colitis may be different phases of the same condition rather than separate conditions.

In both types of microscopic colitis, an increase in the number of lymphocytes, a type of white blood cell, can be seen in the epithelium—the layer of cells that lines the colon. An increase in the number of white blood cells is a sign of inflammation. The several types of colitis affect the colon tissue in slightly different ways

  • Lymphocytic colitis – The number of lymphocytes is higher, and the tissues and lining of the colon are of normal thickness 20 or more intraepithelial lymphocytes per 100 epithelial cells, typically without crypt distortion, defines lymphocytic colitis
  • Collagenous colitis – A collagen band greater than 10 micrometers in diameter in the subepithelial layer defines this type of microscopic colitis.
  • Microscopic colitis not otherwise specified – This terminology is used to describe a subgroup of patients with typical symptoms such as diarrhea, increased cellular infiltrate, and either an abnormal collagenous layer or increased intraepithelial lymphocytes that do not match the above criteria.

When looking through a microscope, the health care provider may find variations in lymphocyte numbers and collagen thickness in different parts of the colon. These variations may indicate an overlap of the two types of microscopic colitis.

What is the colon?

The colon is part of the gastrointestinal (GI) tract, a series of hollow organs joined in a long, twisting tube from the mouth to the anus—a 1-inch-long opening through which stool leaves the body. Organs that make up the GI tract are the

  • mouth
  • esophagus
  • stomach
  • small intestine
  • large intestine
  • anus

The first part of the GI tract, called the upper GI tract, includes the mouth, esophagus, stomach, and small intestine. The last part of the GI tract, called the lower GI tract, consists of the large intestine and anus. The intestines are sometimes called the bowel.

The large intestine is about 5 feet long in adults and includes the colon and rectum. The large intestine changes waste from liquid to a solid matter called stool. Stool passes from the colon to the rectum. The rectum is 6 to 8 inches long in adults and is between the last part of the colon—called the sigmoid colon—and the anus. During a bowel movement, the stool moves from the rectum to the anus and out of the body.

What Causes Microscopic Colitis?

The exact cause of microscopic colitis is unknown.

  • Infection  Bacterial infections including Campylobacter jejuni, Escherichia coli, Salmonella, Shigella, Mycobacterium tuberculosis, and Clostridium difficile responsible for Pseudomembranous colitis. Parasites such as Entamoeba histolytica, and viruses such as cytomegalovirus.
  • Inflammatory bowel disease  This refers to Crohn’s disease (CD) and Ulcerative colitis (UC).
  • Microscopic colitis  This condition is a relatively common cause of chronic watery diarrhea, especially in the elderly. The disease has two main subtypes, collagenous colitis (CC) and lymphocytic colitis (LC), which are very similar clinically with the main distinction being the presence or absence of a thickened subepithelial collagen band. The disease is associated with autoimmune disorders such as celiac disease, type 1 diabetes, thyroid dysfunction, and psoriasis.
  • Ischemic colitis occurs when there is hypoperfusion in the blood supply below that required for the metabolic needs of the colon resulting in colonic mucosal ulceration, inflammation, and hemorrhage.
  • Secondary to immune deficiency disorders
  • Tuberculous colitis
  • Radiation colitis This can occur secondary to pelvic radiotherapy for gynecological, urological and rectal cancers.

Several factors may play a role in causing microscopic colitis. However, most scientists believe that microscopic colitis results from an abnormal immune-system response to bacteria that normally live in the colon. Scientists have proposed other causes, including

  • autoimmune diseases
  • medications
  • infections
  • genetic factors
  • bile acid malabsorption
Autoimmune Diseases

Sometimes people with microscopic colitis also have autoimmune diseases—disorders in which the body’s immune system attacks the body’s own cells and organs. Autoimmune diseases associated with microscopic colitis include

  • celiac disease—a condition in which people cannot tolerate gluten because it damages the lining of the small intestine and prevents absorption of nutrients. Gluten is a protein found in wheat, rye, and barley.
  • thyroid diseases such as
    • Hashimoto’s disease—a form of chronic, or long-lasting, inflammation of the thyroid.
    • Graves’ disease—a disease that causes hyperthyroidism. Hyperthyroidism is a disorder that occurs when the thyroid gland makes more thyroid hormones than the body needs.
  • rheumatoid arthritis—a disease that causes pain, swelling, stiffness, and loss of function in the joints when the immune system attacks the membrane lining the joints.
  • psoriasis—a skin disease that causes thick, red skin with flaky, silver-white patches called scales.
Medications

Researchers have not found that medications cause microscopic colitis. However, they have found links between microscopic colitis and certain medications, most commonly. Drugs such as non-steroidal inflammatory drugs, aspirin, proton pump inhibitors, Hreceptor antagonists, beta-blockers, statins, immunosuppressive drugs, vasopressors may cause colitis.

  • nonsteroidal anti-inflammatory drugs such as aspirin, ibuprofen, and naproxen
  • lansoprazole (Prevacid)
  • acarbose (Prandase, Precose)
  • ranitidine (Tritec, Zantac)
  • sertraline (Zoloft)
  • ticlopidine (Ticlid)

Other medications linked to microscopic colitis include

  • carbamazepine
  • clozapine (Clozaril, FazaClo)
  • dexlansoprazole (Kapidex, Dexilant)
  • entacapone (Comtan)
  • esomeprazole (Nexium)
  • flutamide (Eulexin)
  • lisinopril (Prinivil, Zestril)
  • omeprazole (Prilosec)
  • pantoprazole (Protonix)
  • paroxetine (Paxil, Pexeva)
  • rabeprazole (AcipHex)
  • simvastatin (Zocor)
  • vinorelbine (Navelbine)
Infections
  • Bacteria – Some people get microscopic colitis after infection with certain harmful bacteria. Harmful bacteria may produce toxins that irritate the lining of the colon.
  • Viruses – Some scientists believe that viral infections that cause inflammation in the GI tract may play a role in causing microscopic colitis.
Genetic Factors

Some scientists believe that genetic factors may play a role in microscopic colitis. Although researchers have not yet found a gene unique to microscopic colitis, scientists have linked dozens of genes to other types of inflammatory bowel disease, including

  • Crohn’s disease—a disorder that causes inflammation and irritation of any part of the GI tract
  • ulcerative colitis—a chronic disease that causes inflammation and ulcers in the inner lining of the large intestine
Bile Acid Malabsorption

Some scientists believe that bile acid malabsorption plays a role in microscopic colitis. Bile acid malabsorption is the intestines’ inability to completely reabsorb bile acids—acids made by the liver that work with bile to break down fats. Bile is a fluid made by the liver that carries toxins and waste products out of the body and helps the body digest fats. Bile acids that reach the colon can lead to diarrhea.

What are the Symptoms of Microscopic Colitis?

The most common symptom of microscopic colitis is chronic, watery, non-bloody diarrhea. Episodes of diarrhea can last for weeks, months, or even years. However, many people with microscopic colitis may have long periods without diarrhea. Other signs and symptoms of microscopic colitis can include

  • a strong urge to have a bowel movement or a need to go to the bathroom quickly
  • pain, cramping, or bloating in the abdomen—the area between the chest and the hips—that is usually mild
  • weight loss
  • fecal incontinence—accidental passing of stool or fluid from the rectum—especially at night
  • nausea
  • dehydration—a condition that results from not taking in enough liquids to replace fluids lost through diarrhea

The symptoms of microscopic colitis can come and go frequently. Sometimes, the symptoms go away without treatment.

How is Microscopic Colitis Diagnosed?

A pathologist—a doctor who specializes in examining tissues to diagnose diseases—diagnoses microscopic colitis based on the findings of multiple biopsies taken throughout the colon. Biopsy is a procedure that involves taking small pieces of tissue for examination with a microscope. The pathologist examines the colon tissue samples in a lab. Many patients can have both lymphocytic colitis and collagenous colitis in different parts of their colon.

To help diagnose microscopic colitis, a gastroenterologist—a doctor who specializes in digestive diseases—begins with

  • a medical and family history
  • a physical exam

The gastroenterologist may perform a series of medical tests to rule out other bowel diseases—such as irritable bowel syndrome, celiac disease, Crohn’s disease, ulcerative colitis, and infectious colitis that cause symptoms similar to those of microscopic colitis. These medical tests include

  • lab tests
  • imaging tests of the intestines
  • endoscopy of the intestines

Medical and Family History

The gastroenterologist will ask the patient to provide a medical and family history, a review of the symptoms, a description of eating habits, and a list of prescription and over-the-counter medications in order to help diagnose microscopic colitis. The gastroenterologist will also ask the patient about current and past medical conditions.

Physical Exam

A physical exam may help diagnose microscopic colitis and rule out other diseases. During a physical exam, the gastroenterologist usually

  • examines the patient’s body
  • taps on specific areas of the patient’s abdomen

Lab Tests

Lab tests may include

  • Complete blood count – Laboratory workup including complete blood count, ESR, CRP, arterial blood gases, activated partial thromboplastin time, serum albumin, total protein, blood urea, creatinine, electrolytes, and purified protein derivative, should be ordered.
  • Blood tests – A blood test involves drawing blood at a health care provider’s office or a commercial facility and sending the sample to a lab for analysis. A health care provider may use blood tests to help look for changes in red and white blood cell counts.
  • Red blood cells – When red blood cells are fewer or smaller than normal, a person may have anemia—a condition that prevents the body’s cells from getting enough oxygen.
  • White blood cells – When the white blood cell count is higher than normal, a person may have inflammation or infection somewhere in the body.
  • D-lactate levels Test – in the blood could be a sensitive marker of colonic ischemia; however, it is an experimental laboratory test.
  • Stool tests – A stool test is the analysis of a sample of stool. A health care provider will give the patient a container for catching and storing the stool. The patient returns the sample to the health care provider or a commercial facility that will send the sample to a lab for analysis. Health care providers commonly order stool tests to rule out other causes of GI diseases, such as different types of infections—including bacteria or parasites—or bleeding, and help determine the cause of symptoms.
  • Perinuclear antineutrophil cytoplasmic antibodies (P-ANCA)  – Several laboratory tests specific to certain colitis may be ordered including perinuclear antineutrophil cytoplasmic antibodies (P-ANCA), which may present in Crohn disease, anti-saccharomyces cerevisiae antibodies (ASCA), a feature in both ulcerative colitis and Crohn disease, and carcinoembryonic antigen (CEA), which is elevated in patients with active ulcerative colitis.

Imaging Tests

Imaging tests of the intestines may include the following:

  • Electrocardiogram – transthoracic and even Holter monitoring may be necessary in patients with ischemic colitis.
  • Plain X-ray – is of limited value; however, it may be useful in the diagnosis of toxic megacolon, bowel obstruction, and intestinal perforation (pneumoperitoneum). Thumbprinting is a classic finding for mucosal edema though not specific for ischemic colitis.
  • Multidetector CT – and thin sections, can accurately demonstrate inflammatory changes in the colonic wall and help assess the extent of disease. Ulcerative colitis is distinguishable from granulomatous colitis (Crohn’s disease) in terms of location of involvement, extent, and appearance of colonic wall thickening, and type of complications.
  • Proctosigmoidoscopy – is essential for the final diagnosis; it typically appears normal in microscopic colitis although edema or erythema may present. Ulceration suggests an alternative diagnosis, although these can be present in patients on non-steroidal anti-inflammatory drugs. Other colonoscopy changes, depending on the etiology, include loss of typical vascular pattern, granularity, friability, and ulceration.
  • CT scan – CT scans use a combination of x-rays and computer technology to create images. For a CT scan, a health care provider may give the patient a solution to drink and an injection of a special dye called contrast medium. CT scans require the patient to lie on a table that slides into a tunnel-shaped device where the technician takes the x-rays.
  • MRI – MRI is a test that takes pictures of the body’s internal organs and soft tissues without using x-rays. Although a patient does not need anesthesia for an MRI, some patients with a fear of confined spaces may receive light sedation, taken by mouth. An MRI may include a solution to drink and injection of contrast medium. With most MRI machines, the patient will lie on a table that slides into a tunnel-shaped device that may be open-ended or closed at one end. Some machines allow the patient to lie in a more open space. During an MRI, the patient, although usually awake, must remain perfectly still while the technician takes the images, which usually takes only a few minutes. The technician will take a sequence of images to create a detailed picture of the intestines. During sequencing, the patient will hear loud mechanical knocking and humming noises.
  • Upper GI series – This test is an x-ray exam that provides a look at the shape of the upper GI tract. A patient should not eat or drink before the procedure, as directed by the health care provider. Patients should ask their health care provider about how to prepare for an upper GI series. During the procedure, the patient will stand or sit in front of an x-ray machine and drink barium, a chalky liquid. Barium coats the upper GI tract so the radiologist and gastroenterologist can see the organs’ shapes more clearly on x-rays. A patient may experience bloating and nausea for a short time after the test. For several days afterward, barium liquid in the GI tract causes white or light-colored stools. A health care provider will give the patient-specific instructions about eating and drinking after the test.

Endoscopy of the Intestines

Endoscopy of the intestines may include

  • colonoscopy with biopsy
  • flexible sigmoidoscopy with biopsy
  • upper GI endoscopy with biopsy

A gastroenterologist performs these tests at a hospital or an outpatient center.

  • Colonoscopy with biopsy – Colonoscopy is a test that uses a long, flexible, narrow tube with a light and tiny camera on one end, called a colonoscope or scope, to look inside the rectum and entire colon. In most cases, light anesthesia and pain medication help patients relax for the test. The medical staff will monitor a patient’s vital signs and try to make him or her as comfortable as possible. A nurse or technician places an intravenous (IV) needle in a vein in the arm or hand to give anesthesia.
  • Flexible sigmoidoscopy with biopsy – Flexible sigmoidoscopy is a test that uses a flexible, narrow tube with a light and tiny camera on one end, called a sigmoidoscope or scope, to look inside the rectum and the sigmoid colon. A patient does not usually need anesthesia. For the test, the patient will lie on a table while the gastroenterologist inserts the sigmoidoscope into the anus and slowly guides it through the rectum and into the sigmoid colon. The scope inflates the large intestine with air to give the gastroenterologist a better view. The camera sends a video image of the intestinal lining to a computer screen, allowing the gastroenterologist to carefully examine the tissues lining the sigmoid colon and rectum. The gastroenterologist may ask the patient to move several times and adjust the scope for better viewing. Once the scope reaches the end of the sigmoid colon, the gastroenterologist slowly withdraws it while carefully examining the lining of the sigmoid colon and rectum again.
  • Upper GI endoscopy with biopsy – Upper GI endoscopy is a test that uses a flexible, narrow tube with a light and tiny camera on one end, called an endoscope or a scope, to look inside the upper GI tract. The gastroenterologist carefully feeds the endoscope down the esophagus and into the stomach and first part of the small intestine called the duodenum. A small camera mounted on the endoscope transmits a video image to a monitor, allowing close examination of the intestinal lining. A health care provider may give a patient a liquid anesthetic to gargle or may spray an anesthetic on the back of the patient’s throat. A health care provider will place an IV needle in a vein in the arm or hand to administer sedation. Sedatives help patients stay relaxed and comfortable. This test can show blockages or other conditions in the upper small intestine. A gastroenterologist may biopsy the lining of the small intestine during an upper GI endoscopy.

How is Microscopic Colitis Treated?

Non – pharmacological

  • Drink plenty of fluids – Water is best, but fluids with added sodium and potassium (electrolytes) may help as well. Try drinking broth or watered-down fruit juice. Avoid beverages that are high in sugar or sorbitol or contain alcohol or caffeine, such as coffee, tea, and colas, which may aggravate your symptoms.
  • Choose soft, easy-to-digest foods – These include applesauce, bananas, melons, and rice. Avoid high-fiber foods such as beans and nuts, and eat only well-cooked vegetables. If you feel as though your symptoms are improving, slowly add high-fiber foods back to your diet.
  • Eat several small meals rather than a few large meals – Spacing meals throughout the day may ease diarrhea.
  • Avoid irritating foods – Stay away from spicy, fatty, or fried foods and any other foods that make your symptoms worse.

Medications

The gastroenterologist may prescribe medications to help control symptoms. Medications are almost always effective in treating microscopic colitis. The gastroenterologist may recommend eating, diet, and nutrition changes. In rare cases, the gastroenterologist may recommend surgery.

Medications

The gastroenterologist may prescribe one or more of the following:

  • Antidiarrheal medications – such as bismuth subsalicylate (Kaopectate, Pepto-Bismol), diphenoxylate/atropine (Lomotil), and loperamide. Initial management of symptoms includes antidiarrheal agents such as loperamide. These medications alone may be enough to control symptoms, but other medicines may be necessary for control.
  • Bismuth subsalicylate – If diarrhea continues to persist after 2 weeks, bismuth subsalicylate can be given at a dose of 524mg (3 tabs) 3 times daily.
  • Corticosteroids such as budesonide – (Entocort) and prednisone. If the patient continues to have three or more stools daily with at least one being watery, the addition of a glucocorticoid such as budesonide is a recommended therapy. Prednisone is another glucocorticoid that is an option for therapy; however, current research indicates that budesonide is more effective. With budesonide, 6 to 8 weeks of therapy is typically necessary for complete resolution. After this duration of therapy, the drug must be tapered. A typical dose starts at 9mg daily.
  • Anti-inflammatory medications –  such as mesalamine and sulfasalazine (Azulfidine)
  • Cholestyramine resin (Locholest, Questran)—a medication that blocks bile acids. Cholestyramine at a dose of 4g four times per day may help until diarrhea resolves. Cholestyramine is a bile acid-binding resin utilized for diarrhea with concurrent bile acid malabsorption, which can occur.
  • Antibiotics – such as metronidazole (Flagyl) and erythromycin, azithromycin
  • Immunomodulators –  such as mercaptopurine (Purinethol), azathioprine (Azasan, Imuran), and methotrexate (Rheumatrex, Trexall)
  • Anti-TNF therapies – such as infliximab (Remicade) and adalimumab (Humira). Other therapies then need to be pursued. Anti-tumor necrosis factor and immunomodulators currently have limited evidence from case series and need further research.
  • Corticosteroids – are medications that decrease inflammation and reduce the activity of the immune system. These medications can have many side effects. Scientists have shown that budesonide is safer, with fewer side effects than prednisone. Most health care providers consider budesonide the best medication for treating microscopic colitis.
  • Biological therapies – tumor necrosis factor-oe, such as infliximab, adalimumab, and certolizumab are available for the management of microscopic colitis, to get the disease under control, and long-term maintenance.
  • Bile Acid Sequestrants – These include colestyramine, colestipol, or colesevelam (which can contribute to diarrhea) such as cholestyramine/aspartame or cholestyramine (Prevalite), or colestipol (Colestid). If Microscopic Colitis is related to bile acid malabsorption (BAM), or you continue to have diarrhea despite other treatment, you may be offered this type of medicine.  These bind to the bile acids in your gut and help to improve symptoms of diarrhea. It has been suggested that this may be effective even where BAM isn’t present.
  • 5-aminosalicylic acid (5-ASA) drugs –  are the standard treatment in ulcerative colitis for induction and maintenance of remission of mild and moderate cases. The place of 5-ASA in the management of microscopic colitis is controversial. Immunomodulators including azathioprine, 6-mercaptopurine, and methotrexate, are the mainstay of treatment in maintenance therapy for patients with mild to moderately severe Crohn disease and frequently relapsing ulcerative colitis where 5-ASA drugs failed.
  • Pentoxifylline – Pentoxifylline, a xanthine oxidase derivative with anti-tumor necrosis factor (TNF)-alpha properties, has been used in alcoholic hepatitis and intermittent claudication and may play a role in the treatment of MC according to a recent case report. Nine patients with MC either refractory to, intolerant of, or dependent on budesonide received pentoxifylline 400 mg three times a day for a median of 3 months.
  • Probiotics – AGA recommends against treatment with Boswellia serrata as well as other probiotics. While there has been evidence showing some efficacy, including a single randomized controlled trial of 31 patients in which 44% of patients treated with Boswellia showed clinical improvement (however, no histologic or quality of life improvement) compared with 27% of patients treated with placebo, the results were not statistically significant. There is also concern about the lack of standardization between preparations of B. Serrata. Similar concerns apply to the wide variety of probiotics available on the market at present. A randomized placebo-controlled trial of Lactobacillus acidophilus LA-5 and Bifidobacterium animalis AB-Cap-10 failed to demonstrate a benefit over placebo.


Patients with microscopic colitis generally achieve relief through treatment with medications, although relapses can occur. Some patients may need long-term treatment if they continue to have relapses.

Surgery

  • Microscopic colitis surgery – are severe and medications aren’t effective, a gastroenterologist may recommend surgery to remove the colon. Surgery is a rare treat for microscopic colitis. The gastroenterologist will exclude other causes of symptoms before considering surgery. Surgical therapy for MC includes ileostomy, subtotal colectomy, and ileal pouch-anal anastomosis; however, data on this matter remain limited to individual reports.
  • Fecal transplant – Due to advances in the understanding of the gut microbiome, the fecal transplant has become a new therapeutic avenue in diseases such as Clostridium difficile. Its use in MC (specifically CC) has been examined in one case report of a patient refractory to budesonide who received three fecal transplants and achieved remission after the third for 11 months.

Eating, Diet, and Nutrition

To help reduce symptoms, a health care provider may recommend the following dietary changes:

  • avoid foods and drinks that contain caffeine or artificial sugars
  • drink plenty of liquids to prevent dehydration during episodes of diarrhea
  • eat a milk-free diet if the person is also lactose intolerant
  • eat a gluten-free diet

People should talk with their health care provider or dietitian about what type of diet is right for them.


Histopathological features of collagenous colitis and lymphocytic colitis.

Collagenous colitis Lymphocytic colitis
(1) Thickening of a subepithelial collagen layer of more than 10 um (1) Intraepithelial lymphocytosis (≥20 IEL per 100 surface epithelial cells)
(2) Inflammation in the lamina propria consisting of main lymphocytes and plasma cells (2) Inflammation in the lamina propria consisting of main lymphocytes and plasma cells
(3) Epithelial damage, such as flattening and detachment. (3) Epithelial damage, such as flattening and detachment
(4) Intraepithelial lymphocytosis (IEL) could be present but is not necessary for the diagnosis of CC (4) Subepithelial collagen layer not present or less than <10 um

Complications

Complications include:

  • Intestinal perforation
  • Bowel strictures, fistulas, abscess, and intestinal obstruction
  • Fecal incontinence
  • Pelvic abscess
  • enterocutaneous fistulas, particularly in Crohn disease
  • Pouchitis
  • Guillain-Barre syndrome (Campylobacter jejuni colitis, cytomegalovirus colitis, and reported in ulcerative colitis)
  • Hemolytic uremic syndrome (enterohemorrhagic E coli, Shigella)
  • Encephalopathy, seizures (Shigella)

References

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