Collagenous colitis is a rare digestive disorder that primarily affects females and typically becomes apparent during middle age. The disorder is characterized by inflammatory changes of the mucous membranes (mucosa) of the colon (colitis) and abnormal accumulation (excessive deposition) of the protein collagen beneath the surface (epithelial) layer of the mucosa (thickened subepithelial collagenous bands). The colon is the major portion of the large intestine. The medical literature often refers to collagenous colitis as a form of "microscopic colitis," since evidence of inflammation and other abnormalities may only be confirmed through microscopic (i.e., histologic) examination of multiple tissue samples.
Individuals with collagenous colitis typically experience episodes of chronic, watery, nonbloody diarrhea. In some instances, episodes may often occur at night (nocturnal diarrhea). Diarrheal episodes may be persistent or may occur at intervals (intermittent) over a period of weeks, months, or years. Other symptoms and findings that may occasionally be associated with such episodes include vague abdominal pain, abdominal swelling (distension), nausea, vomiting, and/or weight loss.
The exact cause of collagenous colitis is unknown. Possible immunological, environmental, genetic, and/or other factors are under investigation as potential causes of the disorder.
The main symptom associated with collagenous colitis is chronic, watery (secretory), nonbloody diarrhea. “Watery diarrhea” is frequently used synonymously with the term “secretory diarrhea.” The latter refers to a large volume of watery diarrhea that may result from impaired absorption and/or increased secretion of water and certain electrolytes within body fluids. (Electrolytes are substances that split into electrically charged particles [ions] when dissolved in water. Such ions, including sodium, potassium, chloride, etc., play an essential role in regulating multiple bodily processes. For proper functioning, the concentrations of electrolytes must be maintained within certain limits; the body achieves this by moving electrolytes into and out of body cells.)
In many individuals with collagenous colitis, the onset of chronic diarrhea occurs gradually over time (insidious). However, in other cases, the onset may be sudden and abrupt (e.g., after an infection). Many affected individuals produce approximately four to nine watery stools daily. In addition, in some instances, episodes of diarrhea may often occur during the night (nocturnal diarrhea). In some affected individuals, diarrhea may be urgent, with an inability to control the passage of stool (fecal incontinence). In rare cases, the stools may contain an excessive amount of fat (steatorrhea).
Some individuals with collagenous colitis may have additional symptoms and findings in association with diarrheal episodes. These may include vague abdominal pain, cramping, abdominal swelling (distension), increased gas (flatulence), weight loss, nausea, vomiting, and/or fatigue. In some cases, severe attacks of chronic diarrhea may result in excessive loss of fluids from body tissues (dehydration) and excessive loss of certain electrolytes (e.g., sodium, chloride, potassium, magnesium). Associated symptoms may include severe thirst, decreased sweating and urine production, dry tongue and lips, headache, cramps, pale dry skin, confusion, dizziness, falling blood pressure, and/or other potentially serious findings.
In individuals with collagenous colitis, episodes of diarrhea may be persistent or may occur at intervals (intermittent) over a period of weeks, months, or years. According to reports in the medical literature, most affected individuals have a chronic intermittent course, with many experiencing temporary periods with normal bowel function. In addition, some affected individuals may experience a long-term cessation of symptoms (remission), in some cases without having received treatment. However, relapses can occur.
In some cases, collagenous colitis may occur in association with certain other conditions, such as inflammation of joints (arthritis); certain inflammatory conditions of the eyes (uveitis); other digestive (gastrointestinal) diseases (e.g., celiac sprue); certain disorders in which the body’s natural defenses against invading microorganisms mistakenly attack healthy tissue (autoimmune disorders, e.g., certain thyroid gland disorders); pernicious anemia; and/or other disorders. The implications of these findings are not fully understood. (For more information on celiac sprue, see the “Related Disorders” section below. For more information on pernicious anemia, choose “pernicious” as your search term in the Rare Disease Database.)
The exact cause of collagenous colitis is unknown. Possible immunological, environmental, genetic, and/or other factors are under investigation as potential causes of the disorder.
Evidence suggests that certain pain-relieving (analgesic) drugs that also help to reduce joint inflammation (nonsteroidal anti-inflammatory drugs [NSAIDs]), such as those widely used to relieve symptoms of arthritic disorders, may be a factor in causing or aggravating collagenous colitis in some cases. Some studies have demonstrated that significant numbers of individuals with collagenous colitis were regularly using NSAIDs at the time of their diagnosis (as compared to individuals without the disorder). However, although NSAIDs are commonly used in the general population, collagenous colitis rarely occurs. Therefore, researchers stress that additional factors, such as genetic predisposition, may play a role in causing the disorder.
Collagenous colitis has been reported in more than one family member (e.g., siblings) in a few cases, supporting the possibility of genetic susceptibility as a factor in some cases. A person who is genetically predisposed to a disorder carries a gene (or genes) for the disease, but it may not be expressed unless it is triggered or “activated” under certain circumstances, such as due to particular environmental factors (multifactorial inheritance).
Some researchers suggest that, in some cases, infection with certain invading bacteria may cause the initial injury to mucous membranes (mucosa) of the colon, leading to inflammation and abnormal collagen deposition. In addition, some speculate that the abnormal accumulation of collagen beneath the surface layer of the colon’s mucous membranes (subepithelial collagen bands) occurs as part of the body’s repair process in response to such chronic inflammation. Collagen, the body’s major structural protein, forms an essential part of connective tissues. Others suggest that the thickened collagen bands may result due to a primary or local abnormality in the production of collagen (since the composition of the collagen found in the colon’s mucous membranes is of a different type from that normally found in individuals unaffected by the disorder).
In addition, evidence suggests that improper bile salt absorption may, in some cases, injure cells in the colon’s mucous membranes, potentially playing a role in causing collagenous colitis. Bile, a liquid secreted by the liver, includes bile salts, which play a role in breaking down and absorbing fats during digestion. According to reports in the medical literature, underlying bile salt malabsorption is common in individuals with collagenous colitis, with many benefiting from treatment with cholestyramine, a drug that acts on the liver’s bile acids. (For more information on cholestyramine, see the “Standard Therapies” section below.)
As discussed above, in some cases, certain autoimmune disorders may occur in association with collagenous colitis. Autoimmunity occurs when the body’s natural defenses against invading microorganisms mistakenly attack healthy tissue. As a result, some researchers speculate that autoimmune factors may also play some role in causing collagenous colitis. However, studies to date have not provided conclusive evidence supporting autoimmunity as a cause of the disorder.
Further studies are needed to determine the potential role(s) that immunological, environmental, genetic, and/or other factors may play in causing collagenous colitis.
Researchers suggest that the chronic, watery diarrhea associated with collagenous colitis may be directly related to inflammatory changes of the mucous membranes of the colon (rather than the thickened subepithelial collagen bands), with the diarrhea resulting from decreased intestinal absorption of water and electrolytes. As noted above, watery (secretory) diarrhea results when the intestines secrete more water and electrolytes than they absorb.
Collagenous colitis is a rare disorder that was originally reported in the medical literature in 1976 (Lindstrom CG). Estimates suggest that the disorder may be up to 10 times as common in females as males. Collagenous colitis generally becomes evident in middle age at approximately 60 years of age or greater. However, the disorder may develop at any age. According to reports in the medical literature, the disorder has been diagnosed in young children and in adults in their mid-80s. Several hundred cases of the disorder have been reported in the literature.
Because the characteristic symptoms of collagenous colitis are also associated with many other disorders, several specialized tests may be needed to exclude other disorders and confirm a diagnosis of collagenous colitis. When an individual exhibits such symptoms as chronic, watery, nonbloody diarrhea, screening tests may often include x-ray procedures; blood, hormone (endocrine), and stool (fecal) evaluations; testing for microorganisms; and/or colonoscopy, visualization of the mucosal lining of the colon through the use of an illuminated instrument (endoscope). In individuals with collagenous colitis, such studies will usually provide normal results. In rare cases, blood tests may reveal a decrease in the levels of the oxygen-carrying compound (hemoglobin) in red blood cells (anemia). Rarely, fecal evaluations may reveal that the stools contain an excessive amount of fat (steatorrhea). In addition, in most cases, the digestive tract will appear normal by colonoscopy. Therefore, such testing usually helps to eliminate several other disorders in the process of obtaining a differential diagnosis.
According to the medical literature, to definitively obtain a diagnosis of collagenous colitis, further testing must include removal (biopsy) and microscopic evaluation of multiple tissue samples obtained from various portions of the different segments of the colon and the rectum. The biopsy samples may be retrieved during colonoscopy, which, as noted above, enables examination of the mucosal lining of the entire colon. The colon, the major portion of the large intestine, forms a large loop that consists of four segments: ascending colon, transverse colon, descending colon, and sigmoid colon. The rectum forms the lowest portion of the colon that joins with the anal canal.
In individuals with collagenous colitis, microscopic examination of such tissue samples may reveal injury of cells in the surface layer (epithelium) of the colon's mucous membranes (mucosa), with inflammatory changes of the epithelium and the underlying connective tissue layer (lamina propria) and abnormal deposition of the protein collagen beneath the surface layer (thickened subepithelial collagenous bands).
The treatment of collagenous colitis may require the coordinated efforts of a team of medical professionals, such as internists (or, in rare cases, pediatricians), physicians who diagnose and treat disorders of the digestive system (gastroenterologists), and/or other health care professionals.
Because studies are limited, further research is needed to evaluate the long-term safety and effectiveness of various treatment options; to determine the most appropriate, optimal therapeutic measures; and to learn more about the variable severity and course of the disorder.
Because it is important to prevent the dehydration and electrolyte loss that may be associated with severe diarrhea, treatment is directed toward alleviating diarrhea. According to the medical literature, initial recommended treatment may include the use of antidiarrheal medications, such as loperamide, and the withdrawal of any nonsteroidal anti-inflammatory drugs (NSAIDs) or other medications that may play a role in causing the disorder. Loperamide is a drug that may alleviate diarrhea by acting directly on intestinal muscles to inhibit peristalsis, thereby diminishing fluid and electrolyte loss. (Peristalsis refers to the rhythmic contractions of involuntary muscle that propel food and waste materials through the digestive tract.)
If symptoms continue, some affected individuals may benefit from the use of certain anti-inflammatory medications known as 5-aminosalicylic acid (5-ASA) derivatives, such as sulfasalazine or other agents for those who cannot tolerate sulfasalazine (e.g., olsalazine).
If such therapy is not effective, physicians may recommend treatment with cholestyramine, particularly for those with bile acid malabsorption. Cholestyramine is a medication that acts on the liver's bile acids and serves to lower blood cholesterol levels.
Affected individuals who do not benefit from the use of such medications or who have extremely severe symptoms may receive therapy with certain corticosteroids (e.g., prednisone, prednisolone). Due to their potential adverse effects, such agents should be reserved for those without a response to the above agents (e.g., 5-ASA derivatives, cholestyramine). In addition, reports indicate that relapses often occur when such therapy is lowered in dosage or discontinued.
In some cases, if diarrhea is resistant (refractory) to the above therapies, treatment may be recommended with other agents that may be effective in some cases. Such medications may include certain antibiotics (e.g., metronidazole); the antidiarrheal agent bismuth subsalicylate (e.g., Pepto-Bismol); the corticosteroid budesonide, which has low “whole body” (systemic) effects as compared to certain other steroids; the synthetic antidiarrheal agent octreotide; or the immunosuppressant agent, methotrexate. Other immunosuppressants that may be useful include 6-mercaptopurine and azathioprine.
In rare, severe cases, if drug therapies fail to relieve symptoms, surgical intervention may be recommended.
In refractory cases, experts advise that other potential causes of diarrhea must be considered and excluded (e.g., celiac disease, persistent NSAID use, chronic infection, etc.). Additional treatment for this disorder is symptomatic and supportive.
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