Collagenous Colitis in a Patient With Chronic Diarrhea: An Underdiagnosed and Undertreated Condition
Key words: Abdominal pain, budesonide, collagenous colitis, corticosteroids, diarrhea, weight loss.
Diarrhea is one of the most common and frequently reported gastrointestinal symptoms. Common causes of diarrhea include infection, irritable bowel syndrome, lactose intolerance, inflammatory bowel disease, celiac disease, colon cancer, pancreatic cancer, carcinoid syndrome, hyperthyroidism, and medication effects. Microscopic colitis, a type of inflammatory bowel disease that includes collagenous colitis and lymphocytic colitis, is increasingly recognized as a major cause of persistent diarrhea, especially in middle-aged and elderly persons. This condition is an idiopathic, clinicopathologic syndrome of chronic, watery, nonbloody diarrhea that is associated with normal laboratory studies, radiology findings, and colonoscopy findings, but with characteristic histopathologic changes. Weight loss, abdominal pain and cramping, and fatigue are common in persons with the condition.
It should be noted that there is some difference of opinion regarding how microscopic colitis is classified, with some researchers considering collagenous colitis and lymphocytic colitis as distinct entities, whereas others consider them different phases of the same condition.1 Collagenous colitis, the focus of this article, is characterized by a thickened subepithelial band of collagen in the colonic mucosa, in association with mononuclear inflammatory cells in the lamina propria, as shown in Figure 1. Collagen is not affected in persons with lymphocytic colitis; tissue samples show an increase of lymphocytes between the cells that line the colon.2 A list of the clinical features of collagenous colitis is provided in Table 1.3
Collagenous colitis has a high rate of spontaneous resolution and relapse, making it difficult to diagnose, and effective treatment options are limited. We present the case of an 82-year-old woman with a 10-year history of collagenous colitis, marked with numerous remissions and relapses. Information on the course, prognosis, diagnosis, and management of collagenous colitis is provided in the discussion.
An 82-year-old woman presented to our clinic in 2006 with episodic, light-brown, nonbloody, watery diarrhea daily for 2 weeks. She had been having these episodes approximately 10 times per year for the past 10 years, with a gradual weight loss of approximately 10 to 15 lb. Her diarrhea was associated with flatus, nausea, abdominal pain, bloating, fatigue, and leg cramps. The patient reported that citrus fruit, milk, and nonsteroidal anti-inflammatory drugs (NSAIDs) aggravated her symptoms and that bland food (eg, potatoes, bread, rice) relieved them. She had not traveled outside of her local area, had not used an antibiotic, and had no knowledge of contact with any sick persons.
Her medical history was significant for Raynaud’s phenomenon, osteoarthritis, hypertension, atrial fibrillation, esophageal reflux, and stroke. Her current medications were hydrochlorothiazide, benazepril, atenolol, propoxyphene/acetaminophen (no longer available in the United States), potassium chloride, clopidogrel, nisoldipine, and esomeprazole. The physical examination revealed a thin woman with a body mass index of 19.5 kg/m2 and stable vital signs. Pertinent findings included a soft, nondistended abdomen with no mass or tenderness observed on palpation. Bowel sounds were normal on auscultation. The patient reported arthritic changes in her fingers for several years.
Laboratory testing performed earlier that year at a different institution yielded unremarkable results, including a normal complete blood cell count, comprehensive metabolic panel, thyroid-stimulating hormone level, vitamin B12 level, stool studies (including for Clostridium difficile toxins A and B), and serology test results. An abdominal and pelvic computed tomography scan from 2005 did not show any inflammatory changes around the patient’s cecum. A colonoscopy performed in 2001 (5 years after the onset of symptoms) had revealed completely normal–appearing mucosa up to the cecum; however, random biopsies of tissue obtained throughout the colon were consistent with collagenous colitis, but were either not recognized as collagenous colitis at the time or the patient was lost to follow-up. The patient had tried loperamide in the past without success. No other specific pharmacotherapy for collagenous colitis had been tried.
The patient had learned to live with her symptoms and was somewhat resigned to having them for the rest of her life; however, her chronic diarrhea was impairing her quality of life and limiting her social interactions. Therefore, she sought to get another opinion and established care with our institution after having had primary care with another physician in another health system for a number of years.
Upon making the diagnosis, we made the patient aware of dietary triggers, such as caffeine and dairy products, and started her on a 6-week course of budesonide sustained-release (SR), with 9 mg daily for 2 weeks, then 6 mg daily for 2 weeks, and then 3 mg daily for 2 weeks. Within 5 weeks, the patient was experiencing a dramatic reduction in stool frequency, having a bowel movement one to two times per day, and her stool was less watery, leading to improved quality of life. Five months after the treatment ended, her weight had stabilized without use of nutritional supplements and her diarrhea improved, but was occasionally aggravated by certain foods that contained high amounts of sodium, such as soy sauce. The patient’s esomeprazole for her esophageal reflux was stopped because it was determined to be a possible offending medication. She relapsed several months later, and budesonide SR was restarted.
First described in 1976 by Lindstrom,4 collagenous colitis often remains undiagnosed for several years after the onset of symptoms and, even after it is diagnosed, it may remain untreated for several years, as occurred with the case patient. The exact etiology of microscopic colitis is unknown. Some theories include drug effects, bacteria, smoking, and concurrent autoimmune disorders, such as celiac disease (Table 2).5-9
Although collagenous colitis is generally less common and less severe than other types of inflammatory bowel disease, such as Crohn’s disease and ulcerative colitis, its incidence is increasing, and it affects older women more often than older men. In a 2007 population-based study conducted in Minnesota from 1985 to 2001, the incidence of microscopic colitis increased significantly from 1.1 per 100,000 early in the study to 19.6 per 100,000 by the end of the study (P<.001).10 This incidence reported at the conclusion of the study exceeded that of Crohn’s disease and ulcerative colitis. Also, the incidence rates increased statistically with age (P<.001), with researchers calculating a peak annual incidence of 37 per 100,000 at age 80 years and older. The prevalence of microscopic colitis was reported as 103 per 100,000. By subtype, the incidence of collagenous colitis was 3.1 per 100,000 and was associated with being a woman, as 87% of study participants were women (P<.001), and the median age at diagnosis was 70 years. The prevalence of collagenous colitis was 39.3 per 100,000.10 Similar results and trends, some of which have been statistically significant, have been observed in other studies from Europe. For example, a 2004 Swedish epidemiologic study showed an incidence peak for collagenous colitis of 26.9 per 100,000 in women aged 60 to 69 years, which was as high as the incidence of ulcerative colitis, and the annual incidence of collagenous colitis increased during the study.11 Also, researchers found that the diagnostic yield was higher in older patients, and microscopic colitis was diagnosed in nearly 20% of persons older than 70 years.