Collagenous colitis, a subtype of microscopic colitis, is a chronic inflammatory disease of the colon and is associated with abnormal collagen metabolism and inflammation of the colon. Colonoscopic and radiographic examinations of collagenous colitis are usually normal, hence a colonic biopsy is required to make a definite diagnosis. Microscopic colitis has been linked to smoking as a risk factor, and it is thought to be related to some pharmaceutical exposure, such as nonsteroidal anti-inflammatory drugs, proton pump inhibitors, and selective serotonin reuptake inhibitors. The epidemiology of collagenous colitis is only 2.0 to 10.8 per 100,000 persons and is estimated to be higher in northern Europe and America. However, cases are relatively rare in eastern countries, including Taiwan.
We report the case of a 51-year-old man with no known underlying disease, who had watery diarrhea for 2 months before presenting to our clinic. He was initially diagnosed with unspecified functional bowel disorder, but further analysis at follow-up revealed collagenous colitis.
2 Case report
A 51-year-old man with no known underlying disease visited our clinic for treatment of diarrhea that had been ongoing for 2 months. The stool was light brown and watery, and bowel movement occurred 4 to 5 times per day. Diarrhea was exacerbated especially after meals. The patient did not report abdominal pain, or bloody or tarry stools. He also did not report any history of relevant travel, occupational risks, contact with other individuals, or any allergy to medication or food that may have explained his symptoms. Prior to these symptoms, he had regular stool movements once to twice per day with normal stool shape and characteristics. The patient did not report alcohol or betel nut consumption but had smoked one pack of cigarettes per day for 30 years up until 3 months prior. He also took Chinese herbal medicines to maintain liver function. Family history revealed no malignancies or significant gastrointestinal tract disorders.
Initially, esophagogastroduodenoscopy and colonoscopy were performed. We observed reflux esophagitis, chronic gastritis with Helicobacter pylori infection, terminal ileum ulcers, and patchy dark blue pigmentation of the colonic mucosa (Fig. 1) with non-specific chronic inflammatory infiltration and bacterial clump identified by histologic examination. We first treated the Helicobacter pylori infection and subsequently the unspecified functional bowel disorder by medication, diet education, and lifestyle modification. Regular follow-up appointments were scheduled after this initial treatment. After the 6-month follow-up visit, the patient responded poorly to our treatment. He reported the persistence of diarrhea, leading to disturbed sleep quality. Blood tests, including infection parameters and autoimmune profiles, revealed nearly normal results, except for slightly elevated serum immunoglobulin A levels. Stool examination showed no specific findings and was negative for parasitic infections. Abdominal computed tomography revealed no significant abnormalities. Therefore, we suggested that the patient stop the consumption of the Chinese herbal medicine. A second colonoscopy was performed after 10 months of treatment.
In this follow-up colonoscopy, terminal ileum ulcers and patchy pigmentation of the colonic mucosa were still present. Eleven random mucosal specimens were collected from the terminal ileum and all colon segments in this colonoscopy examination. Pathological examination of the colonic biopsy revealed that the colonic mucosa had preserved crypt architecture, lymphocyte and eosinophil infiltration in the lamina propria and a thickened layer of subepithelial collagen, which was positive for Masson's trichrome staining, leading to the diagnosis of collagenous colitis (Fig. 2). Based on this diagnosis, we not only discontinued all anti-diarrheal medicines and administered mesalamine 1600 mg twice daily, but also encouraged him to quit smoking. The patient recovered to normal bowel movements after two weeks of treatment adjustment, and no more recurrent diarrhea was noted under mesalamine use in one-year outpatient follow-up.
The clinical manifestation of collagenous colitis is characterized by chronic, watery, and non-bloody diarrhea. Pathogenesis could be associated with abnormal collagen metabolism, which causes increased production of nitric oxide in the colonic epithelium, inducing secretory diarrhea. This typically occurs in middle-aged patients, and although it is three times more prevalent in females than in males, our case study is of a male patient. Generally, the colonic mucosa appears normal or almost normal in the colonoscopy examination of patients with collagenous colitis. The first colonic biopsy did not identify the subepithelial collagen deposition lesions. This could be attributed to the patchy distribution of histological changes associated with the lesions, and the differences in clinical judgement between pathologists. Moreover, the clinical manifestations of unspecified functional bowel disorders and collagenous colitis can be easily confused. Both conditions can present with chronic diarrhea, abdominal pain, and bloating. Therefore, tissue examination is exceptionally important for identification. However, the challenge facing endoscopists in the diagnosis of collagenous colitis is the absence of macroscopic features on colonoscopy. To improve diagnostic sensitivity, we took multiple random biopsies throughout the colon to obtain more specimen in the follow-up colonoscopy. This method is proven to be able to enhance diagnostic accuracy according to the American Society for Gastrointestinal Endoscopy recommendations. Some autoimmune diseases, such as celiac disease, autoimmune thyroid disease, and Sjögren's syndrome, could also be concomitant with collagenous colitis. In our patient, no parenteral symptoms, such as fatigue, itchy rashes, ataxia, arthralgia, tachycardia and perspiration which might be seen in collagenous colitis patients, were observed, other than abnormal levels of serum immunoglobulin A, which has no diagnostic relevance to autoimmune diseases and collagenous colitis. It is worth noting that cigarette smoking is a well-known contributing factor for the pathogenesis of the disease, which can exacerbate watery diarrhea, and decrease the likelihood of achieving clinical remission.[12,13] Therefore, the cessation of cigarette smoking accompanied with lifestyle modifications can be extremely beneficial for the clinical course of disease.
Finally, in patients with symptomatic microscopic colitis, the American Gastroenterological Association recommends treatment with budesonide over mesalamine to induce clinical remission. We chose mesalamine instead of budesonide as the first-line treatment because the payment policy of the Taiwan National Health Insurance Administration regulates budesonide use only after mesalamine failure.
In conclusion, collagenous colitis is a rare etiology of chronic diarrhea, which can only be diagnosed by pathology of colonic mucosa. Consequently, repeat colonoscopy with multiple stepwise random colonic biopsies at suspicious lesion sites or even normal-appearing mucosa should be considered in refractory chronic diarrhea patients without established diagnoses.
The authors thank the patient described for allowing us to share his details, and also thank Department of Pathology of Kaohsiung Medical University Hospital to provide the pathology images of the patient.
Jiunn-Wei Wang was involved with patient assessment, examination, medication prescription, and follow-up. Ping-Ju Wu, Chien-Chieh Lin and Jiunn-Wei Wang reviewed the available literatures. Ping-Ju Wu and Chien-Chieh Lin drafted the manuscript. Jiunn-Wei Wang made corrections to the drafted manuscript. All authors have read and approved the manuscript.
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