Summary of the mucosal abnormalities associated with collagenous colitis.
Microscopic colitis (MC) are clinical pathologic entities characterized by secretory-like aqueous chronic diarrhea, in its large majority without hematochezia. From the first descriptions of MC, normal endoscopic and radiological findings have been a pathognomonic feature. It is thought that up to 20% of adults with chronic diarrhea who have an endoscopically normal colonoscopy may have MC.
Most common MC are collagenous colitis and lymphocytic colitis. They are two morphologically distinct entities of MC. They are similar in presentation but differ histologically. Endoscopic biopsy is required for the diagnosis of MC. As there are usually no mucosal abnormalities, the biopsies taken must be random. However, several authors have described different mucosal abnormalities related to the MC, most of them related to collagenous colitis.
Our aims were to review the medical literature and to describe the mucosal patterns and mucosal abnormalities that have been associated with the microscopic colitis, especially those related to the collagenous colitis.
A MEDLINE search (1966-December 2010), was done using the terms "Colitis, Microscopic"[Mesh] or "Colitis, Collagenous"[Mesh] or "Colitis, Lymphocytic"[Mesh] and "Endoscopy, Digestive System"[Mesh] or "Endoscopy, Gastrointestinal"[Mesh] or "Colonoscopy"[Mesh] to find relevant articles. The search was carried out without restrictions or limits. The selection process of the articles was done independently by both authors. Agreement was measured using kappa coefficient (k). First, relevant studies were selected by the title (k 0.80, CI95% 0.63-0.97) and differences were resolved by consensus. Then, the fulltexts of selected articles were read.
2. Role of endoscopy in microscopic colitis
Endoscopy is essential for the diagnosis of microscopic colitis. The diagnosis of microscopic colitis is based on mucosal biopsies taken during colonoscopy at the appropriate sites. It is essential to take colonic biopsies when endoscopic examinations are carried out in the clinical context of chronic diarrhea, even if the functional nature of the diarrhea is suspected. By definition, the colonic mucosa has an endoscopically normal appearance in microscopic colitis. However, some authors have reported endoscopic abnormalities and mucosal patterns in patients with MC (see below).
2.1. Colorectal biopsy samples: where and how much?
Histological abnormalities in MC are generally pancolonic as they can be distributed throughout the colon as well as limited to the right colon. In collagenous colitis, thickening of the subepitelial collagen band is in some cases more marked in the proximal colon than in the distal colon. The two endoscopically normal sites in which biopsies should be taken for optimal diagnosis of MC are the ascending colon and the sigmoid colon. Three to four biopsies should be taken per site.
3. Mucosal patterns and mucosal lesions associated to microscopic colitis
In the colonoscopy, the colonic mucosa has usually a normal aspect or it can present minimum and unspecific abnormalities such as erythema patches, edema or alterations in the vascular pattern.
In our search, we found several case reports and case series of endoscopic findings that would suggest the presence of this type of colitis, most of the findings related to collagenous colitis. In Table 1 there is a summary of the different endoscopic manifestations of the collagenous colitis and the authors of these findings.
|Author||Colorectal findings in collagenous colitis|
|Richieri et al (1993)||mucosal tears|
|Katsinelos et al (1997)||multiple red spots|
|Sato et al (1998)||spindle network pattern|
|Cruz−Correa et al (2002)||mucosal tears|
|Buchman et al (2004)||pseudomembranous collagenous colitis|
|Koulaouzidis et al (2006)||mucosal tears and scars|
|Tysk et al (2006)||mucosal tears, longitudinal mucosal lacerations|
|Smith et al (2007)||mucosal tears on insufflattion, colonic perforation|
|Allende et al (2008)||bleeding linear ulcers, colonic perforations|
|Hashimoto et al (2008)||linear ulcers, scar−like areas; crowded vascularity of the colonic mucosa and dilated, circling or winding blood capillaries|
|Dunzendorfer et al (2008)||mucosal tears|
|Umeno et al (2008)||linear mucosal defects|
|Couto et al (2009)||scars; mucosal tears, superficial lacerations or ‘‘cat scratches’’ enhanced with air insufflation during colonoscopy|
|Hashimoto et al (2009)||mucosa similar to ischemic colitis|
|Cimmino et al (2010)||colorectal mosaic pattern|
|Nomura et al (2010)||linear mucosal defects|
3.1. Mucosal tears
Mucosal tears were the most frequent endoscopic findings in our search. The terms “linear mucosal defects” have been used by several authors to describe mucosal tears and sharp longitudinal ulcers (characteristic colonoscopic findings in patients with collagenous colitis).
In 2006, Koulaouzidis et al.  described discrete linear mucosal breaks in the caecum after gentle insufflation, suggesting that this mucosal tears in the colon could occur spontaneously in patients with collagenous colitis.
In the same year, Curl Tysk et al. reviewed the medical literature and reported longitudinal mucosal lacerations in the colon of patients with collagenous colitis (Figure 1 and 2), emphasizing that these lesions may be a sign of underlying collagenous colitis, and that mucosal biopsies should be obtained to confirm the diagnosis. Based on the previous reports that they had found, they advised that these lesions might be associated with an increased risk of colonic perforation, and that the colonoscopist should be aware that the risk of perforation is likely to be increased.
In 2008, Hashimoto et al  described a surprising finding in a patient with chronic diarrhea: a 20 cm long linear ulcer or scar like area of mucosal damage without bleeding in the descending colon. The biopsies taken revealed that it was a collagenous colitis.
In 2009, Couto et al  suggested that the scars found in the colonic mucosa were signs of scaring of previous spontaneous mucosal tears, superficial lacerations or ‘‘cat scratches’’ enhanced with air insufflation during colonoscopy in patients with collagenous colitis.
3.1.1. Drugs associated with mucosal tears
Umeno et al  and Nomura et al  have associated the presence of these linear mucosal defects to the drug lansoprazole, a proton bomb inhibitor. They found that linear mucosal defects and friable mucosa may be characteristic colonoscopic findings in cases of lanzoprale-associated collagenous colitis (Figure 2).
3.1.2. Risk of colonic perforation in patients with collagenous colitis
Several authors have suggested that patients with collagenous colitis have an increased risk of colonic perforation during the colonoscopy procedure. Most of them agree that the mucosal tears might be the initial lesion of the perforations.
Sherman et al  and Smith et al  found mucosal tears (linear “fractures” of the colon) following diagnostic colonoscopies in patients with severe collagenous colitis. They theorized that the stiffness of the colon in areas of collagenous colitis with submucosal fibrosis could made it susceptible to linear "fractures" during colonoscopic air insufflation with subsequent transmural air dissection. They urged extreme caution if these lesions were recognized at colonoscopy and recommended aborting the examination and obtaining plain radiographs to detect free intraperitoneal air.
Allende et al  published the largest series up to date about 12 patients with collagenous colitis complicated with colonic perforations. In their series the most outstanding colonoscopic findings were bleeding linear ulcers. They observed that the colon in collagenous colitis perforates not only with colonoscopy, but also with barium enema. Colonoscopic perforations were more common than barium enema, probably due to its higher intraluminal pressures. They thought that marked collagenous colitis severity was implicated as a risk factor for perforation. They found that the right colon was the most common perforation site, corresponding to its preferential involvement by collagenous colitis and predisposing physical properties of the right colonic wall.
In 2010, Hussain et al  published a systematic review about the colonic perforations in patients with collagenous colitis. They did an exhaustive and systematic search and found 21 case reports of colonic perforation, mainly following colonoscopy. The site of colonic perforations and mucosal tears were predominantly in the right colon.
3.2. Other mucosal abnormalities
In 1997, Katsinelos et al  reported the presence of multiple red spots in the lower part of the ascending colon in a patient with chronic diarrhea. The histological examinations of the biopsies taken from this pathological area showed it was a collagenous colitis.
In 1998, Sato et al  reported a spindle network pattern after indigo carmine dye-spraying, in association with collagenous colitis.
In 2004, Alan Lewis Buchman et al  described an interesting endoscopic manifestation of collagenous colitis in two patients with chronic diarrhea: pseudomembrane formations (Figure 3) in the absence of Clostridium difficile infection. They used the term of “pseudomembranous collagenous colitis”.
In 2008, Hashimoto et al  reported numerous crowded, small, dilated, circling or winding blood vessels on the mucosal surface of the entire colon, especially the transverse colon (appearing like a spider web) in association with this type of colitis.
In 2009, Hashimoto et al  found an actively hemorrhagic linear ulcer and a linear ulcer scar in a woman with abrupt onset of lower abdominal pain and heavy blood in her stool. Histopathological examination of biopsy samples taken showed subepithelial collagen bands and the diagnosis of collagenous colitis was made. They thought it was a case of lansoprazole-associated collagenous colitis with a unique presentation similar to an ischemic colitis.
In 2010, Cimmino et al  described a mosaic pattern as an endoscopic finding in the collagenous colitis (Figure 4). They compared the presence of this mosaic pattern in patients with chronic diarrhea, and they found that the presence of this colorectal mosaic pattern would have a high specificity (99%) and a high positive likelihood ratio (LR+ 17) for the diagnosis of collagenous colitis in patients with chronic diarrhea who undergo a colonoscopy.
4. The future of endoscopy in microscopic colitis
Endomicroscopy is a newly developed endoscopic modality, which allows in vivo microscopy of the mucosal layer in about 1000-times magnification with subcellular resolution during ongoing gastrointestinal endoscopy. This technique enables subsurface imaging of living tissue during ongoing endoscopy and allows confocal microscopy in addition to standard video endoscopy.
Kiesslich et al  showed that endomicroscopy allows localization and measurement of the amount of collagenous bands in the mucosal layer, offering the possibility of targeted biopsies, which would be a new approach in collagenous colitis.
The term microscopic colitis includes the collagenous colitis and the lymphocitic colitis, both entities are characterized by chronic diarrhea and normal colonoscopy, and the diagnosis is confirmed by biopsies taken at random. In recent years, abnormalities in the mucosa, mainly related with collagenous colitis, have been described. In Table 1 we summaries the mucosal patterns and the endoscopic manifestations which have been associated with collagenous colitis. Most of the reports mentioned the mucosal tears as the most frequent abnormality. Scars following mucosal lacerations were also a frequent finding. The risk of colonic perforations seems to be slightly higher in patients with collagenous colitis during colonoscopy. The main reason appears to be the lacerations done during air insufflations in the procedure. Other endoscopics findings were blood vessels alterations, pseudomembranes and mosaic pattern.
Several mucosal patterns and mucosal abnormalities have been reported in association with collagenous colitis. Knowledge of these endoscopic manifestations of the collagenous colitis could help to a better understanding of this disease and to target the colonic biopsies.
We want to thank Dr. Curl Tysk, Dr. Eiki Nomura and Dr. Alan Lewis Buchman for providing us the pictures and photos of their endoscopic findings. They have been very kind.