Collagenous colitis presenting as spontaneous perforation in an 80 year old woman: Report of a Case

Perforation of the colon in CC may occur in two settings: 1) procedure-related (during or shortly following colonoscopy or barium enema), and 2) “spontaneous”, that is, unrelated to any intervention.

Although the first reported case of perforation was of the spontaneous type [4], subsequent reports have shown procedure-related perforations to be more frequent, with at least 22 reported cases [1, 10]. Patients with procedure-related perforations are mainly elderly women with a history of chronic diarrhea, with perforation occurring during the intervention or up to seven days afterwards [3, 5]. The endoscopist may note, presaging perforation, “a long, shallow, linear or serpiginous mucosal ulcer, appearing like a ‘crack’ or ‘fracture’ … usually orientated along the longitudinal axis of the colon and, in all cases, extended over several haustral segments” [11]. The right colon is the most common site, followed by the transverse colon, and, exceptionally, the left colon. As to pathogenesis, it is conjectured that the deposition of collagen in the lamina propria renders the mucosa stiff and non-distensible and therefore susceptible to “cracking” when, for example, air is introduced during colonoscopy, leading to perforation [1, 11].

Spontaneous perforation in CC has been described in five previous patients [4–8] (Table 1). In all cases except one (Freeman, [4]), photomicrographs are provided which demonstrate the characteristic histologic features of CC. All individuals have been female with a history of non-bloody diarrhea and no previous diagnosis of CC. Thus, colonic perforation was the initial manifestation of CC, with pathologic study of the resected bowel allowing diagnosis of the underlying disease. All patients recovered following resection of the perforated segment. Of note, all perforations occurred in the left colon, in contrast to the transverse/right-sided predominance in procedure-related perforations.

Reported cases of spontaneous perforation in collagenous colitis

CC collagenous colitis, F female

Regarding differential diagnosis, as the clinical findings of ischemic colitis (frequent) and CC with perforation (very rare) would seem to significantly overlap, diagnosis of CC will depend upon high clinical suspicion and histologic analysis of a biopsy or surgical resection specimen. Patients in both CC and IC tend to be middle-aged to elderly, with a female predominance in CC. IC classically presents with abdominal pain and blood in the stool, whereas CC is typified by frequent episodes of non-bloody diarrhea.

Risk factors for IC include a number of cardiovascular pathologies such as peripheral vascular disease, diabetes, dyslipidemia, heart failure and abdominal aortic aneurysm repair [12]. Risk factors for CC include autoimmune disease, malignancy, and organ transplantation [13]. Of the autoimmune diseases, celiac disease has the closest association (12.9-20 % of patients) [2, 13], with diabetes, thyroiditis, Sjogren’s syndrome, spondylitis and pyoderma gangrenosum also described. Both IC and CC are associated with use of various medications [12, 13]. Digoxin and aspirin have been implicated in IC (and, of the illicit drugs, cocaine). Of the large number of medications associated with development of CC, noteworthy are proton pump inhibitors, beta-blockers, angiotensin II receptor antagonists, aspirin, NSAIDs and selective serotonin reuptake inhibitors.

Colonoscopy and histologic examination both provide findings that will usually allow separation of IC from CC. The colonoscopic appearance of the mucosa in CC is usually normal, whereas IC features a range of abnormalities including erosions, longitudinal ulcerations, petechial hemorrhages, and necrosis, usually involving watershed areas of the splenic flexure and sigmoid.

Histologically, CC and IC are distinct entities. CC is characterized by thickening of the subepithelial collagen band, often associated with separation of the epithelium from the lamina propria, and lymphocytic infiltrates in the mucosa. IC at biopsy shows atrophic glandular crypts, hyalinizing fibrosis and often hemorrhage in the lamina propria with acute inflammation, micro-thrombi in the superficial capillaries, and, when severe, necrosis. Inflammatory pseudomembranes similar to those found in Clostridium difficile-associated pseudomembranous colitis may be present.

In the present case, the histologic findings typical of collagenous colitis were clearly present. However, as distinction from ischemic colitis is critical, we further examined the histologic sections with a view to eliminating concomitant ischemic colitis contributing to the clinico-pathological picture. A careful examination of the non-ulcerated mucosa showed no evidence of atrophic glandular crypts, hyalinizing fibrosis or hemorrhage in the lamina propria, or intra-capillary micro-thrombi. The absence of these changes allowed for confident exclusion of associated ischemic colitis. In contrast, photomicrographs in five of the six previously reported cases show the characteristic features of CC, but the authors did not explicitly address whether they considered ischemic colitis as a complicating factor (nor do the photomicrographs provided allow for exclusion of this complication). We believe it is worth keeping in mind that CC and IC should not be considered as mutually exclusive diagnoses.

Whereas risk factors, as described above, have been identified for iatrogenic perforation in CC, an explanation for spontaneous perforation is not so evident. One factor may be the degree of thickening of the collagen band, which in our case was focally severe, resulting in very tenuous integrity of the overlying epithelium. In this situation normal peristaltic activity or the repeated bowel movements characteristic of CC may have been sufficient to provide enough stress on the mucosa to lead to tearing and ulceration.

We conclude that, although decidedly rare, knowledge of spontaneous perforation as a possible complication of CC may be helpful in the evaluation and management of patients presenting with colonic perforation, especially those with risk factors for CC.