Collagenous Enterocolitis: A Rare Condition with Simultaneous Involvement of the Upper and Lower Gastrointestinal Tract

1. Assistant Professor, Department of Pathology, Seth GS Medical College and KEM Hospital, Thane, Maharashtra, India. 2. Fellow, Department of Pathology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India. 3. Fellow, Department of Pathology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India. 4. Resident, Department of Pathology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India. 5. Associate Professor, Department of Pathology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India.

Abstract

Collagenous colitis is a form of microscopic colitis, while Collagenous Sprue (CS) is a malabsorptive disorder that mimics celiac disease. Both conditions show increased Intraepithelial Lymphocytes (IELs) and basement membrane thickening due to collagen deposition. The simultaneous occurrence of both disorders is rare, and only a few such cases have been reported in the literature. A 60-year-old female presented with chronic, non bloody diarrhoea persisting for two years. Investigations revealed megaloblastic anaemia and hypoalbuminaemia. Gastroenteroscopy showed flattening and atrophy of the small intestinal mucosa. Biopsy results showed increased IELs, normal crypt architecture, and stripping of the epithelium. There was also patchy deposition of hyalinised band subepithelially, confirmed to be collagen through Masson’s stain. As both the upper and lower Gastrointestinal (GI) tracts were involved, a diagnosis of collagenous enterocolitis was made. A 70-year-old female presented with intermittent watery diarrhoea for the past 10 days, accompanied by urgency and tenesmus. She had a history of colicky abdominal pain four years ago, which improved with steroids, but the symptoms recurred. Clinically, she was considered to have inflammatory bowel disease, with recurrent anaemia. Both gastroduodenoscopy and colonoscopy were normal. Mapping biopsy showed increased IELs and focal atrophy in the duodenum, while the colon exhibited mild mononuclear inflammation with occasional minimal activity. Focal, irregular deposition of subepithelial collagen was also observed and confirmed through Masson’s stain. A diagnosis of collagenous enterocolitis was made. She is currently being monitored for any recurrence of symptoms, after which steroid treatment will be initiated. Collagenous colitis, CS, and collagenous duodenitis share similar histological features and can rarely co-exist. Further studies are needed to better understand their aetiology and association.

Collagenous sprue, Intraepithelial lymphocytes, Malabsorption, Microscopic colitis, Subepithelial collagen

Case Report

Case 1

A 60-year-old female, known to be diabetic and hypertensive, presented with watery diarrhoea for the past two and a half years, sometimes occurring at night, with a stool frequency of 4-5 times per day and associated urgency. There is no history of blood or mucus in the stool, tenesmus, or incontinence. Laboratory investigations revealed megaloblastic anaemia {Haemoglobin: 6.6 gm/dL, Mean Corpuscular Volume (MCV): 108 fL} and hypoalbuminaemia with an albumin level of 2.9 g/dL (Reference range: 3.5-5.5 g/dL).

Stool examination revealed mucus, 4-6 pus cells per High-Power Field (HPF), and no blood. Colonoscopy examination showed no abnormalities, while upper GI endoscopy revealed flattened duodenal and ileal folds (Table/Fig 1)a. Consequently, a clinical diagnosis of coeliac sprue was made. Focal flattening of the duodenal and ileal mucosa was observed (Table/Fig 1)c,d. All biopsies, including colonic samples, showed increased IELs (30-40/100 enterocytes) and a locally thickened subepithelial collagen band (>10 um), which was confirmed by Masson’s trichrome staining (Table/Fig 1)e,f. Focal stripping of the epithelium, entrapped capillaries, stroma, and inflammatory cells were also present (Table/Fig 2)a-d, and Congo red stain was negative. Therefore, a diagnosis of “Collagenous enterocolitis” was made. The patient was started on steroids and a gluten-free diet, which provided symptomatic relief. After correcting the hypoalbuminaemia and receiving folate therapy, she was discharged with instructions for follow-up. However, due to the pandemic, she could not attend the follow-up appointment. According to recent telephonic communication, she is partially compliant, taking medication only when symptomatic and stopping whenever she experiences relief.

Case 2

A 70-year-old female presented in January 2023 with intermittent watery diarrhoea, both large and small bowel type, in the last 10 days. She experienced a large stool volume and a frequency of 10-12 times per day, along with urgency and tenesmus. Four years ago, she had a history of anaemia and periumbilical colicky abdominal pain that worsened after meals, as mentioned in her papers from outside. This pain was relieved with the administration of steroids, such as budesonide, at a dose of 3 mg three times daily for six weeks. However, she presented again with similar symptoms and was clinically considered to have inflammatory bowel disease with recurrent anaemia (haemoglobin around 6.5 g/dL). Her gastroduodenoscopy and colonoscopy showed normal results (Table/Fig 1)b. On mapping biopsy, the duodenum showed a significant increase in IELs with focal mild villous atrophy, while the ileum showed only non specific mucosal inflammation. The colonic mucosa exhibited features similar to the first case, along with minimal focal neutrophilic activity. Therefore, a diagnosis of collagenous enterocolitis was made. The patient became asymptomatic immediately after admission and was not put on any treatment. She was discharged within a week and is currently being followed-up to monitor the reappearance of symptoms, in case steroids need to be initiated.

Discussion

Collagenous colitis is a form of microscopic colitis that typically presents in elderly women and is characterised by watery diarrhoea (1). CS, a rare malabsorptive disorder of the small intestine, mimics coeliac disease (2). The exact aetiology of these disorders remains unknown, and biopsies reveal a characteristic thickening of the subepithelial collagen layer, with or without an increase in IELs (3). The occurrence of these disorders simultaneously is very rare but has been reported as early as 1988, leading to the suggestion of the term “Collagenous enterocolitis” (4). This indicates that the unusual mucosal process may be highly heterogeneous and more extensive in the intestinal tract than previously recognised. The present cases also showed involvement of both the upper and lower gastrointestinal tracts. Six cases have been reported where CC was associated with Protein-Losing Enteropathy (PLE) (5),(6). Here, the authors report two such cases of collagenous enterocolitis in elderly women presenting with watery diarrhoea, one with recurrent symptoms, and involvement of both the upper and lower gastrointestinal tracts, as suggested by the clinical features and confirmed by histopathology.

The term “Collagenous colitis” was first described in 1976 by Lindstrom and is characterised by collagen deposition beneath the surface epithelium of the colorectal mucosa (7). Classically, the mucosa appears normal during endoscopy, although ulcerations may be observed in a few cases. The mean age of presentation is 63 years, with a predominance of females, and the common symptom is chronic watery, non bloody diarrhoea lasting for more than 24 months. CS is a rare disease of the small bowel, first described in 1947, occurring in a younger age group and characterised by patchy villous atrophy as a hallmark endoscopic finding. It is associated with persistent diarrhoea, progressive weight loss, and severe malabsorption, leading to multiple nutrient deficiencies (8). Similar features were observed in our cases as well. In the first case, diarrhoea, anaemia, and hypoalbuminaemia were present, suggesting malabsorption, while the second case had only anaemia.

Although collagenous colitis is typically considered “benign,” a few serious colonic complications have been reported. These include the spontaneous development of peritonitis associated with free perforation of the colon, submucosal dissection, and colonic “fracturing,” particularly during endoscopic procedures. Extensive ulcerative colitis progressing from collagenous colitis may occur within one to two years of the initial diagnosis (8). On the other hand, CS carries a guarded prognosis with a substantial risk of malabsorption that could be fatal.

The exact aetiology of both the aforementioned disorders is unknown. Genetic sensitivity, hypersensitivity to a specific food component, medication, and environmental factors may all contribute. Certain drugs such as Non Steroidal Anti-inflammatory Drugs (NSAIDs), proton pump inhibitors, Angiotensin Receptor Blockers (ARBs), and autoimmune conditions have also been associated (9),(10). Other causes include paraneoplastic syndrome due to colon cancer, Yersinia infection, and Hashimoto’s thyroiditis (11). The first patient had diabetes and was also on long-term ARB for hypertension. However, in the second patient, no obvious cause could be identified.

Histologically, both of these disorders exhibit increased IELs in the mucosa, irregular deposition of subepithelial collagen bands demonstrated by Masson’s trichrome staining (with a thickness greater than 10 μm, approximately the diameter of two lymphocytes), negative Congo red staining, and characteristic entrapment of capillaries, stroma, and inflammatory cells. Additionally, flattening and/or atrophy of the villi in the small intestine can be observed in CS. Similar findings were present in the cases as well. Both collagenous colitis and CS typically respond to steroids. Other medications used include bismuth nitrate, sulfasalazine, and a lactose- or gluten-free diet (12). The patients also showed a response to steroids with a decrease in the frequency of stools. Details of only 12 cases (Table/Fig 3) (4),(5),(9),(10),(11),(13),(14),(15),(16),(17),(18),(19) were found after an extensive review, and these cases have been tabulated.

Conclusion

In conclusion, the clinical presentation of collagenous colitis can be misleading at times. The disease can occasionally involve both the upper and lower gastrointestinal tracts simultaneously, which can pose a diagnostic challenge. However, histopathological examination is crucial for arriving at a definitive diagnosis. Limited reporting of such cases has been done so far, and the present report will contribute further to the existing literature.

Acknowledgement

The authors would like to thank Department of Gastroenterology, Seth GS Medical College and KEM Hospital, Mumbai.

DOI and Others

DOI: 10.7860/JCDR/2023/64706.18778

Date of Submission: Apr 15, 2023
Date of Peer Review: May 24, 2023
Date of Acceptance: Oct 10, 2023
Date of Publishing: Dec 01, 2023

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was informed consent obtained from the subjects involved in the study? No
• For any images presented appropriate consent has been obtained from the subjects. No

PLAGIARISM CHECKING METHODS:
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• iThenticate Software: Oct 07, 2023 (9%)

ETYMOLOGY: Author Origin

EMENDATIONS: 8