Collagenous gastritis is a rare disease characterized by subepithelial deposition of collagen bands within the gastric mucosa.3 While this disorder demonstrates similar histologic characteristics to the more welldescribed collagenous colitis, little is known about collagenous gastritis. Whereas the reported annual incidence of collagenous colitis is 1.1 to 5.2 cases per 100,000, collagenous gastritis is thought to be much rarer.2,3
Based on current published case reports, the disease has been identified as having two phenotypes, pediatric and adult. The pediatric phenotype commonly manifests as iron deficiency anemia and abdominal pain, which is thought to be related to chronic inflammation in the upper gastrointestinal tract.3,5 In contrast, the adult phenotype is typically characterized by more widespread disease, and is associated with collagenous colitis, usually presenting with watery diarrhea.3 Adult collagenous gastritis has also been seen in association with a variety of autoimmune disorders including celiac disease, thyroid disease, Sjögren’s syndrome, amongst others.1,2,3
Collagenous gastritis is diagnosed histologically as subepithelial deposition of collagen bands thicker than 10mm with evidence of chronic inflammation characterized by the presence of lymphocytes, plasma cells, and eosinophilic infiltrates. 5 Endoscopically, findings of mucosal nodularity have been described in this disease. 2,3 While the pathogenesis is unclear, the mucosal nodularity seen on endoscopy is thought to represent islands of normal cells surrounded by crypts of collagen deposition from chronic inflammation. 3
A 32 year-old man was referred for evaluation of iron deficiency anemia, intermittent upper abdominal pain, and dysphagia. His history was significant for a partial right lower lobe lobectomy for a carcinoid tumor 11 years prior. Upper endoscopy and colonoscopy were performed for additional workup of his symptoms and anemia.
Initial endoscopy demonstrated deep linear furrows throughout the esophagus with distal esophageal rings. Duodenal and gastric biopsies were negative for celiac disease or Helicobacter pylori, while esophageal biopsies demonstrated squamous mucosa with up to 50 eosinophils per high powered field (HPF) throughout the distal, mid, and proximal esophagus, consistent with a diagnosis of eosinophilic esophagitis. Celiac serologies were unremarkable. Biopsies of the cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum were negative for active or chronic inflammation, with no increase in subepithelial collagen or other evidence of collagenous or lymphocytic colitis, the two main subtypes of microscopic colitis. Iron supplementation was started, and the patient was initiated on a proton-pump-inhibitor (PPI) for an eight-week course which improved of his dysphagia and abdominal discomfort. Following his PPI treatment, repeat upper endoscopy with biopsies demonstrated resolution of his esophageal eosinophilia with no eosinophilic infiltration noted on histology. Iron supplementation was discontinued upon normalization of iron levels.
After initially showing improvement, he re-presented two years later now with similar symptoms. Repeat upper endoscopy was performed demonstrating linear furrows and esophageal rings (Figure 1), as well as gastric erythema with slight nodularity (Figure 2). Interestingly, biopsies of the gastric antrum and fundus at this time demonstrated subepithelial collagen deposition confirmed by trichrome stain, consistent with collagenous gastritis (Figures 3a, 3b). Esophageal biopsies performed were also notable for intraepithelial eosinophils, up to 10 eosinophils per HPF (Figure 4). Patient also underwent small intestinal capsule endoscopy which was unrevealing. The patient was restarted on both iron supplementation and a PPI, with improvement of his symptoms.
Collagenous gastritis is a rare and complex disease that has been associated with various autoimmune disorders and chronic inflammatory states, as well as a possible link to eosinophilic esophagitis, as demonstrated above. The pathogenesis of collagenous gastritis is still unclear.1 A multiinstitutional series of 40 patients with collagenous gastritis suggested three distinct histologic patterns for the disease, including a lymphocytic-gastritis pattern, an atrophic pattern, and an eosinophilrich pattern.1 This latter histologic pattern may in part demonstrate how chronic eosinophilic infiltration could relate these two conditions, however further studies need to be performed to clarify this hypothesis.
The diagnosis of collagenous gastritis requires histology demonstrating subepithelial collagen deposition with chronic inflammation, as demonstrated in Figures 3a and 3b.3,4 While the disease classically presents with mucosal nodularity, data have shown that some adult cases can also present predominantly with mucosal erythema as demonstrated in this case (Figure 2).3,4
There is no clear consensus on the treatment of collagenous gastritis. Multiple therapies have been attempted, including acid suppression, iron supplementation, hypoallergenic diets, sucralfate, azathioprine, among others, however to date there are no randomized control trials demonstrating treatment efficacy of any of these approaches.3 Data demonstrate that iron supplementation effectively manages iron deficiency anemia in those with collagenous gastritis, however, it is unclear if the clinical course or natural history of this disease is altered with this therapy.5
Overall, the prognosis remains unclear in this condition. Based on current information, there have been cases of histologic resolution; however, other case reports have demonstrated the persistence of subepithelial collagen deposits despite resolution of symptoms,3,4 suggesting the heterogeneity of this condition and perhaps that further subtypes may exist. For now, awareness of this disorder and pointed discussion with our expert pathology colleagues is essential in its recognition. As with any condition, the existence of this disorder must be realized in order for the diagnosis to be considered. Ultimately, given the rarity of this condition, more information is needed to further understand collagenous gastritis, and determine how best to treat patients affected by this intriguing and insufficiently understood disease.
1. Arnason, T., Brown, I. S., Goldsmith, J. D., Anderson, W., Obrien, B. H., Wilson, C., Lauwers, G. Y. (2014). Collagenous gastritis: a morphologic and immunohistochemical study of 40 patients. Modern Pathology, 28(4), 533–544. doi: 10.1038/ modpathol.2014.119
2. Brain, O., Rajaguru, C., Warren, B., Booth, J., & Travis, S. (2009). Collagenous gastritis: reports and systematic review. European Journal of Gastroenterology & Hepatology, 21(12), 1419– 1424. doi: 10.1097/meg.0b013e32832770fa
3. Kamimura, K., Kobayashi, M., Sato, Y., & Terai, S. (2015). Collagenous gastritis: Review. World Journal of Gastrointestinal Endoscopy, 7(3), 265–273. doi: 10.4253/ wjge.v7.i3.265
4. Mandaliya, R., DiMarino, A., Abraham, S., Burkart, A., & Cohen, S. (2013). Collagenous Gastritis a Rare Disorder in Search of a Disease. Gastroenterology Research, 6(4), 139–144. doi: 10.4021/gr564w
5. Matta, J., Alex, G., Cameron, D. J., Chow, C. W., Hardikar, W., & Heine, R. G. (2018). Pediatric Collagenous Gastritis and Colitis. Journal of Pediatric Gastroenterology and Nutrition, 67(3), 328–334. doi: 10.1097/ mpg.0000000000001975