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Original Articles: Gastroenterology

Pediatric Collagenous Gastritis and Colitis: A Case Series and Review of the Literature

Matta, Judy∗,†,‡; Alex, George∗,§; Cameron, Donald J.S.∗,||; Chow, Chung W.§,¶; Hardikar, Winita∗,§,||; Heine, Ralf G.∗,§,||

Author Information
Journal of Pediatric Gastroenterology and Nutrition: September 2018 - Volume 67 - Issue 3 - p 328-334
doi: 10.1097/MPG.0000000000001975


What Is Known

  • Collagenous gastritis is characterized by subepithelial deposition of dense collagen bands.
  • There are pediatric and adult-onset phenotypes.
  • Iron deficiency anemia is a common clinical presentation.
  • The adult-onset type is associated with collagenous colitis and autoimmune disorders.

What Is New

  • Some children may develop collagenous colitis or autoimmune phenomena at a very young age, in keeping with the “adult” phenotype.
  • It appears possible that the pediatric and adult phenotypes are part of a continuous disease spectrum. Treatment with azathioprine and corticosteroids may be effective in treating collagenous gastritis, but reliable clinical data are missing.

Collagenous gastritis is a rare gastrointestinal disorder first described in 1989 by Colletti and Trainer (1) in a 15-year-old girl presenting with recurrent abdominal pain and upper gastrointestinal bleeding. This patient and a further 5 cases were identified and reported by Colletti et al in 1998 (2). That report included 2 of the patients described in our case series. Collagenous gastritis is characterized histologically by the presence of a subepithelial collagen band in association with an inflammatory cell infiltrate in the lamina propria. To date, the pathophysiology remains unclear. It has been hypothesized that the deposition of collagen and protein exudate occurs due to an increase in vascular permeability (3).

Based on previous published case reports, 2 phenotypes of the disease have been described: a pediatric-onset and an adult-onset type. It is unclear whether these are part of the same disease spectrum or distinct clinical entities. The typical presentation of collagenous gastritis in children includes recurrent abdominal pain and iron deficiency anemia (4). In children, inflammatory changes and mucosal collagen deposition are usually limited to the stomach. By contrast, the adult-onset form is associated with collagenous colitis and other autoimmune disorders, such as celiac disease or diabetes mellitus. The collagen deposition and inflammation in adults are more extensive and can be seen throughout the gastrointestinal tract (3). Gastrointestinal symptoms in adults include abdominal pain, voluminous nonbloody diarrhea, malabsorption, and protein-losing enteropathy. In 1998, Colletti et al (2) reported the first adult-onset phenotype seen in an 11-year-old boy. In 2003, Camarero et al (5) reported another adult-onset phenotype seen in a 15-year-old girl. To date, there are only 4 reported cases of so-called “adult-onset” phenotype in pediatric patients (2,4–7).

We report a series of 12 children with collagenous gastritis who were diagnosed at the Royal Children's Hospital, Melbourne, Australia. We aim to describe the clinical features and outcomes of patients in our cohort and also provide a summary of pediatric cases with collagenous gastritis reported to date.


We performed a retrospective chart review of all patients with collagenous gastritis and/or colitis who were treated at the Royal Children's Hospital between 1997 and 2016. Cases were identified from the hospital's pathology database. Before accessing the patients’ records, approval was obtained from the local Human Research Ethics Committee. Clinical and demographic data were collated, including age, sex, presenting symptoms, endoscopic findings, histological features, treatment modalities, and clinical course during follow-up (Table 1 ).

Pediatric patients with collagenous gastritis and colitis
TABLE 1 (Continued)
TABLE 1 (Continued):
Pediatric patients with collagenous gastritis and colitis
TABLE 1 (Continued)
TABLE 1 (Continued):
Pediatric patients with collagenous gastritis and colitis


Demographics and Clinical Presentation

A total of 12 cases of collagenous gastritis were identified (7 female; mean age at presentation 11.5 years [range 5–18 years]). Of these, 3 patients (25%) also suffered from collagenous colitis. The clinical presentation included recurrent abdominal pain (n = 6), iron deficiency anemia (n = 11), chronic diarrhea (n = 3), upper gastrointestinal bleeding/hematemesis (n = 1), recurrent vomiting (n = 1), and retrosternal pain (n = 1). All patients who presented with chronic diarrhea (n = 3) were found to have the adult-onset phenotype characterized by concomitant collagenous gastritis and colitis. This included a 5-year-old patient with type-1 diabetes mellitus and an 11-year-old boy with achalasia and psoriasis. A 13-year-old patient with adult-type disease had no known autoimmune disorder.

Endoscopic and Histological Findings

The endoscopic appearance in all patients with collagenous gastritis was grossly abnormal. Features included nodularity of the gastric mucosa, mucosal edema and erythema, as well as hyperplastic rugae. By contrast, the patients with collagenous colitis had macroscopically normal colonoscopic findings. The mucosal appearance in one of the patients was suggestive of a mild distal proctocolitis, but histological changes were more extensive. Histopathologic findings in biopsies from the stomach show characteristic subepithelial hyaline deposits with an inflammatory infiltrate in the lamina propria of the affected areas (Fig. 1).

Mucosa of the gastric body showing a thick subepithelial layer of hyaline (arrow) and prominent plasma cells and eosinophils in the lamina propria. Hematoxylin and eosin stained.


Treatment modalities in our cohort of patients were fairly heterogeneous, as there are no guidelines for treatment of this condition, and responses to treatments used were generally disappointing. Eleven patients with iron deficiency anemia were treated with oral iron supplements. Four patients were commenced on proton pump inhibitors (PPIs). Dietary modulation was trialed in 4 of our patients. Of these, a gluten-free diet was prescribed in 2 of the patients, 1 of whom had concurrent celiac disease. A combination of a gluten and dairy-free diet was trialed in the third patient and a 4-food elimination diet (cow's milk, soy, wheat/gluten, egg) was trialed in the fourth patient. One male patient (aged 11 years) with adult-type disease had been treated with oral prednisolone and was subsequently weaned onto long-term treatment with azathioprine.

Clinical Course and Follow-up

Documented follow-up information was available for 9 of the 12 patients (median duration = 30 months; range 1–78). All 9 patients who were treated with oral iron supplementation had resolution of their anemia but required ongoing therapy. Repeat endoscopic examinations with biopsy were performed in 8 patients. In 7 of these, histological findings were either unchanged or had progressed. For the patient who was diagnosed with celiac disease, the initial gastroscopy performed led to the diagnosis of celiac disease and collagenous gastritis concomitantly. There were large numbers of plasma cells, moderate numbers of eosinophils and scattered neutrophils, as well as a thick layer of hyaline in the gastric fundus. The antral biopsies showed similar inflammatory infiltration, but no discernible hyaline layer. Changes in the duodenum included prominent shortening of the villi with an increase in intraepithelial lymphocytes, consistent with untreated celiac disease. The repeat biopsy 3 years later, while on a gluten-free diet, showed restoration of the villous architecture in the duodenum, but there was still a focal increase in intraepithelial lymphocytes. In addition, there was worsening of the changes of collagenous gastritis with an increase in plasma cell infiltration and a thick layer of hyaline in both fundus and antrum. A further gastroscopy performed 1 year afterwards showed no changes in the extent of the collagenous gastritis, whereas the duodenal biopsies were entirely normal. Colonoscopic biopsies from 6 colonic levels showed mild and nonspecific changes, but no features suggestive of collagenous colitis. The patient treated with oral corticosteroids and azathioprine was the only patients who showed clinical amelioration and improvement of the histological features of both collagenous gastritis and colitis. However, despite the histologic improvement with a marked reduction of subepithelial collagen deposition of the previously affected areas, this patient had additional histological changes in the duodenum on follow-up biopsy. One patient later developed type 1 diabetes mellitus as a young adult; another, who also had collagenous colitis, developed achalasia and psoriasis.


Collagenous gastritis and colitis are relatively uncommon diseases, which are characterized by marked subepithelial collagen deposition in association with a mucosal inflammatory infiltrate. The clinical presentation is related to the region of the gastrointestinal tract involved. Based on the published literature and our case series, the presenting symptoms of the pediatric type are related to the upper gastrointestinal tract, including abdominal pain, recurrent vomiting, and upper gastrointestinal bleeding. Iron deficiency was a common clinical problem in these patients. In contrast, the pediatric patients who had also chronic diarrhea had evidence of concomitant collagenous colitis, in keeping with the adult phenotype.

Nodularity of the gastric corpus is the most characteristic endoscopic finding in collagenous gastritis. Other endoscopic findings included mucosal erythema, ulceration, erosions, polypoid lesions and hyperplastic rugal folds.

The histologic features of collagenous gastritis include the deposition of collagen bands thicker than 10 μm in the subepithelial layer, especially in the lamina propria, with a chronic inflammatory infiltrate consisting of lymphocytes, plasma cells, and eosinophils. The thickness of the collagen deposits may be influenced by the location of the biopsy; however, it may also increase with the disease duration. Several mucosal biopsies are needed for diagnosis, as well as for mapping of the disease extent which is required for the long-term follow-up.

In our pediatric case series, which is the largest, reported to date in the literature, we followed patients both clinically and histologically for a median period of 30 months. There was a female predominance. Iron deficiency anemia was the most prevalent initial clinical presentation. The iron deficiency anemia resolved in all patients after oral iron supplementation, but no histologic improvement was noted with this treatment modality. Furthermore, neither clinical nor histological improvement was seen in response to elimination diets or PPI treatment. Only one of our patients with the adult phenotype of the disease had clinical and histological documented improvement after treatment with corticosteroids and azathioprine.

As outlined in Supplemental Table 2 (Supplemental Digital Content,, we identified a total of 32 reported pediatric cases of collagenous gastritis, some of whom had associated collagenous colitis (defined as the adult phenotype). Many of the presenting features that we described were similar to those in the existing published literature. Our findings of a female preponderance were in keeping with published data. The most common presenting features in our, as well as other studies were iron deficiency anemia and recurrent abdominal pain (Supplemental Table 2, Supplemental Digital Content, The pathophysiology of the iron deficiency anemia remains unclear, but the response to enteral iron supplements suggests that the cause is microscopic blood loss rather than iron malabsorption.

In our series, 2 patients with the adult phenotype suffered from an associated autoimmune disease. The 5-year-old girl presented with type 1 diabetes mellitus and the 11-year-old boy developed achalasia and psoriasis. Other studies have also reported an association between the adult-type disease and other autoimmune conditions, including celiac disease, thyroid disease, or diabetes mellitus.

None of the patients in the present series with a pediatric phenotype progressed into an adult phenotype during the documented follow-up period. However, some patients had worsening involvement of the antrum and duodenum over time. Furthermore, one of our patients with collagenous gastritis developed autoimmune thyroid disease as an adult. Camarero et al (5) reported Aeromonas hydrophila infection in 2 patients with collagenous colitis and proposed that a possible infective trigger may be involved in the pathogenesis. In our case series, no infectious agents were isolated.

Because of the rarity of the disease and the unknown etiology, there is no established standard therapy. A review of the literature showed that several treatment modalities have been utilized (Supplemental Table 2, Supplemental Digital Content, Antisecretory agents, including PPIs and H2-receptor antagonists, sucralfate, bismuth subsalicylate, corticosteroids, iron supplementation, hypoallergenic diets, and 5-aminosalicylic acid have been used with limited success (1–22). Recently, Bajwa et al (9) published the case of a 13-year-old boy who presented with abdominal pain, loose stools, and weight loss. That patient had the typical endoscopic features of collagenous gastritis which was subsequently confirmed on histology. There was evidence of celiac disease. The patient was commenced on a gluten-free diet, and symptoms resolved within 6 weeks. However, no endoscopic or histologic improvement was noted on repeat endoscopy 6 months later (9). In our series, 2 patients were started on a gluten-free diet; one of them had celiac disease and the other had collagenous gastritis with associated collagenous colitis. The patient with celiac disease had clinical improvement of the duodenal villus lesion, but no endoscopic or histologic improvement of the collagenous gastritis was noted. The other patient with collagenous gastritis and colitis had neither clinical nor histologic amelioration. Gluten- and dairy-free diets, or 4-food elimination diet were otherwise not associated with any clinical or histological improvement. Elimination diets therefore do not seem to be an efficacious treatment modality in collagenous gastritis, as also suggested by Bajwa et al (9).

Three out of the reported 7 patients outlined in Table 2 (Supplemental Table 2, Supplemental Digital Content, who presented with diarrhea had the adult-onset phenotype of collagenous gastritis and colitis. Two patients were treated with 5-aminosalicylic acid, an anti-inflammatory aminosalicylate drug. Symptoms of 1 patient resolved but no follow-up biopsy was performed, whereas the other patient had neither a reduction in symptoms nor histologic improvement on biopsy. The third patient was lost to follow-up.

Of the 3 patients with collagenous gastritis and colitis in our series, only 1 patient achieved clinical improvement and a reduction of the subepithelial collagen deposition after treatment with corticosteroids, and with further improvement on azathioprine. Azathioprine had not previously been used in pediatric patients with collagenous gastritis and colitis. One reported adult patient with collagenous gastritis treated with steroids and azathioprine showed improvement of symptoms but no histologic improvement was noted on biopsy (17). On reviewing adult case reports, few patients had amelioration of their clinical symptoms, but no change in histologic findings was found (8). Therefore, no clear standard therapeutic strategy can be formulated. Further randomized clinical trials are needed.

In conclusion, collagenous gastritis is a rare clinical entity in children, which tends to be limited to the stomach. A small proportion of children presents with more extensive disease and collagenous colitis, in keeping with the adult phenotype. The investigation of children with collagenous gastritis and lower gastrointestinal symptoms should therefore include a colonoscopy to rule out collagenous colitis. A specific therapy for collagenous colitis has not yet been established. Although clinical improvement was observed in some cases, no resolution of endoscopic or histologic abnormalities has been documented. In our case series, only one patient with collagenous gastritis and colitis had clinical, endoscopic, and histopathologic improvement after treatment with corticosteroids and azathioprine. However, further evidence is required to confirm this observation. Oral iron supplementation is effective in treating the iron deficiency anemia, one of the main presenting features of this disease. Given the chronic nature of the condition, patients with collagenous gastritis require careful long-term follow-up, including repeat endoscopies to monitor for the extent of mucosal involvement. Creating a disease registry of patients with collagenous gastritis from many centers will allow gathering stronger and more generalizable diagnostic and prognostic information. These data may ultimately allow identifying the underlying pathogenic mechanisms and lead to effective clinical treatments for collagenous gastritis in the future.


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abdominal pain; children; collagen; iron deficiency anemia; subepithelial

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