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Collagenous Gastritis: A Rare Cause of Abdominal Pain and Iron-deficiency Anemia

Kori, Michal*; Cohen, Shlomi; Levine, Arie; Givony, Shlomo; Sokolovskaia-Ziv, Nadia§; Melzer, Ehud*; Granot, Esther*

Journal of Pediatric Gastroenterology and Nutrition: November 2007 - Volume 45 - Issue 5 - p 603–606
doi: 10.1097/MPG.0b013e31803cd545
Case Reports

*Departments of Pediatric Gastroenterology, Israel

§Pathology, Kaplan Medical Center, Rehovot, Israel

Department of Pediatric Gastroenterology, Dana Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

Department of Pediatric Gastroenterology, Wolfson Medical Center, Holon, Israel

Address correspondence and reprint requests to Michal Kori, MD, Pediatric Gastroenterology, Kaplan Medical Center, PO Box 1, Rehovot, Israel (e-mail:

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Collagenous gastritis is a rare histopathological disorder characterized by thick subepithelial collagen bands (>10 μm) associated with an inflammatory infiltrate of the gastric mucosa. There is mixed chronic inflammation in the lamina propria and surface epithelial damage of varying degree. The etiology, pathogenesis, and pathology remain poorly understood.

Two subsets of patients with collagenous gastritis have been described. The first occurs in children and young adults presenting with severe anemia, a nodular pattern on endoscopy, and disease limited to the gastric mucosa without evidence of colonic involvement. The second has been described in adult patients who present with chronic watery diarrhea and manifest collagenous gastritis associated with collagenous colitis.

To date, we are aware of only 5 pediatric cases of collagenous gastritis that have been published (1–5). Herein we describe 3 new pediatric cases of collagenous gastritis, presenting in early adolescence with anemia and upper gastrointestinal symptoms.

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Case 1

A 12-year-old girl presented with a 4-month history of nausea and recurrent vomiting without associated abdominal pain or diarrhea. Despite a decrease in appetite, weight loss was not documented. Six months before onset of her symptoms, the patient had been evaluated for pallor and iron-deficiency anemia and was diagnosed with a hemoglobin level of 7.5 mg/dL. Iron therapy was instituted and her hemoglobin level returned to normal. Physical examination disclosed a thin, well-appearing girl (weight 39 kg, 25–50th percentile; height 155 cm, 75th percentile), and was otherwise unremarkable. Her initial laboratory evaluation disclosed a hemoglobin level of 13.1 mg/L, white blood count of 7.46 × 10/L, and platelet count of 246,000/L. Blood chemistry, albumin, and aminotransferase levels were normal. Antigliadin, tissue transglutaminase, and antiendomysial antibodies were negative. Immunoglobulin (Ig) levels were IgG, 439 mg/dL; IgM, 92 mg/dL; IgA, 59 mg/dL; and IgE, 35 mg/dL.

On upper endoscopy the esophagus and gastric antrum appeared normal. The gastric body and fundus appeared thickened and nodular and the mucosa was friable with exudates. In the duodenal bulb, round elevated lesions were observed, without ulcerations. The second and third parts of the duodenum were normal. Biopsies from the second part of the duodenum and antrum were normal, whereas those from the duodenal bulb showed erosive duodenitis with gastric-type mucosa/gastric heterotopia. Biopsies from the stomach body demonstrated erosions with focal pseudomembrane formation, acute and chronic inflammation, and severe regenerative changes of the epithelium. Staining for cytomegalovirus was negative, as was staining for Helicobacter pylori.

The patient started a regimen of omeprazole 20 mg twice daily. Vomiting ceased and nausea improved but did not resolve. By 3 months, while she was still receiving omeprazole, her symptoms recurred and further evaluation was performed. An upper gastrointestinal series with small bowel follow-through was normal. Assessments of blood gastrin, C-reactive protein, thyroid-stimulating hormone, and immunoglobulin G subclasses were normal; cytomegalovirus and HIV serological tests were negative.

A colonoscopy and ileoscopy were performed to rule out inflammatory bowel disease. Apart from a juvenile polyp found in the cecum, which was removed, the findings of the examination were normal. Biopsies of specimens obtained throughout the colon and ileum were also normal. A repeat upper endoscopy performed 3.5 months after the initial endoscopy demonstrated a severely inflamed gastric body and fundus, with elevated erythematous plaques and areas with multiple small polypoid lesions (Fig. 1). The duodenal bulb appeared scarred (ie, deformed). Histopathological examination at this time demonstrated gastric mucosal erosions and focal atrophy. The lamina propria was characterized by a moderate to severe acute and chronic inflammatory infiltrate with eosinophils and focal fibrosis, which were not present in the first biopsy specimens. A third gastroscopy (2 months later) revealed similar macroscopic findings. Biopsies from the duodenum at this time showed 1 fragment with preserved villous architecture, whereas the second fragment had an absence of villi and acute and chronic inflammation with lymphoid formation. A thickened subepithelial collagen band was seen. Biopsy specimens taken from the stomach showed moderate atrophy, severe acute and chronic inflammation in the lamina propria, severe regenerative changes, focal fibrosis of lamina propria, and thickened subepithelial collagen bands (Figs. 2 and 3). H pylori was identified for the first time. It is unclear whether this represents a new acquisition of H pylori or the possibility that it was not identified in earlier biopsies. The patient received triple therapy for H pylori without marked improvement of her symptoms. She continues to have intermittent nausea and vomiting and receives omeprazole intermittently, but is gaining weight and functioning well. A follow-up endoscopy performed 1 year later revealed severe erosive gastritis macroscopically and histologically.

FIG. 1

FIG. 1

FIG. 2

FIG. 2

FIG. 3

FIG. 3

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Case 2

A 12-year-girl was referred for evaluation of persistent iron-deficiency anemia refractory to iron therapy (hemoglobin level, 8.7 g/dL). She had intermittent postprandial epigastric pain throughout the previous year and had lost weight during the preceding 3 months. There was no history of nonsteroidal medication use, diarrhea, arthralgia, or oral lesions. Physical examination disclosed a short, thin (weight, 30 kg; height, 142 cm), pale female with a pubertal stage of Tanner 1. Findings of the physical examination were otherwise unremarkable. Laboratory tests disclosed a hemoglobin level of 9.4 g/dL, mean corpuscular volume of 54, iron level of 26 μg/dL, and ferritin level of 1.5 ng/mL; folic acid, vitamin B12, hemoglobin electrophoresis, endomysial antibodies, immunoglobulins, and occult blood in the stool were normal or negative. A gastroscopy was performed, which demonstrated a dense array of raised plaques and nodules with paler intervening areas in the body and fundus, without erosions. The esophagus, antrum, and duodenum were normal macroscopically. Biopsies from the duodenum and esophagus were normal. Antral biopsies showed chronic active gastritis with H pylori organisms on Giemsa stain. The biopsies from the gastric body demonstrated chronic active gastritis, consisting mainly of lymphocytes and plasma cells. A barium meal with small bowel follow-through and ileocolonoscopy were normal. The patient was treated with omeprazole for 2 months, as well as with a clarithromycin-based triple therapy regimen for the H pylori infection, with subsequent eradication documented 2 months later. Because the anemia was refractory to 3 months of iron therapy, she was treated with intravenous iron, and her hemoglobin level increased to 12.0 g/dL. Three months after the endoscopy, she continued to have ongoing abdominal pain and a poor appetite and had not gained any weight since her initial visit. A second gastroscopy was performed with similar macroscopic findings, but the inflammatory component was noted to have numerous eosinophils as well as intraepithelial eosinophils and focal atrophy.

Omeprazole treatment was renewed. Immunoglobulin E antibodies to a wide food allergy panel were found to be negative. Nine months after her initial visit, her hemoglobin level started to drift down, and she was still underweight but otherwise asymptomatic. Nutritional supplementation was added. At the age of 13 years and 8 months, due to positive occult blood in the stool, she had a third gastroscopy performed. The macroscopic appearance of the stomach remained unchanged, but the biopsies showed a thick subepithelial collagen band, dense polyclonal infiltrate of plasma cells, and eosinophils with eosinophilic crypt abscesses and areas of atrophic gastritis. A diagnosis of collagenous gastritis was made. A course of prednisone administered for 10 weeks led to significant clinical improvement, which manifested as weight gain, a growth spurt, and normal appetite. Over the course of 6 months she reached the 10th centile for weight, and by age 15.5 years reached the 50th centile for height and weight. Despite her marked clinical improvement, repeat biopsies after 6 months showed no change. During the following 2 years she failed to return for regular clinic visits. She continued to experience intermittent epigastric pain, necessitating occasional treatment with omeprazole for 2 to 3 months. Blood counts remained normal and anemia did not recur. A repeat endoscopy performed at age 18 demonstrated a polypoid mass in the fundus, with significant decrease in the plaques and nodules in the body. On histological examination, the mass consisted of an inflammatory infiltrate with subepithelial collagen deposits.

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Case 3

The third patient, also a 12-year-old girl, was referred for evaluation of abdominal pain of a few months duration. She had epigastric pain with heartburn but without vomiting, nausea, or diarrhea. Her appetite was normal and so was her weight. Her medical history was unremarkable; there was no history of nonsteroidal antiinflammatory medication use, diarrhea, arthralgia, or oral lesions. Her father had been diagnosed with gastritis due to H pylori 1 year before.

Physical examination was unremarkable, with appropriate weight-to-height ratio. Laboratory examination disclosed a normal blood count, normal iron levels, and negative celiac screening tests. Abdominal ultrasound examination was normal. As part of her investigation, she underwent an upper endoscopy that revealed a nodular appearance in the gastric body and antrum with erosions. In the duodenum there was erythema and erosions. Rapid urease test result was negative. Gastric biopsy showed oxyntic mucosa with chronic inflammation and patchy subepithelial collagenous deposition. Duodenal biopsy findings were also normal. Therapy with a proton pump inhibitor (omeprazole) was initiated, and on follow-up 2 months later, improvement in her symptoms of abdominal pain and heartburn was noted.

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Collagenous gastritis was first described in 1989 by Colletti and Trainer (1) in a 15-year-old girl presenting with recurrent abdominal pain and severe iron-deficiency anemia due to upper gastrointestinal bleeding. Nodularity and erythema of the gastric corpus were persistent endoscopic findings. Biopsies revealed patchy chronic active gastritis with a striking focal thick band of collagen immediately beneath the surface epithelial cells. Since this initial patient, we are aware of 18 more cases that have been reported in the literature, with only 5 in the pediatric age group (6–9,11,12).

We describe 3 new pediatric cases, all female, presenting in early adolescence with anemia and upper gastrointestinal symptoms. On endoscopy, the gastric mucosa appeared thickened and nodular, predominantly in the gastric body. Gastric biopsies demonstrated intense inflammation accompanied by eosinophils with subepithelial collagen bands. The 5 previous pediatric cases reported in the literature (2 girls and 3 boys) presented with upper gastrointestinal symptoms and significant anemia at an age range of 9–20 years. Our 3 patients were girls who were each 12 years of age at presentation. Only 2 of the 3 girls had iron-deficiency anemia before or during follow-up. The anemia was not severe, and in case 1, anemia responded to oral iron treatment. In case 2, intravenous iron therapy was required. We are able to report relative long-term follow-up (1.5–6 years) in 2 of our patients (cases 1 and 2). These 2 girls received continuous or intermittent treatment with proton pump inhibitors, yet still had intermittent upper gastrointestinal symptoms. Steroid treatment given to the patient in case 2 led to significant clinical improvement. However, in both patients, on repeated endoscopies, there was no resolution of pathological findings consistent with previous reports in the literature.

Lagorce-Page et al (2) delineated 2 subsets of patients with collagenous gastritis. The first occurs in children and young adults presenting with severe anemia, a nodular pattern on endoscopy, and a disease limited to the gastric mucosa without evidence of colonic involvement. Our 3 patients' clinical symptoms and pathologic findings are compatible with those described in this group, although their anemia was not as severe. The second subset of patients has been described to include adults who present with chronic watery diarrhea and manifest collagenous gastritis associated with collagenous colitis. Collagenous colitis is a fairly common cause of chronic watery diarrhea, especially in elderly women. The other main clinical symptoms are weight loss and abdominal pain. Laboratory studies are nondiagnostic, and the diagnoses rely on histopathologic examination of colonic mucosal biopsies. There is an association with autoimmune diseases such as thyroid disorders, diabetes mellitus, celiac disease, and arthritis. Steroids (eg, budesonide) remain the best-documented treatment for collagenous colitis.

The etiology, pathogenesis, and pathology of collagenous gastritis remains poorly understood. The proposed mechanism of subepithelial deposits delineates that chronic inflammation, reparative or autoimmune response to toxic or infectious agents, and abnormal function of pericryptal fibroblasts cause collagenization of exudate plasma proteins. The etiology of anemia in collagenous gastritis may be associated with gastric bleeding resulting from damage of dilated capillaries entrapped in the subepithelial fibrous bands. There is no effective treatment; all of the reported cases were treated with acid suppression and some were treated with courses of steroids, with no apparent improvement. In cases reporting long-term follow-up, no resolution has been observed. Development of endocrine cell hyperplasia, intestinal metaplasia, and epithelial changes indeterminate for dysplasia have been reported on long-term follow-up (13 years) of the first reported patient (10).

In conclusion, collagenous gastritis, although rare, should be assessed in biopsy specimens obtained form pediatric patients presenting with upper gastrointestinal symptoms, anemia, and a prominent nodular pattern of the gastric body or antrum on upper endoscopy. Pathological findings are long-standing and treatment is disappointing.

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