Gastric Siderosis Due to Oral Ferrous Sulfate Supplements : ACG Case Reports Journal

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CASE REPORT: STOMACH

Gastric Siderosis Due to Oral Ferrous Sulfate Supplements

Tun, Kyaw Min DO1; Naga, Yassin MD1; Mesgun, Sami BS2; Aponte-Pieras, Jose MD3; Jinadasa, Priyanthi MD4; Ohning, Gordon MD, PhD3

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doi: 10.14309/crj.0000000000000870
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Abstract

INTRODUCTION

Iron deficiency is the most common cause of anemia worldwide.1 Oral ferrous sulfate supplements are widely used to treat iron deficiency anemia (IDA). A surplus of iron in the stomach can lead to accumulation in the mucosa known as gastric siderosis. It is frequently associated with hemochromatosis, oral iron medications, alcohol abuse, cirrhosis, frequent or chronic need for blood transfusions, and use of proton pump inhibitors (PPIs).2,3 Gastric siderosis is often asymptomatic; however, patients can have dyspepsia, nausea, dysphagia, coffee ground emesis, or melena.4 Gastric siderosis occurs when there is local overload of iron in the stomach that overwhelms the iron absorption mechanism. While mucosal injury due to acute iron overdose or due to chronic conditions such as hemochromatosis is well documented, mucosal iron deposition with or without mucosal injury due to standard dosage of oral iron supplements is underrecognized.

CASE REPORT

Case 1

A 72-year-old woman with IDA on oral ferrous sulfate supplements and chronic kidney disease stage 4 presented with fatigue and lightheadedness. The patient was found to have symptomatic normocytic anemia with hemoglobin 6.7 g/dL, for which she received blood transfusion. Esophagogastroduodenoscopy (EGD) revealed an abnormal, oval-shaped, 1.5 × 3 cm erythematous area on the gastric body. Biopsy of the area revealed benign gastric mucosa with iron accumulation in the lamina propria consistent with gastric siderosis (Figure 1). This was attributed to her chronic supplementation with ferrous sulfate tablets. There was no histological evidence of Helicobacter pylori, dysplasia, or neoplasm. Other possible causes of gastric siderosis such as cirrhosis, hemochromatosis, and chronic need for blood transfusions were investigated and excluded. Hemoglobin remained stable during the hospital course after the transfusion. On discharge, the patient was started on darbepoetin alfa weekly and was continued on ferrous sulfate 325 mg orally every other day with close monitoring.

F1
Figure 1.:
(A) Hematoxylin and eosin stain of gastric glands showed irregularities (arrow) in the mucosa of the gastric body because of iron-induced gastropathy. (B) Further staining with hydrochloric acid/potassium ferrocyanide revealed iron deposition in the lamina propria.

Case 2

A 70-year-old man with hepatitis C and gastroesophageal reflux disease (GERD) was admitted for progressively worsening dysphagia over the past 2 years. The patient took PPI daily for previously diagnosed nondysplastic Barrett's esophagus. In addition, he reported long-term use of oral ferrous sulfate supplements. No evidence of anemia was noted on his laboratory test results. There was no evidence of cirrhosis or other abnormalities of the liver on imaging. However, a moderate reactive gastropathy of the gastric antrum was discovered on EGD. There was chronic inflammation and intestinal metaplasia on the biopsy of the esophagus and gastroesophageal junction that was also noted in a prior specimen. Biopsy of the gastric body was remarkable for reactive gastropathy with positive iron stain consistent with iron deposition (Figure 2). Otherwise, there were no signs of H. pylori, dysplasia, or malignancy. The patient was instructed to taper the use of iron supplements while being periodically monitored with serum hemoglobin and iron studies. Gastric siderosis in this patient was attributed to oral ferrous sulfate supplements.

F2
Figure 2.:
(A) Specimen from the gastric body showed reactive gastropathy with dark brown mucosa indicative of iron deposition (black arrow). (B) The mucosa of the gastric body was positive for Prussian blue stain (iron stain).

Case 3

A 72-year-old man with GERD, IDA, and cirrhosis from hepatitis C presented with a 2-week history of melena. The patient reported taking PPI and oral ferrous sulfate for GERD and IDA, respectively. Moreover, the patient recently started receiving intravenous iron infusion at an outpatient facility. On admission, the patient was found to have normocytic anemia with hemoglobin 7.1 g/dL and received blood transfusion. During EGD with enteroscopy, 2 small arteriovenous malformations (AVMs) were discovered in the proximal jejunum and were treated with argon plasma coagulation (APC). There were no varices. Notably, the gastric body and fundus showed gastritis with erosions. On pathology, hemosiderin deposits were identified with positive iron stain (Figure 3). There was no evidence of H. pylori organisms or neoplasm. There were no stigmata of active bleeding in both upper and lower endoscopies. The patient did not require further transfusions and was discharged with ferrous sulfate, sucralfate, and proton pump inhibitors (PPI).

F3
Figure 3.:
(A) Random gastric biopsies showed deposits (black arrow) in the gastric mucosa. (B) The deposits were positive on Prussian blue stain suggestive of hemosiderin deposits.

DISCUSSION

Accumulation of iron in the stomach increases the risk of mucosal injury because iron, in either ferric or ferrous state, induces oxidative stress and promotes submucosal venous thrombosis.4–7 However, gastric siderosis due to oral iron supplements does not always cause mucosal injury. In a study by Abraham et al, mucosal injury caused by iron tablets constitutes approximately 0.7% of EGD examinations (9 of 1,300).8 Ingestion of iron tablets can result in various endoscopic findings such as erythema, hemorrhage, mucosal erosion, and dark brown appearance of the gastric mucosa.7,9 Although the third patient had cirrhosis, the underlying cause of iron deposition was more likely iron supplements because there was no sign of esophageal varices, and the patient had a recent increase in iron supplementation intravenously in addition to the oral form.

Different etiologies of gastric siderosis manifest 3 distinct histopathological patterns in the stomach: patterns A, B, and C (Table 1). The patterns of iron deposition in the gastric body biopsies of our patients were consistent with pattern B (Figures 1–3). In pattern A, iron is deposited into stromal cells and macrophages localized to the epithelium.2,10 Pattern B occurs with extracellular deposition of iron in the lamina propria2,10 and is most commonly associated with oral iron supplements and frequent blood transfusions.2,7,10,11 In pattern C, which is seen in cases of chronic systemic iron overload such as hemochromatosis, iron is deposited in the antral and fundic glandular epithelium.2,10,11

Table 1. - Characteristics of and conditions associated with different patterns of gastric siderosis
Pattern of gastric siderosis Characteristics Associated with
Pattern A Iron deposition in stromal cells
Localized to the epithelium
Inflammation
Mucosal hemorrhage
Ulcers
Pattern B Iron deposition in the lamina propria Oral iron supplements
Blood transfusion
Pattern C Iron deposition in the antral and fundic glandular epithelium Hemochromatosis

This case series raises awareness of the potential complications of oral ferrous sulfate supplements to the gastrointestinal system. Overall, gastric siderosis from iron tablets is an underreported entity in the literature despite their prevalent use and may be related to the symptoms experienced by the patients in this case series. Therefore, it is crucial to be aware of potential toxicities of iron supplements, to consider gastric siderosis as a differential diagnosis in symptomatic patients, to constantly monitor their necessity, and to initiate alternative therapies if indicated.

DISCLOSURES

Author contributions: KM Tun and J. Aponte-Pieras did the conceptualization. KM Tun drafted the original manuscript. Y. Naga, S. Mesgun, J. Aponte-Pieras, and G. Ohning reviewed and edited the manuscript. KM Tun completed the final edits. Images provided by P. Jinadasa. G. Ohning did the supervision. KM Tun is the article guarantor.

Financial disclosures: None to report.

Previous presentation: Case 1 of this case series was presented at the annual meeting of the American College of Gastroenterology on October 24, 2021, in Las Vegas, Nevada. Neither cases 2 and 3 nor the case series have been previously presented.

Informed consent was obtained for this case report.

REFERENCES

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