What is the cause of severe recurrent iron deficiency anemia (IDA) with consistently low iron levels refractory to correction in a patient with a 10-year history, normal bone marrow examination, hiatus hernia, minor mucosal tears, and narrowing of the gastroesophageal (GE) junction?

Severe Refractory Iron Deficiency Anemia with Hiatus Hernia

The most likely cause of this patient's severe recurrent iron deficiency anemia refractory to oral iron correction is chronic occult bleeding from Cameron lesions (linear gastric erosions at the diaphragmatic impression of the large hiatus hernia), and this patient requires treatment with proton pump inhibitors combined with intravenous iron replacement therapy, with consideration for surgical repair if medical management fails.

Primary Pathophysiology

The hiatus hernia identified on endoscopy is the critical finding here. Large hiatus hernias cause iron deficiency anemia through Cameron lesions—linear gastric ulcers or erosions positioned on the crests of mucosal folds at the diaphragmatic impression—which bleed slowly and chronically 1, 2. This occurs in approximately 9.2% of patients with iron deficiency anemia undergoing endoscopic evaluation 3.

Key Clinical Features Supporting This Diagnosis:

• Cameron lesions are often endoscopically subtle or missed: Only 33% of patients with large hiatus hernia causing anemia have visible Cameron erosions on initial endoscopy 3. The "minor mucosal tears" described in this patient likely represent these lesions 1.

• Bleeding is intermittent and occult: Fecal occult blood testing is frequently negative, and the blood loss rate may exceed intestinal iron absorption capacity, explaining refractoriness to oral supplementation 4, 2.

• The narrowing at the GE junction represents the mechanical traction point where respiratory movements cause repetitive trauma to the gastric mucosa 1, 5.

Why Oral Iron Has Failed

This patient's iron deficiency is refractory because the rate of gastrointestinal blood loss from the Cameron lesions exceeds the intestinal capacity to absorb oral iron 4. Even with adequate oral supplementation (ferrous sulfate 200 mg three times daily), patients with ongoing bleeding from hiatus hernias cannot maintain iron stores 6, 2.

Recommended Management Algorithm

Immediate Treatment (First 3-6 Months):

1. Initiate high-dose proton pump inhibitor therapy: Acid suppression promotes healing of Cameron erosions. Studies show that H2-receptor antagonists heal erosions in 64% of patients (7 of 11) versus 0% with iron alone 2. Modern PPI therapy is likely more effective 3.

2. Switch to intravenous iron replacement: Given 10 years of failed oral therapy, this patient requires IV iron to replenish stores while addressing the ongoing blood loss 7, 4. Oral iron alone cannot overcome the chronic bleeding 4.

3. Continue iron supplementation for 3 months after hemoglobin normalizes to replenish body stores 6.

Monitoring and Surgical Consideration:

• Monitor hemoglobin and ferritin at 3,6, and 12 months 7, 6.

• If anemia recurs despite PPI therapy and IV iron, surgical repair (laparoscopic fundoplication with hiatal hernia repair) should be performed 1, 3. One study showed that PPI therapy alone was as effective as PPI plus surgery in preventing anemia recurrence at 1 year (hemoglobin 13.8 g/dL in both groups) 3, but this patient's 10-year refractory course suggests medical management has already failed.

Critical Diagnostic Pitfalls to Avoid

The normal bone marrow examination confirms this is true iron deficiency anemia, not anemia of chronic disease 7. The consistently low iron levels over 10 years with refractoriness to correction strongly suggests ongoing blood loss rather than malabsorption alone 7.

Additional Investigations Still Required:

Despite identifying the hiatus hernia, further investigation is warranted given the severity and duration 7:

• Repeat bidirectional endoscopy if previous studies are >2 years old to exclude concurrent pathology, as dual pathology is common 7.

• Small bowel capsule endoscopy should be considered if anemia persists after hiatus hernia treatment. The diagnostic yield is 66.6% in recurrent IDA, with common findings including angioectasia, Crohn's disease, and NSAID enteropathy 7.

• Formal renal tract imaging should be performed regardless of urinalysis results, given the recognized association between renal cell carcinoma and IDA 7.

• Celiac disease serology should be checked if not already done, as it accounts for 3-5% of IDA cases 8, 9.

Long-Term Management

If the cause remains irreversible despite optimal medical and surgical management, long-term iron replacement therapy (likely intravenous given the refractory nature) is an appropriate strategy 7. The British Society of Gastroenterology explicitly recommends this approach when recurrent IDA is due to unknown or irreversible causes 7.

Monitoring Schedule:

• Every 3 months for the first year after correction 7
• Every 6-12 months thereafter 7
• Additional iron supplementation if hemoglobin or MCV falls below normal 6

The combination of large hiatus hernia with 10 years of refractory anemia makes Cameron lesions the leading diagnosis, but the comprehensive workup must continue to exclude concurrent pathology that could contribute to this severe presentation.