How I treat unexplained refractory iron deficiency anemia

Endoscopic gastrointestinal workup fails to establish the cause of iron deficiency anemia (IDA) inasubstantial proportion of patients. In patients referred for hemato-logic evaluation with unexplained or refractory IDA, screening for celiac disease, autoimmune gastritis, Helicobacter pylori, and hereditary forms of IDA is recommended. About 4% to 6% of patients with obscure refractory IDA have celiac disease, and autoimmune gastritis is encountered in 20% to 27% of patients. Stratification by age cohorts in autoimmune gastritis implies a disease presenting as IDA many years before the establishment of clinical cobalamin deficiency. Over 50% of patients with unexplained refractory IDA have active H pylori infection and, after excluding all other causes of IDA, 64% to 75% of such patients are permanently cured by H pylori eradication. In young patients with a history suggestive of hereditary iron deficiency with serum ferritin higher than expected for IDA, mutations involving iron trafficking and regulation should be considered. Recognition of the respective roles of H pylori, autoimmune gastritis, celiac disease, and genetic defects in the pathogenesis of iron deficiency should have a strong impact on the current diagnostic workup and management of unexplained, or refractory, IDA.