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Abstract：
The use of iron supplementation for anemia in erythropoietic protoporphyria (EPP) is controversial with both benefit and deterioration reported in single case reports. There is no systematic study to evaluate the benefits or risks of iron supplementation in these patients. We assessed the potential efficacy of oral iron therapy in decreasing erythrocyte protoporphyrin (ePPIX) levels in patients with EPP or X-linked protoporphyria (XLP) and low ferritin in an open-label, single-arm, interventional study. Sixteen patients (≥18 years) with EPP or XLP confirmed by biochemical and/or genetic testing, and serum ferritin ≤30 ng/mL were enrolled. Baseline testing included iron studies, normal hepatic function, and elevated plasma porphyrins and ePPIX levels. Oral ferrous sulfate 325 mg twice daily was administered for 12 months. The primary efficacy outcome was the relative difference in total ePPIX level between baseline and 12 months after starting treatment with iron. Secondary measures included improvement in serum ferritin, plasma porphyrins, and clinical symptoms. Thirteen patients had EPP (8 females, 5 males) and 3 had XLP (all females) and the mean age of participants was 38.8 years (SD 14.5). Ten patients completed all study visits limiting interpretation of results. In EPP patients, a transient increase in ePPIX levels was observed at 3 months in 9 of 12 (75%) patients. Iron was discontinued in 2 of these patients after meeting the protocol stopping rule of a 35% increase in ePPIX. Seven patients withdrew before study end. Ferritin levels increased on iron replacement indicating an improvement in iron status. A decrease in ePPIX was seen in both XLP patients who completed the study (relative difference of 0.67 and 0.5 respectively). No substantial changes in ePPIX were seen in EPP patients at the end of the study (n = 8; median relative difference: -0.21 (IQR: -0.44, 0.05). The most common side effects of iron treatment were gastrointestinal symptoms. Hepatic function remained normal throughout the study. Our study showed that oral iron therapy repletes iron stores and transiently increases ePPIX in some EPP patients, perhaps due to a transient increase in erythropoiesis, and may decrease ePPIX in XLP patients. Further studies are needed to better define the role of iron repletion in EPP. Trial registration: NCT02979249.
摘要：
在红细胞生成性原卟啉症（EPP）的贫血中使用铁补充剂存在争议，单例报告中报告了益处和恶化。没有系统的研究来评估这些患者补充铁的益处或风险。我们评估了口服铁疗法降低EPP或X连锁原卟啉（XLP）和低铁蛋白患者红细胞原卟啉（ePPIX）水平的潜在疗效。单臂,介入研究。16例（≥18岁）EPP或XLP患者经生化和/或基因检测证实，纳入血清铁蛋白≤30ng/mL。基线测试包括铁研究，肝功能正常,血浆卟啉和ePPIX水平升高。口服硫酸亚铁325mg，每日两次，持续12个月。主要疗效结果是基线和开始用铁治疗后12个月之间总ePPIX水平的相对差异。次要措施包括血清铁蛋白的改善，血浆卟啉，和临床症状。13例患者患有EPP（8例女性，5名男性）和3名具有XLP（均为女性），参与者的平均年龄为38.8岁（SD14.5）。十名患者完成了所有研究访问，限制了对结果的解释。在EPP患者中，12例患者中有9例(75%)在3个月时观察到ePPIX水平短暂升高.在这些患者中，有2名患者在符合方案停止规定的ePPIX增加35%后停止铁。7名患者在研究结束前退出。铁替代后铁蛋白水平增加，表明铁状态有所改善。在完成研究的两名XLP患者中观察到ePPIX的降低(相对差异分别为0.67和0.5)。在研究结束时，EPP患者的ePPIX没有实质性变化（n=8；中位数相对差异：-0.21（IQR：-0.44，0.05）。铁治疗最常见的副作用是胃肠道症状。肝功能在整个研究中保持正常。我们的研究表明，口服铁剂治疗可在某些EPP患者中复制铁储备并短暂增加ePPIX，也许是由于红细胞生成的短暂增加，并可能降低XLP患者的ePPIX。需要进一步的研究来更好地确定铁补充在EPP中的作用。试用注册：NCT02979249。
