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Anemia and hyperferritinemia are frequent findings at diagnosis of Gaucher disease (GD). Macrophage-independent dyserythropoiesis and abnormal iron metabolism have been shown. We evaluated hematological and iron status at diagnosis (T0) and the effect of enzyme replacement therapy (ERT) on erythropoiesis and iron utilization over 5-year follow-up in type 1 GD patients and in an ex vivo model of erythropoiesis from CD34 + peripheral blood cells. At T0, 41% of patients had anemia and 51% hyperferritinemia. Hemoglobin increased from 12.6 (T0) to 13.9 g/dL (T6), GFD15, a marker of ineffective erythropoiesis, decreased from 5401 to 710 pg/ml, and serum ferritin decreased from 614 to 140 mcg/L (p < 0.001). In parallel, transferrin saturation (TSAT) increased. Hepcidin, although in the normal range, decreased from T0 to T6. Ex vivo studies showed that ERT restores the erythroid cells derived from CD34 + impaired ability to differentiate. During ERT, an increase in TFRC expression, consistent with the ability of erythroid precursors to uptake iron, and a reduction in HAMP and concomitant increase in SLC40A1 were observed. This is the largest study with a longitudinal follow-up evaluating erythropoiesis and iron metabolism, combining clinical and ex vivo data in GD. Iron dysregulation likely contributes to anemia, and ERT, by improving iron distribution, improves erythropoiesis., Competing Interests: Declarations. Ethics approval: The study was approved by the ethical review committee of the center “Comitato Etico Milano Area 2” (Protocol number 1678/2016) and was carried out in compliance with the principles established in the Helsinki Declaration. Competing interests: Irene Motta has been or is a current consultant for Sanofi, Bristol Myers Squibb, and Amicus Therapeutics and has received honoraria for lectures, financial support, and grants from Sanofi.Fabio Nascimbeni has been or is a current consultant for Sanofi.Francesca Carubbi received financial support and grants from Sanofi, Amgen.Maria Domenica Cappellini has been or is a current consultant for Sanofi, Novartis, Celgene Corp (Bristol Myers Squibb), Vifor Pharma and Ionis Pharmaceuticals, and received research funding from Sanofi, Novartis, Celgene Corp (Bristol Myers Squibb), La Jolla Pharmaceutical Company, Roche, Protagonist Therapeutics, and CRISPR Therapeutics., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ferritin (Ftn), a globular protein, sequesters 4500 atoms of iron per molecule. Elevated serum Ftn levels (hyperferritinemia) is an indicator of iron homeostasis disorders. We present the results of an observational study involving 17 patients with hyperferritinemia unrelated to hereditary hemochromatosis (HH). All participants received treatment with 200 mg of bovine lactoferrin (bLf) once ( n  = 14) or twice ( n  = 3) a day before meals. The patients, treated with 200 mg/day of bLf, exhibited a significant increase in red blood cells (+10%, p  < 0.001), hemoglobin (+4%, p  < 0.001), and hematocrit (+15%, p  = 0.004), accompanied by a significant reduction in serum Ftn levels (-52%, p  < 0.001), C-reactive protein (CRP) (-85.0%, p  < 0.001), and D-dimers (-19%, p  < 0.001). Among the three patients treated with 400 mg/day of bLf, two had effects similar to those of patients bLf-treated with 200 mg/day and one experienced a strong reduction of Ftn, CRP, and erythrocyte sedimentation rate (from -97% to -75%). The decrease in serum Ftn levels due to bLf treatment was largely independent of gender ( p  = 0.78), age ( p  = 0.66), baseline symptoms ( p  = 0.20), and concomitant acute ( p  = 0.34) and chronic ( p  = 0.53) infections. Although this observational pilot study yields positive effects in patients with hyperferritinemia unrelated to HH treated with bLf, a larger sample size is needed for conclusive results., Competing Interests: Anna Maria Costanzo is an employee of Pharmaguida s.r.l. The other authors declare there are no competing interests.

Introduction: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease, which is mainly characterized by joint swelling, pressure pain and joint destruction. Some patients may suffer from a variety of serious complications, which require prompt diagnosis and treatment. Otherwise, the patient condition may deteriorate rapidly, leading to premature death., Objective: We reported a case of RA combined with hyperferritinemic syndrome and capillary leak syndrome (CLS) that was successfully treated with tocilizumab (TCZ), with the aim of improving diagnostic ideas for clinicians and consequently improving the diagnosis and treatment of the hyperferritinemic syndrome and CLS., Case Summary: A 55-year-old female patient was admitted to the Department of Infectious Diseases of our hospital due to "recurrent fever for more than 1 month and aggravation for 3 days." The patient was diagnosed with fever of unknown origin (lung infection?) and received anti-infective therapy with large encirclement of anti-bacterial, antifungal and empirical anti-tuberculosis successively during hospitalization in the Department of Infectious Diseases. Yet her condition continues to progress. The patient was eventually diagnosed with RA combined with hyperferritinemic syndrome and CLS. Then she received glucocorticoids (GC) (160 mg qd) combined with intravenous immunoglobulin (IVIG, 20 g/d, for 3 days). We considered that the patient also had an overwhelming proinflammatory cytokine storm, so she received a strong anti-inflammatory treatment with TCZ (400 mg qm). The patient symptoms and follow-up chest CT showed significant improvement following treatment., Conclusion: TCZ has good efficacy in the treatment of RA combined with hyperferritinemic syndrome and CLS and is expected to be a promising treatment., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

We report a newborn with hemolytic disease of the fetus and newborn (HDFN) with rapid resolution of extreme hyperferritinemia without chelation. An infant born at 35+3 weeks with HDFN and a history of 3 intrauterine transfusions developed severe hyperferritinemia (maximum, 8258 mcg/L) without evidence of toxic iron deposition on liver biopsy. Her hyperferritinemia was managed with observation alone, and ferritin levels normalized rapidly. This case supports observation as being the preferred alternative to chelation therapy for significant hyperferritinemia in newborns with HDFN in the absence of demonstrated toxic end-organ iron deposition. We also include a review of the related available literature., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Studies from China on COVID-19 revealed that nonsurvivors had cytokine storm with high IL-6 and hyperferritinemia. Iron liberated from necrotic cells may catalyze free radical production and amplify lipid peroxidation causing membrane dysfunction and multiorgan failure. Consequently, iron chelators have been successfully utilized in various experimental and clinical models of cytokine storm and multiorgan damage, such as in ischemia-reperfusion injury, sepsis, and infections. Since viral replication may be influenced by iron accumulation, iron chelation has been proven beneficial in a variety of viral infections, such as HIV-1, hepatitis B virus, Mengovirus, Marburg hemorrhagic fever, Enterovirus 71, and West Nile virus. In this commentary, we elaborate on the idea of considering iron chelation as a therapeutic modality in patients with severe COVID-19 infection. For critically ill patients in the ICU, intravenous deferoxamine would provide sufficient and rapid iron chelation to ameliorate cytokine storm, whereas in less severe cases an oral chelator could prevent the development of excessive inflammatory response., (© 2020 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Background: Hyperferritinemic syndromes are systemic inflammatory disorders characterized by a dysfunctional immune response, which leads to excessive activation of the monocyte-macrophage system with hypercytokinemia and may pursue a rapidly fatal course., Case Presentation: We describe two patients of 11 and 9 years of age with hyperferritinemic syndromes, one with impending macrophage activation syndrome (MAS) and one with overt MAS, who were refractory or intolerant to conventional therapies, but improved dramatically with canakinumab., Conclusions: Our report indicates that canakinumab may be efficacious in the management of hyperferritinemic syndromes, including MAS.