Ferritin in Adult-Onset Still's Disease: Just a Useful Innocent Bystander?

Background. Adult-Onset Still's Disease (AOSD) is an immune-mediated systemic disease with quotidian-spiking fever, rash, and inflammatory arthritis. Hyperferritinemia is a prominent feature, often used for screening. Methods. The key terms “ferritin” and “hyperferritinemia” were used to search PubMed and Medline and were cross-referenced with “Still's Disease.” Results. Hyperferritinemia, although nonspecific, is particularly prevalent in AOSD. While most clinicians associate ferritin with iron metabolism, this is mostly true for the H isoform and not for the L isoform that tends to increase dramatically in hyperferritenemia. In these situations, hyperferritinemia is not associated with iron metabolism and may even mask an underlying iron deficiency. We review, in systematic fashion, the current basic science and clinical literature regarding the regulation of ferritin and its use in the diagnosis and management of AOSD. Conclusion. Serum hyperferritinemia in AOSD has been described for 2 decades, although its mechanism has not yet been completely elucidated. Regulation by proinflammatory cytokines such as interleukin (IL)-1b, IL-6, IL-18, MCSF, and INF-α provides a link to the disease pathogenesis and may explain rapid resolution of hyperferritinemia after targeted treatment and inhibition of key cytokines.

• Publication year

  2012

• Venue

  International Journal of Inflammation

• Publication date

  2012-03-25

• Fields of study

  Medicine

• Identifiers
  DOI 10.1155/2012/298405PMID 22536541PMCID 3321299
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Autoimmunity in hepatitis C virus carriers: involvement of ferritin and prolactin.

  2011cited by this paper
• An International Consensus Survey of Diagnostic Criteria for Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis

  2011cited by this paper
• A series of 22 patients with adult-onset Still's disease presenting with fever of unknown origin. A difficult diagnosis?

  2011cited by this paper
• Causes, clinical symptoms, and outcomes of infectious diseases associated with hemophagocytic lymphohistiocytosis in Taiwanese adults.

  2011cited by this paper
• Iron Deficiency Anemia in Adult Onset Still's Disease with a Serum Ferritin of 26,387 μg/L

  2011cited by this paper
• Ferritin and prolactin levels in multiple sclerosis.

  2011cited by this paper
• Clinical consequences of iron overload from chronic red blood cell transfusions, its diagnosis, and its management by chelation therapy

  2010cited by this paper
• Mechanisms of action of spa therapies in rheumatic diseases: what scientific evidence is there?

  2010cited by this paper
• Immature cell populations and an erythropoiesis gene-expression signature in systemic juvenile idiopathic arthritis: implications for pathogenesis

  2010cited by this paper
• Clinical features and hyperferritinemia diagnostic cutoff points for AOSD based on ROC curve: a Chinese experience

  2010cited by this paper
• Hyperferritinemia and iron overload in type 1 Gaucher disease

  2010cited by this paper
• Serum HO-1 is useful to make differential diagnosis of secondary hemophagocytic syndrome from other similar hematological conditions

  2010cited by this paper
• Adult-onset Still’s disease

  2009influential reference
• Identification of a Novel Mutation in the L Ferritin Iron-Responsive Element Causing Hereditary Hyperferritinemia-Cataract Syndrome

  2009cited by this paper
• Hyperferritinemia in autoimmunity.

  2008cited by this paper
• Ten years of clinical experience with adult onset Still’s disease: is the outcome improving?

  2007cited by this paper
• Ferritin in autoimmune diseases.

  2007cited by this paper
• Cellular regulation and molecular interactions of the ferritins

  2006cited by this paper
• Reactive haemophagocytic syndrome in adult-onset Still’s disease: a report of six patients and a review of the literature

  2006cited by this paper
• Ferritins: dynamic management of biological iron and oxygen chemistry.

  2005cited by this paper
• [Aetiological spectrum of hyperferritinemia].

  2005cited by this paper
• Still's disease in children and adults: A distinct pattern of acute-phase proteins

  2005cited by this paper
• Increased serum HO-1 in hemophagocytic syndrome and adult-onset Still's disease: use in the differential diagnosis of hyperferritinemia

  2005cited by this paper
• Ferritin in atherosclerosis.

  2005cited by this paper
• Anti-serum amyloid component P antibodies in patients with systemic lupus erythematosus correlate with disease activity

  2005cited by this paper
• Serum ferritin, transferrin and soluble transferrin receptor levels in multiple sclerosis patients

  2005cited by this paper
• Article originalSpectre étiologique des hyperferritinémiesAetiological spectrum of hyperferritinemia

  2005cited by this paper
• Spectre étiologique des hyperferritinémies

  2005cited by this paper
• Serum ferritin levels are increased in patients with glomerular diseases and proteinuria.

  2004cited by this paper
• Diabetes is the main factor accounting for the high ferritin levels detected in chronic hepatitis C virus infection.

  2004cited by this paper
• Six-Year Effect of Combined Vitamin C and E Supplementation on Atherosclerotic Progression: The Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) Study

  2003cited by this paper
• Serum cytokine profiles in patients with adult onset Still's disease.

  2003cited by this paper
• The Impact of Iron and Selenium Deficiencies on Iodine and Thyroid Metabolism: Biochemistry and Relevance to Public Health

  2002cited by this paper
• Regulation of ferritin genes and protein.

  2002influential reference
• Low body stores of iron and restless legs syndrome: a correctable cause of insomnia in adolescents and teenagers.

  2002cited by this paper
• Ferritin levels in adult Still's disease: any sugar?

  2002cited by this paper
• A prospective study of coronary heart disease and the hemochromatosis gene (HFE) C282Y mutation: the Atherosclerosis Risk in Communities (ARIC) study.

  2001cited by this paper
• Diagnostic value of ferritin and glycosylated ferritin in adult onset Still's disease.

  2001influential reference
• Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease

  2001cited by this paper
• Comparison of Different Immunoassays for CA 19-9

  2001cited by this paper
• Iron saturation of serum ferritin in patients with adult onset Still's disease.

  2001cited by this paper
• Association of increased ferritin with premature coronary stenosis in men.

  2001cited by this paper
• Elevated serum transferrin receptor concentration in children with juvenile chronic arthritis as evidence of iron deficiency.

  2000cited by this paper
• Redox reactions of neurotransmitters possibly involved in the progression of Parkinson's Disease.

  2000cited by this paper
• Evaluation of Iron Status in Anemic Patients with Rheumatoid Arthritis Using an Automated Immunoturbidimetric Assay for Transferrin Receptor

  2000cited by this paper
• Interleukin-1beta increases binding of the iron regulatory protein and the synthesis of ferritin by increasing the labile iron pool.

  2000cited by this paper
• Effects of TNF-α and IL-1β on iron metabolism by A549 cells and influence on cytotoxicity.

  1999cited by this paper
• Mineralization in ferritin: an efficient means of iron storage.

  1999cited by this paper
• Percentage of glycosylated serum ferritin remains low throughout the course of adult onset Still's disease

  1998influential reference
• HYPERFERRITINEMIA AS A MARKER OF STILL'S DISEASE. AUTHOR'S REPLY

  1998cited by this paper
• Hyperferritinemia as a marker of Still's disease.

  1998cited by this paper
• Secretion of ferritin by rat hepatoma cells and its regulation by inflammatory cytokines and iron.

  1997cited by this paper
• Pulmonary ferritin: differential effects of hyperoxic lung injury on subunit mRNA levels.

  1997cited by this paper
• Very high serum ferritin levels in adult-onset Still's disease.

  1997cited by this paper
• The ferritins: molecular properties, iron storage function and cellular regulation.

  1996cited by this paper
• Embryonic genes expressed in Alzheimer's disease brains.

  1996cited by this paper
• Defective iron supply for erythropoiesis and adequate endogenous erythropoietin production in the anemia associated with systemic-onset juvenile chronic arthritis.

  1996cited by this paper
• Superoxide and hydrogen peroxide‐dependent inhibition of iron regulatory protein activity: a protective stratagem against oxidative injury

  1996cited by this paper
• Anaemia in juvenile chronic arthritis

  1996cited by this paper
• Ferritin levels and response to treatment in patients with Adult Still's disease.

  1996cited by this paper
• Mutation in the iron responsive element of the L ferritin mRNA in a family with dominant hyperferritinaemia and cataract

  1995cited by this paper
• Extremely elevated serum ferritin levels in a university hospital: associated diseases and clinical significance.

  1995cited by this paper
• Iron status in Still's disease.

  1995cited by this paper
• Body iron stores and the risk of coronary heart disease.

  1994cited by this paper
• The role of cytokines in the regulation of ferritin expression.

  1994cited by this paper
• Intravenous iron therapy for severe anaemia in systemic-onset juvenile chronic arthritis.

  1994cited by this paper
• Body iron stores and the risk of coronary heart disease.

  1994cited by this paper
• Serum ferritin and isoferritins are tools for diagnosis of active adult Still's disease.

  1994cited by this paper
• [Hemianopsia as the presenting form of Staphylococcus epidermidis endocarditis].

  1993cited by this paper
• Translational regulation via iron‐responsive elements by the nitric oxide/NO‐synthase pathway.

  1993cited by this paper
• Differential regulation of ferritin H and L subunit mRNA during inflammation and long‐term iron overload

  1993cited by this paper
• [Hyperferritinemia in hyperthyroidism].

  1993cited by this paper
• Hyperferritinemia in adult onset Still's disease and the hemophagocytic syndrome.

  1992cited by this paper
• Adult-onset Still's disease.

  1991cited by this paper
• Translational control during the acute phase response. Ferritin synthesis in response to interleukin-1.

  1990cited by this paper
• Diagnosis of iron-deficiency anemia in the elderly.

  1990cited by this paper
• Immunocytochemical detection of ferritin in human bone marrow and peripheral blood cells using monoclonal antibodies specific for the H and L subunit

  1990cited by this paper
• Interleukin 1 induces ferritin heavy chain in human muscle cells.

  1990cited by this paper
• Induction of ferritin subunit synthesis by iron is regulated at both the transcriptional and translational levels.

  1988cited by this paper
• The molecular cloning and characterization of murine ferritin heavy chain, a tumor necrosis factor-inducible gene.

  1988cited by this paper
• Adult Still's disease: review of 228 cases from the literature.

  1987influential reference
• Differences in the regulation of messenger RNA for housekeeping and specialized-cell ferritin. A comparison of three distinct ferritin complementary DNAs, the corresponding subunits, and identification of the first processed in amphibia.

  1987cited by this paper
• Increased serum ferritin levels in adult Still's disease.

  1987cited by this paper
• Interleukin-1 and the pathogenesis of the acute-phase response.

  1984cited by this paper
• [Still's disease in the adult].

  1983cited by this paper
• Serum ferritin levels in celiac disease.

  1982cited by this paper
• Iron and the sex difference in heart disease risk.

  1981cited by this paper
• PAIN IN GASTRIC ULCER

  1974cited by this paper
• Letter: Herpes simplex and herpes zoster in neoplasia.

  1974cited by this paper
• Still's disease in the adult.

  1971cited by this paper

• Diagnostic Complexity in Systemic Inflammation: Adult-Onset Still's Disease.

  2026cites this paper
• Advancing Precision Medicine in Adult-Onset Still’s Disease: Insights into Biomarkers, Therapies, and COVID-19 Impacts

  2025cites this paper
• Adult-Onset Still’s Disease in a 49-Year-Old Female in the UAE: A Case Report and Literature Review

  2025cites this paper
• Evaluation of clinical biomarkers for differential diagnosis of intravascular lymphoma and Still’s disease

  2025cites this paper
• Enfermedad de Still del adulto

  2025cites this paper
• Diagnostic accuracy of ferritin and glycosylated ferritin in adult-onset Still’s disease: a meta-analysis

  2025cites this paper
• Adult-Onset Still’s Disease (AOSD) in Patient with Previous Lyme Disease

  2025cites this paper
• Adult-Onset Still's Disease With Normal Ferritin Levels and Severe Sulfasalazine-Induced Probable Case of Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Syndrome: A Unique Presentation and Management Challenges

  2025cites this paper
• Adult-Onset Still’s Disease With Suspected Steroid Hypersensitivity: A Case Report

  2025cites this paper
• Diagnostic Challenges and Therapeutic Considerations in Adult-Onset Still’s Disease: A Clinical Case Report

  2024cites this paper
• Naproxen-induced liver injury in a case of adult-onset Still's disease

  2024cites this paper
• Self-Assembled Ferritin Nanoparticles for Delivery of Antigens and Development of Vaccines: From Structure and Property to Applications

  2024cites this paper
• Beyond the Norm: A Unique Case of Adult-Onset Still’s Disease

  2024cites this paper
• Adult-onset Still's disease in clinical practice of infectious diseases: A case report

  2023cites this paper
• Serum Ferritin Levels: A Clinical Guide in Patients With Hair Loss.

  2023cites this paper
• Adult-onset Still's Disease with Acute Kidney Injury Requiring Hemodialysis: A Case Report and Literature Review

  2023cites this paper
• Inflammatory markers in rheumatic diseases

  2022cites this paper
• Acute Phase Reactants: Relevance in Dermatology

  2022cites this paper
• Ferritin triggers neutrophil extracellular trap-mediated cytokine storm through Msr1 contributing to adult-onset Still’s disease pathogenesis

  2022cites this paper
• High procalcitonin is a marker of activity in Adult onset of still's disease

  2022cites this paper
• Methotrexate Failure in the Treatment of Adult-Onset Still’s Disease: A Case Report

  2022cites this paper
• Adult-Onset Still's Disease (AOSD): A Case Report

  2022cites this paper
• Iron overload disorders

  2022influential citation
• Ferritin – from iron, through inflammation and autoimmunity, to COVID-19

  2021cites this paper
• Diagnostic Challenges in Sepsis

  2021cites this paper
• Treatment outcomes in a 10-year geographic cohort of patients with Adult-onset Still ’ s Disease : Case series and literature review

  2021cites this paper
• Evaluating the multivisceral involvement on adult-onset Still’s disease to retrieve imaging-based differences in patients with and without macrophage activation syndrome: results from a single-centre observational study

  2021cites this paper
• The utility of liver transplantation to treat acute liver failure caused by adult-onset Still’s disease: case reports

  2021cites this paper
• Elevated serum gasdermin D N-terminal implicates monocyte and macrophage pyroptosis in adult-onset Still's disease.

  2021cites this paper
• Atypical adult-onset Still’s disease with an initial and sole manifestation of liver injury: A case report and review of literature

  2021cites this paper
• An elderly female with adult-onset Still’s disease initially misdiagnosed as prosthetic joint infection after total knee arthroplasty: lessons in differential diagnosis and treatment

  2020cites this paper
• Successful treatment of adult-onset still disease caused by pulmonary infection-associated hemophagocytic lymphohistiocytosis: A case report.

  2020cites this paper
• Clinical case of a patient with Adult-onset Still disease: A diagnostic challenge or a late diagnosis?

  2020cites this paper
• Non-Conforming Still’s Disease With Low Ferritin and No Skin Rash: A Case Report

  2020cites this paper
• Adult Onset Still's Disease: A Retrospective, Single-Center Study

  2020cites this paper
• Hyperferritinaemia: An Iron Sword of Autoimmunity.

  2019cites this paper
• Proposal for a simple algorithm to differentiate adult-onset Still’s disease with other fever of unknown origin causes: a longitudinal prospective study

  2019cites this paper
• Biologics for the treatment of adult-onset still’s disease

  2019cites this paper
• Diagnosis of hyperferritinemia in 2019

  2019cites this paper
• Pathogenesis, disease course, and prognosis of adult-onset Still's disease: an update and review

  2019cites this paper
• Adult Onset Stills Disease- “A Need for Early Diagnosis and Detection of Systemic Score”

  2019cites this paper
• Macrophage Activation Syndrome in Patients Affected by Adult-onset Still Disease: Analysis of Survival Rates and Predictive Factors in the Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale Cohort

  2018cites this paper
• Intractable Hemophagocytic Syndrome Associated with Systemic Lupus Erythematosus Resistant to Corticosteroids and Intravenous Cyclophosphamide That Was Successfully Treated with Cyclosporine A

  2018cites this paper
• A comprehensive review on adult onset Still's disease.

  2018cites this paper
• Adult-onset Still’s Disease in a Female Patient with Schizophrenia: A Case Report and Literature Review

  2018cites this paper
• Mechanisms, biomarkers and targets for adult-onset Still’s disease

  2018cites this paper
• Hemophagocytic Lymphohistiocytosis in a Patient with Adult-Onset Still’s Disease – a Diagnostic Dilemma

  2017cites this paper
• Treatment of adult-onset still’s disease: up to date

  2017cites this paper
• Serum ferritin as an activity marker for granulamotosis with polyangiitis

  2017cites this paper
• Evidence for genetic overlap between adult onset Still’s disease and hereditary periodic fever syndromes

  2017cites this paper
• Adult-Onset Still’s Disease: Still a Serious Health Problem (a Case Report and Literature Review)

  2017cites this paper
• Severe hyperferritinemia—a clue for severe hepatitis in a patient with adult-onset Still’s disease

  2016cites this paper
• Adult onset Still's disease associated with malignancy-Cause or coincidence?

  2016cites this paper
• Hyperferritinemic syndrome: Still’s disease and catastrophic antiphospholipid syndrome triggered by fulminant Chikungunya infection: a case report of two patients

  2015cites this paper
• Conditions associated with extreme hyperferritinaemia (>3000 μg/L) in adults

  2015cites this paper
• Comment on the Scientific Letter “Adult-Onset Still’s Disease Mimicking Acute Rheumatic Fever”

  2015cites this paper
• Pathogenesis of systemic inflammatory diseases in childhood: “Lessons from clinical trials of anti-cytokine monoclonal antibodies for Kawasaki disease, systemic onset juvenile idiopathic arthritis, and cryopyrin-associated periodic fever syndrome”

  2015influential citation
• Predictors of the response to treatment in acute lupus hemophagocytic syndrome

  2015cites this paper
• Adult-onset Still's disease as a mask of Hodgkin lymphoma

  2015cites this paper
• Pyrexia of unknown origin 90 years on: a paradigm of modern clinical medicine

  2015cites this paper
• Presentation and diagnosis of adult-onset Still’s disease: the implications of current and emerging markers in overcoming the diagnostic challenge

  2015cites this paper
• Adult-onset Still's disease.

  2014cites this paper
• Enfermedad de Still del adulto: falsas apariencias

  2014cites this paper
• sCD163 in AOSD: a biomarker for macrophage activation related to hyperferritinemia

  2014cites this paper
• The hyperferritinemic syndromes and CD163: a marker of macrophage activation.

  2014cites this paper
• Pathogenesis of adult-onset Still’s disease: new insights from the juvenile counterpart

  2014cites this paper
• Magnetic Characterization of Ferritin

  2013cites this paper
• A Case of Extremely Elevated Ferritin Levels in a Patient with Fever of Unknown Etiology

  2013cites this paper
• Adultonset Stills Disease Presenting as Persisten t Fever of Unknown Origin: Case Report and Review of Literature

  2013cites this paper
• N2010 adult-onset Still's disease complicated by hemophagocytic syndrome and catastrophic antiphospholipid syndrome resulting in four limb amputation.

  2013cites this paper
• Unremitting pyrexia, pancytopenia, hepatosplenomegaly, and extreme hyperferritinemia

  2013cites this paper
• Adult Onset Still's Disease and Autoinflammation

  2012influential citation
• A Case of Adult–Onset Still's Disease Complicated with Macrophage Activation Syndrome

  2011cites this paper