• Humans
• Precision Medicine/methods
• Disease Progression
• Still's Disease, Adult-Onset/therapy
• Still's Disease, Adult-Onset/diagnosis
• Still's Disease, Adult-Onset/drug therapy
• Still's Disease, Adult-Onset/immunology
• Cytokines/metabolism

• Cytokine storm
• Emapalumab
• Hemophagocytic lymphohistiocytosis
• Pathogenic mechanisms
• Targeted therapy

• Lymphohistiocytosis, Hemophagocytic/drug therapy
• Lymphohistiocytosis, Hemophagocytic/therapy
• Humans
• Cytokine Release Syndrome/etiology
• Cytokine Release Syndrome/drug therapy
• Molecular Targeted Therapy/methods
• Interferon-gamma/therapeutic use
• Antibodies, Monoclonal
• Antibodies, Neutralizing

• Humans
• Still's Disease, Adult-Onset/drug therapy
• Still's Disease, Adult-Onset/diagnosis
• Male
• Female
• Adult
• Middle Aged
• Methotrexate/therapeutic use
• Antirheumatic Agents/therapeutic use
• Cohort Studies
• Young Adult
• Aged
• Fever/etiology
• Follow-Up Studies
• Exanthema/etiology
• Arthritis/drug therapy

• Adult-onset Still’s disease
• Delphi
• IL-1
• Still’s disease
• diagnosis
• guideline
• treatment

• Still's Disease, Adult-Onset/drug therapy
• Still's Disease, Adult-Onset/diagnosis
• Still's Disease, Adult-Onset/therapy
• Humans
• Delphi Technique
• Consensus
• Antirheumatic Agents/therapeutic use
• Methotrexate/therapeutic use
• Glucocorticoids/therapeutic use
• Evidence-Based Medicine
• Adult
• Netherlands
• Algorithms
• Practice Guidelines as Topic

• SP 006.19 Novartis pharma
• HCC-4445 Sobi

• Adult-onset Still's disease
• Delphi method
• Expert opinion statements
• Treatment algorithm

• Adult
• Humans
• Still's Disease, Adult-Onset/diagnosis
• Still's Disease, Adult-Onset/drug therapy
• Goals
• Methotrexate/therapeutic use
• Glucocorticoids/therapeutic use

• Adult-onset Still’s disease
• Anakinra
• Macrophage activation syndrome
• Tocilizumab

• 21K08462 Japan Society for the Promotion of Science
• 22K08567 Japan Society for the Promotion of Science

• AOSD
• interleukin-6 inhibitors
• tocilizumab
• treatment

• funded by the Research Capacity Enhancement Hundred Talents Program of Hospital of Chengdu University of Traditional Chinese Medicine

• Autoimmune diseases
• Corticosteroids
• Immunosuppressive agents
• Infections
• Neoplasms

• Adult
• Humans
• Lymphohistiocytosis, Hemophagocytic/diagnosis
• Immunosuppressive Agents/therapeutic use
• Adrenal Cortex Hormones/therapeutic use
• Prognosis
• Interleukin 1 Receptor Antagonist Protein/therapeutic use

• chimeric antigen receptor T-cell therapy
• cytokine release syndrome
• hemophagocytic lymphohistiocytosis
• refractory/relapsed multiple myeloma

• Humans
• Receptors, Chimeric Antigen/genetics
• Cytokines
• Cytokine Release Syndrome/etiology
• Cytokine Release Syndrome/therapy
• T-Lymphocytes
• Lymphohistiocytosis, Hemophagocytic/etiology
• Lymphohistiocytosis, Hemophagocytic/therapy
• Immunotherapy, Adoptive/adverse effects

• Corticosteroids
• Hemophagocytic lymphohistiocytosis
• Hyperferritinemia
• Immunosuppressive therapy
• Sepsis

• Adult
• Child
• Humans
• Lymphohistiocytosis, Hemophagocytic/diagnosis
• Critical Illness
• Hyperferritinemia
• Immunotherapy
• Intensive Care Units

• COVID-19
• SARS-CoV-2
• cytokine storm syndrome (CSS)s
• macrophage activation syndrome (MAS)
• therapy

• National Natural Science Foundation of China

• Antibody drugs
• Drug delivery nanosystem
• Rheumatoid arthritis

• 2022R005 university level scientific research project of Zhejiang Shuren University
• 81874302 National Natural Science Foundation of China

• abscess
• mediastinum
• methicillin-susceptible Staphylococcus aureus
• multicentric Castleman disease
• psoas
• tocilizumab

• Humans
• Castleman Disease/complications
• Castleman Disease/drug therapy
• Castleman Disease/diagnosis
• Abscess
• Staphylococcus aureus

• Adult-onset Still's disease
• Age
• Clinical characteristics
• Mortality
• Outcome

• Adult-onset Still disease
• anti-cytokine therapy
• neutrophil activation
• pro-inflammatory cascade

• Adult
• Humans
• Still's Disease, Adult-Onset/diagnosis
• Still's Disease, Adult-Onset/drug therapy
• Interleukin-18
• Tumor Necrosis Factor-alpha/therapeutic use
• Interleukin-6
• Antirheumatic Agents/therapeutic use
• Adrenal Cortex Hormones/therapeutic use
• Interleukin-1/therapeutic use

We discuss a single case of Hemophagocytic lymphohistiocytosis (HLH) due to NK-type non-Hodgkin lymphoma and Epstein-Barr virus reactivation with multiorgan dysfunction and distributive shock in which we performed cytokine hemoadsorption with Cytosorb ^®. A full microbiological panel was carried out, including screening for imported disease, standard serologies and cultures for bacterial and fungal infection. A liver biopsy and bone marrow aspirate were performed, confirming the diagnosis. The patients fulfilled the HLH-2004 diagnostic criteria, and according to the 2018 Consensus Statements by the HLH Steering Committee of the Histiocyte Society, dexamethasone and etoposide were started. There was an associated hypercytokinemia and, due to refractory distributive shock, rescue therapy with cytokine hemoadsorption was performed during 24 h (within day 2 and 3 from ICU admission). After starting this procedure, rapid hemodynamic control was achieved with a significant reduction in vasopressor support requirements. This case report highlights that cytokine hemoadsorption can be an effective since rapid decrease in IL-10 levels and a significant hemodynamic improvement was achieved.

Adult-onset Still Disease (AoSD) is a rare disorder without standardized diagnostic criteria. People are paying more and more attention to its research. At present, no published studies have assessed the AoSD field using bibliometric tools. This study aimed to analyze research hotspots and frontiers through bibliometrics to provide a scientific and accurate reference for new and existing researchers.

Data were obtained from the Web of Science core database and analyzed by CiteSpace, VOSviewer, and Microsoft Excel.

Involving 86 countries and regions, a total of 11,121 authors published 2,199 articles in 676 journals. These studies were published from 1976 to 2020. The United States published the most related articles (397). The United States, France, Italy, and Germany were the top four countries with a high H-index. Authors and institutions with high number of published articles and high citations are mainly located in France and Italy. High-frequency keywords include classification, criteria, diagnosis, and therapy method. Keyword clustering covers the connection between AoSD and rheumatoid arthritis, disease diagnosis, classification, and risk factors.

The research on AoSD focuses on the diagnosis and differential diagnosis of the disease. Targeted therapy will become a research hotspot in the future, and relevant clinical research needs to appropriately expand the sample size and improve the credibility of the conclusions. The data reported in this study can serve as a useful resource for researchers studying AoSD.

• Bibliometrics
• Cluster Analysis
• Databases, Factual
• Humans
• Risk Factors
• Still's Disease, Adult-Onset
• United States

Adult-onset Still’s disease (AOSD) is a rare multifactorial autoinflammatory disorder of unknown etiology, characterized by an excessive release of cytokines triggered by dysregulated inflammation and articular and systemic manifestations. The clinical spectrum of AOSD ranges from self-limiting forms with mild symptoms to life-threatening cases and presents clinical and biological similarities with the juvenile form (sJIA). Nowadays, the advances in biologic agents no longer limit the treatment to NSAIDs, glucocorticoids, or conventional synthetic DMARDs. The blockade of IL-1 and IL-6 is effective in the treatment of systemic and articular inflammation of AOSD patients; however, novel compounds with different properties and targets are now available and others are being studied. In this review, starting from the pathogenesis of AOSD, we summarized the current and emerging biological therapies, possible effective agents for achieving AOSD control and remission.

Bei der hämophagozytischen Lymphohistiozytose (HLH) handelt es sich um ein Hyperinflammationssyndrom bedingt durch aberrant aktivierte Makrophagen und T‑Zellen. Beim Erwachsenen ist in erster Linie die erworbene Form anzutreffen. Häufige Auslöser sind Infektionen, Malignome und Autoimmunerkrankungen. Zuletzt wurden zudem zunehmend Fälle berichtet, in denen das Auftreten im Zusammenhang mit stattgehabten Immuntherapien zu sehen war. Auf der Intensivstation ist die HLH aufgrund des ähnlichen klinischen Erscheinungsbilds oft schwer von der Sepsis abzugrenzen. Zum Teil liegen beide zeitgleich vor. Die frühzeitige Diagnosestellung und Einleitung einer adäquaten immunsuppressiven Therapie ist für den weiteren Verlauf und die Prognose der HLH essenziell. Deshalb muss bei kritisch kranken Patienten mit persistierendem Fieber und entsprechenden Symptomen (z. B. Splenomegalie, neurologische Auffälligkeiten) oder Laborveränderungen (z. B. erhöhter Ferritinwert, Zytopenie von 2 oder 3 Zellreihen, erhöhte Transaminasen) das Vorliegen einer HLH in Betracht gezogen werden. Die Diagnose wird mithilfe der HLH-2004-Kriterien gestellt. Mit dem HScore kann die Wahrscheinlichkeit des Vorliegens einer HLH berechnet werden. Hochdosierte Kortikosteroide stellen den Grundpfeiler der HLH-Therapie dar. Je nach Auslöser werden Etoposid, Immunglobuline, Anakinra oder weitere Medikamente ergänzt. Der Verlauf hängt neben einem frühzeitigen Behandlungsbeginn vom Auslöser sowie dem Ansprechen auf die Therapie ab. Insgesamt ist die Prognose der HLH trotz maximaler intensivmedizinischer Behandlung ungünstig und sie ist mit einer hohen Letalität assoziiert.

• Adult-onset Still’s disease
• Effectiveness
• Subtype
• Therapy
• Tocilizumab

• adult-onset Still’s disease
• biological therapy
• cytokine storm

• AOSD
• Adult-onset Still's disease
• Anti-IL-1β
• Autoinflammatory disease
• Canakinumab

Increasing evidence indicates a pivotal role of macrophages in innate immunity, which contributes to the pathogenesis of adult-onset Still's disease (AOSD). Despite the available reviews that summarized the pathogenic role of proinflammatory cytokines in AOSD, a systematic approach focusing on the crucial role of macrophages in this disease is still lacking. This review summarizes the updated functions of macrophages in AOSD and their implication in clinical manifestations and therapeutics. We searched the MEDLINE database using the PubMed interface and reviewed the English-language literature as of 31 March 2021, from 1971 to 2021. We focus on the existing evidence on the pathogenic role of macrophages in AOSD and its implication in clinical characteristics and novel therapeutics. AOSD is an autoinflammatory disease mainly driven by the innate immune response. Among the innate immune responses, macrophage activation is a hallmark of AOSD pathogenesis. The pattern recognition receptors (PRRs) on macrophages recognize pathogen-associated molecular patterns and damage-associated molecular patterns and subsequently cause overproduction of proinflammatory cytokines and recruit adaptive immunity. Some biomarkers, such as ferritin and gasdermin D, reflecting macrophage activation were elevated and correlated with AOSD activity. Given that macrophage activation with the overproduction of proinflammatory cytokines plays a pathogenic role in AOSD, these inflammatory mediators would be the therapeutic targets. Accordingly, the inhibitors to interleukin- (IL-) 1, IL-6, and IL-18 have been shown to be effective in AOSD treatment. Gaining insights into the pathogenic role of macrophages in AOSD can aid in identifying disease biomarkers and therapeutic agents for this disease.

• Adult
• Antibodies, Monoclonal, Humanized/adverse effects
• Female
• Humans
• Male
• Retrospective Studies
• Still's Disease, Adult-Onset/drug therapy
• Treatment Outcome

Bei der hämophagozytischen Lymphohistiozytose (HLH) handelt es sich um ein Hyperinflammationssyndrom bedingt durch aberrant aktivierte Makrophagen und T‑Zellen. Beim Erwachsenen ist in erster Linie die erworbene Form anzutreffen. Häufige Auslöser sind Infektionen, Malignome und Autoimmunerkrankungen. Zuletzt wurden zudem zunehmend Fälle berichtet, in denen das Auftreten im Zusammenhang mit stattgehabten Immuntherapien zu sehen war. Auf der Intensivstation ist die HLH aufgrund des ähnlichen klinischen Erscheinungsbilds oft schwer von der Sepsis abzugrenzen. Zum Teil liegen beide zeitgleich vor. Die frühzeitige Diagnosestellung und Einleitung einer adäquaten immunsuppressiven Therapie ist für den weiteren Verlauf und die Prognose der HLH essenziell. Deshalb muss bei kritisch kranken Patienten mit persistierendem Fieber und entsprechenden Symptomen (z. B. Splenomegalie, neurologische Auffälligkeiten) oder Laborveränderungen (z. B. erhöhter Ferritinwert, Zytopenie von 2 oder 3 Zellreihen, erhöhte Transaminasen) das Vorliegen einer HLH in Betracht gezogen werden. Die Diagnose wird mithilfe der HLH-2004-Kriterien gestellt. Mit dem HScore kann die Wahrscheinlichkeit des Vorliegens einer HLH berechnet werden. Hochdosierte Kortikosteroide stellen den Grundpfeiler der HLH-Therapie dar. Je nach Auslöser werden Etoposid, Immunglobuline, Anakinra oder weitere Medikamente ergänzt. Der Verlauf hängt neben einem frühzeitigen Behandlungsbeginn vom Auslöser sowie dem Ansprechen auf die Therapie ab. Insgesamt ist die Prognose der HLH trotz maximaler intensivmedizinischer Behandlung ungünstig und sie ist mit einer hohen Letalität assoziiert.

• Diagnostic techniques and procedures
• Intensive care unit
• Prognosis
• Therapy

• Abscess
• Arthritis
• Diagnosis
• Psoas
• Rheumatoid
• Tocilizumab
• Treatment

Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disease, which is characterized by daily fever and arthritis, with an evanescent rash and neutrophilic leukocytosis. To date, there has been no definite laboratory or imaging test available for diagnosing AOSD; the diagnosis is one of exclusion, which can be very challenging. In particular, AOSD patients may experience different complications affecting their clinical picture, management, and prognosis. The treatment of AOSD remains largely empirical and involves therapeutic agents.

We report the case of a 36-year-old woman who presented with fever, red rash, arthralgia, and sore throat. Her serum ferritin level and white blood cell count were markedly elevated, and the first diagnosis 22 years prior was "juvenile rheumatoid arthritis of systemic type". The patient was treated with prednisone, sulfasalazine, methotrexate, and leflunomide. After remission of her symptoms, the patient stopped taking the medications, and the disease recurred. Ultimately, the patient was diagnosed with adult-onset Still's disease. Relapse occurred several times due to self-medication withdrawal, and an interleukin-6 antagonist (tocilizumab/Actemra) was administered to control the disease. Recently, she was hospitalized because an incision did not heal, and the patient suddenly developed high fever and diarrhea during hospitalization. The patient's disease progressed violently and quickly developed into macrophage activation syndrome, disseminated intravascular coagulation, shock, and multiple organ failure. The patient had sudden cardiac arrest, and she died despite emergency rescue efforts.

AOSD patients need regular follow-up in the long-term treatment process, and must press formulary standard medication, and do not voluntarily withdraw or reduce the dose. Otherwise it may cause disease back-and-forth or serious life-threatening complications. Meanwhile, strict management of trauma, infections, tumors, and other diseases may contribute to improved outcomes in patients with complications.

• Adult-onset Still's disease
• Macrophage activation syndrome
• Disseminated intravascular coagulopathy
• Multiple organ failure
• Death
• Case report

Macrophage activation syndrome (MAS) is a severe, potentially fatal complication of rheumatic diseases. This case demonstrates the significant challenges and therapeutic considerations in adult-onset Still’s disease (AOSD) complicated with MAS at initial presentation, which will be discussed. MAS in our patient was refractory to the first-line therapy with high-dose corticosteroids, early administration of anakinra at a standard dosage and subsequent add-on treatments with cyclosporine A, IVIG, etoposides and tocilizumab. At 2 months after presentation, the patient was still critically ill with clinical, laboratory and histological signs of an active uncontrolled MAS. Notably, adoption of anakinra at a high dosage finally induced remission. This case confirms that adjusted dosage of anakinra is an effective therapeutic strategy in a severe AOSD-related MAS. It is tempting to speculate that anakinra at a high dosage, if used earlier, would have significantly changed the course of the disease in our patient and could have led to earlier remission.

• Adult-onset Still’s disease
• Anakinra
• Macrophage activation syndrome

• Adult-onset Still disease
• TNF inhibitors
• anakinra
• bDMARD
• biologic drugs
• canakinumab
• safety
• tadekinig
• tocilizumab
• treatment

A 32-year-old-man, with a history of chronic urticaria from the age of 27, diagnosed with an adult-onset Still’s disease and received a low dose of glucocorticoids, methotrexate and tocilizumab. Despite the long-term combined treatments, he suffered from chronic urticaria, low-grade fever and bone pain. He was found to have high inflammatory markers, hypogammaglobulinemia, monoclonal IgM – kappa light chain in serum and increased radiotracer uptake in the whole bone scintigraphy. No pathological variants for monogenic autoinflammatory diseases were present in the genome exome sequencing. These investigations confirmed the diagnosis of Schnitzler syndrome, which is an exception before the age of 35. Switching from tocilizumab to interleukin 1 receptor inhibitor, anakinra led to a full clinical response and normalisation of inflammatory markers. Patients with a history of fever and chronic urticaria are routinely tested for monoclonal gammopathy in the context of malignancy, but it should also be considered as a sign of the autoinflammatory syndrome. The Schnitzler syndrome and the adult-onset Still’s disease share common features, so the diagnosis requires a thorough investigation to establish an optimal treatment. In the diagnostic algorithm, monoclonal gammopathy is usually considered red flag for malignancy but might be overlooked as a criterion of Schnitzler syndrome, particularly in young adults. We confirm that the interleukin 1 inhibitor should be the first line of therapy in Schnitzler syndrome, and in the presented case we found it more effective than the interleukin 6 blockade. The main goal of this paper is to increase awareness of Schnitzler syndrome among health care professionals. We aim to present features which can be helpful in differential diagnosis.

• anakinra
• autoinflammation
• chronic urticaria
• monoclonal gammopathy
• tocilizumab

Anakinra, canakinumab and tocilizumab are all effective alternative treatment choice in patients with Still’s disease including both systemic juvenile idiopathic arthritis (SJIA) and adult onset Still’s disease (AOSD).

Aim of this study was to estimate the budget impact of the use of anakinra compared to canakinumab and tocilizumab in the treatment of patients with AOSD or SJIA.

Considering the perspective of the Italian National Health Service (iNHS), a budget impact model (BIM) was developed to estimate the drug costs of anakinra, canakinumab and tocilizumab up to 12 months. The BIM showed the difference of drug expenditure generated by the base case calculated for current prescription volumes, and for different prescription volume scenarios with increased anakinra prescription. Key variables were tested in the sensitivity analysis.

Compared to the current scenario for SJIA, an increase in the market share of anakinra (40% or 50%) would lead to a reduction in the drug expenditure sustained by iNHS (–€1,087,494 [–12.4%] or –€2,023,990 [–23.1%]). Compared to the current scenario for AOSD, an increase in the market share of anakinra (40% or 50%) would lead to a reduction in the drug expenditure sustained by iNHS (–€4,024,585 [–13.5%] or –€8,049,169 [–27.0%]).

According to the present analysis, the use of anakinra, as an alternative to canakinumab or tocilizumab in patients with AOSD or SJIA, could represent a cost-saving option for the iNHS.

• anakinra
• still’s disease
• systemic juvenile idiopathic arthritis
• adult onset still’s disease
• budget impact
• italian national health service

Adult-onset Still’s disease (AOSD) is a rare autoimmune disease of unknown etiology with systemic inflammatory manifestations consisting of a triad of fevers, evanescent skin rash, and arthritis. Although steroids are the first line of therapy, about 20%-30% of patients are refractory, intolerant, and or relapse during tapering or upon discontinuation of steroids. There are no clinical guidelines in treating such patients and treatment in these patients is challenging. Previously used biological agents have limited efficacy and hence there is a need for new therapies. Tocilizumab (TCZ), an interleukin (IL)-6 receptor antibody has been used with a clinical benefit and has shown to decrease the dose of steroids in patients with adult-onset still disease. The aim of this case report is to highlight the use of tocilizumab in relapsing and steroid intolerant cases of AOSD. The use of this drug in patients with AOSD is currently off-label. Randomized control studies can provide additional information that offers better visibility in treating AOSD patients who are steroid-resistant or intolerant. The rarity of disease possesses additional challenges in conducting these studies.

• clinical pharmacy
• immunology
• respiratory medicine (see thoracic medicine)
• rheumatology
• thoracic medicine

• COVID-19
• immunomodulatory drugs
• immunosuppressive drugs
• rare skin diseases

• Abatacept
• fertility
• rheumatoid arthritis
• safety
• testicle

The novel coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is sorely testing health care systems and economies around the world and is rightly considered as the major health emergency in a century. Despite the course of the disease appearing to be mild in many cases, a significant proportion of symptomatic patients develop pneumonia requiring hospitalisation or progress to manifest respiratory complications leading to intensive care treatment. Potential interventions for SARS-CoV2-associated pneumonia are being tested, some of which holding promise, but as of today none of these has yet demonstrated outstanding efficacy in treating COVID-19. In this article, we discuss fresh perspectives and insights into the potential role of immune dysregulation in COVID-19 as well as similarities with systemic inflammatory response in sepsis and the rationale for exploring novel treatment options affecting host immune response.

• Checkpoint inhibitors
• Covid-19
• Cytokine storm
• Immune dysregulation
• Inflammatory receptors
• Sepsis

• Canakinumab
• IL-1
• adult-onset still’s disease
• anakinra
• autoinflammatory diseases
• rilonacept
• systemic juvenile idiopathic arthritis
• treatment

• Anti-Inflammatory Agents/therapeutic use
• Antibodies, Monoclonal, Humanized/therapeutic use
• Arthritis, Juvenile/drug therapy
• Autoimmunity
• Clinical Trials as Topic
• Humans
• Interleukin 1 Receptor Antagonist Protein/therapeutic use
• Interleukin-1beta/immunology
• Still's Disease, Adult-Onset/drug therapy

• Adult-onset Still’s disease
• Autoinflammatory disease
• Cytokines
• Pathophysiology
• Targeted therapy

• Autoimmune Diseases
• Autoimmunity
• Biomarkers
• Cytokines/metabolism
• Disease Management
• Disease Susceptibility/immunology
• Humans
• Molecular Targeted Therapy
• Still's Disease, Adult-Onset/diagnosis
• Still's Disease, Adult-Onset/epidemiology
• Still's Disease, Adult-Onset/etiology
• Still's Disease, Adult-Onset/therapy

• 81571969 The National Natural Science Foundation of China
• 81673045 The National Natural Science Foundation of China

• adult-onset still's disease
• corticosteroids
• first-line therapy
• monocyclic pattern
• remission

• Adrenal Cortex Hormones/administration & dosage
• Adrenal Cortex Hormones/adverse effects
• Adult
• Disease Management
• Dose-Response Relationship, Drug
• Female
• Follow-Up Studies
• Humans
• Male
• Methotrexate/therapeutic use
• Middle Aged
• Prospective Studies
• Remission Induction
• Retrospective Studies
• Still's Disease, Adult-Onset/therapy
• Treatment Outcome