• 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

• Yamaguchi criteria
• adult-onset Still’s disease
• arthritis
• case report
• fever of unknown origin

• LDH
• adult-onset Still’s disease
• albumin
• fever of unknown origin
• inflammation
• lactate dehydrogenase/albumin

• histiocytic necrotizing lymphadenitis
• kikuchi-fujimoto disease
• overlap syndrome
• still disease
• yamaguchi criteria

• Humans
• Lymphohistiocytosis, Hemophagocytic/diagnosis
• Lymphohistiocytosis, Hemophagocytic/epidemiology
• Lymphohistiocytosis, Hemophagocytic/mortality
• Still's Disease, Adult-Onset/diagnosis
• Still's Disease, Adult-Onset/epidemiology
• Still's Disease, Adult-Onset/complications
• Male
• Female
• Middle Aged
• Adult
• Hospital Mortality
• United States/epidemiology
• Disseminated Intravascular Coagulation/epidemiology
• Disseminated Intravascular Coagulation/diagnosis
• Disseminated Intravascular Coagulation/etiology
• Liver Failure/etiology
• Liver Failure/epidemiology
• Liver Failure/diagnosis
• Risk Factors
• Aged
• Thrombotic Microangiopathies/epidemiology
• Thrombotic Microangiopathies/diagnosis
• Retrospective Studies
• Respiratory Insufficiency/etiology
• Respiratory Insufficiency/epidemiology
• Hospitalization/statistics & numerical data
• Databases, Factual

• adult-onset still’s disease
• hospital charges
• in-hospital mortality
• length of stay

• adult-onset still's disease
• guillain-barre syndrome
• lung involvement
• neurological involvement
• steroids

• Cryopyrin-associated periodic syndrome
• Familial Mediterranean fever
• Schnitzler syndrome
• Stillʼs disease
• VEXAS syndrome

• Humans
• Hereditary Autoinflammatory Diseases/genetics
• Hereditary Autoinflammatory Diseases/diagnosis
• Adult
• Syndrome
• Fever of Unknown Origin/etiology
• Fever of Unknown Origin/genetics

• adult-onset Still disease
• biologics
• corticosteroids
• disease-modifying antirheumatic drugs
• metaanalysis
• systematic review

• Adult
• Humans
• Adrenal Cortex Hormones/therapeutic use
• Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
• Antibodies, Monoclonal, Humanized/therapeutic use
• Antirheumatic Agents/therapeutic use
• Biological Products/therapeutic use
• Interleukin 1 Receptor Antagonist Protein/therapeutic use
• Remission Induction
• Still's Disease, Adult-Onset/drug therapy
• Treatment Outcome

• Anakinra and pregnancy
• adult-onset Still's disease
• disorders
• hemophagocytic lymphohistiocytosis
• macrophage activation syndrome
• management of AOSD during pregnancy
• pregnancy complications
• rheumatology

• adult-onset Still’s disease
• autoinflammatory disease
• biologics
• macrophage activation syndrome
• systemic juvenile idiopathic arthritis

• adult-onset Still’s disease
• autoimmunity
• autoinflammatory diseases
• fever of unknown origin
• hemophagocytic lymphohistiocytosis
• immune system
• inflammation
• macrophage activation syndrome
• monocytes/macrophages
• steroids

• Non applicable. Ministero della Salute

• adult-onset still's disease
• atypical
• case report
• skin rash

• Female
• Humans
• Middle Aged
• Exanthema/complications
• Fever/complications
• Neoplasms/complications
• Pruritus
• Still's Disease, Adult-Onset/complications
• Still's Disease, Adult-Onset/diagnosis
• Still's Disease, Adult-Onset/drug therapy
• Urticaria/diagnosis
• Urticaria/etiology

• Adult-onset Still's disease
• Atypical hemolytic uremic syndrome
• Autoinflammation
• Macrophage activation syndrome

• Adult
• Female
• Humans
• Young Adult
• Macrophage Activation Syndrome/genetics
• Still's Disease, Adult-Onset/complications
• Still's Disease, Adult-Onset/genetics
• Atypical Hemolytic Uremic Syndrome/genetics
• Lymphohistiocytosis, Hemophagocytic/genetics
• Cyclosporine/therapeutic use

• Adult
• Female
• Humans
• Still's Disease, Adult-Onset/complications
• Still's Disease, Adult-Onset/drug therapy
• Still's Disease, Adult-Onset/diagnosis
• Hepatomegaly/complications
• Hepatomegaly/drug therapy
• Anti-Inflammatory Agents/therapeutic use
• Hepatitis, Autoimmune/complications
• Hepatitis, Autoimmune/drug therapy

• Adult-onset Still’s disease
• Case report
• Hyperferritinaemia
• Myocarditis
• Tocilizumab

• Adult-onset Still’s disease
• aseptic meningitis
• elderly

• arthralgia
• case reports
• fever

• Adult
• Humans
• Female
• Young Adult
• Still's Disease, Adult-Onset/complications
• Still's Disease, Adult-Onset/diagnosis
• Still's Disease, Adult-Onset/drug therapy
• Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
• Fever/etiology
• Arthritis/drug therapy
• Arthralgia/complications
• Arthralgia/drug therapy

• adult‐onset Still's disease
• fever of unknown origin
• pleural effusion

• AOSD
• Adult-onset Still's disease
• Still's disease
• atypical Still's

• Adult-onset Still’s disease
• Classification criteria
• Diagnostic algorithm
• Glycosylated ferritin
• Neutrophil-to-lymphocyte ratio
• Typical rash

• Adult-onset
• COVID-19
• Morbus Still
• Rare disease
• SARS-CoV-2
• Vaccination

• Adult
• Humans
• COVID-19/complications
• COVID-19/prevention & control
• COVID-19 Vaccines/adverse effects
• Incidence
• Retrospective Studies
• Still's Disease, Adult-Onset/chemically induced
• Still's Disease, Adult-Onset/diagnosis
• Vaccination/adverse effects

• Charité - Universitätsmedizin Berlin (3093)

• adult onset still's disease (aosd)
• adult-onset still’s disease
• fever of unkown
• hyperferritinemia
• major hyperferritinemia
• still’ s disease
• upper respiratory tract infection

• SARS‐CoV‐2
• Still's disease
• adult‐onset
• autoimmune diseases
• hyperferritinemia

• Adult
• Humans
• Still's Disease, Adult-Onset/diagnosis
• Rheumatology
• Diagnosis, Differential

• adult-onset still’s disease
• arthritis
• autoinflammatory disease
• prognosis
• systemic juvenile idiopathic arthritis

• Still's disease
• adults
• comorbidity
• epidemiology
• lookback
• survival

• Schnitzler’s syndrome
• VEXAS
• adult onset Still’s disease
• autoinflammation
• inflammasome

• adult-onset still disease
• case report
• corticosteroids
• covid-19
• hyperferritinemia

• Adrenal Cortex Hormones/therapeutic use
• Adult
• Arthritis/diagnosis
• Biomarkers
• COVID-19/complications
• COVID-19/diagnosis
• Exanthema/drug therapy
• Female
• Ferritins
• Fever/etiology
• Humans
• Methotrexate/therapeutic use
• Still's Disease, Adult-Onset/complications
• Still's Disease, Adult-Onset/diagnosis
• Still's Disease, Adult-Onset/drug therapy

• Adamantiades-Behçet’s disease
• adult-onset Still’s disease
• autoinflammatory diseases
• cytokines
• interleukins

• adult onset still disease
• diagnostic utility
• ferritin

• Adult
• Area Under Curve
• Biomarkers
• Ferritins
• Humans
• Still's Disease, Adult-Onset/diagnosis

Adult-onset Still’s disease (AOSD) is a rare disease affecting multiple systems and organs with unknown etiology, and the clinical symptoms are usually described as spiking fever, arthritis, evanescent salmon-pink eruptions, lymphadenopathy, splenomegaly, and other manifestations. The laboratory indicators are not specific, often presenting as increased leukocyte counts and neutrophil percentage, elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), hyperferritinemia, and increased inflammatory factors. ANA, ENA, and RF are negative. According to those unspecific clinical presentations and laboratory findings, infection, tumor, connective tissue disease, and other diseases must be ruled out before diagnosis. The diagnosis of AOSD is a great challenge for clinicians. The mechanism of AOSD pathogenesis is complicated and still being studied. There is a new opinion that atypical persistent skin eruptions (APSEs) with specific histological manifestations are unique for AOSD, and APSEs might be on a spectrum with classical evanescent eruptions. Studies on APSEs showed that IL-1β and IFN-γ are strongly correlated with the pathogenesis of necrosis keratinocytes in APSEs. IL-1β is strongly involved in inflammatory disease when it is abnormal, and plays an important role in the pathogenesis of neutrophil dermatosis. In the early stage of AOSD, skin lesions appear to be evanescent urticaria-like eruptions accompanied by fever, and only neutrophils infiltrate around the blood vessels in the dermis pathologically. As the course of the disease progresses, IL-1β is gradually released. Through the stimulation of other inflammatory factors and the influence of unknown factors, IL-1β gradually infiltrates into the stratum corneum and finally accumulates around the necrotic keratinocytes of the stratum corneum. However, the detailed mechanism is still unknown. IFN-γ could play a pro-inflammatory or regulatory role in some disorders. IL-1β can enhance the expression of IFN-γ, and IFN-γ can cause keratinocyte apoptosis by activating the autocrine of caspase. Also, several pieces of evidence indicate that adaptive immunity is also involved in the pathogenesis of AOSD. Increased α-soluble receptors of IL-2 may suggest T-cell activation and proliferation in AOSD patients. Increased IL-4- and IFN-γ-producing T cells were found in active AOSD and related to disease severity. Frequencies of Treg cells in AOSD were significantly lower and were inversely correlated with disease severity. According to these, more and more researchers have reached a consensus that AOSD is a disease at the crossroads of innate immunity and autoimmunity. In this review, we will provide a comprehensive insight into AOSD, describing research progress and the immunological mechanism contribution to the disease. In the meantime, different treatment options and the efficacy and safety of various biologic agents are also discussed. A further understanding of AOSD requires closer cooperation among doctors from different departments, and this review will provide a new idea for diagnosis and therapeutic options.

Adult-onset Still's disease (AOSD) is a rheumatological condition associated with significant morbidity and mortality. Typically a diagnosis of exclusion, the therapeutic management has relied mainly on symptom control and immune suppression. Methotrexate (MTX), a disease-modifying anti-rheumatoid drug (DMARDs), has become a drug of choice in treating several autoimmune conditions, including AOSD. Unfortunately, despite being largely effective, this medication can result in treatment failure, exacerbation, and a flare of symptoms. We present the case of a 31-year-old male who presented to us with weakness and palpitations, who was ultimately found to have a flare of his Still's disease, despite being on MTX therapy. Our hope is to encourage a suspicion for treatment failure in patients with similar symptoms, in order to encourage a faster initiation of alternative therapies to alleviate their discomfort.

The aim of this research is to discuss the research status, hotspots, frontiers and development trends in the field of adult-onset Still’s disease (AOSD) based on bibliometrics and visual analysis by CiteSpace software.

The relevant research articles on AOSD from 1921 to 2021 were retrieved from the Scopus database. CiteSpace software was used to form a visual knowledge map and conduct analysis for the countries/regions, journals, authors, keywords, clusters, research hotspots and frontiers of the included articles.

There were 2,373 articles included, and the number of articles published during 1921-2021 is increasing. The country with the highest number of articles published was Japan (355, 14.96%), followed by the United States (329, 13.86%) and France (215, 9.06%). The author with the highest number of publications is Ansell, Barbara M. (30, 1.26%), and the author with the highest co-citation frequency is Yamaguchi, Masaya (703). Clinical Rheumatology is the journal with the highest publication frequency. The top five cluster groups were “joint”, “differential diagnosis”, “prednisolone”, “methotrexate” and “macrophage activation syndrome”. The diagnosis, treatment and pathogenesis of AOSD form the main research fields, and prognosis and complications are the research hotspots and trends.

The global research field in AOSD has expanded in the past 100 years. The complications and new pathogenesis of AOSD are hotspots in this field and need further study in the future.

• Bibliometrics
• Humans
• Macrophage Activation Syndrome
• Methotrexate/therapeutic use
• Prognosis
• Still's Disease, Adult-Onset/diagnosis
• United States

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)—a systemic inflammatory disease—often occurs at a young age. Recently, elderly onset patient proportion has been increasing; however, data are limited. To evaluate the characteristics of elderly patients with AOSD in a multicenter cohort, we retrospectively analyzed 62 patients with AOSD at five hospitals during April 2008–December 2020. Patients were divided into two groups according to age at disease onset: younger-onset (≤ 64 years) and elderly onset (≥ 65 years). Clinical symptoms, complications, laboratory findings, treatment, and outcomes were compared. Twenty-six (41.9%) patients developed AOSD at age ≥ 65 years. The elderly onset group had a lower frequency of sore throat (53.8% vs. 86.1%), higher frequency of pleuritis (46.2% vs. 16.7%), and higher complication rates of disseminated intravascular coagulation (30.8% vs. 8.3%) and macrophage activation syndrome (19.2% vs. 2.8%) than the younger onset group. Cytomegalovirus infections were frequent in elderly onset patients (38.5% vs. 13.9%) but decreased with early glucocorticoid dose reduction and increased immunosuppressant and tocilizumab use. Elderly AOSD is not uncommon; these patients have different characteristics than younger-onset patients. Devising a way to control disease activity quickly while managing infections may be an important goal in elderly AOSD.

• adult-onset Still disease
• dermatomyositis
• heliotrope-like manifestation
• macrophage activation syndrome
• tocilizumab

Adult-onset Still’s disease (AOSD) is a rare autoinflammatory disease that typically presents with a triad of fever, evanescent rash, and arthritis. There is often a delay in diagnosis of AOSD due to its nonspecific clinical presentation, which may mimic other infectious, rheumatological disorders, and malignancies. Corticosteroids have been the cornerstone for the management of AOSD for the past many years. However, with the expanding understanding of its pathogenesis, novel therapeutic options targeting various cytokines are being increasingly recognized. Herein, we present a case of AOSD that was successfully treated with tocilizumab, a monoclonal antibody against the interleukin-6 (IL-6) receptor. For the purpose of this article, we also conducted a literature search to review the current therapeutic options available for the treatment of AOSD.

• Interluekin-6
• adult-onset Still’s disease
• tocilizumab

Distinguishing between macrophage activation syndrome (MAS) and a simple flare of Still’s disease (SD) may be challenging. We sought to clarify the clinical features and outcome of MAS in SD and to explore predictive factors of MAS development. Demographic and clinical data, treatments, and outcomes were recorded in a cohort of 206 SD patients. SD patients with and without MAS were compared. To explore predictive factors for the development of MAS, patients were compared at the time of SD diagnosis. Twenty (9.7%) patients experienced MAS, which was inaugural in 12 cases. Patients with MAS were more likely to have hepatomegaly (OR, 3.71; 95% CI, 1.14–11.2; p = 0.03) and neurological symptoms (OR, 4.43; 95% CI, 1.08–15.3; p = 0.04) than patients without MAS. Cytopenias, abnormal liver tests, and coagulation disorders were significantly more frequent in patients with MAS; lactate dehydrogenase and serum ferritin levels were significantly higher. An optimized threshold of 3500 μg/L for serum ferritin yielded a sensitivity (Se) of 85% and a negative predictive value (NPV) of 97% for identifying patients with/without MAS. Survival analysis showed that a high ferritin level at the time of SD diagnosis was predictive of MAS development (p < 0.001). Specific factors, including neurological symptoms, cytopenias, elevated LDH, and coagulopathy, may contribute to the early detection of MAS. Extreme hyperferritinemia at the onset of SD is a prognostic factor for the development of MAS.

• adult-onset Still’s disease
• autoinflammatory disease
• ferritin
• macrophage activation syndrome
• systemic-onset juvenile idiopathic arthritis

To define different clinical phenotypes and assess prognostic factors of adult-onset Still’s disease (AOSD).

Overall, 492 patients with AOSD seen between 2004 and 2018 at a single centre were retrospectively studied.

Of these patients, 78% were female, and the median age at onset was 34 (25–49) years [median (25th–75th percentile)]. The median follow-up time was 7 (3–10) years [median (25th–75th percentile)]. Clinical manifestations at admission were used to subdivide patients with AOSD as follows: systemic inflammation (cluster 1), pure (cluster 2), and intermediate (cluster 3). Each subtype had distinct clinical manifestations and prognoses: cluster 1 (34.6%)—multiple organ manifestations, highest infection rate and mortality, and more than half of the patients with at least one relapse during follow-up; cluster 2 (21.3%)—exclusively female, rash and joint involvement, no internal organ involvement, no mortality, and most of the patients with a monocyclic course; and cluster 3 (44.1%)—less infection rate, no serious complications, and lower mortality rate. The 5- and 10-year survival rates after diagnosis were 92.4% and 86.9%, respectively. Independent risk factors for mortality were age at onset ≥50 (hazard ratio (HR): 6.78, 95% CI: 2.10–21.89), hepatomegaly (HR: 5.05, 95% CI: 1.44–17.70), infection (HR: 15.56, 95% CI: 5.88–41.20), and MAS (HR: 26.82, 95% CI: 7.52–95.60).

Three subtypes of AOSD were identified with distinct clinical manifestations and prognoses. Age at onset ≥50, hepatomegaly, infection, and MAS were prognostic factors for AOSD mortality.

The online version contains supplementary material available at 10.1186/s13075-021-02688-4.

• Adult-onset Still’s disease
• Clinical phenotypes
• Prognosis

The aim of this study was to understand the reasons for canakinumab initiation among patients with Still’s disease, including systemic juvenile idiopathic arthritis (SJIA) and adult-onset Still’s disease (AOSD), in US clinical practice.

Physicians retrospectively reviewed the medical charts of patients with Still’s disease (regardless of age at symptom onset) who were prescribed canakinumab from 2016 to 2018. Patients aged < 16 years at symptom onset were classified as having SJIA and those aged ≥ 16 years at symptom onset (calculated from case-record forms) were classified as having AOSD. Patient treatment history and physician reasons for canakinumab initiation were analyzed. Overall results were presented as SJIA/AOSD. Sensitivity analyses were performed for the robustness of the results.

Forty-three physicians in the USA (rheumatologists/dermatologists/immunologists/allergists: 51.2/27.9/11.6/9.3%; subspecialty in adults/pediatrics: 67.4/32.6%) abstracted information for 72 patients with SJIA/AOSD (SJIA/AOSD/age unknown at symptom onset: 75.0/18.1/6.9%; mean age 19.4 years; children 61.1%; females 56.9%). Most patients (90.3%) received treatment directly preceding canakinumab initiation (etanercept 27.7%; anakinra 18.5%; adalimumab 16.9%); the respective treatment was discontinued due to lack of efficacy/effectiveness (43.1%) and availability of a new treatment (27.8%). Most common reasons for canakinumab initiation were physician perceived/experienced efficacy/effectiveness of canakinumab (77.8%; children/adults: 81.8/71.4%), lack-of-response to previous treatment (45.8%; children/adults: 36.4/60.7%), convenient administration/dosing (26.4%; children/adults: 29.5/21.4%) and ability to discontinue/spare steroids (25.0%; children/adults: 20.5/32.1%). The sensitivity analysis provided similar results.

In US clinical practice, physician perceived/experienced efficacy/effectiveness of canakinumab and lack-of-response to previous treatment were the primary reasons for canakinumab initiation among patients with SJIA/AOSD. Physician perceived/experienced efficacy/effectiveness and convenient administration/dosing of canakinumab were the most common reasons for canakinumab initiation among children, whereas lack-of-response to previous treatment and ability to discontinue/spare steroids being the most frequent reasons among adults.

The online version contains supplementary material available at 10.1007/s40744-021-00402-z.

• Adult-onset Still’s disease
• Canakinumab
• Medical charts
• Real-world
• Systemic juvenile idiopathic arthritis

Lipid peroxidation (LPO) and hyper-ferritinemia are involved in inflammatory responses. Although hyper-ferritinemia is a characteristic of AOSD, its link to LPO remains unclear. We investigated the association between LPO and ferritin expression, and evaluated the relationship between LPO-related metabolites and inflammatory parameters. Mean fluorescence intensity (MFI) of LPO (C11-Biodipy^581/591)-expressing PBMCs/monocytes in AOSD patients and healthy control (HC) subjects was determined by flow-cytometry analysis. Expression of ferritin and cytokines on PBMCs/macrophages was examined by immunoblotting. Plasma levels of LPO-related metabolites and cytokines were determined by ELISA and the MULTIPLEX platform, respectively. LPO MFI on PBMCs/monocytes were significantly higher in patients (median 4456 and 9091, respectively) compared with HC (1900, p < 0.05, and 4551, p < 0.01, respectively). Patients had higher ferritin expression on PBMCs (mean fold, 1.02) than HC (0.55, p < 0.05). Their ferritin expression levels on PBMCs stimulated with LPO inducers erastin or RSL3 (2.47 or 1.61, respectively) were higher than HC (0.84, p < 0.05, or 0.74, p < 0.01). Ferritin expression on erastin-treated/IL-1β-treated macrophages from patients were higher than those from HC (p < 0.001). The elevated levels of LPO-related metabolites, including malondialdehyde and 4-hydroxyalkenals, were positively correlated with disease activity scores, suggesting LPO involvement in AOSD pathogenesis. Increased ferritin expression on PBMCs/macrophages stimulated with LPO inducers indicates a link between LPO and elevated ferritin.

• LPO inducer
• LPO-related metabolites
• adult-onset Still’s disease (AOSD)
• ferritin
• lipid peroxidation (LPO)

• Adult-Onset
• Autoimmune Diseases
• Case report
• Limited
• Scleroderma
• Still's Disease

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