• Humans
• Precision Medicine/methods
• Disease Progression
• Still's Disease, Adult-Onset/drug therapy
• Still's Disease, Adult-Onset/immunology
• Still's Disease, Adult-Onset/genetics
• Cytokines/antagonists & inhibitors
• Molecular Targeted Therapy

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

• JIA
• juvenile idiopathic arthritis
• molecular mechanisms
• paediatric rheumatology

• Child
• Humans
• Arthritis, Juvenile/genetics
• Cytokines/genetics
• Interleukin-1/genetics
• HLA Antigens/genetics
• Genetic Background

• Adult-onset Still’s disease
• Disease severity
• Modified Pouchot score
• Modified Systemic Manifestation Score

• Adult
• Humans
• Still's Disease, Adult-Onset/complications
• Still's Disease, Adult-Onset/diagnosis
• Arthritis, Juvenile
• Cytokines
• Ferritins
• Biomarkers

• Adult-onset Still’s Disease
• COVID-19
• hyperinflammation
• protectin D1
• specialized pro-resolving mediators (SPMs)

• 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

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.

Remitting-RelapsingMultiple Sclerosis (RRMS) and Neuro-Behçet Disease (NBD) are two chronic neuroinflammatory disorders leading to neurological damage. Herein, we investigated in these patients the IL-10-producing cells during the early stages of these disorders. Cellular and molecular investigations were carried out on treatment naive patients suffering from RRMS and NBD recruited at the first episode of clinical relapse. Our findings demonstrate that CSF-B cells from NBD patients, but not RRMS, are the major source of intrathecal IL-10 as compared to T-CD4 cells. Moreover, we showed a lower expression of TGF-β and IL35, in the CSF cells of NBD patients as compared to the control group. Specific in vitro CpG stimulation of peripheral blood B cells from NBD patients resulted in a concomitant early mRNA expression of IL6 and IL10 but was limited to IL10 for RRMS patients. Furthermore, mRNA expression of IL-6 and IL-10 receptors was assessed and intriguingly IL6ST receptor subunit was significantly lower in NBD CSF, but not RRMS while IL10RB was increased in both. Deciphering the role of increased IL-10-producing B cells and IL10RB despite relapsing disease as well as the discordant expression of IL6 and IL6ST may pave the way for a better understanding of the pathophysiology of these neuro-inflammatory disorders.

• B cells
• IL-10
• IL-6
• Neuro-Behçet
• multiple sclerosis

• B-Lymphocytes/metabolism
• Behcet Syndrome/complications
• Behcet Syndrome/metabolism
• Humans
• Interleukin-10/genetics
• Interleukin-6
• RNA, Messenger/genetics
• RNA, Messenger/metabolism

• Dextran sulfate sodium
• Immune regulation
• PI3K/AKT/NF-κB signaling pathway
• Periplaneta americana
• Ulcerative colitis

Adult-onset Still’s disease (AOSD) is a systemic auto-inflammatory disease characterized by the presence of immunologically mediated inflammation and deficient resolution of inflammation. Canakinumab is an approved IL-1β inhibitor in the treatment of AOSD with a balanced efficacy and safety profile. Since inflammatory cytokines play a major role in the pathogenesis of AOSD, we investigated the effects of canakinumab on the cytokine profile of AOSD patients from a randomized controlled trial. Multiplex analysis and ELISA were used to test the concentrations of several cytokines at three time points—week 0 (baseline), week 1 and week 4—in two patient groups—placebo and canakinumab. Two-way repeated-measures analysis of variance revealed a significant temporal effect on the concentrations of MRP 8/14, S100A12, IL-6 and IL-18 with a significant decrease at week 4 in the canakinumab group exclusively. Comparing responders with non-responders to canakinumab showed a significant decrease in MRP 8/14, IL-1RA, IL-18 and IL-6 in responders at week 4, while S100A12 levels decreased significantly in responders and non-responders. In summary, canakinumab showed a striking effect on the cytokine profile in patients with AOSD, exhibiting a clear association with clinical response.

• adult-onset Still’s disease
• canakinumab
• cytokines

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

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

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

The catastrophic outbreak of coronavirus disease 2019 (COVID-19) is currently a public emergency. Adult-onset Still’s disease (AOSD) is an autoinflammatory disease characterized by life-threatening complications. Systemic hyperinflammation and cytokine storm play a critical role in the pathogenesis of both COVID-19 and AOSD. We aimed to compare the similarities and differences focusing on ferritin and cytokine levels between severe COVID-19 and active AOSD. A literature search was performed using the databases PubMed, EMBASE, and Web of Science to collect the levels of cytokine including IL-1β, IL-6, IL-18, TNF-α, IL-10, and ferritin in severe COVID-19 patients. After extracting available data of indicators of interest, we acquired these statistics with a single-arm meta-analysis. Furthermore, a comparison was conducted between 52 patients with active AOSD in our center and severe COVID-19 patients from databases. The levels of IL-6 and IL-10 were higher in severe COVID-19 compared with those in active AOSD. There were no significant differences on the cytokine of IL-1β and TNF-α. Fold changes of IL-18 were defined as the mean expression level ratio of severe COVID-19 to healthy controls in the COVID-19 study and active AOSD to healthy controls in our study, individually. Although the fold change of IL-18 in patients with AOSD was significantly higher than patients with severe COVID-19 (fold change: 594.00 vs 2.17), there was no statistical comparability. In addition, the level of ferritin was higher in active AOSD in comparison with severe COVID-19. Our findings suggest that severe COVID-19 and active AOSD have differences in cytokine panel and ferritin level, indicating the pathogenic role of ferritin in overwhelming inflammation. And it paves the way to make efficacy therapeutic strategy targeting the hyperinflammatory process in COVID-19 according to AOSD management, especially in severe COVID-19.

• adult-onset Still’s disease
• coronavirus disease 2019
• cytokine storm
• hyperferritinemia
• inflammation

Objective: Adult-onset Still's disease (AOSD) is a systemic disorder commonly accompanied by liver involvement. This study aims to illustrate the detailed information of liver abnormalities in patients with AOSD and evaluate the impact on the prognosis.

Methods: A total number of 128 hospitalized patients, who met the Yamaguchi criteria of AOSD in the Department of Rheumatology and Immunology, Ruijin Hospital from July 2016 to August 2019 were consecutively enrolled and followed up. The demographic characteristics, clinical features, laboratory tests, treatments and prognosis were recorded. Correlations of liver function tests (LFTs) with disease activity and laboratory parameters were analyzed by the Spearman test. Risk factors of the refractory AOSD were evaluated by multivariate logistic regression analysis.

Results: Liver involvement was presented in 104 (81.3%) patients with AOSD. We observed that 34 (32.7%) patients were with mild elevation, 32 (30.8%) patients were with moderate elevation, and 38 (36.5%) patients were with severe elevation. The majority of elevated ALT, AST and ALP decreased to normal within the range of 2 months, except for GGT. Furthermore, the LFTs were found significantly correlated with disease activity. Besides, we found patients with higher levels of LFTs tended to require more intensive treatments and suffered from poorer prognosis. Multivariate logistic regression analysis showed ALP ≥ 141 IU/L and GGT ≥ 132 IU/L are independent risk factors of refractory AOSD.

Conclusion: Liver involvement is common in patients with AOSD, the levels of LFTs are associated with disease activity and related to the treatment strategies and prognosis.

• adult-onset Still's disease
• liver involvement
• prognosis
• refractory
• treatment

• adult-onset still disease
• arthritis
• lymphadenopathy
• relapse

• Adult
• Arthritis/complications
• Female
• Humans
• Logistic Models
• Lymphadenopathy/complications
• Male
• Middle Aged
• Recurrence
• Republic of Korea/epidemiology
• Retrospective Studies
• Risk Factors
• Still's Disease, Adult-Onset/epidemiology
• Still's Disease, Adult-Onset/etiology

• AOSD
• Anxiety
• Depression
• HADS
• HRQoL
• SF-36

• Adult
• Anxiety/epidemiology
• Anxiety Disorders
• Depression/complications
• Depression/epidemiology
• Female
• Humans
• Quality of Life
• Still's Disease, Adult-Onset/complications

• adult-onset still's disease
• biomarkers
• disease course
• pathogenesis
• treatment

• Biomarkers/metabolism
• Disease Progression
• Humans
• Interleukin-1beta/therapeutic use
• Interleukin-6/therapeutic use
• Still's Disease, Adult-Onset/drug therapy
• Still's Disease, Adult-Onset/pathology
• Tumor Necrosis Factor-alpha/therapeutic use

Objective: Adult-onset Still's disease (AOSD) is a rare, polygenic, systemic autoinflammatory disease. The aim of this study is to evaluate the serum levels of cysteine-rich angiogenic inducer 61 (Cyr61), a secreted, extracellular protein in AOSD patients.

Methods: A total of 60 AOSD patients (39 of active phase and 21 of inactive phase), 16 rheumatoid arthritis patients as a disease control, and 34 sex- and age-matched healthy control subjects (HC) were enrolled in the study. The data of the clinical manifestations and laboratory examinations were collected. The serum levels of Cyr61, interleukin (IL)-17, and IL-37 were detected by ELISA assay, and the serum levels of IL-10, IL-1β, IL-6, IL-18, and tumor necrosis factor (TNF)-α were examined by electrochemiluminescence assay.

Results: The serum levels of Cyr61 were significantly increased in inactive AOSD than those in active patients and HCs, and the levels of Cyr61 were dramatically increased after treatment. The levels of Cyr61 were inversely correlated with systemic score, the counts of leukocyte and neutrophil, and the levels of inflammatory cytokines (IL-1β, IL-6, and IL-17). Moreover, the levels of Cyr61 were higher in patients without the clinical symptoms of fever, skin rash, sore throat, arthralgia, and lymphadenopathy compared with those in patients with these symptoms.

Conclusion: The serum levels of Cyr61 were inversely correlated with disease activity in AOSD patients; thus, we proposed that Cyr61 was a biomarker for the remission of AOSD.

• adult-onset Still's disease
• biomarker
• cysteine-rich angiogenic inducer 61
• disease activity
• disease remission