Materiały źródłowe

• #1 Pathogenesis, disease course, and prognosis of adult-onset Still’s disease: an update and review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6940076/

  Adult-onset Still’s disease (AOSD) is a rare but clinically well-known polygenic systemic autoinflammatory disease. […] Pathogenesis of AOSD involves genetic background, infectious triggers, and immunopathogenesis, mainly the activation of macrophages and neutrophils followed by a cytokine storm. […] The etiology of AOSD is still unclear, while there is evidence that various mechanisms contribute to the pathogenesis of AOSD, mainly including genetic susceptibility, infectious triggers, activation of inflammation, and deficient resolution of inflammation. […] Genetic background and environmental triggers like PAMPs and DAMPs are the beginning points of inflammation in AOSD. […] Neutrophils are also extensively activated in AOSD and release more NETs, which can further stimulate NLRP3 activation.

• #2 Mechanisms, biomarkers and targets for adult-onset Still’s disease | Nature Reviews Rheumatology

  https://www.nature.com/articles/s41584-018-0081-x

  Adult-onset Stills disease (AoSD) is a rare but clinically well-known, polygenic, systemic autoinflammatory disease. […] Central to the pathogenesis of AoSD is the intense activation of innate immune cells and overproduction of several pro-inflammatory cytokines including IL-1, IL-6 and IL-18. […] This paper is a recent review of the pathogenic mechanisms involved in AoSD.

• #3 Pathogenesis, disease course, and prognosis of adult-onset Still’s disease: an update and review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6940076/

  Adult-onset Still’s disease (AOSD) is a rare but clinically well-known polygenic systemic autoinflammatory disease. […] Pathogenesis of AOSD involves genetic background, infectious triggers, and immunopathogenesis, mainly the activation of macrophages and neutrophils followed by a cytokine storm. […] The etiology of AOSD is still unclear, while there is evidence that various mechanisms contribute to the pathogenesis of AOSD, mainly including genetic susceptibility, infectious triggers, activation of inflammation, and deficient resolution of inflammation. […] Genetic background and environmental triggers like PAMPs and DAMPs are the beginning points of inflammation in AOSD. […] Neutrophils are also extensively activated in AOSD and release more NETs, which can further stimulate NLRP3 activation.

• #4

  https://link.springer.com/article/10.1007/s40265-024-01993-x

  Adult-onset Stills disease (AOSD) is a multisystemic complex disorder clinically characterised by episodes of spiking fever, evanescent rash, polyarthritis or diffuse arthralgias; multiorgan involvement may develop according to the hyper-inflammatory extent. The pathogenesis of AOSD is not completely recognised. The central role of macrophage activation, which results in T helper 1 (Th1) cell cytokine activation, is well established. Pro-inflammatory cytokines such as interleukin (IL)-1, IL-6 and IL-18 play a fundamental role in disease onset and progression. […] AOSD pathophysiology is not clearly understood. Indeed, as for the majority of autoimmune and autoinflammatory disorders, an association between environmental factors and a genetic predisposition is conceivable. A single gene responsible for AOSD has not been identified, but several studies demonstrated a genetic susceptibility to AOSD and sJIA.

• #5

  https://link.springer.com/article/10.1007/s40265-024-01993-x

  Adult-onset Stills disease (AOSD) is a multisystemic complex disorder clinically characterised by episodes of spiking fever, evanescent rash, polyarthritis or diffuse arthralgias; multiorgan involvement may develop according to the hyper-inflammatory extent. The pathogenesis of AOSD is not completely recognised. The central role of macrophage activation, which results in T helper 1 (Th1) cell cytokine activation, is well established. Pro-inflammatory cytokines such as interleukin (IL)-1, IL-6 and IL-18 play a fundamental role in disease onset and progression. […] AOSD pathophysiology is not clearly understood. Indeed, as for the majority of autoimmune and autoinflammatory disorders, an association between environmental factors and a genetic predisposition is conceivable. A single gene responsible for AOSD has not been identified, but several studies demonstrated a genetic susceptibility to AOSD and sJIA.

• #6 Adult-Onset Still Disease (AOSD) – Rheumatology – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.16.2.

  Adult-onset Still disease (AOSD) is a disease occurring in persons aged 16 years and resembling a systemic form of juvenile idiopathic arthritis. […] The exact etiology of AOSD is still unknown. It has been associated with several different human leukocyte antigens (HLAs), including HLA-Bw35, HLA-DR4, and HLA-DrW6; however, the strengths of these associations remain unclear. […] It is also proposed that a preceding infection may play a role in the etiology of AOSD, leading to an epigenetic effect. Different inflammatory mediators, including interleukin 1 (IL-1), IL-6, IL-18, and tumor necrosis factor (TNF)-alpha, likely play a role in the mechanism of the disease and may be targeted by therapeutic interventions.

• #7

  https://www.archivesofmedicalscience.com/Coexistence-of-adult-onset-Still-s-disease-and-SAPHO-syndrome,189502,0,2.html

  SAPHO syndrome and adult-onset Stills disease (AOSD) are both rare polygenic auto-inflammatory diseases. […] The etiology of AOSD remains unknown, and its clinical presentation includes a typical triad of high fever, joint pain/arthritis, and rash, often accompanied by hyperlipidemia, lymphadenopathy, and leukocytosis. […] AOSD is typically described as the adult type of systemic juvenile idiopathic arthritis (JIA), which is characterized by a combination of autoimmune and auto-inflammatory conditions. […] Studies have suggested that HLA-DRB1*11 and variant major histocompatibility complex (MHC) class II genes contribute to JIA development, while the shared epitope encoded by HLA-DRB1 alleles is associated with typical JIA characteristics. […] Genetic testing conducted by Li et al. has revealed significant susceptibility loci for AOSD in the HLA class II region among Chinese AOSD patients.

• #8 Aberration of Histone Lysine Methylation in Adult-Onset Still’s Disease Are Novel Biomarker Candidates Associated with the Disease Activity – ACR Meeting Abstracts

  https://acrabstracts.org/abstract/aberration-of-histone-lysine-methylation-in-adult-onset-stills-disease-are-novel-biomarker-candidates-associated-with-the-disease-activity/

  Aberration of Histone Lysine Methylation in Adult-Onset Stills Disease Are Novel Biomarker Candidates Associated with the Disease Activity […] Adult-onset Stills disease (AOSD) is a systemic autoinflammatory disorder characterized by spiking fever, transient rash, arthritis and leukocytosis. […] Although a line of evidence has suggested a genetic contribution to AOSD, the pathogenesis of the disease is still unclear. Non-genetic factors, such as environment, infection and epigenetics, may play pivotal roles in the pathogenesis. […] Differences in histone modifications were detected by FACS in different subsets of peripheral WBCs in AOSD patients. Aberrant histone methylations in CD14++CD16- monocytes were associated with the disease activity of AOSD. It is indicated that histone methylation could be a novel biomarker for AOSD.

• #9 Still Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK538345/

  Adult-onset Still disease (AOSD) is a rare systemic inflammatory disorder characterized by daily fever, inflammatory polyarthritis, and a transient salmon-pink maculopapular rash. […] The etiology of AOSD remains unknown. The prevailing hypothesis suggests that AOSD is a reactive syndrome wherein various infectious agents may act as triggers in individuals with a genetic predisposition. Both genetic factors and various infectious agents, including viruses and bacteria like Yersinia enterocolitica and Mycoplasma pneumoniae, have been proposed as significant contributors to the development of AOSD. […] Two immune dysregulations play a crucial role in the pathogenesis of AOSD: innate and adaptive immunity. […] Furthermore, the role of Th-17 responses is emerging in the pathogenesis of AOSD. Elevated levels of Th-17-related cytokines, including IL-1,6,17,18,21, and 23, contribute to the complex immunopathology associated with the disease.

• #10 Adult-Onset Still’s Disease—A Complex Disease, a Challenging Treatment

  https://www.mdpi.com/1422-0067/23/21/12810

  Some clinical signs of AOSD, such as fever spikes, lymphadenitis, and elevated liver enzymes, resemble viral or bacterial infections, suggesting that infection may initiate the inflammatory response in AOSD. […] The disease’s specific pathogenic pathways are still partially known. Neutrophil activation, a defining feature of the pathophysiology of AOSD, is responsible for the onset and progression of inflammation by releasing a vast array of granular enzymes and antimicrobial proteins. […] Neutrophil and macrophage activation is a characteristic of AOSD, potentially due to pro-inflammatory IL-18 signaling. […] The pro-inflammatory cascade is most likely initiated by danger signals such as pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs). […] IL-1β is the main pro-inflammatory cytokine.

• #11 Treatment outcomes in a 10-year geographic cohort of patients with adult-onset Still’s Disease: Case series and literature review | Tasman Medical Journal

  https://tasmanmedicaljournal.com/2021/03/treatment-outcomes-in-a-10-year-geographic-cohort-of-patients-with-adult-onset-stills-diseasecase-series-and-literature-review/

  Adult-onset Stills Disease (AOSD) is a rare inflammatory disease with an estimated prevalence of 1 in 100,000 and an annual incidence of 0.16 to 0.40 per 100,000 depending on the population studied. The underlying pathophysiology remains unclear. However, factors including an imbalance in innate and adaptive immunity geared towards a CD4-Th1 cell response and elaboration of associated inflammatory cytokines including tumour necrosis factor-alpha (TNF-), interleukin (IL)-1 and IL-6 are thought to contribute to disease development and lend weight to an auto-inflammatory hypothesis. Several infectious triggers including viruses (Parvovirus B19, Epstein Barr virus, Cytomegalovirus) and bacteria (Yersinia and Mycoplasma), as well as genetic factors related to HLA linkage have also been implicated. Some patients who meet classification criteria may have a subacute or chronic unidentified viral infection that may take a different trajectory in respect to recovery compared to auto-inflammatory AOSD.

• #12 Still Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK538345/

  Adult-onset Still disease (AOSD) is a rare systemic inflammatory disorder characterized by daily fever, inflammatory polyarthritis, and a transient salmon-pink maculopapular rash. […] The etiology of AOSD remains unknown. The prevailing hypothesis suggests that AOSD is a reactive syndrome wherein various infectious agents may act as triggers in individuals with a genetic predisposition. Both genetic factors and various infectious agents, including viruses and bacteria like Yersinia enterocolitica and Mycoplasma pneumoniae, have been proposed as significant contributors to the development of AOSD. […] Two immune dysregulations play a crucial role in the pathogenesis of AOSD: innate and adaptive immunity. […] Furthermore, the role of Th-17 responses is emerging in the pathogenesis of AOSD. Elevated levels of Th-17-related cytokines, including IL-1,6,17,18,21, and 23, contribute to the complex immunopathology associated with the disease.

• #13 Adult-onset Still’s Disease Associated with Scrub Typhus | Volume 30 – Issue 3 – September 2015 | Archives of Rheumatology

  https://archivesofrheumatology.org/full-text/718

  Adult-onset Stills disease (AOSD) is a rare autoinflammatory disorder with typical features of spiking fever, evanescent rash, and arthritis/ arthralgia. Pathogenesis of AOSD is not well known, and it is hypothesized that environmental triggers may initiate disease in individuals with genetic susceptibility. […] Infectious triggers have been suggested for the cause of AOSD. […] To develop AOSD, infectious triggers and immunological processes may interact in individuals with genetic susceptibilities. […] In our patient, close temporal relationship between scrub typhus and AOSD strongly suggested that scrub typhus triggered AOSD. […] In this article, we report a case of AOSD following scrub typhus and suggest that scrub typhus may be a trigger for the development of AOSD.

• #14 Adult-Onset Still’s Disease: Clinical Aspects and Therapeutic Approach

  https://www.mdpi.com/2077-0383/10/4/733

  Adult-onset Still’s disease (AoSD) is a rare systemic autoinflammatory disease characterized by arthritis, spiking fever, skin rash and elevated ferritin levels. […] Immune dysregulation plays a central role in AoSD and is characterized by pathogenic involvement of both arms of the immune system. […] The past two decades have seen a large body of immunological research on cytokines, which has attributed to both a better understanding of AoSD and revolutionary advances in treatment. […] The exact underlying cause of AoSD is not fully understood. We still do not know what exactly triggers DAMPs and PAMPs. […] The causal inferences between genetics and AoSD are controversial. Human genetic factors apparently contribute to SoJIA in children, whereas the underlying genomic susceptibility in the adult form is unclear.

• #15 Mechanisms, biomarkers and targets for adult-onset Still’s disease | Nature Reviews Rheumatology

  https://www.nature.com/articles/s41584-018-0081-x

  Adult-onset Stills disease (AoSD) is a rare but clinically well-known, polygenic, systemic autoinflammatory disease. […] Central to the pathogenesis of AoSD is the intense activation of innate immune cells and overproduction of several pro-inflammatory cytokines including IL-1, IL-6 and IL-18. […] This paper is a recent review of the pathogenic mechanisms involved in AoSD.

• #16

  https://journals.lww.com/cmj/fulltext/2019/12050/pathogenesis,_disease_course,_and_prognosis_of.13.aspx

  Pathogenesis of AOSD involves genetic background, infectious triggers, and immunopathogenesis, mainly the activation of macrophages and neutrophils followed by a cytokine storm. […] The etiology of AOSD is still unclear, while there is evidence that various mechanisms contribute to the pathogenesis of AOSD, mainly including genetic susceptibility, infectious triggers, activation of inflammation, and deficient resolution of inflammation. […] Genetic background and environmental triggers like PAMPs and DAMPs are the beginning points of inflammation in AOSD. They drive to stimulate macrophages and activate NLPR3 inflammasomes. Then NLRP3 inflammasomes facilitate caspase-1 activation, leading to the proteolytic cleavage of pro-IL-1 and pro-IL-18 to its bioactive and mature forms, which further generate a burst of a cytokine storm with IL-6, IL-8, and TNF- involvement.

• #17 Adult-Onset Still’s Disease—A Complex Disease, a Challenging Treatment

  https://www.mdpi.com/1422-0067/23/21/12810

  Some clinical signs of AOSD, such as fever spikes, lymphadenitis, and elevated liver enzymes, resemble viral or bacterial infections, suggesting that infection may initiate the inflammatory response in AOSD. […] The disease’s specific pathogenic pathways are still partially known. Neutrophil activation, a defining feature of the pathophysiology of AOSD, is responsible for the onset and progression of inflammation by releasing a vast array of granular enzymes and antimicrobial proteins. […] Neutrophil and macrophage activation is a characteristic of AOSD, potentially due to pro-inflammatory IL-18 signaling. […] The pro-inflammatory cascade is most likely initiated by danger signals such as pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs). […] IL-1β is the main pro-inflammatory cytokine.

• #18

  https://journals.lww.com/cmj/fulltext/2019/12050/pathogenesis,_disease_course,_and_prognosis_of.13.aspx

  Pathogenesis of AOSD involves genetic background, infectious triggers, and immunopathogenesis, mainly the activation of macrophages and neutrophils followed by a cytokine storm. […] The etiology of AOSD is still unclear, while there is evidence that various mechanisms contribute to the pathogenesis of AOSD, mainly including genetic susceptibility, infectious triggers, activation of inflammation, and deficient resolution of inflammation. […] Genetic background and environmental triggers like PAMPs and DAMPs are the beginning points of inflammation in AOSD. They drive to stimulate macrophages and activate NLPR3 inflammasomes. Then NLRP3 inflammasomes facilitate caspase-1 activation, leading to the proteolytic cleavage of pro-IL-1 and pro-IL-18 to its bioactive and mature forms, which further generate a burst of a cytokine storm with IL-6, IL-8, and TNF- involvement.

• #19

  https://journals.lww.com/cmj/fulltext/2019/12050/pathogenesis,_disease_course,_and_prognosis_of.13.aspx

  Pathogenesis of AOSD involves genetic background, infectious triggers, and immunopathogenesis, mainly the activation of macrophages and neutrophils followed by a cytokine storm. […] The etiology of AOSD is still unclear, while there is evidence that various mechanisms contribute to the pathogenesis of AOSD, mainly including genetic susceptibility, infectious triggers, activation of inflammation, and deficient resolution of inflammation. […] Genetic background and environmental triggers like PAMPs and DAMPs are the beginning points of inflammation in AOSD. They drive to stimulate macrophages and activate NLPR3 inflammasomes. Then NLRP3 inflammasomes facilitate caspase-1 activation, leading to the proteolytic cleavage of pro-IL-1 and pro-IL-18 to its bioactive and mature forms, which further generate a burst of a cytokine storm with IL-6, IL-8, and TNF- involvement.

• #20 Biological treatment in resistant adult-onset Still’s disease: A single-center, retrospective cohort study | Volume 37 – Issue 1 – March 2022 | Archives of Rheumatology

  https://archivesofrheumatology.org/full-text/1304

  Although many cytokines play a role in the development of the clinical findings of AOSD, IL-1b is the main cytokine that is responsible for the clinical manifestations. […] The triggering factors, such as infections or environmental factors, lead to secretion and activation of proinflammatory cytokines IL-1b and IL-18 by provoking dysregulation of NOD-like receptor 3 protein (NLRP3). […] The IL-1b may induce TNF-a, IL-6, and IL-8 secretion. […] Although many cytokines are implicated in the formation of the broad clinical spectrum of AOSD, particularly IL-1, IL-6, and TNF-a are target cytokines for the treatment of the patients whose clinical findings cannot be suppressed with conventional therapies. […] In conclusion, in the course of AOSD, biological drugs may be rarely required for patients with active disease and arthritis resistant to conventional therapies. However, many cytokines play a role in the pathogenesis of the disease, inhibition of the main cytokines with biological drugs is crucial.

• #21 Adult-onset Still’s disease: Clinical manifestations and diagnosis – UpToDate

  https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-adult-onset-stills-disease

  Adult-onset Still’s disease (AOSD) is an inflammatory disorder characterized by quotidian (daily) fevers, arthritis, and an evanescent rash. Diagnosing AOSD is challenging as patients may have a variety of nonspecific symptoms and laboratory abnormalities. […] Although the specific etiology of AOSD remains unknown, it is likely the manifestation of an autoinflammatory cascade due to innate immune cell activation. This differentiates it from autoimmune mediated inflammatory diseases in which autoantibodies or autoantigen-specific T and/or B cells lead to inflammation and tissue damage. The pathologic amplification of the inflammatory response (ie, “cytokine storm”) in AOSD is likely multifactorial, possibly due to infectious and/or genetic triggers. The final common pathway of the inflammatory response has been attributed to NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation with interleukin 18 (IL-18) overproduction.

• #22 Pathogenesis, disease course, and prognosis of adult-onset Still’s disease: an update and review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6940076/

  Activated neutrophils also generate more S100 proteins, responsible for the amplified inflammatory response. […] The activation and amplification of inflammation, characterized by a cytokine storm, is the hallmark of AOSD. […] Among them, macrophage and neutrophil activation play a major role in the pathogenesis of AOSD. […] Many biomarkers reflecting macrophage activation are increased in patients with AOSD and correlated with disease activity, including macrophage-colony stimulating factor and interferon- (IFN-). […] Macrophage activation leads to increased release of ferritin. […] It is well recognized that AOSD is characterized by high levels of ferritin in serum, called hyperferritinemic syndrome. […] Neutrophil activation is also a hallmark of AOSD. […] CD64 (FcR1), a neutrophil activation marker, is upregulated in active AOSD.

• #23 Pathogenesis, disease course, and prognosis of adult-onset Still’s disease: an update and review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6940076/

  Activated neutrophils also generate more S100 proteins, responsible for the amplified inflammatory response. […] The activation and amplification of inflammation, characterized by a cytokine storm, is the hallmark of AOSD. […] Among them, macrophage and neutrophil activation play a major role in the pathogenesis of AOSD. […] Many biomarkers reflecting macrophage activation are increased in patients with AOSD and correlated with disease activity, including macrophage-colony stimulating factor and interferon- (IFN-). […] Macrophage activation leads to increased release of ferritin. […] It is well recognized that AOSD is characterized by high levels of ferritin in serum, called hyperferritinemic syndrome. […] Neutrophil activation is also a hallmark of AOSD. […] CD64 (FcR1), a neutrophil activation marker, is upregulated in active AOSD.

• #24

  https://journals.lww.com/cmj/fulltext/2019/12050/pathogenesis,_disease_course,_and_prognosis_of.13.aspx

  Activated neutrophils also generate more S100 proteins, responsible for the amplified inflammatory response. […] Notably, macrophage activation leads to release of ferritin, which may exacerbate inflammation in AOSD by unclear mechanisms. […] Deficiency in resolution of inflammation has been hypothesized to play a role in the pathogenesis of AOSD. […] However, the hypothesis lacks sufficient supporting data.

• #25 Pathogenesis, disease course, and prognosis of adult-onset Still’s disease: an update and review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6940076/

  Activated neutrophils also generate more S100 proteins, responsible for the amplified inflammatory response. […] The activation and amplification of inflammation, characterized by a cytokine storm, is the hallmark of AOSD. […] Among them, macrophage and neutrophil activation play a major role in the pathogenesis of AOSD. […] Many biomarkers reflecting macrophage activation are increased in patients with AOSD and correlated with disease activity, including macrophage-colony stimulating factor and interferon- (IFN-). […] Macrophage activation leads to increased release of ferritin. […] It is well recognized that AOSD is characterized by high levels of ferritin in serum, called hyperferritinemic syndrome. […] Neutrophil activation is also a hallmark of AOSD. […] CD64 (FcR1), a neutrophil activation marker, is upregulated in active AOSD.

• #26 Pathogenesis, disease course, and prognosis of adult-onset Still’s disease: an update and review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6940076/

  Activated neutrophils also generate more S100 proteins, responsible for the amplified inflammatory response. […] The activation and amplification of inflammation, characterized by a cytokine storm, is the hallmark of AOSD. […] Among them, macrophage and neutrophil activation play a major role in the pathogenesis of AOSD. […] Many biomarkers reflecting macrophage activation are increased in patients with AOSD and correlated with disease activity, including macrophage-colony stimulating factor and interferon- (IFN-). […] Macrophage activation leads to increased release of ferritin. […] It is well recognized that AOSD is characterized by high levels of ferritin in serum, called hyperferritinemic syndrome. […] Neutrophil activation is also a hallmark of AOSD. […] CD64 (FcR1), a neutrophil activation marker, is upregulated in active AOSD.

• #27 Pathogenesis, disease course, and prognosis of adult-onset Still’s disease: an update and review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6940076/

  Activated neutrophils also generate more S100 proteins, responsible for the amplified inflammatory response. […] The activation and amplification of inflammation, characterized by a cytokine storm, is the hallmark of AOSD. […] Among them, macrophage and neutrophil activation play a major role in the pathogenesis of AOSD. […] Many biomarkers reflecting macrophage activation are increased in patients with AOSD and correlated with disease activity, including macrophage-colony stimulating factor and interferon- (IFN-). […] Macrophage activation leads to increased release of ferritin. […] It is well recognized that AOSD is characterized by high levels of ferritin in serum, called hyperferritinemic syndrome. […] Neutrophil activation is also a hallmark of AOSD. […] CD64 (FcR1), a neutrophil activation marker, is upregulated in active AOSD.

• #28 Pathogenesis, disease course, and prognosis of adult-onset Still’s disease: an update and review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6940076/

  Activated neutrophils also generate more S100 proteins, responsible for the amplified inflammatory response. […] The activation and amplification of inflammation, characterized by a cytokine storm, is the hallmark of AOSD. […] Among them, macrophage and neutrophil activation play a major role in the pathogenesis of AOSD. […] Many biomarkers reflecting macrophage activation are increased in patients with AOSD and correlated with disease activity, including macrophage-colony stimulating factor and interferon- (IFN-). […] Macrophage activation leads to increased release of ferritin. […] It is well recognized that AOSD is characterized by high levels of ferritin in serum, called hyperferritinemic syndrome. […] Neutrophil activation is also a hallmark of AOSD. […] CD64 (FcR1), a neutrophil activation marker, is upregulated in active AOSD.

• #29 Pathogenesis, disease course, and prognosis of adult-onset Still’s disease: an update and review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6940076/

  The spontaneous enhancement of NETs in AOSD is dependent on the high level of reactive oxygen species. […] Lower percentages, decreased absolute numbers and defective cytotoxic function of NK cells have been reported in AOSD, which may contribute to persistent macrophage and lymphocyte activation. […] Significant higher IFN–producing Th1 cells and Th1/Th2 cells ratio have been found in peripheral blood in AOSD patients. […] Deficiency in resolution of inflammation has been hypothesized to play a role in the pathogenesis of AOSD. […] A study published in 2010 discovered a diminished level of circulating CD4+CD25high Treg cells and the transforming growth factor- in AOSD patients, and the level was inversely correlated with disease activity of AOSD and on the rise after clinical remission.

• #30 Pathogenesis, disease course, and prognosis of adult-onset Still’s disease: an update and review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6940076/

  Activated neutrophils also generate more S100 proteins, responsible for the amplified inflammatory response. […] The activation and amplification of inflammation, characterized by a cytokine storm, is the hallmark of AOSD. […] Among them, macrophage and neutrophil activation play a major role in the pathogenesis of AOSD. […] Many biomarkers reflecting macrophage activation are increased in patients with AOSD and correlated with disease activity, including macrophage-colony stimulating factor and interferon- (IFN-). […] Macrophage activation leads to increased release of ferritin. […] It is well recognized that AOSD is characterized by high levels of ferritin in serum, called hyperferritinemic syndrome. […] Neutrophil activation is also a hallmark of AOSD. […] CD64 (FcR1), a neutrophil activation marker, is upregulated in active AOSD.

• #31

  https://journals.lww.com/cmj/fulltext/2019/12050/pathogenesis,_disease_course,_and_prognosis_of.13.aspx

  Activated neutrophils also generate more S100 proteins, responsible for the amplified inflammatory response. […] Notably, macrophage activation leads to release of ferritin, which may exacerbate inflammation in AOSD by unclear mechanisms. […] Deficiency in resolution of inflammation has been hypothesized to play a role in the pathogenesis of AOSD. […] However, the hypothesis lacks sufficient supporting data.

• #32

  https://link.springer.com/article/10.1007/s40265-024-01993-x

  The pathophysiology of AOSD is known to be based on an imbalance between innate and adaptive immunity and is characterised by a substantial increase in pro-inflammatory cytokines that contribute to disease progression. A pivotal role is played by cells of innate immunity, mostly macrophages and neutrophils; Toll-like receptors (TLR) are widely expressed on the surface of dendritic cells (DCs), neutrophils, natural killer (NK) cells, macrophages, mast cells, B cells, T cells and other non-immune cells. […] The final result of the immunological imbalance is the massive release of pro-inflammatory cytokines and the exuberant production of mediators that may amplify and perpetuate, including IL-1, IL-6, IL-8, IL-17, TNF- and IFN-; when the production is uncontrolled, the exacerbation of this inflammatory upregulation may provoke the so-called cytokine storm.

• #33 Adult-Onset Still’s Disease—A Complex Disease, a Challenging Treatment

  https://www.mdpi.com/1422-0067/23/21/12810

  Increasing concentrations of IL-1β cause the most important AOSD symptoms, including fever, an increase in acute-phase reactants, neutrophilia, rash, musculoskeletal discomfort, hepatosplenomegaly and lymphadenopathies, serositis, hypotension, and shock. […] IL-1β is also a critical cytokine in the promotion of adaptive immunity. […] Kudela et al. discovered a considerable increase in IL-18 blood levels in active AOSD compared to other rheumatic diseases, as well as a strong connection between IL-18 serum levels and disease activity in AOSD. […] In contrast to other inflammatory conditions, including RA, systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and psoriatic arthritis (PsA), the circulation amount of free IL-18 is higher in individuals with AOSD during both the active and inactive phases of the condition.

• #34 Biological treatment in resistant adult-onset Still’s disease: A single-center, retrospective cohort study | Volume 37 – Issue 1 – March 2022 | Archives of Rheumatology

  https://archivesofrheumatology.org/full-text/1304

  Although many cytokines play a role in the development of the clinical findings of AOSD, IL-1b is the main cytokine that is responsible for the clinical manifestations. […] The triggering factors, such as infections or environmental factors, lead to secretion and activation of proinflammatory cytokines IL-1b and IL-18 by provoking dysregulation of NOD-like receptor 3 protein (NLRP3). […] The IL-1b may induce TNF-a, IL-6, and IL-8 secretion. […] Although many cytokines are implicated in the formation of the broad clinical spectrum of AOSD, particularly IL-1, IL-6, and TNF-a are target cytokines for the treatment of the patients whose clinical findings cannot be suppressed with conventional therapies. […] In conclusion, in the course of AOSD, biological drugs may be rarely required for patients with active disease and arthritis resistant to conventional therapies. However, many cytokines play a role in the pathogenesis of the disease, inhibition of the main cytokines with biological drugs is crucial.

• #35 Adult-Onset Still’s Disease—A Complex Disease, a Challenging Treatment

  https://www.mdpi.com/1422-0067/23/21/12810

  Increasing concentrations of IL-1β cause the most important AOSD symptoms, including fever, an increase in acute-phase reactants, neutrophilia, rash, musculoskeletal discomfort, hepatosplenomegaly and lymphadenopathies, serositis, hypotension, and shock. […] IL-1β is also a critical cytokine in the promotion of adaptive immunity. […] Kudela et al. discovered a considerable increase in IL-18 blood levels in active AOSD compared to other rheumatic diseases, as well as a strong connection between IL-18 serum levels and disease activity in AOSD. […] In contrast to other inflammatory conditions, including RA, systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and psoriatic arthritis (PsA), the circulation amount of free IL-18 is higher in individuals with AOSD during both the active and inactive phases of the condition.

• #36 Pathogenesis, disease course, and prognosis of adult-onset Still’s disease: an update and review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6940076/

  The spontaneous enhancement of NETs in AOSD is dependent on the high level of reactive oxygen species. […] Lower percentages, decreased absolute numbers and defective cytotoxic function of NK cells have been reported in AOSD, which may contribute to persistent macrophage and lymphocyte activation. […] Significant higher IFN–producing Th1 cells and Th1/Th2 cells ratio have been found in peripheral blood in AOSD patients. […] Deficiency in resolution of inflammation has been hypothesized to play a role in the pathogenesis of AOSD. […] A study published in 2010 discovered a diminished level of circulating CD4+CD25high Treg cells and the transforming growth factor- in AOSD patients, and the level was inversely correlated with disease activity of AOSD and on the rise after clinical remission.

• #37 Pathogenesis, disease course, and prognosis of adult-onset Still’s disease: an update and review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6940076/

  The spontaneous enhancement of NETs in AOSD is dependent on the high level of reactive oxygen species. […] Lower percentages, decreased absolute numbers and defective cytotoxic function of NK cells have been reported in AOSD, which may contribute to persistent macrophage and lymphocyte activation. […] Significant higher IFN–producing Th1 cells and Th1/Th2 cells ratio have been found in peripheral blood in AOSD patients. […] Deficiency in resolution of inflammation has been hypothesized to play a role in the pathogenesis of AOSD. […] A study published in 2010 discovered a diminished level of circulating CD4+CD25high Treg cells and the transforming growth factor- in AOSD patients, and the level was inversely correlated with disease activity of AOSD and on the rise after clinical remission.

• #38 Pathogenesis, disease course, and prognosis of adult-onset Still’s disease: an update and review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6940076/

  The spontaneous enhancement of NETs in AOSD is dependent on the high level of reactive oxygen species. […] Lower percentages, decreased absolute numbers and defective cytotoxic function of NK cells have been reported in AOSD, which may contribute to persistent macrophage and lymphocyte activation. […] Significant higher IFN–producing Th1 cells and Th1/Th2 cells ratio have been found in peripheral blood in AOSD patients. […] Deficiency in resolution of inflammation has been hypothesized to play a role in the pathogenesis of AOSD. […] A study published in 2010 discovered a diminished level of circulating CD4+CD25high Treg cells and the transforming growth factor- in AOSD patients, and the level was inversely correlated with disease activity of AOSD and on the rise after clinical remission.

• #39

  https://www.archivesofmedicalscience.com/Coexistence-of-adult-onset-Still-s-disease-and-SAPHO-syndrome,189502,0,2.html

  The pathogenesis of AOSD remains unclear; however, previous studies have suggested that it may be a result of a combination of inflammatory immune cells and cytokines, influenced by genetic factors. […] Recent studies have shown that cytokines such as IL-1, IL-6 and IL-18 jointly drive the occurrence and development of AOSD. […] Inflammatory cytokines also play a crucial role in the pathogenesis of SAPHO syndrome. […] The elevation of cytokines such as IL-1, IL-8, IL-17 and IL-18 also supports the idea of an inflammatory origin of SAPHO syndrome, and that cytokines, such as IL-8 and IL-18, may be responsible for maintaining the clinical manifestations of SAPHO syndrome. […] Chen et al. observed an increase in circulating Th17 cells, which correlates with disease activity in AOSD, suggesting that the dysregulation of Th17 cells may represent a significant mechanism underlying the pathogenesis of AOSD.

• #40 B cell subsets in adult-onset Still’s disease: potential candidates for disease pathogenesis and immunophenotyping | Arthritis Research & Therapy | Full Text

  https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-023-03070-2

  Adult-onset Stills disease (AOSD) is a systemic autoinflammatory disorder of unknown etiology. B cells are critical participants in different rheumatic diseases, and their roles in AOSD are rarely investigated. This study aimed to unveil the B cell subset features in AOSD and provide evidence for B cell-based diagnosis and targeted therapies of AOSD. […] The frequencies of B cell subsets were altered in AOSD patients. Disease-promoting subsets (such as nave B cells, double negative B cells (DN B cells), and plasmablasts) increased, and potential regulatory subsets (such as unswitched memory B cells (UM B cells) and CD24hiCD27+ B cells (B10 cells)) decreased in the peripheral blood of AOSD patients. […] B cell subsets are significantly altered in AOSD patients, potentially contributing to the disease pathogenesis.

• #41 B cell subsets in adult-onset Still’s disease: potential candidates for disease pathogenesis and immunophenotyping | Arthritis Research & Therapy | Full Text

  https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-023-03070-2

  Adult-onset Stills disease (AOSD) is a systemic autoinflammatory disorder of unknown etiology. B cells are critical participants in different rheumatic diseases, and their roles in AOSD are rarely investigated. This study aimed to unveil the B cell subset features in AOSD and provide evidence for B cell-based diagnosis and targeted therapies of AOSD. […] The frequencies of B cell subsets were altered in AOSD patients. Disease-promoting subsets (such as nave B cells, double negative B cells (DN B cells), and plasmablasts) increased, and potential regulatory subsets (such as unswitched memory B cells (UM B cells) and CD24hiCD27+ B cells (B10 cells)) decreased in the peripheral blood of AOSD patients. […] B cell subsets are significantly altered in AOSD patients, potentially contributing to the disease pathogenesis.

• #42 B cell subsets in adult-onset Still’s disease: potential candidates for disease pathogenesis and immunophenotyping | Arthritis Research & Therapy | Full Text

  https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-023-03070-2

  The alterations of the frequencies of B cell subsets indicate their potential roles in AOSD. The increased B cell subsets, including naive B cells, DN B cells, and plasmablasts, may promote the development of the AOSD. In the same way, the decreased B cell subsets, such as UM B cells and B10 cells, may play immune regulatory roles in AOSD. […] Higher nave B cells and lower UM B cells, SM B cells, total CD27+ memory B cells, DN B cells, and B10 cells are shown in AOSD patients with abnormalities of parameters related to liver function. […] The correlation between B cell subsets and coagulation may also be related to liver function abnormalities. […] The abnormal B cell subset distribution in AOSD can also inspire targeting B cell therapy, but the mechanisms behind it need to be clarified before going further.

• #43 Pathogenesis, disease course, and prognosis of adult-onset Still’s disease: an update and review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6940076/

  The spontaneous enhancement of NETs in AOSD is dependent on the high level of reactive oxygen species. […] Lower percentages, decreased absolute numbers and defective cytotoxic function of NK cells have been reported in AOSD, which may contribute to persistent macrophage and lymphocyte activation. […] Significant higher IFN–producing Th1 cells and Th1/Th2 cells ratio have been found in peripheral blood in AOSD patients. […] Deficiency in resolution of inflammation has been hypothesized to play a role in the pathogenesis of AOSD. […] A study published in 2010 discovered a diminished level of circulating CD4+CD25high Treg cells and the transforming growth factor- in AOSD patients, and the level was inversely correlated with disease activity of AOSD and on the rise after clinical remission.

• #44

  https://journals.lww.com/cmj/fulltext/2019/12050/pathogenesis,_disease_course,_and_prognosis_of.13.aspx

  Activated neutrophils also generate more S100 proteins, responsible for the amplified inflammatory response. […] Notably, macrophage activation leads to release of ferritin, which may exacerbate inflammation in AOSD by unclear mechanisms. […] Deficiency in resolution of inflammation has been hypothesized to play a role in the pathogenesis of AOSD. […] However, the hypothesis lacks sufficient supporting data.

• #45 Pathogenesis, disease course, and prognosis of adult-onset Still’s disease: an update and review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6940076/

  The spontaneous enhancement of NETs in AOSD is dependent on the high level of reactive oxygen species. […] Lower percentages, decreased absolute numbers and defective cytotoxic function of NK cells have been reported in AOSD, which may contribute to persistent macrophage and lymphocyte activation. […] Significant higher IFN–producing Th1 cells and Th1/Th2 cells ratio have been found in peripheral blood in AOSD patients. […] Deficiency in resolution of inflammation has been hypothesized to play a role in the pathogenesis of AOSD. […] A study published in 2010 discovered a diminished level of circulating CD4+CD25high Treg cells and the transforming growth factor- in AOSD patients, and the level was inversely correlated with disease activity of AOSD and on the rise after clinical remission.

• #46 Pathogenesis, disease course, and prognosis of adult-onset Still’s disease: an update and review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6940076/

  The spontaneous enhancement of NETs in AOSD is dependent on the high level of reactive oxygen species. […] Lower percentages, decreased absolute numbers and defective cytotoxic function of NK cells have been reported in AOSD, which may contribute to persistent macrophage and lymphocyte activation. […] Significant higher IFN–producing Th1 cells and Th1/Th2 cells ratio have been found in peripheral blood in AOSD patients. […] Deficiency in resolution of inflammation has been hypothesized to play a role in the pathogenesis of AOSD. […] A study published in 2010 discovered a diminished level of circulating CD4+CD25high Treg cells and the transforming growth factor- in AOSD patients, and the level was inversely correlated with disease activity of AOSD and on the rise after clinical remission.

• #47 Progress in biological therapies for adult-onset Stills | BTT

  https://www.dovepress.com/progress-in-biological-therapies-for-adult-onset-stills-disease-peer-reviewed-fulltext-article-BTT

  These proinflammatory cytokines, in turn, lead to amplifying the inflammatory cascade through the exuberant production of downstream mediators, such as IL-6, IL-8, IL-17, TNF-, and interferon (IFN)-, a so-called cytokine storm. […] The insufficient control of inflammatory activity in AOSD patients is even associated with a risk of serious and different complications. […] Secondary hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS) is one of the most severe and life-threatening complications in predisposed AOSD patients. […] Continuous high fever, lymphadenopathy, hepatosplenomegaly, and remarkably elevated levels of serum ferritin and IL-18 contribute to the clinical work-up of MAS patients. […] However, there is evidence that cytokine blockade, such as IL-1 and IL-18 inhibitions, might confer additional advantages in the treatment of MAS.

• #48 Progress in biological therapies for adult-onset Stills | BTT

  https://www.dovepress.com/progress-in-biological-therapies-for-adult-onset-stills-disease-peer-reviewed-fulltext-article-BTT

  In light of novel evidence about AOSD pathogenesis and the use of biological treatments, a different cytokine profile has been observed associated with distinct AOSD manifestations. […] The systemic subset, indeed, presents an excessive level of interleukin (IL)-1 and IL-18, while the chronic articular AOSD is principally driven by IL-6 and tumor necrosis factor (TNF)-.

• #49

  https://link.springer.com/article/10.1007/s12026-014-8561-9

  Adult-onset Stills disease (AOSD) is a rare inflammatory disease characterized by the classical triad of daily fever, arthritis, and typical salmon-colored rash. Recent accumulation of knowledge, mostly arising from hereditary autoinflammatory diseases and from the systemic-onset juvenile idiopathic arthritis (sJIA), has given raise to new hypotheses on the pathophysiology of AOSD. […] Then, we summarize current hypotheses on the underlying pathogenesis: (1) an infectious hypothesis; (2) an autoinflammatory hypothesis; (3) a lymphohistiocytic hypothesis; and (4) a hyperferritinemic hypothesis. […] Finally, we present the recent data suggesting that patients with AOSD fall into two distinct subgroups with different courses, one with prominent systemic features and one with chronic arthritis.

• #50 Biological treatment in resistant adult-onset Still’s disease: A single-center, retrospective cohort study | Volume 37 – Issue 1 – March 2022 | Archives of Rheumatology

  https://archivesofrheumatology.org/full-text/1304

  Adult-onset Stills disease (AOSD) is a rare systemic inflammatory disease with an unknown etiology. The main clinical manifestations of the disease are fever, maculopapular salmon-pink rash, arthralgia, and arthritis. Additionally, sore throat or pharyngitis, lymphadenopathy, hepatomegaly and splenomegaly, serositis, and myalgia can be seen. […] It is well known that proinflammatory cytokines such as ferritin, interleukin (IL)-1, IL-6, IL-8, IL-18, tumor necrosis factor-alpha (TNF-a), and interferon-gamma (IFN-g) are responsible for manifestations of AOSD. […] Due to the well-known effects of IL-1, IL-6, and TNF-a in the pathogenesis of the disease, inhibition of these pathways are favorable treatment options. […] The current study showed that tocilizumab was predominantly preferred for musculoskeletal manifestations and anakinra was mainly prescribed for systemic involvement for patients who were resistant to the conventional therapies.

• #51 Biological treatment in resistant adult-onset Still’s disease: A single-center, retrospective cohort study | Volume 37 – Issue 1 – March 2022 | Archives of Rheumatology

  https://archivesofrheumatology.org/full-text/1304

  Although many cytokines play a role in the development of the clinical findings of AOSD, IL-1b is the main cytokine that is responsible for the clinical manifestations. […] The triggering factors, such as infections or environmental factors, lead to secretion and activation of proinflammatory cytokines IL-1b and IL-18 by provoking dysregulation of NOD-like receptor 3 protein (NLRP3). […] The IL-1b may induce TNF-a, IL-6, and IL-8 secretion. […] Although many cytokines are implicated in the formation of the broad clinical spectrum of AOSD, particularly IL-1, IL-6, and TNF-a are target cytokines for the treatment of the patients whose clinical findings cannot be suppressed with conventional therapies. […] In conclusion, in the course of AOSD, biological drugs may be rarely required for patients with active disease and arthritis resistant to conventional therapies. However, many cytokines play a role in the pathogenesis of the disease, inhibition of the main cytokines with biological drugs is crucial.

• #52 Progress in biological therapies for adult-onset Stills | BTT

  https://www.dovepress.com/progress-in-biological-therapies-for-adult-onset-stills-disease-peer-reviewed-fulltext-article-BTT

  These proinflammatory cytokines, in turn, lead to amplifying the inflammatory cascade through the exuberant production of downstream mediators, such as IL-6, IL-8, IL-17, TNF-, and interferon (IFN)-, a so-called cytokine storm. […] The insufficient control of inflammatory activity in AOSD patients is even associated with a risk of serious and different complications. […] Secondary hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS) is one of the most severe and life-threatening complications in predisposed AOSD patients. […] Continuous high fever, lymphadenopathy, hepatosplenomegaly, and remarkably elevated levels of serum ferritin and IL-18 contribute to the clinical work-up of MAS patients. […] However, there is evidence that cytokine blockade, such as IL-1 and IL-18 inhibitions, might confer additional advantages in the treatment of MAS.

• #53 Canakinumab for Treatment of Adult-Onset Still’s Disease to Achieve Reduction of Arthritic Manifestation (CONSIDER): phase II, randomised, double-blind, placebo-controlled, multicentre, investigator-initiated trial | Annals of the Rheumatic Diseases

  https://ard.bmj.com/content/79/8/1090

  In agreement with the postulation that sJIA and AOSD represent the same disease, it has been shown in numerous studies that similar approaches with IL-1 and IL-6 inhibiting drugs are sufficient to control disease activity in both conditions. […] Furthermore, it is known that a significant proportion of patients with AOSD have a self-limited course of their disease. […] The discussion concerning an individualised treatment for specific manifestations of AOSD is ongoing. The main question is whether IL-6 blockade could be more effective in the control of arthritic manifestation, whereas IL-1 could be a better target in case of predominant systemic manifestation. […] These results provide additional evidence for the role of the IL-1 signalling pathway and support the concept of a Still’s disease continuum that includes both a paediatric/juvenile-onset (sJIA) and an adult-onset (AOSD) form. […] Thus, the results also indicate that inhibition of IL-1 signalling in AOSD represents a valuable treatment approach.

• #54 A Diagnostic Dilemma: Adult-Onset Still’s Disease With Secondary Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome? | Parkash | Journal of Medical Cases

  https://www.journalmc.org/index.php/JMC/article/view/3858/3305

  In secondary forms of HLH, identifying and addressing disease triggers (infection, drugs, and malignancy) is a critical therapy component. […] Treatment targets are different if we consider secondary HLH/MAS in AOSD. There is still confusion in the literature on when to consider specific treatments in case complications arise from AOSD. The early use of steroids is a widely accepted treatment in the literature. TNF- inhibitors (etanercept, adalimumab, and infliximab), IL-6 receptor inhibitors (tocilizumab and sarilumab), and IL-1 Inhibitor (anakinra, canakinumab) have demonstrated efficacy both as monotherapy and in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the treatment of acute to chronic inflammatory immune-mediated diseases including AOSD. These drugs selectively inhibit the pathways involved in disease pathogenesis, as mentioned above.

• #55 Adult-onset Still’s disease evolving with multiple organ failure and death: A case report and review of the literature

  https://www.wjgnet.com/2307-8960/full/v9/i4/886.htm

  It has been reported that the incidence of MAS is up to 15% among those AOSD patients and it is considered the most severe complication, with a high mortality rate ranging from 10% to 41%. […] The treatment of AOSD remains largely empirical, and therapeutic agents for AOSD include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) such as methotrexate, and biological disease-modifying anti-rheumatic drugs (bDMARDs). […] Some studies have shown that NSAIDs may fail to control the symptoms of AOSD, and a large percentage of patients may afflict drug adverse reactions. […] Biologic agents or biologic DMARDs (bDMARDs) targeting specific cytokines are suggested for the treatment of those cases that are refractory to csDMARDs and corticosteroids.

• #56 Canakinumab for Treatment of Adult-Onset Still’s Disease to Achieve Reduction of Arthritic Manifestation (CONSIDER): phase II, randomised, double-blind, placebo-controlled, multicentre, investigator-initiated trial | Annals of the Rheumatic Diseases

  https://ard.bmj.com/content/79/8/1090

  In agreement with the postulation that sJIA and AOSD represent the same disease, it has been shown in numerous studies that similar approaches with IL-1 and IL-6 inhibiting drugs are sufficient to control disease activity in both conditions. […] Furthermore, it is known that a significant proportion of patients with AOSD have a self-limited course of their disease. […] The discussion concerning an individualised treatment for specific manifestations of AOSD is ongoing. The main question is whether IL-6 blockade could be more effective in the control of arthritic manifestation, whereas IL-1 could be a better target in case of predominant systemic manifestation. […] These results provide additional evidence for the role of the IL-1 signalling pathway and support the concept of a Still’s disease continuum that includes both a paediatric/juvenile-onset (sJIA) and an adult-onset (AOSD) form. […] Thus, the results also indicate that inhibition of IL-1 signalling in AOSD represents a valuable treatment approach.

• #57 Adult-onset Still’s disease—pathogenesis, clinical manifestations, and new treatment options | Scilit

  https://www.scilit.com/publications/6e0b56805d77b9ead2804832ff852178

  Adult-onset Still’s disease (AOSD), a systemic inflammatory disorder, is often considered a part of the spectrum of the better-known systemic-onset juvenile idiopathic arthritis, with later age onset. […] Recent advances have revealed a pivotal role of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1, IL-6, IL-8, and IL-18 in disease pathogenesis, giving rise to the development of novel targeted therapies aiming at optimal disease control. […] The review aims to summarize recent advances in pathophysiology and potential therapeutic strategies in AOSD.

• #58 Adult-Onset Still’s Disease: Clinical Aspects and Therapeutic Approach

  https://www.mdpi.com/2077-0383/10/4/733

  Adult-onset Still’s disease (AoSD) is a rare systemic autoinflammatory disease characterized by arthritis, spiking fever, skin rash and elevated ferritin levels. […] Immune dysregulation plays a central role in AoSD and is characterized by pathogenic involvement of both arms of the immune system. […] The past two decades have seen a large body of immunological research on cytokines, which has attributed to both a better understanding of AoSD and revolutionary advances in treatment. […] The exact underlying cause of AoSD is not fully understood. We still do not know what exactly triggers DAMPs and PAMPs. […] The causal inferences between genetics and AoSD are controversial. Human genetic factors apparently contribute to SoJIA in children, whereas the underlying genomic susceptibility in the adult form is unclear.

• #59 Adult-onset Still’s disease and the role of dermatological manifestations: A case report and literature review

  https://www.spandidos-publications.com/10.3892/etm.2020.9515

  Adult-onset Still’s disease (AOSD) is a rare inflammatory condition (annual incidence of 0.1-0.4 new cases per 100,000 inhabitants) associating articular and systemic symptoms, which may occur at any age, although in 75% of the cases the onset of the disease is between the ages of 16 and 35, with a relatively equal distribution between the two sexes (1). […] The AOSD etiology remains unclear, despite several hypotheses that have been formulated. Viral infections, genetic factors and immune dysfunction, cytokine-mediated inflammation and apoptosis disorder may be involved in the pathogenesis of this disease. […] Recent advances in the medical field have highlighted that a key role in AOSD pathology is played by the activation of neutrophils and macrophages due to proinflammatory cytokine release (possibly through IL-18), which has led to the development of new therapeutic targets. Elevated TNF- levels were detected in both serum and tissues of AOSD patient compared with the healthy group, values that did not correlate with disease activity (8). On the other hand, the serum level of the soluble tumor necrosis factor-receptor 2 (sTNF-R2) correlated with the CRP level, may be used in the future as a disease activity marker (9). Elevated levels of IL-1 were detected in the serum of patients with untreated active disease, and IL-1 was found to be a major mediator of the inflammatory cascade, which is why IL-1 is a target for therapy. IL-1b is also a marker that could be used in assessing disease activity status and in monitoring the treatment (5). Elevated IL-6 levels were found in the blood of AODS patients compared with healthy subjects, this being dependent on disease activity, fever occurrence, and CRP increase. Moreover, skin biopsies from the specific salmon pink maculae were also sampled, which also revealed an elevated level of IL-6 (10,11). The persistence of high IL-8 values is associated with joint impairment due to the disease, and it could also be used as a predictive marker (11). IL-18 in patients with AODS is predominantly found in the synovial fluid and lymph nodes, and may be used as a marker of the severity of the disease and response to corticoid therapy, the IL-18 level being in good correlation with ferritin (12).

• #60 Pathogenesis of adult onset Still’s disease: current understanding and new insights.

  https://www.epistemonikos.org/ar/documents/622ccec7c8c35eabc3a554ef49eaba2c683c8394

  Adult-onset Still’s disease (AOSD) is a rare inflammatory disorder typically characterised by fever, arthritis and hyperferritinemia. […] Concerning AOSD pathogenesis, it is categorised as a multigenic autoinflammatory disease, at the „crossroads” of autoinflammatory and autoimmune diseases, because of the involvement of both arms of immune system. […] Although pathogenesis of the disease is not fully clarified, the role of the pro-inflammatory cytokines is well-recognised and biologic drugs, blocking these molecules, are routinely used in clinical practice. […] Finally, given that multiple recent lines of evidence have suggested new insights in AOSD pathogenesis, new therapeutic targets have been highlighted and the results of studies with new drugs could further improve the management of these patients.

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