Mechanisms, biomarkers and targets for adult-onset Still’s disease

Feist, Eugen; Mitrovic, Stéphane; Fautrel, Bruno

doi:10.1038/s41584-018-0081-x

Cited by 262 publications

(314 citation statements)

References 150 publications

(201 reference statements)

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“…The most consistent diagnosis for our patient was MAS, as he had high persistent fevers without an infectious cause, lymphopenia and anemia, marked hyperferritinemia, hypertriglyceridemia, splenomegaly, and the presence of hemophagocytes on bone marrow biopsy. The diagnosis of The image on the right shows a histiocyte with an engulfed neutrophil adult-onset Still's disease (AoSD) was excluded due to his axSpA [6]. The leading explanations for his MAS were adalimumab, an undetected viral infection, or his underlying axSpA.…”

Section: Discussionmentioning

confidence: 99%

Macrophage activation syndrome in a patient with axial spondyloarthritis on adalimumab

et al. 2018

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Macrophage activation syndrome (MAS) is a rare and potentially fatal condition characterized by excessive activation and uncontrolled proliferation of T lymphocytes and macrophages, leading to overwhelming systemic inflammation and cytokine release. MAS has been reported with viral infections, autoimmune disorders, malignancies, and medications. We describe a case of a patient with axial spondyloarthritis (axSpA) treated with adalimumab, who presented with MAS.

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Section: Discussionmentioning

confidence: 99%

Macrophage activation syndrome in a patient with axial spondyloarthritis on adalimumab

et al. 2018

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“…ASD is a systemic autoin ammatory disease characterized by spiking fever, arthralgia and skin rash, similar to systemic-onset juvenile idiopathic arthritis (sJIA) [4]. This disease is characterized by a dysregulated cytokine network [19].…”

Section: Discussionmentioning

confidence: 99%

“…ASD is considered to be an autoin ammatory disease because of the absence of autoantibodies, similar to other autoin ammatory diseases [2]. Although numerous studies have described potential biomarkers, none have been validated in clinical research, except the IL-1 family cytokine IL-18 [3,4]. IL-18 was originally described as an IFN-g-inducing factor primarily produced by activated macrophages [5].…”

Section: Introductionmentioning

confidence: 99%

Elevated serum levels of checkpoint molecules in patients with adult Still’s disease

Fujita¹,

Asano²,

Matsumoto³

et al. 2020

Preprint

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Background: The interaction between galectin-9 (Gal-9) and its ligand, T cell immunoglobulin and mucin-containing-molecule-3 (TIM-3), one of the coinhibitory receptors, transduce the inhibitory signaling to regulate immune responses. The dysregulated expression of checkpoint molecules has been reported under various inflammatory or autoimmune conditions. The aim of this study is to investigate the levels of these checkpoint molecules and their associations between proinflammatory markers in patients with adult Still’s disease (ASD). Methods: Serum samples were collected from 47 patients with active ASD, 116 patients with rheumatoid arthritis (RA), and 37 healthy controls (HCs). Serum levels of Gal-9, soluble TIM-3 (sTIM-3), and IL-18 were determined using enzyme-linked immunosorbent assay (ELISA). Results were compared with clinical features of ASD. Results: Serum Gal-9 levels in patients with ASD (median: 21.57 ng/ml, interquartile range IQR [11.41–39.72]) were significantly higher compared to those in patients with RA (7.58 ng/ml, IQR [5.57–10.20] p < 0.001) as well as those in HCs (4.51 ng/ml, [IQR; 3.58–5.45], p < 0.001). Similarly, serum sTIM-3 levels in patients with ASD were significantly higher than those in patients with RA and HCs. Serum levels of Gal-9 or sTIM-3 showed positive correlations with IL-18 levels (Gal-9; r = 0.90, p< 0.001, sTIM-3; r = 0.78, p< 0.001) in patients with ASD. Serum levels of Gal-9 or sTIM-3 correlated with serum ferritin (Gal-9; r = 0.77, p< 0.001, sTIM-3; r = 0.71, p< 0.001) and ASD disease activity score (Pouchot’s score, Gal-9; r = 0.66, p< 0.001, sTIM-3; r = 0.59, p< 0.001). Whereas there was no significant correlation between serum Gal-9 or sTIM-3 and CRP. ASD patients with chronic arthritis phenotype had a significantly higher Gal-9/ferritin and sTIM-3/ferritin ratio than those without this phenotype. After immunosuppressive treatment, Gal-9 and sTIM-3 levels showed a significant decline in parallel to the disease activity scores. Conclusions: Serum levels of the coinhibitory checkpoint molecules were elevated and correlated with disease activity in patients with ASD. These coinhibitory checkpoint molecule may be implicated in the autoinflammatory process seen in ASD.

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“…Adult-onset Still's disease (AOSD) is a rare, systemic inflammatory disorder (Feist, Mitrovic, & Fautrel, 2018) of mostly unknown etiology.…”

Section: Introductionmentioning

confidence: 99%

“…It is thought to belong to the spectrum of multigenic autoinflammatory diseases (Feist et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Urticarial rash, fever, and arthritis: A case of refractory Adult‐onset Still's disease with good response to tocilizumab

Wawrzycki

Krasowska

Pietrzak

et al. 2019

Dermatologic Therapy

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Adult‐onset Still's disease (AOSD) is a rare, systemic inflammatory disorder of not completely understood etiology. Aberrant activation of the innate immune system and overproduction of several pro‐inflammatory mediators are considered a critical component in disease pathogenesis. AOSD still poses a challenge due to the broad range of differential diagnoses and no specific biomarkers. Four cardinal symptoms are quotidian spiking fever, joint involvement, evanescent salmon pink‐rash rash, and leukocytosis with neutrophilia. We present a case of a 61‐year‐old female with a recurrent urticarial rash accompanied by attacks of high fever, tender joints, sore throat, enlarged liver, elevated inflammatory reactants, and hyperferritinemia. After an extensive workup, the patient fulfilled the criteria of AOSD. She was refractory to the glucocorticosteroids and disease‐modifying anti‐rheumatic drugs (DMARDs). Finally, after several unsuccessful attempts to achieve disease control with traditional DMAR's administration of Tocilizumab (TCZ), a humanized anti‐IL‐6 receptor antagonist resulted in substantial disease improvement. Since skin manifestations are a common feature of AOSD, it should be among differential diagnoses in patients with skin lesions and constitutional symptoms. Biologic agents represent a significant therapeutic advance in patients with AOSD refractory to conventional therapy.

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Mechanisms, biomarkers and targets for adult-onset Still’s disease

Cited by 262 publications

References 150 publications

Macrophage activation syndrome in a patient with axial spondyloarthritis on adalimumab

Macrophage activation syndrome in a patient with axial spondyloarthritis on adalimumab

Elevated serum levels of checkpoint molecules in patients with adult Still’s disease

Urticarial rash, fever, and arthritis: A case of refractory Adult‐onset Still's disease with good response to tocilizumab

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