Elevated serum levels of interleukin-10 in adult-onset Still’s disease are associated with disease activity

Objective.The differential diagnosis between rheumatic diseases and infectious conditions is a great challenge in clinical practice. Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory syndrome that shares several clinical and laboratory variables with sepsis. Interleukin (IL)-18 is overexpressed in AOSD, suggesting a possible role as a disease biomarker. The aim of our study was to detect IL-18 serum levels in a cohort of patients with AOSD and sepsis and to address its possible role as a biomarker for differential diagnosis.Methods.A group of unselected patients with AOSD diagnosed according to the Yamaguchi criteria and consecutive patients with sepsis diagnosed according to the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference criteria were enrolled. The clinical and laboratory data were collected. In the AOSD group, disease activity was assessed by Pouchot’s and Rau’s criteria. IL-18 serum levels were detected by ELISA.Results.Thirty-nine patients with AOSD and 18 patients with sepsis were enrolled. Two out of 18 patients with sepsis (11.1%) also fulfilled the Yamaguchi criteria. A significant difference was found in IL-18 serum levels between patients with active and inactive disease (p < 0.001), and it positively correlated with disease activity (p = 0.0003), ferritin serum level (p = 0.016), and erythrocyte sedimentation rate (p = 0.041). IL-18 was significantly increased in patients with AOSD when compared with sepsis (p = 0.014). For a cutoff of 148.9 pg/ml, this test had a specificity of 78.3% and a sensitivity of 88.6%.Conclusion.We have demonstrated that IL-18 can be a biomarker for differential diagnosis between AOSD and sepsis.

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Elevated serum levels of free interleukin-18 in adult-onset Still’s disease

Rheumatology ◽

10.1093/rheumatology/kew300 ◽

2016 ◽

Vol 55 (12) ◽

pp. 2237-2247 ◽

Cited By ~ 59

Author(s):

Charlotte Girard ◽

Jürgen Rech ◽

Michael Brown ◽

Danièle Allali ◽

Pascale Roux-Lombard ◽

...

Keyword(s):

Elevated Serum ◽

Serum Levels ◽

Adult Onset Still’S Disease ◽

Adult Onset ◽

Still’S Disease ◽

Interleukin 18 ◽

Still's Disease ◽

Adult Onset Still's Disease

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Different Features of Interleukin-37 and Interleukin-18 as Disease Activity Markers of Adult-onset Still’s Disease

10.21203/rs.3.rs-147805/v1 ◽

2021 ◽

Author(s):

Seoung Wan Nam ◽

SuMan Kang ◽

Jun Hyeok Lee ◽

Dae Hyun Yoo

Keyword(s):

Disease Activity ◽

Serum Levels ◽

High Disease Activity ◽

Expression Level ◽

Adult Onset Still’S Disease ◽

Adult Onset ◽

Still’S Disease ◽

Low Disease Activity ◽

Still's Disease ◽

Adult Onset Still's Disease

Abstract Backgrounds/Aims: The aim of this study was to evaluate the usefulness of serum interleukin (IL)-37 and IL-18 as disease activity markers of adult-onset Still’s disease (AOSD) and to compare their related clinical features. Methods: Forty-five patients with a set of high and subsequent low disease activity status of AOSD that fall within a 12-month period were enrolled. Modified Pouchot (mPouchot) score and serologic disease activity markers including serum levels of IL-37 and IL-18 were compared between high and low disease activity status. The relationships between disease activity parameters and differences in serum levels of IL-37 and IL-18 according to the presence of each disease manifestation of AOSD were evaluated in high disease activity status. Results: mPouchot score and all serologic disease activity markers including ESR, CRP, ferritin, IL-37, and IL-18 significantly declined in low disease activity status (p<0.01). Though both serologic cytokines positively correlated with mPouchot score, the two did not correlate with each other in high disease activity status. IL-18 positively correlated with ferritin, AST, and LDH (p<0.05). In contrast, IL-37 correlated better with CRP (p<0.01). The expression level of IL-37 and presence of leukocytosis were closely related. However, the expression level of IL-18 was closely related to presence of pleuritis. pneumonitis, abnormal LFT, and hyperferritinemia. Conclusions: Both IL-37 and IL-18 can be useful serologic markers of AOSD activity, but their pathologic roles in disease activity might be different.

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IL-18 Serum Level in Adult Onset Still’s Disease: A Marker of Disease Activity

International Journal of Inflammation ◽

10.1155/2012/156890 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 33

Author(s):

Serena Colafrancesco ◽

Roberta Priori ◽

Cristiano Alessandri ◽

Carlo Perricone ◽

Monica Pendolino ◽

...

Keyword(s):

Disease Activity ◽

Lupus Erythematosus ◽

Therapeutic Option ◽

Serum Levels ◽

Adult Onset Still’S Disease ◽

Adult Onset ◽

Still’S Disease ◽

Still's Disease ◽

Human Sera ◽

Adult Onset Still's Disease

Introduction. Immunological factors seem to play a pivotal role in Adult Onset Still's Disease (AOSD). Among all, IL-18 cytokine is overexpressed and drives the inflammatory process.Objective. We aimed to investigate the levels of IL-18 in sera of Italian patients with AOSD and to assess its possible role as a marker of disease activity.Methods. IL-18 serum levels were determined by ELISA in 26 Italian patients with AOSD. Disease activity was assessed using Pouchot’s criteria. As controls, 21 patients with Rheumatoid Arthritis (RA), 21 patients with Sjogren's Syndrome (SS), 20 patients with Systemic Lupus Erythematosus (SLE), and 21 healthy subjects (normal human sera, NHS) were evaluated.Results. IL-18 serum levels were significantly higher in patients with active AOSD than in non-active (P=0.001) and control groups (RAP=0.0070, SSP=0.0029, SLEP=0.0032, NHSP=0.0004). A significant correlation between IL-18 serum levels and disease activity (P<0.0001), and laboratory parameters as ferritin (P=0.0127) and C-reactive protein (P=0.0032) was demonstrated.Conclusions. Higher levels of IL-18 are detected in active AODS patients and correlate with disease activity and inflammatory laboratory features. ROC-AUC analysis of the serum concentration of IL-18 suggests that it can be considered a diagnostic marker of AOSD. This paper supports the targeting of this cytokine as a possible therapeutic option in AOSD.

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Case Report: Intracranial hypertension in an adult-onset Still’s disease patient initially presented with prolonged fever

F1000Research ◽

10.12688/f1000research.73095.1 ◽

2021 ◽

Vol 10 ◽

pp. 1050

Author(s):

Gerasimos Eleftheriotis ◽

Elias Skopelitis

Keyword(s):

Intracranial Hypertension ◽

Elevated Serum ◽

Disease Patient ◽

Adult Onset Still’S Disease ◽

Adult Onset ◽

Still’S Disease ◽

Prolonged Fever ◽

Still's Disease ◽

Serum Igg4 ◽

Adult Onset Still's Disease

This article describes the case of a 19-year-old woman who presented with prolonged fever, positive antinuclear antibodies (ANA) and splenomegaly. Pulmonary infiltrates were discovered and the patient was treated for community-acquired pneumonia, with no clinical amelioration. A more thorough evaluation was subsequently made, revealing elevated serum IgE and IgG4 levels and negative ANA tested by the hospital’s laboratory with two methods. During hospitalization thrombocytopenia, liver function test impairment, and evanescent rash during some febrile episodes developed. Vomiting also presented without any concomitant symptoms or signs; a funduscopic examination was consequently ordered, showing bilateral papilledema. Brain imaging was totally normal but a lumbar puncture revealed elevated opening pressure and lymphocytic pleocytosis along with low cerebrospinal fluid lactate dehydrogenase (CSF LDH). The patient was empirically treated with antimicrobials, dexamethasone, and acetazolamide and had immediate clinical and laboratory improvement. Diagnostic workup, however, was negative for an infectious agent; antimicrobials were ceased but the patient continued to improve. Adult-onset Still’s disease (AOSD) was considered as the working diagnosis because the patient fulfilled Yamaguchi criteria, responded to corticosteroids, and an alternative diagnosis was lacking. Nevertheless, because of the patient’s atypical features a trial to discontinue dexamethasone was undertaken, leading to immediate recurrence; the possibility of a self-limiting viral illness was excluded. Thrombocytopenia was attributed to hemophagocytic lymphohistiocytosis (HLH) that complicated AOSD. Corticosteroid reinitiation combined with methotrexate fully controlled all clinical and laboratory parameters. One month later papilledema had disappeared and the patient remained symptom-free even without acetazolamide. To our knowledge, this is the first report in the literature of an AOSD case presenting intracranial hypertension without cerebral imaging abnormalities and neurological or meningeal symptoms and signs, as well as with the initial observation of serum IgG4 elevation. A classic regimen combined with acetazolamide led to a positive outcome.

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Serum sTREM-1 in adult-onset Still’s disease: a novel biomarker of disease activity and a potential predictor of the chronic course

Rheumatology ◽

10.1093/rheumatology/keaa135 ◽

2020 ◽

Vol 59 (11) ◽

pp. 3293-3302 ◽

Cited By ~ 2

Author(s):

Zhihong Wang ◽

Huihui Chi ◽

Yue Sun ◽

Jialin Teng ◽

Tienan Feng ◽

...

Keyword(s):

Disease Activity ◽

Multivariate Logistic Regression Analysis ◽

Soluble Form ◽

Adult Onset Still’S Disease ◽

Adult Onset ◽

Still’S Disease ◽

Potential Predictor ◽

Still's Disease ◽

Chronic Course ◽

Adult Onset Still's Disease

Abstract Objectives Triggering receptor expressed on myeloid cells-1 (TREM-1) is an amplifier of inflammatory signals. Recently, a soluble form of TREM-1 (sTREM-1) was described. This study aimed to investigate the role of serum sTREM-1 in patients with adult-onset Still’s disease (AOSD). Methods Serum sTREM-1 levels were detected in 108 AOSD patients, 88 RA patients and 112 healthy controls (HC). The correlations of sTREM-1 with disease activity, clinical characteristics and laboratory parameters in AOSD patients were analysed by the Spearman correlation test. Risk factors for the chronic course of AOSD were evaluated by multivariate logistic regression analysis. Results AOSD patients had significantly higher serum sTREM-1 levels than RA patients and HC, and serum sTREM-1 levels were correlated with the systemic score, ferritin, leucocyte count, CRP, IL-1β and IL-6. The elevation in the initial sTREM-1 level by itself could discriminate patients developing the chronic course from patients developing the nonchronic course. Moreover, an elevated sTREM-1 level (> 526.4475 pg/ml) was an independent risk factor for the chronic course in active AOSD patients. Furthermore, interfering with TREM-1 engagement led to reductions in the secretion of pro-inflammatory cytokines, such as IL-1β, IL-6 and TNF-α, in neutrophils and monocytes from active AOSD patients. Conclusion Serum sTREM-1 levels are correlated with disease activity, and an elevation in the initial serum sTREM-1 level is a potential predictor of the chronic course in AOSD patients, which currently provides the best predictive model for identifying patients prone to developing the chronic course of AOSD.

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Response to: ‘Changing the outcome measures, changing the results? The urgent need of a specific Disease Activity Score to adult-onset Still’s disease’ by Ruscitti et al

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-218143 ◽

2020 ◽

pp. annrheumdis-2020-218143

Author(s):

Claudia Kedor ◽

Joachim Listing ◽

Jan Zernicke ◽

Eugen Feist

Keyword(s):

Disease Activity ◽

Outcome Measures ◽

Disease Activity Score ◽

Activity Score ◽

Adult Onset Still’S Disease ◽

Adult Onset ◽

Still’S Disease ◽

Specific Disease ◽

Still's Disease ◽

Adult Onset Still's Disease

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Elevated Levels of G-CSF in Patients with Active Phase of Adult-onset Still’s Disease

The Journal of Rheumatology ◽

10.3899/jrheum.200617 ◽

2020 ◽

pp. jrheum.200617

Author(s):

Yudong Liu ◽

Shulan Zhang ◽

Changshe Xia ◽

Jiali Chen ◽

Chunhong Fan

Keyword(s):

Disease Activity ◽

Therapeutic Potential ◽

Assessment System ◽

Adult Onset Still’S Disease ◽

Adult Onset ◽

Still’S Disease ◽

Still's Disease ◽

Elevated Liver Enzymes ◽

Csf Levels ◽

Adult Onset Still's Disease

Objective Neutrophilia is a hallmark of adult-onset Still’s disease (AoSD). We aimed to investigate the levels of granulocyte colony-stimulating factor (G-CSF), an essential regulator of neutrophil production and function, in the pathogenesis of AoSD. Methods Sera were collected from 70 patients with AoSD and 20 healthy controls (HCs). The levels of G-CSF were determined by ELISA. Low-density granulocytes (LDGs) were quantified by flow cytometry. Correlations between G-CSF levels and disease activity, laboratory parameters, or LDGs levels in patients with AoSD were analyzed by Spearman’s correlation test. Results Active AoSD patients presented significantly higher levels of G-CSF compared to inactive AoSD patients (p<0.001) and HCs (p<0.0001). The levels of G-CSF were significantly decreased after active AoSD patients achieved disease remission (p=0.0015). The levels of G-CSF were significantly correlated with CRP, ESR, ferritin and systemic score in AoSD (p<0.0001). Significant correlations between the levels of G-CSF and circulating neutrophils (p<0.0001), neutrophil-to-lymphocyte ratio (p<0.0001), percentages of LDGs in the PBMCs (p=0.0042) as well as absolute numbers of circulating LDGs (p=0.0180) were identified. Patients with fever, evanescent rash, sore throat, arthralgia, myalgia, lymphadenopathy or hepatomegaly/elevated liver enzymes displayed significantly higher levels of G-CSF compared to patients without these manifestations (p<0.05). Conclusion Our findings indicate that G-CSF is implicated in the pathogenesis of AoSD, and targeting G-CSF may have therapeutic potential for AoSD. In addition, introducing circulating G-CSF levels into the clinical assessment system may help to monitor disease activity.

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